2 Flashcards
Fulminant (acute) liver failure
Rapid development over <26 weeks, usually in a previously normal liver
Mental status changes and elevated INR required for Dx
More common in young people, ass. w/ high M&M
Common etiologies: drug induced (acetaminophen), viral, autoimmune, shock
Acute on chronic liver failure
Underlying liver disease + acute decompensating event (bleeding, infection, ascites, encephalopathy)
Leads to worsening liver failure and other organ failure
Very high short term mortality
Chronic liver disease
Accounts for majority of cases
Progressive fibrosis over many years
Often asymptomatic (compensated) –> decompensation leads to manifestations of liver failure
Potential for reversal in some cases
Portal hypertension
- Increased hepatic resistance to portal inflow d/t architectural distortion and intrahepatic vasodilation from cirrhosis
- Increased splanchnic vasodilation from excess NO and vasodilators
Pressure > 5 mmHg seen in 80% cirrhosis patients
Pressure >10 mmHg = clinically significant, decompensated
Pressure > 12 mmHg = threshold for bleeding varices
Ascites
Most common complication of cirrhosis/most common cause of hospital admission
Portal hypertension –> increased hydrostatic pressure/decreased oncotic pressure from albumin
AND splanchnic vasodilation –> effective hypovolemia –> RAAS activation –> Na/H20 retention
Hypervolemia + decreased oncotic pressure
Management: 2 G Na diet, diuretics (furosemidse 40 mg, spironolactone 100 mg), paracentesis, TIPS procedure
SAAG
Serum albumin – ascitic albumin
If > 1.1, ascites likely caused by portal hypertension
NEXT STEP: ascitic protein
Ascitic fluid data
Cell count/differential
Albumin
Total protein
+/- cultures
+/- glucose
+/- lactate
Ascitic protein
<2.5 indicates ascites from cirrhosis, late Budd-Chiari syndrome, liver mets
Spontaneous bacterial pleuritis
PMN > 500
> 250 in ascites fluid or > 250 w/ +bacterial culture in lung fluid
Varices
Body’s attempt to find alternative roads back to heard
Thin, fragile walls which can easily reach critical point of pressure and burst (size of varices proportional to bleeding risk)
Acute bleeding event typically lasts 5 days, but risk of rebleeding
Ceftriaxone, octreotide, nonselective beta blocker
TIPS
Reduce HVPG <12, open up new roads to liver by placing stent through inflow/outflow of liver connecting one branch of portal vein to hepatic vein
Contraindications: HF, uncontrolled infection, biliary obstruction, severe pulm HTN, thrombocytopenia
Complications: encephalopathy, decomp HF, liver failure, infections, bleeding
Hepatic encephalopathy
stage 1. subtle personality changes, decreased attention
stage 2. lethargy, disorientation, asterixis,
stage 3. stupor, severe confusion, incomprehensible speech
stage 4. coma
from increased ammonia crossing BBB –> edema of brain and astrocyte swelling
Don’t trend ammonia to monitor clinical response in chronic liver failure, but may be helpful in fulminant
Tx: underlying cause (infection, dehydration, electrolyte imbalance, bleeding), lactulose, rifaximin
Hepatorenal syndrome
Only seen in presence of advanced portal HTN w/ ascites, corrects after liver txp
Increased blood into portal circ/increased NO, decreased PVR, activation of RAAS =renal vasonconstriction/decreased renal blood flow
Child Pugh Score
Objective criteria (bili, INR, albumin) + subjective criteria (encephalopathy, ascites)
Class A-C. Class C eval for Txp
STI Screening Recommendations (CDC)
Gonorrhea-yearly for patients at risk/in high burden communities
Chlamydia-yearly for women <25 or w/ multiple risk factors
Syphilis-yearly for MSM or w/ multiple/anonymous partners. Twice during pregnancy
HIV-all adults and adolescents screened at least once
W/ any new STI Dx, also screen for HIV, Syphilis, Hep C (and retest at 2-3 months)
Genital ulcers
painful = genital herpes
painless = syphilis
all ulcers should prompt screening for syphilis
also think monkeypox
Primary syphilis
incubation: 10-90 days
starts w/ chancre (early macule/papule, then erodes)
resolves in 1-6 weeks
highly infective
Tx: PCN G (Ceftriaxone if PCN allergy)
Secondary syphilis
2-8 weeks after chancre, spirochetes have disseminated
Painless rash on whole body, including hands and feet
-mucous patches
-condylomata lata
-constitutional symptoms
-lymphadenopathy
Tx: PCN G weekly x3 for late latent
Tertiary syphilis
Does not always develop in untreated syphilis, can take 10-30 years to develop
Involvement = neuro, cardiac, eyes
Neurosyphilis can occur at any stage: CNS dysfunction, meningitis, AMS, stroke
TX: Aqueous PCN G IV q4 x2 wk
Genital herpes (HSV 2)
transmission: direct contact (can occur w asymptomatic shedding)
primary infection can be asymptomatic, symptomatic infections may be severe and prolonged
complications: neonatal exposure, enhanced HIV transmission
Sx: buzzing sensation, painful vesicles/ulcerations/crusting
Dx: NAAT, culture and PCR
Tx: Acyclovir/Famciclovir/ Valacyclovir 10-14 days
First episode, episodic, and suppressive therapies
HPV
associated with cervical cancer, genital warts and some oral/anal/penile cancers.
risk factors: old age, immune suppression, non-circumcised men, multiple partners, persistent infection
HPV 16 and 18 responsible for 80% cervical cancers
Cervical cancer screening
Screening should begin at 21 years of age
Age 21-29 years= Cytology alone
Age 30-65 years – Anyone of the following
Cytology alone every 5 years
FDA approved hr HPV testing along every 5 years
Co testing for hr HPV and cytology every 5 years
Over 65- No screening after adequate negative
Hysterectomy with removal of Cervix- no screening
if there is no history of high grade cervical
precancerous lesion or cervical cancer
Genital warts
HPV 6 and 11 cause 90% of genital warts
Incubation: 3 weeks–months
Sx: bumps, itching, irritation,
burning (or may be asymptomatic)
Gonorrhea
Causative organism: Neisseria Gonorrhae
Incubation: 2-5 days
Treatmnt for both partners is essential, treatment resistance on the rise
Sx (Males)- dysuria, discharge, disseminated can cause rash/joint pain/endocarditis
Sx (Females)-majority asymptomatic. discharge, dysuria, labia pain and swelling
Dx: NAAT (urine, cervical, urethral testing)
Tx: Ceftriaxone 500 mg (1 G if pt > 150 kg) + Doxycycline if chlamydia not excluded
Suspect tx failure if sx do not resolve w/in 3-5 days after tx: ensure pt has had no sexual contact and test for cure
Notify health department for tx resistant
PID
usually caused by gonorrhea/chlamydia
Sx: pelvic/abd pain, abnormal vaginal bleeding, dyspareunia, fever, cervical motion tenderness, adnexal tenerness
Dx: purulent cervical discharge, elevated ESR
Tx: Ceftotetan or Ceftriaxone and Doxy
Chlamydia
Most common in adolescent females, high rate of reinfection
Risk factors: age, gender, # partners, mucopurulent cervicitis, Hx STIs
Sx (Males) often asymptomatic, tingling in urethra, discharge
Sx (Females) vaginal discharge, cervical friability, poorly differentiated abd pain, bleeding after intercourse
Complications: infertility, increased risk ectopic pregnancy, chronic abd pain, premature ROM, low birth weight, conjunctivitis, blindness in infants
NAA testing, pt collected swabs
Tx: Doxy 7 days (Alt: Levo) If compliance is an issue Azithromycin
Trichomonas
flagellated protozoan
resistance escalating, infections can last months-years
Sx: malodorous discharge, burning/pruritis/urinary frequency
chronic infections may be asymptomatic
Associated w/ premature ROM, low birth weight, preterm birth
Tx: Metro 500 BID x7 days
Bacterial vaginosis
polymicrobial clinical syndrome resulting from
replacement of the normal hydrogen peroxide
producing Lactobacillus sp. in the vagina with
high concentrations of anaerobic bacteria
Increased risk for other STIs
Tx: Metro 500 mg BID x7d
Multiple sclerosis
Immune mediated, chronic inflammatory disease of CNS
Hallmarks inflammation, demyelinating plaques, axonal loss in CNS triggered by autoimmune mech
Risk factors: Age (predominantly female), geography, sun exposure, EBV, cigarette smoking, high dietary salt intake
Sx: acute optic neuritis, partial transverse myelitis, bladder/bowel sx, vertigo/impaired balance, banding around trunk (MS hug), Lhermitte’s, Uhthoff’s
Dx: Clinical Sx + MRI of brain, cervical/thoracic spine w/wo contrast, labs to r/o mimics , LP, evoked potentials
Lhermitte’s phenomenon
Tingling down the back and into the shoulder when flexing neck
Uhthoff’s phenomenon
MS symptoms are worsened by increasing body temp
Relapsing-remitting
No new disability between flares
Primary progressive
Steady increase in disability w/o attacks
Secondary progressive
No new disability btwn attacks, followed by steady increase in disability
Interferon beta
Promote shifts from T-helper (Th)1 to Th2.
Pegylation is the addition of polyethylene glycol and is thought to increase the potency and half life of interferon beta.
ADE: Injection-site reactions, flu-like symptoms, mood changes.
Glatiremer acetate
Copolymer originally designed to mimic
myelin basic protein in animal studies
Promote differentiation into Th2 and T-reg cells
ADE: injection site rxn, post injection tachycardia
Safe for use in pregnancy
Fingolimod
S1P1 receptor
modulator, prevents lymphocyte migration from
lymph organs into peripheral circulation
ADE: 1st dose bradycardia, infections, macular edema, worsening PFTs
Contraindicated w/ beta blockers, check for hx skin cancer and heart/pulm disease
No live vaccines while receiving this med
Teriflunomide
Blocks the replication of rapidly dividing T- and
B-lymphocytes
Monitor for GI/liver abnormalities, hair thinning
Teratogenicity
Dimethyl fumarate (DMT)
Promotes anti-inflammatory and cytoprotective
mechanisms
ADE: GI sx, flushing, lymphopenia, risk of infection
Monoclonal antibodies
Natalizumab: binds
α4-intergin on lymphocytes, preventing their interaction with vascular adhesion molecules –> reducing migration into CNS
ADE: opportunistic CNS infections
Alemtuzumab: against CD52 that results in lymphocyte depletion
ADE: infections, secondary autoimmune, malignancies
Ocrelizumab: against CD20 receptors on B-cells
ADE: injection site rxns
No live vaccines on this therapy
DMT injectables
Monitor CBC, liver enzymes annually
Considered safest in tx of MS
Can get live vaccines on this therapy
Some safe in pregnancy
DMT Orals
Monitor for infection (ass. w lymphocytopenia)
No live vaccines before consulting neurologist
Monitor LFTS
Most teratogenic
MS Relapse
Acute episodes of new or increasing neuro dysfunction, followed by full/partial recovery.
(In the absence of fever or infection)
New sx of neurological dysfunction, in a new
area of the body, lasting more than 24-48 hours
consistently.
(Not attributable to another cause such as infection or
other cause (not a pseudo-exacerbation).)
Pseudo-exacerbation
Flare up of old symptoms caused by trigger: infections, stress, sleep deprivation, heat sensitivity, healing wounds from surgery, pre-menstrual time.
Tx: if infection present treat infection, steroids are
usually contraindicated in these instances. Address root
cause
Hs&Ts
Hypovolemia
Hypoxia
Hypothermia
Hypo/Hyperkalemia
Hydrogen ion
Tension pneumo
Tamponade (cardiac)
Toxins
Thrombus (pulm, cardiac)
NULL-PLEASE Score
Nonshockable rhythm
Unwitnessed arrest
Long no-flow period (no bystander CPR)
Long low-flow period (>30 minutes before ROSC
pH (arterial) <7.2
Lactate >7 mmol/L
End-stage kidney disease on dialysis
Age ≥85 years
(Still) Ongoing CPR on arrival to hospital
Extracardiac cause
Patients with ≥5 features on the NULL-PLEASE score had a greater than threefold risk of
mortality compared with patients with a score from 0 to 4
CREST Score
Coronary artery disease (preexisting)
Rhythm nonshockable
Ejection fraction <30 percent
Shock at presentation
Ischemic time prior to ROSC >25 minutes
Risk of circulatory death increased with every additional point, from 10 percent
mortality with CREST = 0 up to 50 percent mortality with CREST = 5.
TTM
To improve neuro outcomes for comatose pt post cardiac arrest:
Inhibits cell death by reducing glutamate
release, decreasing concentrations of
intracellular ca, inducing anti-apoptotic factors and suppressing propoptotic factors
Oxidative injury and global cerebral inflammation also decreased
Decreased cerebral metabolism by 6-7% by 1C, also decreases blood flow and ICP
Cooling to 33C = 25% reduction in metabolism
Implementing TTM
All comatose pt post cardiac arrest (regardless of initial rhythm/location of arrest) up to 12 hr-post ROSC
Exclusions:
GCS >6
Severely impaired cognitive state prior to arrest
Sustained non-perfusing rhythm
DNR
Target temp: 33 (36 if bleeding risk)
Sedation/analgesia: propofol./fentanly
Consider NMB to prevent shivering
Continuous temperature monitoring device req
TTM considerations
Glucose/electrolytes: cold diuresis, replete as needed. caution of extracellular shifts during rewarming, caution in renal failure. avoid K containing fluids but check BMP Q6 and replete as needed. Hyperglycemia during hypothermia may req insulin gtt but caution for hypoglycemia during rewarming
Shivering: EKG and EEG to watch for micro shivering. NMB, tylenol, BuSpar, Mag, and analgesia/sedation
CV: Myocardium less response to defib and meds <30C, need hourly VS and art line for BP, repeat EKG @ target temp, dysrhythmias more common <30
Pulm: hyperoxia associated w/ worse outcomes. Goal SpO2 90-96%
Neuro: Q2 h neuro checks and cont. EEG 12 hours after initiation
Adrenals: Often see adrenal insufficiency post-resusc. Stress dose steroids recommended in refractory shock
Active normothermia 72 hours post rewarming (Cooling packs and tylenol)
Epidural hematoma
Bleeding between dura mater and skull
Mostly from arterial injury
Lens shaped
Subdural hematoma
Bleeding between dura and arachnoid space
Rupture of bridging veins
Crescent shaped
Traumatic subarachnoid hemorrhage
Tearing of small vessels in pia mater
Diffuse axonal injury
Tissue shearing at gray/white matter junctions
Visualized only on MRI
Skull fractures
Linear–most common, usually non-emergency. Temporal fx = risk of seizures
Stellate/comminuted–multiple associated linear fx
Depressed/penetrating–pressure causes injury, neuro signs evident. Req surgical repair, seizure prophylaxis and abx
Basilar–Difficult to see on XR, Dx by Sx (raccoon eyes, battle sign, CSF otorrhea/rhinorrhea)
Monroe-Kellie Doctrine
After TBI, any of the intracranial compartments can expand w/in fixed space (skull) leading to increased pressures
Brain parenchyma
CSF
Blood
Indications for surgery
Hemorrhagic lesions (evacuation and decompressive craniotomy)
-midline shift >5mm
-expanding hemorrhage or >10 mm
-GCS <8
Intracerebral contusions
-If refractory to medical therapy
Chronic SDH (Burr hole + subdural drain)
Herniation S/Sx
ipsilateral dilated pupils, Cushing reflex (HTN, bradycardia, resp depression), cortical blindness
ICP
Goal < 22
Clinical exam: herniation, Cushing reflex
Invasive monitoring: Intraventricular (Gold standard), Intraparenchymal (Bolt), Subarachnoid, Subdural
ICP Waveform: P1>P2 in normal, compliant cranium. P2>P1 indicates high pressure, noncompliant
Tx Elevated ICP
Tier 1
1. Optimize venous drainage: position HOB @ 30, keep head midline, remove C collars. Decrease metabolic demand: sedation/analgesia, seizure/fever prophylaxis, TTM
Tier 2
2. Slight hyperventilation
- CSF Fluid diversion
- Hyperosmolar therapy (brain edema therapy): mannitol vs. hypertonic saline
Tier 3
5. Salvage therapies: decompressive hemicraniectomy, laparotomy, neuromusc paralysis
Mannitol (sugar alcohol)
Filtered in kidney causing diuresis of Na/H20 –> TOTAL BRAIN & BODY DEHYDRATION
1g/kg Q6 H. Replete urine 1:1 for 2 H post admin
Monitor renal function, BMP, serum osmolarity
Not for renal failure
Hypertonic saline (3%, 5%)
No diuretic effect, so can be used in renal dysfunction
Expands intravascular volume and CO
Initial bolus, followed by infusion
Trend Na, stop when Na>160
Brain tissue oxygen
Partial pressure of O2 in brain interstitial space available for oxidative energy production
Determined by cerebral blood flow and arterial O2 content
Monitoring = regional or global
SjvO2
Global monitoring: Jugular bulb catheter measures O2 sat in jugular vein
Normal: 60-70% (Danger <50%)
Decreased SjvO2 = inadequate delivery of O2 relative to demand
Increased SjvO2 = delivery > metabolic requirements
pbtO2
Regional monitoring:
Licox measures the partial pressure of O2 in brain interstitial tissue
Normal pbtO2 range 25-50mmHg
Cerebral autoregulation
Maintains cerebral blood flow at a constant, despite fluctuations in cerebral perfusion pressure.
Determined by resistance of the cerebral blood vessels (diameter)
Disruptions seen in trauma and stroke–>Even minor changes in CPP can result in significant changes to blood flow
CPP
MAP-ICP
Goal >60
Cerebral blood flow: thermal diffusion flowmetry cath. Goal 15-50
Cerebral microdialysis
Part of intraparenchymal bolt, measures cerebral metabolism
-Extracellular glucose
-Lactate
-Pyruvate
-Glutamate
Lactate: Pyruvate ratio >40 indicates anaerobic metabolism (suggestive of secondary injury)
Zona glomerulosa
Mineralocorticoids (aldosterone)
Zona fasciculata
Glucocorticoids (cortisol)
Maintenance of homeostasis:
promote gluconeogeniss in liver, decrease uptake in skeletal muscle/adipose, role in immune/inflamm response, BP regulation, cognitive function
Release:
Thalamus –CRH
Ant. Pit –ACTH
Adrenals–Cortisol (negative feedback on CRH and ACTH)
Zona reticularis
Androgens
Medulla
Neuroendocrine (Epi, NorEpi)
Cortisol (role in illness)
Maintains CO:
-Supports vascular tone
-Endothelial integrity
-Vasc permeability
-Maintains total body water w/in vasc compartment
Primary adrenal insufficiency
Defect in adrenal gland leads to low levels of cortisol and other adrenal hormones
High ACTH d/t loss of negative feedback from cortisol
Typically 90% cortex destroyed before symptoms present
Nonspecific Sx: fatigue, reduced appetite, nausea, myopathy, hyperpigmentation (increased ACTH increases melanin), salt craving
Hyponatremia, hypoglycemia, hypotension (loss of glucocorticoids AND mineralocorticoids)
Etiologies: autoimmune, infection (TB/HIV/CMV/funal), congenital/genetic, bilateral hemorrhage, metastatic disease, drugs (etomidate, ketoconazole, rifampin, phenytoin)
Labs: Early AM cort <5 w/ ACTH x2 ULN
Check renin and aldosterone levels
Aldosterone
From Zona glomerulosa, release regulated by RAAS system
Loss =hypotension, hyperkalemia
Replacement is with fludrocortisone (Flornief): 100 mcg daily
*Glucocorticoids act on the mineralcorticoid receptor; therefore hydrocortisone doses >50 mg/day do not need to add fludrocortisone
Secondary adrenal insufficiency
Defect in the hypothalamic-pituitary area (adrenals fine)
Usually from loss of correct signals on adrenals
Etiologies: prolonged steroid use, pituitary tumor, sarcoidosis, empty sella syndrome, head trauma
May not need physiologic steroids in daily life, but will in times of illness
Cosyntropin stimulation test (ACTH stim test)
IM/IV injection of synthetic ACTH –> Cortisol measured 30, 60 min later
Phys steroid dosing
Goal is to avoid over-replacement of glucocorticoids
~5-10 mg/m2/day. Take in AM immediately on waking
Primary AI also needs fludrocortisone
*Hypotensive w/ strong clinical suspicion? Tx w steroids first, make Dx later
Adrenal crisis
acute deficiency in glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Often masquerades as other conditions
Hypotension, shock
Fatigue, weakness, malaise
Fever, lethargy
Abdominal pain, nausea, vomiting
Anorexia
Hypoglycemia
Etiologies: New primary failure, known insufficiency w/ new acute illness or under-replacement, acute withdrawal of high dose glucocorticoids, pituitary apoplexy
Tx: volume expansion (1-3 L isotonic), stress dose steroids, monitor electrolytes and BP
Critical Illness Related Cortisol Insufficiency (CIRCI)
The maximum output by the adrenals is not enough to address the severe stress of the illness
Random cortisol<10 mcg/dL or <9 mcg/dL increase in response to ACTH stim test (Stim test less reliable in critical illness)
In critically ill, check random cortisol. When in doubt, treat
Thyroid hormones
T4: only produced by the thyroid. Active
T3: 20% produced by thyroid, 80% extra-thyroidal conversion from T4 via deiodinase. Iodine=essential trace element for conversion
T3 is active version
T3 increases O2 consumption in all tissues except spleen and testes. Also: HR, contractility, mood, protein synth, lipid metabolism, increased gut motility, EPO/increased bone turnover, menstrual function, free water excretion
TSH is optimal screening assay for thyroid function in healthy patients
Nonthyroidal illness (NTIS) euthyroid sick
Altered thyroid function tests found in seriously ill or starving patients without preexisting thyroid disease
LOW TSH, T3, (T4 if prolonged)
May be seen in up to 75% hospitalized patients
Management: benign neglect (and recheck 2-6 wks). TSH may rise 20x normal during acute recovery
Primary hypothyroidism
Etiology: autoimmune (Hashimoto’s), thyroidectomy, agenesis of thyroid
Tx: Levothyroxine sodium and recheck labs 6-8 wks
Education: separate from calcium, iron, soy, estrogen, food, and coffee by 4 hours, take at night, consistency is key
Myxedema coma
Severe, life threatening hypothyroidism
Seen mostly in elderly patients w/ preexisting hypothyroidism and acute illness
Hypothermia, coma (mental status changes including stupor, confusion)
Labs: High TSH, Low T3/T4, hyponatremia, hypocholsterolemia, high LDL, high CPK
Hypoxemia, hypercapnia, acidosis
Management: usually req ICU management and mech. ventilation, supplement steroids and thyroid hormone
*Give steroids FIRST because TH supplementation increases glucocorticoid metabolism
Postpone surgeries unless emergent
Hyperthyroidism
Overproduction of thyroid hormone (Grave’s disease, toxic multinodiular goiter)
Leakage of thyroid hormone (autoimmune thyroiditis, viral thyroiditis)
Signs: goiter, hyperreflexia, muscle weakness, exophthalmos, systolic HTN, tachycardia, tremor, warm/moist skin
Symptoms: appetite changes, menstrual disturbances, HA, DOE, fatigue, heat intolerance, hyperactivity, palpitations, tremor
Thyroiditis
Damage to the thyroid gland –> leakage of stored thyroid hormone leading to hyperthyroidism (6-8 weeks until stored thyroid hormone is depleted) –> return to euthyroid state or swing to hypothyroidism
Typically asymptomatic
Antithyroid drugs (methimazole, PTU)
1st line Tx for Grave’s
Lowers thyroid hormone levels by 4-6 weeks
Need baseline CBC, LFTs (BBW for hepatotoxicity)
Thyroid storm
Extreme manifestation of thyrotoxicosis:
multisystem disorder d/t tissue exposure to excessive thyroid hormone levels
Precipitants: infections, surgery, iodine, DKA, I-131, PE, trauma, meds (pseudoephedrine, salicylates)
Management: HD stability (beta blockers), cooling techniques, adjunctive steroids, IV fluids/pressors/diuretics, avoid contrast
Transduction
Activation of nociceptors and depolarization of the nerve ending, resulting in release of an electrical signal
Mediated by glutamate release from central terminals
Transmission
Propagation of electrical signal from the periphery to the spinal cord
Via A-delta (thinly myelinated) fibers for acute/sharp pain and C (unmyelinated) fibers for dull/throbbing pain
Modulation
Ascending signals originating in the spinal cord promote pain response and descending signals from the brain dampen pain response
NE and 5-HT modulate pain response in the descending pathway
Perception
Awareness of pain sensation in the thalamus and higher cortical areas
Nociceptive pain
due to mechanical, thermal, or chemical stimulation of normally functioning pain nerves
Neuropathic pain
due to damaged, malfunctioning nerve fibers and can have either a peripheral or central origin
Central sensitization
Dorsal horn neurons show an exaggerated response to incoming pain signals
Repeated C-nociceptor activation leads to “wind-up,” hyperexcitability of dorsal horn neurons
Can lead to hyperalgesia and allodynia
Risk factors: pre-existing pain, anxiety, capacity overload
Preventive analgesia
Initiating multimodal regimens not only post-op, but also pre-op
effective pain control extending into the post-op period beyond expected nociceptive activity from the injury
Somatic pain
Nociceptive pain resulting from activation of nociceptors in the cutaneous (skin and underlying tissues) or deep tissues such as bone, blood vessels, muscles, and other supporting structures
Ex: fx, muscle sprains, post-op incision pain
Visceral pain
Nociceptive pain: Activation of nociceptors in the organs and linings of the body cavities capable of responding to stimuli caused by stretching, inflammation, or ischemia to visceral structures
Ex: pancreatitis, hepatic masses, IBS
Not well localized
NSAIDs
Nonselective – ibuprofen, naproxen sodium, diclofenac
COX-2 selective - celecoxib
Analgesia/inflammatory via inhibition of prostaglandin synth
Activity @: peripheral nociceptors of the spinal cord
ADE: Bleeding with nonselective NSAIDs, impaired hemosatsis, GI ulcers, CV risk, renal toxicity
Opioids
Long-acting opioids provide more consistent pain relief
Start low and go slow in older adults
Methadone is believe to have NMDA antagonist activity
TCAs
Nortriptyline, desipramine, amitriptyline, maprotiline
Inhibit NE and 5HT to varying degrees, may have local anesthetic-like activity
ADE: Blurred vision
Cognitive changes
Constipation
Dry mouth
Orthostatic hypotension
Sedation
Sexual dysfunction
Tachycardia
Urinary retention
Slow onset to therapeutic effects and requires dose titration to minimize side effects
Co-treatment of neuropathic pain and depression
SNRIs
Venlafaxine, duloxetine
Co-treatment of neuropathic pain and depression
Anticonvulsants
Gabapentin and pregabalin
Calcium channel modulation of the NMDA receptor
Gabapentin: sedation and cognitive slowing, peripheral edema
Pregabalin: more rapid titration possible but expensive
Requires dose titration to pain relief and dose adjustments to minimize side effects
Frequently used as part of multimodal analgesia
Prodromal
Sensations hours to days prior to a seizure (Not always experienced). Can include mood changes, lightheadedness, insomnia, poor
concentration
Aura
sensory symptoms at the very beginning of seizure onset (Not always experienced). Can include a sense of déjà vu, noxious smells, sense of panic, dizziness, etc
Ictal
Sensations from the first seizure symptoms to the end of the seizure activity. Corresponds to abnormal electrical activity in the brain.
Can include LOA, confusion, LOC, convulsions
Post-ictal
Symptoms immediately after ictal phase. Knowns as the recovery phase when the physical affects of the seizure can be felt. Can take minutes to hours to days for complete recovery depending on the type of the seizure.
Can include fatigue, HA, psychosis, sore muscles, weakness on one side of the
body (Todd’s paralysis). Often have poor memory of the event.
Temporal lobe epilelpsy
Most common
Most can be further localized to mesial temporal lobe (hippocampus, amygdala, parahippocampal gyrus)
Typically bland, staring, unrest, epigastric rising, automatisms
Neocortical epilepsy
Extrahippocampal temporal lobe seizures & those outside the temporal lobe
Neocortical TLE: often associated w structural abnormalities (automatisms less common than TLE)
Frontal lobe epilepsy: TBI, neoplasm, vasc malformation
More often cluster and progress to status epilepticus
Occipital lobe epilepsy
Less common
Often caused by neoplasm, vascular malformation, developmental abnormality
Semiology: visual aura (flashing white/colored lights, hallucinations), ictal blindness
Parietal lobe epilepsy
Less common and difficulty to characterize
Semiology: tingling/numbness, anxiety
Lamotrigine (Lamictal)
Great treatment for generalized epilepsy.
Mood stabilizing effects.
Long titration period – can take up to 8 weeks to get to therapeutic dose
ADE: SJS, may widen QRS interval (Consider baseline EKG)
Special populations:
Excellent pregnancy safety data
Well tolerated in the elderly (Beers Criteria)
Appropriate for hemodialysis patients
Levetiracetam (Keppra)
Most common prescribed AED medication for first seizure of life
Great generalized epilepsy medication, easy titration
Special populations:
Appropriate for hemodialysis – undergoes renal metabolism so will likely need
supplemental dose after dialysis
Generally well tolerated in the elderly but may experience more fatigue
Consider history of mood/psychiatric disorders
Excellent pregnancy safety data
Valproic acid (Depakote)
Great for generalized epilepsies
Easy titration
Synergistic effects with Lamotrigine – need close monitoring if using meds together
Benefit for mood stabilization and headache therapy
ADE:
hepatotoxicity and pancreatitis (monitor LFTs)
risk of hyperammonemia
Special populations:
Absolute contraindication in women of childbearing age who are not on a reliable contraceptive –
Valproate can cause major congenital malformations, particularly neural tube defects
Topiramate (Topamax)
Generalized epilepsy medication
Generally easy titration but can take up to 4 weeks to get on a therapeutic dose
Great treatment of headaches, can also treat essential tremor
ADE: weight loss, cognitive slowing
Combined therapy with Depakote increases risk for hyperammonemia
Special populations:
Increased risk for low birth weight and oral cleft after uterine exposure
Oxcarbezepine (Trileptal)
Focal epilepsy medication – can potentially worsen absence in those with
generalized epilepsy.
Mood stabilizing
ADE
Possibility of rash – potential cross reactivity with Lamotrigine
Hyponatremia, neutropenia
Osteopenia
Hepatic ulcers
Special populations:
test for the HLA-B*1502 allele in patients at increased genetic risk
Good pregnancy safety data
Carbamazepine (Tegretol)
Focal epilepsy medication (Also a tx for neuropathic pain and BPD)
ADE:
Risk of bone loss – monitor DEXAs closely and ensure vitamin D supplement
Rash, neutropenia, aplastic anemia
Special populations:
Good pregnancy safety data
Lacosamide (Vimpat)
Focal epilepsy medication, (newly prescribed for general epilepsy)
ADE: prolonged PR interval
Special populations:
Pregnancy data is promising but limited
Good for HD patients
Caution in cardiac arrhythmias
Drug resistant epilepsy
Failure of adequate trials of two tolerated and appropriately chosen AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom
Refer to EMU and surgical workup
PET, fMRI, visual field testing, neuropsych
SEEG
Minimally invasive procedure which uses electrodes placed directly in the brain
Allows for more precise identification of ictal onset zone
Electrodes implanted directly into the brain
without need for craniotomy
Vagus Nerve Stimulation
neuromodulation which involves implanting a device into the chest wall which sends regular, mild pulses of electrical
through the left vagus nerve to the brain
Improve blood flow to critical areas of your brain.
Alter the chaotic electrical pattern that happens during a seizure.
Increase the level of neurotransmitters (esp NE and 5HT)
Also for adults w/ drug resistant major depression and as add-on therapy for those who have moderate to severe loss of motor function due to ischemic stroke.
Multiple titration visits to limit side effects
Side effects – dry cough, hoarseness, tingling sensation, potentially worsen OSA
Deep Brain Stimulation
Bilateral stimulation of the anterior nucleus of the thalamus (ANT)
Indicated as an adjunctive therapy for reducing seizures in adults with medically
refractory partial-onset seizures
A pulse generator is surgically placed under the skin in the chest which sends electrical pulses through thin, insulated leads
Also for: Parkinson’s disease, Essential tremor, Dystonia, drug resistant OCD
Side effects: potential for mood changes, tingling with activation
Responsive Neurostimulation System
For adjunctive treatment of medical refractory focal epilepsy.
Continuously monitors electrocorticographic
activity and delivers electrical stimulation in response to specified pre-set patterns
SUDEP
Sudden unexplained death in epilepsy patients (when all other causes of death
have been ruled out)
Cause is unknown but suspected contributing factors include:
Apnea/cardiac arrest/arrhythmias
Risk for injury
Risk Factors:
Uncontrolled, frequent seizures
Generalized convulsive seizures
Seizures beginning at a young age
Duration of epilepsy diagnosis
Poor compliance
Alcohol use
Stroke BP goals
<185/110 prior to thrombolysis (and 24 hr post TPA/TNK)
Nitro paste
IV labetalo
IV Nicardipine
Permissive HTN: Only treat if MAP >140
Increased risk hemorrhage (post-thrombolysis)
Stroke severity (NIHSS)
Early CT findings of significant acute hypodensity, edema, or mass effect
Endovascular therapy
Pt w/ exclusions to Alteplase (on Warfarin or DOAC, post-op, onset >4.5 hr)
NIHSS >6 or <6 but w/ cortical sx (aphasia, neglect, field cut)
Basilar thrombosis
Up to 24 hr post-onset w/ perfusion mismatch
SAH
Blood under high pressure is forced
into subarachnoid space at the base
of the brain, spreading by way of
the sylvian fissures into the basal
cisterns
Most common cause: trauma
Nontraumatic most commonly caused by ruptured aneurysm
Other: AV malformation/fistula, sympathetic drug use, coagulopathies, neoplasm
Risk factors: age, tobacco/alcohol/sympathomimetics, HTN, estrogen deficiency, female sex, hereditary syndromes/family history
Fusiform aneurysm
Involves normal wall of artery. No defined neck
Most common in vertebrobasilar system
aneurysmal SAH
Rupture of an aneurysm releases blood directly into CSF under arterial pressure –> spreads quickly, increasing ICP
Bleeding usually brief in survivors (few seconds) but re-bleeding is common and occurs more often in 1st day
Most commonly bleeding is stopped by tissue pressure and formation of fibrinogen platelet plug at rupture site
S/Sx: Sudden onset/severe HA, photophobia, N/V, LOC, seizure, ocular hemorrhage
Surgical clipping
Clips made from MRI-compatible alloys placed across neck of aneurysm, excluding it from circulation
Requires craniotomy
Complications: vascular occlusion and rebleeding (<5%)
Tx of choice for wide neck aneurysms
Endovascular coiling
Microcatheter is advanced into the aneurysm,
and detachable coils of various sizes and shapes are deployed to decrease the amount of blood or to stop blood from filling the aneurysm
Arterial access. Performed under general or conscious sedation
Tx of choice for aneurysms difficult to clip
Complications: rebleed, vascular occlusion
Vasospasm
Angiographic observation of
narrowing in intracranial arteries,
resulting from vasoconstriction,
swelling of the vascular endothelium,
remodeling of the media and/or
subendothelial fibrosis.
Seen during Cerebral Angiography
or CTA
May or may not have a clinical
correlate
Delayed ischemic neuro injury
Clinical neurologic deficits that mimic ischemic deficits; Gradual, may progress or fluctuate
S/sx: New or increasing headache, alt LOC/ Disorientation, Meningismus, cranial nerve palsies, Focal motor deficits
Cerebral infarction MAY occur if the artery remains in spasm (untreated)
Oral Nimodipine to decrease risk
GI hemorrhage
Free intraperitoneal hemorrhage from injured organ/ruptured vessels
-Free blood in abd causes distention/irritable peritoneum –> peritonitis
Retroperitoneum: not always manifested as acute abd pain
GI/HPB/GU tracts: may be painless (GI = ulcers, varices, divertic, AV malformations, tumors, hemorrhoids)
Spleen is #2 most common organ to bleed, likely will req splenectomy in adults
Anterior perf
XR shows free air. Peritonitis/abd pain
Peptic ulcer
Erosion of stomach or intestinal lining. Free air, acute abd, septic shock
Complicated PUD: perforation, bleeding, obstruction (more common when ulcers recurrent)
Diverticular disease
Common in West d/t diet
-diverticulosis causes bleeding risk
-infected = diverticulitis
Obstruction
Tumors
Volvulus (hollow organ)
Torsion (solid organ)
Acute pain when tissue is infarcted. Surgical emergency!
SBO
Primarily caused by adhesions
Usually in abd that has had surgery
Rarely cause acute abd unless does not resolve and bowel becomes ischemic. Often will operate preventatively
Secondary cause = internal/external hernias
Tumors
LBO
Cancer, volvulus, chronic diverticulitis
Emergency (closed loop) likely need stoma
Obstrution not warranting surgery = gallstones w/o cholecystitis, CBD stones, renal stones
Mesenteric angina
not enough blood supply to abd when eating, post-prandial pain
Weight loss/pain out of proportion
Rarely acute abd unless bowel infarction
RUQ
Biliary colic/cholecystitis
Cholangitis
Hepatitis/hepatic masses
Pyelonephritis
Other: RLL PNA, MI, UTI, rib fx
LUQ
Pancreatitis
PUD, gastritis, gastric CA
Splenic rupture
Pyelonephritis
Other: LLL PNA, MI, UTI, rib fx
RLQ
Appendicitis
Torsion
Ectopic pregnancy
Renal colic
Mesenteric adenitis
PID
Crohns
Divertic
UTI
LLQ
Diverticulitis
Torsion
Pregnancy (ectopic)
Renal colic
Mesenteric adenitis
PID
Ruptured ovarian follicle
LBO
UTI
Amiodarone and thyroid
Iodine rich (37% iodine by weight)
Inhibits Type I Deiodinase in liver (decreased T4–> T3 conversion)
Initial changes: High TSH, High T4, Low or normal T3
Usually return to normal, but can become both hypo/hyper-thyroid
Check TFTs Q6 months when taking
Amiodarone Induced Thyrotoxicosis (Type 1 and Type 2)–difficult to differentiate. When in doubt, treat both w/ thionamides and steroids
Parkinson’s
Neurodegenerative disease caused by depletion of DA producing cells –> depletion of DA in nigrostriatal system causes imbalance of DA/Acth –> irregular bursting of neurons and low frequency electrical activity
Chronic and progressive characterized by cardinal signs:
resting tremor
rigidity
gait disturbance/postural instability
bradykinesia
Lewy bodies = hallmark
PD motor feautres
Begins on one side and remains asymmetric
Progressive
Masked facies (hypomimia)
Micrographia
Hypophonia
Small, shuffling gait
Stooped posture
PD non-motor features
Cognitive dysfunction
Depression
Daytime sleepiness/REM behavior disorders
Anosmia
Fatigue
Dysautonomia (GI/GU, orthostatic hypotension, erectile dysfunction)
Carbidopa/Levodopa
Levodopa: dopamine precursor, crosses BBB
Carbidopa:blocks peripheral metabolism of L-dopa
ADE: N/V confusion, sedation, orthostasis, sleep disturbances, vivid dreams, hallucinations, dyskinesias
On/off periods
Weaning off phenomenon
DA agonists
(pramipexole, ropinirole, rotigotine)
Used early in disease in younger patients
Lower likelihood of dyskinesias, but less efficacious compared to levodopa
ADE: N/V, orthostasis, somnolence,
hallucinations, edema, sleep attacks, Impulse control disorders: (hypersexuality, compulsive
gambling, compulsive shopping, eating)
MAO-B inhibitors
(Selegiline, Rasagiline)
MAO-B selective for dopamine metabolism. Inhibitors block metabolism.
Provides mild symptom relief; reduces fluctuations
ADE: nausea, headache, orthostasis, confusion, psychosis, insomnia (selegiline)
COMT Inhibitors
(Entacapone)
Blocks peripheral degradation of levodopa
Can be helpful for motor fluctuations
Available as combo pill:
– Levodopa-carbidopa-entacapone (Stalevo)
ADE: like levodopa; diarrhea; dyskinesias
Anticholinergics
Trihexyphenidyl, Benztropine
Only for tremor in younger patients
ADE: Confusion (central); dry mouth, constipation, urinary retention (peripheral).
NOT for elderly patients!
Amantadine
Improves tremor, dyskinesias, motor fluctuations.
ADE: cognitive changes, livedo reticularis (benign rash), peripheral edema
Myasthenia Gravis
An autoimmune disorder (anti-AChR and anti-MuSK antibodies), causing:
Dysfunction @ NMJ leading to:
Fluctuating weakness of skeletal muscle
Hallmark Sign: Fluctuating degree and variable combination of muscle weakness and fatigue in ocular, bulbar, limb, and respiratory muscles.
Increased by activity and improved with rest
Exacerbations r/t: stress, heat, wounds, hyperkalemia, infection, fever, menses/pregnancy, thyroid dysfunction, meds
Dx: clinical findings, blood tests and electrodiagnostic tests
Thymoma
Some individuals with MG develop thymomas or tumors of the thymus gland.
Generally thymomas are benign, but they can become malignant and should be removed
Minimal Manifestation Status
The patient has no symptoms or functional limitations from MG but has some weakness on examination of some muscles
Pyridostigmine (Mestinon)
1st line Tx of MG
Acetylcholinesterase inhibitor, increases Acth in synaptic cleft by preventing breakdown
Onset 30 min, T1/2 6 hr (requires freq dosing)
ADE: resp secretions, diarrhea, muscle twitches
Overdose = cholinergic crisis (mimic myasthenic crisis)
Corticosteroids
For MG management in patients uncontrolled by Mestinon
@ high doses, risk of worsening MG symptoms. Start low and increase slow
Wean gradually once tx goals met
ADE: weight gain, hyperglycemia, osteopenia, stomach ulcers, poor wound healing, easy bruising, insomnia
Steroid sparing immunosuppressants
When steroids + mestinon do not control symptoms or pt cannot take steroids d/t side effects/contraindications
Mycophenolate Mofetil (CellCept)
Azathioprine (Imuran)
Rituximab (Rituxan)
Eculizumab (Soliris)
IVIg
Pooled donor antibodies
Rapid-acting and often used to treat Myasthenic Crisis (2gm/kg 5 days) or as maintenance therapy in pt with severe MG
MOA unclear
ADE: infusion reaction, aseptic meningitis, blood clotting, infection, AKI
PLEX
Plasma (containing antibodies) removed and exchanged with donor plasma.
Rapid-acting/often used to treat Myasthenic Crisis (slightly faster than IVIG)
Maintenance therapy in pt with severe MG
MOA: removal of pathologic antibodies (AChR, MuSK)
ADE: hemodynamic instability with fluid shifts, complications of pheresis catheter (infection, bleeding)
Manifest myasthenic crisis
worsening of myasthenic weakness that requires ventilatory support
Precipitants: infection, stress, trauma/surgery, pregnancy, childbirth
Certain meds: Abx (FQs, macrolides, aminoglycosides), cardiac (beta blockers), magnesium, NMBs
Tx: IVIG or PLEX (institutional availability)
Active resp monitoring, elective intubation preferred over emergent
Most in crisis will req PPV (can trial non-invasive if expected to resolve quickly)
Stop mestinon to help manage secretions
Consider NG to prevent aspiration
Guillain-Barre Syndrome
Neuromuscular: group of acute immune-mediated disorders of the peripheral nerves (autoimmune rxn against nerve/myelin)
Areflexic paralysis, sensory changes
Monophasic course w/ nadir @ 4 weeks
High CSF protein w/ normal WBC count
Presentation:
Bilateral weakness, progressive over hrs-days
Motor: ascending weakness, facial palsy, resp insufficiency
Sensory: ascending paresthesias, limb pain, numbness
Reflexes: Hyporeflexia/areflexia
Autonomic: GI dysmotility, arrhythmias, BP fluctuations
Management:
30% will require mechanical ventilation
PLEX or IVIG
Treat dysautonomia (HR/BP/GI)
Pain management
Immobility comorbidities
