Sepsis

Indications for Testing

Individuals with one or more risk factors and relevant clinical presentation (eg, possible source of infection and systemic signs of inflammation or organ dysfunction) should be screened for sepsis.

Clinical Definition

Sepsis

Sepsis was redefined in the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) as “life threatening organ dysfunction caused by dysregulated host response to infections.” ⁵

This definition was endorsed by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). 5

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

For clinical purposes, organ dysfunction is represented by an increase in the Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) Score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. 5

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

A baseline SOFA score of 0 is used unless the patient has preexisting organ dysfunction before the onset of current infection. 6

American College of Emergency Physicians. DART: an evidence-driven tool to guide the early recognition and treatment of sepsis and septic shock. Accessed Sep 2022.

 Sepsis inflammatory response syndrome (SIRS) criteria are no longer considered in the identification of sepsis and septic shock.

Adult patients outside of intensive care units (ICUs) (ie, in the inpatient or outpatient setting) with suspected infection are at risk of sepsis development if they meet two or more quick SOFA (qSOFA) Score criteria. ⁵

Septic Shock

Septic shock is a subset of sepsis characterized by circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone. Septic shock can be identified by the presence of sepsis in addition to the following ⁵

:

• Persistent hypotension requiring vasopressors to maintain mean arterial pressure of ≥65 mmHg
• Serum lactate level of >2 mmol/L in the absence of hypovolemia

Laboratory Testing

Initial Workup for Suspected Sepsis

Although there is no definitive confirmatory diagnostic test for sepsis, the following laboratory tests can help assess organ dysfunction and contribute to the clinical diagnosis and appropriate medical management of sepsis.

Serum Lactate

Sepsis-induced hypoperfusion may manifest with acute organ dysfunction and/or decreased blood pressure and increased serum lactate. Lactate >2 mmol/L is considered abnormal and levels >4 mmol/L often suggest occult hypoperfusion and should trigger resuscitation. ⁶

Increases in serum lactate concentrations are associated with a higher risk of developing overt septic shock and with poor outcome in general. 6

American College of Emergency Physicians. DART: an evidence-driven tool to guide the early recognition and treatment of sepsis and septic shock. Accessed Sep 2022.

 7

Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304-377.

Blood Culture

Two sets of blood cultures (aerobic and anaerobic) should be obtained from two different sites before administering antibiotics to ensure accurate identification of pathogens and proper medical management of infection. ¹

Procalcitonin

Procalcitonin (PCT) is an acute phase reactant that is used as a biomarker for the diagnosis of sepsis and as a guide for antibiotic stewardship. ⁴

 7

Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304-377.

Refer to the Monitoring section below.

C-Reactive Protein

C-reactive protein (CRP) is a nonspecific marker of acute inflammation. CRP does not peak for up to 48 hours after the onset of sepsis and its concentration does not correlate with sepsis severity or prognosis. However, there is good evidence that the use of CRP testing may help rule out neonatal sepsis in full-term infants. Recent studies suggest similar efficacy in preterm infants. 

Other Testing

CBC, bilirubin, and creatinine tests are also used in calculating SOFA scores and may help identify patients with sepsis. ⁵

Monitoring

Serum Lactate

Lactate levels >2 mmol/L should be remeasured within 2-4 hours to guide resuscitation and normalization of lactate. ¹

The American College of Emergency Physicians (ACEP) suggests remeasuring lactate at least 1-2 hours after starting resuscitation in patients with initially abnormal lactate concentrations; remeasuring lactate levels sooner than this does not appear to be helpful. 6

American College of Emergency Physicians. DART: an evidence-driven tool to guide the early recognition and treatment of sepsis and septic shock. Accessed Sep 2022.

Procalcitonin

The SSC suggests that PCT measurements can be used to support shortening the duration of antimicrobial therapy in some patients with sepsis, such as those with bacterial pneumonia or lower respiratory tract infections. ⁷

PCT measurements also provide supportive evidence that systemic inflammation is due to bacterial infection and can be used to predict 28-day cumulative mortality risk for patients diagnosed with sepsis. Decreased PCT levels are independent predictors of mortality in patients with sepsis. The multicenter Procalcitonin Monitoring Sepsis (MOSES) study found that a PCT concentration that has not declined by 80% or more between days 1 and 4 of admission is consistent with a higher cumulative mortality risk. ³

 4

Schuetz P, Birkhahn R, Sherwin R, et al. Serial procalcitonin predicts mortality in severe sepsis patients: results from the multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study. Crit Care Med. 2017;45(5):781-789.