Quickies

Question 1

Abdo Pain

Answer 1

DDx
Haim]
Acute mesenteric ischemia
i) SMA embolism (50%) – Classic triad
1. sudden pain (visceral pain) poorly localized and out of proportion to exam
2. underlying cardiac disease, ie embolus dislodged from left atrium (A fib), left ventricle, or heart valves
3. gut emptying through V or D

ii) SMA thrombus (15-25%) – “ACS of the gut”, postprandial pain, weight loss, “food fear”, risk factors are smoking and CAD risk factors

iii) non-occlusive ischemia (20-30%) – low flow state from cardiac failure, cocaine, digoxin, dialysis, vasopressors

iv) mesenteric venous thrombus (5%), hypercoaguable state, hx of DVT/PE or malignancy, portal HTN

Org(Vasculo)]
AAA – usually asymptomatic until rupture, epigastric and back pain, can mimic renal colic and diverticulitis, wide pulsatile abdominal mass, risk factors are age, male, HTN, smoking, CAD/PAD, syncope and shock

Org(Intestino)]

• *Gastritis** – epigastric pain, N, V, anorexia
• *GERD** – cough, heartburn, atypical angina
• *PUD** – gastric ulcer gives epigasric pain worsened by food as the acid increases in the stomach irritating the ulcer, or duodenal ulcer relieved by food as the pyloric sphincter closes stopping acid from reaching the duodenal ulcer but reoccurs 2-3 hours after a meal as the food enters the duodenum, pain awakens patient at night

Bowel obstruction – colicky abdominal pain, abdominal distention, vomiting (bilious, feculent), obstipation/constipation

Bowel perforation – sudden onset, sharp and severe abdominal pain, peritoneal signs (rigidity, rebound, guarding), motionless on bed, in distress

Diverticulitis – hypogastric pain that migrates to LLQ (like appendicitis), fever, WBC, D

• *Appendicitis – periumbilical abdominal pain that migrates to the LRQ,** N, V, anorexia, fever, tachycardia, localized peritoneal irritation at McBurneys point, Rosvings sign (LLQ palpation produces RLQ), psoas sign (active flexion of hip, or passive extension reproduces pain in a retrocecal appendix), obturator sign (flexion and internal rotation of hip reproduces pain), WBC, CRP
• *Appy triad
  1. peritoneal irritation (McBurneys point tenderness)
  2. migration of pain (epigastric to RLQ)
  3. inflammatory markers (raised WBC, CRP)**

Org(Cholecystos)]
biliary colic – obstruction of cystic duct by gallstones, symptomatic cholelithiasis, episodic pain in RUQ lasting minutes to hours, precipitated by meals

Cholecystitis – obstruction of cystic duct by gallstones, symptomatic cholelithiasis with inflammation, pain >6 hours, N, V, murphys sign (localized peritonitis over gall bladder causing the arrest of inspiration on gall bladder palpation), 1/2 will improve spontaneously in 7-10 days, 1/3 will worsen to choledocholithiasis and cholangitis, gallbladder wall thickening >3mm, pericholecystic fluid

Choledocholithiasis – gallstone lodged in bile duct, similar presentation to cholecystitis with jaundice, elevated total bilirubin, elevated Alk phos,

Ascending cholangitis – choledocholithiasis causing infection proximal to obstruction
Charcot’s triad
1. jaundice
2. fever
3. RUQ pain
Reynolds pentad
1. charcots triad
2. ALOC
3. HypoTN

Gallstone pancreatitis – gallstone lodged at the pancreatic duct at the ampulla of vater causing a backup of pancreatic enzymes that irritate and inflame the pancreas, elevated lipase

Org(Pancreos)]
Acute pancreatitis – epigastric pain radiating to back, N, V, fever, +/- jaundice, peritoneal signs, cullens sign (periumbilical eccymosis), gray turner sign (flank eccymosis), common etiology is gallstones and alcohol

Org (Nephros)
Renal colic – obstruction of urinary tract from a kidney stone, increased pressure leading to renal capsular distention causing visceral pain, N, V, and peristalsis of ureter leading to colicy pain – coming in waves with patient writhing unable to sit still – with flank pain radiating to groin, CVA tenderness

Org(Uros)]
Uncomplicated UTI (Cystitis) – young, healthy, non-pregnant women, with normal urinary urinary tract, dysuria, frequency, urgency, suprapubic and low back pain, new or increased incontinance in older patients with AMS/delirium

Complicated UTI (Cystitis) – pregnancy, DM, male gender, immunosupression, fuctional GU abnormality (neurogenic bladder or catheter), structural GU abnormality (stones, fistula, PCKD, transplant)

Org(Genitos)]
Ruptured ectopic – first trimester bleeding and abdominal pain

I]
Abdo US
Org (Vasculos)
AAA
Risk of rupture: <4cm 0%, 4-5cm 0.5-5%, 5-6cm 3-15%, 6-7cm 10-20%, 7-8cm 20-40%, >8cm 30-50%
AAA>5 – admit for surgical evaluation

Org(Cholecystos)
Cholelithiasis – gallstones
Cholecystitis – gallstones obstucting cystic duct, gallbladder wall thickening >3mm, pericholecystic fluid
Choledocholithiasis–dilated CBD >6mm
Ascending cholangitis–dilated CBD with charcots triad – jaundice, fever, RUQ pain (and reynolds pentad)
Gallstone pancreatitis–gallstones obstructing pancreatic duct at the ambulla of vater to the small intestine causing enzymes to back up into the pancreas

Org(Pancreos)
Acute pancreatitis – peripancreatic free fluid, diffusely enlarged hypoechoic gland

Org(Intestino)

• *Appendicitis** – aperistaltic and non-compressivle structure >6mm
• *Diverticulitis** – diverticula, abscess, hypoechoic around bowel wall

Org(Genitos)
Ectopic pregnancy – IUP

Question 2

Abscesses

Answer 2

• A Placebo-Controlled Trial Of Antibiotics For Smaller Skin Abscesses Daum, R.S., et al, N Engl J Med 376(26):2545, June 29, 2017
• *CONCLUSIONS:** Antibiotic therapy in addition to incision and drainage appears to improve short-term outcomes in patients with small uncomplicated skin abscesses.
• *EDITOR’S COMMENTARY:** This double-blinded, randomized controlled trial compared the use of clindamycin vs. trimethoprim-sulbactam (TMP) vs. placebo for the treatment of small abscesses <5 cm in addition to incision and drainage. Approximately 800 adult and pediatric patients were enrolled from 6 University of Chicago sites (including emergency departments, urgent cares, and affiliated clinics). The clinical cure rates and adverse event rates at 7-10 days were as follows: Clindamycin 83%/22% (high adverse events mostly diarrhea), TMP-SMX 82%/11%, Placebo 69%/12.5%. Overall the number needed to treat for clinical cure with antibiotics was approximately 7-8 patients. The authors conclude that antibiotics likely help improve short-term outcomes in small uncomplicated abscesses. Potential limitations to the ED application of this study include the non-ED population enrolled as well as the inclusion of abscesses with surrounding erythema (ie. if there is surrounding erythema/cellulitis then TMP should be given).

Question 3

ACS

Answer 3

• Utility Of The History And Physical Examination In The Detection Of Acute Coronary Syndromes In Emergency Department Patients Dezman, Z.D.W., et al, West J Emerg Med 18(4):752, June 2017​

RESULTS: The ECG and cardiac troponin are the standard diagnostic tests for ACS and AMI. Evolution in technology, such as increasingly sensitive troponin testing, has resulted in more ACS cases being detected, larger proportions of milder disease, and atypical presentations. In contrast, physician judgment alone based on clinical experience, history of the presenting illness, and physical exam appear to have little diagnostic value, and the same is true of risk factors for cardiovascular disease identified in the Framingham Heart Study (age, male sex, family history, hypertension, hyperlipidemia, smoking and diabetes). Research on test characteristics (e.g., predictive value and likelihood ratios) suggests three clinical signs that increase the risk of ACS:

• *1. pain with diaphoresis or vomiting
  2. radiating pain (especially to the arms)
  3. pain that is worse with exertion**

The ACS risk is lower in patients with reproducible chest wall tenderness or pain characterized as sharp, pleuritic or positional. However, because neither typical nor atypical symptoms can definitively diagnose or rule out ACS, the authors conclude that most patients with chest pain without an obvious cause will need further evaluation with ECG and troponin testing.

EDITOR’S COMMENTARY: This is a nice review of the literature that looks at the predictive value of various elements of the history and physical when assessing for likelihood of acute coronary syndrome. **The bottom line is that the history and physical, traditionally accepted risk factors and physician gestalt all have limited value in definitively ruling ACS in or out in any single case when studied objectively. However, likelihood ratios do vary between features of the H&P so combining this knowledge with objective data points like ECG and troponin will help risk stratify.

• Pitfalls In Electrocardiographic Diagnosis Of Acute Coronary Syndrome In Low-Risk Chest Pain Tewelde, S.Z., et al, West J Emerg Med 18(4):601, June 2017

Although only a fraction of patients presenting to the emergency department with chest pain have acute coronary syndrome, making the right disposition decision is crucial. Both the history of present illness and electrocardiogram (ECG) have a pivotal diagnostic role. The authors, coordinated at the University of Maryland, review several subtle ECG findings, in patients otherwise stratified as low-risk, which physicians often overlook as normal or irrelevant and yet they may have fatal consequences. Of note, in a nondiagnostic ECG, nonspecific ST-segment and T-wave changes are not consistent with a normal ECG. Even minimal ST-segment elevation may indicate a developing infarction. Serial ECG tracings are required in such cases.

1. Diffuse STD, STE aVR >1mm, STE V1, aVR>V1. This electrocardiographic finding has been observed in patients with left main, proximal left anterior descending, and triple vessel disease. Elevation in lead aVR with concomitant diffuse STD has been found in association with diffuse subendocardial ischemia and infarction of the basal septum. Lead aVR is termed the “forgotten lead” for good reason. When an ECG shows diffuse ST-segment depression, typically managed as ischemia, elevation in lead aVR could mean infarction of the basal septum. This is an indication for acute reperfusion therapy.

2. STD V1-V4 with tall R-waves and upright T waves. Isolated posterior myocardial infarctions are the most common infarct pattern to be mistaken for ischemia because they only produce ST-segment depression, specifically in leads V1-V3. When doubtful regarding infarct versus ischemia, a posterior ECG should be obtained by placing leads V4–6 in the left scapular region. ST elevation of only 0.5 mm in any one lead is diagnostic.

3. Lone TWI aVL. Isolated ECG findings are often ignored, but lone T-wave changes in lead aVL may be associated with an imminent inferior acute myocardial infarction. A number of studies have demonstrated the importance of aVL T-wave changes in recognition of right ventricular involvement, specifically its association with an imminent inferior AMI.

4. Tall T wave V1 (Specifically when it’s taller than the T wave in lead V6 it is referred to as loss of precordial T-wave balance). Broad upright T wave V1>V6 with subtle septal (V1–V2) ST elevation and anterolateral (V4–V6, I) ST depression. An upright and large T wave in lead V1 may be suggestive of coronary artery disease and ischemia.

5. Biphasic (25%) or deeply inverted (75%) T waves V2–V3 with minimal ST elevation (Wellens’ syndrome). The syndrome has two forms. Type A, the more common form (occurring in ~75% of cases), is characterized by deeply inverted T waves in V2 and V3. Type B, characterized by biphasic T waves in V2 and V3, occurs in ~25% of cases. Urgent cardiac catheterization should be considered.

While computer-based analysis of ECGs is on the rise, physicians are advised to keep a sharp eye out for these critical findings.

• Oxygen Therapy In Suspected Acute Myocardial Infarction Hofmann, R., et al, N Engl J Med 377(13):1240, September 28, 2017

BACKGROUND: Myocardial ischemia and infarction is associated with a mismatch between oxygen supply and demand. As such, supplemental oxygen has been considered routine in patients with suspected acute myocardial infarction (AMI). However, it is now known that supra-normal oxygen levels can result in coronary vasoconstriction and reperfusion injury due to increased production of reactive oxygen species.

METHODS: This multicenter, parallel-group, open-label, registry-based, randomized, controlled trial from Sweden included 6,629 patients who had symptoms suggestive of AMI, an oxygen saturation of at least 90%, and ischemic ECG changes or an elevated cardiac troponin level. After 1:1 randomization, 3,311 patients received supplemental oxygen therapy while 3,318 received room air. The primary outcome was all-cause mortality at one year.

CONCLUSIONS: In patients with suspected AMI who were not hypoxemic at baseline, supplemental oxygen therapy did not improve all-cause mortality or rehospitalization for acute myocardial infarction at one year.

EDITOR’S COMMENTARY: Prior literature suggests that non-hypoxemic patients with suspected or confirmed myocardial infarction (MI) do not benefit and may experience harm from the routine use of inhaled oxygen. The authors from Sweden performed a multi-center, open label, randomized controlled trial of approximately 6600 patients to determine whether oxygen therapy (6 Liters/minute via facemask) vs room air would have any impact on mortality or rehospitalization with MI at 1 year. Both mortality rates and rehospitalization rates were equivalent in both groups adding more compelling evidence to the existing literature that routine oxygen for non-hypoxemic chest pain patients provides no benefit.

• Stable High-Sensitivity Cardiac Troponin T Levels And Outcomes In Patients With Chest Pain Roos, A., et al, J Am Coll Cardiol70(18):2226, October 31, 2017

CONCLUSIONS: In this large study of patients with chest pain, morbidity and mortality increased in a graded manner with increasing levels of hs-cTnT, even in the absence of MI or other underlying conditions and even at levels well below the normal upper limit (e.g., 5-9ng/L).

EDITOR’S COMMENTARY: In this large Swedish observational cohort study, the authors studied approximately twenty-thousand adult chest pain patients to evaluate the clinical outcomes of patients with elevated but stable high sensitivity troponin levels. They found that even in the absence of ACS and other underlying conditions, patients with elevated, stable high sensitivity troponins had higher rates of death, MI, and hospitalizations for CHF.

• Sex Differences In Diagnoses, Treatment, And Outcomes For Emergency Department Patients With Chest Pain And Elevated Cardiac Troponin Humphries, K.H., et al, Acad Emerg Med 25(4):413, April 2018

SUMMARY: There is a longstanding and sordid history in the medical literature documenting that women are less likely to be referred for cardiac evaluation or cath compared to men. Some suggest this arises from implicit biases about women and chest pain (e.g., women are less likely to die from cardiac event, they are more anxious/ depressed, etc.) This study attempts to examine gender biases in the diagnosis and management of suspicion chest pain in the ED.

It was a retrospective study looking at all chest pain visits at 2 Canadian ED’s in British Columbia in men and women who had elevated troponins with cardiac risk factors/ features. The key outcomes were 1) proportion diagnosed with MI by gender 2) proportion who got cath’d and 3) the proportion who had a major adverse cardiac event (MACE) on follow up.

Ultimately, they found 250 women and 687 men with elevated troponin levels and cardiac chest pain as documented in the ED charting. Women were less likely to be diagnosed with MI (46 vs 57%), less likely to receive a cath (48% vs. 64%), less likely to use cardiac meds, but had equal or higher risk of MACE at 1 year than their male counterparts who also had cardiac chest pain and positive troponins.

EDITOR’S COMMENTARY: This was a retrospective study looking at cardiac chest pain in men and women with elevated troponins and subsequent management. The goal was to examine whether gender biases exist between men and women in managing cardiac chest pain. They found that women were less likely to be diagnosed with MI, less likely to receive a cath and less likely to be put on cardiac medications. However, women had an equal if not greater risk of MACE at 1-year follow-up compared to men. This study has a lot of limitations given it retrospective nature. We don’t know how high the troponins actually were, the clinical presentation, etc. However, it does suggest that providers are viewing the objective data differently when it comes to men versus women and this is to say nothing of all the women who may have been seen and never had a troponin drawn. I think this is pretty concerning and tends to confirm other reports in the literature that providers tend to discount evidence for cardiac cause of disease among women. There is no solution proposed in this article and I can’t offer one other than to be aware that this tendency seems to continue despite decades of exposure in the literature.

• Coronary Angiographic Findings And Outcomes In Patients With Sudden Cardiac Arrest Without ST-Elevation Myocardial Infarction: A SWEDEHEART Study Wester, A., et al, Resuscitation 126:172, May 2018

SUMMARY: The number one cause of sudden cardiac arrest (SCA) is acute thrombotic coronary occlusion. A famous study PROCAT showed an association with improved mortality if the patient had a successful PCI following SCA whether there was a STEMI on ECG following ROSC or not. Other studies have failed to confirm these results. None of the studies were RCT’s and were based on a small population of 200-400’s patients.

This has led to different practices–some SCA patients will go directly to cath regardless of EKG, others only if post-ROSC EKG shows a STEMI, etc. This current study asks: 1) what do the coronary arteries look like in SCA patients with post ROSC who have STEMI compared to those with NO STEMI and 2) among those with NO STEMI, does getting a PCI improve outcomes? Using the Swedish Coronary Artery Angioplasty Registry (SCAAR) the authors identified 4,306 patients who went to the cath lab after SCA. Of these, 1,400 had STEMI and 2,900 did not (67%).

Those with SCA and STEMI had a very high incidence of severe coronary disease – 90% had at least 1 vessel that was > 90% occluded, and 56% of these cases were thought to have an acute occlusion. PCI or CABG was performed 94% of the time. Of the NO STEMI group, 43% had at least 1 vessel that was a 90% lesion and only 26% were thought to have an acute occlusion. Still PCI was performed in 67% of cases.

Unadjusted mortality was actually higher for the NO STEMI group who got a PCI compared to those that did not, but this probably reflects that this group had higher overall coronary disease. After adjustment for confounders the mortality rate was the same for those who got PCI and those who did not.

EDITOR’S COMMENTARY: This retrospective study looked at SCA patients with post-ROSC STEMI and NO STEMI and compared outcomes of PCI in these patients. They found SCA patients with post-ROSC STEMI had greater vessel disease and higher rates of acute occlusion compared to the NO STEMI group.

***In the NO STEMI group after adjustment for confounders, there was no mortality difference. So this study stands in opposition to the PROCAT study that found a big survival advantage if there was a PCI. In my mind, this is more evidence that going to cath lab is not a great idea for the average post arrest non-STEMI case. I suspect pretty strongly that those non-STEMI patients who went to cath lab were assessed to be more likely to have a culprit lesion than those who did not – but we don’t know anything about those who didn’t go to cath. However, even in this selected group there was no benefit to cath. Some will probably argue that the cath was not performed early enough and maybe if it had been performed within 5 minutes of arrival then we would have seen the difference in outcomes. I tend to doubt this, mostly because so few of the non-STEMI cases had an acute thrombus. What does it mean? It means that we still do not have anything remotely amounting to good evidence for immediate cath following SCA – seems useful to have a hospital plan in place, but whatever the plan is – it is not seriously evidence based. There are several RCTs ongoing that will hopefully answer this question in the coming years.

EMU (2017)

• Pain radiates bilateral or R>L
• Diaphoresis (observred>reported)
• Vomiting (not nausea)
• Hx of PAD
• Abnormal stress test
• Troponins negative does not totally rule out ACS
• HEART score used for Rapid Rule Out (RRO) tool
• ACS in women – painless presentations more common **fatigue, malaise, unexplained SOB, sleep disturbance
• Exertional chest pain

Note: In a review of over 430,000 patients with confirmed acute MI from the National Registry of Myocardial Infarction (NRMI) 2, one-third had no chest pain on presentation to the hospital. These patients may present with dyspnea alone, nausea and/or vomiting, palpitations, syncope, or cardiac arrest. **They are more likely to be older, diabetic, and women.

The absence of chest pain has important implications for therapy and prognosis. In the Registry report, patients without chest pain were much less likely to be diagnosed with a confirmed MI on admission (22 versus 50 percent in those with chest pain) and were less likely to be treated with appropriate medical therapy and to receive fibrinolytic therapy or primary angioplasty (25 versus 74 percent). Not surprisingly, these differences were associated with an increase in in-hospital mortality (23.3 versus 9.3 percent, adjusted odds ratio 2.21, 95 percent confidence interval 2.17 to 2.26).

Angina – described as squeezing, pressure, heaviness, tightness or pain in the chest, substernal discomfort precipitated by exertion, with a typical radiation to the shoulder, jaw or inner aspect of the arm relieved by rest or nitroglycerin in less than 10 minutes.

• *ACS is a syndrome (set of signs and symptoms)** such that decreased blood flow to the coronary arteries of the heart so that the heart muscle is unable to function properly or dies:
• *1. STEMI (tronponins and ECG)
  2. NSTEMI (troponins)
  3. UA (clinical diagnosis)**

STEMI
i) Positive troponins
ii) STE > 1mm (1 box) in two contiguous leads of V1, V4-6, I, II, III, avL, avF. In leads V2, V3 women need > 1.5mm (1 1/2 boxes) and men > 2mm (2 boxes). In right heart leads V3R, V4R > 0.5mm, and posterior leads V7-9 >0.5mm (Task force for the universal definintion of MI, 2012).
In addition to patients with STE on the ECG, two other groups of patients with an ACS are considered to have an STEMI: those with new or presumably new LBBB and those with a true posterior MI.

Sgarbossa’s Criteria, in simplest terms, rely on the presence of inappropriate concordance or excessive discordance.

Normally, in LBBB, we’d expect the J-point or ST segment to move in opposite direction of the QRS complex. In other words, in those leads where the QRS complex is normally a positive deflection, the J-point and ST-segment should be slightly below the isoelectric line, and in those leads where the QRS is negative (primarily V1-V3), the J-point and ST-segment should rise slightly above the isoelectric line. This is known as discordance, and a small amount of discordance is appropriate and expected in LBBB.

The presence of left bundle branch block often obscures the classical ECG diagnosis of acute MI. Assessment of ST-segment changes may be useful in this setting. ST-segment shifts that occur in the same direction as the major QRS vector (so-called “primary” or concordant ST changes) can indicate ischemia or infarction. Such shifts may include STD of at least 1 mm in leads V1, V2, or V3, or in leads II, III, or aVF, with STE of at least 1 mm in lead V5. Extremely discordant ST changes (changes in the opposite direction of the major QRS vector of >5 mm) were also reported to be suggestive of MI, although exceptions occur, importantly limiting the specificity of this sign.

• *NSTEMI**
• *i) Positive troponins**
• *Downsloping ST depression** in two contigious leads is suggestive of cardiac ischemia. ST depression > 1mm (1 box) is highly specific and conveys worse prognosis, > 2mm (2 boxes) in > 2 leads gives a high probability of NSTEMI and predicts significant mortality (35% in 30 days). T wave inversions can be considered evidence of myocardial ischemia if > 1mm (1 box), present in > 1 lead with dominant R waves, and/or are not seen on previous EKG or changing. Q waves pathological if > 40ms (1 box), > 2mm (2 boxes), seen in V1-V4 (right heart leads).

Unstable Angina (Clinical Diagnosis)
Non-diagnostic troponins.
With or without ECG changes.
One of the following:
1. Angina is new and severe (CCS III) – within one month and when climbing < 1 flight of stairs or walking < 2 blocks.
2. Angina at rest (CCS IV)usually lastingmore than 20 min.
3. Angina is more frequent, with longer duration, and with less exertion.

Canadian Cardiovascular Society (CCS)
Angina severity grading I-IV
Reference: minimal exertion climbing 1 flight of stairs, walking 2 blocks
I - Angina only with strenuous exertion (more than ordinary activty)
II - Angina with moderate exertion (ordinary activity)
Angina when climbing > 1 flight of stairs or walking > 2 blocks
III - Angina with minimal exertion (less than ordinary activity)
Angina when climbing < 1 flight of stairs or walking < 2 blocks
IV - Angina at rest

ID]
​male, female bias
age > 65

HPI]
1. Pain with exertion
2. Pain with vomiting or diaphoresis (observed>>reported)
3. Pain with radiation (right shoulder>>left/both shoulders/left arm)
Note:ACS risk islowerin patients withreproducible chest wall tenderness or pain characterized as sharp, pleuritic or positional.

PMHx]
Prior abnormal stress test
PAD (Peripheral Arterial Disease, ie limb claudication)
Prior CAD (Coronoary Artery Disease)
Note:CAD is chronic, ACS is acute.
DM
HTN
DL

FMHx]
1st degree relative with early age MI
Note: Early MI is a male < 55 or female < 65.
1st degree relative is a parent, sibling or child.

SHx]
Smoking

O/E] unstable vitals, bradycardia (inferior MI, RCA supplies the SAN, AVN)
Cardios – S34 or M, pain not reproducable with palpation

INVESTIGATIO]
L(H)/Haim]
CBC
L(H)/Meta]
SMA7 (Lytes)
L(H)/Org(Cardios)]
Troponins
L(H)/Org(Nephros)]
Cr (Imaging)
Note: Repeat troponin and ECG q3h if high sensitivity troponin, q6h if low sensitivity troponin. Troponin elevation following cardiac cell necrosis starts within 2–3 hours, peaks in approx. 24 hours, and persists for 1–2 weeks. ** Even if troponins are negative ACS can still exist. I]

CODE STEMI/NSTEMI
NP/A,B]
O2 (ONLY if SpO2<94%)
NP/C]
2 large bore IVs (18g-14g) in each antecubital fossa or IO
Art-line
NP/Mon]
BP on right arm cycling q15m
SpO2 on left index finger
cardiac monitoring – ECG leads, pacing pads

P/Poin]

• *Morphine 2-4mg IV q5-15min**
• *Note: **Only use if severe** as it may decrease cardiac output so use with caution in hypotension and inferior MI. Morphine decreases the effect Plavix.

P/Naus]
{Zofran} Ondansetron 4mg IV

P/Haim]
ASA 325mg chewed
Note: If oral not feasible then given as rectal suppository.
(anti-platlet, irreversible COX1 inibitior)
{Plavix} Clopidogrel 600mg PO
(anti-platelet prodrug that is affected by morphine, irreversible purinergic (ADP) receptor inhibitor)
{Lovenox} Enoxaparin (LMWH) 30mg IV loading dose, then 1mg/kg SC BID OR
{Arixtra} Fondaparinux 2.5mg SC (used at LRO)

Note: Adjust for CrCl<30 and age >75.
(anticoagulant)
OR
UFH 60U/kg (max 4000U), then 12U/kg/hour (max 1000U) infusion
Note: Use for CrCl<20.
Note: Heparin half lifemechanism representsclearance of heparin by the reticuloendothelial system (more pecisely known as the mononuclear phagocytic system or MPS are phagocytic cells such as macrophages and dendritic cells found in reticular connective tissue) and endothelial cells, to whichheparin binds with a high affinity. Assuming a 70 kg adult, a 7,000 unit IV heparin dose will have ahalf-life of 60 minutes whereas an 1,800 unit dose would have a half-life of 30 minutes.

Note: All ST-elevation myocardial infarction (STEMI) patients receiving fibrinolytic therapy should be treated with an anticoagulant. In patients who will likely receive percutaneous coronary intervention (PCI) after fibrinolytic therapy, unfractionated heparin (UFH) is preferred. For patients who will not receive PCI, give either UFH or {Lovenox} enoxaparin. Although the evidence presented below suggests an advantage to enoxaparin in patients treated with fibrinolytic therapy, we often use UFH since it leaves open the option to proceed with bailout PCI if there is evidence of failed reperfusion.

P/Meta]
{Lipitor} Atorvastatin 80mg PO
(antilipid)

P/Org(Vasculos)]
NTG 0.4mg SPRAY/SL x2 q5min x3
(reduce pre/after load), if no response then
NTG 20mcg/min IV, increase 10mcg/min q3-5min to 150-200mcg/min
Note: Hold NTG if SBP<90 in RV infarction and preload dependant, or if no more pain. Suspected RV infarct when STE in V1, STE in III > II and confirmed when STE in V4R. Hypotension will worsen ischemia. Contraindicated in PGE inhibitors. If no relief from sublingual NTG then start NTG 20mcg/min IV.

P/Org(Cardios)]
Metoprolol 50mg PO
(initated in 24 hours for protection contraindicated in heart failure, hypotension, bradycardia or heart block)
Note: In cocaine related ACS DO NOT give betablockers, treat with lorazepam 2-4mg IV q15min.

P/Surg]
i) D2B time (for PCI) of 90 minutes (1 and a half hours) if at a STEMI centre.

ii) D2B time (for PCI) of 120 minutes (2hours) if not at a STEMI centre. If D2B time greater than 120 minutes, fibrinolytics should administered with door to needle time (D2N) of 30 minutes.
Tenecteplase (TNKase, tPA) dose based on weight from 30mg to 50mg over 5 seconds, ranging in weight fom 60kg to 90kg
Alteplase (tPA, tissue plasminogen activator) total dose of 100mg, 15mg over 2min then 50mg over 30min

Similar to patients who present to an emergency department, prehospital fibrinolysis should be administered within 30 minutes of first medical contact. In patients with an acute STEMI, fibrinolytic therapy should not await the availability of results of cardiac biomarkers.

As the length of time between patient’s presentation and delivery of fibrinolytic therapy (D2N) increases, the benefit from therapy decreases. The survival benefit is greatest when fibrinolytic agents are administered within the first four hours after the onset of symptoms and particularly within the first 70 minutes. Although this conclusion is largely derived from clinical trials, similar findings have been noted in the community as demonstrated in the second National Registry of Myocardial Infarction (NRMI). Early therapy also has the greatest impact on infarct size and left ventricular ejection fraction.

Fibrinolytics for patients within 12 hours of the onset of STEMI who have no absolute contraindications to fibrinolytic therapy and for whom reperfusion with primary PCI cannot be performed within the recommended time, fibrinolytic therapy should be given as opposed to no reperfusion therapy.

For symptomatic patients who present after 12 (but before 24) hours of symptom onset and when PCI is not readily available, fibrinolytic therapy should be given as opposed to no reperfusion therapy.

• *Note: ACS Risk Stratification** **HEART score for separating high, medium, low risk and how to triage patients for follow up. Can also use TIMI score.
• *1.** Low risk – Exercise Treadmill Test (ETT)
• *2.** Intermediate risk – Exercise/Pharmacologic ECHO looks for worsening of wall motion abnormalities at rest and under stress. ECHO can also look at valve function, ejection fraction and for a pericardial effusion.
• *Exercise/Pharmacologic MPI (Myocardial Perfusion Imaging)** looks for the perfusion (**via tracer) at rest and under stress. Less perfusion under stress indicates ischemia, less perfusion both under stress and at rest indicates infarction. Can also detect wall motion abnormalities and ejection fraction.
• *3.** High risk – Angiogram with catheterization.

Question 4

Antibiotics

Answer 4

• *Gram Positive**
  1. Penicillins (ampicillin, amoxacilin), if beta lactamase producing (dicloxacillin, oxacillin)
  2. Cephalosporin (1st and 2nd generation – cefazolin {Ancef}/cephalexin {Keflex}, cefuroxime)
  3. Macrolide (azithromycin, clarithromycin)
  4. Quinolone (ciprofloxacin, moxifloxacin, less so levofloxacin)
  5. Sulfamethoxazole (SMX) /Trimethoprim (TMP) {Septra} (increasing resistance)
  6. Clindamycin (good for neutralizing staph toxin)
  7. Vancomycin (MRSA)
• *Gram Negative**
  1. Broad-spectrum penicillins (pipercillin-tazobactam, amoxicillin-clavulanic acid)
  2. Cephalosporin (2nd, 3rd and 4th – cefuroxime, ceftriaxone/ceftazadime, cefipime)
  3. Sulfamethoxazole (SMX)/Trimethoprim (TMP) {Septra}
  4. Aminoglycoside (gentamicin, tobramycin) Note: renal and ototoxicity
  5. Quinolones
  6. Carbapenems
  7. Marcolides (limited coverage)
• *Anaerobe**
  1. Metronidazole {Flagyl}
  2. Clindamycin
  3. Broad-spectrum penicillins (piperacillin-tazobactam, amoxicillin-clavulanic acid)
  4. Quinolones (only Moxifloxacin)
  5. Carbapenems
• *Atypicals**
  1. Macrolides
  2. Tetracycline
  3. Quinolone
• *Pseudomonas**
  1. Ciprofloxacin (antipseudomonal fluoroquinolone)
  2. Ceftazidime (3rd generation)
  4. Piperacillin-tazobactam
  5. Imipenam, meropenam (antipseudomonal carbapenam)
  5. Gentamicin (aminoglycoside)

Question 5

Anaphylaxis

Answer 5

• Biphasic anaphylaxis: A review of the literature and implications for emergency management. Ali Pourmand, Chelsea Robinson, Wahab Syed, Maryann Mazer-Amirshahi. American Journal of Emergency Medicine 2018 May 9.

BACKGROUND: The biphasic reaction is a feared complication of anaphylaxis management in the emergency department (ED). The traditional recommended ED observation time is 4-6 h after complete resolution of symptoms for every anaphylaxis patient. However, there has been great controversy regarding whether this standard of care is evidence-based.
CONCLUSIONS: There is a need for further research to identify true risk factors associated with biphasic anaphylaxis and to clearly define the role of corticosteroids in biphasic reactions. However, given the low incidence and rare mortality of biphasic reactions, patients who receive epinephrine within one hour of symptom onset and who respond to epinephrine with rapid and complete symptom resolution can probably be discharged from the ED with careful return precautions and education without the need for prolonged observation.​

• *Clinical Diagnosis**
• *1.** Acute onset (minutes to hours) after exposure to KNOWN antigen AND
• *i)** Vascular – SBP<90, or less than 30% decrease from baseline
• *2.** Acute onset (minutes to hours) after exposure to LIKELY antigen AND two or more of:
• *i)** Skin
• *ii)** Lungs
• *iii)** Vascular
• *iv)** GI (cramping abdomina pain, vomiting)
• *Note:** Skin symptoms are absent in up to 20% of presentations.
• *3.** Acute onset (minutes to hours) involving skin, mucosal tissue, or both such as hives, pruiritis/flushing, swollen lips, tongue, uvula AND ONE of the following:
• *i)** Lungs – respiratory compromise such as dyspnea, wheeze, stridor, hypoxemia
• *ii)** Vascular – HypoTN or signs of malperfusion such as syncope, ALOC, incontinence

RECIPERE]
Epinephrine 0.3-0.5mg (1:1000 or 1mg/mL) IM, q5-15min x3 (stabilizes mast cells)
Note: Auto injector has (Epi-pen) has 0.3mg/0.3mL. Resuscitation epinephrine has 1mg/10mL (0.1mg/1mL).
IF no response THEN epinephrine 0.1mcg/kg/min IV infusion
Note:Can put 1mg in 1L normal saline (1mcg/mL) and infuse2-15mcg/min. IV tubing has a drop factor (gtt/mL), typically 10, 12, 15 and 20. To calculate the drip rate take total mL/min x drop factor, giving drops per minute (gtt/min). If 7mcg/min is desired of 1mcg/mL, thats 7mL/min x 20gtt/mL is 140gtt/min. If 1mg in 250mL normal saline the concentration is 0.004mg/mL or 4mcg/mL. If 1mg in 100mL normal saline the concentration is 0.01 mg/mL or 10mcg/mL.
{Benadryl} Diphenhydramine 50mg IV
(H1 antagonist)
{Zantac} Ranitidine 50mg IV
(H2 antatonist)
{Solu-Medrol} Methylprednisolone 125mg IV
(glucocorticoid inhibits prostaglandins and leukotrienes)
{Ventolin} Salbutamol 2-5-5mg NEBS
(brochospasm)

• *Note:** Patients on beta-blockers may not respond to epinephrine due to beta blockade.
• *Glucagon 1-5mg IV over 5 minutes then 5-15mcg/min infusion (activates adenyl cyclase). If given too fast may induce vomiting.**

Question 6

Aortic Stenosis

Answer 6

Etiology]
Infect]
Rheumatic aortic stenosis
Note:Rheumtic aortic stenosis is triggered by an autoimmune reaction from group A streptococci (GAS, strep pyogenes) from strep throat.Rheumatic heart disease typically only involves the mitral valve (70% of cases),though insome cases the aortic and mitral valves are both involved (25%). Involvement of other heart valves without damage to the mitral are exceedingly rare.
Cong]
Congenital valvular aortic stenosis with bicuspid valves
Struct]
Degenerative calcified aortic stenosis

HPI]
Syncope
1. Exertional dizziness, presyncope or syncope – less blood going to the head on exertion will cause lightheadedness.

• *CPOE/Angina**
• *2.** Exertional angina – left and right main coronary arteries come off the aortic bulb above the leaflets. Less blood going to heart on exertion will cause angina like pain.
• *SOBOE/Heart Failure**
• *3. Exertional shortness of breath** or decreased exercise tolerance – less blood going to the muscles and more blood backed up in the lungs on exertion will cause sensation of shortness of breath.

O/E]
Cardios – midsystolic ejection murmur in a crescendo and decrescendo pattern with radiation to right carotid, pulses parvus et tardus (late and weak) at radial pulse

Valsalva
Breathing out against a closed glottis (vocal cord). Causes an increase in the intrathorcic pressure (ITP0 as the muscles are applying a force inward and the glottis keeps the air trapped in the lungs.

Stage 1 (3s), held breath against a closed glottis and increased ITP – Increased AP, decreased HR.
Increase in intrathoracic pressure (ITP) causes an increase in aortic pressure (AP) due to blood sqeezed out of the lungs and the increased ITP acting on the aortic walls externally. The increased ITP also acts on the SVC/IVC and the right atrium causing less venous return.

Aortic body baroreceptors through CNX detect increase pressure sending an afferent impulse to the NTS. NTS sends a signal to the nucleus ambiguus (NAmb) causing increased parasympathetic outflow to the SAN/AVN and a decreased HR.

Stage 2 (3-20s), held breath against a closed glottis and increased ITP – Decreased AP, increased HR.
Continued increased ITP and reduced venous return and preload causes a drop in the AP.

Aortic body barorecpetors detect decreased pressure through CNX sending an afferent impulse to the NTS. NTS sends a signal to the RVLM increasing sympathetic outflow to the cervical ganglion and the interomediolateral nucleus of T1-T4 causing an increase in HR.

Stage 3 (20-23s), pressure release – Decreased AP, increased HR. Similar to breathing in, blood is trapped in the lungs and venous return increases. AP decreases due to less prelaod and decreased external pressure causing an increased HR. CNX to NTS to NAmb (and CVLM) and increased parasympathetic to SAN/AVN.

Stage 4 (23s-33s), pressure release – Increased AP, decreased HR. Continued release of ITP creates a large bolus of preload and a sustained increase in AP caussing a decreased HR . CNX to NTS to RVLM to cervical ganglon and IML/T1-T4 and increased sympathetic to SAN/AVN.

INVESTIGATIO]
I]
ECG - LVH
ECHO
Severe
transvalvular aortic valve velocity >4.0m/s
transvalvular aortic pressure gradiant >40mmHg
aortic valve area <1cm²
LVEF <50% for severe
thickened leaflets and calcified
possible bicusped valve

RECIPERE]
P/Surg]
Aortic valve replacement
Transcathetic Aortic Valve Implementation (TAVI)

Question 7

Neuromyelitis Optica Spectrum Disorders (NMOSD)

and

Area Postrema Syndrome (APS)

Answer 7

• *Dx]**
• *Diagnostic criteria for** neuromyelitis optica spectrum disorders (NMOSD) with AQP4-IgG
  1. At least one core clinical characteristic.

2. Positive test for AQP4-IgG using best available detection method (cell-based assay strongly recommended)
3. Exclusion of alternative diagnoses

OR

Diagnostic criteria for NMOSD without AQP4-IgG or NMOSD with unknown AQP4-IgG status
1. At least two core clinical characteristics occurring as a result of one or more clinical attacks and meeting all of the following requirements:

a. At least one core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome
b. Dissemination in space (two or more different core clinical characteristics)
c. Fulfillment of additional MRI requirements, as applicable
2. Negative tests for AQP4-IgG using best available detection method, or testing unavailable
3. Exclusion of alternative diagnoses

• Core clinicial characteristics*
• *i)** Area postrema syndrome (APS)
• *Note:** APS is characterized by episodes of otherwise unexplained hiccups OR nausea and vomiting.
• *ii)** Acute brainstem syndrome (midbrain, pons, medulla oblongata)
• *Note:** Brainstem syndromes typically cause ipsilateral cranial nerve lesions and contralateral long tract signs. Cranial nerve cell bodies are destroyed accounting for the ipsilateral cranial nerve signs, and adjacent spinothalamic, corticospinal tracts are destroyed which affects the motor function and sensation to the contralateral side.
• Spinothlamic tract relays ascending afferent sensory information from the body.
• Corticospinal tracts controls the descending efferent somatic striated mucles of the body.
• Corticobulbar tract control the muscles of the CNs (as they end at the CN nuclei in the brainstem)/ The corticospinal and corticobulbar tracts run through the crus cerebri (large peduncles in the ventral midbrain. ​

​Brainstem syndromes are commonly due to brainstem ischaemia, but can also be caused by neoplasia, demyelination, infective and hamartomatous lesions. Imaging, ideally with MRI rather than CT, is obligatory.

Note: The corticobulbar tract innervates cranial nerve (CN) nuclei bilaterally with the exception of the lower facial nerve CNVII which are innervated only unilaterally (below the eyes) and hypoglossal nerve CNXII. Both the lower part of CNs VII and XII are innervated by the contralateral cortex (however if the cranial nerve nucleus is destroyed there will be ispilateral signs whether innervated ispilaterally or bilaterally).

Among those nuclei that are bilaterally innervated a slightly stronger connection contralaterally is observed than ipsilaterally. The corticobulbar tract directly innervates the nuclei of the trigeminal nerve CNV, facial nerve CNVII, accessory nerve CNXI, and hypoglossal nerve CNXII. The corticobulbar tract also contributes to the motor regions of the vagus nerve CNX via the NAmb. The corticospinal tract innervates the arms, torso and legs and dessicates at the lower end of the medulla pyramids at the top of the spinal cord.

Note: Nucleus ambigious (NAmb) aka cardioinhibitory centre CIC, contains cell bodies for the preganglionic parasympathetic vagal neurons CNX. The preganglionic vagus nerve synapses with the parasympathetic postganglionic vagus nerve, which reside near the sinoatrial (SA) node and atrioventricular (AV) node. The parasympathetic postganglionic vagus nerve releases Ach onto M2R at the SA and AV node decreasing the heart rate.

The NAmb also gives rise to the special visceral efferents (SVE), aka brachiomotor, efferent motor cell bodies of CNX that innervates voluntary striated muscles of the soft palate, pharynx, and larynx which are strongly associated with speech and swallowing, in the proximal one third of the esophagus (as opposed to smooth muscle from the distal one third of the esophagus to the rest of the GI tract which is innervated by the dorsal motor nucleus of vagus). The NAmb also containts special visceral efferents (SVE), aka brachiomotor, efferent motor cells bodies of CNIX that innervates the voluntary striated stylopharyngeus muscle.

• *iii) Optic neuritis**
• *Note: Pain on eye movement**, the subacute onset of worsening of vision, a relative afferent pupillary defect (RAPD), and normal-appearing fundus (with at most mild papilledema) are the typical symptoms and signs of optic neuritis.​ Typical optic neuritis is an acute, severe visual disturbance without any clear diagnostic findings on ocular examination. It generally affects young, otherwise healthy individual and typically caused by an autoimmune reaction directed against the optic nerve.

iv) Acute myelitis

• *v)** Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions
• *Note:** Diencephalic syndrome is a rare disorder caused by a tumor that is usually located in the diencephalon, a portion of the brain just above the brainstem. The diencephalon includes the hypothalamus and the thalamus. Affected infants and young children may develop symptoms that include the failure to gain weight and grow as would be expected based upon age and gender (failure to thrive) and abnormal progressive thinness and weakness (emaciation).

The most striking feature of diencephalic syndrome is profound emaciation including a uniform loss of body fat (adipose tissue). Emaciation occurs despite normal or near normal caloric intake. Emaciation may progressively worsen. Because of the loss of body fat, affected children may appear muscular.

Affected infants and children may behave in an alert, happy and outgoing manner, which is in contrast to their outward appearance. Additional symptoms such as vomiting, vision abnormalities, headaches, and pallor can also develop. Diencephalic syndrome can progress to cause severe, life-threatening complications.

vi) Symptomatic cerebral syndrome with NMOSD-typical brain lesions

Etiology/Pathophysiology]
Neuromyelitis optica (NMO, previously known as Devic disease) and neuromyelitis optica spectrum disorders (NMOSD) are **inflammatory disorders of the central nervous system** characterized by severe, **immune-mediated demyelination** and axonal damage predominantly targeting **optic nerves** and spinal cord. Traditionally considered a variant of multiple sclerosis, NMO is now recognized as a distinct clinical entity based on unique immunologic features. The discovery of a disease-specific serum NMO-**immunoglobulin G (IgG) antibody** that selectively binds **aquaporin-4 (AQP4)** has led to increased understanding of a diverse spectrum of disorders.

Question 8

Atrial Fibrillation

Answer 8

• *Unstable**
• *Pulmonary edema** – backup flow into lungs
• *Ischemic pain** – heart not perfusing itself
• *Hypotension, ALOC** – weak forward pressure

RECIPERE]
NP/Pro]
Synchronized cardioversion (150-200J biphasic)
P/Haim]
Immediate OAC in ED for >or= 4 weeks

Stable
What is the immediate risk of stroke?

• *High**
• *1.** Onset > 48hours or unknown
• *2.** CVA/TIA < 6months
• *3.** Mechanical/rheumatic valve disease (typically mitral)

RECIPERE]
P/Haim]
OAC x 3 weeks before cardioversion
P/Org(Cardios)]
Rate Control (or TEE Guided Cardioversion)
Metoprolol 5mg IV bolus over 3min, x3 if needed
Metoprolol 25-100mg PO BID
OR
Diltiazem 20mg IV bolus over 2min, 5-15mg/h
Diltiazem 120-360mg PO OD

Low
Clear onset < 48hours
Therapeutic OAC >or= 3weeks

RECIPERE]
NP/Pro]
Synchronized cardioversion (150-200J biphasic)
OR
P/Org(Cardios)]
Flecainide 2mg/kg IV over 10 min
Flecainide 200-300mg PO
P/Haim]
No OAC needed before cardioversion.
After cardiovesion OAC by CHADS65.

Note: Flecainide blocks Nav1.5 sodium channel in the heart, slowing phase 0 of the cardiac action potential. The effect of flecainide on the sodium channels of the heart increases as the heart rate increases, known as use-dependence. Use dependence is why flecainide is useful to break a tachyarrhythmia.

Question 9

Bradycardia

Question 10

NOAC and Afib

Non-vitamen K antagonist Oral Anti-coagulants

Answer 10

{Pradaxa} Dabigatran - prothrombin (II) inhibitor, and thrombin (IIa) bound to fibrin (Ia).
CrCl>50 mL/minute – 150mg PO BID
CrCl 30-50 mL/minute – generally no issues
CrCl<30 mL/minute – Avoid

Xarelto {Rivaroxaban} – factor Xa inhibitor
CrCl ≥50 mL/minute – 20mg PO OD
CrCl 30 to 49 mL/minute – 15 mg PO OD
CrCl <30 mL/minute – Avoid

Apixaban {Eliquis} – factor Xa inhibitor.
5mg PO BID
2.5mg PO BID if any two of the following:
1. Age >or= 80
2. Weight
3. Cr >or= 132umol/L
CrCl <15 mL/minute – Avoid

Question 11

C-spine rules

Answer 11

• Cervical Spine Clearance in Obtunded Patients After Blunt Traumatic Injury: A Systematic Review. Ann Intern Med. 2015; 162(6):429-437
• *CONCLUSION:** Cervical spine clearance in obtunded adults after blunt traumatic injury with negative results from a well-interpreted, high-quality CT scan is probably a safe and efficient practice.
• *Note:** In the case of the inebriated but alert patient with a GCS of 15, one reasonable approach would be to leave the patient in a c-collar until they are clinically sober.

Inclusion criteria
Acute – injury within 48 hours
Alert (GCS 15 – converses, fully oriented, follows commands)
Stable vitals (Revised trauma score – SBP>90, RR 10-24)
Trauma to the head and neck:
i) neck pain with any mechanism of injury (subjective complaint by the patient of any pain in the posterior midline or posterolateral aspect of the neck)
ii) no neck pain but ALL of:
1) some visible injury above the clavicles
2) non ambulatory
3) dangerous mechanism of injury:
Fall from > 3 feet or 5 stairs
Axial load to head ex. diving
Bicycle collision
MVC high speed (>100km/h), rollover, ejection
MVC with pedestrian, motorcycle, or recreation vehicle

High Risk for ANY ONE of the following:
i) Age > or = to 65
ii) Dangerous mechanism:
Fall from > 3 feet or 5 stairs
Axial load to head ex. diving
Bicycle collision
MVC high speed (>100km/h), rollover, ejection
MVC with pedestrian, motorcycle, or recreation vehicle
iii) Paresthesia in extremities

LOW risk and NO scan if ANY one of:
Simple rear end MVC
Ambulatory
Delayed onset of pain
Sitting position in the ER
No midline C-Spine tenderness

O/E]

• *LOW risk** and NO scan if:
• *Can move neck 45 degrees left and right**

Summary
If a patient has any high risk factors (age > 65, a defined dangerous mechanism or paresthesias in the arms or legs) then they require c-spine imaging.

If a patient has no high risk factors and meets none of the defined low risk criteria (see list), they require c-spine imaging.

If a patient has no high risk factors and meets any one low risk factor, then it is safe to assess whether the patient is able to rotate their neck 45 degrees to the left and right. If they can do this (even with some pain or discomfort), then they do not require further imaging. If they cannot rotate their neck 45 degrees in both directions then they require c-spine images.

Exclusion criteria
Injury > 48h
Age < 16
GCS < 15
Unstable
Penetrating trauma
Acute paralysis
Known vertebral disease (ankylosing spondylitis, rheumatoid arthritis, spinal stenosis, previous spinal surgery)
Return visit for reassessment of same injury
Pregnant

Question 12

Cannabis Hyperemesis

Answer 12

• Resolution Of Cannabis Hyperemesis Syndrome With Topical Capsaicin In The Emergency Department: A Case Series Dezieck, L., et al, Clin Toxicol 55(8):908, September 2017
• *CONCLUSIONS:** In patients with cannabinoid hyperemesis syndrome, treatment with topical capsaicin is associated with relief of symptoms. The authors call for additional study of this noninvasive and low-risk management strategy for cannabinoid hyperemesis syndrome.
• *EDITOR’S COMMENTARY:** This is a descriptive, retrospective case series of 13 patients with cannabis hyperemesis syndrome who were successfully treated with capsaicin cream. The capsaicin cream was applied to the abdomen. Varying concentrations of the cream were used - most commonly 0.25% but 0.075% was also used. The most common adverse effects were local burning and nonproductive cough.
• *Cannabis Hyperemesis:
  1. long term marijuana use
  2. history of recurrent cyclic vomiting
  3. absence of other symptoms to explain the emesis**

Question 13

Centor Criteria

Answer 13

HPI]

• *No cough**
• *Fever >38 OR subjective**

O/E]
HEENT]
Anterior CLAD
Tonsillar exudates

Score:
0-1 no need for Abx
2-3 rapid strep test or culture
4 Abx

Amoxicillin 50mg/kg x 10 days OR
Penicillin V 250mg PO BID x 10 days
If Pencillin hypersensitivity then: Clindamycin

Question 14

Cerebral Vein Thrombosis (CVT)

Answer 14

• Misdiagnosis Of Cerebral Vein Thrombosis In The Emergency Department. Liberman, A.L., et al, Stroke 49(6):1504, June 2018.

SUMMARY: The annual incidence of cerebral vein thrombosis (CVT) may be as high as 15.7 cases per million persons. CVT is a condition affecting mostly women often during pregnancy or in the postpartum period but can affect any age and gender.

There is often a prothrombotic state, a gradual onset headache with neurological symptoms (e.g., focal deficits, seizure, encephalopathy) and CT findings are often normal or very subtle.

The authors used administrative data to identify all the cases coded as CVT in 3 states (New York, California, Florida) from 2007-2015. They identified 5,966 patients with CVT diagnosis from the ED. They then looked in the previous 2 weeks of patients diagnosed with CVT for any previous ED visits where they were diagnosed with headache, seizure and released. These were labeled “missed diagnosis”.

Finally, they looked at the ‘missed’ cases and compared their outcomes with ‘not missed cases’ to determine if missing the disease had an impact on favorable neurological outcomes (defined as being discharged to a skilled nursing facility) or death. Of the 5966, only 216 (3%) had an ED visit within the 2 weeks previously for headache or seizure. Missed cases were younger and more likely to have a primary hypercoagulable state (probably diagnosed after the ED visit – e.g. they had no risk factor on arrival). Missed cases actually had a much lower inpatient mortality (OR 0.14) compared with not missed cases and had similar rates of favorable neurological outcome.

EDITOR’S COMMENTARY: This was a retrospective study looking at cases of missed CVT diagnosis in the ED. The authors found that 3% of patients diagnosed with CVT had a previous ED visit in the 2-weeks prior to their formal diagnosis. They found that missed cases had a much lower inpatient mortality (OR 0.14) compared to not-missed cases and had similar rates of favorable neurological outcome. This was likely because missed cases were clinically subtle and not as severe as the not-missed cases. I think this study is largely reassuring – this is an impossible diagnosis – and we only miss it 3% of the time and, even when we do, it doesn’t not seem to affect outcomes.

Etiology]
Hypercoagulopathic states (see PE/Virchow’s Triad).
1. Stasis
2. Endothelial changes (damage and inflammation)
3. Hypercoaguability

The most frequent risk factors for CVT are the following:

ii) endothelial damage and inflammation from infection, head injury, or inflammatory conditions
iii) hypercoaguability from mutations, estrogen, pregnancy, cancer

• *Hypercoaguability**
• *Hyperviscosity** (high hematocrit) from polycythemia, change in clotting factors (mutations, pregnancy, malignancy, nephrotic syndrome), hormones (increased estrogen from exogenous, endogenous or obseity).
• Change in clotting factors*
• *Mutations. Factor V Leiden mutation** is an autosomal dominant genetic condition with incomplete penetrance. The factor V Leiden is resistant to aPC (activated Protein C) degredation which leads to increased amounts of factor V and increased clotting. Factor II (prothrombin) G20210A mutation leads to in increase in factor II leading to a higher chance of clotting.

Pregnancy. Fibrinogen increases during pregnancy. Hepatocytes produce more fibrinogen which can rise to 3x the normal levels.

Malignancy. Cancer cells express (i) procoagulant proteins and (ii) release microparticles (soluble fragments of tumour cell membranes) leading to a systemic hypercoagulable state. Two common procoagulant proteins are tissue factor (TF) and cancer procoagulant, which directly activate factor X to Xa.

• Hormones*
• *Estrogen** causes increased gene transcription in the hepatocytes, mainly increased levels of VII (TF/VIIa) leading to conversion of X to Xa, and thrombin (IIa) formation. Estrogen can be increased from obesity, there is more adipose tissue and aromatase enzyme which converts testosterone to estrogen, endogenous or exogenous sources.

Estrogen containing oral contraceptives increase the plasma concentrations of clotting factors II, VII, X, XII, factor VIII, fibrinogen, and thrombin activatable fibrinolysis inhibitor (TAFI). Not all of the increases in clotting factors are of the same magnitude. Factor VII (which binds to and is activated by TF, TF/VIIa as above) appears to have the greatest magnitude of increase and factor VIII made in the endothelial cells (which sequesters vWF in the blood, VIII/vWF) the least magnitude of increase, comparatively.

Question 15

CT Head Rules

Answer 15

• Is Routine Head CT Indicated In Awake Stable Older Patients After A Ground Level Fall?” Sartin, R., et al, Am J Surg 214(6):1055, December 2017

CONCLUSIONS: Head CT scanning resulted in a change in management in just over one in five of these older patients presenting with minor head trauma after a ground-level fall. The authors suggest that a CT scan should be considered a component of standard management in this circumstance.
EDITOR’S COMMENTARY: In this retrospective study of 437 patients greater than 55 years of age with GCS 15 after a minor ground level fall, the authors looked at the impact of head CT result on management. They found that 146 (33.4%) of patients had a positive head CT finding, 95 (21.7%) patients had a change in management; 76 (17.4%) were medication changes and 19 (4.3%) required neurosurgical intervention. Additionally, a neurological deficit on exam and age 85 years and older were found to be associated with need for neurosurgery.

• *Inclusion criteria:**
• *i)** Injury within 24 hrs
• *ii)** Blunt trauma to the head
• *iii) Witnessed LOC** or witnessed disorientation, or definite amnesia to the event
• *iv)** GCS ≥13 in the ED
• *Exclusion criteria:**
  i) Returned for reassessment of same head injury
  ii) Age <16 years
  iii) Bleeding disorder or anticoagulation
  iv) Pregnancy
  v) Absence of clear history of trauma as inciting event (eg, syncope or seizure as inciting event)
  vi) Minimal head injury (no loss of consciousness, disorientation or amnesia)
  vii) Seizure prior to ED assessment
  viii) Penetrating skull injury or depressed skull fracture
  ix) Acute focal neurological deficit
  x) Unstable vital signs

HIGH risk if ANY ONE:
ID]
Age > or = 65

HPI]
Vomiting > or = 2 times

O/E] GCS <15, 2 hours after injury

• *Basal skull fracture –** hemotympanum, CSF otorrhea/rhinorrhea, racoon eyes, battle sign.
• *Open or depressed skull fracture**

MEDIUM risk if ANY ONE:
Amnesia before impact >30min
Dangerious mechanism – fall from >3 feet or 5 stairs, pedestrian stuck, MVC occupant ejected

Question 16

Chest Pain

Answer 16

DDx
Haim]
STEMI (ACS) – visceral pain described as pressure-like, heaviness, and aching, tightness, squeezing, radiates to right arm or shoulder/both shoulders/left arm, diaphoresis, dyspnea (SOB), worse with exertion, vomiting, nausea

Org(Cardios)]
Tamponade – Becks heart triad (HypoTN, JVD, muffled heard sounds), dyspnea (SOB), decreased exercise tolerace, , pulses paradoxus, shock

Org(Pulmos)]
Tension pneumothorax (TPX) – Becks lung triad (HypoTN, JVD, deviated trachea), dyspnea(SOB)/tachypnea, tachycardia

Org(Vasculos)]
TAD (Thoracic Aortic Dissection) – HTN, sudden and intense “tearing” or “ripping” pain radiating to the back, 1/3 have neurological complaints, diaphoresis, syncope,

Org (Gastrointestino)]
Boerhaave’s syndrome – crepitus, alcohol consumption, febrile, septic
Incarcerated diaphragmatic hernia – history of hernia

Infla]
Pericarditis – pleuritic pain, worse with inspiration and supine,improved with leaning forward, retrosternal or left precordial, not affected by exertion

• *HPI]**
• *STEMI** (ACS) – visceral pain described as pressure-like, heaviness, and aching, tightness, squeezing, radiates to right arm or shoulder/both shoulders/left arm, diaphoresis, dyspnea (SOB), worse with exertion, vomiting, nausea
• *PE** – dyspnea(SOB)/tachypnea, pleuritic chest pain, persistent tachycardia, syncope, hemoptysis
• *Note:** PERC, Wells

Tamponade – Becks heart triad (HypoTN, JVD, muffled heard sounds), dyspnea (SOB), decreased exercise tolerace

Tension pneumothorax – Becks lung triad (HypoTN, JVD, deviated trachea), dyspnea(SOB)/tachypnea, tachycardia

TAD – sudden and intense “tearing” or “ripping” pain that radiates to the back, diaphoresis, syncope

Boerhaave’s – crepitus, EtOH, febrile, septic

Incarcerated diaphragmatic hernia – history of hernia

Percarditis – pleuritic pain, worse with inspiration and supine, improved pain with leaning forward

PMHx]
History of DVT, PE (PE)
Immobilization (>3d) or surgery in the last 4 weeks (PE)
DM, DL, HTN (ACS, TAD), Uremia/ESRD (tamponade)
Marfans (TAD)
Lung disease – infectious or interstitial (tension pneumo)
Cardiac disease – coarctation, bicuspid aortic valve (TAD)
Inflammatory – SLE, RA (pericarditis/tamponade, PE)
Malignancy – treatment in the last 6 months (tamponade, PE)
Infectious – Viral, bacterial, TB (pericarditis/tamponade)
Iatrogenic – Central lines (tension pneumo, PE)

Meds]
Anti-coagulants (tamponade)

SHx]
EtOH (Boerhaave)
Smoking (ACS, PE)
Cocaine/Meth (TAD)
Pregnancy (TAD, PE)

FHx]
1s degree releative with early CAD
(male < 55, female < 65)

• *O/E] TC** (persistent in PE, tension pneumo), HypoTN (tamponade, tension pneumo, PE when massive), HTN (TAD), Dyspnea (SOB)/Tachypnea (PE, tension pneumo, tamponade), SpO2 <94% (PE), febrile (boerhaave)
• *Pulses paradoxus/pulse deficit** (tamponade) – dropped radial pulse upon inspiration
• *General** – ALOC (alert, confused, lethargic, obtunded, stuporous, comatose), orientation, creptius (boerhaave)
• *Neuros** – focal deficits, motor or sensory (TAD)
• *Cardios** – new murmur (STEMI), aortic regurg (TAD), JVD (tamponade, TPX, PE), pulse deficit/pulsus paradoxus (tamponade), muffled heart shounds (tamponade), unequal pulses (TAD)
• *Pulmos** – crackles, wheeze or pleural rub (PE), decreased air entry (TPX)
• *PV** – edema (pitting CHF vs non-pitting DVT), unilaterial leg swelling (PE)

INVESTIGATIO]
L(H)/Haim]
CBC (anemia)
WBC (pneumoniae/pericarditis)
D-Dimer (PE)
INR
PTT

L(H)/Meta]
SMA7 (Lytes)

L(H)/Org(Cardios)]

• *Troponins**
• *Note:** Repeat troponin and ECG q3h if high sensitivity troponin, q6h if low sensitivity troponin. Troponin elevation following cardiac cell necrosis starts within 2–3 hours, peaks in approx. 24 hours, and persists for 1–2 weeks

L(H)/Org(Nephros)]
Cr (imaging, pericarditis, tamponade)

L(H)/Infla]
ESR (pericarditis, tamponade), CRP

I]
ECG (see ACS)
Note: Pericarditis
Stage 1 – (acute pain) diffuse STE except aVR and V1 with PR depression
Stage 2 – (days later) ST return to baseline with flattening T waves
Stage 3 – inverted T waves
Stage 4 – (weeks to months) EKG returns to baseline with +/- persistent T wave inversions (chronic pericarditis)

• *CXR** – widened mediastinum (TAD, Boerhaave, TPX, Tamponade)
• *CTPA w contrast** – (PE)
• *V/Q –** (PE) if cant take radiation (pregnancy) or contrast (ESRD)
• *U/S Leg Doppler** – (PE) to look for DVT
• *CTAorta w contrast –** (TAD)
• *TEE** – (TAD) if cant have contrast
• *POCUS -**- A lines, NO lung sliding or B lines (tension pneumo), pericardial effusion (tamponade, pericarditis), aortic flap (TAD)
• *RECIPERE]**
• *CODE STEMI/NSTEMI**
• *see ACS**
• *Note:** ACS Risk Stratification – HEART score for separating high, medium, low risk and how to triage patients for follow up. TIMI score.
• *1. Low risk** - Exercise Treadmill Test (ETT)
• *2. Intermediate risk** – Exercise/Pharmacologic ECHO looks for worsening of wall motion abnormalities. Can also look at the valves and for effusion.
• *Exercise/Pharmacologic MPI** (Myocardial Perfusion Imaging) looks for the perfusion (**via tracer) at rest and under stress. When there is less pefusion under stress this indicates ischemia, less perfusion both under stress and at rest indicates infarction. Can also detect wall motion and ejection fraction.
• *3. High risk** – Angiogram with catheterization.

Tamponade
NP/C]
PIV, 500mL to 1000mL fluid Bolus

NP/Proc]
Pericardiocentesis

• *Pericarditis (clinical diagnosis or medical diagnosis)**
• *Need two of:**
  1. Chest pain - typical
  2. Pericardial friction rub
  3. ECG changes
  4. Pericardial effusion (POCUS)
• *Myocarditis** – Pericarditis and one of:
  1. Increase in troponins
  2. New LV dysfunction

P/Infla]
Indomethacin 50mg PO q8h x 2 weeks
(COX1 and COX2) OR
Ibuprofen 400-800mg PO q6-8h max 3200mg x 2 weeks (COX1 and COX2) OR
Colchicine 0.5mg PO BID (OD if <70kg) x 3 months

• *PE**
• *see PE**

Tension Pneumothorax
NP/A,B]
O2 3-10L NP
NP/Proc]
Needle thoracostomy followed by tube thoracostomy

TAD
pain, heart rate and blood pressure control
goal of HR<60 and BP<120/80
Fentanyl for pain, beta blockers (esmolol, labetalol) first to stop tachycardia and shearing forces of heart each time it pumps, and nitroprusside for after load control.

P/Poin]

• *Morphine 4-6mg IV q5-15min OR**
• *Fentanyl 1-2mcg/kg IV q30-60min**

PNaus]
Zofran 4mg IV

P/Org(Cardios)]
Labetalol 20mg IV push over 2 min
40-80mg q10min
300mg max
(stop tachycardia and shearing forces)

Target HR<60 and BP<120/80
If BP > 120/80 after HR control then start vasodilators.
Note: **DO NOT use vasodilators without first beta blockers as it can cause reflex tachycardia.

P/Org(Vasculo)]
Nitroprusside 0.3-0.5 mcg/kg/min
titrated 0.5mcg/kg/min
10mcg/kg/min max
(reduce afterload)
Note: Get BPs in both arms and tirate to the higher BP.​

Surg/Consult]
In Stanford classification, type A dissection involves the ascending arch of the aorta (including the brachiocephalic, left common carotid and left subclavian) where it can rip into the pericardium, also causing an MI and aortic valve deficiency – mostly operative repair. Type B involves the descending aorta distal to left subclavian artery and typically can be handled with medical management.

Boerhaave
NP/C]
PIV, Art-line
NP/Nut]
NPO

P/Poin]
Morphine 4-6mg IV q5-15min

P/Org(Gastro)]
{Pantoloc} Pantoprazole 80mg bolus, then 8mg/hour infusion

P/Infect]
Piperacillin-tazobactam

Surg/Consult]
Cardiothoracic surgeon

Question 17

CHADS65

Answer 17

ID]
Age > 65 or > 75 – OAC

PMHx]
CHADS2 – OAC
CHF
HTN
DM
Stroke/TIA/DVT

Arterial disease = ASA
CAD
PAD
AAA/TAA

Question 18

Community Acquired Pneumonia (CAP)

Answer 18

1. Diagnosis
   ii) lab/imaging
   CXR
   Radiographic findings consistent with the diagnosis of CAP include lobar consolidations, interstitial infiltrates, and/or cavitations. Although certain radiographic features suggest certain causes of pneumonia (eg, lobar consolidations suggest infection with typical bacterial pathogens), radiographic appearance alone cannot reliably differentiate among etiologies.
2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – starting from acute to benign
5. Investigations (rule in/out)
6. Treatment/Management

Question 19

Constipation

Answer 19

RECIPERE]
P/Org (gastrointestino)]
First Line
Softener/osmotic
​{Restoralax, Peg-Lyte} PEG 240mL PO q10min
Lactulose 15-30mL or 10-20g PO daily
{Colace} Docusate 240mg PO daily
Note: Colace reduces surface tension of the oil-water interface of the stool resulting in enhanced incorporation of water and fat allowing for stool softening. Colace not used anymore as an approved softener.

Stimultent
{Senokot} Senna 2 tabs, 1 tsp, 10-15mL PO
{Dulcolax} Bisacodyl 5-15mg PO PRN
Cascara 5mL PO QHS

• *Second Line**
• *Rectal Suppository and Enema**
• *{Dulcolax} Bisacodyl** 10mg PR PRN
• *{Fleet enema} Sodium Phosphate**

Third Line
Manual enema
{Relistor} Methylnaltrexone 38kg-61kg 8mg SQ, if opioid induced constipation

Question 20

COPD Exacerbation

Answer 20

** Taken from GOLD recommendations 2017
HPI]
3 Cardinal signs
1. Increased dyspnea (cough, wheeze).
2. Increased sputum volume.
3. Increased sputum purulence.

If 1 of 3 then NO Abx only bronchodilators and symptomatic therapy.
If 2 of 3 then COPDE either uncomplicated or complicated.

Uncomplicated COPDE
ID]
Age < 65
HPI]
FEV1 >50% of predicted
PMHx]
No frequent exacerbations <2 per year
No cardiac disease

RECIPERE]
Note: Therapy should cover the following:
Haemophilus influenzae (GN) 10-50%
Streptococcus pneumoniae (GP) 10-20%
Pseudomonas aeruginosa (GN) 1-10%
Moraxella catarrhalis (GN)

P/Infect]
Amoxicillin 1000mg PO TID OR
Doxycycline 100mg PO BID​

Complicated COPDE
One or more of the following RISK factors:
ID]
Age > 65
HPI]
FEV1 <50% of predicted
PMHx]
Frequent exacerbations >or= 2 per year
Cardiac disease

RECIPERE]
P/Infect]
{Clavulin} Amoxicillin-Clavulanate 875mg PO BID OR
Levofloxacin {Levaquin} 750mg PO OD OR
Moxifloxacin {Avalox} 400mg PO OD​

Pseudomonas is a GN pathogen. Most common pathogen in hospital acquired ventilator associated pneumoniae. Comminity acquired Pseudomonas has been seen in people with identifyable risk factors including:
1. Hospitalized >2days in the past 3 months.
2. Antbiotics >or=4 courses in the 12 months.
3. Pseudomonas identified in a previous
hospitalization.
4. Severe COPD, FEV1<50% of predicted.
5. Immunocompromised, structural lung disease (cystic fibrosis or bronchiectasis).

Ceftazidime 500mg-1g IV TID
Ciprofloxacin 750mg PO BID
Pip/Tazo 4.5g IV q6-8h (renal dosing)

Cefepime 2g IV TID

Less effective Fluoroquinolones for Pseudomonas :
{Levaquin} Levofloxacin 750mg PO/IV OD OR
{Avalox} Moxifloxacin 400mg PO/IV OD

If suspecting Influenza:

• *{Tamiflu} Oseltamivir 75 mg PO q12h** OR
• *Peramivir 600 mg IV x1**

O/E] RR,SpO2 <92% (mod to severe)
General – ALOC
Pulmos – tripoding, decreased A/E, wheeze, barrel chest, pursed lip breathing, indrawing (suprasternal retractions/tracheal tug, intercostal retractions, substernal retractions, subcostal retractions), accessory respiratory muscle use (sternocleidomastoids, scalenes), paradoxal chest wall movements, cyanosis

No respiratory failure:
RR 20-30 (12-20)
No ALOC
No accessory muscle use
No increase in PaCO2 (35-45)
Hypoxemia improved with supplemental oxygen FiO2 28-35%.

Acute respiratory failure — non-life-threatening
RR > 30
No ALOC
Accessory muscle use
Hypercarbia i.e., PaCO2 (35-45) elevated 50-60 mmHg or increased compared with baseline.
Hypoxemia improved with supplemental oxygen FiO2 35-40%.

Acute respiratory failure — life-threatening
RR > 30
ALOC
Accessory muscle use
Hypercapnia i.e., PaCO2 (35-45) elevated > 60 mmHg or increased compared with baseline or the presence of acidosis (pH < 7.35, 7.35-7.45).
Hypoxemia not improved with supplemental oxygen or requiring FiO2 > 40%.

POCUS]
lung sliding
A Lines
no B Lines

INVESTIGATIO]
L(H)/Haim]
CBC
VBG
ABG (if NIPPV or intubation)
Note: ABG used to establish a baseline for pH, PaO2, PaCO2 before and after NIPPV or intubation. While VBG is accurate enough to guide treatment in DKA, in COPD the PCO2 does not correlate well enough, so it is recommended to use ABG initially to help guide difficult intubation decisions and a VBG to monitor therapy after.

VBG vs ABG
The approach to interpreting a VBG consists of using the VBG to estimate the corresponding arterial values, then using these estimated values for clinical decision-making exactly as if an ABG had been performed.

The central venous pH is usually 0.03 to 0.05 pH units lower than the arterial pH and the PCO2 is 4 to 5 mmHg higher, with little or no increase in serum HCO3. Mixed venous blood gives results similar to central venous blood.

The peripheral venous pH range is approximately 0.02 to 0.04 pH units lower than the arterial pH, the venous PCO2 is approximately 3 to 8 mmHg higher, and the venous serum HCO3 concentration is approximately 1 to 2 meq/L higher. The correlation between arterial and venous blood gas measurements varies with the hemodynamic stability of the patient. Not useful in severe shock or when PaCO2 > 45mmHg.

There are conflicting data regarding the correlation between arterial and venous blood gas measurements in patients with hemodynamic instability. Using PvCO2 is 100% sensitive in detecting arterial hypercarbia in COPD exacerbations using cutoff of PaCO2 45mmHg i.e. if PvCO2 is normal then PaCO2 will be normal, hypercapnia ruled out. The correlation dissociates in hypercapnia, values correlate poorly with PaCO2 >45mmHg.

This observation has two practical consequences. First, clinicians should be wary of VBG results and preferentially base clinical decisions on ABG in hypotensive patients. Second, periodic correlation of the venous measurements with arterial measurements should be performed whenever venous measurements are used for serial monitoring.

_**ABG may be necessary:_

• *i)** to accurately determine PaCO2 in severe shock
• *ii)** to accurately determine PaCO2 if hypercapnic (i.e. PvCO2 >45 mmHg) and deciding to use NIV or intubation
• *iii)** to accurately determine arterial lactate >2mEq/L (rarely necessary)

In general, ABGs rarely need to be performed unless an arterial line is in place (for arterial blood pressure monitoring and ease of blood sampling).

I]
CXR
ECG

RECIPERE]
NP/A,B]
**SpO2 88-92%
(Venturi mask, NP, face mask, non-rebreather, NIPPV)
NP/C]
PIV
NP/Mon]
SpO2

• *Note: **Indications for NIPPV** (Non-invasive positive pressure ventilation)
• *1. ALOC**
• *2. Severe dyspnea with signs of respiratory fatigue** such as increased WOB, intercostal retractions, accessory muscle use, paradoxal motion of abdomen. Persistent hypoxemia despite supplemental O2.
• *3. Acidosis – pH<7.35 (7.35-7.45)
  4. Hypercapnia – PaCO2>45mmHg (PaCO2 35-45, PvCO2 41-50)**

Note: Supplemental oxygen is a critical component of acute therapy. Because of the risk of prompting worsened hypercapnia with excess supplemental oxygen, administration of supplemental oxygen should target a pulse oxygen saturation (SpO2) of 88 to 92 percent or an arterial oxygen tension (PaO2) of approximately 60 to 70 mmHg. In two small randomized trials, titrating supplemental oxygen to SpO2 88 to 92 percent resulted in a lower mortality compared with high flow (nontitrated) oxygen.

There are numerous devices available to deliver supplemental oxygen during an exacerbation of COPD:

• Venturi masks are the preferred means of oxygen delivery because they permit a precise delivered fraction of inspired oxygen (FiO2). Venturi masks can deliver an FiO2 of 24, 28, 31, 35, 40, or 60 percent.​
• Nasal cannula can provide flow rates up to 6L per minute with an associated FiO2 of approximately 40 percent. They are more comfortable and convenient for the patient, especially during oral feedings.
• When a higher FiO2 is needed, simple facemasks can provide an FiO2 up to 55 percent using flow rates of 6 to 10 L per minute. However, variations in minute ventilation and inconsistent entrainment of room air affect the FiO2 when simple facemasks (or nasal cannula) are used.
• Non-rebreathing masks with a reservoir, one-way valves, and a tight face seal can deliver an inspired oxygen concentration up to 90 percent, but are generally not needed in this setting.

Note: Respiratory drive uses central, and peripheral chemoreceptors – carotid (CNIX) and aortic bodies (CNX).

• *Central chemoreceptors (respiratory control)**
• *Central chemoreceptors** are located on the ventrolateral medullary surface in the vicinity of the exit of the CNIX and CNX cranial nerves and are sensitive to the pH of their environment (through CO2). Central chemoreceptors detect changes in the pH of CSF (cerebral spinal fluid) from the diffusion of CO2 across the BBB (blood brain barrier). CO2 in the blood diffuses across the BBB into the CSF reacting with H2O forming H2CO3 (carbonic acid) creating H+ and HCO3- (bicarbonate) lowering the pH of the CSF and activating the CAC, VMC and RC. The activated CAC causes increased heart rate and force of contraction, VMC causes increase in blood pressure, and the activated RC causes an increase in resiratory rate and force.

Note: **A change in plasma pH alone will NOT stimulate central chemoreceptors as H+ are not able to diffuse across the blood–brain barrier into the CSF. Central chemoreceptors, in this way, are distinct from peripheral chemoreceptors.

An increase in CO2 (and decrease in pH) in the CSF causes the central chemoreceptors to activate the CAC and the pressor centre of the VMC which increases the number of impulses going to the sympathetic preganglionic neurons (T1-L2).

Vasoconstrictor impulses going to the arterioles are increased, leading to vasoconstriction of the resistance vessels and an increase in blood pressure. Venoconstriction is is also increased pushing blood back to the heart through the capacitance vessels. The extra blood volume contributes to a larger ejection fraction and increase in blood pressure.

An increase in CO2 (and decrease in pH) in the CSF causes the central chemoreceptors to send a neuronal signal activating the Inspiratory Centre (IC) of the RC. The RC increases the rate and force of inspiration.

***The overall increase in cardiac output and blood pressure, in addition to increased respiratory rate and force, work together to remove CO2 from the blood and CSF. Conversely a decrease in CO2 from hyperventilating can cause systemic vasodilation and a decrease in blood pressure leading to syncope.

Peripheral chemoreceptors reflex (respiratory control)
Peripheral chemoreceptors at the carotid bodies (CN IX) and aortic bodies (CN X) are mainly directed to the NTS and the RC through changes in PaO2 (hypoxia).

Peripheral chemoreceptors respond to changes in H+, PaCO2 and PaO2. High H+ (low pH acidosis), high CO2 (hypercapnia) and low O2 (hypoxia) stimulate these chemoreceptors. Peripheral chemoreceptors primarly respond to a reduction in oxygen tension PaO2 (hypoxia). The reduced PaO2 (hypoxia) causes the repiratory centre (RC) to increase respiratory rate and force. ​

Note: Hypoxia pulonary vasoconstriction (HPV) in the pulmonary circulation (pulmonary vasoconstriction in response to alveolar hypoxia), which likely involves the formation of reactive oxygen species, endothelin-1 (potent vasoconstrictor) or products of arachidonic acid metabolism (phospholipase A2 acting on phospholipids producing prostanoids or eicosanoids, ie. leukotrienes (LTs), prostaglandins (PGs), thromboxane (TX)).

Normal respiratory drive uses CO2 concentration and H+ in the CSF to affect CVC and RC/IC, but in conditions of high CO2 levels it is thought that a hypoxic drive occurs using O2 chemoreceptors in the aortic and carotid bodies predominately. In the hypoxic drive the body no long responds to CO2 levels at the central chemoreceptors and instead responds to O2 levels at the peripheral chemoreceptors. When there is a decrease in O2 levels the body increases the input to the RC/IC and when there is an increase in O2 levels the body will decrease the input to the RC/IC. As a result of this mechanism, high O2 levels is thought to be detrimental in COPD as it decreases RR leading to an increase in CO2 levels and further acidosis.

BUT it has been shown that in COPD the hypoxic drive is not the most important cause of CO2 retention. The CO2 retention is due to the Haldane effect and V/Q mismatch.

The Haldane effect is the result of the increased O2 in the lungs causing an increased displacement of CO2 from hemoglobin and a rising PaCO2. Hemoglobin exhibits cooperative binding. As oxygen binds to hemoglobin a conformation change occurs ehancing the binding of more oxygen. This rise in CO2 is normally excreted through increased minute ventilation (RR x TV) however those with chronic COPD cannot increase their minute ventilation. In the Aubier study, the Haldane effect accounted for 25% of the increase in PaCO2.

The other mechanism is V/Q mismatching. When oxygen within the alveoli is reduced there is vasoconstriction of pulmonary capillaries supporting that alveoli, known as hypoxic pulmonary vasoconstriction (HPV).

In the lungs, some parts are more well ventilated than others due to the destruction of the alveoli and bullae formation in COPD. COPD patients optimise their gas exchange through HPV, by decreasing the perfusion to the damaged alveoli that are not well ventilated, leading to altered alveolar ventilation-perfusion (V/Q) ratios.

Excessive oxygen administration disturbes the altered V/Q ratios established in COPD. **Poorly ventilated areas in the lungs (destroyed alveoli and bullae) now receive higher levels of oxygen leading to increased blood flow (reversal of the HPV) to poorly ventilated alveoli, and thus increased V/Q mismatch and increased physiological shunting. Essentially gas exchage does not occur and CO2 rich blood bypasses the lungs. The increase in shunted blood will then cause CO2 levels to continue to rise in the blood.

P/Org(Pulmos)]
{Ventolin} Albuterol (mainstay of treatment)
NEBS 5mg or MIDI (6 puffs) q20min x 3
{Atrovent} Ipratropium
NEBS 0.5mg or MIDI (4 puffs) x 1
THEN
Ventolin MIDI 6 puffs q1hour
Atrovent MIDI 6 puffs q4hours

P/Infla]

• *Prednisone 50mg PO x 5days (REDUCE trial)** OR
• *{Solu-Medrol} Methylprednisolone 125mg IV** OR
• *MgSO4**

P/Infect] see above
Antibacterial
{Clavulin} Amoxicillin-Clavulanate 875mg PO BID OR
{Levaquin} Levofloxacin 750mg PO/IV/OD OR
{Avalox} Moxifloxacin 400mg PO/IV/OD​

Antiviral
{Tamiflu} Oseltamivir 75 mg PO q12h

Question 21

CURB-65

and

MDR
(Multidrug Resistance Risk Factors)

Answer 21

CURB-65
5 point decision rule in oder to decide
patient can be managed as an outpatient.
ID]
Age > 65

O/E] SBP<90 RR>30
General – ALOC
INVESTIGATIO]
L(H)/Org(Nephros)] BUN>7mmol/L

CURB-65 CURB-65 >or= 2 – consider admission

Note: CURB-65 does not evaluate hypoxia which should be considered in the evaluation of the patient. The patient should be maintaining their typical O2 saturation that they receive at home, on supplementary O2.

MDR
Four point scale based on:
1. Poor functional status – significant debilitation with incontinence, inability to perform ADLs.
2. Hospitalized >2days in the past 90 days.
3. Antibiotics in past 90 days.
4. Immunosupression – ANC<1000, asplenia, hematological malignancy, predisone equivalent to >10mg daily for 2 or more weeks, congenital immunodeficiency, HIV, other immunosupression therapy.

Score;
0-1 is low risk
>or= 2 is high risk

Antibiotic Coverage (EMRAP Dec 2016)
i) Discharge
CURB-65 <2 patient can probably go home unless there is critical hypoxia.
Levofloxacin 750mg PO OD x5days

ii) Admit
CURB 65 >or=2
Levofolxacin 750mg PO/IV OD
**The decision to start oral therapy in the ER is associated with positive outcomes. Aside from critical illness, there is no proven benefit IV therapy. Shorter times to treatment and shorter hospitalizations have been found with oral antibiotics. Most PO antibiotics have similar bioavailability to the IV formulations.

iii) MDR
MDR >or= 2
Cefepime 2g IV q8h x10days - Psuedomonas
Vancomycin 1g IV BID - MRSA
{Biaxin} Clarithromycin 500mg PO q12h - Atypicals

iv) Aspiration
If parenteral therapy is required,
Pipercillin-tazobactam 4.5g IV q8h
If oral therapy is sufficient,
Amoxicillin-clavulanate 875 mg PO BID
For penicillin-allergic patients,
Clindamycin 600 mg IV q6h

Alternative agents include the combination of metronidazole 500 mg PO/IV BID plus either amoxicillin 500 mg PO BID or penicillin G (1 to 2 million units IV every 4 to 6 hours).

Question 22

Croup

Answer 22

• Failure Of Outpatient Management With Different Observation Times After Racemic Epinephrine For Croup. Smith, N., et al, Clin Pediatr 57(6):706, June 2018.

SUMMARY:
Croup occurs most commonly in children 6 months to 3yrs. Responds well to steroids (dexamethasone 0.6mg/ kg) and for moderate-to-severe croup, racemic epinephrine (RE). About 2% of cases will require admission.

Traditionally, teaching has been that if RE is given patients need an observation time >2 hours to monitor for rebound reactions after RE has worn off. However, not much data exists to characterize this concern. This study investigated whether patients became worse after initial improvement with RE in the setting of steroid treatment. The key outcome of interest was successful discharge – meaning the patient did not need another round of RE and was able to go home and not bounceback to that ED within 24 hours.

Patients were grouped into observation for 2-3 hours post-RE treatment vs those observed more than 3-4 hours post-RE treatment. Ultimately, they found 299 cases over 2 years: 163 in the < 3 hours group and 136 in the >3 hours group. 16% of the 2-3 hour group had treatment failure while only 7% of the 3-4 hour group had treatment failure. 90 patients were observed for < 2 hours and none of them bounced back.

EDITOR’S COMMENTARY: This was retrospective chart review study looking at treatment failure after RE in patients with croup who also received steroids. The group found 16% of patients observed for 2-3 hours had treatment failure, while 7% of those observed for 3-4 hours had treatment failure. Interestingly, of all 90 patients observed for < 2 hours, there were no bouncebacks. So this study tends to argue that the bounceback rate following RE in the era of dexamethasone is very low and about equal whether the patient was observed < 2, 2-3 or 3-4 hours. This is what is consistent with the rest of the literature and supports discharge after 2 hours.

Etiology]
Croup is a respiratory illness characterized by inspiratory stridor, cough and hoarseness, and is more specifically called laryngotracheitis. Laryngotracheitis (croup) refers to inflammation of the larynx and trachea. Although lower airway signs are absent, the typical barking cough will be present. Spasmodic croup is characterized by the sudden onset of inspiratory stridor at night, short duration (several hours), and sudden cessation. This is often in the setting of a mild upper respiratory infection, but without fever or inflammation. A striking feature of spasmodic croup is its recurrent nature, hence the alternate descriptive term, “frequently recurrent croup.”

The symptoms result from inflammation (dolar, tumor, rubor, calor) in the larynx and subglottic airway. A barking cough is the hallmark of croup among infants and young children, whereas hoarseness predominates in older children and adults. Although croup usually is a mild and self-limited illness, significant upper airway obstruction, respiratory distress, and, rarely, death, can occur.

Parainfluenza virus type 1 is the most common cause of acute laryngotracheitis, especially the fall and winter epidemics. Respiratory syncytial virus (RSV) and adenoviruses are relatively frequent causes of croup. The laryngotracheal component of disease is usually less significant than that of the lower airways such as in bronchiolitis. Rhinoviruses, enteroviruses (especially Coxsackie types A9, B4, and B5, and echovirus types 4, 11, and 21), and herpes simplex virus are occasional causes of sporadic cases of croup that are usually mild. Croup was once deadly and caused by the diphtheria bacteria. Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae the bacteria part of the vaccination DTaP-IPV-Hib: Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenzae type b.

The anatomic hallmark of croup is narrowing of the subglottic airway, the portion of the larynx immediately below the vocal folds. The cricoid cartilage of the subglottis is a complete cartilaginous ring, unlike the tracheal rings which are horseshoe shaped. Because it is a complete ring, the cricoid cannot expand, causing significant airway narrowing whenever the subglottic mucosa becomes inflamed.

ID]
male 1.4: female 1
6 months to 3 years

HPI]
Fall or early winter, with the major incidence peaks coinciding with parainfluenza type 1 activity (often in October) and minor peaks occurring during periods of respiratory syncytial virus or influenza virus activity.

In mild cases, the child is hoarse and has nasal congestion. There is minimal, if any, pharyngitis. As airway obstruction progresses, stridor develops, and there may be mild tachypnea with a prolonged inspiratory phase. The presence of stridor is a key element in the assessment of severity. Biphasic stridor (stridor heard on both inspiration and expiration) at rest is a sign of significant upper airway obstruction. As upper airway obstruction progresses, the child may become restless or anxious.

O/E] TC (mod-sev) SpO2 <90% (sev), afebrile suggestive of spasmatic croup
General – ALOC (if severe)
Pulmos – WOB (head bobbing, nasal flaring, retractions, paradoxal abdominal breathing)

• Westley Croup score calculator*
• *color** (normal, dusky, cyanotic, cyanotic on O2)
• *stridor** (none, mild, moderate, severe/obstructed)
• *retractions** (none, mild, moderate, severe)
• *air movement** (normal, mild decreasesed, moderate decreased, marked decreased)

Note: Inspiratory stridor suggests supraglottic (above vocal cords) obstruction, biphasic stridor suggests subglottic obstruction (just below vocal cords, ex. croup), expiratory stridor suggest tracheal obstruction.

Note: Retractions are visible indrawing on the muscles (and overlying skin) of the abdomen due to breathing in against an obstruction. Suprasternal (tracheal tug), intercostal, substernal, subcostal.

RECIPERE]
NP/A,B]
O2 to maintain SpO2>92%
(humidified not proven to provide any clear benefit, Heliox insufficient evidence)
BMV – ALOC, persistent severe hypoxemia despite O2 administration, inadequate ventilation

NP/C]
PIV/IO

NP/Mon]
SpO2, HR, BP

P/Infla]
{Decadron} Dexamethasone 0.6 mg/kg PO/IV/IO/IM (mild, moderate or severe)
AND
Racemic epinephrine 0.5mL (2.25% solution) in 2mL NS NEBS
OR
L-isomer epinephrine 5mL of (1:1000) in 5mL NS NEBS

Note: Currently literature supports monitoring for at least 2 hours before discharge.

Question 23

Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

Answer 23

• Guidelines For The Diagnosis And Management Of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) In Critically Ill Patients (Part II): Society Of Critical Care Medicine (SCCM) And European Society Of Intensive Care Medicine (ESICM) 2017 Pastores, S.M., et al, Intens Care Med 44(4):474, April 2018

SUMMARY: Recently there was a large meta-analysis we covered that showed a slight benefit (length of stay and respiratory failure) using corticosteroids in the treatment of community acquired pneumonia. However, there was no change in mortality, there were higher readmission rates and a greater incidence of hyperglycemia. The meta-analysis above used 6 high-quality RCT’s to come up with their conclusion of no mortality benefit.

The current paper uses all studies worldwide including numerous small studies with flawed methods to come up with guidelines issued here by the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM). They recommend use of corticosteroids for CAP, no steroids for use with influenza and use steroids in bacterial meningitis.

The literature across the good and bad quality studies tends to show that steroids are associated with shorter duration of mechanical ventilation and shorter LOS, but higher readmission and incidences of hyperglycemia.

EDITOR’S COMMENTARY: The recommendations in this paper are to give corticosteroids in CAP despite a high-quality meta-analysis demonstrating no mortality benefit, greater hospital readmissions and increased incidence of hyperglycemia. This is a very controversial topic and I would expect better evidence before changing practice or issuing this type of recommendation. Other authors suggest only giving adjunctive steroids in severe cases of CAP (> 50% FIO2 requirement etc.) There is no evidence addressing the timing of steroids in CAP and certainly no evidence suggesting it should be done in the ED. The authors note there are 5 RCTs addressing this issue right now – so hopefully we can get some higher quality evidence to confirm or refute these recommendations in the coming couple years.

Question 24

CVA

Answer 24

• Tenecteplase Versus Alteplase For Management Of Acute Ischaemic Stroke (NOR-test): A Phase 3, Randomised, Open-label, Blinded Endpoint Trial Logallo, N., et al, Lancet Neurol 16(10):781, October 2017

CONCLUSIONS: Tenecteplase was not superior to alteplase in patients undergoing IV thrombolysis for acute ischemic stroke. The safety profile of the two agents was similar.

EDITOR’S COMMENTARY: This paper evaluated tenecteplase vs. alteplase for acute ischemic stroke in a randomized, blinded, superiority trial (phase III). Tenecteplase is the newer thrombolytic with some putative advantages and this comparison was made in 13 stroke units across Norway. The bottom line is that tenecteplase was not better than alteplase when they compared it in 1100 stroke patients with an average age of 77 years and a median NIHSS of 4 (mild stroke). Serious adverse events were similar in both groups and included an intracranial hemorrhage rate of 9% (2-3% symptomatic) and a background rate of angioedema of 1%.

• Tenecteplase Versus Alteplase Before Thrombectomy For Ischemic Stroke Campbell, B.C.V., et al, N Engl J Med 378(17):1573, April 26, 2018

SUMMARY: The was a prospective randomized control trial of 204 patients with ischemic stroke due to large vessel occlusion who were eligible to undergo both thrombolysis (<4.5 hours symptom onset) and thrombectomy at 13 centers across Australia and NZ. Patients were also randomized by vessel involvement (ICA, basilar A, first segment of middle cerebral A or second segment of middle cerebral A).

One group of patients received tenecteplase “TNK” (0.25 mg/kg) while the other got alteplase “TPA” (0.9mg/ kg). The potential benefits of TNK are that it is given over a one minute injection rather than a one hour infusion and it is genetically engineered to be more specific for thrombin.

Primary outcome was restoration of 50% of involved territory or no retrievable clot seen when they went for thrombectomy. Secondary outcomes were modified Rankin score at 90 days and early neurologic improvement. The study was designed without a primary outcome related to patient clinical outcome because the authors believed patients in both arms would likely do the same as all received thrombectomy in the end.

Primary outcome (reperfusion of >50% or no more clot) was met in 22% of the tenecteplase group vs. 10% of the alteplase group. Interestingly, in patients who were transferred to another hospital there was no difference in time to arterial puncture for thrombectomy across the groups.

Score on modified a Rankin scale at 90 days was 2 for the tenecteplase group vs 3 for the alteplase group. Patients functionally independent at 90 days and those with early neurologic recovery were the same between groups. The incidence of intracranial hemorrhage was the same in each group (1 patient). While death was more common in patients receiving alteplase (18 vs. 10), it was not significantly different.

EDITOR’S COMMENTARY: In sum, in this was a small randomized control trial of strokes patients from CT proven large vessel of occlusions, that showed TNK was superior TPA in terms of improving clot burden at the time of thrombectomy. Larger studies with more mild strokes and stroke mimics still need to be done to show non-inferiority compared with TPA. Currently there is a proposal from Genentech to study TPA vs. TNK in patients being transferred for thrombectomy. **The hypothesis is that the one-minute injection will make it easier to transport than the one-hour infusion allowing more patients to get to a comprehensive stroke center faster. At this moment in time there is not sufficient evidence to use TNK in clinical practice, but this is definitely a topic of significant interest in the stroke literature. In a few years TNK will likely be the preferred intravenous thrombolytic agent.

• Effect Of Alteplase vs Aspirin On Functional Outcome For Patients With Acute Ischemic Stroke And Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial Khatri, P., et al, JAMA 320(2):156, July 10, 2018.

SUMMARY: Guidelines have been generally vague on what to do with people having low NIHSS scores (0-5). Literature shows that 20-30% of these people have significant disability at 90 days.

More and more of these strokes with low NIHSS scores are being given TPA even though the evidence base is not strong. This paper asked the question if giving alteplase versus aspirin improves functional outcomes in patients with mild stroke (NIHSS 0-5) judged “not clearly disabling” by the treating physician.

Patients were randomized to receive either IV alteplase at standard dosing or 325 mg aspirin or the corresponding placebos. The primary outcome was a modified Rankin Scale (mRS) of 0-1 at 90 days (minimal disability).

This study was terminated early due to slow enrollment and the sponsoring drug company pulling the drug. They enrolled 313 patients over 2.5 years, the mean NIHSS score was 2. 78.2% of the alteplase group had a good neurologic outcome compared with 81.5% of the aspirin group (not significant). Five patients in the alteplase (3.3%) developed a symptomatic ICH within 36 hours (compared with 0 in the aspirin group). Serious adverse events occurred 26% in the alteplase group compared with 13% in the aspirin group.

Because of under-powering and stopping early – the authors conducted a Bayesian analysis that demonstrated there was < 25% chance that alteplase could offer any benefit and less than 2% chance that the benefit would be at least 6% (which was what the study was powered to detect).

EDITOR’S COMMENTARY: This was a randomized clinical trial of 313 patients looking at TPA vs ASA in mild stroke cases. They found no significant difference in neurological outcomes and serious adverse effects occurred 26% in the alteplase group, which included ICH. Basically, this is a big fat negative study – with fair evidence that alteplase will harm people with mild stroke. A couple important points: 1) Even a patient with low NIHSS score may be ‘disabled’ for example with severe aphasia – and they may not have been included in this study (at least potentially), so your stroke teams may push for TPA in that case (dangerous!), 2) For these seemingly mild strokes about 20% have a mRS ≥2 indicating a level of disability that is problematic – unfortunately TPA just doesn’t help reduce the number. Basically, this is a big fat negative study with fair evidence that TPA will harm people with mild stroke.

Question 25

Diverticulitis

Answer 25

• A Systematic Review And Meta-Analysis Of Outpatient Treatment For Acute Diverticulitis Van Dijk, S.T., et al, Internat J Colorectal Dis 33(5):505, May 2018

SUMMARY: About two-thirds of diverticulitis cases are uncomplicated (no abscess, no perforation, no sepsis) and are therefore safe for outpatient treatment. There is even some evidence that antibiotics are unnecessary for uncomplicated diverticulitis. In this study, the authors conducted a meta-analysis to estimate the risks associated with outpatient treatment of uncomplicated diverticulitis.

The meta-analysis used 19 studies involving 2,303 patients - almost all studies were observational, one was a RCT. Seventeen of the studies used antibiotics (the majority oral antibiotics) and 2 studies used no antibiotics. Outcomes were 1) Readmission, 2) Need for emergency surgery or percutaneous abscess drainage and 3) costs.

In terms of readmission roughly 7% of people were readmitted – most commonly due to PO intolerance or pain. In the only study that made a reasonable attempt to compare readmission rates between cases initially managed outpatient vs. those initially managed as inpatient, the bounceback rate was similar (5%).

Only 2 patients (0.2%) ended up requiring emergency surgery following outpatient management. An additional 2 patients ultimately require percutaneous drainage; no one died. Costs were lower with outpatient management.

EDITOR’S COMMENTARY: This was a meta-analysis that looked at the safety of treating uncomplicated diverticulitis in the outpatient setting. They found that ~7% of patients were readmitted, namely due to PO intolerance or pain. They also found a very low rate (~0.2%) of required emergency surgery or percutaneous drainage for failed outpatient management. Both inpatient and outpatient management had similar bounceback rates. **Basically, this affirms that patients who are not severely immunocompromised and who are tolerating oral hydration and pain can be safely treated as outpatients with minimal risk for something terrible. Patients being sent home should probably be told that there’s a one in 20 chance of worsening pain, etc, and be encouraged to come back if that occurs.

Dx] Imaging CT
The diagnosis of acute diverticulitis should be suspected in a patient with lower abdominal pain and abdominal tenderness on physical examination. The pain is usually in the left lower quadrant in Western populations but may be suprapubic or in the right lower quadrant, particularly in Asians. Laboratory findings of leukocytosis, while not sensitive or specific for acute diverticulitis, can support the diagnosis. Imaging (preferably computed tomography [CT] scan) is required to establish the diagnosis of acute diverticulitis.

CT scan with oral and intravenous (IV) contrast to establish the diagnosis of acute diverticulitis has a high sensitivity and specificity for acute diverticulitis and can exclude other causes of abdominal pain.

Pathophysiology
A diverticulum is a sac-like protrusion of the colonic wall. Diverticula are actually micro-hernias of the colonic mucosa and submucosa through the colonic muscular layer where blood vessels penetrate it.

In North America and Europe the abdominal pain is usually on the left lower side, while in Asia it is usually on the right. Left sided diverticula are actually pseudodiverticula (does not include the muscularis propria or adventitia) since the herniation is not through all the layers of the colon; right-sided diverticula are true diverticula, including all layers (including the muscularis propria and adventitia).

Diverticulosis is defined by the presence of diverticula and may be asymptomatic or symptomatic. Diverticular bleeding is characterized by painless hematochezia due to segmental weakness of the vasa recta (strait arteries coming off the mesentary) associated with a diverticulum.​

Diverticulitis is defined as inflammation of a diverticulum. Diverticulitis may be acute or chronic, uncomplicated or complicated by a diverticular abscess, fistula, bowel obstruction, or free perforation.

Risk factors

Question 26

DKA

Answer 26

Diagnostic Criteria
A consensus statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2014 defined the following biochemical criteria for the diagnosis of DKA:

L(H)/Haim]
pH<7.3 (7.35-7.45)
L(H)/Meta]
HCO3<15 (22-28)
hyperglycemia BG>11
ketonemia (or ketouria)

Note: The severity of DKA can be categorized according to the degree of acidosis as:
mild – pH<7.3 and/or HCO3<15
moderate – pH<7.2 and/or HCO3<10
severe – pH<7.1 and/or HCO3<5
Note: K may be low from osmotic diuresis or high form acidosis (acidosis drives K out of cells).

Etiology]
Insulin deficiency and the body cannot use glucose so it converts free fatty acids to energy. Byproducts are ketones such as acetone (gas that makes breath fruity), acetoacetic acid, beta-hydroxybutyric acid (keto acids). Acetoacetic acid and beta-hydroxybutric acid lose a proton leaving behind the conjugate base, which accounts for the anion gap metabolic acidosis.

Body’s response to the stress is to incease adrenergic response leading to increased cortisol (glucocorticoid), gluconeogenesis and a further increase in hyperglycemia. The hyperglycemia creates an osmotic effect causing dehydration.

Acidosis in the blood causes the cells to uptake H+ ions to compensate and release K+ ions. Along with the diuresis and K+ exchange, there is a whole body K+ depletion and initially hyperkalemia and then hypokalemia.

HPI]
vomiting, polydipsia, polyuria, fatigue, fever, precipitating event such as infection – strep throat, viral symptoms, gastroenteritis, appendicitis

O/E] TP
Note:Kussmaul breathing is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis (DKA) but also kidney failure. It is a form of hyperventilation, which is any breathing pattern that reduces carbon dioxide in the blood due to increased rate or depth of respiration.

Kussmaul is respiratory compensation for a metabolic acidosis, most commonly occurring in diabetics in diabetic ketoacidosis. Blood gases of a patient with Kussmaul breathing will show a low partial pressure of CO2 in conjunction with low bicarbonate because of a forced increased respiration (blowing off the carbon dioxide). Base excess is severely negative. The patient feels an urge to breathe deeply, an “air hunger”, and it appears almost involuntary.

Note: In peds there is tachypnea WITHOUT indrawing which separates DKA from respiratory tachypnea.
Pulmos – clear chest
Abdos – soft, tender

INVESTIGATIO]
L(H)/Haim]
VBG (pH)

L(H)/Meta]
SMA7 (K+, Na+, Cl-, HCO3-, BG, Cr, Urea)
X-Lytes (Mg2+, PO4-), bHCG, TSH
Note: Anion gap

L(O)]
Urinanalysis (ketones)
L(O)/Meta]
bHCG

I]
ECG, CXR

RECIPERE] (Hurry up and wait)

• Fluids (correct hypovolemia)
• K replacement
• Insulin

NP/C]
2PIV
1L NS Bolus wide open THEN
NS 500mL/hr q1h x4 (Add K if necessary) THEN
NS 250mL/hr q1h x4
Note: In Peds fluid resusitation is NOT as aggressive as in adults. NS fluid resusitation will be gradual. NO bolus unless in shock 70+ (age x 2), small bolus used 5-10mL/kg IF AT ALL.

NP/Mon]
Cardiac monitoring if hypo/hyperkalemia

P/Meta]
IF K>5.0
Insulin infusion 0.1U/kg/hr, stop when BG<15

IF K>3.5 and <5.0
20mEq PO (K-Dur) x1 THEN
20mEq KCl/L at 500mL/hr (10mEq/hr) infusion AND
Insulin infusion 0.1U/kg/hr, stop when BG<15

IF K<3.5
Hold insulin drip for 30min.
40mEq PO (K-Dur) x1 AND
40mEq KCl/L at 500mL/hr (20mEq/hr) infusion until K>3.3 THEN Insulin infusion 0.1U/kg/hr, stop when BG<15

Repeat SMA7 q1hr and VBG q2h.
After 1.5 hour if AG >25 then consider ICU. If AG<25 continue treatment. Switch to SQ insulin when BG<15.

Peds
K+ replacement is not as rigid as in adults.
Mild DKA (pH<7.3, HCO3<15) – Replace fluids PO and administer insulin SQ. Treat as outpatient unless age<5 then treat as inpatient.

Moderate DKA (pH<7.2, HCO3<10)
SLOW and STEADY replacement of fluids NS over 48h. Do not exceed twice the maintenance dose of fluid replacement. DELAY in starting insulin, 1-2 hour of of NS until insulin started.
Insulin 0.1U/kg/hr. Add 40mEq KCl/L into the NS at the time of starting insulin unless K>5.5.

Severe DKA (pH<7.1, HCO3<5)
May be presenting with cerebral edema – ALOC (GCS<14), abnormal neurological exam. Red flags if <5, new onset DKA, present later in DKA. DONT BOLUS (may precipitate cerebral edema). Look for fluid replacement guidelines. Contact ICU or eqivalent.

If signs of cerebral edema in ANY patient:

Elevate head of the bed 30 degrees

Mannitol 0.5-1g/kg IV over 20min AND/OR

Hypertonic (3%) NaCl 5-10cc/kg IV over 30min

Question 27

Eicosanoids (PGs, LTs) and Drugs

Answer 27

Arachidonic acid (AA) is esterified in the phospholipid membrane. Phospholipase C/A2 cleaves off the arachidonic acid. COX and LOX enzymes use the AA substrate to produce eicosanoids (eikosi, greek for 20). LOX produces leukotrienes (LT) and lipotoxins (LX), COX produces prostanoids – prostaglandins PGD2, PGE1 (alprostadil), PGE2 (dinoprostone), PGF2alpha (dinoprost), PGI2 (prostacyclin) and TXA (thromboxane). In inflammation, eicosanoids (PGs, LTs) are involved in vasodilation and chemoattraction.

PGH synthase-1 (COX-1) is expressed constitutively in most cells. In contrast, PGH synthase-2 (COX-2) is more readily inducible, its expression varies depending on the stimulus.

COX-1 generates prostanoids for “housekeeping” functions, such as gastric epithelial cytoprotection, whereas COX-2 is the major source of prostanoids in inflammation and cancer. This distinction is overly simplistic. There are both physiologic and pathophysiologic processes in which each enzyme is uniquely involved and others in which they function coordinately.

COX-2 is an immediate early-response gene product that is markedly up-regulated by shear stress, growth factors, tumor promoters, and cytokines. COX-2 expression is induced by the cytokines interleukin (IL)-1, IL-2, and TNFalpha, as well as by lipopolysaccharide (LPS) produced by Gram-negative bacteria.

• *COX-1**
• *i) Lungs** – bronchodilation.
• *PGI2 (prostacyclin)** binds to IPR on bronchiole smooth muscle to cause bronchodilation. PGI2 (prostacycin) production in lung endothelial cells (EC) is critical in maintaining vasodilation in the pulmonary microcirculation. ​PEG2 (dinoprostone) binds to EP2R on bronchiole smooth muscle to cause bronchodilation. PGF2alpha (dinoprost) binds to the FPR on bronchiolie smooth muscle to cause bronchoconstriction.

Cells cultured from aspirin-sensitive or control human donors contained similar levels of COX-1 and COX-2 immunoreactivity. COX activity in cells from aspirin-sensitive or tolerant patients was inhibited by aspirin which blocks COX-1 selectively, but not by rofecoxib, which is a selective inhibitor of COX-2. These observations show that despite the presence of COX-2, COX-1 is functionally predominant in the airways and explains clinical observations relating to drug specificity in patients with aspirin-sensitive asthma.​

Note: ASA and NSAID induced asthma works on the inhibtion of COX-1 and subsequently PGI2 (prostacyclin) and PEG2 (dinoprostone) production leading to bronchoconstriction (through the absence of brochnodilation). Epoprostenol is also known as PGI2 (prostacyclin) is used in pulmonary arterial hypertension (PAH) due to its vasodiatory effects.

ii) Stomach – protects gastric mucosa, decreasing gastric acid secretion and increasing gastric mucous secretion.
In the gastric mucosa PGI2 (prostacyclin) and PGE2 (dinoprostone) are produced by the action of the COX-1. Several prostanoids, especially PGI2 (prostacyclin) and PGE2 (dinoprostone), are crucial to protect the gastric mucosa from the erosive effects of stomach acid, as well as to maintain the naturally healthy condition of the gastric mucosa. PGE2 (dinoprostone) binds to EP3R to decrease gastric acid secretion and increase gastric mucus secretion.

Longitudinal muscle is contracted by PGE2 (dinoprostone) by binding to EP3R on smooth muscle. Circular muscle is contracted weakly by PGI2 (prostacyclin) by binding to the IPR on smooth muscle, and is relaxed by PGE2 (dinoprostone) by binding to the EP4R on smooth muscle.

iii) Endothelial Cells (ECs) – constitutive vasodilation.
In vitro studies consistently demonstrate that EC cultured under static conditions express COX-1. COX-1 is expressed under basal conditions and was not influenced by the shear stress (unlike COX-2 which is influenced by sheer stress).

PGI2 (prostacyclin) is the main product from arachodonic acid (AA) in vascular endothelial cells. PGI2 (prostacycin) synthesis is greatest in the intima and decreases progressively toward the adventitia. Among cultured vascular cells, ECs are the most active PGI2 (prostacycin) producers. PGI2 (prostacyclin) synthesis takes place in highly vascularized organs such as the lung, kidney, uterus, testis, stomach, and spleen. PGI2 (prostacycin) production in lung ECs is critical in maintaining vasodilation in the pulmonary microcirculation.

Note: Epoprostenol is also known as PGI2 (prostacyclin) is used in pulmonary arterial hypertension (PAH) due to its vasodiatory effects.

• *iv) Platelets** – aggregation.
• *TXA2 (thromboxane)** is the major product of COX-1, the only COX isoform expressed in mature platelets. TXA (thromboxane) binds to TPR on platelets to activate the integrin GPIIb-IIIa to a high affinity state allowing fibrin to create crossbridges and platelte aggregation.
• *v) Kidney** – hemodynamics (volume retracted vasodilation).
• *COX-1** is found in the afferent arteriole endothelial cells, glomerular mesangial cells, parietal cells of Bowman’s capsule, and in the collecting ducts (medulla and cortical) ensuring the maintenance of the kidney’s physiological functions, such as hemodynamic regulation and glomerular filtration rate (GFR).

COX-1 which is responsible for physiological functions, is expressed mainly as a constitutive isoform and, in normal conditions is responsible for vasodilation ensuring adequate blood flow. COX-1 produces predominately PGE2 (dinoprostone), where PGI2 (prostacyclin) is COX-2 dependant (opposite of endothelial cells).

COX-1 levels do not appear to be dynamically activated. The factors affecting the tissue specific expression of COX-1 are uncertain.

• *COX-2**
• *i) Lungs** – ?

ii) Stomach – ?

iii) Endothelial Cells (EC) -- induced vasodilation by sheer stress.
COX-2 produces PGI2 (prostacycin)in theECswhich binds toIPRon smooth muscle andcauses vasodilation,in addition to inhibiting platelets.COX-2protein expressionis induced (not under basal conditions)inECs by avascular lesion causing sheer stress,and inmacrophagesandmonocytesduring acute andchronic inflammatory states.

Although endothelial cells do not express COX-2 under basal conditions, several factors promote its expression and activity including endogenous IL1, IL2, TNF, TXA (thromboxane), LDL, HDL, hypoxia (metabolic theory of blood flow), and sheer stress.

COX-2 can be induced in normal endothelium by the application of shear stress. COX-2 has also been found in the endothelium overlying atherosclerotic lesions.

Note: COX-2 inhibitors (NSAIDS, and COX-2 inhibitors) cause an increase in heart attacks and strokes, due to the decreased affect of PGI2 vasodilation and platelet inhibition at the sites of arthrosclerosis and throbosis.

iv) Kidney – volume depleted states (ie. hypotension) by the cortex, and volume expansion states (hypertension) by the medulla.

COX-2 be found in endothelium, arteriolar smooth muscle cells, cortical thick ascending limb of the Henle loop, macula densa, medulla interstitial cells, and vasa recta (efferent arteriole intertwines and supples the entire nephron with a venous return to the interlobular vein, eventually back to the renal vein), and podocytes.

COX-2 expression in the kidney is regulated by both physiologic and pathophysiologic perturbations, with effective volume depletion (and salt depletion) upregulating cortex and macula densa COX-2 expression, and effective volume expansion (and salt loading) upregulating medullary interstitial COX-2 expression.

In volume contracted states (hypotension, heart failure, fursomide), prostaglandin PGE2 (dinoprostone) signal is sent from the macula densa to the juxtaglomerular cells (afferent areteriole smoooth muscles cells around the endothelial cells) for renin seretion. PGE2 (dinoprostone) released from the macula densa transverses and binds to the EP4R on the juxtaglomerular cells (afferent areteriole smoooth muscles cells around the endothelial cells) releasing renin. PGE2 (dinoprostone) also binds to the EP4R on the afferent arteriole smooth muscle which decreases the tone of the afferent arteriole smooth muscle causing vasodilation.

Osmoreceptors swelling in the macula densa responds to a decrease in Cl- concentation (ex. from low Cl- by hypotension or furosemide). Macula densa sensing of luminal Cl- concentration is mediated by the luminal Na+/K+/2Cl- cotransporter, NKCC2 (furosemide inhibits the NKCC2 co-transporter). Loop diuretics, which inhibit NKCC2 in the ascending loop of Henle, increase renin activity, even in the absence of volume depletion.

The increased cortical COX-2 expression seen with HCTZ, amiloride, or spironolactone presumably results from systemic volume depletion, also decresing the Cl- the osmoreceptors at the macula densa.

PGE2 (dinoprostone) contributes to sodium balance and blood pressure control in two ways:

i) Inhibition of the Na+-K+-2Cl- cotransporter type 2 (NKCC2) and decreased reabsorption at the thick ascending loop of Henle, causing a diuretic effect.
Note: NKCC2 is the same cotransporter that furosemide inhibits.
ii) ADH antagonism at the cortical collecting duct, decreasing H2O reabsorption.

PGI2 (prostacyclin) is increased in juxtaglomerular cells afferent smooth muscle cells from the activation of COX-2 as a result of baroreceptors in afferent arteriole under conditions associated with decreased actual or effective circulating volume (ECV). PGI2 (prostacyclin) binds to IPR relaxeing afferent smooth muscle cells causing vasodilation and increased blood flow. The vasodilatory effect of PGI2 (prostacycin) increases renal blood flow and glomerular filtration rate (GFR). Renin is also secreted due to the baroreceptor effect from juxtaglomerular cells and activates the renin-angiotensin system, ultimately resulting in increased secretion of aldosterone.
The renal medulla is a rich source of COX-2, with the greatest concentrations in the medullary interstitial cells. Prostaglandin PGE2 (dinoprostone) signal is sent from the renal medullary (COX-2) osmoreceptors shrinking in response to an increase in concentation (ex. from systemic salt loading) in the interstitium. Renal medullary PGE2 (dinoprostone) functions as an important natriuretic mediator that is activated by systemic salt loading, promoting Na+ excretion,and contributing to maintenance ofsodium balance and blood pressure.

Note: NSAIDs raise blood pressure through the inhibition COX2 and PGE2 production in the medulla interstitial cells, thereby decreasing natriuresis, through decreased inhibition of NKCC, and decreasing diuresis, through decreased antagonism of ADH. NSAIDS cause kidney injury in volume contracted states through inhibition of COX2 and PGE2 in the macula densa, in addition the PGI2 in the afferent endothelium, thereby decreasing the perfusion to the afferent vasodilation and vasa recta to the nephron), and decreasing renin secretion.

Note: Hypotension causing a volume depleted state and renal insufficiency, also typically causes low Na+/Cl- to the macula densa.

• *COX1 and COX2**
• *Uterus/Cervix/Penis** – contractions, menstration, cervical ripening, vasodilation

PGI2 (prostacyclin) binds to IPR and causes vasodilation and inhibits platelet aggregation.

PGE2 (dinoprostone) binds to the EP1R, EP2R, EP3R, EP4R. EP1R and EP3R are more likely to cause smooth muscle contraction such as in the uterus, where EP2R and EP4R are more likely to cause smooth muscle relaxation such as in the cervix.

PGE1 (alprostadil) binds to EP1-4R, which has varying effects from vasodilation in men for penile erections, to uterine contractions and cervical ripening in women (misolprostol). In babies with congential heart defects, alprostadil can keep the ductus arteriosos open until surgery, likely through the vasodilation effect on smooth muscle.

PGF2alpha (dinoprost) binds to the FPR and causes uterine contractions, in addition to platelet aggregation and vasoconstriction (such as in the endometrium). PGF2alpha is increased after progesterone withdrawal and starts the menstrual cycle.

Drugs
Epoprostenolis also known asPGI2 (prostacyclin)is a strongvasodilator of all vascular beds. In addition, it is a potent endogenousinhibitor of platelet aggregation.The reduction in platelet aggregation results from epoprostenol’sactivationof intracellularadenylate cyclaseand the resultantincrease in cAMPconcentrations within the platelets. Medical use in controllingpulmonary arterial hypertension (PAH).

Dinoprostone (PGE2) {Cervidil} is an endogenous hormone found in low concentrations in most tissues of the body. When administered as an abortifacient (tablet), it stimulates uterine contractions similar to those seen during natural labor. When administered for labor induction (vaginal gel), it relaxes the smooth muscle of the cervix allowing dilation and passage of the fetus through the birth canal.

Carboprost {Hemabate} is an analog of naturally occurring PGF2alpha (dinoprost). Carboprost stimulates uterine contractility which usually results in expulsion of the products of conception and is used to induce abortion between 13-20 weeks of pregnancy. When used postpartum, hemostasis at the placentation site is achieved through endomentrial thrombosis and myometrial contractions.

Alprostadil (PGE1), which binds to the E1-E4R. Aprostadil {Muse} is the naturlly occuring prostaglandin used in erectile dysfunction as a intracavernous injection or intraurethral pill, that in this setting primarily acts as a vasodilator. Misoprostol is an orally active synthetic analog of alprostadil. Misoprostol is used as an abortifactant and for PUD. The FDA-approved indication is for prevention of NSAID-induced peptic ulcers and as an abortifacient. PGE1 decreases gastric acid secretion, and increases mucous and bicarbonate secreation. In the uterus, binding to E1 and E3 causes uterine contractions, and binding to E4 casues cervix ripening.

Question 28

Epistaxis

Answer 28

Topical Tranexamic Acid Compared With Anterior Nasal Packing For Treatment Of Epistaxis In Patients Taking Antiplatelet Drugs: Randomized Controlled Trial Zahed, R., et al, Acad Emerg Med Epub ahead of print, November 10, 2017
CONCLUSIONS: Topical application of the injectable form of tranexamic acid appears to be safe and effective in patients with anterior epistaxis in the setting of antiplatelet therapy.
EDITOR’S COMMENTARY: These Iranian authors performed an RCT of a TXA vs. anterior packing approach in patients with epistaxis taking antiplatelet medications. They enrolled 62 patients into each treatment arm and they found that the TXA group had improved complete bleeding control at 10 minutes when compared to the nasal packing group (73% vs. 29%). The TXA group also had lower rates of rebleed at 24 hours and 7 days and higher rates of patient satisfaction in this study.

Question 29

NSAIDS

Kidney

Answer 29

In the kidney, COXs are locally produced at many sites, including glomerular and vascular endothelium, the medullary and cortical collecting tubules, and medullary interstitial cells. COX-1 is expressed ubiquitously in most tissues, while COX-2 expression is low at basal levels, but increases with stimulation in the setting of acute or chronic inflammation and other physiologic challenges. The tubules predominantly synthesize PGE2, while the glomeruli synthesize both PGE2 and PGI2.

Renal PGs are primarily vasodilators in the kidneys. Under basal conditions, PGs have no significant role in the regulation of renal perfusion. However, in the setting of hypotension and reduced renal perfusion from vasoconstriction stimulated by angiotensin II, norepinephrine, vasopressin, or endothelin, PG synthesis is increased to maintain renal perfusion and minimize ischemia.

In addition to modulating renal hemodynamics, PGs also increase renin secretion, antagonize ADH, and enhance sodium excretion.

COX1 – Glomerulus, mesangial cells, collecting duct, medullary interstitial cells – PGI2, PGE2 – hemodynamic regulation under physiologic conditions.

COX2 – Glomerulus, macula densa, thick ascending limb, medullary institial cells – PGE2, PGI2 – dominant contributor to Na+, Cl- (natriuresis) and water (diuresis) homeostasis under physiological conditions.

Note: Under normal physiologic conditions the functions of the COX isoforms overlap.

• *PGI2 (mainly vascular)** – regulate renal vascular tone
• *PGE2 (mainly tubular)** – promotes natriuresis (sodium excretion) and diuresis (water excretion) and renin release.

1. Secretion of renin – NaCl sensors in the macula densa detect low NaCl concentration. COX2 is activated and produces PGE2 which translocates to the juxtaglomerular cells surronding the afferent arteriole and binds to EP4 causing release of renin.
2. Natriuresis - Inhibits Na+ reabsorption in the thick ascending limb and cortical collecting tubule (mostly COX2, PGE2) – ie. enhances Na+ excretion.
3. Diuresis – Partially antagonize ADH (mostly COX2 from medullary interstitial cells)

• *Hyperkalema**
  1. Decreased secretion of renin and impaired angiotensin II aldosterone release (COX2, PGE2).
• *Edema**
  1. Sodium retention - no longer promotes Na+ excretion (COX2, PGE2).
  2. ADH water retention - no longer antagonizes ADH (mostly COX2, PGE2).
• *Hyponatremia**
  1. ADH and water retention - no longer antagonizes ADH (mostly COX2, PGE2).
• *Hypertension**
  1. Sodium retention (COX2, PGE2).
  2. ADH and water retention (mostly COX2, PGE2),

Question 30

GCS

Answer 30

• *Eyes**
  4. Spontaneous
  3. To voice
  2. To pain
  1. None
• *Verbal**
  5. Oriented
  4. Confused
  3. Incomprehensible words
  2. Incomprehensivle sounds
  1. None
• *Motor**
  6. Obeys commands
  5. Localize to pain
  4. Withdraw to pain
  3. Decorticate (flexed)
  2. Decerebrate (extended)
  1. None
• *Decorticate** is arms flexed with hands on chest.
• *Decerebrate** is arms extended by the side.

Pain stimulus
There are many ways to elicit a pain stimulus including sternal rub, trapezius squeeze, supraorbital ridge pressure and nail bed pressure. The stimulus can elucidate whether the person localizes to the painful stimulus. A true localizing stimulus in involves the patient bringing their hand up to chin level to remove the painful stimulus. The trapezius squeeze and supraorbital pressure can confirm a localizing response.

Question 31

GI Bleed

Answer 31

• Digital Rectal Examination Reduces Hospital Admissions, Endoscopies, And Medical Therapy In Patients With Acute Gastrointestinal Bleeding Shrestha, M.P., et al, Am J Med 130(7):819, July 2017

BACKGROUND: Digital rectal examination (DRE) is considered an important element in the evaluation of patients with GI bleeding, but has been reported to be underutilized.
CONCLUSIONS: Digital rectal exam is a simple and inexpensive procedure for acute GI bleeding that has the potential to decrease hospital admissions and resource use.
EDITOR’S COMMENTARY: This chart review found that in 1237 patients with acute GI bleeding, the rectal exam was recorded on the ED provider notes only 44% of the time. When it was performed, it seemed to be associated with decreased admissions, endoscopies and medical therapies.

Question 32

Glucocorticoids

Answer 32

GCs cause anti-inflammatory, immunosupression and metabolic changes.

1. Anti-inflammatory
Eicosanides
GCsupregulate the synthesis ofAnnexin A1inphagocytic cells whichinhibits phospholipase A2 (PLA2).PLA2 converts phospholipids into arachidonic acid (arachis, from Latin for peanut) which are converted into eicosanoids through COX and LOX enzymes. **GCs do not seem to affect constitutive COX1 products.

Note: Eicosanoid (eicosa, from Greek for twenty, such as in icosahedron) is the collective term for straight-chain polyunsaturated fatty acids (PUFAs) of 20 carbon units in length that have been metabolized or otherwise converted to oxygen-containing products. There are multiple subfamilies of eicosanoids, including most prominently prostaglandins (PGs), thromboxanes (TX), leukotrienes (LT).

• *Bradykinin**
• *GCs** upregulate the synthesis of angiotensin-converting enzyme (ACE) (and increase blood pressure) and neutral-endopeptidase enzymes that degrade bradykinin. Bradykinin is a vasodilatory and proinflammatory peptide central to the generation of some forms of angioedema. By upregulating ACE, bradykinin levels fall thereby reversing the angioedema. **GCs increase ACE, angiotensin II and aldosterone, causing intravascular fluid retention and vasoconstruction thereby raising blood pressure.

Note: ACE breaks down bradykinin, and ACEIs would thus increase bradykinin which from the proinflammatory reactions cause angioedema. GCs are a treatment for angioedema by increasing ACE and decreasing the effect of bradykinin.

2. Immunosupression
Innate immunity
GS cause reduction transcription of pro-inflammatory cytokines, TNFalpha (CAMs) (migration of leukocytes/neutrophils), IL1 (fever), IL5 (eosinophils), and phagocytosis (macrophages).

Neutrophils
GCs inhibit the synthesis of IL1 and TNFalpha (thereby decreasing NF-kB),leading todecreased fever andsynthesis CAMs and leukocytes migration to the sites of inflammation. By decreasing L-selectin, neutrophil adherence to endothelium is reduced becoming free floating in the blood, called “demargination”.

Note: TNFalpha is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. TNF binds to receptors TNFR1 and TNFR2. This cytokine is involved in the regulation of a wide spectrum of biological processes primarily apoptosis (through the death receptor, TNFR that has a death domain) and inflammation (pro-inflammatory cytokine). TNFalpha increases the transcription of CAMs (cell adhesion molecules), such as ICAM (endothelial cell and respiratory epithelial cells), VCAM (endothelial cells after being stimulated by cytokines), E-selectin (endothelial cells after being stimulated by cytokines), L-selectin (lymphocytes/neutrophils), allowing immune cells to reach the site of inflammation.

Note: ICAM is exploited by rhinovirus to gain entry into the respiratory epithelium.

Blood exposure to collagen and tissue factor (TF), leads to platelet adhesion, activation and aggregation (see below) and clot formation. TF expression on the surface of monocytes and endothelial cells is increased by TNF-alpha released by monocytes/macrophages during inflammation. TF activates VII to VIIa and the extrinsic clotting cascade. Inflammatory conditions leading to increased TNF-alpha states are seen in diseases such as inflammatory bowel disease, lupus, rheumatoid arthritis, and nephrotic syndrome.

Note: NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex and transcription factor that is increased by TNFalpha and controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. TNF alpha (targeted in autoimmune disorders) binds to the TNFR1 increasing NF-κB activity.

Note: The neutrophil uses cell adhesion molecules called L-selectin to loosely attach itself to the endothelial lining of the blood vessel. L-selectin adhesion molecules undergo constant turn over as it moves long the blood vessel. As L-selectin is removed from the cell surface by the enzyme sheddase, it is replaced by newly produced L-selectin from within inside the neutrophil. Glucocorticoids are known to decrease gene transcription of L-selection thereby decreasing the amount produced and transferred to the surface to replace recently shed L-selectin. Without this replacement, the neutrophil will detach (or undergo “demargination”) to then enter into the circulatory compartment.

Extravasation is reduced and there are reduced numbers of neutrophils to sites of inflammation and infection. GSs also inhibits neutrophil apoptosis due to its effect on reducing TNFalpha. TNF alpha increases the FADD (Fas-associated protein with death domain​) activation which leads to apoptosis.

Eosinophils
GCsreduced synthesis of IL5 from Th2 cells,which thenpromoteseosinophil apoptosis (Th2 interacts APCs to secrete IL5 for Eosinophil recruitment. Eosinophils are increased in the mucosa of asthma).Blood and tissueeosinophiliais manifested in a number of inflammatory states, particularly in allergic diseases.Corticosteroids are the most effective anti-inflammatory drugs used in the treatment of eosinophilic disorders, including bronchial asthma.

Macrophages (Dendritic cells)
Reduced synthesis of inflammatory cytokines, IL1, TNFalpha, eicosanides, and phagocytic function. Reduced clearance of opsonized bacteria by the mononuclear phagocytic system (MPS) is reduced.

Note: The MPS is a part of the immune system that consists of phagocytic cells located in reticular connective tissue. The cells are primarily monocytes and macrophages, and they accumulate in lymph nodes and the spleen. The Kupffer cells (liver macrophages) of the liver and tissue dendritic cells (tissue macrophages) are also part of the MPS.

The spleen is the largest unit of the mononuclear phagocyte system. Monocytes are formed in the bone marrow and transported by the blood where it migrates into the many areas of the body to become a macrophage (name depending on the area it functions).

Macrophages are diffusely scattered in the connective tissue and in liver (Kupffer cells), spleen and lymph nodes (sinus histiocytes), lungs (alveolar macrophages), and central nervous system (microglia). The half-life of blood monocytes is about 1 day, whereas the life span of tissue macrophages is several months or years. The mononuclear phagocyte system is part of both humoral and cell-mediated immunity. In the humoral immunity, macrophages bind DAMPs (damage associated molecular patterns) and PAMPs (pathogen associated molecular patterns) to their toll like receptors (TLRs) and phagocyize these antigens. The mononuclear phagocyte system has an important role in defense against microorganisms, including mycobacteria, fungi, bacteria, protozoa, and viruses. Macrophages remove senescent erythrocytes, leukocytes, and megakaryocytes by phagocytosis and digestion.

Acquired Immunity
GC cause reduced transcription of pro-inflammatory cytokines TNFalpha (CAMs) (migration of leukocytes/neutrophils), IL2 (T cells).

Cell-mediated immunity
GCs reduce the number of circulating T cellsby theinhibition of IL2,a T cell growth factor. Immature T cells undergo apoptosis in thethymus (Bcl-2), in glucocorticoid induced apoptosis.

Humoral immunity
B cells are less affected and antibody production is largely preserved,although a mild decrement in immunoglobulin G (IgG) and immunoglobulin A (IgA) levels may develop in some patients with chronic use. Immunoglobulin E (IgE) levels may increase.

• 3. Metabolic*
• *GCs** have metabolic effects by stimulating gluconeogenesis in the liver to make glucose from non-hexose substrates, such as amino acids (found in muscle) and glycerol (adipose tissue and blood triglycerides).

i) Skeletal muscle breaks down muscle to produce amino acids used in gluconeogenesis (reverse Krebs cycle) to produce.

ii) Adipose tissue undergoes lipolysis to produce glycerol and fatty acids (beta oxidation) used in gluconeogenesis, through increased GC lipoprotein lipase expression.

Note: Beta oxidation is the process of using fatty acids to make energy by cabolizing Acyl-CoA (by HMG-CoA lyase) into Acetyl-CaA (which gets converted to glucose), and ketone bodies byproducts (beta-hydroxybutyric acid, acetoacteate/acetone) the ketone which causes DKA.

Note: Lipoprotein lipase (LPL) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-soluble enzyme that hydrolyzes triglycerides into fatty acids and glycerol.

Note: Glycerol (also called glycerine or glycerin) is a simple polyol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in all lipids known as triglycerides. It is widely used in the food industry as a sweetener and humectant and in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water

iii) Increase in caloric intake. Along with the increase in calories, there is an increase in GC mediated lipoprotein lipase expression. Lipoprotein lipase is found on the surface of endothelial cells, and an increase in activity leads to higher levels of fatty acids in circulation. Fatty acids are then available for ectopic fat distribution to liver, muscles and central adipocytes.

Note: There is a balance of GC induced lipoprotein lipase activity that causes the production of fatty acids and glycerol. Glycerol is used in gluconeogenesis. Fatty acids are deposited in ectopic tissue and used in gluconeogenesis.

Question 33

Headache

Answer 33

DDx]
Primary
Org(Cephalos)]
Tension – bilateral, “band like”, associted with cause such as sleep, stress, depression.

Migraine – unilateral, pulsating, photophobia, phonophobia, auras, worse with physical activity, gradual onset 4-72 hours, nausea, vomiting, neurological deficits such as aphasia, hemiparesthesias, hemiparesis. POUND – Pulsatile, One day duration 4-72 hours, Unilateral, Nausea/Vomiting, Disabling

Cluster – unilateral orbital, supraorbital or temporal, lasting 15-180 minutes, myosis, ptosis, lacrimation, nasal congestion, rhinorrhea, conjunctival injection, typically middle aged men, precipated by exertion/stress.

Medication overuse syndrome – on medication for headaches such as opioids, caffeine, OTC meds.

DDx]
Secondary – NEW ONSET
Haim]
Central venous thrombosis (CVT, thrombus in the dural venous sinus that drains the head) – seizure, stroke, hypercoagulable state (thrombophilia, pregnancy, medications (OCP), cancer), inflammatory disorders, waxing and waning neurological findings, papilledema, complications include ICH -> coma -> death.

Meta]
CO poisioning – nausea, vomiting, syncope, exposure, multiple patients, cherry red mucous membranes, cerebeller ataxia.

Org(Cephalos)]
IIH (Ideopathic Intracranial Hypertension, Pseudotumour cerebri) – young female of child bearing age not necessarily obese, visual loss/disturbance, headache x weeks/months, nausea, vomiting, OCP, vitamen A, tetracycline, papilledema with normal LOC.
Diagnostic criteria:
1. Signs of elevated ICP
2. Non-focal neuro exam except abducens nerve palsy.
Note:The abducens nerve (CN VI) emerges from the bottom of the brainstem and it is the first nerve compressed when there is increased ICP. Most common etiologies are vasculopathies such asdiabetes and hypertension, and less common are cavernous sinus mass.
3. Normal neuroimaging study CT with contrast
4. Increased CSF pressure
5. No other cause of increased ICP (tumour, encephalitis)

Sinusitis – anterior face (maxillary sinus), forehead (frontal sinus), behind eyes (ethmoid sinus), diffuse (sphenoid sinus)
Diagnostic criteria (4 or more):
1. Colored nasal discharge
2. Visible purulent nasal discharge
3. Maxillary toothache
4. Poor response to decongestants
5. Abnormal transillumination

Org(Vasculo)]
SAH – “thunderclap” sudden onset with maximal intensity, WHOL, precipated by exertion such as weight lifting, sexual activity, defacation, coughing; nausea, vomiting, syncope, photophobia, neurological deficits, meningismus, ALOC

SDH (Subdural hematoma) – history of trauma, elderly, alcoholics, on anticoagulants, ALOC

CAD (Cervical Artery Dissection, ie. internal carotid artery, vertebral artery)–unilateral anterior headache(ICA),posterior neck pain(VA) precipitated bymajor traumapenetrating or blunt force injury, orminor traumawith rotational neck movement (yoga), couging, whiplash, chiropractor, stroke symptoms, age<40.Internal carotid artery– MCA (face, arm), ACA (leg, arm).Vertebral artery– posterior fossa symptoms such as vertigo, ataxia or dysmetria.Horners syndrome – miosis, ptosis, anhydrosis.

Org(Ophthalamos)]
Acute glaucoma – eye pain, blurred vision, nausea, vomiting, mid-dilated non reactive pupil, elevated IOP>20

Infla]
Temporal (Giant Cell) arteritis – unilateral, throbbing, tender temporal artery, jaw claudication, vision changes, age>50 and more commonly women
Diagnostic criteria (3/5):
1. New onset localized headache
2. Age>50
3. Temperal artery tender/decreased pulse
4. ESR>50
5. Biopsy – vasculitis, granuloma

Oncos]
​Brain mass/lesion – progressive morning nausea and vomiting, exertional, new onset seizure, papilledema, focal neurological deficits, aphasia

Infect]

• *Meningitis** – traid of nuchal rigidity, fever, ALOC. All three has high sensitivity for ruling out meningitis, where a negative for all three rules out meningitis. Photophobia, nausea, vomiting, lethargy, neurological deficits.
• *Jolt accentuation** is a test where the patient turns their head right and left, 2-3 rotations per second. If the headache gets worse the test is positive, if the headache does not get worse the test is negative. Jolt accentuation has high sensitivity. A negative test has a sensitivity of 100% for ruling out meningitis. Kernig (cannot passively extend knee) Brudzinski (passive flexion of the neck causes legs to flex) has a low sensitivity (cant rule out), but high specificity (can rule in).
• *Note:** Bacteria most common organisms are neisseria meningitidis, streptococcus pneumoniae, haemophilus influenza, listeria monocytogenes. Viral most common organisms are enteroviruses (85%), herpes viruses.
• *HPI]**
• *Primary**
• *Tension – bilateral, “band-like”,** associated stress, sleep, depression

Migraine – unilateral, aura, photophobia, phonophobia, worse with activity. POUND – Pulsatile, One day onset, Unilateral, Nausa/Vomiting, Disabling

Cluster – unilateral orbital, lacrimation, congestion, lasting 15 min to 2 hours, middle aged men, precipitated by stress/exertion

Medication Overuse – on medication for headaches, opioids, OTC

• *Secondary – NEW ONSET**
• *CVT** – HA->seizure->stroke, hypercoaguable state such as pregnancy, thrombophillia, OCP, cancer

CO poisioning – nausea, vomiting, group exposure

IIH -- young female of child bearing age not necessarily obese, visual loss/disturbances
Diagnostic criteria:
1. Signs of elevated ICP
2. Non focal neuro exam except abducens nerve paresis
3. Normal neuroimaging study CT w contrast
4. Increased CSF pressure
5. No other cause of increased ICP (tumour, encephalitis)

Sinusitis – tenderness over sinuses.
Diagnostic criteria (4 or more):
1. Colored nasal discharge
2. Visible purulent nasal discharge
3. Maxillary toothache
4. Poor response to decongestants
5. Abnormal transillumination

Acute glaucoma – eye pain, blurred vision, mid-dilated non reactive pupil, elevated IOP>20.

SAH – “thunderclap” (sudden onset, maximal onset, differnt from other HAs), WHOL, on exertion, neck pain, nausea, vomiting

SDH – history of trauma, elderly, alcoholics, anticoagulation

CAD – major or minor trauma (yoga, chiropractor), unilateral anterior headache (ICAD), posterior neck pain (VCAD), age <40

Temporal (Giant cell) arteritis – throbbing, unilateral, jaw claudication, age>50, women
Diagnostic criteria (3/5):
1. New onset localized headache
2. Age>50
3. Temperal artery tender/decreased pulse
4. ESR>50
5. Biopsy – vasculitis, granuloma

Brain mass/lesion – progressive, morning nausea and vomiting, exertional

Meningitis – triad of nuchal rigidity, fever, ALOC, where absence of all 3 rules out

PMHx]
HTN (SAH)
Cancer (CVT)
Inflammatory disease (CVT)
Immunocopromised ie. HIV (meningitis, brain mass lesion)

Meds]
OCP (CVT, IIH)
Tetracycline (IIH)
Anticoagulants (SDH)

SHx]
EtOH (SAH, SDH)
Smoking (SAH)
Living conditions – college dorms, military barracks (Meningitis)
Pregnant (CVT)

• *O/E]** HTN (SAH), febrile (meningitis) GCS (SAH, SDH, meningitis)
• *General** – ALOC (SAH, SDH, meningitis), jolt accentuation test (meningitis), neurological deficits – brain mass/lesion, migraine, meningitis, CVT, CAD

Neuros (general) – truncal ataxia (CAD/VA), hemiparesis/paraesthesias/decreased power to arms or legs, spasticity (increased tone), increased reflexes (migraine, CAD/ACA, CAD/MCA, CVT)

Neuros (CN) – visual disturbances (migraine, IIH, temporal arteritis), blurred vision (glaucoma), mid-dilated pupil (glaucoma), papilledema (CVT, brain mass/lesion, IIH, SAH), photophobia (migraine, meningitis), facial asymmetries/paraesthesias (CAD/MCA)

Neuros (Cerebeller) – dysmetria (VA), dysdiadochokinesia (VA)

HEENT – elevated IOP>20 (acute glaucoma).

POCUS – papilledema (CVT, brain mass/lesion, IIH, SAH) - 3mm down from the retina and >5mm across the optic nerve sheath indicates papilledema, or crescent sign

INVESTIGATIO]
L(H)/Haim]
WBC (meningitis), INR, PTT (SAH)
COHb level (CO poisoning)
L(H)/Meta]
SMA7
L(H)/Infla]
ESR (temporal arteritis), CRP

L(I)/Haim]
Blood C&S (meningitis)

L(I/F)/CSF]
SAH
<12h Xanthochromia may/may not be present, large RBC should be present
>12h Xanthochromia is HIGHLY suggestive, large RBC +/- present
12h-2w Xanthochromia or RBC may be absent

Meningitis
Tube 1&4 - cell count and differential
Tube 2 - glucose and protein
Tube 3 - gram stain, culture, HSV, PCR
Other – india ink (cryptococcus), acid fast for mycobacteria
Bacteria meningitis (protein high, glucose low) – gram stain positive , WBC>2000, neutrophils>80%, protein>200 (high), glucose<40 (reference or low)

IIH
Increased opening pressure otherwise normal.

• *I]**
• *CT wo contrast (SAH)** - **100% sensitivity and 100% specificity <6h, CT scan <6h should NOT need an LP to rule out SAH, CT misses 2% 6-12 hours, and 7% 12-24h

CT wo contrast (CVT) - normal in 30% of cases, dense triangle sign (thrombosed superior sagitus sinus posteriorly), cord sign (thrombosed cortical vein), bilateral edema/ICH

CT w contrast (brain mass/lesion, IIH, HIV with new HA) - normal in IIH

CT w contrast venogram (CVT) – empty delta sign (flow defect in superior sagital sinus)

CT angiography (CAD, SAH)

MRI w venogram (CVT) – study of choice for CVT

MRI/MRA (CAD, IIH)

Angiography (CAD)

B]
Temporal artery (TA)

RECIPERE] Primary
Tension
P/Poin]
Tylenol 975mg PO x1 (max 3000mg) OR
{Toradol} Ketorolac 15mg IM x1

Migraine
NP/C]
PIV, NS 1L bolus

P/Poin]
{Toradol} Ketorolac 15mg IV/IM x1

P/Poin,N,V]
{Maxeran} Metoclopramide 10mg IV/IM x1
Note: Dopamine antagonists have 80-90% effectiveness when given IV, 60-80% IM, and 40% PO.

P/Org(Neuros)]
Sumatriptan 50mg PO x1
(early in migraine when aura is present)

P/Infla]
{Decadron} Dexamethasone 10mg IV/IM x1
(if migraine >72hours)

Cluster
NP/A,B]
High flow O2 3-10L NP
Intranasal lidocaine

RECIPERE] Secondary
CVT
P/Haim]
Heparin 10,000U IV now,
50-70U/kg (5000-10,000U) IV q4-6h

Consult]
Neurosurgery

CO Poinsoning
NP/A,B]
100% NRM

IIH
P/Org(Cephalos)]
{Diamox} Acetazolamide 1-4g/day divided q8-12h
Surg/Consult] Neurology Consult
If vision loss then ONSF (Optic Nerve Sheath Fenestration) and VP shunt

Acute Glaucoma
P/Ophthalamos]
0.5% timolol maleate {Timoptic} one drop
1% apraclonidine {Lopidine} one drop
2% pilocarpine {Isopto Carpine}
{Diamox} Acetazolamide 500mg IV then 500mg PO

SAH (for increased ICP)
NP/A,B]
SpO2>94%

NP/C]
PIV, NS fluids for maintanence

NP/Mon]
cardiac monitor, BP, SpO2

NP/Nut]
NPO

NP/Pro]
Elevate the head of the bed 30 degrees and hyperventilation to PaCO2 25-30mmHg (35-45mmHg). Hyperventilation causes decreased PaCO2 and vasoconstriction.

P/Poin]
Morphine 4-8mg IV q5-15min

P/N,V]
{Zofran} 4mg IV/SL

P/Haim]
Vitamin K 10mg slow influsion
(if anticoagulation of Warfarin)
Protamine sulfate
(if anticoagulation on Heparin)

P/Meta]
Insulin for hyperglycemia

P/Neuros]
Propofol, Etomidate, Midazolam
(sedation if unstable)
{Dilantin} Phenytoin
(for seizures)

P/Org(Cephalos)]
Mannitol 1g/kg IV bolus,
then 0.25 to 0.5 g/kg q6h to plasma Osm 300-310

P/Org(Vasculos)]
**DO NOT overcorrect ​BP
IF SBP>200 or MAP>150
Labetalol 10-20mg IV over 1-2 min
THEN 2mg/min influsion titrated to MAP reduction 10% to 20%
{Nimotop} Nimodipine 60mg PO q4h
(CCB for vasospasm)

P/Consult]
Neurosurg consult

SDH
I]
CT 6-8 hours
(reassessment)
Surg/Consult]
Neurosurgry – Burr hole, craniotomy (hemotoma thickness ≥10 mm or midline shift ≥5 mm on initial brain scan)

CAD
P/Haim]
Aspirin 325mg PO
P/Consult]
Neurosurgery/Vascular consult

Temporal giant cell arteritis
P/Infla]
Prednisone 50mg PO
(if no vision loss)
{Solu-Medrol} Methylprednisolone 1000mg IV OD
(if vision loss)

P/Consult]
Vascular surgery

Brain mass/lesion
P/Poin]
{Tylenol} 650mg PO x1
P/N,V]
{Zofran} 4mg SL/IV
P/Infla]
{Decadron} Dexamethasone 10mg IV x1, then 4mg IV/IM q6h

Meningitis
P/Infect]
Vancomycin 1g IV AND
Ceftriaxone 2g IV AND
Ampicillin 2g IV
(age>50, for H. influenza and Listeria monocytogenes)

P/Infla]
Dexamethasone 10mg IV
15 min before Abx has proven to be helpful in adults

Question 34

Heart Block

Answer 34

1. Diagnosis
   i) clinical
   ii) lab/imaging
   iii) time
2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – starting from acute to benign
5. Investigations (rule in/out)
6. Treatment/Management
   Isoproterenol 2.5 mcg/min (if stable)
   Pacing pads (if unstable)

Question 35

• *Acute Decompensated Heart Failure (ADHF)**
• *HFpEF, HFmEF, HFrEF**

Answer 35

• *1. Diagnosis**
• *HFrEF**

HFpEF (clinical, labs and imaging)
Suspected when SOBOE, fatigue, orthopnea, PND.
H2FPEF score: In patients with suspected HFpEF, we suggest using the H2FPEF score to estimate the probability of HFpEF versus noncardiac causes of dyspnea.

●Heavy – Body mass index >30 kg/m2 (two points).

●Hypertensive – Two or more antihypertensive medicines (one point).

●Atrial Fibrillation (AF) – Paroxysmal or persistent (three points).

●Pulmonary hypertension (PH) – Pulmonary artery systolic pressure >35 mmHg using Doppler echocardiography (one point).

●Elder – Age >60 years (one point).

●Filling pressure – Doppler echocardiographic E/e’ >9 (one point).

A low H2FPEF score of 0 or 1 is associated with a low (<25 percent) probability of HFpEF. A low score suggests that symptoms are most likely due to a noncardiac cause, and such causes should be investigated.

An intermediate H2FPEF score of 2 to 5 is associated with an intermediate (40 to 80 percent) probability of HFpEF. In this setting assess the following. If both criteria are met, the clinical findings are diagnostic for HFpEF:

i) N-terminal proBNP [NT-proBNP] >300 pg/mL
OR [BNP] >100 pg/mL

ii) Abscence of lung disease.

A H2FPEF score of 6 or greater is associated with a greater than 90 percent probability of HFpEF and is thus considered diagnostic for HFpEF.

Lab/Imaging

N-terminal proBNP [NT-proBNP] >300 pg/mL

HF with preserved ejection fraction (HFpEF): LVEF ≥ 50%

HF with a mid-range ejection fraction (HFmEF): LVEF 41-49%

HF with a reduced ejection fraction (HFrEF): LVEF ≤ 40%

Time course

• *2. Pathophysiology/Etiology**
• *Approximately 50 percent of patients hospitalized for HF have HF with preserved ejection fraction** (HFpEF; left ventricular ejection fraction [LVEF] >50 percent); the remainder of patients have HF with reduced ejection fraction (HFrEF; LVEF ≤40 percent) or HF with mid-range ejection fraction (LVEF 41 to 50 percent).

Patients present to the emergency department with a myriad of chief complaints, symptoms, and physical examination findings. Such heterogeneity prompts an initially broad differential diagnosis, thus securing the correct diagnosis can be challenging. For practical purposes, it is helpful to view the presentation of ADHF according to the predominant clinical characteristics on admission. Most patients presenting with ADHF have known chronic HF and may or may not have had a prior episode of decompensation. In many patients with chronic HF, symptoms have gradually worsened over the preceding days and weeks but have not been sufficient for the patient to seek medical attention. In a minority of patients, an episode of ADHF may be the first presentation of HF.

3. Risk factors/Red flags

4. Other diagnosis – acute to benign
Pulmonary embolism
Pmeumoniea
Asthma

5. Investigations (rule in/rule out)

6. Treatment/management

• ​​Misconceptions in acute heart failure diagnosis and Management in the Emergency Department. Brit Long, MD, Alex Koyfman, MD, Eric J. Chin, MD American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.05.077

CONCLUSIONS:
i) Natriuretic peptides should only be used in conjunction with clinical evaluation, rather than using the test in isolation.

• *ii)** A more valuable means of diagnosis for pulmonary edema associated with AHF is POCUS.
• *US alone with the presence of ≥3 B lines in ≥2 bilateral thoracic lung zones possesses a positive likelihood ratio (+LR) of 7.4, sensitivity approaching over 90%, and specificity 92.7% for pulmonary edema**, while the absence of B lines possesses a negative likelihood ratio (−LR) of 0.16. The number of B lines correlates with AHF severity
• *iii) **In** acute pulmonary edema WITH hypertension, nitroglycerin and noninvasive positive pressure ventilation (NIPPV) should be first-line therapies before diuresis.
• *Note:** In acute pulmonary edema (APE), >50% of patients do not have true volume overload, but rather volume distribution, with movement of fluid into the lungs. Zile et al. found patients with APE demonstrated no significant increase in dry weight during their exacerbation, and another study found approximately half of patients have less than a two pound increase during their episode of APE. Fluid shifts from other body compartments such as the splanchnic circulation into the pulmonary circulation may result in pulmonary edema. Patients receiving furosemide first may experience decreased LV function, increased ventricular filling pressures, and increased systemic vascular resistance through activation of the neurohormonal system. The medication can also decrease glomerular filtration rate (GFR), potentially even further decreasing diuresis. In this setting, harm may result with diuretic therapy if the patient is not truly volume overloaded.

**Diuretics are beneficial in normotensive patients with systemic congestion from true volume overload, which includes signs and symptoms such as ascites and extensive peripheral edema accumulating over an extended period of time. However, in hypertensive APE with AHF and little to no evidence of systemic congestion, nitroglycerin (NTG) and noninvasive positive pressure ventilation (NIPPV) should be administered. These measures improve work of breathing, decrease preload, and can decrease afterload, and in particular, NIPPV is associated with reduced need for intubation (NNT of 8) and mortality (NNT of 13).

iv) A variety of diuretic strategies may be utilized in patients with systemic congestion, and ultrafiltration may improve diuresis in patients refractory to IV diuretics.

Note: The AHA/ACCF Heart Failure Guidelines recommend an initial IV dose equivalent or greater than the home dose given bolus or continuously. If this does not improve symptoms, the dose of loop diuretic can be increased, or a second diuretic added (thiazide). Bolus versus continuous infusion of diuretic is controversial. The DOSE trial evaluated four groups: low dose continuous infusion (home dose administered continuously over one day), high dose continuous infusion (2.5 X home dose administered continuously over one day), low dose bolus (home dose divided into two daily boluses), and high dose bolus (2.5 times daily home dose divided into two daily doses) loop diuretics. Comparisons included bolus versus continuous and low-dose versus high-dose. The trial found high-dose loop diuretics may improve symptoms but increase serum creatinine (Cr), while continuous versus intermittent boluses were not clinically significant.

• *v)** Nitroglycerin (NTG) IV may be provided safely in higher doses, including bolus or infusion, which will rapidly relieve symptoms.
• Misconception: the safest means of providing nitroglycerin IV is to begin with small doses and titrate to relief of symptoms to ensure patient safety in those with pulmonary edema​.*

Nitrates cause vasodilation through activation of guanylyl cyclase on nitrate-derived nitric oxide, increasing cyclic guanosine 3′, 5′ monophosphate (cGMP) bioavailability and cGMP-dependent protein kinases activation.

Ultimately, intracellular calcium decreases, resulting in venous and arterial vasodilation, reducing biventricular filling pressures, systemic arterial blood pressure, and pulmonary vascular resistance. In AHF, the most common nitrates are nitroglycerin and nitroprusside. NTG is more commonly used in AHF, as it improves coronary blood flow, reduces myocardial ischemia, and has relatively no effect on neurohormones. Nitroprusside reduces coronary blood flow, increases myocardial ischemia, and increases neurohormones.

***The greatest benefit is in those with pulmonary edema due to systemic improvements in preload (decreased) and fluid redistribution.

The ESC (European Society of Cardiology) recommends use in patients with SBP > 110 mmHg, and the Heart Failure Association of the ESC, European Society of Emergency Medicine, and Society of Academic Emergency Medicine recommend providing nitroglycerin to those with SBP > 110 mmHg.

NTG is typically initiated at initial IV dose of 10–20 mcg/min, which is increased by 10–20 mcg/min until symptom improvement. Sublingual NTG can be started first, with 400 mcg (0.4 mg) tablet/spray. However, NTG is contraindicated in hypotension, obstruction of the LV outflow tract, recent use of phosphodiesterase inhibitors, and conditions similar to AHF where vasodilation is not beneficial (COPD).

A 2017 retrospective observational cohort study included patients over 18 years with AHF, comparing NTG bolus (500–2000 mcg every 3–5 min), NTG infusion (20–35 μg/min), and NTG bolus plus infusion. Authors found decreased ICU admission in the bolus group compared with the other groups. Secondary outcomes included shorter length of stay in the bolus group, with no differences in adverse outcomes (intubation). At this time, administering NTG more aggressively at higher doses, whether bolus or infusion, is likely safe and may be associated with reduced need for intubation and need for ICU admission, compared with lower infusion rates. However, further evaluation on its effect on mortality is required, as well as investigation into the potential harms.

Bolus NTG group included patients who received 1 or more intermittent bolus doses at least 500 mcg of IV nitroglycerin. When administered by bolus, 10 mg of nitroglycerin is prepared in a 10 mL syringe and given by IV push in increments up to 2 mg every 3 to 5 minutes.

Intravenous NTG infusion is one of the mainstay treatments in acute pulmonary edema (aka acute decompensated heart failure (ADHF)), but is associated with increased hospital length of stay (LOS) and health care costs. Optimal NTG dosing isn’t established though physiologically higher infusion doses (> 100 mcg/min) are helpful as they affect both preload and afterload. Recent studies suggest that intermittent high-dose bolus therapy may be as or more effective than infusions, however the impact on ICU admissions has not been studied.

Note: NTG mechanism of action. Venodilation affects venous return, decreasing filling pressures and myocardial work. The effects of NTG are dose-dependent, in low dose (< 150 mcg/min) causes venodilation, higher doses (> 150 mcg/min) causes arteriolar vasodilation. NTG decreases diastolic blood pressure, however because filling pressures are decreased, theoretically myocardial perfusion can be preserved. The end result of NTG administration is dependent on the totality of its various hemodynamic effects (venodilation, decreased venous return, decreased systemic pressure, increased HR).

Standard SL NTG tablets or sprays most commonly come as 0.4 mg (or 400 mcg) per tablet or spray and are given every 3 to 5 minutes up to 3 doses. This means each tablet or spray of NTG provides about 130 mcg/min (every 3 minutes) to 80 mcg/min (every 5 minutes). If 2 sprays are given 0.8 mg (or 800mcg) NTG provides 260 mcg/min to 160 mcg/min. **If two sprays of NTG are given then in 5 minutes enough NTG would be given for both preload and after load reduction.

• Morphine Use In The ED And Outcomes Of Patients With Acute Heart Failure Miro, O., et al, Chest 152(4):821, October 2017

CONCLUSIONS: In a propensity-matched analysis, early morphine treatment was associated with increased 30-day mortality in patients with acute heart failure. These findings are in line with current international guidelines that recommend against routine morphine use for acute heart failure.
EDITOR’S COMMENTARY: These Spanish authors evaluated approximately 6500 patients with acute cardiogenic pulmonary edema in 34 EDs to assess the effect of early administration of IV morphine on 30 day mortality. Approximately 400 patients were given morphine within 3 hours of presentation vs. approximately 6100 patients not given morphine. A propensity-matched group of 275 pairs of patients in these two groups revealed an association of increased mortality in the morphine group (20%) vs. the non-morphine group (13%). Overall, it appears that morphine confers no benefit for patients with acute exacerbation of CHF and administration of IV morphine in this study was associated with increased 30-day mortality.​

• Time-to-Furosemide Treatment and Mortality in Patients Hospitalized With Acute Heart Failure. J Am Coll Cardiol. 2017;69(25):3042.

CONCLUSIONS: A multicenter, prospective observational study of 1291 patients with acute heart failure treated with intravenous furosemide within 24 hours of arrival in an emergency department found that treatment within one hour was associated with a lower in-hospital mortality than later treatment. Thus, the expeditious initiation of an intravenous loop diuretic regimen may improve in-hospital outcomes, in addition to controlling symptoms of volume overload. ***Note there is controversy over this study and the idea of door to Lasix time. Use nitroglycerine first before diuretics.

• *ADHERE Registry**
• *The Acute Decompensated Heart Failure National Registry (ADHERE)** is a large multicenter registry that records data from patients hospitalized with ADHF with more than 175,000 hospitalizations from over 250 hospitals across America. To be included in this registry patients must be >18years of age, admitted to an acute care hospital and receive a discharge diagnosis of ADHF. Data for this registry are collected by retrospective chart review and entered via an electronic web-based case report form for all consecutive eligible patients.

ADHF
Although they involve a variety of phenotypes and etiologies, the most common cardiomyopathies often present with similar symptoms. Hypertrophic (HCM), dilated (DCM), and restrictive cardiomyopathy may each present with signs and symptoms that are common in heart failure with reduced ejection fraction, including peripheral edema, fatigue, orthopnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, presyncope, syncope, and cardiac ischemia.
Acute decompensated heart failure (ADHF) is a sudden worsening of the signs and symptoms of heart failure, which typically includes difficulty breathing (dyspnea), leg or feet swelling, and fatigue. ADHF is a common and potentially serious cause of acute respiratory distress.

Acute decompensated heart failure (ADHF) is a common and potentially fatal cause of acute respiratory distress. The clinical syndrome is characterized by the development of dyspnea, generally associated with rapid accumulation of fluid within the lung’s interstitial and alveolar spaces, which is the result of acutely elevated cardiac filling pressures (cardiogenic pulmonary edema). ADHF can also present as elevated left ventricular filling pressures and dyspnea without pulmonary edema.

ADHF is most commonly due to left ventricular systolic or diastolic dysfunction, with or without additional cardiac pathology, such as coronary artery disease or valve abnormalities. However, a variety of conditions or events can cause cardiogenic pulmonary edema due to an elevated pulmonary capillary wedge pressure (PCWP) in the absence of heart disease, including primary fluid overload (eg, due to blood transfusion), severe hypertension (particularly renovascular hypertension), and severe renal disease.

In the large majority of patients who present with ADHF, acute or subacute decompensation is in the context of chronic HF with reduced ejection fraction (HFrEF, also known as systolic HF) or HF with preserved ejection fraction (HFpEF, also known as diastolic HF) and in many cases, there is a prior history of episodes of decompensation. In such patients, information regarding the precipitating factors, workup for HF, and the elements of successful therapy for prior episodes (eg, types and doses of diuretics used) can be of great value in approaching the current episode.

Heart Failure
Heart failure is broken down into two classes:
1. HF with reduced EF (HFrEF) <40%, systolic HR
2. HF with preserved EF (HFpEF) >or= 50%, diastolic HR
Note: Borderline is between 40% and 50%.

NYHA Functional Classes
(New York Heart Association)
Class I - SOB with greater than normal activity
Class II - SOB with ordinary activity, comfortable at rest
Class III - SOB with minimal activity (e.g. walking short distances 20m-100m), comfortable at rest
Class IV - SOB at rest, mostly bedbound

HPI]
Dyspnea (SOB)
SOBOE
orthopnea
PND
nocturia
fatigue
new cough

PMHx]
CHF
ACS(NSTEMI, STEMI)

O/E] TC, HTN/HypoTN (narrow PP), DP, Low SpO2, Wt
Cardios – JVD, Kussmaul sign (rise in JVD on inspiration), S3/S4, new murmur
Pulmos – crackles
Abdos – hepatomegaly, ascites, abdominojugular test
PV – pedal pitting edema

Note: In HFrEF there is less blood leaving the left ventricle and more blood left behind in the left ventricle. SBP will decrease due to less blood leaving throught the aortic valve, and DBP will increase due to more blood left behind in the ventricle. Combined decrease in SBP and increase DBP leads to narrow PP.

INVESTIGATIO]
L(H)/Haim]
CBC
L(H)/Meta]
K+
L(H)/Org(Cardios)]
troponins, BNP
(BNP <100 rules out, BNP >500 rules in)
Note:BNP released when the ventricles are stretched and kidneys cannot excrete the extra volume.

I]
ECG – rule out infarction, arrythmias, LVH
CXR – cephalization (vascular redistribution of pulmonary vessels in upper chest due to venous hypertension from the increased pressure in the left atrium) pulmonary interstitial edema, Kerly B lines, pulmonary alveolar edema, cardiomegaly
POCUS – plural sliding AND B Lines, pericardial effusion/tamponade, or gross LV dysfunction

Note: US alone with the presence of ≥3 B lines in ≥2 bilateral thoracic lung zones possesses a positive likelihood ratio (+LR) of 7.4, sensitivity approaching over 90%, and specificity 92.7% for pulmonary edema, while the absence of B lines possesses a negative likelihood ratio (−LR) of 0.16. The number of B lines correlates with AHF severity

RECIPERE]
NP/A,B] (ONLY if hypoxic SpO2 <90%)
NRB, NIPPV (Non invasive Postive Pressure Ventiation – CPAP, BiPAP), Intubation
NP/C]
PIV
NP/Mon]
SpO2

Note: Oxygen therapy not recommended unless SpO2<90% as it may cause vasoconstriction and reduced cardiac output. CPAP and BiPAP is preferred as it decreases the rate of intubation and mortality.

P/Poin]

• *ADHERE –** In this preliminary registry analysis of ADHF, the use of morphine was associated with a longer stay in the hospital, more frequent and longer ICU admissions, and a greater risk of in-hospital mortality.
• ***The use of IV morphine in ADHF is associated with increased morbidity and mortality and should be abandoned completely as a “first-line” medical therapy. If you want to decrease diastolic filling pressures in ADHF use nitroglycerin.**

P/ Org(Vasculos)]

• *NTG 0.4mg SPRAY/SL x2 q5min x3** OR
• *NTG patch 0.4mg/hr** OR
• *NTG 5mcg/min IV infusion**, titrated to 200mcg/min

Note: Optimal NTG dosing isn’t established though physiologically higher infusion doses (>100 mcg/min) are helpful as they affect both afterload and preload. Start nitroglycerin infusion at 5 to 10 mcg/min and titrate every three to five minutes as needed and tolerated based upon mean arterial blood pressure or SBP to a dose range of 10 to 200 mcg/min. **Caution of the use of nitrates for PDE-5 inhibitors such as Viagra or Cialis.

P/ Org(Nephros)]
Furosemide 20-100mg IV
(up to 2xmaintainence dose)

HFrEF (systolic) and Cardiogenic Shock SBP <90
Dobutamine 5mcg/kg/min IV, titrated to max 40mcg/kg/min
(sympathomimetic/inotrope)
Milrinone 0.125 to 0.75 mcg/kg/minute IV
Note: Milrinone is a selective phosphodiesterase inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects with little chronotropic activity.
Dopamine 5mcg/kg/min IV, titrated to max 50mcg/kg/min
(vasopressor)
Note: Discontinue beta blocker.

• *HFpEF (diastolic) and Cardiogenic Shock SBP <90**
• *Norepinephrine 0.05mcg/kg/min (5mcg/min) IV**, titrate as needed to 0.15mcg/kg/min for PIV and 0.3mcg/kg/min for CIV

Question 36

Hepatitis

Question 37

Hyperkalemia

Answer 37

Hyperkalemia

SAN
The higher concentration of K+ outside the cell, causes LESS K+ to leak out of the K+ leak channels, and increased intracellular voltage. The cell is now closer to threshold potential with increased RMP (resting membrane potential). Due to the increased RMP, there are less f-channels (HCN channels) on nodal tissue available to open as HCN channels work on hypyerpolarization (and cyclic nucleotides/cAMP), leading to an increased in the slope of phase 4 and bradycardia.

Note: f-channel is a HCN channel (hyperpolarization-activated cyclic nucleotide-gated), and has a duel feature of activation:
i) Voltage – Hyperpolarization
Mixed Na+/K+ INWARD current – If (funny current) – activated on hyperpolarization (-60mV, with threshold at -40mV). Without the membrane voltage becoming very negative, f-channels remain inactivated which suppresses If currents and decreases the slope of phase 4 causing bradycardia.

ii) Cyclic nucleotides (cAMP)
ATP is converted to cAMP by adenyl cyclase. cAMP binds directly to f-channels intracellularly and increases the open probablility.

• *Myocytes**
• *1.** More K+ outside the cell causes LESS K+ to leak out the K+ leak channels shifting the RMP toward depolarization (more positive). Early on in hyperkalemia the cells are more excitable.

2. The shifted RMP causes “some” fast Na+ channels to activate. The fast Na+ channels once activated have a mechanism to stop them from being reactivated, into an inactivates state (ball and chain), not allowing Na+ ions through.

3. There are “fewer” fast Na+ channels left that can respond raising the threshold potential. At this stage in hyperkalemia, the cells are LESS excitable. Due to “fewer” fast Na+ channels available at phase 0 depolarization, the action potential is slowed causing a widened QRS complex.

4. In phase 2 and 3, K+ leaves the cell through K+ voltage gated (VGKC) delayed rectifier channels. K+ currents are sensitive to external K+ levels (an external K+ ion holds the K+ channel open). As the external K+ concentration increases, K+ current (IKr) increases out of the myocyte. Due to the increased IKr, phase 2 and 3 are shortened causing a shortened QT interval and peaked T waves (stronger repolarization currents and larger voltage).

Serum Potassium (mmol/L)Predicted ECG status

5. 5-6.5 – Tall tented T waves
6. 5-7.5 – Loss of P wave
7. 5-8.5 – Widening QRS

>8.5 – QRS continues to widen, approaching to sine wave

Classic Causes of Hyperkalaemia
1. Excessive exogenous
(increased Intake)
Potassium supplements (IV or Oral)
Excess in diet
Salt substitutes (e.g. potassium salts of penicillin)

2. Excessive endogenous
(increased production)
Cells bust open – Hemolysis, rhabdomyolysis, extensive burns, tumor lysis syndrome, intense physical activity, and
trauma (especially crush injuries and ischaemia)

3. Redistribution
(shift from intracellular to extracellular fluid)
Acidosis (metabolic or respiratory)
Insulin deficiency
Drugs (succinylcholine, digoxin toxicity)
Hyperkalemic familial periodic paralysis

Insulin binds to tyrosine kinase receptors which autophosphorylates leading to phosphorylation of second messenger proteins and activation of Na+/K+ ATPase. A deficiency of insulin would cause an increase in K+ outside the cell.

Succinylcholine acts like acetylcholine and binds to NAChR at the muscle cells causing depolarization (Na+ in and K+ out). Succinylcholine has a longer effect than acetylcholine and is not degraded by acetylcholinesterase.

Digoxin’s primary mechanism of action involves inhibition of the Na+/K+ ATPase, mainly in the myocardium. This inhibition causes an increase in intracellular Na+ (and increased extracellular K+), resulting in decreased activity of the Na+/Ca2+ exchanger (NCX), which normally imports three extracellular Na+ into the cell and transports one intracellular Ca2+ ion out of the cell. The inaction of this exchanger causes an increase in the intracellular Ca2+ concentration that is available to the contractile proteins leading to its inotropic effect. Increased intracellular Ca2+ lengthens phase 4 and phase 0 of the SAN and AVN action potential, which leads to a decrease in heart rate.

4. Diminished excretion
(decreased excretion)
Decreased GFR (renal failure)
Decreased mineralcorticoid (aldosterone) ie Addisons
Defect in tubular secretion (renal tubular acidosis II and IV)
Drugs – NSAIDs, potassium-sparing diuretics (aldosterone antagonists such as aldosterone) , ACEIs, ARBs, cyclosporine

Pseudohyperkalemia
(factitious)
Haemolysis (in laboratory tube) most common
Thrombocytosis
Leukocytosis
Venopuncture technique (e.g. prolonged tourniquet application)

RECIPERE] CBIGK (10)
C - Calcium
Calcium gluconate (10%) 10cc IV, over 10 min
Calcium is a cardiac stabilizer.

B - Beta Agonist
{Ventolin} Salbutamol 10mg NEBS, over 10 min
OR
Sodium bicarbonate 1 ampoule IV over 5 minutes
Both of these agents cause temporary intracellular shift.

I - Insulin (Regular, short acting)
Insulin 10U IV push

G - Glucose ** Given before or with insulin
D50W 1 ampule IV, over 10 minute given with insulin
Insulin causes temporary intracellular shift and glucose is given to maintain blood glucose levels.

K – Kayexalate
Kayexalate 10g in 60mL suspension PO
Kayexalate may facilitate– gastrointestinal removal.]

Note: Below is mainly for CHRONIC renal failure. Not for use in the ACUTE phase.

D – Diuretics
Furosemide 40mg IV
This facilitates renal removal.

ROP – Renal unit for dialysis Of Patient
Dialysis achieves extracorporeal removal.

A Cochrane review concluded that, when ECG changes due to hyperkalemia are present, IV calcium is effective in preventing deterioration. Thereafter, emergent therapies for lowering potassium levels are nebulized or inhaled salbutamol and/or IV insulin-and-glucose.

There is no evidence supporting the use of bicarbonate as monotherapy. Existing evidence does not support the use of bicarbonate for inducing intracellular shift in treating acute hyperkalemia.

Kayexalate is an exchange resin used to bind potassium in the intestine when given orally. The two concerns with Kayexalate are its ineffectiveness in lowering serum potassium and its potential toxicity. This has been the subject of a useful review.

Dialysis is efficient, but usually takes about 2 hours to get started in a patient with no dialysis access.

Question 38

Hypertensive Urgency/Emergency

Answer 38

• Overtreatment Of Asymptomatic Hypertension-Urgency Is Not An Emergency: A Teachable Moment ,Yang, J.Y., et al, JAMA Intern Med 178(5):704, May 2018.

SUMMARY: Everyone listening can relate to this case – an asymptomatic patient with a elevated blood pressure is sent in from their PMD or a clinic for “r/o hypertensive emergency.”

The most common manifestations of a real hypertensive emergencies are chest pain, SOB, neurologic deficits with outcomes including stroke, acute pulmonary edema and renal failure. These need to come to the ED, be treated aggressively, and usually admitted to the ICU – but this is different than asymptomatic HTN.

A retrospective cohort study of 58,000 patients seen in the outpatient setting demonstrated that there was no difference in the rate of major adverse cardiovascular events (MACE) in those patients referred to the emergency department vs treated in the ambulatory setting and resulted in more costs through hospitalizations.

Note: Despite widespread use of the term in clinical trials, the definitions of MACE can differ, which makes comparison of similar studies difficult. The so-called “classical 3-point MACE” is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.

EDITOR’S COMMENTARY: This Teachable Moment article in JAMA, the authors argue that less is more when it comes to sending patients the ER for “hypertensive emergency.” In fact, treating an “urgency” aggressively resulted in hypotension, stroke and organ injury – the very things we were trying to prevent! Although ACEP guidelines on this issue have been clear for years saying hypertensive urgency should be treated as an outpatient with oral therapy for long term control, this article tells us there are finally guidelines from ACC/ AHA saying:
**For a patient with hypertensive urgency there is “No indication for immediate reduction of blood pressure in the emergency department or hospitalization.”

Hypertensive Urgency

• *SBP>or=180 or DBP>or=120**
• *WITHOUT signs/symptoms of end organ damage** (often with mild headache)

Occurs more frequently in patients with medication or low sodium diet non-compliance. Severe hypertension can also develop in medication-adherent patients following ingestion of large quantities of salt and can be controlled by resuming a low-salt diet.

• *Hypetensive Emergency**
• *SBP>or=180 or DBP>or=120**
• *WITH signs/symptoms of end organ damage** such as the following:
• *i)** Neurological (stroke, ALOC, encephalopathy, papilledema)
• *iii) CP/ACS
  iv) SOB/acute pulmonary edema**
• *v) AKI**

Immediate but careful reduction in blood pressure is often indicated in these settings. However, an excessive hypotensive response is potentially dangerous, possibly leading to ischemic complications such as stroke, myocardial infarction, or blindness. **Thus, in patients who are severely hypertensive but asymptomatic, slower reductions in blood pressure may be achieved with oral agents.

Note: AKI is diagnosed by increase in the serum Cr and/or a decrease in U/O. The Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging system is the most recent and preferred definition. The KDIGO criteria allow for correction of volume status and obstructive causes of AKI prior to classification. Before diagnosing and classifying AKI, one should assess and optimize volume status and exclude obstruction. The proposed criteria for AKI include ANY of the following:

i) increase in serum Cr of 27 micromol/L within 48 hours
ii) increase of serum Cr ≥1.5 times from baseline in prior 7 days
iii) decrease in urine volume to <0.5 mL/kg/hour over 6 hours

Note: In encephalopathy, the pathologic process is the dilatation of cerebral arteries following a breakthrough of the normal autoregulation of cerebral blood flow. Under normal conditions, cerebral blood flow is kept constant by cerebral vasoconstriction in response to increases in BP. In patients without hypertension, flow is kept constant over a mean pressure of 60-120 mm Hg. In patients with hypertension, flow is constant over a mean pressure of 110-180 mm Hg because of arteriolar thickening.

**When BP is raised above the upper limit of autoregulation, arterioles dilate. This results in hyperperfusion and cerebral edema, which cause the clinical manifestations of hypertensive encephalopathy.

• *i)** loss of cerebrovascular autoregulation causing hyperperfusion and loss of BBB integrity
• *ii) cerebral edema** and microhemorrhages
• *iii)** posterior leukoencephalopathy seen on MRI

HPI]
Neurologial (stroke, ALOC, seizures, visual disturbances, nausea, vomiting)
CP
SOB
U/O reduced

O/E] SBP>180 and/or DBP>120
General – ALOC (confused, lethargic)
Neuros – papilledema, focal deficits
Pulmos – crackles
POCUS – papilledema

INVESTIGATIO]
L(H)/Haim]
CBC, INR, PTT

L(H)/Meta]
Lytes, XLytes, BG

L(H)/Hor]
betaHCG

L(H)/Org(Cardios)]
troponins, CK

L(H)/Org(Nephros)]
Cr

I]
ECG
CXR
CT Head
MRI

RECIPERE]
NP/A,B]
O2
NP/C]
PIV (wide bore), Art-line
NP/Mon]
Cardiac monitoring, BP, SpO2, U/O

P/Poin]
Morphine 4-6mg IV q5-15min OR
Fentanyl 1mcg/kg IV q30-60min (70mcg for 70kg)

P/Naus]
Zofran 4mg IV

P/Org(Cardios)]
Labetalol 10mg IV,
q10min to SBP<180mmHg, max 300mg
(beta and alpha-adrenergic blocker)

P/Org(Vasculos)]

• *Hydralazine 10 mg IV**, q4h
• *Note:** Hydralazine is a direct arterial vasodilator with no effect on the venous system. Fall in blood pressure can be sudden and begins within 10 to 30 minutes and lasts two to four hours. A beta blocker should be given concurrently to minimize reflex tachycardia.

Question 39

Hypokalemia

Answer 39

Hypokalemia

SAN
The lower concentration of K+ outside the cell, causes more K+ to leak out of the K+ leak channels, and decreased intracellular voltage.

• *Myocytes**
  1. Less K+ outside the cell causes more driving force for “leaky” K+ to leave the cell shifting the resting membrane potential (RMP) toward hyperpolarization (less positive).

2. Hyperpolarization causes “more” fast Na+ channels to be available. The fast Na+ channels once activated have a mechanism to stop them from being reactivated (ball and chain), not allowing Na+ ions through. Since the cell is hyperpolarized more Na+ channels are available (less fast Na+ channels are blocked) in the inactivated state “ball and chain”.
3. “More” fast Na+ channels can respond. At this stage in hypokalemia, the cells are MORE excitable. Due to having more fast Na+ channels available, the phase 0 depolarization of the myocyte is steep causing normal/narrow QRS complex.
4. In phase 2 and 3, K+ leaves the cell as there is a large Na+ influx in depolarization. K+ leaves through voltage gated K+ channels (VGKC) delated K+ rectifier channels creating the K+ currents (IKr). VGKC delayed rectifiers are sensitive to external K+ levels (a K+ ion holds the K+ channel open). In hypokalemia, with a decreased external K+ concentration, the IKr flow decreases out of the myocyte as there are less K+ ions holding the K+ channels open. Due to the depressed IKr, phase 2 and 3 are legthened represented as a lengthened QT interval.

Question 40

Infusions

Answer 40

Post Intubation Sedation
Propofol 30 mcg/kg/min IV, titrated up
Ketamine 1 mcg/kg/min IV, titrated up

Blood Pressure
Levofed 0.05 mcg/kg/min IV, titrated up to desired MAP
Dopamine 2.5 mcg/kg/min IV, titrated up to desired MAP
Epinephrine 0.05 mcg/kg/min IV, titrated up

Push Pressor
Epinephrine 10 mcg bolus
Note: 10cc of a 10 mcg/cc bolus dose can be made by taking 1 NS 10cc flush and adding 1cc from the 0.1 mg/cc 10cc epinephrine syringe used in resusitations giving 0.1mg/10ccs, or 0.01mg/1cc (10 mcg/cc).

Inotrope – heart block, bradyarrythmias
Isoproterenol 2.5 mcg/min IV, titrated up to 20 mcg/min

Venodilation/Vasodilation – acute heart failure
NTG 5 mcg/min IV, titrated up to 20 mcg/min

Question 41

Nephrolithiasis

Answer 41

Dx]
i) Clinically suspected

ii) Confirmed with imaging
iii)

Pathology/Etiology]
In a liquid, crystallization occurs when a solution becomes supersaturated with the solute causing nucleation and crystal growth. In the kidney, crystals form when there is an increase in the solute and/or decrease in the solvent (urine). Typical solutes are Ca²⁺ (calcium), PO₄^3-(phosphate), C₂O₄^2- (oxalate), NH₄⁺ (ammonium), C₅H₄N₄O₃ (uric acid), (SCH₂CH(NH₂)CO₂H)₂ (cystine). Crystal stones produces in order of frequency are the following:

i) calcium oxalate or calcium phosphate ~80%
ii) uric acid ~17%
iii) cystine ~2%

Risk factors/Red flags]

DDx – acute to benign]

Investigatio – rule in/rule out]

Recipere]

Sexual Intercourse As A New Option In The Medical Expulsive Therapy Of Distal Ureteral Stones In Males: A Prospective, Randomized, Controlled Study Bayraktar, Z., et al, Int Urol Nephrol 49(11):1941, November 2017
CONCLUSIONS: Sexual activity may facilitate the passage of distal ureteral stones in men.
EDITOR’S COMMENTARY: This was a randomized controlled trial of 190 married adult men with radiographically confirmed ureteral stones (5-10mm in size) in Turkey who were assigned to one of three treatment arms: sexual intercourse 3 times/week, tamsulosin 0.4 mg daily, or placebo. The rate of spontaneous passage was similar in patients in the sexual intercourse and tamsulosin groups (82% in each group) when compared to placebo (52% passage rate). The authors conclude that sexual activity may facilitate the passage of distal ureteral stones in men.

Question 42

Low Back Pain

Answer 42

DDx
Org(Vasculo)]
AAA – older, HTN, “ripping pain”, syncope, pulsatile abdominal mass, POCUS >5cm

Org(Nephros)]
Nephrolithiasis – renal colic (obstruction of urinary tract) causing increased peristalsis of urreter and renal capsular distention leading to visceral pain, intermittent pain that waxes and wanes with writhing and inability to sit still, N, V, unilateral flank pain radiating to groin, CVA tenderness,

Infla]

• *OA** – age
• *Anklyosing spondylitis** – young, HLA-B27 positive, pain/stiffness from cervical to lumbar worse in the morning and with inactivity
• *Psoriatic spondylitis** – psoriasis

Oncos]

• *Mets** – prior history of cancer, constitutional symptoms, midline tenderness (over specific vertebrae)
• *MM** – CRAB (Hypercalcemia, renal failure (bence jones proteins), anemia, bony lytic lesions

Infect]
OM, Discitis (endocarditis), Psoas abscess – IV drugs, indwelling catheter, fever, new onset back pain, bacteremia, immune compromise (DM, HIV), midline tenderness, neurological deficits
Spinal Epidural Abscess (SEA) – SEA triad – fever, mindline tenderness, neurological deficits
UTI (Cystitis) – dysuria, frequency, urgency, suprapubic pain, low back pain
Pyelonephritis – flank or abdominal pain, CVA tenderness, fever, N, V
Herpes zoster – rash

Struct]
Cauda Equina/cord compression – bilateral sciatica, lower extremity weakness, urinary retention, bowel incontinence, loss of anal tone, sacral anesthesia
Note: Cauda equina is L2 and below resulting in LMN lesion. Conus medullaris is L2 and above resulting in UMN lesion.
Herniated disk (radiculopathy)/spondylolithesis/ligamental strain – clear casual event, degenerative changes
Fracture (vertebral, compression) – age, osteoporosis, osteopenia, trauma, steriods

HPI]
AAA – syncope, lightheaded, diaphoresis, “ripping pain”
Anklyosing/Psioratic Spondylitis – young, worse with inactivity (morning), psoriasis
Mets, MM – fevers, night sweats, weight loss
OM (discitis), Psoas abscess – fevers, IV drugs, midline tenderness
SEA – fever, midline tenderness, neurological deficit, IV drugs
Cauda equina – bilateral sciatica, urinary retention, bowel incontinence, saddle anesthesia

PMHx]
Cancer (Mets, MM)
Osteoporesis (fracture)
DM, HIV, Immunocompromised (OM, SEA, Psoas abscess)
Renal failure (MM)

Meds]
Anti-coagulants
Steriods (compression fracture)

SHx]
IV drug use (OM, SEA, Psoas abscess)

• *O/E] TC (AAA), HypoTN (AAA) , Fever (Infect, Oncos)**
• *Neuros** – gait, strength, tone (anal if necessary), reflexes, sensation, 95% of disc herniations occur at the L4/L5, L5/S1
• *L4** - sqauat and rise, knee jerk reflex - extension of quadriceps; sensory loss to anterior leg, first toe, medial malleolus; pain to anterior medial thigh
• *L5** - heel walking - dorsiflexion of great toe and foot; sensory loss to dorsal foot, middle 3 toes; pain to lateral thigh and leg
• *S1** - toe walking, ankle jerk reflex - plantar flexion of great toe and foot, sensory loss to lateral foot, pinky toe, and heel; pain to posterior thigh and leg, lateral foot
• *S2,S3,S4** - anal tone, saddle anesthesia
• *Strait leg exam** – pain produced in raised leg, crossed strait-leg test produces pain in unraised leg
• *Cardios** – new murmur (endocarditis)
• *Vasculo** – symmetric pulses – femoral, popliteal, dorsalis (AAA)
• *Abdos** – pulsatile abdominal mass (AAA) , abdominal distention
• *MSK** - midline tenderness (SEA, OM, malignancy, fracture)

POCUS – AAA>5cm, hydronephrosis

INVESTIGATIO]
L(H)/Infect]
ESR (90-98% sensitive) (OM, SEA), CRP

L(O)/Haim | Meta | Infect]
Urine dip (Hemoglobin | Protein | Leukocytes & Nitrates) (UTI, pyelonephritis)
Note: Psuedomonas (GN), Enterococci (GP cocci in pairs), and Staph. sparophyticus (GP) do NOT reduce nitrates
L(O)/Meta]
beta HCG

L(I)/Haim]
Blood C&S (OM, SEA, urosepsis)
L(I)/Ouron]
Urine C&S (UTI, pyelonephritis)

I]
XR Spine (Mets, MM, fracture, spondylolithesis)

• *KUB** (nephrolithiasis, radioopaque - calcium, struvite – ammonium, magnesium, phosphate, cystine)
• *Note:** KUB has limited utility as some stones such as uric acid are radiolucent.

CT with contrast (OM, SEA) without contrast (nephrolithiasis, fracture, spondylolisthesis, cord compression)

MRI with contrast (OM, SEA, mets, MM) without contrast (fracture, spondylolithesis)

U/S PVR >100mL (cord compression), U/S kidney (hydronephrosis, stones)

RECIPERE]
NP/C]
PIV and Fluids (AAA, nephrolithiasis), type and cross (AAA)
NP/Mon]
cardiac, BP, SpO2 (Trauma)

P/Poin]
Acetaminophen 650-1000mg q6h PRN
Ibuprofen 400-600 mg q6h PRN
Diazepam 5-10mg q8h PRN (muscle relaxant)
Toradol 15mg IM/IV (IV for nephrolithiasis)
Tramadol 50mg q12h PRN titrated up to 400mg/day
Percocet 1-2 tabs PO q4-6h PRN (short course)

P/N,V]
{Zofran} 4mg IV
{Gravol} 50mg IV/PO

P/Org(Vasculo)]
{Adalat} Nifedipine 10mg PO TID x4weeks
(CCB causes vasodilation for nephrolithiasis )
{Flomax} Tamsulosin 0.4mg PO OD x4weeks
alpha1 blocker on smooth muscle causes vasodilation for nephrolithiasis)

P/Infla, Struct]
Dexamethasone 10mg IV (cord compression)

P/Infect]
Pip-Tazo 3.375g IV
Vancomycin 1g IV

Consult]
Neurosurg (cord compression, OM, SEA)
Gensurg (AAA)
Urology (Nephrolithiasis, stone>10mm)

Question 43

Meningitis

Answer 43

1. Diagnosis (suspected on clinical, confirmed by lab)
Meningitis can be caused by infectious or noninfectious etiologies. Noninfectious etiologies of meningitis include malignancy, autoimmune conditions, medications, trauma, and iatrogenic procedures. Infectious meningitis can be caused by a variety of bacterial, viral, fungal, and parasitic organisms. Bacterial and viral organisms account for the most common types of infectious meningitis. In general, viral meningitis is a self-limited disease that resolves with supportive care. In contrast, bacterial meningitis is associated with significant morbidity and mortality.

Clinical (suspected)
headache
fever
neck stiffness
(nuchal rigidity, brudzinski, kernig, jolt accentuation)
ALOC
nausea/vomiting

Note: The most common clinical features include a severe headache (84 percent), fever greater than 38°C (74 percent), stiff neck (74 percent), a Glasgow Coma scale <14 (71 percent), and nausea (62 percent). Although patients may not complain specifically of a stiff neck, it is important to assess for meningeal irritation. Passive or active flexion of the neck will usually result in an inability to touch the chin to the chest. Difficulty in lateral motion of the neck is a less reliable finding.

Lab/imaging (confirmed)

• *CSF analysis**
  i) Gram stain and C&S

ii) Cell count and differential
WBC > 1000/uL, neutrophils > 80%

iii) Glucose concentration
<40 mg/dL (<2.22 mmol/L) AND
Protein concentration
>200 mg/dL (>2000 mg/L)

iv) Extra analysis, PCR etc

Note: CT of the brain before LP is indicated in the following subset of patients: age >60, a history of central nervous system (CNS) disease, immunocompromised state, a history of seizure <1 wk before presentation, altered level of consciousness, or focal neurological deficits.

An important early decision relates to whether a head computed tomography (CT) should be performed prior to LP to exclude a mass lesion or increased intracranial pressure. These abnormalities might rarely lead to cerebral herniation during removal of large amounts of CSF, and cerebral herniation could have devastating consequences.

_Time course (from CDC)_
Symptoms of bacterial meningitis can appear quickly or over several days. Typically they **develop within 3 to 7 days after exposure.**

2. Pathophysiology/Etiology (from CDC)
1) Streptococcus pneumoniae (nasopharynx)
Gram positive diplococcus (pneumococcal).
Vaccines: Pneumovax 23, Prevnar 13, both do various strains.

2) Neisseria meningitidis (nasopharynx)
Gram negative diplococcus (meningococcal).
Vaccines: Bexsero (B), Menjugate (C), MCV4 (A,C,W-135,Y)
A, B, C, W-135, and Y.

3) Listeria monocytogenes (GI tract)
Gram positive coccobacillus
Patients over 50 years of age or those who have deficiencies in cell-mediated immunity.

4) Group B Streptococcus (aka Streptococcus agalactiae)
Gram positive coccus found on the body as natural flora.

5) Haemophillus influenze B
Gram negative coccobacillus.
Vaccine: Hib

From CDC the following bacteria infect different age groups:
Newborns
GBS (Group B Streptococcus, from vagina)
S. pneumoniae
L. monocytogenes
E. coli

Babies and children
S. pneumoniae
N. meningitidis
H. influenzae type b (Hib)
GBS (group B streptococcus)

Teens and young adults
N. meningitidis, S. pneumoniae

Older adults
S. pneumoniae
N. meningitidis
L. monocytogenes
Hib
GBS

Group B Streptococcus (GGC, aka streptoccus agalatia) and E. coli: Mothers can pass these bacteria to their babies during birth.

Haemophillus influenza b and Streptococcus pneumoniae: People spread these bacteria by coughing or sneezing while in close contact with others, who breathe in the bacteria.

Nisseria meningitidis: People spread these bacteria by sharing respiratory or throat secretions (saliva or spit). This typically occurs during close (coughing or kissing) or lengthy (living together) contact.

E. coli: People can get these bacteria by eating food prepared by people who did not wash their hands well after using the toilet.

People usually get sick from E. coli and Listeria monocytogenes eating contaminated food.

3. Risk factors/Red flags
unimmunized
immunocompromised
immunosupressed
very young, very old

4. Other diagnosis – starting from acute to benign
Fungal Meningitis
ICH
CVA
Viral Meningitis

5. Investigations (rule in/out)
CSF (LP) C&S rules in bacterial meningitis

• *6. Treatment/Management**
• *Dexamethasone 10mg IV** (0.15 mg/kg) prior to antibiotics and until cultures are negative for S. pneumoniae
• Ceftriaxone 2 g IV q12h*AND
• *Vancomycin 2 g IV (25-30 mg/kg)**

Add ampicillin 2 g IV, patients > 50 y old or with chronic illness

Add acyclovir 700 mg IV (10 mg/kg) IV when herpes simplex virus (HSV) meningitis/encephalitis meningitis is suspected (e.g., negative gram stain)

Question 44

Migraine

Answer 44

​

Diagnosis – Clinical (imaging not necessary)
International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria

_Migraine without aura_
1) 5 or more attacks

2) 4 to 72 hours (untreated or unsuccessfully treated)

3) 2 of:
pulsating
unilateral
moderate or severe pain
aggravation by (or avoidance of) routine physical activity (eg, walking or climbing stairs)

4) 1 of (during attack):
nausea, vomiting, or both
photophobia and phonophobia

5) Not better accounted for by another diagnosis

Note: POUND acronym. Pulsatile quality (headache described as pounding or throbbing), One-day duration (episode may last 4-72 hours if untreated), Unilateral in location, Nausea or vomiting, and Disabling intensity (altered usual daily activities during headache episode).

_Migraine with aura_
Note: Some patients may experience aura without an associated headache. Migraine aura without headache manifests as isolated aura unaccompanied by headache. Auras without headache may be confused with transient ischemic attacks, especially when they first present in older patients as late-life migraine accompaniments.

Note: Aura without headache. Late-life migraine symptoms related to the onset after the age of 50 years of migraine aura without headache. The most common symptoms are visual auras, followed by sensory auras (paresthesia), speech disturbances, and motor auras (weakness or paralysis). The most common presentation is gradual evolution of aura symptoms with spread of transient neurologic deficits over several minutes and serial progression from one symptom to another.

1) 2 or more attacks

2) Reversible aura
* *Note:** ***The slow spread of positive symptoms (cortical excitation) followed by negative symptoms (cortical depression) is quite characteristic of migraine aura and is not typical for an ischemic event.

Typical migraine auras are characterized by gradual development, duration no longer than one hour, a mix of positive and negative features, and complete reversibility. Positive symptoms indicate active discharge from central nervous system neurons. Typical positive symptoms can be visual (eg, bright lines, shapes, objects), auditory (eg, tinnitus, noises, music), somatosensory (eg, burning, pain, paresthesia), or motor (eg, jerking or repetitive rhythmic movements). Negative symptoms indicate an absence or loss of function, such as loss of vision, hearing, feeling, or ability to move a part of the body. Auras are most often visual, but can also be sensory, verbal, or motor disturbances.

The aura of migraine usually develops gradually over more than five minutes. Less often, the aura develops more acutely (ie, in less than five minutes). The acute onset of aura can confuse migraine with a transient ischemic attack (TIA) or stroke.

i) Visual
* *Note:** A visual aura affecting both eyes which classically begins as a small area of visual loss often just lateral to the point of visual fixation. It may either appear as a bright spot (positive symptom) or as an area of visual loss (negative symptom). Over the following five minutes to one hour, the visual disturbance expands to involve a quadrant or hemifield of vision. Along the expanding margin geometric shapes or zigzagging lines often appear. The shapes account for one of the common names for aura, the “fortification spectrum”, because of the resemblance of the aura to the walls of a medieval fortress. The positive visual phenomena may assume a sickle or C-shape, expanding over time toward the peripheral visual field, leaving a scotoma or area of complete visual loss in their wake. As the aura moves off into the peripheral visual field, it often assumes a shimmering or scintillating quality. As the aura resolves, vision usually returns first to the areas of central vision initially affected by the aura

ii) Retinal (retinal migraine) – Only one eye affected.
Note:Retinal migraine is averyrare conditionthat is characterized by repeated attacks ofmonocular scotoma(blindness, a negative symptom) lasting less than one hour, associated with or followed by headache. The International Headache Society prefers the term retinal migraine, but ocular migraine has been suggested as a more precise term, since bothretinal and ciliary circulations may be involved. Occasionally the onset may be abrupt and difficult to distinguish from amaurosis fugax.

iii) Sensory
* *Note:** The sensory aura is common and typically follows the visual aura within minutes, although it may also occur without the visual aura. A sensory aura usually begins as a tingling in one limb or on one side of the face. As the tingling sensation migrates across one side of the face or down the limb, numbness is left in its wake that may last up to an hour. The sensory aura may also move inside the mouth, affecting the buccal mucosa and half the tongue. The slow spread of positive symptoms (scintillations or tingling) followed by negative symptoms (scotoma or numbness) is quite characteristic of migraine aura and is not typical for an ischemic event.

iv) Speech
* *Note:** Less common than the visual and sensory auras is the language or dysphasic aura. Language auras cause transient problems that may run the gamut from mild wording difficulties to frank dysphasia with paraphasic errors.

v) Motor (hemiplegic migraine)
Note:The primary feature that separates hemiplegic migraine from other types of migraine with aura is thepresence of motor weaknessas a manifestation of aura in at least some attacks. In addition to motor weakness during the aura phase, which is typically unilateral, the manifestations of hemiplegic migraine attacks may variously include severe headache,scintillating scotoma, visual field defect, numbness, paresthesia, aphasia, fever, lethargy, coma, and seizures.

vi) Brainstem (migraine with brainstem aura)
* *Note:** Migraine with brainstem aura (basilar-type migraine) is an uncommon form of migraine with aura wherein the primary signs and symptoms are referable to the brainstem without weakness. Occurs more often in females than in males with onset usually between ages 7 to 20. The auras consist of some combination of vertigo, dysarthria, tinnitus, diplopia, ataxia, decreased level of consciousness, and hypacusis (hearing impairment). Attacks nearly always include two or more brainstem-related aura symptoms.

3) 3 or more of:
i) aura spreads gradually over ≥5 minutes

ii) aura lasts 5 to 60 minutes
iii) 1 aura symptom is unilateral
iv) 1 aura symptom is positive
v) aura is accompanied, or followed within 60 minutes, by headache
vi) 2 or more symptoms occur in succession
4) Not better accounted for by another ICHD-3 diagnosis

Pathophysiology/Etiology
Migraine is a neurovascular phenomenon that involves the trigeminal nerve, upper cervical nerves, astrocytes, the dural and pial vasculature, and the dura membrane. The current state of knowledge suggests that migraine is caused by a primary neuronal dysfunction that leads to aura and headache. A causal association between migraine aura and headache is supported by evidence that both are linked to the phenomenon known as cortical spreading depression (CSD). Cortical spreading depression is a slowly propagating wave of altered brain activity (excitation followed by depression) that involves dramatic changes in neuronal, glial (astrocyte, microglia) and vascular function.

Various experimental triggers can be used to evoke CSD in animal models, including local mechanical changes, tetanic or DC electrical stimulation, glutamate receptor agonists, microemboli (possibley from patent foramen ovale), hypoosmotic medium (possibley from hyponatremia), endothelin, KCl, ouabain. In humans, traumatic brain injury, stroke and SAH have been found to cause CSD.

Note: Ouabain is a plant derived toxic substance that was traditionally used as an arrow poison in eastern Africa for both hunting and warfare inhibiting the Na⁺/K⁺ -ATPase.

Models of CSD typically include elevations in extracellular K⁺ as a critical event in the initiation of CSD. The activation of CSD by glutamate receptor agonists, and the inhibition of CSD by glutamate receptor antagonists in most preparations, also suggest a key role for activation of neuronal glutamate receptors in the initiation of CSD. The source of the increased K⁺ and glutamate, however, remains unknown.

The migraine attack is initiated in the putative migraine generators of the brain such as the thalamus, hypothalamus and pons.

3. Risk factors/Red flags
4. Other diagnosis – starting from acute to benign
5. Investigations (rule in/out)
6. Treatment/Management
   * Randomized Study Of IV Prochlorperazine Plus Diphenhydramine Vs. IV Hydromorphone For Migraine Friedman, B.W., et al, Neurology 89(20):2075, November 14, 2017

CONCLUSIONS: {Stemetil} Prochlorperazine 10mg IV plus diphenhydramine 25mg IV was superior to hydromorphone 1mg IV in these adult ED patients with moderate to severe migraine. The authors feel that it should be considered first-line therapy in these cases.
EDITOR’S COMMENTARY: These authors compared outcomes in adult patients with moderate to severe migraine headache following IV hydromorphone versus IV prochlorperazine plus diphenhydramine. The primary outcome was sustained headache relief. The study was stopped prematurely due to the overwhelming superiority of prochlorperazine over hydromorphone for sustained headache relief (60% versus 31%; difference of 28%; 95% CI 12-45), with a number-needed-to-treat (NNT) of only four patients.

HPI]
unilateral, pulsating, photophobia, phonophobia, auras, worse with physical activity, gradual onset 4-72 hours, nausea, vomiting, neurological deficits such as aphasia, hemiparesthesias, hemiparesis.
POUND – pulsatile, one day duration 4-72 hours, unilateral, nausea/vomiting, disabling

RECIPERE]
NP/C]
NS 1L bolus

P/Poin]
{Toradol} Ketorolac 15mg IV/IM x1

P/Poin,N,V]

• *{Maxeran} Metoclopramide 10mg IV/IM x1**
• *Note: Dopamine antagonists have 80-90% effectiveness when given IV**, 60-80% IM, and 40% PO.

P/Org(Neuros)]
Sumatriptan 50mg PO x1
(early in migraine when aura is present)

P/Infla]
{Decadron} Dexamethasone 10mg IV/IM x1
(if migraine >72hours)

Question 45

Myotomes/Dermatomes/Nerves

Answer 45

Taken from the ASIA – American Spinal Injury Association.

Myotomes
Upper body (all with patient seated and against resistance)
C1 - neck flexion
C2 - neck extension
C3 - lateral neck flexion
C4 - shoulder raise [accessory nerve]
C5 - elbow flexion (biceps reflex)
Note: Same direction arm would go when reflex induced.
C7 - elbow extension (triceps reflex)
Note: Same direction arm would go when reflex induced.
C6 - wrist extension (brachioradialis reflex) [radial nerve]
Note: The brachioradialis reflex causes slight supination or pronation and slight elbow flexion. The reflex does NOT cause wrist extension as the brachioradialis does not cross the wrist.
C8 - thumb in opposition [median nerve]
T1 - finger abduction pinky finger [ulnar nerve]
C7, C8, T1 - grip strength

Lower body (all with patient seated and against resistance)
L2 - hip flexor
L3 (L4) - knee extension
Note: L4 is the same direction lower leg would go when reflex induced.
S2 - knee flexion
L4 - ankle dorsiflexion
L5 - great toe extension
S1 - ankle plantarflexion
Note: Same direction foot would go when reflex induced.

Dermatomes
Upper body
C2 - occipital protuberance
C3 - supraclavicular midclavicular line
C4 - AC joint
C5 - radial side proximal antecubital fossa
C6 - dorsal thumb proximal phalanx (thumb ring) [radial nerve]
Note: thumb tip [median nerve]
C7 - dorsal ring finger proximal phalanx (ring finger ring) [radial nerve]
Note: ring finger tip [median nerve]
C8 - dorsal pinky finger proximal phalanx (pinky finger ring) [ulnar nerve]
Note:pinky finger tip[ulner nerve]
T1 - ulnar side proximal antecubital fossa
T2 - axilla apex

Mid body
T3 - MCL 3rd IC space
T4 - nipple, MCL4th IC space
T5 to T9 - MCL corresponding IC space
T10 - umbilicus, MCL 10th IC space
T11 - MCL 11th IC space
T12 - MCL mid inguinal ligament

Lower body
L1 - groin
L2 - mid anterior thigh
L3 - medial femoral condyle (upper)
L4 - medial malleolus [saphenous nerve]
L5 - dorsum of 3rd MTP [superficial peroneal nerve]
S1 - lateral calcaneus [sural nerve]
S2 - mid popliteal fossa
S3 - gluteal fold, ischeal tuberosity
S4/S5 - perianal
Note: saddle area is around the L5-S2 dermatome.

Question 46

Na+/K+ ATPase

Answer 46

Na+/K+ ATPase brings 3Na+ out of the cell and 2K+ into the cell, in order to rebalance the ions of the cell.

Adrenergics bind to beta2 receptors causing an increase in cAMP and the phosporylation of Na+/K+ ATPase by PKA. beta2 receptors are found on all smooth muscle including vascular smooth muscle, and striated muscle.

The Na+/K+ ATPase is upregulated by cAMP. Substances causing an increase in cAMP upregulate the Na+/K+ ATPase. These include the ligands of the Gs-coupled GPCRs, such as norepinephrine (NE). In contrast, substances causing a decrease in cAMP downregulate the Na+/K+ ATPase. These include the ligands of the Gi-coupled GPCRs, such as acetlycholine (Ach).

Insulin binds to tyrosine kinase receptors which autophosphorylates leading to phosphorylation of second messenger proteins and activation of Na+/K+ ATPase.

Aldosterone binds to the MR (Mineralcorticoid Receptor) and causes rapid and sustained increased activity, sustained through gene transcription, inducing the synthesis of Na+/K+ channels and Na+/K+ ATPase.

Digoxin’s primary mechanism of action involves inhibition of the Na+/K+ ATPase, mainly in the myocardium. This inhibition causes an increase in intracellular Na+, resulting in decreased activity of the Na+/Ca2+ exchanger (NCX), which normally imports three extracellular Na+ into the cell and transports one intracellular Ca2+ ion out of the cell. The inaction of this exchanger causes an increase in the intracellular Ca2+ concentration that is available to the contractile proteins leading to its inotropic effect. Increased intracellular Ca2+ lengthens phase 4 and phase 0 of the SAN and AVN action potential, which leads to a decrease in heart rate.

Question 47

National Emergency X-Radiography Utilization Study

(NEXUS)

Answer 47

Scan if ANY of the following present:

HPI]

• *1. Intoxication**
• *2. Painful distracting injury**
• *Note:** Painful distracting injury is an a condition thought by the clinician to be producing pain sufficient to distract the patient from a second (neck) injury. The Canadian C-spine rule describes distracting injuries as “injuries […] that are so severely painful that the neck examination is unreliable.” Common examples include long bone fractures, visceral injuries requiring surgical consultation, large lacerations, degloving injuries, crush injuries, large burns, and injuries producing acute functional impairment.

O/E]

• *3. ALOC**
• *4. Midline cervical spine tenderness**
• *5. Focal neurological deficits**

Question 48

Ottawa Ankle Rules

Answer 48

An ankle X-Ray is required ONLY if:

1. Medial or lateral malleolus tenderness 6cm at the posterior portion.
   AND
2. Unable to bear weight immediately at the time of injury and in the ER.

A foot X-Ray is required ONLY if:

1. Medial tenderness at the navicular or lateral tenderness at the base of the 5th metatarsal.
   AND
2. Unable to bear weight immediately at the time of injury and in the ER.

Question 49

PALS

Answer 49

Initial Impression
Appearance, Breathing, Circulation (from the bedside 2-3seconds)
Appearance
TICLS – tone, interactiveness, consolability, look/gaze, speech

Work of Breathing
stridor (inspiratory, expiratory)
gasping
grunting
WOB (nasal flaring, head bobbing, suprasternal/tracheal retractions, intercostal, substernal, subcostal, paradoxal abominal)

Circulation
color (pallor or cyanotic skin/mucous membranes, mottling)
temperature (cold, pale extremities vs warm pink extremities)
petechia/purpura

Primary Assessment
Note: Patient should have monitors on already, if not designate someone to put monitors on.
ABCDE
Airway (designate)
RR
Inspection – stridor, gasping, grunting, apnea, chest/abdoment movement, WOB
Palpation – signs of trauma, c-spine
Ascultation – air entry, stridor (inspiratory, expiratory), crackles, wheeze, RR
Rx]
head tilt
chin lift
suctioning
oropharyngeal tube

Breathing
SpO2 >94% RA (adequate oxygenation), <90% on 100% needs NIPPV (BMV, CPAP, BiPAP), ETT
Rx]
NP (up to 4L), facemask (up to 6L), NRB (10-15L), high flow NP (4-40L)
NIPPV

Circulation
HR/pulse, BP (70 + (age x 2))
peripheral/central (mucous membranes) pallor or cyanosis, warm shock vs cold shock
Rx]
CPR/medications
Correctable causes of shock – fluids, vaspressors, iontropes

Disability
Neuros – pupils, GCS, AVPU, CNs
AVPU (alert, voice, pain, unresponsive)
Rx]
BG, Labs

• Exposure*
• *T**

Secondary Assessment
HPI – events, pertinant positives and negatives
PMHx
Meds
Allergies
SHx – including last meal

Question 50

Platelets, Coagulation and Drugs

Answer 50

• *Adhesion – Activation – Aggregation**
• *Unactivated in blood** – Essentially all the coagulation factors –Factors I (fibrinogen), II (prothrombin), V, VII, IX, X, XI, XIII, as well as protein C, protein S and antithrombin – except VIII are made in the liver and circulate in the blood. VIII is made in the endothelial cells and is bound to vWF, in a VIII/vWF complex. The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation. It is also responsible for a large part of amino acid synthesis. The liver plays a role in the production of clotting factors as well as red blood cell production.

Presented to the blood – Collagen fibers and tissue factor (TF). TF (also called coagulation factor III) is a cell surface glycoprotein found on the surface SMC, fibroblasts and on activated endothelium and monocytes after exposure to TNFalpha.

Note: TNFalpha is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by activated macrophages. It can bind to, and thus functions through its receptors TNFR1 and TNFR2. TNFR1 is expressed in most tissues, and can be fully activated by both the membrane-bound and soluble trimeric forms of TNFalpha, whereas TNFR2 is found typically in cells of the immune system, and respond to the membrane-bound form of the TNFalpha homotrimer.

TNFalpha has a number of actions on various organ systems, generally together with interleukin-1 (IL-1) and interleukin-6 (IL-6), the proinflammatory cytokines. Nearly all cells that have a nucleus are capable of producing interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFalpha), particularly endothelial cells, epithelial cells and resident macrophages.

TNFalpha also causes an effect on these other tissues:
Hypothalamus
By stimulation of the hypothalamic-pituitary-adrenal axis by stimulating the release of corticotropin releasing hormone (CRH), suppressing appetite and causing fever.

Liver
By stimulating the acute phase response, leading to an increase in C-reactive protein (CRP) and a number of other mediators and induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs insulin signaling. Interleukin-6 (IL-6) is the major inducer of CRP from the hepatocytes.

Immune system
By acting on macrophages stimulates phagocytosis, and production of IL-1 and the inflammatory lipid Prostaglandin E2 (PGE2). TNFalpha is a potent chemoattractant for neutrophils, and promotes the expression of adhesion molecules on endothelial cells (VCAM, ICAM, E-Selectin), helping neutrophils migrate. Activated endothelium and monocytes express TF on their surface after being exposed to TNFalpha. A local increase in concentration of TNFalpha will cause the cardinal signs of inflammation to occur: heat (calor), swelling (tumor), redness (rubor), pain (dolar) and loss of function.

Whereas high concentrations of TNFalpha induce shock-like symptoms, the prolonged exposure to low concentrations of TNFalpha can result in cachexia, a wasting syndrome found, for example, in cancer patients.

TNFalpha promotes the inflammatory response, which, in turn, causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma. These disorders are sometimes treated by using a TNFalpha inhibitor. This inhibition can be achieved with a monoclonal antibody such as infliximab (Remicade) binding directly to TNFα, adalimumab (Humira), certolizumab pegol (Cimzia) or with a decoy circulating receptor fusion protein such as etanercept (Enbrel) which binds to TNFalpha with greater affinity than the TNFR.

Anti-TNF therapy has shown only modest effects in cancer therapy. Treatment of renal cell carcinoma with infliximab (Remicade) resulted in prolonged disease stabilization in certain patients. Etanercept was tested for treating patients with breast cancer and ovarian cancer showing prolonged disease stabilization in certain patients via downregulation of IL-6 and CCL2. Chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection.

On the other hand, adding infliximab or etanercept to gemcitabine for treating patients with advanced pancreatic cancer was not associated with differences in efficacy when compared with placebo

TNFalpha is involved in the regulation of a wide spectrum of biological processes including coagulation, cell proliferation, differentiation, apoptosis, and lipid metabolism, and has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer.

Collagen fibers and TF are exposed to the blood during damage or inflammation. TF is exposed to the blood on the surface of activated endothelium and monocytes during inflammation through activation by TNFalpha (mainly secreted by macrophages). Platelet glycoproteins (as per below) bind to collagen fibers and VII binds to TF activating the extrinisic pathway eventually forming thrombin (IIa). Thrombin (IIa) separates vWF/VIII, and converts fibrinogen to fibrin. vWF binds to a platelet glycoprotein complex (as per below) and to collagen stabilizing the platelet from high sheer stress. ADP, TXA2 and thrombin (IIa) bind to their platelet receptors activating GPIIb-IIIa to a high affinity state. vWF and fibrinogen bind to the high affinity GPIIb-IIIa forming crossbridges to other platelets.

Note: Purinogenic G-coupled protein receptor (PY2, ADP), Thromboxane G-coupled protein receptor (TP, thromboxane), Protease Activated Receptor (PAR, thrombin).

Note: ADAMTS13 protease inactivates vWF. Deficiencies of ADAMTS13 had been found in Thrombotic Thrombocytopenia Purpura (TTP), and Hemolytic Uremic Syndrome (HUS). In TTP and HUS, the platelets get used up as vWF is not inactivated. The microclotting of platelets sheers red blood cells causing hemolysis.

Note: Tissue Factor (TF) is expressed on the surface of fibroblasts, smooth muscle cells (SMCs) and on activated endothelium and activated monocytes during inflammation processes (when activated by TNFalpha). TF is not normally exposed to blood. Factor VII (circulating in the blood) binds to TF on the activated endothelium, fibroblasts and SMCs, and is activated to form TF/VIIa. VIIa then activates factor IX into IXa, and factor X into Xa, leading to the activation of factor II into IIa (thrombin). Thrombin converts fibrinogen into fibrin, forming the fibrin mesh in coagulation.

**TF/VIIa activates the proteases Factor IX into IXa, and X into Xa leading to the formation of thrombin which forms the fibrin mesh.

Note: Thromboplastin is the combination of TF and phospholipids and historically was a lab reagent usually derived from placental sources. Thromboplastin is needed to activate the extrinsic pathway. Phospholipids were later termed the partial thromboplastin as they were needed to activate the intrinsic pathway, where TF is not needed to activate the intrinsic pathway. The intrinsic pathway was thus named the partial thromboplastin time, PTT. Now the PTT is named the contact activation pathway.

Adhesion
Collagen is first exposed to the blood. Integrin GPIa-IIa and then GP receptor GPVI bind to collagen for low sheer adhesion. GPIb-V-IX complex binds to vWF bound to collagen leading to tight adhesion under high sheer stress.

When collagen is exposed to the blood, platelets bind to collagen by the integrin GPIa-IIa first, which then allows GPVI receptor binding (glycoprotein receptor for collagen). The binding stabilizes the platelets but not sufficient under high sheer stress.

Note: Integrins are proteins that function mechanically, by attaching the cell cytoskeleton to the extracellular matrix (ECM), and biochemically, by sensing whether adhesion has occurred through intracellular cascades.

To ensure platelet adhesion under high sheer stress, vWF binds to the glycoprotein complex GPIb-V-IX, and to collagen.

• *Activation**
• *Once platelet has adhereed by the glycoproteins and integrins under high sheer stress, intracellular cascades cause a change in cytoskeleton and the release of ADP and TXA2 through alpha and dense granules.**
• *Aggregation**
• *The binding of IIa, ADP, TXA2 to their corresponding receptors activates the integrin GPIIb-IIIa to a high affinity state. Once activated, fibrinogen and vWF can bind to GPIIb-IIIa creating crossbridges to other platelets.**

Note: **ADP and TXA2 are platelet aggregating agents by binding to platelet membrane receptors. Medications used against these receptors (ASA, Plavix) leads to less platelet adhesion.

**Thrombin (IIa) is the **most potent platelet aggregating agent and strongest agonist **. When IIa binds to platelet membrane receptors, PARs, it is is converted to IIa on the activated platelet surface.

By binding of ADP, TXA2 (thromboxane), IIa (thrombin), to their receptors P2Y, TP, PAR, causes integrin GPIIb-IIIa to be converted to a high affinity state. Fibrinogen and vWF bind to the high affinity integrin GPIIb-IIIa creating crossbridges to other platelets, by also binding to GPIb-V-IX and GPIIb-IIIa on the other platelets.

Note: P2YR is a G-coupled receptor and is activated by ADP. ADP binds to the P2Y12 receptor that leads to inhibition of adenyl cyclase and thereby decreases the intracellular levels of cAMP, and activation of GPIIb-IIIa.

• *Note: vWF** is produced constitutively by endothelium and circulates in the blood bound to Factor VIII in a vWF/VIII complex. Factor VIII is degraded when not bound by vWF. vWF is produced and stored in endothelial cell granules called Weibel Palade bodies (along with P-Selectin), and found in platelets in alpha granules.
• ***vWF is needed for platelet high sheer stress adhesion and platelet aggregation.**

Medications
DDAVP (Desmopressin-synthetic Vasopressin)
Enhances release of vWF from endothelial cell granules.

ASA
Blocks cytosolic enzyme COX1 and as a consequence the formation of TXA2 (thromboxane). TXA2 cannot bind to its receptor TP on the platelet. Limits the activation of high affinity integrin GPIIb-IIIa and subsequent binding of fibrinogen and vWF to create crossbridges.

Unfractionated Heparin
Sequesters thrombin and factor Xa through the activation of anti-thrombin (AT) and limits the amount of thrombin binding (through sequestration) to its platelet receptor PAR. Limits the activation of high affinity integrin GPIIb-IIIa and subsequent binding of fibrinogen and vWF to create crossbridges.

• *{Plavix} Clopidogrel**
• *ADP receptor P2Y** (Purinogenic G-coupled protein receptor) antongonist. Antatonizes ADP to its receptor P2YR. Normally ADP binds to the P2YR that leads to inhibition of adenyl cyclase decreased intracellular levels of cAMP. By antagonizing the ADP from binding cAMP levels are increased and the high affinity integrin GPIIb-IIIa is inhibited. Subsequent binding of fibrinogen and vWF to create crossbridges does not occur.

Adciximab (ReoPro) and Eptifibatide (Integrilin)
Blocks GPII-IIIa receptors.

Question 51

Pneumonia Types and Treatments

Answer 51

• Corticosteroids In Patients Hospitalized With Community-Acquired Pneumonia: Systematic Review And Individual Patient Data Meta-Analysis Briel, M., et al, Clin Infect Dis 66(3):346, January 18, 2018

METHODS: These multinational authors performed a meta-analysis of individual patient data from six randomized controlled trials that included 1506 adults (median age, 70) hospitalized with CAP who were randomized to low-dose oral or IV corticosteroids (maximum 1mg/kg/day of methylprednisolone or equivalent) or placebo. The primary outcome was 30-day mortality. Analyses were performed in prespecified patient subgroups stratified by baseline characteristics.
CONCLUSIONS: Adjunctive corticosteroids do not appear to reduce 30-day all-cause mortality in patients with CAP. A shorter time to clinical stability and hospital discharge with corticosteroid treatment seem to be offset by a higher risk of hyperglycemia and rehospitalization.
EDITOR’S COMMENTARY: This was a meta-analysis of individual patient data from 6 trials including 1506 patients looking at the benefits and harms of adjunctive corticosteroids in patients with community-acquired pneumonia. The primary outcome was 30-day mortality. There was no difference in 30-day mortality, although patients with steroid treatment had decreased length of stay by one day and time to clinical stability was decreased by one day. However, patients with steroid treatment had a greater incidence of hyperglycemia requiring insulin and CAP-related rehospitalization at 30-days.​

• Are Corticosteroids Beneficial in the Treatment of Community-Acquired Pneumonia? Thomas Seagraves, Michael Gottlieb. Annals of Emergency Medicine 2018 June 21.

CONCLUSION: For adult patients with severe community-acquired pneumonia (PSI index >or= IV) corticosteroids reduce morbidity and mortality. For pediatric patients and adults with nonsevere community-acquired pneumonia, corticosteroids appear to reduce morbidity, but not mortality. There was no limitations on the dose, route, or duration of corticosteroid use.

Note: PO antibiotics has been shown to have better outcomes with hosptial admission.

CAP - Community Acquired, ie outside hospital
** Streptococcus pneumoniae (GP) (20-60%)
Mycoplasma pneumoniae
Chlamydia pneumoniae
Hemophilus influenzea (GN)
Staphylococcus aureus (GP)

RECIPERE]
If <65 and no co-morbid disease then use macrolide:
Clarithromycin {Biaxin} 1000mg PO OD OR
Doxycycline 100mg PO BID

If >65 with co-morbid disease such as,
COPD, DM, malignancy, EtOH, immunosupression, asplenia OR
Abx in last 3 months then use fluoroquinolone:
Levofloxacin {Levaquin} 750mg PO/IV OD OR
Moxifloxacin 400mg PO/IV OD OR

Atypicals
Mycoplasma pneumoniae
Chlamydia pneumoniae
RECIPERE]
Clarithromycin {Biaxin} 1000mg PO OD OR
Levofloxacin {Levaquin} 750mg PO/IV OD OR
Moxifloxacin 400mg PO/IV OD

Legionella pneumophila (GN)​ – Legionnaires disease
Found in fresh water environments such as lakes and streams that then contaminate human water systems.
RECIPERE]
Levofloxacin {Levaquin} 750mg PO/IV OD OR
Moxifloxacin 400mg PO/IV OD

Alcoholics/aspiration/hospital environment
​Klebsiella pneumoniae (GN)
RECIPERE]
Levofloxacin {Levaquin} 750mg PO/IV OD OR
Moxifloxacin 400mg PO/IV OD

HAP - Hospital Acquired
Respiratory infection >48h after being admitted.
** Pseudomonas aeruginosa (GN)
(MRSA) Syaphlyococcus aureus (GP)
Klebsiella pneumoniae (GN)
Escherichia coli (GN)

** Pseudomonas aeruginosa (GN)
RECIPERE]
​Ciprofloxacin 750mg PO BID
Pipercillin-tazobactam 4.5mg IV TID (renal dosing)
Ceftazidime 500mg-1g IV TID
Cefepime 2g IV TID

Less effective Fluoroquinolones:
{Levaquin} Levofloxacin 750mg PO/IV OD
Moxifloxacin 400mg PO/IV OD

(MRSA) Syaphlyococcus aureus (GP)
RECIPERE]
Vancomycin 1g IV BID

Escherichia coli (GN)
Klebsiella pneumoniae (GN)
RECIPERE]
Levofloxacin {Levaquin} 750mg PO/IV OD OR
Moxifloxacin 400mg PO/IV OD

HCAP - Health Care Associated (same as above)
Patient hospitalized for >2days in last 90days.
** Pseudomonas aeruginosa (GN)
(MRSA) Syaphlyococcus aureus (GP)
Klebsiella pneumoniae (GN)
Escherichia coli (GN)

Aspiration Pneumonia – Anaerobes
If parenteral therapy is required,
Pipercillin-tazobactam 4.5mg IV TID

If oral therapy is sufficient,
{Clavulin} Amoxicillin-clavulanate 875 mg PO BID

For penicillin-allergic patients,
Clindamycin 150-450 mg PO q6h, 600 mg IV q6h
Note:Causes C-difficule diarrhea.

IP - Immunocompromised pneumonia
Patient has cancer, HIV etc.
Aspergillus (mold)
Pneumocystis Jiroveci (fungus)
Cytomegalovirus

Question 52

Pneumothorax

Answer 52

1. Diagnosis (Imaging)
   CXR (typically performed in the upright position) is the most common diagnostic imaging modality used for stable patients with suspected pneumothorax. The presence of a pneumothorax is established by demonstrating a white visceral pleural line on the chest radiograph.
2. Pathophysiology/Etiology (UTD)
   PSP is thought to be due to small apical subpleural blebs or bullae (ie, air sacs between the lung tissue and pleura) that rupture into the pleural cavity. The mechanism of bleb/bulla formation is unknown. However, since PSP classically occurs in tall, thin males between the ages of 10 and 30 years the development of subpleural blebs is thought to be due to either increasing negative pressure or greater mechanical alveolar stretch at the apex of the lungs during growth or a congenital phenomenon in which lung tissue at the apex grows more quickly than the vasculature, thereby outstripping its blood supply.

3. Risk factors/Red flags (UTD)
 Cigarette smoking (current or past) is a significant risk factor for PSP, probably due to airway inflammation and respiratory bronchiolitis.

4. Other diagnosis – acute to benign
   PNA
5. Investigations (rule in/rule out)
   CXR
6. Treatment/management
   i) Chest tube
   Note: Chest tube can be removed if it has been clamped for 4 hours and the lung remains expanded. If a patient is coming back to the ER the next day for chest tube removal instruct them to clamp the tube 4 hours before coming back to the ER.
   ii) High flow oxygen
   iii Conservative management

Conservative versus interventional treatment for spontaneous pneumothorax Brown SGA, Ball EL, Perrin K, et al. N Engl J Med. 2020;382(5):405-415.

EDITOR’S COMMENTARY: In this randomized multicenter trial, the authors provide modest evidence that conservative management for moderately sized spontaneous pneumothorax appears noninferior to chest tube and has a lower risk of adverse events. The findings were not robust enough to hold up to sensitivity analyses for missing data, so although you should not change your approach wholesale, these findings should open the door for shared decision-making and discussions with CT surgery about optimal management strategies.

Question 53

Postural Hypotension

Answer 53

DDx]
Haim]
Hemorrhage
Dehydration(vomiting, diarrhea)

Meta]

• *Diabetes (neuropathy)**
• *Drugs –** diuretics, beta blockers, alpha blockers (Terazosin), vasodilators (CCBs, Hydralazine, Nitroglycerine).
• *Synucleinopathies** – Parkinsons, Lewy Body Dementia, Multiple System Atrophy (MSA).

Note: Alpha-synuclein is a protein that is abundant in the human brain. Smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with phospholipids and proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function.

Although the function of alpha-synuclein is not well understood, studies suggest that it plays a role in maintaining a supply of synaptic vesicles in presynaptic terminals by clustering synaptic vesicles. It may also help regulate the release of dopamine, a type of neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements.

Amyloidosis

Hor]
Primary adrenal insufficiency (Addisons)

Org/(Neuros)]
Autonomic failure

Org/(Cardios)]
CHF

Immun]
nAChR autoantibodies

Oncos]
Paraneoplastic autoantibodies
(anti-Hu from small cell lung cancer)

Cong]
Familial dysautonomia (Riley Day Syndrome)

Etiology]
Delayed constriction of lower blood vessels when changing positions. Blood pools in lower legs and is not returned to the heart.

Blood pressure control is through chemoreceptors and baroreceptors found in the aortic arch and carotid bifurcation.

Baroreceptors in the aortic arch responds to increase and decrease in arterial BP transmitted TO CNX Vagus nerve and to the nucleus tractus solitarus in medulla. Baroreceptors in the carotid bifurcation responds to increase in BP trasmitted TO CNIX Glossopharyngeal and to the nucleus tractus solitarus in medulla.

Arteries and veins have ONLY sympathetic innervation to the tunica media – thick smooth muscle in artery, thin smooth muscle in vein.

SAN and AVN have sympathetic (beta1) AND parasympathic innervation (M2). Ventricles have sympathetic innervation (beta1), atrium have slight parasympathetic innervation (M2).

Sympathetic stimulation of arteries and arterioles (resistance vessels) causes increased arterial peripheral resistance, increased arterial pressure and decreased distal blood flow mostly to the splanchnic (superior, celiac and inferior mesenteric arteries) and skeletal muscles. Sympathetic stimulation of veins and venules (capacitance vessels) causes increased venous peripheral pressure and blood return to the heart. Alpha1 and beta2 receptors on the smooth muscle cells of the arteries, arterioles, veins and venules respond to sympathetic stimulation (norepinphrine and epinephrine). Alpha1 causes vasoconstriction and beta2 causes vasodilation.

Standing causes pooling of blood in the lower extremities and splanchnic system (SMV, splenic vein, IMV) –> decreased venous return to the heart –> decreased CO (EF) and BP –> decreased stretch at aortic arch and carotid baroreceptors –> decreased afferent parasympathetic baroreceptor firing CNIX, CNX –> nucelus tractus soltaris prompts compensatory reflex (baroreceptor reflex) by increasing sympathetic outflow and decreasing parasympathetic outflow.

Orthostatic hypotension:

1. Cardiac
2. Fluid volume
3. ANS response

HPI]
Generalized weakness, sensations of dizziness or lightheadedness, visual blurring or less commonly syncope.

O/E] Orthostatic vitals
20mmHg fall in systolic or 10mmHg fall in diastolic upon standing.

Question 54

PERC

Answer 54

8 Criteria
All-or-none proposition used to RULE OUT PE (it’s not for risk-stratification!). While a low-scoring patient may be a low risk patient, if any of the criteria are positive they are not PERC negative and an appropriate combination of Wells/Geneva/DDimer/CTPA should be used to rule out this diagnosis.

ID]
Age <50

HPI]
No hemoptysis

PMHx]
No prior DVT or PE
No hospitalization or surgery within last 4 weeks

O/E] HR <100 (No tachycardia), SaO2 > 95% on RA
No unilateral leg swelling

MEDS]
No OCP or exogenous estrogen use

Question 55

PE/Virchow’s Triad

Answer 55

• ​Simplified Diagnostic Management Of Suspected Pulmonary Embolism (The YEARS Study): A Prospective, Multicentre, Cohort Study van der Hulle, T., et al, Lancet 390(10091):289, July 15, 2017

BACKGROUND: Simplified diagnostic algorithms for suspected pulmonary embolism can improve adherence and reduce the use of CT pulmonary angiography (CTPA). The YEARS algorithm assesses three items of the Wells’ clinical decision rule:

• *1. Hemoptysis
  2. Signs of DVT
  3. PE is the most likely diagnosis**

The YEARS algorithm recommends CTPA at a D-dimer threshold of 500ng/mL when at least one of these three elements is present, and at 1000ng/mL if none is present.

CONCLUSIONS: In patients of all ages with suspected pulmonary embolism, the YEARS algorithm appears to safely and effectively reduce the need for CTPA.

EDITOR’S COMMENTARY: The YEARS algorithm is a decision tool for the diagnosis of patients suspected of having acute PE. It incorporates D-dimer thresholds (500 ng/mL and 1000 ng/mL) with 3 elements of the Wells score (hemoptysis, clinical signs of DVT, PE most likely diagnosis). The score was used in 3,465 patients in 12 hospitals in the Netherlands. Use of the algorithm led to fewer CTPA scans being performed when compared to the number that theoretically may have been performed using the traditional Wells’ rule. 85% of the cohort had PE ruled out using the YEARS algorithm and at 3 month follow-up, less than 1% of the patients had a symptomatic VTE, so it appears to be safe.

• Prevalence Of Pulmonary Embolism In Patients Presenting To The Emergency Department With Syncope Frizell, A., et al, Am J Emerg Med Epub ahead of print, July 31, 2017

CONCLUSIONS: According to these data, PE is an infrequent cause of syncope in patients presenting to the ED. These findings disagree with a recent study reporting a higher rate (nearly one in six), although differences in methodology may explain the discrepancy. This study does not support routine PE evaluation for all patients with syncope.

EDITOR’S COMMENTARY: The authors from the University of Utah retrospectively studied the prevalence of pulmonary embolism (PE) in syncope patients presenting to their emergency department (ED) over a span of 5.5 years. In contrast to the findings of the recently well-publicized PESIT trial showing that 1/6 syncope patients have an underlying PE, these authors found an overall rate of PE in syncope of 1.4% in their ED cohort. Their findings do not support the high PE rates from the PESIT trial.

• Prevalence Of Pulmonary Embolism In Patients Presenting With Syncope: A Systematic Review And Meta-Analysis Oqab, Z., et al, Am J Emerg Med 36(4):551, April 2018

SUMMARY: Syncope is a challenging chief complaint with a broad differential diagnosis. Several years ago, Prandoni et al. published a paper in NEJM (PESIT trial) showing that in a cohort of hospitalized syncope patients in Italy, 17% ended up having a PE. This was thought to be very high at the time, but the paper got a lot of practitioners wondering should we be working up all syncope patients for PE? **We previously showed that the cohort of patients in the Prandoni paper were very old and very sick (not all comers).

Most providers, until this point, have only been working up syncope patients for PE if there is a real suspicion for it (swollen leg, increased RR, etc.). The authors of this paper conducted a systematic review and meta-analysis of 12 papers that looked at the the etiology of syncope (including PE). There were over 7000 patients with data of which 90% of them were from the ED.

The pooled PE prevalence of ED patients with syncope was 0.8% vs. 3.8% in the Prandoni study. The pooled PE prevalence of hospitalized patients with syncope was 1% vs. 17.3% in Prandoni paper. The overall pooled prevalence of PE was 0.9%

EDITOR’S COMMENTARY: This was a systematic review and meta-analysis of 12 papers including 7000 patients who were evaluated for syncope that found the overall prevalence of PE to be 0.9%, far lower than what was previously described in the Pradoni paper. This finding has to be taken with a grain of salt as this was a meta-analysis. For example, not all patients were ruled out for PE, the reason for searching for PE in those who had it was not explicitly stated, there were different tests done to diagnose PE and there was often no follow up with discharged patients to see if they were later diagnosed with a PE. So what is the real prevalence of PE in syncope?

**Our feeling is this study is much more representative of the true prevalence of PE. The results from the Prandoni study (PESIT) can’t be ignored, but using them to conclude the rate is high enough where all patients should get a PE work up is wrong. The Prandoni paper looked at an older, sicker cohort of syncope patients that aren’t representative of most patients presenting to the ER with syncope. This paper gives us more support to limit PE work ups among syncope patients to those who sound like they might actually have a PE!

• *Virchow Triad**
• *1. Stasis**
• *2. Endothelial changes (damage** and inflammation)
• *3. Hypercoaguability**
• *Stasis**
• *General immobility** from obseity, sedentary lifestyle, neurologic disorders, debilitating illness, bed rest (at 72 hours), or travel (contraversial). Limb immobility from trauma, surgery, neurologic paralysis ie. CVA, brain cancer, paralysis.
• *Endothelial changes**
• *i) Damage.** Uncontrolled HTN (sheer) and cigarette smoking (chemical stress) shifts the balance between clot generation and breakdown towards thrombosis due to decreased synthesis of nitric oxide (NO) and prostacyclin (PGI2), and increased endothelin-1 (ET-1) synthesis.

Note: Endothelin (ET-1) is a 21 amino acid peptide and potent vasoconstrictor produced by the vascular endothelium from a 39 amino acid precursor, big ET-1, through the actions of an endothelin converting enzyme (ECE) found on the endothelial cell membrane.

ET-1 formation is stimulated by angiotensin II (AII), antidiuretic hormone (ADH), thrombin (IIa), cytokines, reactive oxygen species, and shearing forces acting on the vascular endothelium. ET-1 formation is inhibited by prostacyclin (PGI2), atrial natriuretic peptide (ANP), and nitric oxide (NO).

Endothelin-1 receptor antagonists (Bosentan) are used in the treatment of pulmonary hypertension. Inhibition of these receptors prevents pulmonary vasculature constriction and thus decreases pulmonary hyptertension.

Trauma, surgery and biomaterials such as chronic indwelling cathethers can also cause endothelial damage. **Catheters directly activate the intrinsic pathway.

ii) Endothelial inflammation (collagen and TF exposure). Blood exposure to collagen and tissue factor (TF), leads to platelet adhesion, activation and aggregation (see below) and clot formation. TF expression on the surface of monocytes and endothelial cells is increased by TNF-alpha released by monocytes/macrophages during inflammation. TF activates VII to VIIa and the extrinsic clotting cascade. Inflammatory conditions leading to increased TNF-alpha states are seen in diseases such as inflammatory bowel disease, lupus, rheumatoid arthritis, and nephrotic syndrome.

Note: TNFalpha is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. TNF binds to receptors TNFR1 and TNFR2. This cytokine is involved in the regulation of a wide spectrum of biological processes primarily apoptosis (through the death receptor, TNFR that has a death domain) and inflammation (pro-inflammatory cytokine). TNFalpha increases the transcription of CAMs (cell adhesion molecules), such as ICAM (endothelial cell), VCAM (endothelial cells after being stimulated by cytokines), E-selectin (endothelial cells after being stimulated by cytokines), L-selectin (lymphocytes/neutrophils), allowing immune cells to reach the site of inflammation.

Blood exposure to collagen and tissue factor (TF), leads to platelet adhesion, activation and aggregation (see below) and clot formation. TF expression on the surface of monocytes and endothelial cells is increased by TNF-alpha released by monocytes/macrophages during inflammation. TF activates VII to VIIa and the extrinsic clotting cascade. Inflammatory conditions leading to increased TNF-alpha states are seen in diseases such as inflammatory bowel disease, lupus, rheumatoid arthritis, and nephrotic syndrome.

Platelet activation: Adhesion – Activation – Aggregation
Unactivated in blood– All the coagulation factors – I (fibrinogen), II (prothrombin), V, VII, IX, X, XI, XIII, as well as protein C, protein S and antithrombin – except VIII, are made in the liver and circulate in the blood.VIII is made in the endothelial cells and platelets and is bound to vWF, in a VIII/vWF complex. The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation.

Presented to the blood – **Collagen and TF are exposed to blood during damage to the endothelium or inflammation by activating macrophages and endothelium, through increased TNFalpha expression from macrophages. Damage to the endothelium exposes collagen found under the endothelium and TF found on the surface of SMC and fibroblasts to the blood. During inflammation, macrophages release TNFalpha activating endothelium and monocytes to express TF on their sufaces, which is then exposed to the blood.

VII circulating in the blood binds to TF. TF activates VII to VIIa and thus the extrinisic pathway. VIIa activates the proteases factor IX into IXa, and X into Xa. Xa converts prothromin (II) to thrombin (IIa) which then converts fibrinogen (I) to fibrin (Ia). Thrombin (IIa) liberates vWF from the vWF/VIII complex, binds to a platelet thrombin receptor, PAR (see below), and converts fibrinogen to fibrin (Ia). vWF has no enzymatic activity and binds to a number of cells and molecules, in particular collagen.

Integrin GPIa-IIa and GPVI (glycoprotein receptor) on the platelet bind to collagen for low sheer adhesion. GPIb-V-IX (glycoprotein) complex on the platelet binds to vWF that is bound to collagen leading to tight adhesion under high sheer stress.

Note: Integrins are proteins that function mechanically, by attaching the cell cytoskeleton to the extracellular matrix (ECM), and biochemically, by sensing whether adhesion has occurred through intracellular cascades.

Once the above integrins glycoproteins are activated, ADP, TXA2 are released from the platelet by alpha and dense granules. ADP, TXA2 and thrombin (IIa) bind to their corresponding platelet receptors – PY2, TP, PAR – activating GPIIb-IIIa to a high affinity state. **vWF and fibrinogen bind to the high affinity GPIIb-IIIa forming crossbridges to other platelets.

Note: Purinogenic G-coupled protein receptor (PY2), thromboxane receptor G-coupled protein receptor (TP), and protease activated receptor (PAR).

Note: vWF is a multimeric protein found in blood plasma bound to factor VIII (VIII/vWF) produced constitutively in endothelium Wiebel Palade bodies, alpha granules of platelets and subendothelial tissue. ADAMTS13 protease inactivates vWF. Deficiencies of ADAMTS13 has been found in TTP (thrombotic thrombocytopenia purpura) and HUS (hemolytic uremic syndrome) subsets of microangiopathic hemolytic anemia (MAHA).

Note: Thrombin (IIa) is the **most potent platelet aggregating agent and strongest agonist ** by binding to platelet membrane receptors, PARs. Prothrombin (II) is converted to thrombin (IIa) on the activated platelet surface by Xa. Prothrombin (II) is sythesized in the liver using vitamen K, along with X, IX, VII, C, S.

• *Note: Fibrinogen** is synthesized in the liver by the hepatocytes. The concentration of fibrinogen in the blood plasma is 200–400 mg/dL (normally measured using the Clauss method). Fibrinogen is an acute-phase protein, i.e. its blood levels rise in response to systemic inflammation, tissue injury, and is elevated in various cancers. Elevated levels of fibrinogen in inflammation as well as cancer and other conditions have been suggested to be the cause of thrombosis and vascular injury that accompanies these conditions. The main function of fibrinogen is:
• *i) platelet aggregation –** binding to the high affinity GPIIb-IIIa (along with vWF) on platelets forming crossbridges to other platelets.
• *ii) fibrin mesh –** individual fibrin strands polymerize and are cross-linked with other fibrin stands by blood factor XIIIa, to form an extensive interconnected fibrin network that is the basis for the formation of a mature fibrin clot.

Hypercoaguability
Hyperviscosity (high hematocrit) from polycythemia, change in clotting factors (mutations, pregnancy, malignancy, nephrotic syndrome), hormones (increased estrogen from exogenous, endogenous or obseity).

• Change in clotting factors*
• *Mutations.** Factor V Leiden mutation is an autosomal dominant genetic condition with incomplete penetrance. The factor V Leiden mutations is resistant to aPC (activated Protein C) degredation which leads to increased amounts of factor V and clotting. Factor II (prothrombin) G20210A mutation leads to in increase in factor II leading to a higher chance of clotting.

Pregnancy. Fibrinogen increases during pregnancy. Hepatocytes produce more fibrinogen which can rise to 3x the normal levels.

Malignancy. Cancer cells express (i) procoagulant proteins and (ii) release microparticles (soluble fragments of tumour cell membranes) leading to a systemic hypercoagulable state. Two common procoagulant proteins are tissue factor (TF) and cancer procoagulant, which directly activate factor X to Xa.

• Hormones*
• *Estrogen. Estrogen** causes increased gene transcription in the hepatocytes, mainly increased levels of VII (TF/VIIa) leading to conversion of X to Xa, and thrombin (IIa) formation. Estrogen can be increased from obesity, there is more adipose tissue and aromatase enzyme which converts testosterone to estrogen, endogenous or exogenous sources.

Estrogen containing oral contraceptives increase the plasma concentrations of clotting factors II, VII, X, XII, factor VIII, fibrinogen, and thrombin activatable fibrinolysis inhibitor (TAFI). Not all of the increases in clotting factors are of the same magnitude. Factor VII (which binds to and is activated by TF, TF/VIIa as above) appears to have the greatest magnitude of increase and factor VIII made in the endothelial cells (which sequesters vWF in the blood, VIII/vWF) the least magnitude of increase, comparatively.

HPI]
history of stasis
dyspnea (SOB)
persistent palpitations
syncope
hemoptysis, pleuritic chest pain (pulmonary infarction syndrome)

ADJUST-PE – Age adjusted D-dimer cutoff (Age x 10) in patients >50

• *PMHx]
  i) stasis (surgery, illness)**
• *ii) endothelial damage and inflamation** (HTN, smoking, inflammatory conditions)
• *iii) hypercoaguability** (mutations, estrogen, pregnancy, cancer)

Meds]
OCP/HRT

SHx]
smoking

O/E] TC, HypoTN (SBP<90 or >40mmHg drop), SpO2<94%
Cardios – JVD
PV – calf/popliteal tenderness, Homen’s sign
PERC
Wells

INVESTIGATIO]
L(H)/Haim]
D-dimer

YEARS algorithm – as above

• *I]**
• *ECG**
• ***Most specific finding is TWI in the leads corresponding to the right ventricle – precordial leads (V1-V4) +/- inferior leads (II, III, aVF) (34% of patients, 90% specific), sinus tachycardia (44% of patients)**, RBBB (complete or incomplete 18% of patients), SIQIIITIII (20% of patients), rigth axis deviation (16% of patients), dominant R wave in V1, non-specific ST-segment and T wave changes, P pulmonale (9% of patients) – peaked p-waves in inferior leads II, III, aVF >2.5mm.

RECIPERE]
Massive PE
Massive PE is defined as acute PE with obstructive shock or SBP <90 mmHg or 40mmHg drop from baseline.

• *i) UFH**
• *UFH 80U/kg bolus (or 5000U),** followed by continues infusion of 20U/kg/hr (or 1000U/hr)
• *Note:** targeted aPTT is defined by hospital lab but generally 1.5-2.5x normal or 60-80.

AND

• *ii) Thrombolytics/embolectomy**
• *{Alteplase} rt-PA (recombinant tissue plasminogen activator), 100mg over 2 hours**
• *Submassive PE**
• *Submassive PE** is acute PE without systemic hypotension ie. SBP ≥90 mm Hg but with either RV dysfunction (RAE or right ventricle strain) or myocardial necrosis (troponins). Strongly consider thrombolytics/embolectomy but need to balance risk of bleeding. If no role for thrombolytics then anti-coagulation as per below.
• *Non-massive PE**
• *Non-massive or low risk PEs** do not have any of the above features.

i) DOAC
{Xarelto} Rivaroxaban 15mg PO BID for 21days, then
20mg PO OD for duration of treatmentOR
{Eliquis} Apixaban 10mg PO BID for 7 days, then
5mg PO BIDOR
{Pradaxa} Dabigatran 150mg PO BID

• *ii) LMWH**
• *{Lovenox} Enoxaparin 1mg/kg SC BID,** 1.5mg/kg SC OD OR
• *{Fragmin} Dalteparin 100 U/kg SC BID,** 200U/kg SC OD
• *Note:** LMWH is the treatment of choice in cancer associated thrombosis.
• *iii) UFH**
• *UFH 80U/kg bolus,** followed by continues infustion of 20U/kg/hr (targeted aPTT is defined by hospital lab but generally 1.5-2.5x normal or 60-80)

Note: The use of UFH should be limited to patients with severe renal deficiency (CrCl<20mL/min) in whom DOAC and LMWH should be avoided, patients with very high risk of bleeding where rapid reversal may be needed, and patients who receive thromblytic therapy.

Stratify risk using PESI (PE Severity Index)
Provoked PE needs anticoagulation for at least 3 months. Unprovoked PE may need anticoagulation indefinitely.

Question 56

PEA/PseudoPEA

Answer 56

• EFFECT OF ADRENALINE ON SURVIVAL IN OUT-OF-HOSPITAL CARDIAC ARREST: A RANDOMISED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL Jacobs, I.G., et al, Resuscitation 82:1138, 2011

BACKGROUND: The use of epinephrine in attempted resuscitation from cardiac arrest has been recommended since 1906, but no randomized controlled human trials have evaluated its effect on patient outcomes.

METHODS: In this double-blind, placebo-controlled Australian study, 534 adults (mean age 65, 73% male) sustaining a prehospital cardiac arrest not responsive to initial defibrillation attempts by paramedics were randomized to administration of IV 1:1000 epinephrine (1mg every three minutes to a maximum of 10mg) or saline placebo.

RESULTS: The initial arrest rhythm was ventricular tachycardia or fibrillation in 46% of the patients, and 51% received bystander CPR. The rate of prehospital return of spontaneous circulation was 23.5% in the epinephrine group vs. 8.4% in controls (odds ratio [OR] 3.4, 95% CI 2.0-5.6). The rate of survival to hospital discharge was not statistically different, 4% in the epinephrine group vs. 2% in controls (95% CI for OR = 0.7-6.3), and good neurologic survival was even more similar (3% vs. 2%). Similar findings were observed following attempted adjustment for potential confounders. Of the 16 survivors to hospital discharge, both of those with an unfavorable neurologic outcome had been randomized to treatment with epinephrine.

CONCLUSIONS: In this randomized, controlled study of prehospital cardiac arrest, administration of epinephrine led to an increased likelihood of return of spontaneous circulation, but no statistical improvement in survival to hospital discharge.

• A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. PARAMEDIC2​ Gavin D., Perkins, M.D., Chen Ji, Ph.D., Charles D. Deakin, M.D., N Engl J Med Aug 2018; 379:711-721

BACKGROUND: Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients.

METHODS: In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]).

RESULTS: At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]).

CONCLUSIONS: In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.

PEA
Heatbeat rhythm on the ECG and no pulse(usually at the carotid artery). The electrical system is working but the heart isnot genenrating enough forceto contract. This is different fromasystole(no electrical activity) ordisorganized electrical activty (VF/VT).

Pseudo PEA
Sufficient cardiac contractility to have a pulse that is present and not detected/palpated.

EARLY recognition of psuedo-PEA:
1. Art-line
2. ETCO2
During CPR, ETCO2 greater than 20mmHg (or at least greater than 10mmHg) is associated with better neurological outcomes. Rise in ETCO2 indicates ROSC.
3. Echo demonstrating pulsatile contractility

Hs and Ts
Hypovolemia
Hypo/hyperthermia
Hypoxia
Hypo/hyperkalemia
Hydrogen ions (acidosis)

Tension pneumo
Tamponade
Thromboembolism (PE, MI)
Toxicity

**Mechanisms are the same that produce circulatory shock.
1. Pathological vasodilation/Distributive Shock (septic shock, anaphlyactic shock)
(loss of vascular resistance and excess capacitance)
2. Impaired cardiac filling – Hypovolemic shock, Obstructive Shock (tension pneumothorax, pulmonary embolism, cardiac tamponade)
(decreased preload and decreased EF)
3. Imparied pumping – MI, hypoxia (O2), hyperglycemia (BG), acidosis (H+), hyper/hypokalemia (K+), toxins and drugs
(decreased EF, HR)

INVESTIGATIO]
L(H)/Haim]
CBC (Hb, WBC)
VGB (pH, PvCO2, HCO3-, lactate)
ABG (pH, PaCO2, PaO2, HCO3-, lactate)
D-dimer
INR/PTT
Type and Cross

L(H)/Meta]
SMA7 – K+, BG, Cr
Drugs – B-blockers, CCB, digoxin, TCA
Note: digoxin blood levels
Toxicology

L(H)/Hor]
TSH
beta-HCG

L(H)/Org (Cardios)]
Troponins

L(O)/Meta]
Toxicology

L(O)/Hor]
beta-HCG

I] POCUS
FAST
pneumothorax
pericardial effusion
right heart strain

RECIPERE]
NP/A,B]
NRB
BVM
Intubation

NP/C]
PIV (large bore)
NS Bolus/pRBCs (Hypovolemia)
Art-line

NP/Mon]
Cardiac monitors
BP
SpO2
ETCO2

NP/Pro]
Thoracostomy (tension pneumothorax)
Pericardiocentesis (tamponade)

P/Haim]
NaHCO3 (acidosis (H+))
tPA (PE, MI)

P/Meta]

• *NaHCO3 (TCA toxicity)**
• *Ca gluconate (hyperkalemia, CCB toxicity)**
• *Digibond (digoxin toxicity)**
• *Glucagon (beta-blocker toxicity)**
• *D25W (hypoglycemia)**
• *Note:** D50W represents 50% dextrose (0.5g/mL) is a solution with 25g of dextrose in 50mL water.
• *HDI (High Dose Insulin) (BB or CCB toxicity)**

P/Org(Vasculo)]
Vasopressers from alpha to beta (PNEDDI)
Phenylephrine
Norepinephrine 0.05mcg/kg/min (peripheral max 0.15mcg/kg/min, central max 0.3mcg/kg/min)
Epinephrine
Dopamine 2.5mcg/kg/min (2.5-20mcg/kg/min)
Dobutamine
Isoproterenol (used in stable heart block 2.5mcg/min)

Until cause is found:

• *1. CPR 2 minutes
  2. Epinephrine 1mg q4min (3-5min) alternating every other CPR cycle.**
• *Note: Keep ETCO2 > 10-20mmHg and ROSC >40mmHg.**
• *Narrow complex QRS (<120mg, 3 boxes)**
• *Likely obstructive cause** (e.g. tamponade, tension pneumothorax, PE) or underfilling (e.g. hypovolemia). Treat cause of obstructive shock, administer fluids and inopressors.
• *Wide complex QRS**
• *Likely metabolic cause**, consider hyperkalemia (K+), hypocalcemia (Ca2+) or cardiotoxicity.

Question 57

Phyarngitis

Question 58

Postobstructive Diuresis

Question 59

Procedure Sedation

Answer 59

• *Ketamine 1-2mg/kg** over 1-2 minutes
• *Note:** Ketamine is a dissociative sedative that has amnesic and algesic effects.

THEN

Propofol in 20mg aliquots until appropriate sedation acheived

Question 60

PSVT–AVNRT, AVRT (WPW, WPW with Afib), AT, MAT

Answer 60

• Comparing The Success Rates Of Standard And Modified Valsalva Maneuvers To Terminate PSVT: A Randomized Controlled Trial Corbacioglu, S.K., et al, Am J Emerg Med 35(11):1662, November 2017

CONCLUSIONS: In patients with paroxysmal supraventricular tachycardia, the modified Valsalva maneuver may be much more effective than the standard maneuver. Moreover, it reduces the adverse effects associated with rescue pharmacotherapy by decreasing the need for such drugs.
EDITOR’S COMMENTARY: This was a prospective, randomized control trial of 56 patients comparing standard valsalva maneuver (VM) to modified valsalva maneuver (MVM) to terminate paroxysmal SVT. The primary outcome was success rate in conversion to sinus rhythm with 3 patients (10.7%) in the VM group converting to sinus rhythm and 10 patients (42.9%) in the MVM group converting to sinus rhythm (p<0.007); patients in the MVM group also needed less rescue treatment compared to VM. Authors conclude that MVM is more effective at terminating pSVT compared to VM.

• POSTURAL MODIFICATION TO THE STANDARD VALSALVA MANOEUVRE FOR EMERGENCY TREATMENT OF SUPRAVENTRICULR TACHYCARDIAS (REVERT): A RANDOMISED CONTROLLED TRIAL Appelboam, A., et al, Lancet 386(10005):1747, October 31, 2015

CONCLUSIONS: A simple, safe, and cost-free postural modification to the standard Valsalva maneuver appears to significantly improve its performance. The authors recommend use of the modified Valsalva maneuver, whenever possible, in cases of supraventricular tachycardia.
Modified valsalva (MVM): Patient is at 45 degrees and blows into a 10mL syringe just enough to move the plunger for 15s, then lay supine and raise legs 45 degrees for 15s.

Valsalva
Breathing out against a closed glottis (vocal cord). Causes an increase in the intrathorcic pressure (ITP) as the muscles are applying a force inward and the glottis keeps the air trapped in the lungs.

Stage 1 (3s), held breath against a closed glottis and increased ITP – Increased AP, decreased HR.
Increase in intrathoracic pressure (ITP) causes an increase in aortic pressure (AP) due to blood sqeezed out of the lungs and the increased ITP acting on the aortic walls externally. The increased ITP also acts on the SVC/IVC and the right atrium causing less venous return.

Aortic body baroreceptors through CNX detect increase in pressure sending an afferent impulse to the NTS. NTS sends a signal to the nucleus ambiguus (NAmb) causing increased parasympathetic outflow to the SAN/AVN and a decreased HR.

Stage 2 (3-20s), held breath against a closed glottis and increased ITP – Decreased AP, increased HR.
Continued increased ITP and reduced venous return and preload causes a drop in the AP.

Aortic body barorecpetors detect decreased pressure through CNX sending an afferent impulse to the NTS. NTS sends a signal to the RVLM increasing sympathetic outflow to the cervical ganglion and the interomediolateral nucleus of T1-T4 causing an increase in HR.

Stage 3 (20-23s), pressure release – Decreased AP, increased HR.
Similar to breathing in blood is trapped in the lungs and venous return increases. AP decreases due to less prelaod and decreased external pressure causing an increased HR. CNX to NTS to NAmb (and CVLM) and increased parasympathetic to SAN/AVN.

Stage 4 (23s-33s), pressure release – Increased AP, decreased HR.
Continued release of ITP creates a large bolus of preload and a sustained increase in AP caussing a decreased HR . CNX to NTS to RVLM to cervical ganglon and IML/T1-T4 and increased sympathetic to SAN/AVN.

Supraventricular tachycardia (SVT) is an abnormally fast heart rhythm arising from improper electrical activity in the atria. There are three main types: atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia – atrioventricular nodal reentry tachycardia, atrioventricular reentry tachycardia/wolf parkinson white, multifocal atrial tachycardia, atrial tachycardia (PSVT–AVNRT, AVRT/WPW, AT, MAT). Symptoms may include palpitations, feeling faint, sweating, shortness of breath, or chest pain.

AVNRT (slow-fast/typical, (slow)-fast-slow/atypical)
ECG features:

• Regular
• Narrow QRS followed by a inverted/buried P-wave
• Short RP/slow-fast (inverted p wave buried just after QRS) OR
• *Long RP/(slow)fast-slow (inverted p wave just before QRS)**

Note: In the slow-fast AVNRT the p wave is often buried in the QRS complex around 66% of the time.

Because of the relationships between the QRS complex and the following p wave, typical (slow-fast) AVNRT is referred to as a short RP tachycardia, while atypical (fast-slow) AVNRT is a long RP tachycardia.

AVNRT occurs when a reentrant circuit forms within or just next to the atrioventricular node. The circuit usually involves two anatomical pathways: the fast pathway and the slow pathway, which are both in the right atrium.

The slow pathway (which is usually targeted for ablation) is located inferior and slightly posterior to the AV node, often following the anterior margin of the coronary sinus. The fast pathway is usually located just superior and posterior to the AV node. These pathways are formed from tissue that behaves very much like the AV node, and some authors regard them as part of the AV node.

• *Typical (slow-fast) AVNRT (short RP)**
• *Approximately 80 to 90% of patients** with AVNRT present with this common form of the arrhythmia.
• A premature atrial contraction (PAC) arrives anterograde at the proximal junction of the AV node when the fast pathway is in its refractory period. Conduction down the fast pathway is blocked.
• The slow pathway has a shorter refractory period than the fast pathway and is available for conduction.
• The premature beat conducts anterograde down the slow pathway, through the final common pathway, to the bundle of His. As a result, the PR interval of the premature beat will be longer than those of normal beats conducted through the fast pathway due to the slow pathway taking more time to conduct.
• If the fast pathway is no longer refractory by the time the slow pathway impulse reaches the distal junction of the two pathways, the impulse can conduct retrograde up the fast pathway. The circuit may then become repetitive with anterograde conduction back down the slow pathway and retrograde conduction up the fast pathway resulting in a sustained tachycardia.
• The retrograde conduction up the fast pathway activating the artium producing the inverted p wave, often occurs in the same amount of time during the conduction down the bundle of His activating the ventricles. As a result, the inverted p wave is often buried or just after the QRS.

This proposed mechanism explains a number of clinical observations in AVNRT:

• A single atrial premature contraction, PAC, (or retrograde penetration of the AV node from a junctional or ventricular premature contraction, PVC) can initiate the arrhythmia.
• Penetration of the reentrant circuit by a premature beat can abruptly terminate the arrhythmia.
• *Atypical ((slow)-fast-slow) AVNRT (long RP)**
• *Up to 20 percent of patients with AVNRT** have uncommon forms of the arrhythmia, referred to as atypical AVNRT.
• A premature ventricular contraction (PVC) arrives retrograde at the distal junction of the AV node when the fast pathway is in its refractory period. Conduction up the fast pathway is blocked.
• The slow pathway has a shorter refractory period than the fast pathway and is available for conduction but takes longer to travel compared to the fast pathway.
• The premature beat conducts retrograde up the slow pathway, and activates the atrium causing an inverted p wave.
• The signal immediately travels anterograde down the fast pathway to the bundle of His depolarizing the ventricles and at the same time the signal travels retrograde up the slow pathway to the atrium for another cycle.
• Due to the longer time for the signal to travel retrograde up the slow pathway, and the quicker time for the signal to travel down the fast pathway depolarizing the ventricles, the inverted p wave immediately precedes the QRS, causing an long RP.

The fast and slow pathways should not be confused with the accessory pathways that give rise to Wolff-Parkinson-White syndrome (WPW syndrome) or atrioventricular reciprocating tachycardia (AVRT). In AVNRT, the fast and slow pathways are located within the right atrium close to or within the AV node and exhibit electrophysiologic properties similar to AV nodal tissue. In contrast, accessory pathways that give rise to WPW syndrome and AVRT are located in the atrioventricular valvular rings. They provide a direct connection between the atria and ventricles, and have electrophysiologic properties similar to muscular heart tissue of the heart’s ventricles.

**_AVRT_**
Atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is a reentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, **the normal AV conduction system and an AV accessory pathway,** linked by common proximal (the atria) and distal (the ventricles) tissues.

In the presence of an accessory pathway, conduction from the atria to the ventricles may occur in a variety of ways i) exclusively via the AV node (orthodromic), ii) exclusively via the accessory pathway (antidromic), iii) or a combination of both (WPW).

Orthodromic (90-95%) - short RP
ECG features:

• Regular rhythm
• Narrow QRS (150-250 bpm)
• Inverted/obscured P-wave following QRS (short RP)

In orthodromic AVRT, a premature atrial contraction (PAC) is conducted down through the AV node activating the ventricles and blocked from the accessory pathway. The impulse travels retrogradely through the accessory pathway rapidly entering atrium producing an inverted P-wave immediately (or often obscured) after the regular narrow QRS. The pattern repeats.

Antidromic (<10%) - long RP
ECG features:

• Regular rhythm
• Wide QRS with delta wave (150-250 bpm)
• Inverted p-wave before QRS (long RP) giving short PR interval (<120ms)

In antidromic AVRT, a prematrue atrial contraction (PAC) is conducted rapidly through the accessory pathway and blocked from the AV node due to the previous repolarization, causing a preexicted ventricle and a delta wave with wide complex QRS. The impulse takes time to travels up through the purkinje, his and AV node depolarizing the atrium producing an inverted p wave that then rapidly travels down the accessory pathway giving a short PR interval and depolarizing the ventricles producing a delta wave and wide complex QRS.

WPW pattern and WPW syndrome
ECG findings:

• Regular rhythym
• Wide QRS with delta wave (>120ms)
• Short PR interval (<120ms)

In WPW the signal travels through the AV node and the accessory pathway at the same time causing a shortened PR interval and delta wave/widened QRS.

• The Wolff-Parkinson-White (WPW) pattern is applied to the patient with preexcitation manifest on an ECG in the absence of symptomatic arrhythmias.
• ​The Wolff-Parkinson-White (WPW) syndrome is applied to the patient with both preexcitation manifest on an ECG and symptomatic arrhythmias involving the accessory pathway.

Persons with either the WPW pattern or WPW syndrome can have identical findings on surface ECG. In either situation, anterograde conduction through the accessory pathway results in earlier activation, or preexcitation, of part of the ventricles.

RECIPERE]
QRS Narrow (<120ms) and Regular
** AV node blockade

i) Hemodynamically Unstable
Synchronized cardioversion starting at 50-100J

• *ii) Hemodynamically Stable**
• *1. Vagal maneuvers** – carotid massage, valsalva, cold water
• *Modified valsalva maneover (MVM)**

2. Adenosine 6mg fast IVP followed by saline bolus,
repeat at 12mg if no response
(like a parasympathetomimetic)
Note: Purinergic receptors A1/A2 (found on pacemaker cells, and vascular smooth muscle cells).
On the SAN and AVN node, adenosine binds to the A1R activating Gi protein which inhibits adenyl cyclase reducing cAMP, and also opens K+ channels hyperpolarizing the cell. The reduction in cAMP causes less binding to f-channel, a reduction in Na+/K+ influx, less steep phase 4 slope, and a drop in heartrate (negative chronotropy), slower conduction through AVN (negative dromotropy),

3. Non-dihyropyridine CCBs
Diltiazem 15-20mg (0.25mg/kg) IV over 2 minutes,then 20-25mg if neededOR
Verapamil 2.5-5mg IV over 2 minutes,then 5-10mg q15-30min, max 20mg
Note: T-type and L-type Ca2+ channels are used in phase 4 of nodal tissue that allow for depolarization from an influx of Ca2+ ions. Blocking the L-type Ca2+ channels in the conduction system will decrease the slope of phase 4 and thereby delay depolarization resulting in antichronotropic and antidromotropic effects (see Cardiac Cellular Function and Drugs).

4. Beta blockers
Metoprolol 5mg IV q5min, max dose 15mg
Atenolol 5mg IV over 5 minutes
(See Cardiac Cellular Function and Drugs)

QRS Wide (>120ms) and Regular

• *** AV node blockade contraindicated except Amiodarone**
• *** Treat like VT**

i) Hemodynamically Unstable
Synchronized cardioversion

ii) Hemodynamically Stable
Procainamide 20mg/min IV, until QRS widens by 50% or dysrhythmia supressed
Amiodarone 150mg IV, over 10 minutes,then infusion
Note: AV node blockers are contraindicated, such as non-dihydropryidine CCBs, beta blockers, adenosine, and digoxin.
Note: Amiodarone is contraindicated in WPW with Atrial fibrillation due to its the nodal blocking effects. Procainamide lengthens the ERP and hence the QTc interval, which can cause torsades. Procainamide must be stopped when the QRS widens by 50%.

_**WPW with Atrial fibrillation_
Atrial fibrillation can occur in up to 20% of patients with WPW and atrial flutter can occur in up to 7% of patients with WPW. The accessory pathway allows for rapid conduction directly to the ventricles bypassing the AV node. Rapid ventricular rates may result in degeneration to VT or VF.

ECG features WPW with atrial fibrillation are:

• Irregular rhythm
• Wide QRS complexes (>120ms) due to abnormal ventricular depolarisation from the disorganized atrium via accessory pathway (>200 bpm)
• QRS complexes change in shape and morphology due to the varied atrial foci
• Axis remains stable unlike Polymorphic VT

RECIPERE]
QRS Wide (>120ms) and Irregular
** AV node blockade contraindicated
** Treat like VT

i) Hemodynamically Unstable
Synchronized cardioversion

• *ii) Hemodynamically Stable**
• *Procainamide 20mg/min IV, until QRS widens by 50% or dysrhythmia supressed**
• *Note:** AV node blockers are contraindicated such as non dihydropryidine CCBs, beta blockers, adenosine, and digoxin.
• *Note:** Amiodarone is contraindicated in WPW with Afib due to its the nodal blocking effects. Procainamide lengthens the ERP and hence the QTc interval, which can cause torsades. Procainamide must be stopped when the QRS widens by 50%.

Atrial tachycadia (AT)
ECG findings:

• Regular rhythm
• Narrow QRS (<120ms)
• Abnormal p-wave

Ectopic (unifocal) atrial tachycardia arises from an independent focus within the atria, distinguished by a consistent p wave of abnormal shape and/or size that falls before a regular narrow QRS. It is caused by automaticity, which means that some cardiac muscle cells, which have the primordial (primitive, inborn, inherent) ability to generate electrical impulses that is common to all cardiac muscle cells, have established themselves as a ‘rhythm center’ with a natural rate of electrical discharge that is faster than the normal SA node.

Multifocal atrial tachycardia (MAT)
ECG findings:

• Irregular rhythym
• Narrow QRS
• Different p wave morphologies

Multifocal atrial tachycardia (MAT) is tachycardia arising from at least three ectopic foci within the atria, distinguished by p wave with at least 3 different morphologies that all fall before irregular narrow QRS. This rhythm is most commonly seen in elderly people with COPD.

RP relationship
In patients with a inverted P wave, the temporal relationship between the P wave and the R wave divides narrow complex (except antidromic AVRT – wide complex) tachycardias into two categories: short RP and long RP tachycardias. The RP interval is defined as the interval from the onset of the QRS to the onset of the P wave.

• *Short RP tachycardias**
• *If the RP interval is less than one-half of the RR interval,** the tachycardia is considered a short RP tachycardia. The differential diagnosis of a short RP tachycardia is generated by considering the P wave morphology.

Inverted P wave – The combination of inverted P waves and a short RP interval is seen in the typical or slow-fast form of AVNRT (p wave is often buried) and in orthodromic AVRT.

Abnormal P wave – The combination of abnormal P waves and a short RP interval is most often seen in the setting of an atrial tachycardia (AT) with AV nodal conduction delay.

Long RP tachycardia
If the RP interval is more than one-half of the RR interval, the tachycardia is considered a long RP tachycardia. As with short RP tachycardias, the differential diagnosis is generated by combining the RP relationship with the P wave morphology.

Inverted P waves – The combination of inverted P waves and a long RP interval is usually caused by atypical or fast-slow AVNRT or by antidromic AVRT (antidromic AVRT is wide QRS tachycardia).

Abnormal P wave – The combination of abnormal P wave morphology and a long RP interval usually suggests some form of atrial tachycardia. However, this pattern can also occur in the atypical or fast-slow form of AVNRT.

Question 61

qSOFA

Quick

Sepsis Organ-related Failure Assessment

Answer 61

qSOFA tool used to identify patients who are at risk for a poor outcome outside the intensive care unit (ICU).

O/E] SBP<100, RR>22
General – ALOC (GCS<15)

2 or more ADMIT

Question 62

RAPD/Positive and Negative Visual Defects

Answer 62

Differentiating serious from less serious occular presentations can be done using RAPD and through positive vs negative visual distuburbances.

Positive vision disturbances are in addition to the visual field ie. scintillating scotoma where negative vision disturbances is where part of the visual field is missing ie. blind spots, tunnel vision, complete loss of vision, or loss of all vision to the left or right side. Negative visual disturbances are generally more concerning and require ophthamology follow up.

RAPD
The Relative Afferent Pupillary Defect (RAPD), or Marcus-Gunn Pupil is an extremely significant and highly objective clinical finding in the examination of the visual system. Even in an unconscious patient, the determination of an RAPD can be made. There are many different conditions which lead to this finding, from severe glaucoma to an optic nerve tumor. Also significantly, there are many conditions which lead to a profound loss of vision, such as a complete vitreous hemorrhage, which will not give an RAPD.

The “swinging flashlight test” is probably the best test for identifying an RAPD. In this test, a strong, steady light is used. The light is shined into one eye, and then quickly switched to the other. This is repeated back and forth, until one of four conclusions is reached (listed below). Since light in one pupil causes both pupils to constrict, quickly switching from one eye to the other will give a “relative” indication of the functioning of each eye and optic nerve. If both eyes are equally dysfunctional, no “relative” defect would be found. The results of the test include:

1. No Relative Afferent Pupillary Defect: Both pupils constrict equally without evidence of pupillary re-dilation with the “swinging flashlight test”, except possibly for “hippus”. Hippus refers to non-rhythmic fluctuations in pupillary size when there is a steady illumination.

2. Mild Relative Afferent Pupillary Defect: The affected pupil shows a weak initial constriction, followed by dilation to a greater size.

3. Moderate Relative Afferent Pupillary Defect: The affected pupil shows a stable or unchanged level of constriction, followed by dilation to a greater size.

4. Severe Relative Afferent Pupillary Defect: The affected pupil shows an immediate dilation to a greater size.

• *Conditions leading to RAPD**
• Optic nerve disorders*
• *Unilateral optic neuropathies** are common causes of an RAPD. **If a condition is bilaterally symmetrical, there will not be an RAPD.

1. Ischemic optic neuropathies - Giant Cell Arteritis causes. Usually there will be a loss of vision or a horizontal cut in the visual field. The ischemic process affects the posterior circulation of the globe, principally vessels (ie. ophthalmic artery and short posterior ciliary arteries) supplying the optic nerve at its exit from the eye.

Note: Giant-cell arteritis (GCA), also called temporal arteritis, cranial arteritis, or Horton disease is a vasculitis, an inflammatory disease of blood vessels most commonly involving large and medium arteries of the head, predominantly the branches of the external carotid artery.

The external carotid artery begins at the upper border of thyroid cartilage, and curves, passing forward and upward, and then inclining backward to the space behind the neck of the mandible, where it divides into the superficial temporal and maxillary artery within the parotid gland. Symptoms of GCA follow from inflammation of the branches of the external carotid artery. Scalp tenderness sensitivity and headache from the superficial temporal artery, jaw claudication (pain in jaw with chewing) from the maxillary artery, and tongue claudication (pain in tongue with chewing) from the lingual artery.

The most serious complication is occlusion of the ophthalmic artery, which is a branch of the internal carotid. It can create a medical emergency which can cause irreversible ischemia and blindness if not treated promptly. GCA is treated with glucocorticoids (steroids), which reduce the inflammation and prevent vascular occlusion. No other drugs are effective or contribute to the effect of glucocorticoids.

2. Optic neuritis (infection or inflammation) - Even very mild optic neuritis with a minimal loss of vision can lead to a very strong RAPD. Neuritis is a demyelinating condition of the optic nerve often seen in multiple sclerosis. Cryptococcus can cause a severe optic nerve infection in the immunocompromised. Sarcoidosis can cause inflammation of the optic nerve. Lyme disease can affect the optic nerve.

3. Orbital disease/compression - This could include compressive damage to the optic nerve from thyroid related orbitopathy (compression from enlarged extraocular muscles in the orbit), orbital tumors.

4. Traumatic optic neuropathy - This includes direct ocular trauma, orbital trauma, and even more remote head injuries which can damage the optic nerve as it passes through the optic canal into the cranial vault.

5. Glaucoma - While glaucoma normally is a bilateral disease, if one optic nerve has particularly severe damage from increased pressure in the eye, an RAPD can be seen.

• Retinal Causes*
• ***Symmetrically bilateral retinal disease will not show an RAPD**. Usually retinal disease has to be quite severe for an RAPD to be clinically evident.

1. Ischemic retinal disease - Causes include ischemic central retinal vein occlusion (CRVO) , central retinal artery occlusion (CRAO) , severe ischemic branch retinal or arterial occlusions, severe ischemic diabetic or sickle-cell retinopathy.

2. Retinal detachment - An RAPD can often be seen if the macula is detached, or if at least two quadrants of retina are detached.

3. Retinal infection (unilateral) - Cytomegalovirus, herpes simplex, and other causes of retinitis can lead to an RAPD if there is extensive disease.

4. Ischemic ocular disease (Ocular ischemic syndrome) - This usually arises from obstruction of the ophthalmic or carotid artery on one side.

5. Severe macular degeneration - If unilateral and severe, an RAPD can be seen. Usually the visual acuity would be less than 20/400.

6. Intraocular tumor - Retinal and choroidal tumors including melanoma, retinoblastoma, and metastatic lesion could lead to an RAPD if severe.

• Other Causes*
  1. Amblyopia, if severe, can lead to a relative afferent pupillary defect. Usually the visual acuity would be 20/400, or worse.

2. Cerebral vascular disease - Usually, it is an optic nerve disorder that leads to an RAPD, rather than an optic tract or visual cortex disorder. However, there tends to be a higher percentage of crossed vs. uncrossed nerve fibers at the optic chiasm. Thus, in a patient with a homonymous hemianopia from an optic tract disorder, an RAPD could be seen in the eye with the temporal visual field defect. The nasal retina serves the temporal visual field, and these are the fibers that would cross at the chiasm.

CONDITIONS WHICH WILL NOT CAUSE A RELATIVE
AFFERENT PUPILLARY DEFECT INCLUDE:
1. Cerebral infarct usually will not cause an RAPD

2. Cataract (even if completely opaque)

3. Corneal scar
4. Hyphema

5. Vitreous hemorrhage

• *Conditions with an Efferent Pupillary Defect**
  1. Third Cranial Nerve Palsy

2. Adie’s Pupil
3. Horner’s Syndrome

Question 63

RSI/Post RSI

Answer 63

Preparation/Preoxygenation
NP/A,B]
BVM, NRB, Apneoic oxygenation
NP/C]
PIV
NP/Mon]
cardiac monitor, BP, SpO2
NP/Nut]
NPO
NP/Pro]
Suction, laryngoscope, stylet, ETT, bougie, glydescope, cricothyrodotomy kit
ETT – cuffed size (age+16)/4
(7.5 for adult female, 8 for adult male)

Induction
1. Ketamine 1-2 mg/kg IV (or more simply 1.5mg/kg) (100mg for 70kg)
Onset: 30s IV, 2-4 min IM
Duration: 5-10 min IV, 15-25 min IM
Note:When administered rapidly (<30 seconds), ketamine produces anesthesia, including respiratory depression, while maintaining hemodynamic stability. Ketamineantagonizes the NMDA receptor,which is a main glutaminergic excitatory receptor in the CNS and creates a functional dissociation between the cortex and the limbic system. Ketamine also causes the release of catecholamines from the adrenals. The evidence regarding ketamine’s support of cardiovascular function is applicable to clinical situations where endogenous catecholamine stores arenot likely to be exhausted. Catecholamine release stabilizes blood pressure and causes bronchodilation.Good choice of agent for hemodynamically unstable and in asthma. Ketamine does not cause adrenal insufficiency (such as in the use of Etomidate), and can be used in shock.As ketamine is metabolized and eliminated,redosing (usually 0.5 mg/kg) may be necessary in 15 minutes to maintain therapeutic concentrations.

Specific concerns about ketamine include increased intracranial pressure (ICP), increased intraocular pressure (IOP), paradoxical myocardial depression, psychodysleptic effects, and accelerated neuronal apoptotic degeneration. Concerns about ICP and IOP are examples of conventional teachings that are supported by their own repetition rather than evidence.

2. Propofol 1.5-2.5 mg/kg (or more simply 1.5mg/kg) (100mg for 70kg)
Onset: 30s
Duration: 3-5 min
Note:Propofol works byincreasing GABA-mediated inhibatory tone in the CNS. Propofol decreases the rate of dissociation of the GABA from the receptor, thereby increasing the duration of the GABA-activated opening of the chloride channel with resulting hyperpolarization of cell membranes.

Side effects include low blood pressure related to vasodilation, transient apnea following induction doses, and cerebrovascular effects. Propofol has more pronounced hemodynamic effects relative to many intravenous anesthetic agents. Reports of blood pressure drops of 30% or more are thought to be at least partially due to inhibition of sympathetic nerve activity. Propofol can also cause decreased systemic vascular resistance, myocardial blood flow, and oxygen consumption, possibly through direct vasodilation. As a respiratory depressant, propofol frequently produces apnea. The persistence of apnea can depend on factors such as premedication, dose administered, and rate of administration, and may sometimes persist for longer than 60 seconds. Possibly as the result of depression of the central inspiratory drive, propofol may produce significant decreases in respiratory rate, minute volume, tidal volume, mean inspiratory flow rate, and functional residual capacity. One of propofol’s most frequent side effects is pain on injection, especially in smaller veins. This pain arises from activation of the pain receptor, TRPA1, found on sensory nerves and can be mitigated by pretreatment with lidocaine.

3. Etomidate 0.3-0.5 mg/kg IV
(20mg for 70kg)
Onset: <1min
Duration: 3-5min
Note:Primary effects of sedation and amnesia are mediated through theγ-aminobutyric acid (GABA) inhibitory neurotransmitter system.Beneficial effects on the central nervous system include adecrease in cerebral metabolic rate for oxygen (CMRO2), in cerebral blood flow, and in ICP.As a result of decreased CMRO2 and cerebral blood flow, with a negligible effect on myocardial performance,etomidate decreases ICP while it maintains CPP (CPP = MAP-ICP).Etomidate inhibits the enzyme 11-β hydroxylase, which is necessary for the production of cortisol, aldosterone, and corticosterone, resulting in a significant decrease in serum cortisol concentration and adrenocorticotropin hormone (ACTH) responsiveness in patients.
**Etomidate causes adrenal insufficiencyby reducing the circulating amounts ofcortisolandshould not be used in shock states.

Cortisol inhibits production of interleukin (IL)-12, interferon (IFN)-gamma, IFN-alpha, and tumor-necrosis-factor (TNF)-alpha by antigen-presenting cells (APCs) and T helper (Th)1 cells, but upregulates IL-4, IL-10, and IL-13 by Th2 cells. This results in a shift toward a Th2 immune response rather than general immunosuppression. The activation of the stress system and resulting increase in cortisol and Th2 shift seen during an infection is believed to be a protective mechanism which prevents an over-activation of the inflammatory response.

Paralytic
1. Succinylcholine 1.5 mg/kg IV
(100mg for 70kg)
Onset: 45-60 seconds
Duration: 6-10 minutes
Note: Phase 1 blocking has the principal paralytic effect. Binding of suxamethonium to the nAChR results in opening of the receptor’s monovalent cation channel causing disorganized depolarization of the motor end-plate. K+ leaves the cell into the interstitium and plasma, which can cause hyperkalemia. Ca2+ release from the sarcoplasmic reticulum. In normal skeletal muscle, ACh dissociates from the receptor following depolarization and is rapidly hydrolyzed by the enzyme acetylcholinesterase. The muscle cell is then ready for the next signal.

Suxamethonium has a longer duration of effect than ACh, and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential above threshold, it does not allow the muscle cell to repolarize. When ACh binds to an already depolarized receptor, it cannot cause further depolarization.

Ca2+ is removed from the muscle cell cytoplasm independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the Ca2+ is taken up by the sarcoplasmic reticulum, the muscle relaxes and explains muscle flaccidity rather than tetany following fasciculations. The results are membrane depolarization and transient fasciculations, followed by paralysis.

Phase 2 block is not abnormal and is a part of its mechanism of action. It is caused by the blood concentration of suxamethonium exceeding the therapeutic window. Desensitization occurs at the nerve terminal, and the myocyte becomes less sensitive to acetylcholine; the membrane repolarizes and cannot be depolarized again.

2. Rocuronium 1 mg/kg IV
(70kg for 70kg)
Onset: 60 seconds
Duration : 45-60 minutes
Note:Rocuronium acts by competing for nAChR at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium. The binding of vecuronium decreases the opportunity for ACh to bind to the nAChR at the postjunctional membrane of the myoneural junction. As a result, depolarization is prevented, Ca2+ ions are not released and muscle contraction does not occur.

Post RSI

1. Propofol 30mcg/kg infusion

2. {Versed} Midazolam 4mg IV q5-15min AND
Fentanyl 25-100mcg IV q15min THEN

{Versed} Midazolam 4mg/min (0.02 to 0.1 mg/kg/min, 1.5 to 10 mg/min for 70kg person)

• ​Intubation Using Apnoeic Oxygenation To Prevent Desaturation: A Systematic Review And Meta-Analysis Holyoak, R.S., et al, J Crit Care 41:42, October 2017

CONCLUSIONS: Overall, apneic oxygenation was associated with a reduced incidence of desaturation and critical desaturation. Its benefits were more pronounced in patients who were being intubated for any indication other than respiratory failure.
EDITOR’S COMMENTARY: This was a systematic review and meta-analysis of 17 studies including 2,422 patients who underwent endotracheal intubation with the objective of comparing apneic oxygenation versus no apneic oxygenation. The main outcomes were incidence of desaturation, critical desaturation and lowest SpO2. The authors found a statistically significant decrease in the incidence of desaturation, critical desaturation and an increase in lowest SpO2 with apneic oxygenation. The authors conclude that apneic oxygenation is ideal prior to endotracheal intubation.

Note: Apnoeic oxygenation is using NP set at 15L under the NRB and keeping the NP on while intubating.

Question 64

SAH (aneurysmal and traumatic)

Answer 64

1. DIAGNOSIS

**ii) lab/imaging**
CT Head (non-contrast) -- the utility of a non-contrast CT head is typically only in the first 6 hours (100% in the first 6 hours and 58% at day 5).

Lumbar puncture – elevated opening pressure, elevated RBC that does not diminish from tubes 1 to 4, and xanthochromia.

CTA – following a positive CT or positive LP, a CTA is performed to investigate the site of an aneurysm.

Note: Xanthochromia (xanthos, yellow) is a yellow tint of the CSF due to hemoglobin degredation products which takes about 2 hours to degrade. If the suspicion for a SAH is under 2 hours xanthochromia may not be a useful sign. By 12 hours post SAH 100% of people will have xanthochromia which lasts 2 weeks or more. Xanthochromia can be detected on gross visual inspection by holding up a vial of CSF and comparing it to a vial of water under bright light. Xanthochromia can also be detected by spectroscopy.

2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – starting from acute to benign
5. Investigations (rule in/out)
   CT Head (non-contrast)
   LP
   ​CTA
6. TREATMENT/MANAGEMENT
   * Blood pressure control*

Note: Optimal therapy is not well established. Cautious use of antihypertensive therapy to decrease the risk of rebleeding may be appropriate in some patients with SBP >160 mmHgorMAP >110 mmHg with adequate cerebral perfusion pressures (AHA/ASA [Connolly 2012]; Singer 2020) (max 300mg). Although manufacturer’s labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in selected patients, while monitoring for accumulation (Goldsmith 1990).

Intermittent IV: Labetalol 10 to 20 mg over 2 minutes; then 20 to 80 mg q10-15 minutes until systolic BP <160 mm Hg or mean arterial pressure <100 mm Hg (Liu-DeRyke 2013; Mocco 2006; Patel 1993; Woloszyn 2012).

Continuous IV infusion: 0.5 to 2 mg/minute titrated to response; based on very limited data (Mocco 2006).

Acute seizure
Lorazepam 1-2mg IV q5min (max 4mg)

Seizure prophylaxis
Phenytoin (Dilantin) 15-20mg IV

Vasospasm prophylaxis
Nimodipine 60mg PO q4h x 21 days
Note: Vasospasm occurs 2 days to 3 weeks ofter SAH.

• Validation Of The Ottawa Subarachnoid Hemorrhage Rule In Patients With Acute Headache Perry, J.J., et al, Can Med Assoc J 189(45):E1379, November 13, 2017

BACKGROUND: While missing subarachnoid hemorrhage (SAH) can have life-threatening consequences, carrying out neuroimaging and lumbar puncture in every patient with acute headache is counterintuitive. The authors previously derived the Ottawa Subarachnoid Hemorrhage Rule among ED patients with headache. The rule calls for investigation for SAH in alert patients aged 15 or older with acute severe nontraumatic headache reaching maximum intensity within one hour of onset who have at least one of the following:

• *1 . Age > 40
  2. Neck pain or stiffness
  3. Witnessed LOC
  4. Exertional headache
  5. Thunderclap headache (peak pain instantly - within an hour)
  6. Limited neck flexion**

CONCLUSIONS: The Ottawa Subarachnoid Hemorrhage Rule demonstrated perfect sensitivity in this new validation cohort. The authors feel that it can effectively identify all patients with acute headache who do not require further investigation to exclude SAH.
EDITOR’S COMMENTARY: This is the validation set for the Ottawa SAH clinical decision rule. The rule involves 6 elements from the H&P and was 100% sensitive (**can use the tool to rule out) for identifying SAH in ED patients presenting with new severe, non-traumatic HA. The specificity is low (13.6%). Using the rule, >85% patients will screen positive meaning that a work-up for SAH is indicated. In the study, not all of those patients received a full work-up nor would they likely receive one in the real-world application of this rule which limits its usefulness.

HPI]
“thunderclap” sudden onset with maximal intensity (within an hour), WHOL, precipated by exertion (such as weight lifting, sexual activity, defacation, coughing), vomiting, syncope, photophobia,

PMHx]
HTN

SHx]
EtOH
Smoking

O/E] HTN, GCS decreased
General – ALOC
Neuros – nuchal rigidity

Note: Nuchal rigidity is the inability to flex the neck forward due to rigidity of the neck muscles preventing flexion due to pain; if flexion of the neck is painful but full range of motion is present, nuchal rigidity is absent. Flexion of the spine leads to stretching of the meninges. Traction on the inflamed meninges is painful, resulting in limited range of motion through the spine (especially in the cervical spine).

POCUS – papilledema – 3mm down from the retina and >5mm across the optic nerve sheath indicates papilledema, or crescent sign

INVESTIGATIO]
L(H)/Haim]
CBC, INR, PTT

L(H)/Meta]
Lytes, XLytes

L(I/F)/CSF]
(if CT head negative)
<12h Xanthochromia may/may not be present, large RBC should be present
>12h Xanthochromia is HIGHLY suggestive, large RBC +/- present
12h-2w Xanthochromia or RBC may be absent
Note: There are 4 tubes with LP tap. If there are RBC’s in only tube 1 then suggestive of a traumatic tap, if there are RBC’s in tubes 1 to 4 then more suggestive of a SAH.

I]

• *CT wo contrast <6h** 100% sensitivity and 100% specificity
• *Note:** CT scan <6h should NOT need an LP to rule out SAH, CT misses 2% in 6-12 hours, and 7% in 12-24h.

RECIPERE]
NP/A,B]
SpO2>94%
Elevate the head of the bed 30 degrees
Hyperventilation to PaCO2 25-30mmHg (35-45mmHg).
Note: Hyperventilation causes decreased PaCO2 and as a result vasoconstriction.

NP/C]
PIV, NS fluids for maintanence

NP/Mon]
cardiac monitor, BP, SpO2

NP/Nut]
NPO

P/Poin]

• *Morphine 4-8mg IV**, q5-15min OR
• *{Dilauded} 0.5mg IV**, q1h

P/N,V]
{Zofran} 4mg IV/SL

P/Haim]
Vitamin K 10mg slow influsion
(if anticoagulated on Warfarin)
Protamine sulfate
(if anticoagulated on Heparin)

P/Meta]
Insulin
(if hyperglycemic and ketosis)

P/Neuros]
{Versed} Midazolam 2.5-5mg IV
(sedation if unstable)
{Dilantin} Phenytoin 20mg/kg IV, max 50mg/kg
(for seizures)

P/Org(Cephalos)]
Hypertonic saline 3% 3-5 mls/kg over 10–20 minutes OR
Mannitol 1g/kg (70g for 70kg) IV bolus over 30 min,
then 0.25 to 0.5 g/kg q6h to plasma Osm 300-310
Note: There is 100g in a 500mL bag of mannitol – hanging a 500mL bag would be appropriate. Hypertonic saline 3% comes in 250mL bag – give 150cc boluses. In one 150cc bolus there is 4500mg of sodium (30g x 150cc).
Note: 1 amp of sodium bicarbonate contains 1150mg of sodium. Giving 2 amps of sodium bicarbonate will be giving 2300mg of sodium.

P/Org(Vasculos)]
**DO NOT overcorrect ​BP in the case of cortical SAH.
IF SBP>200 or MAP>150
Labetalol 10mg IV, over 1-2 min, q10min max 300mg
THEN 2mg/min influsion titrated to MAP reduction 10% to 20%
{Nimotop} Nimodipine 60mg PO q4h
(CCB for vasospasm)
Note: Nimodipine is for aneurysmal SAH and not traumatic SAH.

P/Consult]
Neurosurg consult

Question 65

Salter Harris Classification

Answer 65

S - Type 1 - Strait across the physis

A - Type 2 - Above the physis toward the metaphysis

L - Type 3 - BeLow physis toward the epiphysis

T - Type 4 - Through the physis

ER - Type 5 - ERase the physis or cRushed the physis

Question 66

SEA

Answer 66

• Errors In Diagnosis Of Spinal Epidural Abscesses In The Era Of Electronic Health Records Bhise, V., et al, Am J Med 130(8):975, August 2017

BACKGROUND: It has been reported that the incidence of spinal epidural abscess has doubled over the past two decades, and that related diagnostic errors are increasing over time.
RESULTS: Diagnostic errors (“missed opportunities to make the correct or timely diagnosis”) were identified in 55.5% of these cases. All but three patients presented with multiple red flags (mean, 4.6), but red flags were missed in the 66 patients with diagnostic errors. The most frequently missed red flags were:

• *1.** unexplained fever (most common)
  2. focal neurologic deficits with progressive or disabling symptoms (next most common)
  3. active infection

Other missed red flags included:

• *1. immunosupression
  2. history of cancer
  3. prolonged use of steroids
  4. IV drug use
  5. back pain > 6 weeks
  6. unexplained weight loss**

In just over half the cases, a red flag was documented by the provider but not acted upon, and in one-third the red flag was missed by the provider (even when red flags were documented by providers at the time of prior recent visits). In patients with diagnostic errors, CRP and/or ESR testing was ordered in only about one-fourth of cases, and MRI (the imaging test of choice) was ordered in only 41% of cases. In all of the latter cases, MRI was not ordered as an urgent imaging study, resulting in a median diagnostic delay of six days. All but one of the patients experiencing diagnostic delay sustained moderate to severe harm or death.
CONCLUSIONS: This study documents frequent diagnostic error in patients with spinal epidural abscesses, most commonly due to deficiencies in recognition of red flags, laboratory testing and appropriate imaging.
EDITOR’S COMMENTARY: This study, coordinated at the VA, involved retrospective chart reviews of patients with a known final diagnosis of spinal epidural abscess. The reviewer, who was most often a single physician who knew the final diagnosis, examined the record for diagnostic errors such as missing established red flags of back pain, ordering the wrong diagnostic test and delays in obtaining the MRI (the correct test).

Question 67

Sepsis/Shock

Answer 67

• Comparison of dopamine and norepinephrine in the treatment of shock, Daniel De Backer, Patrick Biston, Jacques Devriendt, Christian Madl, Didier Chochrad, Cesar Aldecoa, Alexandre Brasseur, Pierre Defrance, Philippe Gottignies, Jean-Louis Vincent, New England Journal of Medicine 2010 March 4, 362 (9): 779-89

CONCLUSIONS: Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events.

• Arterial Versus Venous Lactate: A Measure Of Sepsis In Children Samaraweera, S.A., et al, Eur J Pediatr 176(8):1055, August 2017

BACKGROUND: Hyperlactatemia is a marker of a poor prognosis in patients with sepsis. Arterial blood sampling has been considered the standard for measurement of lactate levels; some, but not all, adult studies suggest that venous levels are a reliable surrogate for arterial lactate. Data in the pediatric population are limited.
CONCLUSIONS: The authors suggest that a normal venous lactate level (2 mmol/L or lower) appears to reliably reflect arterial lactate in the early management of children with sepsis, but that arterial levels must be measured if the venous lactate is above 2mmol/L.
EDITOR’S COMMENTARY: The authors retrospectively looked at VBG and ABG lactate samples in critically ill children with sepsis in the ICU. The VBG and ABG were drawn within 1 hour of each other and the lactate values were compared. The VBG and ABG lactate values correlated well up to 2 mmol/L. Above 2 mmol/L, the two tests did not correlate as well. The authors recommend using VBG as an initial test, but if the lactate is above 2 mmol/L, the ABG sample would be the best test if the exact lactate value is needed.

• The Timing Of Early Antibiotics And Hospital Mortality In Sepsis Liu, V.X., et al, Am J Resp Crit Care Med 196(7):L856, October 1, 2017

CONCLUSIONS: Every hour of delay to antibiotic treatment in these patients with sepsis significantly increased the risk of hospital mortality, especially for those with septic shock. These findings confirm the benefits of, and support efforts to promote, early treatment.
EDITOR’S COMMENTARY: This multicenter retrospective study coordinated at Kaiser Permanente examined the association between antibiotic timing and mortality in 35,000 adults with sepsis treated with antibiotics within 6 hours of ED arrival in 2010-2013. The primary outcome was in-hospital mortality as a function of antibiotic timing. Of the total, 35% of patients had sepsis, 52% had severe sepsis, and 13% had septic shock; corresponding mortality rates were 3.9%, 8.8%, and 26.0%, respectively. Every hour of delay to antibiotic treatment in these patients with sepsis significantly increased the risk of hospital mortality, especially for those with septic shock.

• Comparison Of qSOFA Score And SIRS Criteria As Screening Mechanisms For Emergency Department Sepsis Haydar, S., et al, Am J Emerg Med 35(11):1730, November 2017

EDITOR’S COMMENTARY: In a retrospective chart review study of 200 patients diagnosed and treated for sepsis in the emergency department, researchers sought to assess the sensitivity of the qSOFA score in diagnosing sepsis and to compare its timeliness to SIRS criteria. They found that 94.5% of patients met SIRS criteria whereas 58.3% met qSOFA criteria and that the mean-time for documentation of SIRS vs qSOFA was 47.1 min vs 84.0 min. They conclude that the qSOFA score performed poorly in identifying sepsis in the ED and may delay evidence-based treatment to improve sepsis-related outcomes.

• The Surviving Sepsis Campaign Bundle: 2018 UpdateLevy, Mitchell, M., MD, MCCM1; Evans, Laura, E., MD, MSc, FCCM2; Rhodes, Andrew, MBBS, FRCA, FRCP, FFICM, MD (res)3 Critical Care Medicine: June 2018 - Volume 46 - Issue 6 - p 997–1000

Summary: Previous iterations of the sepsis bundle were introduced as a means of providing education and improvement related to sepsis management. The literature supports the use of sepsis bundles for improving outcomes in patients with sepsis and septic shock. This new sepsis “hour-1 bundle,” based on the 2016 guidelines, should be introduced to emergency department, floor, and ICU staff as the next iteration of ever-improving tools in the care of patients with sepsis and septic shock as we all work to lessen the global burden of sepsis.

Surviving Sepsis Campaign (SSC) 2017
The new Surviving Sepsis Guidelines were released in January 2017 as an update to the 2012 guidelines. The 2012 sepsis criteria maintained the model of “early goal-directed therapy” (EGDT) as a guiding principle which became the standard of care after the groundbreaking Emmanuel Rivers’ study in 2001 (Rivers 2001). The 2017 Surviving Sepsis Guidelines now reflect the results of the PRISM analysis (PROCESS, PROMISE, and ARISE) trials; 3 large multicenter studies demonstrating no significant difference in the primary outcome of mortality between EGDT and usual care. (ProCESS Investigators 2014, ARISE Investigators 2014, Mouncey 2015)

• *Sepsis**
• *Sepsis** is a life threatening organ dysfunction due to a dysregulated host response to infection. In layman’s terms it is a life threatening condition that arises when the bodies response to infection injures its own tissues and organs. Presentation is typically tachycardia, hypotension, fever, leukocytosis.

Septic shock
Septic shockis sepsis wheredespite adequate fluid resisitationthere iscontinuing hypotension requiring vasopressors to maintain a MAP>65mmHg (2/3DP + 1/3SP), anddespite adequate fluidslactate>2mmol/L. With these criteria hospital mortality exceeds 40 percent.

Note: BP = CO x SVR, where CO = HR x SV (stroke volume)
SVR is goverened by the smooth muscle on the peripheral resistance vessels (SVR), small arteries and arterioles. BP is also affected by the CO though SV. SV can decrease due to heart ejection difficulty or not enough volume feeding the heart through the venous system or capacitance vessels. In cardiogenic shock the heart is damaged and not able to eject blood efficiently.

In sepsis and anaphylactic shock, the volume of blood reaching the left ventricle is decreased due to leaky capillaries and increased venous elasticity. Not enough blood reaches the right atrium and the right atrium pressure (RAP) drops. Vasopressors increase venous capacitance vessel resistance causing more blood to reach the right atrium. More blood to the right atrium increases RAP, susequently increasing blood to the left ventricle and SV, and thereby CO and BP. At the same time vasopressors increase the SVR at the splanchnic arteries (celiac, inferior and superior mesenteric arteries) and peripheral arteries, shunting more blood to the heart and head.

Note: Elevated lactate in sepsis is not due to low oxygen delivery or anaerobic metabolism but from epinephrine stimulating beta2 adrenergic receptors at skeletal muscle. In skeletal muscle the stimulation of beta2 adrenergic receptors upregulates glycolysis generating more pyruvate that can be used by the TCA cycle. Excess lactate is produced from pyruvate. Lactate serves as a metabolic fuel for the heart and brain in times of stress.

Lactate is a marker for endogenous catecholamine release. In this context, lactate can be used to identify occult shock.

qSOFA (quick Sepsis Organ-related Failure Assessment)
Any 2 of the following:
1. SBP<100
2. RR>22
3. ALOC (including any GCS<15)

SIRS
Any TWO of the following:
O/E] HR>90 RR>20 T>38 or <36

L(H)/Haim]
WBC>12 x10³ cells/mm3 or <4 x10³ cells/mm3 or >10% bands
ABG – PaCO2<32 (35-45)
PaCO2<35 means patient is hyperventilating.
PaCO2>45 means patient is hypoventilating.

INVESTIGATIO]
L(H)/Haim]
CBC (WBC and platlets)
VBG with lactate, or ABG

L(H)/Meta]
SMA7

L(H)/Infla]
CRP (elevated in infection)

L(O)]
Urine dip

L(I)/Haim, Ouron, Cephalo]
Blood C&S x2
Urine C&S
CSF C&S

I]
CXR
POCUS (IVC)

RECIPERE]

• **Fluids 30cc/kg within 3 hours (about 2 L for 70kg)
• Antibiotics within 1 hour
• Sepsis labs

NP/A,B]
O2>90%

NP/C]
PIV, **Fluids 30cc/kg
Note:SSCstipulates fluids of30cc/kg within 3 hoursas astrong recommendation. 70kg male at 30cc/kg would need a fluid 2100mL within 3 hours.

Note: PRISM analysis (ProCESS, ARISE, and ProMISe) showed NO BENEFIT for EGDT (Early Goal Directed Therapy) and concluded that EGDT did not improve survival from sepsis, even in the sickest patients, but did increase use of intensive care, vasoactive infusions, and overall costs.

EGDT is a 6 hour protocol for the administration of IV fluids, vasopressors, inotropes, and pRBC transfusion to acheive pre-specified tragets for arterial blood pressure, central venous pressure, central venous oxygen saturation, and hemoglobin level.

Within 6 hours of presentation to the Emergency Department intensive monitoring of specific circulatory parameters with the aggressive management of 5 key parameters to specified targets to optimise oxygen delivery to tissues.

EGDT Parameters
CVP 8-12 mmHg (pressure in right atrium and SVC)
MAP 65-90 mmHg (mean pressure in arteries)
Urine output >0.5 cc/kg/hr
SvO2 >65% / ScvO2 (central venous) >70%
Haematocrit (HCT) >30%

• In brief,*
• *CVP<8** mmHg – fluids
• *MAP<65** mmHg – vasopressors
• *ScvO2<70%** – pRBCs

Note: SvO2 is mixed venous oxygen saturation measured from a pulmonary artery catheter (PAC). ScvO2 is central venous oxygen saturation measured from a central line.

P/Org(Vasculo)]

• *Norepinephrine 8mcg/min,** titrate to 8-12mcg/min
  0. 01-0.15 mcg/kg/min (peripheral IV), typically 0.05mcg/kg/min
  0. 01-0.30mcg/kg/min (central IV), typically 0.05mcg/kg/min
• *Note: SSC** stipulates to use Norepinephrine (Levofed) as a first choice as a strong recommendation. Dopamine is out of favour due to the increase in arrythmias.

P/Infect]
Among organisms isolated from patients with sepsis, the most common include:
GP – Staphylococcus aureus (**including MRSA), Streptococcus pneumoniae,
GN – Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa

Note: Uptodate – There is growing recognition that methicillin-resistant S. aureus (MRSA) is a cause of sepsis not only in hospitalized patients, but also in community dwelling individuals without recent hospitalization. For these reasons, we suggest empiric intravenous vancomycin (adjusted for renal function) be added to empiric regimens, particularly in those with shock or those at risk for MRSA.

IF pseudomonas is NOT a consideration,
Vancomycin 1g IV BID AND broad spectrum:
Beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate, amoxicilin-clavulanate)
OR
Cephalosporin, 3rd generation (eg, ceftriaxone or cefotaxime) OR
Cephalosporin 4th generation (cefepime)
OR
Carbapenem (eg, imipenem or meropenem)

IF pseodomonas IS a consideration,
Vancomycin 1g IV BID AND ONE pseudomonal coverage antibiotic (no longer double pseudomonal coverage):
Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam)
OR
Antipseudomonal cephalosporin (eg, ceftazidime, cefepime), OR
Antipseudomonal carbapenem (eg, imipenem, meropenem), OR
Fluoroquinolone with good anti-pseudomonal activity (eg, ciprofloxacin)
OR
Aminoglycoside (eg, gentamicin, amikacin)
OR
Monobactam (eg, aztreonam)

Question 68

Seizure First Episode

Answer 68

• Emergency Computed Tomography In Patients With First Seizure Kotisaari, K., et al, Seizure 48:89, May 2017

CONCLUSIONS:The authors suggest that clinical features alone can be used to guide decision making about emergency CT imaging for adults with a first seizure, and that imaging can be deferred for outpatient use when high-risk features are absent.
EDITOR’S COMMENTARY: This retrospective study from Finland attempted to review the charts of 416 adult patients with first-time non-traumatic seizures to evaluate the rates of emergent imaging findings on Head CT. Utilizing non-rigorous chart review methods, the authors noted that approximately 12% of patients had emergent findings (mostly intracranial hemorrhage or tumors). They also noted that the patients with emergent findings were more likely to have:

• *1. History of malignancy
  2. Headaches
  3. Alterted mental status
  4. Focal motor neurologic deficits**

with a NPV of 96%. They conclude that in the absence of the aforementioned high risk features, imaging may be deferred to the outpatient setting. Based on their own results that first time adult seizures have a high association with serious underlying pathology, we disagree with the conclusion of deferring imaging in these patients utilizing a non-validated decision tool that was quasi-derived via chart review.

Question 69

Status Epilepticus

Answer 69

1. Diagnosis
   * *i) clinical**
   * *single seizure >5min** OR
   * *>or= 2 seizures** withough complete recovery between events

ii) lab/imaging
EEG

iii) time
N/A

2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – starting from acute to benign
   * *Infectious**

• Meningitis/Encephalitis

Note: Diagnose with LP/CT treat with ABX/Antivirals

Metabolic

• Hypoglycemia
• Hypo/hypernatremia
• Hypocalcemia
• Hypomagnesmia

Note: Treat with proper replacement.

Drugs

• TCAs
• ETOH

Note: Treat with Sodium bicarbonate, ETOH treat with benzos.

Other

• Eclampsia

Note: Treat with Magnesium Sulphate 2g IV.

5. Investigations (rule in/out)
6. Treatment/Management
   * *i)** Hypoglycemia
   * *D50W 1amp (25g in 50mL) IV,** if BG<3.3
   * *Thiamine 100mg IV**

• *ii)** Hyponatremia
• *Bicarbonate (Na 100mEq in 100mL) 2 amps** OR
• *NaCl 3% 150mL**
• *iii)** Seizure
• *Lorazepam 4mg IV** repeat x 1 if necessary OR
• *Midazolam 10mg IM/IV/IN if >40 kg,** 5mg if 13-40kg OR
• *Diazepam 10mg IV/PP**

THEN

Leviracetam (Keppra) 60mg/kg (max 4500mg) over 10 minutes OR

Valproate 40mg/kg (max 3000mg) over 10 minutes OR

Fosphenytoin 20mg/kg (PE equivalents) at 150mg (PE)/min, if no IV access IM can be used with limited results

Note: ESETT trial (December 2019) has shown that keppra, fosphenytoin and valproate have similiar efficiencies.

The choice among these antiseizure drugs can be made according to individual patient factors such as comorbid conditions and potential adverse effects, as well as local availability. Clinical judgement is required to determine nonbenzodiazepine antiseizure drug selection and dosing for patients on chronic therapy with one of the preferred agents prior to the onset of GCSE (generalized convulsive status epilepticus). As an example, for a patient on phenytoin treatment prior to the onset of GCSE who is known to have a recent therapeutic phenytoin dose or level, it is reasonable to use valproate or levetiracetam (rather than phenytoin or fosphenytoin) as the second agent for GCSE. Similarly, for a patient on chronic valproate who is known to have a recent therapeutic dose or level, it is reasonable to use phenytoin/fosphenytoin or levetiracetam (rather than valproate) as the second agent for GCSE. In contrast, for a patient on chronic phenytoin or valproate who is thought to have a low drug level, an additional, proportionate loading dose of that drug would be worthwhile.

It takes too long to obtain levetiracetam levels in the urgent setting of GCSE. Accordingly, for patients on chronic levetiracetam, it is reasonable to use phenytoin or valproate as the second agent for GCSE if the recent dosing or level of levetiracetam is unknown. An alternative is to reload with levetiracetam, as there is no serious risk to transient supratherapeutic levetiracetam levels.

THEN
(requires intubation and preparation for continous infusion)

Propofol 1-2mg/kg (100mg) IV, THEN titrate up to 10mg/kg/hr until seizure stops OR

Midazolam 0.2mg/kg IV, THEN titrate up to 3mg/kg/hr until seizure stops OR

Phenobarbitol 5mg/kg IV, over 10minutes repeat until seizures stops THEN 1-5mg/kg/hr

Question 70

SIRS

Systemic Inflammatory Response Syndrome

Answer 70

Any TWO of the following:

O/E] HR>90, RR>20, T>38 or <36
PaCO2<35 means patient is hyperventilating
PaCO2>45 means patient is hypoventilating

INVESTIGATIO]
L(H)/Haim]
WBC>12 x 10³ cells/mm³ or <4 x10³ cells/mm³ or >10% bands
ABG – PaCO2<32 (blowing off CO2)

Question 71

STEMI

Answer 71

1. Diagnosis
   i) clinical
   ii) lab/imaging
   iii) time
2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – starting from acute to benign
5. Investigations (rule in/out)
6. Treatment/Management

Question 72

TAD

Answer 72

Diagnostic Accuracy Of The Aortic Dissection Detection Risk Score Plus D-Dimer For Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study Nazerian, P., et al, Circulation Epub ahead of print, October 13, 2017
CONCLUSIONS: The authors suggest that combining assessment with the ADD-RS plus D-dimer (<500ng/mL) testing effectively excludes AAS and avoids unnecessary imaging in patients at low risk (i.e., those with an ADD-RS of 1 or lower). They advise imaging in those with an ADD-RS above 1, regardless of D-dimer results.
EDITOR’S COMMENTARY: These multinational authors prospectively evaluated the diagnostic accuracy of the Aortic Dissection Detection Risk Score (ADD-RS) in combination with a D-dimer test. They enrolled 1850 adults with suspected acute aortic syndrome (AAS) and they found that an ADD-RS score of less than or equal to 1 combined with a negative D-dimer yielded only a 0.3% failure to diagnose rate (1/294 cases were missed in the AAS 0 group and 1/312 cases were missed in the ADD-RS 1 group). The authors conclude that an ADD-RS score of 1 or lower combined with a negative D-dimer (<500ng/mL) effectively excludes AAS and avoids unnecessary imaging in this low risk cohort. The editors recommend that clinical judgment continue to supercede any decision rule.

IRAD
The International Registry of Acute Aortic Dissections (IRAD) is a consortium of research centers that are evaluating the current management and outcomes of acute aortic dissection. It was established in 1996, and currently has 30 large referral centers in 11 countries participating in the registry. The main purpose of IRAD is to assess the etiological factors, modes of presentation, clinical features, treatment, and hospital outcomes of patients with acute aortic dissection around the world.

Everything from dates and times of symptom onset, presentation, diagnosis, hemodynamic signs of aortic dissection, initial and chronic medical therapy, diagnostic imaging chosen, and surgical and medical management is being studied.

Creation of working groups to identify new breakthroughs in diagnosis and treatment have just been developed including groups targeting: the genetic basis of aortic dissection; use of acute and chronic biomarkers; best surgical approach; best medical approach; how patients should be followed; and what is the proper role for percutaneous stent graft therapy.

HPI]
sudden and intense “tearing” or “ripping” pain, WPOL – worst pain of life, radiating to the back, 1/3 have neurological complaints, diaphoresis, syncope

PMHx]

• *Preexisting aortic aneurysm** - more common cause in patients under age 40.
• *Hypertension** - the most important predisposing risk factor. In research published by IRAD, hypertension has been associated in over 70% of patients.
• *Aortic valve** disease - bicuspid, replacement, stenosis.
• *High-intensity weight lifting** - during significant weight training a patient’s blood pressure may increase significantly. Especially in patients with risk factors or family history of aneurysms, strenuous weight lifting can be extremely dangerous.
• *Connective tissue disorders** – Marfan syndrome, Ehlers-Danlos syndrome.
• *Coronary artery bypass graft surgery/cardiac catheterization** - dissection is a rare complication.
• *Inflammatory diseases** that cause a vasculitis (damage to blood vessels) – giant cell arteritis, takayasu arteritis, rheumatoid arthritis, syphilitic aortitis.
• *Turner syndrome**

FHx]
first degree relatives

SHx]
crack cocaine - average time between last cocaine use and dissection was 12 hours.

O/E] HTN
Neuros – Stanford type A - right hemisphere CVA, Horner syndrome (miosis, ptosis, anhydrosis), upper extremity pain/paresthesia/motor weakness; Stanford type B - lower extremity pain/paresthesia/motor weakness/acute paraplegia
Cardios – aortic regurgitation (diastolic murmur), muffled heart sounds (pericardial effusion/tamponade), asymmetric carotid/subclavian/radial pulses, diminished femoral or pedal pulses

INVESTIGATIO]
L(H)/Haim]
CBC, INR, PTT, D-dimer, type & cross x6
(D-dimer <500ng/L less likely to be dissection)

L(H)/Meta]
Na+, K+, Cl-, HCO3-

L(H)/Org(Cardios)]
troponins
(elevated if dissection causes myocardial ischemia)

L(H)/Org(Nephros)]
Cr
(elevation with renal artery involvement)

I]
ECG – normal, inferior ST elevation (right coronary artery dissection) but can be any STEMI (0.1% of STEMIs are dissections), pericarditis changes, electrical alternans (tamponade)

CXR – normal (11-16%), widened mediastinum (56-63%), abnormal aortic contour (48%), aortic knuckle double calcium sign >5mm (14%), pleural effusion (L>R), tracheal shift, left apical cap.

TTE – 75% diagnostic Stanford type A (ascending), 40% Stanford type B (descending) can identify complications (e.g. aortic regurgitation, regional wall abnormalities in cardiac ischaemia, cardiac tamponade).

TEE – much higher sensitivity/specificity, though operator-dependent, need sedation, and is less available.

CTAA (CT aortic angiogram) – as the traditional gold standard, delineating aortic incompetence and associated branch vessel involvement as well.

RECIPERE]
NP/A,B]
O2, intubate if hemodynamically unstable
NP/C]
PIV (wide bore), Art-line
NP/Mon]
ambulatory heart monitoring, BP, SpO2

i) pain
ii) heart rate control HR<60
Note:First stop tachycardia and shearing forces each time the heart pumps.
iii) blood pressure control SBP<120

P/Poin]
Morphine 4-6mg IV q5-15min OR
Fentanyl 1mcg/kg IV q30-60min (70mcg for 70kg)

P/Naus]
Zofran 4mg IV

P/Org(Cardios)]
Labetolol 20 mg IV initially, then 20 to 80 mg IV boluses q10min to a maximal dose of 300 mg, until HR<60
(stop tachycardia and shearing forces)

Note: HR<60 then if BP is still > 120/80 start vasodilators. DO NOT use vasodilators without first beta blockers as it can cause reflex tachycardia.

P/Org(Vasculo)]
** Once HR<60 then vasodilators:
NTG 5-200 mcg/min infusion OR
Nitroprusside 0.5 mcg/kg/min (35mcg/min for 70kg)
titrated 0.5 mcg/kg/min to a maximum of 10mcg/kg/min, until SBP <120 (reduce afterload). Get BPs in both arms and tirate to the higher BP.​

Note: Nitroprusside is first line if needed after beta blockers, and is rapidly titratable. However, nitroprusside is typically avoided due to toxicity and side effects. NTG is second line and has afterload reduction at titrations over 150mcg/min, but more venodilation at lower dosages. NTG may be better if there is also coronary ischemia or acute pulmoary edema.

Surg/Consult]
In Stanford classification, type A dissection involves the ascending arch of the aorta (including the brachiocephalic, left common carotid and left subclavian) where it can rip into the pericardium, also causing an MI and aortic valve deficiency – mostly operative repair. Type B involves the descending aorta distal to left subclavian artery and typically can be handled with medical management.

Question 73

Trauma – Shock Identifiable Stragies

Answer 73

**_EMU_
Shock Index (SI)**=**HR/SBP**

Shock Identifiable Stratgies

1. SI > 1

2. Prehospital hypotension 16% mortailty, 20% if recurs/
Note: Ask EMS if there EVER was hypotension.
SBP < 1105x mortality
SBP < 90 young
SBP < 100 middle age
SBP < 110 elderly

3. Lactate/Base deficit/Urine output
Base excess and base deficit refer to an excess or deficit in the amount of base present in the blood. The value is usually reported as a concentration in units of mEq/L, with negative numbers indicating a deficit of base and positive numbers an excess of base. A typical reference range for base excess is −2 to +2 mEq/L.

A base deficit can be defined in terms of the amount of strong base that must be added (blood is acidic). Base excess is defined as the amount of strong acid that must be added to each liter of fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg (5.3 kPa).

Use a base deficit, delta lactate and urine output to guide ongoing resuscitation. Whether under or over-resuscitation is the issue, clinical judgment can be augmented with tests that more accurately reflect metabolic derangements at the tissue level. Serum lactate and base are tightly coupled with shock and volume loss. Measured from a venous or arterial blood gas, a base deficit of greater than -6 mmol/L is consistently associated with shock, and may provide clues to the presence of “occult shock” in patients whose physiology is otherwise not revealing.

One interesting paper from Anesthesiology (Anesthesiology 2012, 117(6): 1276-88) looked at the association between early (0-2h) lactate clearance and survival in bleeding trauma patients. A 20% per hour drop in serum lactate over the first two hours of resuscitation seems to be a reasonable marker of adequacy of resuscitation, and is associated a lower mortality.

Use a Foley cathteter. In addition to being a useful adjunct for diagnosing genitourinary tract injuries, urine output is a good in vivo marker of end-organ perfusion during the early stages of trauma resuscitation. Producing 30-50 cc/h of urine is a good maker of adequate resuscitation.

• *4. Bedside U/S**
• *RUSH exam** – Rapid Ultrasound for Shock and Hypotension

Question 74

VT/VF

Answer 74

1. Diagnosis

Clinical

Lab/Imaging

Time course

2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – acute to benign
5. Investigations (rule in/rule out)
6. Treatment/management

• *VF**
• *Unsynchronized ventricles contract at** >500bpm resulting in loss of cardiac output. No identifyable P waves, QRS complexes, or T waves. Most commonly seen in severe ischemic heart disease with or without MI. Other causesa are digoxin toxicity, hyper/hypokalemia, hypothermia or chest trauma.
• *VT**
• Three or more successive beats >100bpm from ventricuar ectopic pacemaker. R*egular, wide complex QRS, >100bpm usually 150-200bpm. Most common causes are ischemic heart disease and acute MI.Patients should be considered forurgent vascularization.Other causes arehypertrophic cardiomyopathy, mitral valve prolapse, drug toxicity (digoxin, antiarrhythmics and sympathomimetics), hypoxia, hypo/hyperkalemia.

Torsades de pointes is a form of VT. Drugs that prolong repolarization – quinidine (class I antiarrythmic, blocks fast inward sodium current at phase 0), disopyramide (class I antiarrythmic, blocks fast inward sodium current at phase 0), phenothiazines (five main classes of antipsychotic drugs), TCAs (antidepressants), sotalol.

1. VF/pulseless VT (pVT)
Start CPR and attach defibrillator 200J biphasic
Defibrillation if shockable rhythm – VF/pVT

CPR 2 minutes
Pulse and rhythm check (VF, pVT, or PEA)
Defibrillation if still in VF/pVT AND epinephrine 1mg
Note:If PEA then epinephrine q4min (every other cycle).

CPR 2 minutes
Pulse and rhythm check
Defribrillation if still in VF/pVT AND amiodarone 300mg
Note:If PEA then no amiodarone.

CPR 2 minutes
Pulse and rhythm check
Defibrillation if still in VF/pVT AND epinephrine 1mg

CPR 2 minutes
Pulse and rhythm check
Defribrillation if still in VF/pVT AND amiodarone 150mg
Continue CPR and defibrillation with alternating epi and ami

• *2. Unstable VT** with a pulse
  i) pulmonary edema
  ii) angina
  iii) hypotension (ALOC)
• *Synchronized cardioversion (120-200 biphasic)**
• *3. Stable VT**
• *Amiodarone 150mg IV over 10min, q10min to 2g**
• *4. Torsades de pointes**
• *MgSO4 1-2g IV over 60-90s**
• Beta-blockade for the treatment of cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia: a systematic review and meta-analysis Gottlieb M, Dyer S, Peksa GD. Resuscitation. 2020;146:118-125.

SUMMARY: Medical management strategies such as beta-blockade for shock-refractory ventricular tachycardia (VT) or ventricular fibrillation (VF) have been discussed for many years. In shock-refractory VT/VF, patients usually receive multiple rounds of epinephrine, which might have some positive effects on vasoconstriction and improve coronary circulation, but also might have deleterious effects because of beta hyperstimulation, which could be proarrhythmic.

The authors conducted a systematic review and meta-analysis to synthesize the international literature on this topic through usual metaanalytic techniques. The authors started with 3,682 papers but ended up including only 3 studies with a total of 115 patients. These 3 studies were all observational: 1 prospective and 2 retrospective. There were no RCTs. Two of the studies used esmolol as the beta blocker, and 1 used either propranolol or esmolol.

The key outcomes were (1) return of spontaneous circulation (ROSC) and (2) survival with good neurologic outcomes.

The results were substantially better in the beta-blockade group in terms of both ROSC (59% vs 23%) and survival to discharge (53% vs 11%). Adverse effects were not assessed. Overall, the risk of bias, as assessed by the authors, was high in 2 of the 3 studies. The authors conclude that beta blockers might help in shock-refractory VF/VT.

The data are weak and should not be used as a basis to significantly change practice. However, this strategy is relatively easy, noninvasive, and inexpensive, and could be used near the end of a VF/VT resuscitation.

Question 75

UTI

Answer 75

• Effect Of 5-Day Nitrofurantoin Vs Single-Dose Fosfomycin On Clinical Resolution Of Uncomplicated Lower Urinary Tract Infection In Women: A Randomized Clinical Trial Huttner, A., et al, JAMA 319(17):1781, May 1, 2018.

SUMMARY: Currently nitrofurantoin (macrobid) and fosfomycin are both first line in the treatment of uncomplicated cystitis. There is, however, a paucity of recent trials looking at the clinical efficacy of fosfomycin since the antibiotic gained widespread use in 2011.

These authors conducted an open label trial among women aged 18 or older with at least one symptom of a UTI and a positive urine dip for either leuks or nitrites.

They excluded women with suspected pyelo or any other form of complicated UTI (e.g immunosuppressed). 513 patients were randomized to either nitrofurantoin 100mg TID x 5d or a single dose of 3 gm fosfomycin (255 to nitrofurantoin and 258 to fosfomycin). Follow up was performed at 14 and 28 days.

Primary outcome was a clinical response at 28 days which was defined as either a success (all symptoms resolved) or failure (need more antibiotics) or indeterminate (they still had symptoms, but no clinical evidence of infection). Secondary outcomes were bacteriologic response (did the culture clear) and clinical response both at 14 days after therapy completion.

Of the 487 baseline urine cultures obtained, 77% were positive. There was a similar number of positive cultures between groups and and similar distribution of causative organisms (the vast majority being E. Coli).

For the primary outcome, 70% of nitrofurantoin group had clinical cure vs. 58% of fosfomycin at 28 days. The bacteriologic response also favored nitrofurantoin at 28d (74% cure vs. 63% cure).

EDITOR’S COMMENTARY: This was a well done randomized control trial looking at the the clinical efficacy of nitrofurantoin compared to fosfomycin for uncomplicated UTI in 513 women. The authors founds that nitrofurantoin outperformed fosfomycin for both clinical resolution (70% vs 58%) and bacteriologic response (74% vs 63%) at 28 days. There are a few limitations to this study worth noting. It was conducted in Europe therefore resistance patterns are likely to differ from where you work. Also, they gave the nitrofurantoin three times a day where the most common dosage is BID. The cure rate for both groups was also lower than expected based on previous trials.

Question 76

Vertigo

Answer 76

DDx Peripheral (vestibular apparatus, VIII)
Meta]
Drugs (Ototoxicity)

Org(Otos)]
BPPV (otoliths) – brief (<1min) intermittent episodes that change with head position, positive Dix-Hallpike

Meniere (increased endolymph) – attacks of vertigo preceded or accompanied by reduced hearing, tinnitus, and pressure or sense of fullness in ear, followed by residual hearning loss

Otosclerosis

Infect]
Acute vestibular neuritis (viral) – develops over hours and takes days/weeks to resolve, viral etiology

Acute labyrithitis (viral, bacterial, drugs) – tinnitus and auditory symptoms, ENT or other URT infection, in extreme cases can be febrile or toxic​

Ramsay Hunt syndrome (herpes zoster oticus – deafness, facial nerve palsy, vessicles in the external auditory canal

Struct]
Perilymphatic fistula – activities that can cause barotrauma eg. heavy lifiting

Cholesteatoma

DDx Central (brain stem and cerebellum)
Haim]
Cerebeller CVA/TIA – constant vertigo (VIII), WITH other focal deficits:
diplopia (III, IV, VI) - double vision or abnormal EOM
dysarthia (VII) - speaking or facial asymetries
dysphagia (IX, X) - swallowing
dysmetria (cerebeller) - truncal/appendicular ataxia
weakness or sensory loss – any findings from descending or ascending tracts running through the brainstem, nausea, vomiting

Org(Cephalo)]
Migraine – POUND

Cerebellopontine angle tumour

ID]
men>women

• *HPI]**
• *Peripheral**
• *Drugs (Ototoxocity) – Aminoglycocides** (Gentamycin)

BPPV – brief (<1min), intermittent, changes with head position

Menieres – tinnitus, reduced hearing, sense of fullness

Otosclerosis – age, arthritis

Acute vestibular neuritis (viral) – develops over hours and takes days/weeks to resolve

Acute labrinthitis (viral, bacterial, drugs) – tinnitus, ENT infectious symptoms

Ramsay Hunt syndrome (herpes zoster oticus) – deafness, facial nerve palsy

Perilymphatic fistula – activities that can cause barotrauma eg. heavy lifting

Cholesteatoma

• *Central**
• *CVA/TIA** – constant vertigo, neuro deficits – double vision or abnormal EOM, speaking or facial asymetries, trouble swallowing, walking, weakness or sensory loss, nausea, vomiting

Migraine – POUND

Cerebellopontine angle tumour

PMHx]
HTN (CVA)
CAD (CVA)
DM (CVA, disequilibrium)
Afib (CVA)

Meds]
HTN (dysequilibrium)
Loop directics (dysequilibrium
Baclofin (dysequilibirum)
Anticholinergic drugs (dysequilibrium)
ASA (ototoxicity)
Aminoglycosides (ototoxicity)
Platinum based chemotherapy drugs (ototoxicity)
Anti-coagulants (CVA)

SHx]
Smoking (CVA)

FHx]
TIA/CVA

O/E]
General – ALOC

Neuros (general) – motor or sensory focal deficits

Neuros (CN)

• *(II)** visual field/acuity
• *(pupil light reflex II to III)** unequal/fixed pupils
• *(III, IV, VI)** diplopia or abnormal EOM, vertical nystagmus, direction changing nystagmus
• *(V)** facial anesthesias
• *(VII)** facial asymmetries
• *(VIII)** gross hearing
• *(IX, X)** abnormal gag reflex
• *(XI)** abnormal head turn or shoulder raise
• *(XII)** tongue deviation

Neuros (cerebeller) – trucal ataxia or appendicular ataxia –dysmetria (finger to nose) and dysdiadochokinesia

Note: Balance depends on central (visual) and peripheral (vestibular system and proprioception).The basis of aRomberg test is that balance comes from the combination of vision, vestibular input, and proprioception. If any two of these systems are working the person should be able to demonstrate a fair degree of balance.

The key to the test is that when vision is taken away by asking the patient to close their eyes leaving only proprioception and vestibular input remain. If there is a vestibular disorder or proprioceptive dysfunction, the patient will become much more unbalanced.

Proprioceptive ataxia and vestibular ataxia are different forms of ataxia that have different etiologies. In vestibular ataxia the patient will lose balance to the side of the affected vestibule. In proprioceptive ataxia there is usually degenration of nerves such as in diabetes. In the tandem Romberg test, the patient will lose balance toward the affected vestibular side.

**Romberg is NOT a test of cerebeller function. In cerebeller ataxia, balance is compromised with eyes open AND closed.

Note: Nystagmus that is always the same direction with patients gaze is peripheral – vestibular. If the lesion is peripheral, the fast phase is toward the good side, and away from the affected side. The affected side is the slow phase as this side is not functioning properly.

**Note: HINTS exam is used to differentiate between vestibular neuritis/labrinthitis (peripheral) vs CVA (central). Performed on patients who have hours or days of CONTINOUS ONGOING vertigo and spontaneous nystagmus.

HI - Head Impulse - normal in stroke (central), abnormal in vestibular neuritis (peripheral)

N - Nystagmus (fast beat) - direction changing in stroke, unidirectional in the horizontal plane in vestibular neuritis. In periperal nystagmus the fast beat points toward the good ear, the slow beat is toward the affected ear. Nystagmus has often resolved leaving the HI test, but nystagmus can be brought on by headshake, called headshake induced nystagmus.

TS - Test of skew - vertical corrective saccade of eye when uncovered, abnormal in central finding and normal in vestibular neuritis.

Dix-Halpike (BPPV) - start with pateint seated and head turned 45 degress to side being tested, quickly lower to supine position with head angled backward (head in extension) off bed, positive when there is a 5-10 second delay and then there is rotational or upbeating/downbeating nystagmus.

INVESTIGATIO]
L(H)/Haim]
WBC
(acute labrythitis, non specific dizzyness)
L(H)/Meta]
SMA7
(non specific dizzyness, presyncope)
L(H)/Hor]
TSH

I]

• *ECG** (cardiac causes)
• *CT** (acute labrythitis, trauma) – only 10% sensitive for posterior fossa strokes
• *MRI** – more specific than CT but cannot exclude a stroke diagnosis particularly in the first 24-48 hours

RECIPERE]
BPPV
NP/Pro]
Dix-Hallpike test/Epley maneuver
P/Consult]
ENT outpatient

Meneires
NP/Nut]
Dietary restrictions – salt, caffeine, tobacco

P/Naus, Vom]
{Serc} Betahistine 8-16mg PO TID
Note: Betahistine is an H3 antagonist and an H1 agonist.
Betahistine has a powerful antagonistic effects at H3 receptors. H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release and stimulation of the H1 receptor in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine This stimulation causes potent vasodilatory effects of betahistine in the inner ear, that are well documented.

H1 agonist activity on the blood vessels in the inner ear causes vasodilation.

Together the H3 antagonist effect and the H1 agonist action work together to cause vasodilation and reverse the endolymph hydrops.

P/Org(Nephros)]
{Lasix} Furosemide

P/Consult]
ENT outpatient consult for glycerol testing and vestibular evoked myogenic potentials

Acute vestibular neuritis
P/Naus, Vom]
Antihistamine – Antagonizes H1R at VC, vestibular nuclei

• *{Gravol} Dimenhydrinate 25-50mg PO/IV/PR q4-8h**
• *Note:** Gravol also has anticholinergic activity.
• *{Benadryl} Diphenhydramine 25-50mg PO/IV/IM q4-8h**
• *Note:** Benadryl has stronger anticholinergic activity than Gravol. Gravol and Benadryl are H1R antagonists which depresses labyrith excitibility and vestibular stimulation.
• *{Phenergan} Promethazine 12.5-25mg PO/IM q4-6h**
• *Note:** Promethazine also has anticholinergic and antidopaminergic activity. Has black box warning for IV which can damage tissues.
• *Anticholinergic –** Antagonizes M1R at VC, vestibular nuclei
• *{Transderm-V} Scopolamine 1.5mg transdermal patch**

Uptodate: Despite these somewhat conflicting results and remaining questions, it seems reasonable to treat presumed viral acute labyrinthitis with corticosteroid therapy. We typically prescribe a 10-day course of prednisone; 60 mg daily on days one through five, 40 mg on day six, 30 mg on day seven, 20 mg on day eight, 10 mg on day nine, and 5 mg on day 10.​

P/Consult]
ENT outpatient consult

Acute viral/bacterial labyrinthitis
For viral same treatment as acute vestibular neuritis.
P/Infect]
IV Antibiotics
P/Consult]
ENT consult

Ramsay Hunt (Herpes zoster oticus)
P/Infect]
Valacyclovir 1g PO TID x7days

CVA/TIA
P/Neuros]
tPa if within 4 hours of symptoms
P/Consult]
Neurology/Neurosurgery

Etiology
The anatomic relationships of the labyrinth, middle ear, mastoid, and subarachnoid space are essential to understanding the pathophysiology of labyrinthitis. The labyrinth is composed of an outer osseous framework surrounding a delicate, membranous network that contains the peripheral sensory organs for balance and hearing.

Anatomy of the labyrinth
These sensory organs include the utricle, saccule, semicircular canals, and cochlea. Symptoms of labyrinthitis occur when infectious microorganisms or inflammatory mediators invade the membranous labyrinth and damage the vestibular and auditory end organs.

The labyrinth lies within the petrous portion of the temporal bone adjacent to the mastoid cavity and connects with the middle ear at the oval and round windows. The labyrinth maintains connections with the central nervous system (CNS) and subarachnoid space by way of the internal auditory canal and cochlear aqueduct. Bacteria may gain access to the membranous labyrinth by these pathways or through congenital or acquired defects of the bony labyrinth. Viruses may spread to labyrinthine structures hematogenously or by way of the aforementioned preformed pathways.

Viral and bacterial labyrinthitis are sufficiently different to warrant discussing them as separate disease processes.

Viral labyrinthitis
Viral infections can cause congenital and acquired hearing loss. Rubella and cytomegalovirus are the best-recognized viral causes of prenatal hearing loss. Virally induced hearing loss in the postnatal period is usually due to mumps or measles. Viral infections are also implicated in idiopathic, sudden sensorineural hearing loss (SNHL). Experimental evidence suggests that inflammatory proteins play a critical role in the pathogenesis of cytomegalovirus-induced hearing loss.

A unique form of viral labyrinthitis is herpes zoster oticus, or Ramsay-Hunt syndrome. The cause of this disorder is reactivation of a latent varicella-zoster virus infection occurring years after the primary infection. Evidence suggests that the virus may attack the spinal and vestibular ganglion in addition to the cochlear and vestibular nerves. Auditory and vestibular symptoms develop in approximately 25% of patients with herpes oticus, in addition to the facial paralysis and vesicular rash that characterize the disease.

Bacterial labyrinthitis
Bacterial labyrinthitis is a potential consequence of meningitis or otitis media and may occur by either direct bacterial invasion (suppurative labyrinthitis) or through the passage of bacterial toxins and other inflammatory mediators into the inner ear (serous labyrinthitis). Labyrinthitis is the most common complication of otitis media, accounting for 32% of all intracranial and extracranial complications in one study.

Although bacterial labyrinthitis is rare in the postantibiotic era, bacterial meningitis remains a significant cause of hearing loss. Auditory symptoms, vestibular symptoms, or both may be present in as many as 20% of children with meningitis. Meningitis typically affects both ears, whereas otogenic infections typically cause unilateral symptoms.

• *Suppurative labyrinthitis**
• *In patients with meningitis, bacteria can spread from the cerebrospinal fluid to the membranous labyrinth by way of the internal auditory canal or cochlear aqueduct.** Bacterial infections of the middle ear or mastoid most commonly spread to the labyrinth through a dehiscent horizontal semicircular canal. Usually, the dehiscence is the result of erosion by a cholesteatoma. Suppurative labyrinthitis resulting from otitis media is uncommon in the postantibiotic era. When suppurative labyrinthitis occurs, it is almost always associated with cholesteatoma. Profound hearing loss, severe vertigo, ataxia, and nausea and vomiting are common symptoms of bacterial labyrinthitis.

Labyrinthitis ossificans, the deposition of bone in the fluid-filled spaces of the inner ear, often follows suppurative labyrinthitis; therefore, decisions regarding cochlear implantation must be made early. Meningitis may also result in progressive hearing loss secondary to necrosis and fibrosis of the membranous cochlea and labyrinth.

Serous labyrinthitis
Serous labyrinthitis occurs when bacterial toxins and host inflammatory mediators, such as cytokines, enzymes, and complement, cross the round window membrane, causing inflammation of the labyrinth in the absence of direct bacterial contamination. This condition is associated with acute or chronic middle ear disease and is believed to be one of the most common complications of otitis media.

Toxins, enzymes, and other inflammatory products infiltrate the scala tympani, forming a fine precipitate just medial to the round window membrane. Penetration of the inflammatory agents into the endolymph at the basilar turn of the cochlea results in a mild to moderate, high-frequency SNHL.

Audiometric testing reveals a mixed hearing loss when a middle ear effusion is present. Vestibular symptoms may occur but are less common. Treatment is aimed at eliminating the underlying infection and clearing the middle ear space of effusion. The hearing loss is usually transient but may persist if the otitis is left untreated.

Causative viruses and bacteria
Little direct evidence suggests a viral cause for labyrinthitis; however, a wealth of epidemiologic evidence implicates a number of viruses as potentially causing inflammation of the labyrinth. Viral labyrinthitis is often preceded by an upper respiratory tract infection and occurs in epidemics. The histologic finding of axonal degeneration in the vestibular nerve suggests a viral etiology for vestibular neuritis.

The bacteria that cause labyrinthitis are the same bacteria responsible for meningitis and otitis. Gram-negative organisms are found more commonly when cholesteatoma is the inciting factor.

Potential viral causes of labyrinthitis include the following:
Cytomegalovirus
Mumps virus
Varicella-zoster virus
Rubeola virus
Influenza virus
Parainfluenza virus
Rubella virus
Herpes simplex virus 1
Adenovirus
Coxsackievirus
Respiratory syncytial virus

Potential bacterial causes of labyrinthitis include the following:
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Neisseria meningitidis
Streptococcus species
Staphylococcus species
Proteus species
Bacteroides species
Escherichia coli
Mycobacterium tuberculosis

Autoimmune labyrinthitis
Autoimmune labyrinthitis is an uncommon cause of sensorineural hearing loss and may occur as a local, inner ear process or as part of a systemic autoimmune disease such as Wegener granulomatosis or polyarteritis nodosa.

Question 77

Wells Criteria for PE

Answer 77

HPI]
Hemoptysis (1)

PMH]
Prior DVT/PE (1.5)
Surgery/immobiliztion in previous 4 weeks (1.5)
Active malignancy (trt within 6 months) (1)

O/E] HR>100 (tachycardia) (1.5)
Clinical signs and symptoms of DVT (3)

DIAGNOSIS]
PE is the most likely diangosis (3)

PE unlikely 0-4, PE likely >4

Question 78

Bleeding on oral anticoagulants

Question 79

Vascular Cellular Function and Drugs

Answer 79

NItric Oxide

Nitric oxide (NO), a molecule produced by many cells in the body, and has several important actions. In the cardiovascular system, NO is primarily produced by vascular endothelial cells. This endothelial-derived NO has several important functions including relaxing vascular smooth muscle (vasodilation), inhibiting platelet aggregation (anti-thrombotic), and inhibiting leukocyte-endothelial interactions (anti-inflammatory). These actions involve NO-stimulated formation of cGMP. Nitrodilators are drugs that mimic the actions of endogenous NO by releasing NO or forming NO within tissues. These drugs act directly on the vascular smooth muscle to cause relaxation and therefore serve as endothelial-independent vasodilators.

There are two basic types of nitrodilators: those that release NO spontaneously (e.g., sodium nitroprusside) and organic nitrates that require an enzymatic process to form NO. Organic nitrates do not directly release NO, however, their nitrate groups interact with enzymes and intracellular sulfhydryl groups that reduce the nitrate groups to NO or to S-nitrosothiol, which then is reduced to NO. The nitro group is reduced to form NO in by a mitochondrial enzyme (aldehyde dehydrogenase-2). Nitric oxide activates smooth muscle soluble guanylyl cyclase (GC) to form cGMP. Increased intracellular cGMP inhibits calcium entry into the cell, thereby decreasing intracellular calcium concentrations and causing smooth muscle relaxation (click here for details). NO also activates K+ channels, which leads to hyperpolarization and relaxation. Finally, NO acting through cGMP can stimulate a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to relaxation.

Although organic nitrates can dilate both arteries and veins, venous dilation predominates when these drugs are given at normal therapeutic doses. Venous dilation reduces venous pressure and decreases ventricular preload. This reduces ventricular wall stress and oxygen demand by the heart, thereby enhancing the oxygen supply/demand ratio. A reduction in preload (reduced diastolic wall stress) also helps to improve subendocardial blood flow, which is often compromised in coronary artery disease. Mild coronary dilation or reversal of coronary vasospasm will further enhance the oxygen supply/demand ratio and diminish the anginal pain. Coronary dilation occurs primarily in the large epicardial vessels, which diminishes the likelihood of coronary vascular steal. Systemic arterial dilation reduces afterload, which can enhance cardiac output while at the same time reducing ventricular wall stress and oxygen demand. At high concentrations, excessive systemic vasodilation may lead to hypotension and a baroreceptor reflex that produces tachycardia. When this occurs, the beneficial effects on the oxygen supply/demand ratio are partially offset. Furthermore, tachycardia, by reducing the duration of diastole, decreases the time available for coronary perfusion, most of which occurs during diastole.

Nitrates cause vasodilation through activation of guanylyl cyclase on nitrate-derived nitric oxide, increasing cyclic guanosine 3′, −5′ monophosphate (cGMP) bioavailability and cGMP-dependent protein kinases activation. Ultimately, intracellular calcium decreases, resulting in venous and arterial vasodilation, reducing biventricular filling pressures, systemic arterial blood pressure, and pulmonary vascular resistance. In AHF, the most common nitrates are nitroglycerin and nitroprusside. Nitroglycerin is more commonly used in AHF, as it improves coronary blood flow, reduces myocardial ischemia, and has relatively no effect on neurohormones. Nitroprusside reduces coronary blood flow, increases myocardial ischemia, and increases neurohormones.

Intravenous (IV) nitroglycerin (NTG) infusion is one of the mainstay treatments in acute pulmonary edema (aka acute decompensated heart failure (ADHF)), but is associated with increased hospital length of stay (LOS) and health care costs. Optimal NTG dosing isn’t established though physiologically, higher infusion doses (> 100 mcg/min) are helpful as they affect both afterload and preload. Recent studies suggest that intermittent high-dose bolus therapy may be as or more effective than infusions, however the impact on ICU admissions has not been studied.

Question 80

Paeds Asthma

Answer 80

• Asthma Treatment And Outcomes For Children In The Emergency Department And Hospital Drewek, R., et al, J Asthma 55(6):603, June 2018

SUMMARY: Asthma is the most common chronic illness in children with the biggest impact on quality of life. Inhaled corticosteroids (ICS) have a very significant benefit to asthmatics in terms of reduced symptom severity and even reduced ED visits. Despite this, they are grossly underused, especially in children.

This study is a retrospective chart review looking at the prescription of ICS as a function of whether patients were treated in the ED, hospital or ICU. This is out of Children’s Hospital of Phoenix, they found 287 patient visits for acute asthma over a 2 year period. Only about half of the cases were on an ICS already despite 90% of kids having previous ED visits.

Only 2% of kids seen and discharged from the ED had ICS initiated or ‘stepped up’. Only 50% of the kids admitted to the floor had a step up in their ICS and 72% of those in the ICU.

EDITOR’S COMMENTARY: This was a retrospective chart review looking at prescription of ICS in patients treated in the ED, hospital or ICU. Only 2% of children seen and discharged from the ED had an ICS initiated or increased dosage. Only 50% of children admitted to the floor had their ICS increased and 72% of those were in the ICU. This study is basically a plea to consider adding ICS to your treatment of kids being discharged from the ED with asthma – if you’re at an institution that sees a lot of kids with asthma consider developing a guideline to encourage good use of ICS in accordance with The National Asthma Education and Prevention Program (NAEPP). I get it – the ED purest would argue that it’s not my responsibility to get these kids on ICS. That’s the PMD’s job to do – but we know that the kids don’t follow up with their PMD and when they do, the asthma is well-controlled (thanks oral steroids) so the PMD often elects or neglects to prescribe them.

Question 81

Template

Answer 81

1. Diagnosis

Clinical

Lab/Imaging

Time course

2. Pathophysiology/Etiology
3. Risk factors/Red flags
4. Other diagnosis – acute to benign
5. Investigations (rule in/rule out)
6. Treatment/management

Question 82

Foreign Bodies

Answer 82

Ophtho

Liposic – gives lubrication for the foreign body to come out

Question 83

Tachycardia