Vol. 15 No. 2 March/April 2008

EDITORIAL

REVISED SURVIVING SEPSIS GUIDELINES – A BIT MORE USER-FRIENDLY

The Surviving Sepsis Campaign (SSC) has worked hard to decrease the mortality from sepsis throughout the world. The original guidelines were published in 20041, and the SSC has worked with the Institute for Healthcare Improvement to help hospitals and ICUs implement these guidelines. The SSC recognizes that periodic revision of the guidelines is essential to keep the guidelines current if success in decreasing mortality is to be long-term. In 2007, the guidelines revision committee met, and over the year, revised the guidelines, including the most recent studies relating to sepsis^2,3.
The first major change in the guidelines is the use of the GRADE system for assessment of the quality of the evidence and to determine the strength of the recommendations. The new system is more user-friendly to the clinician. Each recommendation is graded 1 (strong) or 2 (weak), based on the consensus of the guidelines revision group. This gives the clinician an immediate understanding of the consensus on the clinical importance of the recommendation. A strong recommendation indicates that the committee believes that one should (or in the case of a negative recommendation, should not) do that particular intervention. A weak recommendation indicates that the committee does not believe there is sufficient clinical or literature evidence to mandate the treatment, but that it can be considered. The letters A-D for each recommendation reflect the strength of the literature. The new grading system is useful because there are some elements of management that clearly should be done, but will never be tested in randomized controlled trials (RCTs). The more recent RCTs have often been single studies, and the implementation of these therapies is often quite controversial. In the revised guidelines, several of these recommendations are grade 2 despite a positive RCT in the literature, reflecting the committee’s uncertainty as to whether the benefits of some of the newer therapies outweigh the risks.
The guidelines revision committee considered both publications and abstracts that have been published since the 2004 guidelines. Some of the newest (and perhaps most controversial) studies have recently been published in full manuscript form^4-6. Although the guidelines committee did not have the full manuscript to review, some of the authors of the more recent studies participated in the guidelines revision process, and so the data were available for discussion. Like the original guidelines process, a consensus process was used to develop and grade the recommendations.
The revised guidelines continue to emphasize the importance of early resuscitation and prompt, appropriate antibiotic administration. Based on the recent CORTICUS trial, the use of corticosteroids is down-graded, to a suggestion that steroid therapy be used for patients with shock poorly responsive to fluids and vasopressors4. The use of recombinant human activated protein C has been down-graded as well, reflecting the committee’s concerns regarding the risk of bleeding and the cost of the drug, coupled with uncertain benefit. Glucose control continues to be recommended, with a suggested target of <150 mg/dL. The revised guidelines are divided in to a section on the management of severe sepsis and a section on supportive therapy.
Guidelines by themselves are only useful if they are brought to the bedside to improve the management of the critically ill patient. There is a growing body of evidence that implementation of guidelines improves outcome. In a paper commented on in the last issue of the Monitor, Afessa and colleagues reported that the adoption of multiple clinical practice protocols improved outcome in their critically ill medical patients, especially those who were sicker⁷. Zambon et al. evaluated the effect of implementing the sepsis bundles in their ICU, and reported that compliance with the 6 hour bundle was obtained in 72% of their patients, and associated with both lower mortality and shorter ICU stay8. Interestingly, compliance with the 24 hour sepsis bundle within 12 hours was also associated with lower mortality and shorter length of stay, perhaps suggesting that faster implementation of these guidelines may add additional outcome benefit.
The revised guidelines reflect the state of the literature and our clinical experience to date. Periodic revisions of the Guidelines will be important to keep moving toward the target of reducing mortality from severe sepsis and septic shock.

Margaret M. Parker, MD, FCCM,
Professor of Pediatrics, Medicine, and Anesthesia,
Director of Pediatric Critical Care Medicine,
SUNY at Stony Brook, NY 11794-8111 USA.

References (to the Editorial):
1. Dellinger RP, Carlet JM, Masur H et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-872. (See also Intensive Care Monitor 2004;11:41 Editorial).
2. Dellinger RP, Levy MM, Carlet JM, Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327. (See p. 33).
3. Dellinger RP, Levy MM, Carlet JM. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intens Care Med 2008;34:17-60. (See p. 33)
4. Sprung CL, Annane D, Keh D et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111-124. (See also Intensive Care Monitor 2008;15:14).
5. Brunkhorst FM, Engel C, Bloos F et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358:125-139. (See also Intensive Care Monitor 2008;15:2).
6. Russell JA, Walley KR, Singer J et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008;358:877-887.
7. Afessa B, Gajic O, Keegan MT et al. Impact of introducing multiple evidence-based clinical practice protocols in a medical intensive care unit: a retrospective cohort study. BMC Emergency Med 2007;7:10.
(See also Intensive Care Monitor 2008;15:9).
8. Zambon M, Ceola M, Almeida-de-Castro R, Gullo A, Vincent J-L. Implementation of the Surviving Sepsis Campaign guidelines for severe sepsis and septic shock: We could go faster. J Crit Care 2007. In Press. Published online 11 December 2007 (doi:10.1016/j.jcrc.2007.08.003).

Content

CARDIOVASCULAR

The following papers have been extracted and commented upon:

Diaz R, Goyal A, Mehta SR et al. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA 2007; 298: 2399–2405.

Evidence Level: II

McMurray JJV, Teerlink JR, Cotter G et al. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA 2007; 298: 2009–2019.

Evidence Level: II

ICM RECOMMENDED REVIEW PAPER

Tapson VF. Acute pulmonary embolism. N Engl J Med 2008;358:1037-1052. 98 references.

END OF LIFE

ICM RECOMMENDED REVIEW PAPERS

Qaseem A, Snow V, Shekelle P, Casey Jr DE, Cross JT, Owens DK for the Clinical Efficacy Assessment Subcommitttee of the American College of Physicians. Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2008;148:141-146. 54 references.

Lorenz KA, Lynn J, Dy SM et al. Evidence for improving palliative care at the end of life: A systematic review. Ann Intern Med 2008;148:147-149. 152 references.

Goldstein NE, Fischberg D. Update in palliative medicine. Ann Intern Med 2008;148:135-140. 23 references.

GASTROINTESTINAL

The following paper has been extracted and commented upon:

Hickson M, D’Souza AL, Muthu N et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007; 335: 80-85.

Bright idea

Evidence Level: II

ICM RECOMMENDED REVIEW PAPER

Frossard J-L, Steer ML, Pastor CM. Acute pancreatitis. Lancet 2008;371:143-152. 126 references.

HEPATOLOGY

ICM RECOMMENDED REVIEW PAPER

Stravitz RT, Kramer AH, Davern T et al. Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med 2007;35:2498-2508. 136 references.

METABOLISM

ICM RECOMMENDED REVIEW PAPER

Kitabchi AE, Freire AX, Umpierrez GE. Evidence for strict inpatient blood glucose control: time to revise glycemic goals in hospitalized patients. Metabol Clin Experimental 2008;57:116-120. 44 references.

NEUROLOGY

ICM RECOMMENDED REVIEW PAPERS

Sendi P, Bregenzer T, Zimmerli W. Spinal epidural in clinical practice. Q J Med 2008;101:1-12. 88 references.

Logan SAE, MacMahon E. Viral meningitis. BMJ 2008; 336:36-40. 30 references.

ORGANIZATION

ICM RECOMMENDED REVIEW PAPER

Towey RM, Ojara S. Intensive care in the developing world. Anaesthesia 2007;62(Suppl. 1):32-37. 31 references.

OUTCOME

The following paper has been extracted and commented upon:

Garnacho-Montero J, Ortiz-Leyba C, Herrera-Melero I et al. Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis: a matched cohort study. J Antimicrob Chemother 2008; 61: 436–441.

Evidence Level: III

ICM RECOMMENDED REVIEW PAPER

Stroebe M, Schut H, Stroebe W. Health outcomes of bereavement. Lancet 2007;370:1960-1973. 187 references.

PAEDIATRIC

The following paper has been extracted and commented upon:

Duffett M, Choong K, Ng V, Randolph A, Cook DJ.Surfactant therapy for acute respiratory failure in children: a systematic review and meta-analysis. Crit Care 2007: 11: R66 (doi:10.1186/cc5944)

Top Quality Research

Evidence Level: I

RENAL

The following papers have been extracted and commented upon:

Kheterpal S, Tremper KK, Englesbe MJ et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology 2007; 107: 892–902.

Evidence Level: IV

Kelly AM, Dwamena B, Cronin P, Bernstein SJ, Carlos RC. Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med 2008; 148: 284–294.

Top Quality Research

Evidence Level: I

RESPIRATORY

The following papers have been extracted and commented upon:

Lorente L, Lecuona M, Jiménez A et al. Influence of an endotracheal tube with polyurethane cuff and subglottic secretion drainage on pneumonia. Am J Respir Crit Care Med 2007;176:1079-1083.

Evidence Level: II

Meersseman W, Lagrou K, Maertens J et al. Galactomannan in broncho-alveolar lavage fluid. A tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 2008;177:27–34.

Bright idea

Evidence Level: III

ICM RECOMMENDED REVIEW PAPERS

Mazzulli T. Value of RVP in clinical settings: intensive care. J Clin Virol 2007;40:S55-S57. 19 references.

Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza (H5N1) virus infection in humans. N Engl J Med 2008; 358:261-273. 76 references.

Muscarella LF. Reassessment of the risk of healthcare-acquired infection during rigid laryngoscopy. J Hosp Infection 2008;68:101-107. 55 references.

SEPSIS

The following papers have been extracted and commented upon:

Dellinger RP, Levy MM, Carlet JM et al; for the International Surviving Sepsis Campaign Guidelines Committee. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 Crit Care Med 2008;36:296–327. Also published in Intensive Care Med 2008;34:17-60.

Evidence Level: V

Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E. Clinical and microbiological outcomes of serious infections with multidrug-resistant Gram-negative organisms treated with tigecycline. Clin Infect Dis 2008; 46: 567–570.

Evidence Level: IV

Kim S-H, Kim K-H, Kim H-B et al. Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia. Antimicrobial Agents Chemother 2008; 52: 192–197.

Could change clinical practice

Evidence Level: III

Trautmann M, Pollitt A, Loh U et al. Implementation of an intensified infection control program to reduce MRSA transmissions in a German tertiary care hospital. Am J Infect Control 2007; 35: 643-649.

Could change clinical practice

Evidence Level: IV

Pashman J, Bradley EH, Wang H, Higa B, Fu M, Dembry LM. Promotion of hand hygiene techniques through use of a surveillance tool. J Hosp Infect 2007; 66: 249–254.

Evidence Level: V

ICM RECOMMENDED REVIEW PAPERS

Dancer SJ. The effect of antibiotics on methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 2008; 61:246-253. 88 references.

Rice LB. The Maxwell Finland Lecture: For the duration – rational antibiotic administration in an era of antimicrobial resistance and Clostridium difficile. Clin Infect Dis 2008; 46:491-496. 32 references.

Sax H, Allegranzi B, Uçkay I, Larson E, Boyce J, Pittet D. ‘My five moments for hand hygiene’: a user-centred design approach to understand, train, monitor and report hand hygiene. J Hosp Infection 2007;67:9-21. 72 references.

Questions

1. Probiotics:
a. Use of Saccharomyces boulardii in the critically ill has been associated with a high incidence of Saccharomyces boulardii fungaemia.
b. Reduce the incidence of post-operative infections in liver transplant recipients.
c. Have been associated with increased mortality in patients with pancreatitis.
d. A paper reviewed in this in this issue of the Monitor demonstrates that probiotics reduce the incidence of antibiotic-induced diarrhoea in critically ill patients.

2. Invasive Aspergillosis:
a. Cerebral Aspergillosis occurs in 10-20% of cases.
b. Asymptomatic acute pulmonary disease is uncommon.
c. Tracheobronchitis is less common in patients with AIDS.
d. A paper reviewed in this issue of the Monitor demonstrates that bronchoalveolar lavage fluid galactomannan is a highly specific method of diagnosing invasive Aspergillosis.

3. Renal replacement therapy (RRT):
a. Use of shorter (15 cm) femoral catheters prolongs haemofilter life compared with use of longer (20 cm) catheters.
b. Drug sieving coefficient is usually related to protein binding.
c. Effective use of lactate buffer in patients receiving haemofiltration is dependent on liver function.
d. A paper reviewed in this issue of the Monitor demonstrates that RRT is required in 0.01% of patients with normal pre-operative renal function undergoing major non-cardiac non-vascular surgery.

4. Vancomycin:
a. Disrupts DNA synthesis.
b. The intravenous preparation can be given enterally.
c. May cause ototoxicity.
d. A paper reviewed in this issue of the Monitor demonstrates that vancomycin is as efficacious as beta lactams for the treatment of methicillin sensitive Staphylococcus aureus.

Answers

Answers to questions featured in Intensive Care Monitor Vol. 15 No. 2 March/April 2008:

1. Probiotics: TTTF
2. Invasive Aspergillosis: TFFF
3. Renal replacement therapy (RRT): FTTF
4. Vancomycin: TTTF