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Definition
➔ Systemic inflammatory response syndrome (SIRS) is an exaggerated defense response
of the body to a noxious stressor (infection, trauma, surgery, acute inflammation,
ischemia or reperfusion, or malignancy, to name a few) to localize and then eliminate
the endogenous or exogenous source of the insult.
➔ A serious condition in which there is inflammation throughout the whole body. It may
be caused by a severe bacterial infection (sepsis), trauma, or pancreatitis.
➔ SIRS with a suspected source of infection is termed sepsis. Confirmation of infection
with positive cultures is therefore not mandatory, at least in the early stages.
Objectively, SIRS is defined by the satisfaction of any two of the criteria below:
● Body temperature over 38 or under 36 degrees Celsius (fever or hypothermia).
● Heart rate greater than 90 beats/minute (tachycardia).
● Respiratory rate greater than 20 breaths/minute or partial pressure of CO2 less than 32
mmHg (tachypnea)
● Leukocyte count is greater than 12000 or less than 4000 /microliters or over 10%
immature forms or bands (leukocytosis, leukopenia, or bandemia).

Anatomy and physiology

Cause
The following is partial list of the infectious causes of SIRS:

● Bacterial sepsis
● Burn wound infections
● Candidiasis
● Cellulitis
● Cholecystitis
● Community-acquired pneumonia
 ● Diabetic foot infection
● Erysipelas
● Infective endocarditis
● Influenza
● Intra-abdominal infections (eg, diverticulitis, appendicitis)
● Gas gangrene
● Meningitis
● Nosocomial pneumonia
● Pseudomembranous colitis
● Pyelonephritis
● Septic arthritis
● Toxic shock syndrome
● Urinary tract infections (male and female)

The following is a partial list of the noninfectious causes of SIRS:

● Acute mesenteric ischemia

● Adrenal insufficiency
● Autoimmune disorders
● Burns
● Chemical aspiration
● Cirrhosis
● Cutaneous vasculitis
● Dehydration
● Drug reaction
● Electrical injuries
● Erythema multiforme
● Hemorrhagic shock
● Hematologic malignancy
● Intestinal perforation
● Medication side effect (eg, from theophylline)
● Myocardial infarction
● Pancreatitis
 ● Seizure
● Substance abuse - Stimulants such as cocaine and amphetamines
● Surgical procedures
● Toxic epidermal necrolysis
● Transfusion reactions
● Upper gastrointestinal bleeding
● Vasculitis

Risk factor
● Very young people and elderly people
● Anyone who has had a transplant
● People who are being treated with chemotherapy drugs or radiation
● People with long-standing diabetes, AIDS, or cirrhosis
● Someone who has very large burns or severe injuries
● People with an infection:
○ Pneumonia
○ Meningitis
○ Cellulitis
○ Urinary tract infection
○ Ruptured appendix

Sign and symptoms

Clinically, Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more
symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood
leukocyte count.

Complications
Complications vary based on underlying etiology. Potential complications include the
following:

● Respiratory failure, acute respiratory distress syndrome (ARDS), and

nosocomial pneumonia
● Renal failure
 ● Stress ulcers
● Superinfection
● Gastrointestinal (GI) bleeding and stress gastritis
● Anemia
● DVT
● Intravenous catheter–related bacteremia
● Electrolyte abnormalities
● Hyperglycemia
● Disseminated intravascular coagulation (DIC)

Prognosis
The death rate can be as high as 60% for people with underlying medical problems. Mortality
is less (but still significant) in individuals without other medical problems.

Pathophysiology

Diagnostic and laboratory test

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.
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 - Myocardial depressive factors (inflammatory mediators,
endotoxins), microvascular dysfunction and increased myocardial cell
membrane permeability in conjunction with myocardial oxygen
demand–supply mismatch, are potential explanations for sepsis-induced
troponin elevation
● Amylase- the pancreas can become infected, which can spread into
the blood
● Lipase - affected
● Cerebrospinal fluid analysis - CSF values are suggestive of meningitis
● 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. 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.

Lactate

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.

Medical management
Antibiotics, Other
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens
in the context of the clinical setting. The therapy should be guided by available practice
guidelines and knowledge of the local antibiogram, as well as the patient's risk factors for
resistant pathogens and allergies. The key is to stop antibiotics when infection is ruled out or
narrow the antibiotic spectrum once a pathogen is found.

Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic
effects. Corticosteroids modify the body's immune system to diverse stimuli. The initial
research in sepsis and septic shock showed a trend toward worse outcomes when treating
with high doses of steroids (methylprednisolone sodium succinate 30 mg/kg every 6 h for 4
doses) compared with placebo. However, research into low-dose steroids (200-300 mg of
hydrocortisone for 5-7 days) improved survival and the reversal of shock in
vasopressor-dependent patients.

Antidiabetic Agents
These agents are used to treat hyperglycemia. A reduction of in-hospital mortality rates by
34% has been reported with intensive insulin therapy (maintenance of blood glucose at
80-110 mg/dL.

Antifungals, Systemic
Empiric antifungal therapy (fluconazole or an echinocandin) can be considered in patients
who have already been treated with antibiotics, patients who are neutropenic, patients who
are receiving total parenteral nutrition (TPN), or patients who have central venous access in
place.

Surgical management
The details of surgical management are site specific. In general, however, abscesses or
drainable foci of infection should be drained expeditiously to increase the efficacy of
antibiotic therapy and to allow for adequate culture data. Patients with acute surgical issues
(eg, ruptured appendix, cholecystitis) that cause SIRS should be treated with appropriate
surgical measures. Prosthetic devices should be removed in a timely manner, when clinically
feasible.

Nursing management
Diet

Enteral feedings supplemented with arginine and omega-3 fatty acids have been shown to be
beneficial (decreased infectious complications, hospital days, and duration of mechanical
ventilation) in critically ill patients. The ability to feed a patient and the route of nutrition
vary based on the etiology of SIRS.

Activity

Because of the causative illness, many patients are bed bound. Therefore, deep venous
thrombosis (DVT) and gastrointestinal stress ulcer prophylaxis should be considered to help
prevent complications. Patients who are otherwise clinically stable and without
contraindications to mobility should be permitted to perform activities as tolerated.

Transfer

Requirements for patient transfer depend on a facility's capabilities and the comfort level of
the admitting physicians for managing different medical conditions. The availability of
specialists also affects transfer.

Current trends
References:
https://emedicine.medscape.com/article/168943-overview
https://sci-hub.mksa.top/10.1097/md.0000000000005634