Systemic Inflammatory Response Syndrome Workup

Updated: Sep 13, 2017
  • Author: Lewis J Kaplan, MD, FACS, FCCM, FCCP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
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Approach Considerations

At minimum, a complete evaluation for systemic inflammatory response syndrome (SIRS) requires a complete blood cell (CBC) count with differential, to evaluate for leukocytosis or leukopenia. A white blood cell count of greater than 12,000/µL or less than 4,000/µL or with greater than 10% immature (band) forms on the differential is a criterion for SIRS. An increased percentage of bands is associated with an increased incidence of infectious causes of SIRS. [15]

Routine screenings often also include a basic metabolic profile. Other laboratory tests should be individualized based on patient history and physical examination findings. Measuring every possible measurable marker of inflammation, injury, and infection in all patients is discouraged. Since infectious SIRS etiologies have a high mortality if not treated effectively, and since effective treatment for infection often requires bacteriologic identification of the inciting organism, priority for bacteriological cultures in the diagnostic workup needs to be stressed.  Although one can measure almost anything, tests to consider include the following:

  • Blood cultures
  • Urinalysis and culture (even in asymptomatic patients)
  • Sputum Gram stain and culture (if respiratory symptoms)
  • Cardiac enzymes
  • Amylase
  • Lipase
  • Cerebrospinal fluid analysis
  • Liver profiles
  • Lactate
  • Venous or arterial blood gases (for assessment of acid-base status)

Interleukin 6

Patients who meet SIRS criteria and have increased interleukin 6 (IL-6) levels (>300 pg/mL) have been shown to be at increased risk for complications such as pneumonia, multiple organ dysfunction syndrome (MODS), and death. [16] In addition, a decrease in IL-6 by the second day of antibiotic treatment has been shown to be a marker of effectiveness of therapy and a positive prognostic sign in those patients with an infectious etiology for their SIRS. [17]


Blood lactate levels are often measured in critically ill patients. These are thought to be indicators of anaerobic metabolism associated with tissue dysoxia. Although a reasonable presumption in patients presenting in circulatory shock and trauma, in septic patients they reflect more the inflammatory burden rather than level of tissue hypoperfusion and, as such, usually do not decrease, if elevated, in response to fluid resuscitation. Levels are commonly elevated from increased peripheral intraorgan production, reduced hepatic uptake, and reduced renal elimination. Numerous studies have found that lactate levels correlate strongly with mortality.

Imaging studies

No diagnostic imaging studies exist for SIRS. The selection of imaging studies depends on the etiology that required hospital and intensive care unit (ICU) admission.

Special concerns

Patients at the extremes of age, patients with immunosuppression, and patients with diabetes may present with sepsis or other complications of infection without meeting SIRS criteria.

Pregnant patients require intensive evaluation because of the presence of two patients, as well as the propensity of uncontrolled inflammation to lead to preterm labor.



A significant amount of research has evaluated the use of acute-phase reactants to help differentiate infectious from noninfectious causes of systemic inflammatory response syndrome (SIRS). Several studies have found plasma procalcitonin (PCT) levels to be useful in this regard. [18]

In an observational, prospective study in a pediatric ICU, Arkader et al showed that PCT levels could be used to differentiate between infectious and noninfectious SIRS, while C-reactive protein (CRP) levels could not. In this study, PCT levels were increased at admission (median 9.15 ng/mL) in all 14 patients with bacterial sepsis, whereas CRP levels were increased in only 11 of the 14. In addition, PCT levels, but not CRP levels, subsequently decreased in most patients who progressed favorably. [19]

A review of PCT and CRP, as well as IL-6 and protein complement 3a (C3a), by Selberg et al showed that PCT, IL-6, and C3a were more reliable in distinguishing SIRS from sepsis. Plasma concentrations of PCT, C3a, and IL-6 obtained up to 8 hours after clinical onset of sepsis or SIRS were significantly higher in septic patients; the median PCT was 3.0 ng/ml in patients with SIRS, versus 16.8 ng/mL in patients with sepsis. [20]

A study by Balci et al confirmed that PCT is a better indicator of early septic complications than CRP is in complex populations, such as patients with multiple trauma. [21] Hohn et al recently demonstrated, in the ICU, that sepsis protocols using PCT to determine antibiotic utilization was associated with decreased duration of antibiotic therapy without compromising patient outcomes. [22]

Caution must be used in interpreting PCT results in elderly patients. Lai et al demonstrated that PCT is useful in predicting bacteremia in elderly patients but was not an independent marker for local infections. [23] There is also current debate regarding appropriate cut-off levels for PCT at which they are significant.

PCT is becoming increasingly available to physicians as a point-of-care test. Currently, availability of this assay will vary by medical center.



Leptin, a hormone generated by adipocytes that acts centrally on the hypothalamus to regulate body weight and energy expenditure, is an emerging marker that correlates well with serum IL-6 and tumor necrosis factor–alpha (TNF-α ) levels. Using serum leptin levels with a cutoff of 38 µg/L, researchers have been able to differentiate sepsis from noninfectious SIRS with a sensitivity of 91.2% and a specificity of 85%. This test is not yet readily available for clinical practice in the United States. [24, 25]