CCP 226 Immune π Flashcards
target UO in sepsis
- > 0.5mL/kg/hr
this is based on KDIGO definition of AKI being Urine output less than 0.5 mL/kg/h for 6 hours
SIRS Criteria (β₯ 2 meets SIRS definition)
- Temp >38Β°C (100.4Β°F) or < 36Β°C (96.8Β°F)
- Heart rate > 90
- Respiratory rate > 20 or PaCOβ < 32 mm Hg
- WBC > 12,000/mmΒ³, < 4,000/mmΒ³, or > 10% bands
qSOFA (Quick SOFA) Score for Sepsis
- Altered mental status GCS <15
- Respiratory rate β₯22
- Systolic BP β€100
- qSOFA Scores 2-3 are associated with a 3- to 14-fold increase in in-hospital mortality
risk factors for sepsis
- Advancing age of patients
- Immunosuppression (diabetes, cancer, steroids, etc)
- Multi drug resistant infection
definition of sepsis
- Life threatening organ dysfunction caused by a dysregulated host response to infection
definition of septic shock
- Despite adequate fluid resuscitation, requires vasopressors to maintain a MAP >65 mmHg
with a lactate >2mmol/L
qSOFA
- Respiratory rate > 22 per minute
- Altered mental status (GCS <15)
- Systolic blood pressure < 100 mmHg
most common sources of infection in sepsis
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Meningitis Pneumonia Intra-abdominal Genitourinary Skin and soft tissue Endocarditis Lines/Tubes
% increase in mortality for each hour delay in ABX in septic shock
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8% per hour
results of VAAST trial (vasopressin in septic shock)
- can add vasopressin to NE to achieve MAP goal
2. can add vasopressin to NE to decrease NE dose
Type A lactic acidosis
Type A = Tissue Hypoxia
1. Shock: septic, hypovolemic, cardiogenic, obstructive 2. Acute mesenteric ischemia 3. Acute limb ischemia 4. Carbon monoxide poisoning 5. Cocaine use
Type B lactic acidosis
Type B = Independent of Tissue Hypoxia
Seizure
DKA
Thiamine deficiency
Drugs; metformin, isoniazid, beta 2
agonists, epinephrine, Propofol,
salicylates
Inborn errors of metabolism
Malignancy (e.g. lymphoma)
most common type of bacteria in lung infection
- Gram Positive Streptococcus pneumoniae, which is responsible for almost 50% of cases
most common type of bacteria in abdominal infection
- Gram Negative
2. Anerobes
most common type of bacteria in renal infection
- Gram Negative E coli and Klebsiella pneumoniae
Sepsis treatment pathway
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- Cultures and source control (ie. drain abscess)
- Early Antibiotics
- Restore Perfusion (fluid loading)
- Adjuncts (ie. vasopressors, steroids)
sepsis MAP goal in early resuscitation
MAP β₯ 65 (based on original EGDT data)
A higher MAP goal (ie. 80) may be beneficial in what septic populations?
- History of CKD
2. History of chronic HTN
As norepinephrine doses rise, what adjunct should be considered?
- Vasopressin
2. dose 0.03 - 0.04 units/min
What are two pitfalls of epinephrine infusion in sepsis?
- Causes rise in skeletal lactate production, which skews lactate-clearance trending.
- More arrhythmogenic than other pressors.
common gram positive infections
- MRSA.
- Streptococcus .
- Staphylococcus.
PCADS mnemonic in sepsis
- Perfusion
- Cultures
- Antibiotics
- Diagnose
- Source control
Osteomyelitis definition
bone infection
myositis definition
Skeletal muscle infection
pathophysiological process of fluid extravasation in sepsis
- Microbe elicits an innate immune response in host
- Inflammatory response is produced by IL 1, 6, and TNF-a
- Inflammation spreads the membrane-like wall of the vasculature, allowing for fluid to escape into the interstitium.
pathophysiological process of septic cardiomyopathy
- inflammatory mediators such as IL 1, 6, and TNF-a cause disruption of cardiac myocyte activity
- leads to troponin elevation, myocardial depression, and some ECG changes
initial recommended fluid loading in sepsis
30mL/kg based on The Current Surviving Sepsis Campaign βSepsis 3.0β guidelines
passive leg raise test
- Elevate the legs to 45 degrees for 40-60 seconds
- watch for increase in Arterial BP (MAP) or decrease in HR
Indicates volume responsiveness
oxygen delivery equation
DO2 = CO x CaO2
CaO2 = (1.34 x Hgb x SaO2) + (0.003 x PaO2)
oxygen consumption equation
VO2 = CO x (CaO2 - CvO2)
oxygen extraction ratio
O2ER = (CaO2 - CvO2) / CaO2
Normal serum calcium levels
- Serum Ionized = between 1.15 and 1.30 mmol/L (anything over 1.0 is ok)
- Serum Total = 2.2 to 2.7 mmol/L
serum ionized calcium is the only one that is really important because that is the amount of βusefulβ calcium you have in your serum.
ionized is the Ca++ content measured on your EPOC
Components of the 1 hour sepsis bundle
1) Measure lactate
2) Obtain cultures
3) Begin broad-spectrum ABx
4) Isotonic 30mL/kg bolus if MAP < 65 or Lactate > 4
5) Vasopressor if MAP <65 (following fluid admin)
this is based on american βCMS Core Measuresβ protocol for centre for medicare and Medicaid services guidelines
refractory septic shock treatment pathway
1) Optimize DO2 (Preload, afterload, contractility)
2) Source control (remove infected lines)
3) Correct profound metabolic acidosis (pH <7.0)
4) Correct hypocalcemia (serum ionized Ca++ < 1.0)
5) Adjunctive therapies (corticosteroids)
What are some examples of non-infectious aetiologies that can cause SIRS?
Trauma, burns, pancreatitis, transfusion reactions
What is the definition of septic shock as per sepsis 3?
1) Vasopressors required after sufficient fluid resuscitation to maintain map > 65mmHg
2) Lactate greater than 2 And a diagnosis of sepsis
define sepsis
Life threatening organ dysfunction cause by a dysregulated host response to infection
most common type of bacteria in skin infection
Gram positive, generally group A streptococcus (i.e., Streptococcus pyogenes), followed by methicillin-sensitive Staphylococcus aureus
most common type of gram positive organisms
- Step
- Staph
- MRSA
most common type of gram negatives organisms
- salmonella
- e. coli
- space bugs π
what is the role of measuring serum lactate in sepsis resuscitation?
- serum lactate Identifies and can help quantify decreased tissue perfusion
- Trending lactate helps inform resuscitative efforts.
- important to recognize that the use of epinephrine or concomitant liver failure can confound lactate measurements
how do the Organisms found in sepsis cause direct injury that can provoke hemodynamic collapse
excreted toxins cause direct vessel injury which opens endothelial tight junctions leading to vascular collapse
how does host immune response result in endothelial injury and hemodynamic collapse in sepsis
- pathogen-excreted toxins activate the innate immune response and results in vasodilatory cytokine release
- the host immune system continues to release pro-inflammatory chemokines that promote ongoing inflammation and endothelial derangement
how can pulse pressure variation on a-line be used to assess fluid responsiveness in sepsis?
- PPV of >10%-15% is an accurate predictor of fluid responsiveness
- patient must be in sinus rhythm
- patient must be mechanically ventilated with no spontaneous breaths
- patient must have normal lung compliance and abdominal compartment pressures
- patient must have an arterial line
PPV % = PPmax β PPmin Γ 100
Early Goal Directed Therapy (EGDT) definition
- The Rivers trial (2001) randomized patients with severe sepsis or septic shock to early goal-directed therapy (EGDT) vs. standard therapy
- EGDT used aggressive management of 5 key parameters to specified targets to optimise oxygen delivery to tissues in sepsis
Early Goal Directed Therapy (EGDT) cocktail
Target Parameters:
- CVP 8-12 mmHg
- MAP 65 β 90 mmHg
- Urine output >0.5 ml/kg/hr
- Mixed venous oxygen saturation >65% / ScvO2 >70%
- Haematocrit >30%
Target Interventions
- Reduce work of breathing by early use of mechanical ventilation
- Large-volume fluid resuscitation
- Use of vasoactive agents: noradrenaline, dobutamine
- Transfusion
why is normal saline a poor resuscitative fluid
- Normal saline increases systemic inflammation and multiorgan system dysfunction via hyperchloremia and worsened metabolic acidosis
when are Adjunctive corticosteroids recommended in sepsis?
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- shock that are refractory to catecholamines and volume resuscitation
- defined as IV fluids to the limit of volume responsiveness and requires two vasopressors to reach a MAP goal >65 mmHg
sepsis initial treatment pathway
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- Early investigations to determine infectious source
- Early source control with appropriate antibiotics
- Ongoing crystalloid resuscitation (Plasmalyte or LR preferred) as long as fluid responsive
- First line vasopressor NORepinephrine 2 to 200 mcg/min for MAP goal of 65 mmHg
- consider EPInephrine 2 to 50mcg/min if bradycardic
- consider vasopressin 0.03-0.04 units/min when NORepinephrine >15mcg/min
- foley/central line/invasive arterial monitoring
- trend lactate and fluid responsiveness
- If lactate fails to improve on subsequent readings consider septic-induced cardiomyopathy or other source of hyperlactatemia
- adjunctive agents such as corticosteroids if refractory shock
common reasons why sepsis is missed as an inpatient diagnosis
- Lack of knowledge of sepsis risk factors, signs, symptoms
- Observations performed infrequently in certain patients
- Failure of sepsis screening processes
- Rationalize that fever is disease related
- βit canβt be sepsis because there is no feverβ
- Staff do not give high priority to watching for sepsis due to workload and/or lack of knowledge
- Failure to communicate sepsis risk/symptoms in clinical handover
- Not testing lactate when appropriate
- Anchoring on current diagnosis, sepsis not considered
clinical exam findings for sepsis based on source of infection
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- Cough/sputum/chest pain/shortness of breath (lungs)
- Abdominal pain/distension/vomiting/diarrhea (abdomen)
- Dysuria/frequency/indwelling catheter (kidneys)
- Skin or joint (pain/swelling/redness) (skin)
- Central line present (line sepsis)
- Mottled skin, cold extremities (shock)
- Fever/headache/nuchal rigidity (meningitic)
clinical exam findings for lungs as a primary source of infection (identify source/source control)
- Cough
- sputum
- chest pain
- shortness of breath
clinical exam findings for abdomen as a primary source of infection (identify source/source control)
- Abdominal pain
- distension
- N/V/D
clinical exam findings for GU/kidneys as a primary source of infection (identify source/source control)
- Dysuria/frequency
- presence of indwelling catheter
- cloudy/foul smelling urine
clinical exam findings for skin as a primary source of infection (identify source/source control)
- heat (Calor)
- pain (dolor)
- redness (rubor)
- swelling (tumor)
STAT labs in a patient with suspected sepsis
- Serum Lactate (Repeat q2h if initial lactate >2 mmol/L)
- CBC and differential (looking for WBC count >12,000 or <4000 or bands >10%)
- INR, PTT, electrolytes, BUN, creatinine, glucose, LFT, lipase, troponin
- Blood cultures X 2 sets BEFORE antibiotics (include culture from central line, if present)
- Urinalysis and urine C&S
- Sputum for C&S
STAT investigations in a patient with suspected sepsis
- Labs
- CXR
- ECG
initial broad-spectrum ABX coverage for sepsis at any site
- vancomycin + piperacillin-tazobactam
initial broad-spectrum ABX coverage for CNS infection (meningitis)
- vancomycin + cefTRIAXone + acyclovir
initial broad-spectrum ABX coverage for GI/GU infection
- piperacillin-tazobactam
initial broad-spectrum ABX coverage for skin infection
- vancomycin
initial broad-spectrum ABX coverage for Community Acquired Pneumonia (CAP) infection
- cefTRIAXone
2. azithroMYCIN
Comprehensive Head to toe assessment for infection source
- Diagnostic imaging (XR/CT)
- Urine microscopy/culture
- Sputum culture
- Faeces for C.difficile if diarrhoea
- Wound swab for culture
- Nasopharyngeal swabs
- Lumbar puncture (if indicated)
goal for timing of ABX in sepsis
- Administer after blood cultures drawn and within 1 hour of presentation
high risk patient cohorts for sepsis
- Looks unwell (homeless/poor baseline health status)
- Age > 65
- Recent surgery
- Immunocompromised (AIDS; chemotherapy;
neutropenia; asplenia; transplant; chronic steroids) - Chronic illness (diabetes; renal failure; hepatic failure;
cancer; alcoholism; IV drug use)
common sites for culturing in working up sepsis
blood, urine, cerebrospinal fluid [CSF], ascites fluid
preferred vasopressors in order of administration in sepsis
- Norepinephrine 0.01-3.0 ΞΌg/kg/min
- Vasopressin 0.03 units/min (Addition of vasopressin generally utilized once norepinephrine dose is β₯15 ΞΌg/min)
- Epinephrine 0.01-2 ΞΌg/kg/min
steroid dosing in refractory septic shock
Hydrocortisone 50 mg IV q6h for shock refractory to catecholamines and volume resuscitation
what is the role of Methylene blue in refractory septic shock
Can counteract vasoplegia in distributive shock, but benefits to tissue oxygen delivery or mortality have not been demonstrated
last ditch hail mary
discuss βsource controlβ and how to Find and control the source of infection in sepsis
- Remove old indwelling catheters as soon as possible. (The risk of a line-associated bloodstream infection is dependent on the duration and type of access)
- Physical exam requires full exposure and inspection to assess for CNS, odontogenic, sinus, respiratory, GI, GU, and soft tissue infections.
- CXR, Bedside U/S of the heart, lungs, abdominal right upper quadrant, kidneys, and bladder, CT scans as indicated by patient presentation
discuss the approach to ongoing Monitoring for organ dysfunction and inadequate perfusion in Sepsis/critical illness
- Serial exams to evaluate Vital signs, mental status, cardiopulmonary exam, capillary refill, peripheral pulse, and skin
- Urine output (Normal urine output is at least 0.5 mL/kg/h)
- Chem-7/BMP (optimize acid/base status and electrolytes while monitoring renal function and maintaining relative euglycemia)
- Lactate (Identifies and quantifies decreased tissue perfusion. Trending lactate helps inform resuscitative efforts. confounded by epinephrine or liver failure)
- Blood gas (early detection of critical acid-base disturbances and ARDS)
Sepsis definition (sepsis-3)
βlife-threatening organ dysfunction due to a dysregulated host response to infection.β
Sequential Organ Failure Assessment (SOFA) Score
- SOFA Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems
- score is calculated on ICU admission and q24 hours until discharge using the worst parameters measured during the prior 24 hours
give some examples of why a septic patient may not meet SIRS criteria (ie, why does SIRS have shitty sensitivity for sepsis)
- elderly patients not mounting a febrile response
- current beta blocker use
- diagnostic futility of the WBC
discuss the use of vasopressin in sepsis
- Adding low-dose vasopressin (0.01-0.04 units/min) as a catecholamine-sparing agent in patients responding appropriately to norepinephrine infusion offers no survival advantage
- Vasopressin infused at 4 units/h (0.07 units/min) may decrease dysrhythmias and increase cardiac index measurements compared with norepinephrine alone. However, it also increases total bilirubin measurements, should be used with caution in patients with mesenteric ischemia due to its strong effects on splanchnic vasculature, and is generally not recommended
describe the role of ProCESS, ARISE, and ProMISe trials in current best practice guidelines for management of sepsis, and their impact on our understanding of EGDT
- In the initial study of early goal-directed therapy for sepsis, the treatment arm of the study received the majority of its fluid resuscitation early, while the control arm received the same volume but had it administered later, in violation of the treatment protocol.
- When repeated in the ProCESS, ARISE, and ProMISe trials, in which the treatment and control arms all received fluid resuscitation and antibiotics in the same way, the additional measures recommended in Riversβs Early Goal-Directed Therapy protocol (central venous pressure of 8-12 mm Hg, red blood cell transfusion and dobutamine for central venous oxygen saturation <70%, vasodilators for MAP >90 mm Hg) made no difference in ultimate mortality
Patients at highest risk of fungemia
the chronically ill with multiple comorbidities
recent antibiotic exposure
a CVC in situ
known Candida colonization
the addition of antifungal therapy should be considered in which cohorts of patients with sepsis?
patients on TPN, with neutropenia or other immunosuppression, or with peritonitis or another breach of bowel wall integrity
