12. Protocol For Septic Shock

Definitions 

  • Sepsis order sets have been shown to improve 28-day mortality. See local sepsis bundles for institution-specific details. UCSF has a Sepsis Alert that will pop-up when patients meet SIRS criteria. 
  • Identify the patient with sepsis - early recognition is key! 
  • SIRS: initially defined in 1991 as abnormalities in 2 out of 4 areas (see below). While the new Surviving Sepsis Guidelines no longer include SIRS criteria, the SOFA and qSOFA were developed as tools to predict outcomes and not for diagnostic purposes. As a result, SIRS criteria are still used clinically at many institutions to identify patients who may have early sepsis. 
    • Temperature >38 or <36°C. 
    • Heart rate >90. 
    • Respiratory rate >20 or PaCO2 <32mmHg. 
    • WBC >12,000, WBC <4,000, or >10% immature (band) forms. 
  • Sepsis definition: life threatening organ dysfunction due to dysregulated host response to infection. Organ dysfunction is identified with either:  
    • SOFA score (use an online calculator) increase by 2 or more points identifies patients at high risk of mortality (<10%). Developed in ICU patients. 
    • qSOFA much easier to use, developed to identify non-ICU patients at risk for worse outcomes based on 2 or more of: 
      • Respiratory rate >22. 
      • Altered mental status. 
      • SBP ≤100. 
  • Septic shock: serum lactate >2 or hypotension requiring vasopressors to maintain a MAP >65 in patients who are not hypovolemic (i.e. after volume resuscitation). This combination is associated with mortality >40%. 

Step 1: Initial Resuscitation 

  • Early fluid resuscitation: start with 30mL/kg of crystalloid, typically ~2L. Many patients need more fluid, though this generally requires reassessment.  
  • If lactate elevated, can use normalization of lactate as resuscitation target. 
  • For fluid selection, see Critical Care: Fluid Resuscitation. (In brief: avoid high volumes of NS, recommend balanced crystalloids like Plasmalyte or Lactated Ringer’s instead.) 
  • Consider central and arterial line for monitoring when practical. 
  • Fluid responsiveness: consider use of dynamic monitors such as pulse-pressure variability or straight leg raise, as static measures such as CVP predict fluid responsiveness poorly. 
    • Pulse pressure variation with respiration (maximum pulse pressure minus minimum pulse pressure divided by the average) >10-13% from an A-line tracing is a good predictor of fluid responsiveness in mechanically ventilated, sedated patients. Threshold for a positive test is variable depending on the study. 
    • Consider bedside U/S if capable, to assess some of the following (best method is provider and institution-dependent, generally limited to IVC for non-expert ultrasonographers): 
      • IVC diameter and collapsibility (>25% collapse in spontaneously breathing patients). 
      • LV outflow tract velocity time integral (LVOT VTI) as surrogate for stroke volume. 
      • Brachial artery peak velocity. 

  • Step 2: Diagnosis and Source Control 

  • Obtain cultures prior to antibiotics if possible, but do NOT delay antibiotics. Obtain blood cx x2 and consider urine, respiratory, peritoneal, pleural, and CSF cultures as indicated by clinical picture. 
  • Consider imaging (CXR, abdominal imaging) but don’t delay antibiotics. 
  • Source control: if there is an anatomic site of infection (abscess, empyema) or intravascular access source (central line) it should be drained/removed promptly. 

Step 3: Antibiotic Therapy 

  • Start broad-spectrum IV antibiotics within the first hour of recognition of sepsis. 
  • Reassess daily to de-escalate as guided by microbiologic data. 
  • Consider viral/fungal coverage where appropriate as guided by clinical picture and/or immunocompromised state. 
  • Consider early broad-spectrum antibiotic combination therapy (2 antibiotics targeting most likely pathogen) in case of bacterial resistance. This is for initial coverage only, with de-escalation recommended as soon as culture data return. 

Step 4: Vasopressors 

  • Reassess fluid resuscitation with dynamic (pulse pressure variation, stroke volume variation) or static (HR, BP, CVP) measures. 
  • If hypotensive after fluid resuscitation start norepinephrine as first line vasopressor for goal MAP >65. 
  • Second and third line pressors are typically vasopressin and epinephrine, respectively. 
  • See Critical Care: Initial Choice of Vasopressor in Hypotension. 

Step 5: Additional Management Considerations 

  • Corticosteroids: consider in refractory hypotension despite fluids and vasopressors and treat with hydrocortisone 50 mg q6h hours. No need for cosyntropin stimulation test. See Critical Care: Adrenal Insufficiency in the Critically Ill. 
  • Consider IV thiamine (vitamin B1), especially for patients at risk of deficiency or with high vasopressor needs. Low risk for side effects and deficiency can cause profound vasoplegia.  
  • Consider IV ascorbic acid (vitamin C) as another low risk adjunctive medication for patients with high vasopressor needs. However, numerous large RCTs including VITAMINS have shown no significant benefit with vitamin C.  
  • Blood product administration: transfuse if Hb <7. See Critical Care: Transfusion Strategies in the ICU. 
  • Mechanical ventilation: have a low threshold to intubate and ventilate the patient with severe sepsis in order to increase oxygen delivery, decrease work of breathing, and decrease respiratory muscle oxygen use. 
  • Inotropic support: only recommended with evidence of myocardial dysfunction (decreased CO or elevated filling pressures) or ongoing hypoperfusion despite vasopressors and adequate fluid with suggestion of cardiac cause. Dobutamine is preferred. Remember it can cause arrhythmias. 
    • This was used in classic Rivers et al. paper, but unclear which part of the protocol improved mortality and other studies have shown no benefit. Not to be used regularly in sepsis. 
  • Sedation, analgesia and neuromuscular blockade: See Critical Care: ICU Sedation. 
  • Glucose control: goal glucose <180. See Critical Care: Intensive Insulin Therapy in the ICU. 
  • Renal replacement therapy: consider continuous renal replacement therapy (CRRT) to treat acidosis in the setting of renal failure and hypotension. 
  • Acid-base status: acidemia is common in severe sepsis and may limit the effectiveness of vasopressors. 
    • If pH >7.15, little evidence that bicarbonate improves hemodynamics or vasopressor requirement. Bicarb may result in increased CO2 (ensure adequate ventilation), hypernatremia, and decreased ionized calcium levels.  
    • Limit normal saline to avoid hyperchloremic acidosis (see Critical Care: Fluid Resuscitation), use balanced crystalloids such as Plasmalyte or Lactated Ringer’s instead. 
    • THAM is a buffer for severe acidosis and doesn’t increase CO2 but it cannot be used in renal failure. Little evidence supporting its routine use, and not on formulary at most institutions. 
  • Other ICU therapies: 
    • DVT prophylaxis should be given if not contraindicated.  
    • Patients with risk factors (e.g. mechanical ventilation, corticosteroids) should be given stress ulcer prophylaxis (PPI or H2B). 
    • Enteral nutrition is strongly preferred to parenteral nutrition. Early nutrition recommended. 
    • Goals of care should be discussed as early as possible and no later than 72 hours into ICU admission. 
Surviving Sepsis Campaign Bundles
To be completed within 3 hours
  1. Measure lactate level
  2. Obtain blood cultures prior to administration of antibiotics
  3. Administer broad-spectrum antibiotics
  4. Administer 30 mL/kg crystalloid for hypotension or lactate 4 mmol/L
To be completed within 6 hours
  1. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65 mm Hg
  2. In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥4 mmol/L:
  • Measure central venous pressure (CVP)
  • Measure central venous oxygen saturation (ScvO2)
  1. Re-measure lactate if initial lactate was elevated

Keywords: Fluid responsiveness, sepsis, septic shock, surviving sepsis

Angus DC, van der Poll T. Severe Sepsis and Septic Shock. N Engl J Med 2013; 369:840-851

ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. NEJM 2014. 371:1496-1506.

Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb; 41(2):580-637

Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 43, 304–377 (2017).

Marik P, Baram M, Vahid B. Does CVP Predict Fluid responsiveness? Chest 2008; 134:172-178.

Micek ST, Roubinian N, et al. Before-after study of a standardized hospital order set for management of septic shock. Crit Care Med. 2006; 34:2707-13.

Moskowitz A, Andersen LW, Huang DT, et al. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit Care. 2018;22(1):283. Published 2018 Oct 29. doi:10.1186/s13054-018-2217-4

Mouncey P, Osborn T, Power S, et al. Trial of early, goal-directed resuscitation for septic shock (ProMISe Trial). NEJM 2015. 372:1301-1311.

ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. NEJM 2014. 370:1683-1693.

Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-1377.

Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810.