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Systemic Inflammatory Response Syndrome Treatment & Management

  • Author: Lewis J Kaplan, MD, FACS, FCCM, FCCP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
Updated: Mar 30, 2015

Approach Considerations

Treatment of systemic inflammatory response syndrome (SIRS) should focus on possible inciting causes. As the causes of SIRS include a wide range of disorders (eg, acute myocardial infarction, community-acquired pneumonia,[5] pancreatitis), the appropriate interventions will likewise differ from patient to patient.

Studies of tumor necrosis factor–alpha (TNF-α) and interleukin-1 (IL-1) receptor antagonists, antibradykinin, platelet-activating factor receptor antagonists, and anticoagulants (antithrombin III) have not shown statistically significant benefits in SIRS. Variable results for sepsis and septic shock have been reported. These medications have no role in treating patients who meet criteria for SIRS only.

Patients who are hypotensive should receive intravenous fluids. In patients who are still hypotensive after adequate resuscitation, vasopressor agents should be administered while hemodynamic status is carefully monitored. 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 Septic Shock.


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.


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.


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.


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.


Antimicrobial Therapy

Antibiotic therapy

Empiric antibiotics are not indicated for all patients with systemic inflammatory response syndrome (SIRS). Indications for antibiotic therapy include the following:

  • Suspected or diagnosed infectious etiology (eg, urinary tract infection [UTI], pneumonia, cellulitis)
  • Hemodynamic instability
  • Neutropenia or other immunocompromised states
  • Asplenia - Due to the potential for overwhelming postsplenectomy infection (OPSI)

When feasible, culture specimens should always be obtained prior to initiating antibiotic therapy. Antibiotics administered prior to culturing may be a cause of sterile sepsis.

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. The key is to stop antibiotics when infection is ruled out or narrow the antibiotic spectrum once a pathogen is found.

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. Recent exposure to antibiotics (typically within 3 months) must be considered when choosing empiric regimens, because recent antibiotic therapy increases the risk for resistant pathogens.

Gram-negative coverage with cefepime, piperacillin-tazobactam, carbapenem (imipenem, meropenem, or doripenem), or a quinolone is reasonable. Care must be taken not to use an antibiotic to which the patient is allergic, which may be a second hit and lead to worsening SIRS; penicillin allergy is a particular concern, given its prevalence. A quinolone or aztreonam is a reasonable choice for gram-negative coverage in patients with a penicillin allergy. If aztreonam is used, gram-positive coverage (with an agent such as vancomycin) should be initiated as well, until culture results are available.

The FDA recently approved 3 new antibiotics, oritavancin (Orbactiv), dalbavancin (Dalvance), and tedizolid (Sivextro), for the treatment of acute bacterial skin and skin structure infections. These agents are active against Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MSSA, MRSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), among others.

For complete drug information, including dosing, see the following monographs:

Antiviral and antifungal therapy

Antiviral therapy has no role in SIRS unless the patient is immunocompromised or presents for evaluation during influenza season and the clinical picture is consistent with influenza infection.

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.



The inflammatory mediators and receptors associated with infectious insults (ie, septic shock) are the same as those linked to noninfectious insults (ie, trauma, inflammatory conditions, ischemia).

Steroids for sepsis and septic shock have been extensively studied, but no investigations specific to systemic inflammatory response syndrome (SIRS) 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 days) improved survival and the reversal of shock in vasopressor-dependent patients.

Low-dose steroids should be considered on an individual basis for patients with refractory hypotension (ie, septic shock) despite adequate fluid resuscitation and appropriate vasopressor administration.[26] Prior to initiating steroid therapy, however, physicians must consider the potential risks of steroids, such as stress ulcers and hyperglycemia.[27]

Similarly, in the critically ill vasoplegic patient (ie, hypotensive despite fluid resuscitation and vasopressor therapy), the use of vasopressin (0.01-0.02 mcg/kg/h) may be beneficial in decreasing vasopressor requirements without causing more ischemia. Its effects on mortality have not been proven.

Current data do not support using adrenocorticotropic hormone (ACTH) stimulation testing to determine which patients should receive steroid therapy. Patients receiving steroids require careful monitoring for hyperglycemia.


Glucose Control

Hyperglycemia, a common laboratory finding in systemic inflammatory response syndrome (SIRS), even in individuals without diabetes, has numerous deleterious systemic effects.[28, 29]

An increase in 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-α) 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 the surgical and medical intensive care setting. Various trials have demonstrated 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 reported a reduction of in-hospital mortality rates with intensive insulin therapy (maintenance of blood glucose at 80-110 mg/dL) by 34%.[30] The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Subsequent studies by this group and others have failed to demonstrate distinct outcome benefit from tight glucose control, mainly because the complication rate for hypoglycemia and hypokalemia complicate its effects. Presently, the Surviving Sepsis guidelines recommend keeping glucose levels at less than 180 mg/dL.[26]


Supplemental Oxygen

Supplemental oxygen should be provided to any patient who demonstrates an increased oxygen requirement or decreased oxygen availability. Oxygen can be provided via nasal cannula or mask, although 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 the 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).



Consultations vary depending on the admitting physician's training and the cause of systemic inflammatory response syndrome (SIRS); for example, 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 department, early in the course of their 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, human immunodeficiency virus [HIV] infection, acquired immunodeficiency syndrome [AIDS], malignancy, solid organ transplantation). This specialist 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.

Contributor Information and Disclosures

Lewis J Kaplan, MD, FACS, FCCM, FCCP Associate Professor of Surgery, Division of Trauma, Surgical Critical Care, and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania; Section Chief, Surgical Critical Care, Philadelphia Veterans Affairs Medical Center

Lewis J Kaplan, MD, FACS, FCCM, FCCP is a member of the following medical societies: American Association for the Surgery of Trauma, American College of Surgeons, Association for Academic Surgery, Association for Surgical Education, Connecticut State Medical Society, Eastern Association for the Surgery of Trauma, International Trauma Anesthesia and Critical Care Society, Society for the Advancement of Blood Management, Society of Critical Care Medicine, Surgical Infection Society

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM is a member of the following medical societies: American College of Chest Physicians, Association of University Anesthetists, European Society of Intensive Care Medicine, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Shock Society, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.


Heatherlee Bailey, MD Assistant Program Director, Assistant Professor, Department of Emergency Medicine, Division of Critical Care, Medical College of Pennsylvania Hahnemann University

Heatherlee Bailey, MD is a member of the following medical societies: American Academy of Emergency Medicine, Association for Surgical Education, Society for Academic Emergency Medicine, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Steven D Burdette, MD, FIDSA Associate Professor of Medicine, Program Director, Infectious Diseases Fellowship, Wright State University, Boonshoft School of Medicine; Infectious Disease Advisor to Transplant Program, Miami Valley Hospital; Medical Director of Infectious Diseases, Green Memorial Hospital

Steven D Burdette, MD, FIDSA is a member of the following medical societies: Alpha Omega Alpha, American Society for Microbiology, American Society of Transplantation, Infectious Diseases Society of America, and Transplantation Society

Disclosure: Cubist Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Joseph F John Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Miguel A Parilo, MD, FACP Associate Clinical Professor of Medicine, Department of Medicine, Wright State University, Boonshoft School of Medicine; Medical Director, The Bull Family Diabetes Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Venn diagram showing overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.
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