AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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). 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:

• Fever of more than 38°C or less than 36°C

• Heart rate of more than 90 beats per minute

• Respiratory rate of more than 20 breaths per minute or a PaCO2 level of less than 32 mm Hg

• Abnormal white blood cell count (>12,000/µL or <4,000/µL or >10% bands)

SIRS is nonspecific and can be caused by ischemia, inflammation, trauma, infection, or a combination of several insults. SIRS is not always related to infection. 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 blood stream, 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. Sepsis-induced 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 physiological derangements in which organ function is not capable of maintaining homeostasis.

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.

Pathophysiology

SIRS, independent of the etiology, has the same pathophysiologic properties, with minor differences in inciting cascades. Many consider the syndrome a self-defense 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 best summarized the relationship between these complex interactions and SIRS as the following 3-stage process:

• Stage I: Following an insult, local cytokine is produced with the goal of inciting an inflammatory response, thereby promoting wound repair and recruitment of the reticular endothelial system.

• Stage II: Small quantities of local cytokines are released into circulation to improve 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.

• Stage III: If homeostasis is not restored, 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 end-organ dysfunction.

Bone also endorsed a multihit theory behind the progression of SIRS to organ dysfunction and possibly 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.

Trauma, inflammation, or infection leads to the activation of the inflammatory cascade. 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-a (TNF-a) and interleukin (IL)–1 are released first and initiate several cascades. The release of IL-1 and TNF-a (or the presence of endotoxin or exotoxin) leads to cleavage of the nuclear factor-kB (NF-kB) inhibitor. Once the inhibitor is removed, NF-kB is able to initiate the production of mRNA, which induces the production other proinflammatory cytokines.

IL-6, IL-8, and interferon gamma are the primary proinflammatory mediators induced by NF-kB. In vitro research suggests that glucocorticoids may function by inhibiting NF-kB. TNF-a and IL-1 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 cause severe lung injury and hypotension when given together. TNF-a and IL-1 are responsible for fever and the release of stress hormones (norepinephrine, vasopressin, activation of the renin-angiotensin-aldosterone system).

Other cytokines, especially IL-6, stimulate the release of acute-phase reactants such as C-reactive protein (CRP). Of note, infection has been shown to induce a greater release of TNF-a than trauma, which induces a greater release of IL-6 and IL-8. 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, complement cascade, and the release of nitric oxide, platelet-activating factor, prostaglandins, and leukotrienes. 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.

The correlation between inflammation and coagulation is critical to understanding the potential progression of SIRS. IL-1 and TNF-a 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 IL-1 and TNF-a via production of plasminogen activator inhibitor-1. Proinflammatory cytokines also disrupt the naturally occurring anti-inflammatory mediator's antithrombin and activated protein-C (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. Infection-related procoagulant activity is generally more severe than that produced by trauma.

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 counter inflammatory response syndrome (CARS). IL-4 and IL-10 are cytokines responsible for decreasing the production of TNF-a, IL-1, IL-6, and IL-8. The acute phase response also produces antagonists to TNF-a and IL-1 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 determines a patient's prognosis 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.

Frequency

United States

The true incidence of SIRS is unknown. However, because SIRS criteria are nonspecific and occur in patients who present with conditions that range from influenza to cardiovascular collapse associated with severe pancreatitis, such incidence figures would need to be stratified based on SIRS severity.

Rangel-Fausto et al published a prospective survey of patients admitted to a tertiary care center that revealed 68% of hospital admissionsto surveyed units met SIRS criteria. 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 in-hospital incidence of 542 episodes per 1000 hospital days. In comparison, the incidence in the ICU was 840 episodes per 1000 hospital days.

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. The real incidence of SIRS, therefore, must be much higher and likely depends somewhat on the rigor with which the definition is applied.

International

No difference in frequency exists based on world geography.

Mortality/Morbidity

The mortality rates in the previously mentioned Rangel-Fausto study were 7% (SIRS), 16% (sepsis), 20% (severe sepsis), and 46% (septic shock). The medial time interval from SIRS to sepsis was inversely related to the number of SIRS criteria (2, 3, or all 4) met. Morbidity is related to the causes of SIRS, complications of organ failure, and the potential for prolonged hospitalization. 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.

A recently published study by Shapiro et al evaluated mortality in patients with suspected infection in the emergency department. The in-hospital mortality rates were as follows: 2.1% had a suspected infection without SIRS, 1.3% had sepsis, 9.2% had severe sepsis, and 28% had septic shock. The presence of SIRS criteria alone had no prognostic value for either in-hospital mortality or 1-year 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.

Race

No racial predilection exists for this disease entity.

Sex

Using the same logic as expressed in Frequency, the sex-based mortality risk of severe SIRS is also unknown. Females tend to have less inflammation for the same degree of proinflammatory stimuli because of the mitigating aspects of estrogen. 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.

Age

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 CARS). Young people have better outcomes of equivalent diagnoses.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 both 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 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 based on initial history, a complete review of systems is indicated to try an undercover potential diagnosis.
• Patients' medications should be reviewed. Medication side effects or pharmacologic properties may either induce or mask SIRS (ie, beta-blockers prevent tachycardia). Recent changes in medications should be addressed to rule out drug-drug interactions or a new side effect. Allergy information should be gathered and the specifics of the reaction should be obtained.

Physical

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.

• Three of the 4 criteria for SIRS are based on the following vital signs:
• • A fever of more than 38°C or less than 36°C
  • A heart rate of more than 90 beats per minute
  • Respiratory rate of more than 20 breaths per minute or PaCO2 level of less than 32 mm Hg
  • An abnormal white blood cell count (>12,000/µL or <4,000/µL or >10% bands)

• Careful review of initial vital signs is an integral component to making the diagnosis. Repeating the review of vital signs periodically during the initial evaluation period is necessary, as multiple other factors (eg, stress, anxiety, exertion of walking to the examination room) may lead to a false diagnosis of SIRS.
• Key points
• • Extreme of ages (both young and old) may not manifest as typical criteria for SIRS; therefore, clinical suspicion may be required to diagnosis a serious illness (either infectious or noninfectious).
  • Patients receiving a beta-blocker or a calcium channel blocker are likely unable to elevate their heart rate and, therefore, tachycardia may not be present.
  • Although blood pressure is not one of the 4 criteria, 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.
  • Respiratory rate is the most sensitive marker of the severity of illness.

Causes

The differential diagnosis of SIRS is broad and includes infectious and noninfectious conditions, surgical procedures, trauma, and medications and therapies.

• 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

  • Intraabdominal infections (eg, diverticulitis, appendicitis)

  • Gas gangrene

  • Meningitis

  • Nosocomial pneumonia

  • Pseudomembranous colitis

  • Pyelonephritis

  • Septic arthritis

  • Toxic shock syndrome

  • Urinary tract infections (both male and female)

• The following is a partial list of the noninfectious causes of SIRS:
• • Acute mesenteric ischemia

  • Autoimmune disorders

  • Burns

  • Chemical aspiration

  • Cirrhosis

  • Dehydration

  • Drug reaction

  • Electrical injuries

  • Erythema multiforme

  • Hemorrhagic shock

  • Intestinal perforation

  • Medication side effect (eg, theophylline)

  • Myocardial infarction

  • Pancreatitis

  • Substance abuse (stimulants such as cocaine and amphetamines)

  • Surgical procedures

  • Toxic epidermal necrolysis

  • Transfusion reactions

  • Upper gastrointestinal bleeding

  • Vasculitis

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Autoimmune disorders
Chemical aspiration
Dehydration
Medication effects
Pulmonary contusions
Substance abuse (stimulants such as cocaine and amphetamines)
Surgical procedures
Viral infections

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• In order to completely evaluate for systemic inflammatory response syndrome (SIRS), a minimum of a complete blood cell count with differential to evaluate for leukocytosis or leucopenia is required. Routine screenings often also include a basic metabolic profile. Other laboratory tests should be individualized based on the patient history and physical examination findings.
• • A significant amount of research has evaluated the use of acute-phase reactants to help differentiate infectious from noninfectious causes of SIRS. Arkader et al compared procalcitonin (PCT) with CRP in their ability to differentiate infectious from noninfectious causes. Their observational prospective study in a pediatric ICU showed that PCT was able to differentiate between infectious and noninfectious SIRS, while CRP was not.
  • Selberg et al reviewed PCT and CRP, in addition to looking at IL-6 and C3a. Their research showed that PCT, IL-6, and C3a were again more reliable in distinguishing infectious from noninfectious causes.
  • Multiple other studies have analyzed the use of PCT in differentiating SIRS from sepsis and have been fairly consistent in their finding that it is a useful laboratory tool. Unfortunately, these acute-phase reactants (other than sedimentation rates and CRP) are, in general, available only in research institutions, and routine ordering is not likely to provide a significant clinical impact because of delayed turnaround time. Sedimentation rates and CRPs are not sensitive in distinguishing between causes of SIRS but may be helpful in certain circumstances. The lack of specificity significantly diminishes the clinical role of acute-phase reactants in narrowing the differential diagnosis but, when elevated, may have a role in monitoring response to treatment.

Imaging Studies

• No diagnostic imaging studies exist for SIRS. The selection of imaging studies depends on the etiology that required ICU and hospital admission.

Other Tests

• Blood cultures, urinalysis and culture, cardiac enzymes, amylase, lipase spinal fluid, and liver profiles are among the numerous laboratory tests to consider.
• Blood lactate assessments are often performed in critically ill patients. These are felt to be indicators of anaerobic metabolism associated with tissue dysoxia. Levels are commonly elevated from increased peripheral intraorgan production and reduced hepatic uptake and reduced renal elimination. Based on numerous studies, lactate levels correlate strongly with mortality.

Histologic Findings

No histologic findings are specific for the diagnosis of SIRS.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The initial medical care should include prompt initiation of pertinent laboratory testing and imaging studies after obtaining a history and performing a physical examination. Treatment should then be focused based on possible inciting causes of systemic inflammatory response syndrome (SIRS; eg, appropriate treatment of acute myocardial infarction differs from the treatment of community-acquired pneumonia or pancreatitis).

• Empiric antibiotics are not indicated for all patients with SIRS. Indications for antibiotic therapy include (1) suspected or diagnosed infectious etiology (eg, urinary tract infection [UTI], pneumonia, cellulitis), (2) hemodynamic instability, (3) neutropenia (or other immunocompromised states), and (4) asplenia (due to the potential for overwhelming postsplenectomy infection [OPSI]). When feasible, culture data should always be obtained prior to initiating antibiotic therapy. Empiric antibiotic 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. Once a bacteriologic diagnosis is obtained, narrowing the antibiotic spectrum to the most appropriate therapy is critical.


• Because of increasing bacterial resistance, broad-spectrum antibiotics should be initiated when an infectious cause for SIRS is a concern but no specific infection is diagnosed.
  
  
  • With the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the community, vancomycin or another anti-MRSA therapy should be considered.
  
  
  • Gram-negative coverage with either cefepime or a quinolone is reasonable.
  
  
  • Recent exposure to antibiotics must be considered when choosing empiric regimens because recent antibiotic therapy increases the risk for resistant pathogens.
  
  
  • Care must be made not to use an antibiotic to which the patient is allergic. This may be a second hit and lead to worsening SIRS.
  
  
  • Because of the high prevalence of patients with penicillin allergy, a quinolone or aztreonam is reasonable alternatives for gram-negative coverage.
  
  
  • Antiviral therapy has no role in SIRS.
  
  
  • 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.
  
  
  • Although empiric antibiotics may be reasonable in many situations, the key is to stop antibiotics when infection is ruled out or narrow the antibiotic spectrum once a pathogen is found.
  
  
  • Proper culture data must be obtained prior to any antibiotic therapy. Antibiotics prior to culturing a patient may be a cause of sterile sepsis.


• TNF-a and IL-1 receptor antagonists, antibradykinin, platelet-activating factor receptor antagonists, and anticoagulants (antithrombin III) have been studied without showing statistically significant benefits in SIRS (with variable results for sepsis and septic shock). These medications have no role in treating patients who meet criteria for SIRS only.


• Drotrecogin alfa, a recombinant form of APC, warrants further comment. APC reduces microvascular dysfunction by reducing inflammation and coagulation and increasing fibrinolysis.
• • The Patients in the Recombinant Human Activated Protein-C Worldwide Evaluation in Severe Sepsis (PROWESS) study demonstrated its ability to reduce 28-day all-cause mortality following severe sepsis. Further studies have demonstrated that it is best used in patients with gram-negative septic shock. In the PROWESS study, no clinical benefit was found in patients with acute physiology and chronic health evaluation (APACHE) scores of less than 25, and further studies have demonstrated worse outcomes in patients with lower APACHE scores.
  
  
  • Therefore, APC has no role in most SIRS cases unless the clinical presentation is consistent with septic shock. APC has strict inclusion and exclusion criteria that must be considered in all patients prior to initiating therapy. The greatest benefit of APC has been demonstrated when this medication is initiated early in the inflammatory cascade.


• Steroids for sepsis and septic shock have been extensively studied, but no SIRS-specific studies have been performed to date.
• • 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 d) improved survival and the reversal of shock in vasopressor-dependent patients.
  
  
  • As mentioned above, the inflammatory mediators and receptors associated with infectious insults (ie, septic shock) are the same as those of noninfectious insults (ie, trauma, inflammatory conditions, ischemia). Therefore, in patients with severe or progressive SIRS, even without an obvious infectious insult, low steroids could be considered.
  
  
  • Current data do not support using ACTH stimulation testing to determine patients who should receive steroid therapy. Patients receiving steroids require careful monitoring for hyperglycemia.


• Patients who are hypotensive should receive intravenous fluids, and, if still hypotensive after adequate resuscitation, vasopressor agents should be administered while carefully monitoring hemodynamic status. All patients should have adequate intravenous access and commonly require 2 large-bore intravenous lines or a central venous catheter. For further details on the management of hypotension, please refer to the article Septic Shock


• Hyperglycemia, a common laboratory finding in SIRS, even in individuals without diabetes, has numerous deleterious systemic effects.
  
  
  • An increase of counterregulatory hormones, namely cortisol and epinephrine, and relative hypoinsulinemia lead to increased hepatic glucose production, increased peripheral insulin resistance, and increased circulating free fatty acids. This has direct inhibitory action on the immune system. Oxidative stress and endothelial cell dysfunction, along with proinflammatory cytokines (IL-6, IL-8, TNF-a) and other secondary mediators (NF-kB) have all been implicated as causes of cellular injury, tissue damage, and organ dysfunction in patients with hyperglycemia.
  
  
  • Intensive control of blood glucose levels has been shown to diminish in-hospital morbidity and mortality in both the surgical and medical intensive care setting. Various trials have shown that glycemic control with insulin improves patient outcomes (including renal function and acute renal failure), reduces the need for red blood cell transfusions, reduces the number of days in the ICU, lowers the incidence of critical-illness polyneuropathy, and decreases the need for prolonged mechanical ventilation. Van den Berghe et al (2006) reported a reduction of in-hospital mortality rates with intensive insulin therapy (maintenance of blood glucose at 80-110 mg/dL) by 34%. The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus.


• Supplemental oxygen should be provided to any patient that demonstrates an increased oxygen requirement or decreased oxygen availability. Oxygen can be provided via nasal canula or mask, or, in certain situations, ventilator support may be required to maximize oxygen delivery. Supplying supraphysiologic oxygen has shown mixed results in a multitude of studies. Providing too much oxygen in a patient with severe chronic obstructive pulmonary disease (COPD) should be avoided because it can depress their respiratory drive. Patients who do not respond to increased oxygen supply have a poor prognosis. Patients with associated respiratory failure who require mechanical ventilation should be treated with low tidal volume mechanical ventilation (6 mL/kg).

Surgical Care

The details of surgical management are site-specific and are beyond the scope of this article. 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.

Consultations

Consultations vary depending on the admitting physician's training and the cause of SIRS (ie, cardiology consultation for acute myocardial infarction or gastroenterology for acute GI bleeding). Patients with potential surgical issues should undergo a surgical evaluation, often in the emergency room, early in the course of illness.

• Consider consultation with an intensivist, if one is available. If organ dysfunction develops, the intensivist or a consultant specialist in that organ system should be involved.
• Early consultation with an expert in infectious diseases is particularly helpful for patients who are immunocompromised, regardless of the cause (eg, HIV, AIDS, malignancy, solid organ transplantation). They can also provide guidance in situations in which patients are not responding to standard antibiotic therapy, have multiple drug allergies, or are infected with multidrug-resistant organisms or when a diagnosis is still uncertain.

Diet

Enteral feedings 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 GI 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 do activity as tolerated.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No drugs of choice exist for this entity. Medication prescriptions target specific diagnoses, preexisting comorbidities, and prophylaxis regimens for complications. No pharmacologic agents have been demonstrated to improve the systemic inflammatory response syndrome (SIRS) outcome. Broad-spectrum antibiotics, insulin therapy (in patients with hyperglycemia), and steroids should be considered in patients who meet criteria for SIRS.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune system to diverse stimuli.

Drug Category: Antidiabetic agents

These agents are used to treat hyperglycemia.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Specific recommendations for this condition are not available because of the broad differential of potential causes.

Transfer

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

Complications

• Complications vary based on underlying etiology. Routine prophylaxis including deep vein thrombosis (DVT) and stress ulcer prophylaxis should be initiated when clinically indicated. Long-term antibiotics, when clinically indicated, should be as narrow spectrum as possible to limit potential for superinfection (suggested by a new fever, change in white blood cell count, or clinical deterioration). Unnecessary vascular catheters and Foley catheters should be removed as soon as possible.
• Other potential complications include the following:
• • Respiratory failure, acute respiratory distress syndrome (ARDS), and nosocomial pneumonia
  • Renal failure
  • GI bleeding and stress gastritis
  • Anemia
  • DVT
  • Intravenous catheter–related bacteremia
  • Electrolyte abnormalities
  • Hyperglycemia

  • Disseminated intravesicular coagulation (DIC)

Prognosis

• See Mortality/Morbidity. Prognosis depends on etiologic source of SIRS, as well as associated comorbidities.

Patient Education

• 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.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider a diagnosis beyond systemic inflammatory response syndrome (SIRS) is a pitfall. The clinical evaluation should focus on a potential cause of SIRS.

Special Concerns

• Pregnant patients require intensive evaluation because of the presence of 2 patients, as well as the propensity of uncontrolled inflammation to lead to preterm labor.
• 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.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Angus DC, Linde-Zwirble WT, Lidicker J. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310. [Medline].
• Arkader R, Troster EJ, Lopes MR. Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child. 2006;91:117-120.
• Baue AE. Multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome. Why no magic bullets?. Arch Surg. Jul 1997;132(7):703-7. [Medline].
• Bone RC. Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med. Jan 1996;24(1):163-72. [Medline].
• Bone RC. Systemic inflammatory response syndrome: a unifying concept of systemic inflammation. In: Fein A, Abraham A, et al. Sepsis and Multiorgan Failure. Philadelphia, Pa:. Lippencott, Williams, & Wilkins;1997:1-10.
• Bone RC, Balk RA, Cerra FB. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644-1655. [Medline].
• Casey LC. Immunologic response to infection and its role in septic shock. Crit Care Clin. 2000;16:193-211.
• Chelluri L, Mendelsohn AB, Belle SH, et al. Hospital costs in patients receiving prolonged mechanical ventilation: does age have an impact?. Crit Care Med. Jun 2003;31(6):1746-51.
• Clement S, Braithwaite SS, Magee MF. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-91. [Medline].
• Davies MG, Hagen PO. Systemic inflammatory response syndrome. Br J Surg. Jul 1997;84(7):920-35. [Medline].
• Deans KJ, Haley M, Natanson C. Novel therapies for sepsis: a review. J Trauma. 2005;58:867-874.
• Dellinger RP. Inflammation and coagulation: implications for the septic patient. CID. 2003;36:1259-1264.
• Dremsizov T, Gilles C, Kellum JA. Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course?. Chest. 2006;129:965-978.
• Fry DE. Sepsis syndrome. Am Surg. 2000;66:126-132. [Medline].
• Gabay C, Kushner I. Acute-phase proteins and other systemic inflammatory responses to inflammation. NEJM. 1999;340:448-454. [Medline].
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Article Last Updated: Apr 16, 2007