Systemic Inflammatory Response Syndrome

Defining the symptoms of Systemic Inflammatory Response Syndrome (or SIRS) led to a collection of other syndromes, such as Multiple Organ Dysfunction Syndrome (MODS), Compensatory Anti-Inflammatory Response Syndrome (CARS), and Mixed Antagonists Response Syndrome (MARS).

In 1992, the American College of Chest Physicians and Society of Critical Care Medicine convened to address the confusion over the (im)proper use of the terms and definitions for sepsis, where the use of the terms bacteremia, septicemia, sepsis, sepsis syndrome and septic shock were being used almost interchangeably. They agreed to a new set of definitions applied to patients in different stages of sepsis: bacteremia, SIRS, sepsis, severe sepsis, septic shock and Multiple Organ Dysfunction Syndrome (MODS). They also proposed to add the Compensatory Anti-Inflammatory Response Syndrome (CARS), and Mixed Antagonists Response Syndrome (MARS) to the set of clinical definitions, as the massive inflammatory reactions understood of SIRS and MODS was only half the picture.

The first acute immune reaction phase Systemic Inflammatory Response Syndrome (SIRS) is described as a subset of a cytokine storm or cytokine dysregulation, an inflammatory state with both pro- and anti-inflammatory components affecting the whole body, frequently a response of the immune system to infectious or non-infectious insult.

SIRS can be caused by ischemia, inflammation, trauma, surgery complications, infection or several insults combined. Nearly every ICU patient (sometimes reported greater than 90%) fits the SIRS criteria and it is considered a serious condition related to systemic inflammation, potentially leading to organ dysfunction or organ failure.

The criteria for SIRS includes at least two of the following:
- Body temperature hypothermic less than 36°C, or fever greater than 38°C
- Tachycardia (abnormal heart rate) greater than 90 bpm
- Tachypnea (high respiratory rate) greater than 20 breath per minute
- White blood cell count elevated (leucocytosis >12,000/l) or depressed (leucopenia <4 l="">
Also observed are:
- Hyperglycemia (blood glucose >6.66mmol/L [120mg/dL] in absence of diabetes mellitus
- Altered mental status

Severe SIRS is frequently complicated by Multiple Organ Dysfunction Syndrome (MODS). Sepsis often accompanies SIRS and the two share very similar symptoms.

Mixed Antagonist Response Syndrome (MARS), an immunological dissonance where at times there may be surges of hyperactivity (SIRS) and immunosuppression (CARS) which can become increasingly destructive and if severe enough leads to MODS, septic shock or a state of anergy. An uncorrected escalating deviation in either direction may result in death.

A 2012 study on sepsis-induced mice demonstrated that concurrent release of pro-inflammatory and anti-inflammatory cytokines occurs irrespective of the sepsis phase, severity or outcome[1]. In that study, the progression of sepsis was monitored which revealed the lethal outcome in sepsis is not caused by a single mediator but is likely driven by concurrent deregulation of numerous immuno-inflammatory pathways.

[1] Osuchowski et al: Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis in Journal of Immunology – 2012. See here.