First-time guidelines target surviving sepsis

Accounting for about 750,000 cases in this country annually, severe sepsis has an alarming 30% mortality rate. Research indicates that while there are many useful clinical interventions available for sepsis, they are applied inconsistently by many clinicians.

Unprecedented guidelines were recently developed by a group of international critical care and infectious disease experts in an effort to increase awareness and improve outcome in severe sepsis (infection-induced organ dysfunction or hypoperfusion abnormalities) and septic shock (hypotension not reversed with fluid resuscitation and associated with organ dysfunction or hypoperfusion abnormalities). Under the auspices of the Surviving Sepsis Campaign, the evidence-based guidelines were unveiled at the 33^rd annual congress of the Society of Critical Care Medicine in Orlando and reported in the March 2004 issue of Critical Care Medicine. Experts stressed that patient outcome will be heavily influenced by the speed and appropriateness of therapy in the initial hours of syndrome development.

In the guidelines, a most vital recommendation is the initiation of broad-spectrum antibiotic therapy within the first hour of severe sepsis awareness and after appropriate cultures. While it's inappropriate to delay treatment while waiting for culture results, once the results are available, the antimicrobial regimen must be reassessed for a possible switch to a narrow-spectrum antibiotic. "Timely administration of appropriate antibiotics in such critically ill patients is crucial," said Thiri Anandarangam, M.D., department of pulmonary and critical care medicine at Newark Beth Israel Medical Center in Newark, N.J.

The guidelines recommend the use of drotrecogin alfa (Xigris, Lilly), or recombinant human activated protein C (rhAPC), an endogenous anticoagulant having anti-inflammatory properties, in patients at high risk of death. This can be determined by certain listed criteria. A clinical study published in the New England Journal of Medicine in 2001 demonstrated that rhAPC improved survival in patients with sepsis-induced organ dysfunction. "In our institution, we utilize a form that serves as a checklist to assess the patient's eligibility for activated protein C. Timely therapy is initiated in patients meeting eligibility criteria," explained George Shehata, R.Ph., at Clara Maass Hospital in Belleville, N.J.

The guideline panel members also advocate the use of vasopressors and inotropes in such critically ill patients, when appropriate fluid resuscitation fails to restore adequate blood pressure and organ perfusion. In addition, the experts recommended that one week of corticosteroid therapy in patients with septic shock might be beneficial. The authors also emphasized the importance of glycemic control in patients with severe sepsis, since it has been shown to increase the likelihood of survival.

While developing guidelines is definitely an imperative step in the effort to ensure optimal patient care, how can they be applied practically in the clinical setting? Based on the principles of both evidence-based medicine and performance improvement, a number of practical steps that can be employed by clinicians were proposed in a research paper written by Peter J. Provonost, M.D., Ph.D., and Sean M. Berenholtz, M.D., MHS, department of anesthesiology and critical care medicine at Johns Hopkins Medical Institutions in Baltimore.

In this paper, recently published by VHA Inc., the national healthcare cooperative, Provonost described a model where the science of improving sepsis care is converted from cumbersome guidelines into a simple checklist that ensures compliance by the staff in critical care units. "We're not saying clinical personnel should ignore the lists they've already developed entirely, but they must be simple to use and check. At least two people should be verifying completion of each step, not merely the physician," said Provonost.

Experts examined the models of sepsis care at Johns Hopkins as well as other VHA participating hospitals and developed 11 quality indicators for optimum sepsis care. The recommendations for sepsis care in the VHA research paper are quite similar to those of the new guidelines in Critical Care Medicine.

In the VHA paper, clinicians are also advised to assess severely septic patients for rhAPC eligibility within 24 hours following ICU admission and commence therapy in eligible patients within 48 hours following ICU admission. Provonost also indicated that after performing a corticotropin stimulation test on patients with severe sepsis, treating empirically with steroids might prove beneficial. This recommendation was based on a study, published in JAMA in 2002, demonstrating that severely septic patients with relative adrenal insufficiency experienced a significant reduction in mortality when empirically treated with steroids.