| Clinical presentation |
- Findings of severe sepsis and septic shock can include elevated respiratory rate, decreased SpO2, hypotension, elevated HR, positive shock index (HR/SBP>1), elevated or low temperature, altered mentation, signs of compromised end-organ perfusion (eg, cool or mottled skin, decreased capillary refill, decreased urine output, ileus), and other signs or laboratory results showing organ system dysfunction.
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| Diagnostic evaluation and monitoring |
- Measure vital signs and pulse oximetry. Perform continual cardiac and SpO2 monitoring. Monitor urine output. Reassess vital signs frequently.
- Search closely for symptoms and signs of infectious source (eg, productive cough, urinary symptoms, abdominal tenderness or guarding, purulent exudate from surgical wound or catheter site, meningeal irritation, skin lesions). Reassess after urgent interventions initiated.
- Perform bedside ultrasound assessment if available, including assessment of fluid status (eg, IVC diameter) and organ systems as clinically indicated (eg, hydronephrosis, cholecystitis, pulmonary fluid/consolidation).
- Obtain the following tests (if feasible): serum lactate, complete blood count with differential, basic electrolytes, kidney function, liver function, lipase, coagulation studies including venous (or arterial) blood gas, and electrocardiogram. Some centers measure procalcitonin when CAP suspected.
- Obtain aerobic and anaerobic blood cultures from two distinct sites; obtain other cultures as clinically indicated (eg, urine, wound, sputum, CSF, indwelling vascular access devices).
- Perform imaging studies of suspected sources of infection as clinically indicated (eg, chest radiograph, CT of chest and/or abdomen and pelvis, biliary ultrasound).
- Evaluate for source control (eg, abscess/empyema drainage, infected/necrotic tissue debridement, potentially infected indwelling hardware/catheter removal, ongoing microbial contamination control).
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| Initial respiratory and hemodynamic interventions |
- Provide supplemental oxygen as needed to maintain SpO2 ≥92%.
- Possible interventions include low-flow oxygen via nasal cannula, noninvasive ventilation (if no contraindication), high-flow oxygen via nasal cannula, nonrebreather mask, or bag-mask apparatus.
- Perform tracheal intubation and mechanical ventilation as necessary (eg, increased work of breathing, depressed consciousness).
- Use hemodynamically neutral induction agents for RSI (eg, ketamine, etomidate).
- If MAP <65 mmHg, premedicate with phenylephrine 50 to 200 micrograms IV.
- LPPV is preferred strategy for mechanical ventilation.*
- Settings vary by patient, but standard initial settings for LPPV include: volume-limited assist control; tidal volume 6 mL/kg; rate 16 to 36 bpm¶; PEEP 5 to 10 cm H2O; FiO2 1.0 with rapid wean to target O2 saturation; inspiratory flow 60 L/min; and trigger sensitivity –1 to –2 cm H2O.
- Obtain IV access; do not delay urgent interventions to place central venous catheter. Place intraosseous catheter if difficult to obtain IV access.
- Administer rapid IV boluses (typically 500 to 1000 mL) of isotonic crystalloid (eg, Lactated Ringer). Boluses are repeated based on clinical response.
- Volume totals of 30 mL/kg in first hours after presentation are reasonable, but clinical circumstances may warrant larger (eg, severe diarrhea) or smaller (eg, heart failure) volumes.
- Treatment goals include MAP ≥65 mmHg and urine output ≥0.5 mL/kg per hour.
- If hemodynamic response to IV fluids is inadequate or constrained by fluid overload (eg, heart failure), administer vasopressor. Norepinephrine (5 to 15 mcg/minute) is preferred. Peripheral IV may be used temporarily for administration pending placement of central venous catheter.
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| Antimicrobial medication |
- Initiate empiric, broad-spectrum IV antibiotic therapy, ideally within 1 hour of presentation, targeted at suspected source(s) of infection. Maximal dosing should be used. Examples include:Δ
- Vancomycin plus one of these:
- Third- or fourth-generation cephalosporin (eg, ceftriaxone, cefepime [antipseudomonal]) or
- Carbapenem (eg, meropenem, imipenem) or
- Piperacillin-tazobactam.
- When selecting targeted antimicrobial therapy, consider the following factors: history (eg, recent antibiotics received, previous organisms), comorbidities (eg, diabetes, organ failures, immune deficiencies), context (eg, community- versus hospital-acquired infection), suspected infection site, presence of invasive devices, Gram stain data, prior culture data from patient (if available), and local prevalence and resistance patterns (eg, MRSA, Pseudomonas).
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| Additional interventions and therapies |
- Obtain consultation as indicated to address infection source (eg, surgery for peritonitis or necrotizing soft tissue infection, interventional radiology for drainage of cholecystitis/cholangitis or obstructing kidney stone).
- If anemic, transfuse red blood cells to goal hemoglobin concentration >7 g/dL.
- If adrenal insufficiency suspected or refractory shock present (eg, multiple vasopressors at high doses required), administer a stress-dose glucocorticoid (eg, hydrocortisone 100 mg IV).
- If hypotension persists despite adequate IV fluid resuscitation and vasopressor therapy, a second vasopressor (eg, vasopressin) and possibly inotropic medication (eg, dobutamine) may be needed.
- Provide appropriate analgesia and sedation.
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