Essay Grade

6/20/2019
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Systemic Inflammatory Response
Syndrome
Updated: May 07, 2018
Author: Lewis J Kaplan, MD, FACS, FCCM, FCCP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM
Overview
Background
In 1992, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) introduced
definitions for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ
dysfunction syndrome (MODS).[1] The idea behind defining SIRS was to define a clinical response to a nonspecific insult of
either infectious or noninfectious origin. SIRS is defined as 2 or more of the following variables (see Presentation and Workup):
Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)
Heart rate of more than 90 beats per minute
Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) of less than 32 mm Hg
Abnormal white blood cell count (>12,000/µL or 10% immature [band] forms)
SIRS is nonspecific and can be caused by ischemia, inflammation, trauma, infection, or several insults combined. Thus, SIRS is
not always related to infection. Although sepsis has diverged from SIRS criteria for diagnosis and management in recent years,
focusing more on infectious etiologies, the pathophysiologic processes present in sepsis and noninfectious SIRS are remarkably
similar, making a discussion of SIRS in critical illness appropriate.(See Pathophysiology and Etiology.)
Venn diagram showing overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and
multiorgan dysfunction.
Bacteremia, sepsis, and septic shock
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Infection is defined as “a microbial phenomenon characterized by an inflammatory response to the microorganisms or the
invasion of normally sterile tissue by those organisms.”
Bacteremia is the presence of bacteria within the bloodstream, but this condition does not always lead to SIRS or sepsis. Sepsis
is the systemic response to infection and is defined as the presence of SIRS in addition to a documented or presumed infection.
Severe sepsis meets the aforementioned criteria and is associated with organ dysfunction, hypoperfusion, or hypotension. (See
Etiology, Treatment, and Medication.)
Sepsis­induced hypotension is defined as “the presence of a systolic blood pressure of less than 90 mm Hg or a reduction of
more than 40 mm Hg from baseline in the absence of other causes of hypotension.” Patients meet the criteria for septic shock if
they have persistent hypotension and perfusion abnormalities despite adequate fluid resuscitation. MODS is a state of
physiologic derangements in which organ function is not capable of maintaining homeostasis. (See Pathophysiology.)
Although not universally accepted terminology, severe SIRS and SIRS shock are terms that some authors have proposed.
These terms suggest organ dysfunction or refractory hypotension related to an ischemic or inflammatory process rather than to
an infectious etiology.
Complications
Complications vary based on underlying etiology. Routine prophylaxis, including deep vein thrombosis (DVT) and stress ulcer
prophylaxis, should be initiated when clinically indicated in severely ill bed­ridden patients, especially if they require mechanical
ventilation. Long­term antibiotics, when clinically indicated, should be as narrow spectrum as possible to limit the potential for
superinfection (suggested by a new fever, a change in the white blood cell [WBC] count, or clinical deterioration). Unnecessary
vascular catheters and Foley catheters should be removed as soon as possible. (See Prognosis, Treatment, and Medication.)
Potential complications include the following:
Respiratory failure, acute respiratory distress syndrome (ARDS), and nosocomial pneumonia
Renal failure
Gastrointestinal (GI) bleeding and stress gastritis
Anemia
DVT
Intravenous catheter–related bacteremia
Electrolyte abnormalities
Hyperglycemia
Disseminated intravascular coagulation (DIC)
Pathophysiology
Systemic inflammatory response syndrome (SIRS), independent of the etiology, has the same pathophysiologic properties, with
minor differences in inciting cascades. Many consider the syndrome a self­defense mechanism. Inflammation is the body’s
response to nonspecific insults that arise from chemical, traumatic, or infectious stimuli. The inflammatory cascade is a complex
process that involves humoral and cellular responses, complement, and cytokine cascades. Bone[1] best summarized the
relationship between these complex interactions and SIRS as the following 3­stage process.
Stage I
Following an insult, cytokines are produced within immune effector cells de novo at the site. Local cytokine production incites a
cellular inflammatory response, thereby promoting wound repair and recruitment of the reticular endothelial system. This process
is essential for normal host defense homeostasis and if absent is not compatible with life. Local inflammation, such as in the skin
and subcutaneous soft tissues, carries the classic description of rubor, tumor, dolor, calor and functio laesa.
Rubor or redness reflects local vasodilation caused by release of local vasodilating substances like nitric oxide (NO) and
prostacyclin.
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Tumor or swelling is due to vascular endothelial tight junction disruption and the local extravasation of protein­rich fluid into the
interstitium, which also allows activated white blood cells to pass from the vascular space into the tissue space to help clear
infection and promote repair.
Dolor is pain and represents the impact inflammatory mediators have on local somatosensory nerves. Presumably, this pain
stops the host from trying to use this part of his or her body as it tries to repair itself.
Calor is the increased heat primarily due to increased blood flow but also increased local metabolism as white blood cells
become activated and localize to the injured tissue.
Finally, functio laesa is loss of function, a hallmark of inflammation and a common clinical finding of organ dysfunction with the
infection is isolated to a specific organ (eg, pneumonia—acute respiratory failure; kidney—acute kidney injury).
Importantly, on a local level, this cytokine and chemokine release by attracting activated leukocytes to the region may cause
local tissue destruction (eg, abscess) or cellular injury (eg, pus), which appear to be the necessary byproducts of an effective
local inflammatory response.
Stage II
Small quantities of local cytokines are released into the circulation, improving the local response. This leads to growth factor
stimulation and the recruitment of macrophages and platelets. This acute phase response is typically well controlled by a
decrease in the proinflammatory mediators and by the release of endogenous antagonists; the goal is homeostasis. At this
stage, some minimal malaise and low­grade fever may become manifest.
Stage III
If homeostasis is not restored and if the inflammatory stimuli continue to seed into the systemic circulation, a significant systemic
reaction occurs. The cytokine release leads to destruction rather than protection. A consequence of this is the activation of
numerous humoral cascades and the activation of the reticular endothelial system and subsequent loss of circulatory integrity.
This leads to end­organ dysfunction.
Multi­hit theory
Bone also endorsed a multi­hit theory behind the progression of SIRS to organ dysfunction and possibly multiple organ
dysfunction syndrome (MODS). In this theory, the event that initiates the SIRS cascade primes the pump. With each additional
event, an altered or exaggerated response occurs, leading to progressive illness. The key to preventing the multiple hits is
adequate identification of the cause of SIRS and appropriate resuscitation and therapy.
Inflammatory cascade
Trauma, inflammation, or infection leads to the activation of the inflammatory cascade. Initially, a proinflammatory activation
occurs, but almost immediately thereafter a reactive suppressing anti­inflammatory response occurs. This SIRS usually
manifests itself as increased systemic expression of both proinflammatory and anti­inflammatory species. When SIRS is
mediated by an infectious insult, the inflammatory cascade is often initiated by endotoxin or exotoxin. Tissue macrophages,
monocytes, mast cells, platelets, and endothelial cells are able to produce a multitude of cytokines. The cytokines tissue
necrosis factor–alpha (TNF­α) and interleukin­1 (IL­1) are released first and initiate several cascades.
The release of IL­1 and TNF­α (or the presence of endotoxin or exotoxin) leads to cleavage of the nuclear factor­kB (NF­kB)
inhibitor. Once the inhibitor is removed, NF­kB is able to initiate the production of messenger ribonucleic acid (mRNA), which
induces the production other proinflammatory cytokines.
IL­6, IL­8, and interferon gamma are the primary proinflammatory mediators induced by NF­kB. In vitro research suggests that
glucocorticoids may function by inhibiting NF­kB. TNF­α and IL­1 have been shown to be released in large quantities within 1
hour of an insult and have both local and systemic effects. In vitro studies have shown that these 2 cytokines given individually
produce no significant hemodynamic response but that they cause severe lung injury and hypotension when given together.
TNF­α and IL­1 are responsible for fever and the release of stress hormones (norepinephrine, vasopressin, activation of the
renin­angiotensin­aldosterone system).
Other cytokines, especially IL­6, stimulate the release of acute­phase reactants such as C­reactive protein (CRP) and
procalcitonin. Of note, infection has been shown to induce a greater release of TNF­α —thus inducing a greater release of IL­6
and IL­8—than trauma does. This is suggested to be the reason higher fever is associated with infection rather than trauma.
The proinflammatory interleukins either function directly on tissue or work via secondary mediators to activate the coagulation
cascade and the complement cascade and the release of nitric oxide, platelet­activating factor, prostaglandins, and leukotrienes.
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High mobility group box 1 (HMGB1) is a protein present in the cytoplasm and nuclei in a majority of cell types. In response to
infection or injury, as is seen with SIRS, HMGB1 is secreted by innate immune cells and/or released passively by damaged cells.
Thus, elevated serum and tissue levels of HMGB1 would result from many of the causes of SIRS.
HMGB1 acts as a potent proinflammatory cytokine and is involved in delayed endotoxin lethality and sepsis.[2] In an
observational study of patients with traumatic brain injury, multivariate analysis selected plasma HMGB1 level as an independent
predictor for 1­year mortality and unfavorable outcome.[3] Therapeutic studies are under way to evaluate various mechanisms to
block HMGB1, with hopes of improving outcomes in SIRS and sepsis syndromes.[2]
Numerous proinflammatory polypeptides are found within the complement cascade. Protein complements C3a and C5a have
been the most studied and are felt to contribute directly to the release of additional cytokines and to cause vasodilatation and
increasing vascular permeability. Prostaglandins and leukotrienes incite endothelial damage, leading to multiorgan failure.
Polymorphonuclear cells (PMNs) from critically ill patients with SIRS have been shown to be more resistant to activation than
PMNs from healthy donors, but, when stimulated, demonstrate an exaggerated microbicidal response. This may represent an
autoprotective mechanism in which the PMNs in the already inflamed host may avoid excessive inflammation, thus reducing the
risk of further host cell injury and death.[4]
Coagulation
The correlation between inflammation and coagulation is critical to understanding the potential progression of SIRS. IL­1 and
TNF­α directly affect endothelial surfaces, leading to the expression of tissue factor. Tissue factor initiates the production of
thrombin, thereby promoting coagulation, and is a proinflammatory mediator itself. Fibrinolysis is impaired by IL­1 and TNF­α via
production of plasminogen activator inhibitor­1. Proinflammatory cytokines also disrupt the naturally occurring anti­inflammatory
mediators antithrombin and activated protein­C (APC).
If unchecked, this coagulation cascade leads to complications of microvascular thrombosis, including organ dysfunction. The
complement system also plays a role in the coagulation cascade. Infection­related procoagulant activity is generally more severe
than that produced by trauma.
SIRS versus CARS
The cumulative effect of this inflammatory cascade is an unbalanced state with inflammation and coagulation dominating. To
counteract the acute inflammatory response, the body is equipped to reverse this process via the counter­inflammatory response
syndrome (CARS). IL­4 and IL­10 are cytokines responsible for decreasing the production of TNF­α, IL­1, IL­6, and IL­8. In fact,
this proinflammatory and anti­inflammatory activation mirrors other homeostatic processes, like coagulation, anticoagulation,
complement activation, and complement suppression.
Clearly, the normal homeostatic processes attempt to keep these very toxic inflammatory processes in check. Inflammation is an
essential component of host defense and serves a very strongly positive survival function in suppressing and then eliminating
local infection and tissue injury. It is only when this localized aggressive injury process gains access to the whole body through
the blood stream and lymphatics that a SIRS develops.
The acute phase response also produces antagonists to TNF­α and IL­1 receptors. These antagonists either bind the cytokine,
and thereby inactivate it, or block the receptors. Comorbidities and other factors can influence a patient’s ability to respond
appropriately.
The balance of SIRS and CARS helps determine a patient’s outcome after an insult. Some researchers believe that, because of
CARS, many of the new medications meant to inhibit the proinflammatory mediators may lead to deleterious
immunosuppression.
Etiology
The etiology of systemic inflammatory response syndrome (SIRS) is broad and includes infectious and noninfectious conditions,
surgical procedures, trauma, medications, and therapies. The inciting molecular stimuli inducing the above generalized
inflammatory reaction fall into two broad categories, pathogen­associated molecular patterns (PAMPs) and damage­associated
molecular patterns (DAMPs). PAMPs become present when infection of foreign cell lysis releases these foreign molecules
intrinsic to their structure into the circulation, whereas DAMPs arise when cellular injury occurs at rates that overwhelm local
clearance mechanisms. Thus, it can be seen that generalized bacteremia, severe pneumonia (viral or bacterial), severe trauma
with tissue injury, and pancreatitis all share common inflammatory activation pathways.
The following is partial list of the infectious causes of SIRS:
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Bacterial sepsis
Burn wound infections
Candidiasis
Cellulitis
Cholecystitis
Community­acquired pneumonia[5]
Diabetic foot infection
Erysipelas
Infective endocarditis
Influenza
Intra­abdominal 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)
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Myocardial infarction
Pancreatitis[6]
Seizure
Substance abuse ­ Stimulants such as cocaine and amphetamines
Surgical procedures
Toxic epidermal necrolysis
Transfusion reactions
Upper gastrointestinal bleeding
Vasculitis
Epidemiology
Occurrence in the United States
The true incidence of systemic inflammatory response syndrome (SIRS) is unknown but probably very high, owing to the
nonspecific nature of its definition. Not all patients with SIRS require hospitalization or have diseases that progress to serious
illness. Indeed, patients with a seasonal head cold due to rhinovirus usually fulfill the criteria for SIRS. Because SIRS criteria are
nonspecific and occur in patients who present with conditions ranging from influenza to cardiovascular collapse associated with
severe pancreatitis,[6] any incidence figures would need to be stratified based on SIRS severity.
Rangel­Fausto et al published a prospective survey of patients admitted to a tertiary care center that revealed 68% of hospital
admissions to surveyed units met SIRS criteria.[7] The incidence of SIRS increased as the level of unit acuity increased. The
following progression of patients with SIRS was noted: 26% developed sepsis, 18% developed severe sepsis, and 4%
developed septic shock within 28 days of admission.
Pittet et al performed a hospital survey of SIRS that revealed an overall in­hospital incidence of 542 episodes per 1000 hospital
days.[8] In comparison, the incidence in the intensive care unit (ICU) was 840 episodes per 1000 hospital days. It is not clear
what percentage of patients with SIRS have a primary infectious etiology, allowing them to be classified as having sepsis.
However, most likely the proportion of SIRS patients varies across patient and hospital groups, being highest for example in
acute care settings and in those with immune deficiency.
The etiology of patients admitted with severe sepsis from a community emergency department was evaluated by Heffner et al,
who determined that 55% of patients had negative cultures and that 18% were diagnosed with noninfectious causes that
mimicked sepsis (SIRS). Many of the noninfectious etiologies required urgent alternate disease­specific therapy (eg, pulmonary
embolism, myocardial infarction, pancreatitis). Of the SIRS patients without infection, the clinical characteristics were similar to
those with positive cultures.[9]
Another study demonstrated that 62% of patients who presented to the emergency department with SIRS had a confirmed
infection, while 38% did not. Within the same cohort of patients, 38% of infected patients did not present with SIRS.[10]
Still, Angus et al found the incidence of severe SIRS associated with infection to be 3 cases per 1,000 population, or 2.26 cases
per 100 hospital discharges.[11] The real incidence of SIRS, therefore, must be much higher and likely depends somewhat on
the rigor with which the definition is applied.
International occurrence
No difference in the frequency of SIRS exists based on world geography.
Sex­related demographics
The sex­based mortality risk of severe SIRS is unknown. Females tend to have less inflammation from the same degree of
proinflammatory stimuli because of the mitigating aspects of estrogen. The reasons for this are not completely known, but
estrogen sustains adrenergic receptor activity in inflammation, when, in its absence, adrenergic receptor down­regulation occurs.
Thus, premenopausal females tend to have less vasoplegia and respond more vigorously to resuscitation efforts. This equates
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to women having a 10­year age benefit over men. The mortality rate among women with severe sepsis is similar to that of men
who are 10 years younger; however, whether this protective effect applies to women with noninfectious SIRS is unknown.
Age­related demographics
Extremes of age (young and old) and concomitant comorbidities probably negatively affect the outcome of SIRS. Young people
may be able to mount a more exuberant inflammatory response to a challenge than older people and yet may be able to better
modify the inflammatory state (via the counter­inflammatory response syndrome [CARS]). Young people have better outcomes
for equivalent diagnoses.
Prognosis
Comstedt et al, in a study of systemic inflammatory response syndrome (SIRS) in acutely hospitalized medical patients,
demonstrated a 6.9 times higher 28­day mortality in SIRS patients than in non­SIRS patients. Most deaths occurred in SIRS
patients with an associated malignancy.[10]
Prognosis depends on the etiologic source of SIRS, as well as on associated comorbidities. The mortality rates in the previously
mentioned Rangel­Fausto et al study were 7% (SIRS), 16% (sepsis), 20% (severe sepsis), and 46% (septic shock).[7] The
median time interval from SIRS to sepsis was inversely related to the number of SIRS criteria met. Morbidity is related to the
causes of SIRS, complications of organ failure, and the potential for prolonged hospitalization.
However, the large retrospective study of all of Australia and New Zealand ICU care from 2000­2012 demonstrated a clear
progressive decline in severe sepsis and septic shock mortality from 35% to 18% over this period, with equal trends across all
age groups and treatment settings.[12] These data suggest that attention to detail, using best practices and overall quality care,
has nearly halved mortality from severe sepsis independent of any specific treatment. Thus, attention to overall patient status
and use of proven risk reduction approaches (eg, stress ulcer prophylaxis, DVT prophylaxis, daily awakening, and weaning trials
in ventilator­dependent patients) are central to improving outcome from severe sepsis.
Pittet et al showed that control patients had the shortest hospital stay, while patients with SIRS, sepsis, and severe sepsis,
respectively, required progressively longer hospital stays.[8]
A study by Shapiro et al evaluated mortality in patients with suspected infection in the emergency department and found the
following in­hospital mortality rates[13] :
Suspected infection without SIRS ­ 2.1%
Sepsis ­ 1.3%
Severe sepsis ­ 9.2%
Septic shock ­ 28%
In the study, the presence of SIRS criteria alone had no prognostic value for either in­hospital mortality or 1­year mortality. Each
additional organ dysfunction increased the risk of mortality at 1 year. The authors concluded that organ dysfunction, rather than
SIRS criteria, was a better predictor of mortality.
Sinning et al evaluated the SIRS criteria in patients who underwent transcatheter aortic valve implantation (TAVI) and found that
SIRS appeared to be a strong predictor of mortality. The occurrence of SIRS was characterized by a significantly elevated
release of IL­6 and IL­8, with subsequent increase in the leukocyte count, C­reactive protein (CRP), and procalcitonin. The
occurrence of SIRS was related to 30­day and 1­year mortality (18% vs 1.1% and 52.5% vs 9.9%, respectively) and
independently predicted 1­year mortality risk.[14]
In the aforementioned Heffner et al study, patients without an identified infection had a lower hospital mortality rate than did
patients with an infectious etiology for their SIRS (9% vs 15%, respectively).[9]
Patient Education
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Education should ideally target the patient’s family. Family members need to understand the fluid nature of immune
responsiveness and that SIRS is a potential harbinger of other more dire syndromes.
Presentation
History
Despite having a relatively common physiologic pathway, systemic inflammatory response syndrome (SIRS) has numerous
triggers, and patients may present in various manners. The clinician’s history should be focused around the chief symptom, with
a pertinent review of systems being performed. Patients should be questioned regarding constitutional symptoms of fever, chills,
and night sweats. This may help to differentiate infectious from noninfectious etiologies. The timing of symptom onset may also
guide a differential diagnosis toward an infectious, traumatic, ischemic, or inflammatory etiology.
Pain, especially when it can be localized, may guide a physician in differential diagnosis and necessary evaluation. Although
providing a differential for pain in the various body parts is beyond the scope of this article, a physician should carefully obtain
information on the duration, location, radiation, quality, and exacerbating factors associated with the pain to help establish a
thorough differential diagnosis.
In patients for whom a diagnosis cannot be made on the basis of the initial history, a complete review of systems is indicated to
try to uncover a potential diagnosis.
The patient’s medications should be reviewed. Medication side effects or pharmacologic properties may either induce or mask
SIRS (eg, beta­blockers prevent tachycardia). Recent changes in medications should be addressed to rule out drug­drug
interactions or a new side effect. Allergy information should be gathered and the specifics of the reaction should be obtained.
Physical Examination
A focused physical examination based on a patient’s symptoms is adequate in most situations. Under certain circumstances, if
no obvious etiology is obtained during the history or laboratory evaluation, a complete physical examination may be indicated.
Patients who cannot provide any history should also undergo a complete physical examination, including a rectal examination, to
rule out an abscess or gastrointestinal bleeding.
With the exception of white blood cell count abnormalities (>12,000/µL or < 4,000/µL or >10% immature [band] forms), the
criteria for SIRS are based on vital signs, as follows:
Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)
Heart rate of more than 90 beats per minute
Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) of less than 32 mm Hg
Careful review of initial vital signs is an integral component of the diagnosis. Reassessing the vital signs periodically during the
initial evaluation period is necessary, as multiple factors (eg, stress, anxiety, exertion of walking to the examination room) may
lead to a false diagnosis of SIRS.
Key points associated with physical examination are as follows:
Patients at the extremes of age (both young and old) may not manifest typical criteria for SIRS; therefore, clinical
suspicion may be required to diagnosis a serious illness (either infectious or noninfectious)
Patients receiving a beta­blocker or a calcium channel blocker are often unable to elevate their heart rate and, therefore,
tachycardia may not be present
Although low blood pressure is not a criterion for SIRS, it is still an important marker; if the blood pressure is low, the
establishment of intravenous access and fluid resuscitation is of utmost importance; frank hypotension associated with
SIRS is uncommon unless the patient is septic or severely dehydrated (hypotension may lead to the patient being
admitted or transferred to a higher acuity unit)
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Respiratory rate is the most sensitive marker of the severity of illness
DDx
Diagnostic Considerations
Conditions to consider in the differential diagnosis of systemic inflammatory response syndrome (SIRS) include the following:
Abdominal abscess
Diverticulitis
Electrical injuries
Erythema multiforme (Stevens­Johnson syndrome)
Gas gangrene
Posttransplantation infections
Infective endocarditis
Influenza
Intestinal perforation
Meningitis
Meningococcemia
Multisystem organ failure of sepsis
Myocardial Infarction
Nosocomial pneumonia
Acute pancreatitis[6]
Perioperative pulmonary management
Community­acquired pneumonia[5]
Pseudomembranous colitis
Pulmonary embolism
Acute pyelonephritis
Respiratory failure
Bacterial sepsis
Septic arthritis
Septic shock
Toxic epidermal necrolysis
Toxic shock syndrome
Transfusion reactions
Upper gastrointestinal bleeding
Female urinary tract infection
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Male urinary tract infection
Autoimmune disorders
Chemical aspiration
Cutaneous adverse drug reaction
Dehydration
Medication effects
Pulmonary contusions
Substance abuse ­ Stimulants such as cocaine and amphetamines
Surgical procedures
Viral infections
Differential Diagnoses
Acute Coronary Syndrome
Acute Mesenteric Ischemia
Burn Wound Infections
Candidiasis
Cardiogenic Shock
Cellulitis
Cholecystitis
Cirrhosis
Diabetic Foot Infections
Immediate Hypersensitivity Reactions
Workup
Workup
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)
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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 acid­base status)
Interleukin 6
Patients who meet SIRS criteria and have increased interleukin 6 (IL­6) 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 IL­6 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]
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.
Procalcitonin
A significant amount of research has evaluated the use of acute­phase reactants to help differentiate infectious from
noninfectious causes of systemic inflammatory response s