Study type: Blood collected in a gold-, red-, red/gray-, lavender- [EDTA], or green- [lithium or sodium heparin] top tube; related body system: Immune system.

Procalcitonin, blood cultures, C-reactive protein (CRP), and lactic acid levels are all used as indicators of infection and inflammation—and as sepsis markers. Normally, procalcitonin, the precursor of the hormone calcitonin, is produced by the C cells of the thyroid. In sepsis and septic shock, microbial toxins and inflammatory mediator proteins, including cytokines, tumor necrosis factor alpha, interleukin 1, prostaglandins, and platelet-activating factor, are thought to trigger the production of large amounts of procalcitonin (bacterial sources are believed to stimulate production of procalcitonin to a greater degree than viral sources) by nonthyroidal, non-neuroendocrine cells throughout the body. Procalcitonin is detectable within 2 to 4 hr after a sepsis initiating event, peaks within 12 to 24 hr, and remains detectable for up to 7 days. Serial measurements are useful to monitor patients at risk of developing sepsis or to monitor response to therapy.

Sepsis is a serious, potentially life-threatening systemic inflammatory response to infection with a significantly high mortality rate. Sepsis involves a systemic inflammatory response to infectious organisms that suppresses the immune system, activates the coagulation process (reflected by prolonged prothrombin time and activated partial thromboplastin time, elevated D-dimer, and deficiency of protein C), and results in cardiovascular insufficiency, and multiple organ failure. The incidence of sepsis in hospitals is especially high in noncardiac intensive care units.

Another patient population with a high risk of developing sepsis includes neonates in cases of early and late onset. Early-onset neonatal sepsis is also a significant concern. It occurs in the first 72 hr of life with 85% of cases presenting in the first 24 hr. Early-onset neonatal sepsis is the result of colonization of the neonate from the mother as it moves through the birth canal before delivery. The Centers for Disease Control and Prevention recommends universal screening for group B Streptococcus for all pregnant women at 35 to 37 weeks’ gestation. Other organisms associated with early-onset neonatal sepsis include coagulase-negative Staphylococcus, Escherichia coli, Haemophilus influenzae, and Listeria monocytogenes.

Late-onset neonatal sepsis, during days 4 to 90, is acquired from the environment and has been associated with infection by Acinetobacter, Candida, coagulase-negative Staphylococci, Enterobacter, E. coli, group B Streptococcus, Klebsiella, Pseudomonas, Serratia, and Staphylococcus aureus, as well as some anaerobes.

Surviving sepsis depends on rapid, accurate identification, intervention, and management. The host inflammatory reaction was termed systemic inflammatory response syndrome (SIRS) by the American College of Chest Physicians and the Society of Critical Care Medicine in 1992. SIRS is defined by documented clinical evidence of bacterial infection (e.g., culture results) in the presence of two of four other criteria:

• Temperature greater than 100.4°F or less than 96.8°F
• Heart rate greater than 90 beats/min
• Hyperventilation (greater than 20 breaths/minute or PaCO ₂ less than 32 mm Hg)
• White blood cell (WBC) count greater than 12 × 10³/microL or less than 4 × 10³/microL or with 10% immature WBCs/bands

• Evidence or diagnosis of infection in the presence of other factors
• General metabolic factors associated with sepsis (fever, hypothermia, increased heart rate, altered mental status, positive fluid imbalance, hyperglycemia not associated with diabetes)
• Inflammatory factors (elevated WBC count, bandemia, elevated CRP, elevated procalcitonin)
• Hemodynamic factors (arterial hypotension, elevated mixed venous oxygen saturation, elevated cardiac output/index)
• Organ/system dysfunction indicators (arterial hypoxemia, significant oliguria, elevated serum creatinine, abnormally elevated coagulation test levels, thrombocytopenia, elevated total bilirubin)
• Tissue perfusion factors (elevated lactate, hypotension evidenced by decreased capillary refilling, e.g., skin mottling)

In 2016, a revised description, with newer recommendations, was proposed for sepsis and septic shock. The criteria also include clinical guidelines to facilitate more rapid identification of patients at risk. As with any transition of paradigms, it is important to consider the established guidelines as long as the information remains applicable, accurate, and relevant, which is to say that the SIRS and 2001 criteria should not be eliminated from consideration while the new tools are used to collect additional data. The latest recommendations define sepsis as life-threatening organ dysfunction brought about when the body’s normal regulatory response to infection is impaired. Septic shock is defined as a subset of sepsis in which the associated abnormalities place the patient at greater risk of death than from sepsis alone. The newest sepsis assessment tools include objective measurements of parameters widely available in health-care facilities and laboratories. Although blood cultures, lactic acid, and procalcitonin are valued studies, they have the liabilities of turnaround times that exceed the urgent time frame needed for effective intervention. Also, these established markers are not available in all laboratories, and point-of-care testing options may be limited or not available in other facilities. Research continues for more sensitive and specific biomarkers for sepsis and include assays for pancreatic stone protein, soluble CD14 (presepsin), the midregion precursor fragment of adrenomedullin (MR-pro-ADM), and heparin binding protein.

The Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) score is a point system developed to provide an objective tool to assess organ failure. Points (0–4) are assigned for each measurement, representing an organ system. Organ dysfunction is determined by an increase in the SOFA score of 2 points or more when evaluated over a fairly limited period of time, that is, less than 24 hr, using the worst values collected over time in comparison to the baseline values. A number of SOFA calculators are available on the Internet; some scoring methods use additional qualifiers such as vasopressor specific criteria, but the basic assessment covers multiple organs/systems using objective measurements to include the following:

• Respiratory system: Partial pressure of oxygen in arterial blood (PAO ₂)
• Coagulation process: Platelet count
• Liver function: Total bilirubin
• Cardiovascular system: Mean arterial pressure
• Central nervous system/altered mental status: Glasgow Coma Scale score
• Kidney function: Creatinine (serum) or urine output

The bedside companion to SOFA is called the Quick Sepsis-Related Organ Failure Assessment (qSOFA). The qSOFA algorithm utilizes yes/no responses as well as numeric data to calculate a score based on the following:

• Patient location (ICU or outside ICU, e.g., emergency department or noncritical inpatient location; Y or N)
• Evidence of altered mentation (Y or N)
• Respiration rate in bpm (numeric value)
• Systolic blood pressure (numeric value)