Sepsis

Medical Experts

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)

Professor of Pathology (Clinical), University of Utah

Medical Director, Bacteriology, Special Microbiology, and Antimicrobial Susceptibility Testing, ARUP Laboratories

Contributor

Pearson

Lauren N. Pearson, DO, MPH

Associate Professor of Pathology (Clinical), University of Utah

Chief Medical Officer, ARUP at University of Utah Health

Contributor

Rudolf

Joseph Rudolf, MD

Assistant Professor of Pathology (Clinical), University of Utah

Medical Director, Automated Core Lab, ARUP Laboratories

Sepsis is a severe illness characterized by a systemic, whole-body response to infection and is a frequent cause of morbidity and mortality in hospitalized patients. Sepsis is most common in older individuals and infants, and it can be difficult to diagnose due to its variable presentation.^, Because there is no confirmatory diagnostic test, sepsis diagnosis requires clinical judgment based on evidence of infection and organ dysfunction.

The clinical practice guidelines issued by the Surviving Sepsis Campaign (SSC) emphasize the importance of early identification and immediate management of infection, which include obtaining cultures and measuring serum lactate as soon after patient presentation as possible. The SSC recommends beginning sepsis management and treatment immediately at the point of presentation.

Quick Answers for Clinicians

Who is at risk of developing sepsis?

While anyone can develop sepsis, certain individuals are at higher risk, including the following:

Adults 75 years or older
Children 1 year or younger
Individuals with weakened immune systems
Individuals with chronic medical conditions (e.g., diabetes, cancer, lung or kidney disease)
Individuals who have undergone surgery or other invasive procedures within the past 6 weeks
Individuals who use intravenous drugs
Individuals with indwelling lines or catheters

People who are pregnant or have been pregnant in the past 6 weeks are also at higher risk for sepsis, with additional risk factors including:

Confirmed rupture of membranes before the onset of labor
Individuals with group A streptococcal infection or close contact with someone who has a group A streptococcal infection
Individuals with gestational diabetes
Individuals who have continued vaginal bleeding or abnormal vaginal discharge

What role does laboratory testing play in diagnosing and monitoring sepsis?

There is no definitive diagnostic test for sepsis. Along with clinical data, laboratory testing can provide clues that indicate the presence of or risk of developing sepsis. Serum lactate measurement may help to determine the severity of sepsis and is used to monitor therapeutic response. Peripheral blood cultures are useful for investigating the infectious etiology of sepsis and for managing appropriate antimicrobial treatment. Other tests, including CBCs and chemistries, provide a baseline to assess therapeutic response.

What role does procalcitonin play in a sepsis workup?

Procalcitonin (PCT) levels provide supportive evidence that systemic inflammation may be due to bacterial infection. As such, PCT testing can be useful in decreasing the unnecessary duration of antibiotic therapy.^, PCT levels may also be used to predict 28-day cumulative mortality risk for patients diagnosed with sepsis. 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.^,

Indications for Testing

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

Clinical Definition

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.” This definition was endorsed by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). The Sequential Organ Failure Assessment (SOFA) Score may be used to assess organ dysfunction.

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:

Persistent hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mmHg or greater
Serum lactate level greater than 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

Increases in serum lactate concentrations are associated with a higher risk of developing overt septic shock and poor outcome in general.^, An initial measurement of serum lactate is recommended to guide resuscitation.^,

Blood Culture

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

Procalcitonin

Procalcitonin (PCT) is an acute phase reactant (inflammatory marker) that is used as a biomarker for the risk assessment of progression to severe sepsis or septic shock and can help inform decisions on the duration of antibiotic treatment.^, Initial PCT concentrations on the first day of admission to the intensive care unit (ICU) may be used to aid in the assessment of risk for progression to severe sepsis and septic shock. A PCT concentration should be taken shortly after admission to the ICU to establish a baseline to monitor treatment response.^, Refer to the Monitoring section for more information.

Other Testing

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

Monitoring

Serum Lactate

Serum lactate should be remeasured within 2-4 hours of ICU admission if initially measured concentrations exceed 2 mmol/L to guide resuscitation and normalization of lactate. Lactate may be remeasured 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.

Procalcitonin

PCT measurements can be used to support shortening the duration of antimicrobial therapy in patients with sepsis, bacterial pneumonia, or lower respiratory tract infections.^, If the optimal duration of antimicrobial therapy is unclear, PCT measurement and clinical assessment are recommended to guide the discontinuation of treatment.^,

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. PCT concentrations may predict mortality in patients with sepsis and PCT concentrations that have not declined by 80% or more between days 1 and 4 of admission are consistent with higher cumulative mortality risk.^,