A campaign worth joining: improving outcome in severe sepsis and septic shock using the Surviving Sepsis Campaign guidelines.

When the systemic response to infection leads to organ dysfunction, it is termed severe sepsis. (1) Severe sepsis and septic shock are the 10th leading cause of death in the United States and one of the two most common causes of death in the noncoronary intensive care unit. (2) Currently sepsis mortality rates range from 12 up to 85%. The highest mortality rates are present when there is septic shock and multiple organ dysfunction syndrome. (2) A recent review of 22 years of National Hospital Discharge Survey codes demonstrated an increase in the incidence of sepsis among both men and women, as well as all races. (3) This study also demonstrated that Gram positive organisms are more commonly found than Gram negative organisms and there has been a dramatic increase in fungal organisms as the cause of sepsis. Other studies have reported that the most common site of infection is the pulmonary system with the abdomen being the second most common site. (4) Angus et al (5) have also suggested, based on extrapolation of discharge coding data from 7 states, that the annual number of severe septic patients in the United States is 750,000. The forecast for the future is quite depressing since it is expected that the yearly incidence will continue to rise at 1.5% per year, based on the growing number of elderly individuals, increased use of invasive and diagnostic procedures, increased use of immunosuppressive and cytotoxic therapies, growing number of individuals who are immunosuppressed, the increase in antibiotic resistance among common bacteria, and possibly our increased awareness of severe sepsis and its sequelae. (2,5)

In an effort to improve the outcome of patients with severe sepsis, 11 organizations convened a consensus conference to establish recommendations for early diagnosis and management of the septic patient. (6) The conference established guidelines entitled the Surviving Sepsis Campaign. The Campaign emphasizes early diagnosis; source control (early initiation of appropriate antibiotics and, if necessary, timely drainage); early goal-directed fluid resuscitation and initiation of vasopressor support to restore hemodynamic function, support of oxygenation and ventilation as necessary; proper use of sedation and analgesia; prevention of the complications of critical illness (venous thromboembolic disease, stress-related mucosal disease, glycemic control); and early nutritional support. (6) The guidelines stressed the importance of using lung protective ventilatory support strategies when acute lung injury and acute respiratory distress syndrome (ARDS) were present. The guidelines also emphasize the need to incorporate weaning protocols to facilitate the separation of patients from mechanical ventilatory support. (6) Recently, the Institute for Healthcare Improvement (IHI) has partnered with the Surviving Sepsis Campaign to help disseminate the recommendations and improve patient outcome.

To simplify the complex implementation of the surviving sepsis guidelines, components were divided into acute resuscitation (6 hours) bundles and sepsis management (24 hours) bundles. (7,8) The acute resuscitation bundle included measuring serum lactate, obtaining blood cultures before antibiotic therapy, early administration of broad-spectrum antimicrobial therapy, fluid resuscitation for hypotension and/or elevated lactate levels using the central venous pressure and central venous or mixed venous oxygen saturation for guidance. When fluid resuscitation alone is not adequate to achieve a mean arterial pressure [greater than or equal to]65 mm Hg after adequate fluid resuscitation, vasopressor therapy should be initiated. (7) The 24-hour sepsis management bundle includes the use of low-dose corticosteroids for septic shock patients who manifest decreased adrenal function as defined by their ICU policy, glycemic control, lung protective ventilatory support strategies, and prudent use of drotrecogin alfa (activated) according to institutional policy. (7) When these bundles were evaluated in 101 consecutive adults with severe sepsis or septic shock managed at two national teaching hospitals in England, they found compliance with the 6-hour bundle in 52%, and 30% for the 24-hour management bundle. (7) The group of patients that met the 6-hour sepsis bundle requirements had a 23% hospital mortality rate compared with a 49% hospital mortality rate in the noncompliant group (RR 2.12, 95% CI 1.20-3.76, P = 0.01). The hospital mortality rate for those patients who were managed according to the 24-hour sepsis management bundle was 29% as compared with 50% for those who did not meet the requirements (RR 1.76, CI 0.84-3.64, P = 0.16). These data support the benefit of using the guidelines as established by the Surviving Sepsis Campaign to improve the outcome of the severe sepsis and septic shock patient.

Unfortunately, adherence to these guidelines is not the complete solution. There are still a number of unanswered questions and specific issues that require more refinement. Among these issues is a better understanding of abnormal adrenal cortisol response to severe sepsis and enhanced identification of those individuals who require physiologic steroid replacement therapy. (9) While tight glucose control with insulin was beneficial in a predominantly surgical population of critically ill patients, it did not result in improved overall outcome in a medical intensive care unit population. (10,11) There has also been slow uptake and utilization of drotrecogin alfa (activated) in severe sepsis, despite being the only United States Food and Drug Administration (FDA) approved agent for use in severe sepsis. (12) Achieving adherence with evidence-based best practices such as the Surviving Sepsis Guidelines is no small task. Despite convincing evidence of improved outcomes, adherence to sepsis guidelines is suboptimal. (7,13) Developing guidelines, making them available, educating practitioners, and advocating adherence will not be sufficient to change behaviors. Rather, changes in practice will require comprehensive attention to institutional systems and processes that promote guideline acceptance and utilization. (14)

The guidelines and use of sepsis management bundles are an excellent starting point to increase physician awareness and standardize sepsis management. We should encourage all to join the campaign, but like all good movements, we can not just rest on this current platform. We must continue to improve our understanding of the septic process and define interventions and management strategies that will further reduce the morbidity and mortality associated with sepsis.

References

1. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: the ACCP/SCCM Consensus Conference Committee. Chest 1992;101:1644-1655.

2. Balk RA. Optimum treatment of severe sepsis and septic shock: evidence in support of the recommendations. Disease-a-Month 2004;50:163-214.

3. Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546-1554.

4. Brun-Buisson C, Doyon F, Carlet J, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter, prospective study in intensive care units: French ICU group for severe sepsis. JAMA 1995;274:968-974.

5. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-1310.

6. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-873.

7. Gao F, Melody T, Daniels DF, et al. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care 2005;9:R764-R770.

8. Trzeciak S, Dellinger RP, Abate NL, et al. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy to septic shock in the emergency department. Chest 2006;129:225-232.

9. Keh D, Sprung CL. Use of corticosteroid therapy in patients with sepsis and septic shock: an evidence-based review. Crit Care Med 2004;32:S527-S533.

10. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Eng J Med 2001;345:1359-1367.

11. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-461.

12. Fourrier F. Recombinant human activated protein C in the treatment of severe sepsis: an evidence-based review. Crit Care Med 2004;32:S534-S541.

13. De Miguel-Yanes JM, Andueza-Lillo JA, Gonzalez-Ramallo VJ, et al. Failure to implement evidence-based clinical guidelines for sepsis at the ED. Am J Emerg Med 2006;24:553-559.

14. Garland A. Improving the ICU: part 2. Chest 2005;127:2165-2179.

Gourang P. Patel, PharmD, BCPS, Ellen H. Elpern, RN, APN, and Robert A. Balk, MD

From the Division of Pulmonary and Critical Care Medicine, Rush Medical College and Rush University Medical Center, Chicago, IL.

Reprint requests to Dr. Robert A. Balk, Division of Pulmonary and Critical Care Medicine, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612. Email: [e-mail]

Accepted November 30, 2006.