Systemic Inflammatory Response Syndrome Treatment & Management

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^[3] or pancreatitis.

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.

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.

Surgery

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.

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 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.

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 data should always be obtained prior to initiating antibiotic therapy. Antibiotics prior to culturing a patient 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.

Gram-negative coverage with cefepime, piperacillin-tazobactam, carbapenem (imipenem, meropenem, or doripenem), or a quinolone is reasonable.

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.

Care must be taken 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 a reasonable alternative 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 data are available.

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.^[20] Prior to initiating steroid therapy, however, physicians must consider the potential risk of steroids (such as stress ulcers and hyperglycemia).^[21]

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.

Hyperglycemia, a common laboratory finding in systemic inflammatory response syndrome (SIRS), even in individuals without diabetes, has numerous deleterious systemic effects.^{[22, 23]}

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-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 inhospital 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 inhospital mortality rates with intensive insulin therapy (maintenance of blood glucose at 80-110mg/dL) by 34%.^[24] 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, 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 his or her 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); eg, 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 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], 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.