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Correspondence |

Steroids in Patients With Septic Shock FREE TO VIEW

Charles L. Sprung, MD, FCCP; Djillali Annane, MD, PhD; Mervyn Singer, MD; Brian H. Cuthbertson, MD; Josef Briegel, MD, PhD
Author and Funding Information

Affiliations: Hadassah Hebrew University Medical Center Jerusalem, Israel,  Raymond Poincaré Hospital Assistance Publique–Hôpitaux de Paris Garches, France,  University College London London, UK,  University of Aberdeen Aberdeen, UK,  Ludwig-Maximilians-Universitaet Munich, Germany

Correspondence to: Charles L. Sprung, MD, FCCP, Hadassah Medical Center, Department of Anesthesiology, Hadassah University Hospital, PO Box 12000, Jerusalem 91120, Israel; e-mail: sprung@cc.huji.ac.il


The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(1):323-324. doi:10.1378/chest.09-0329
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To the Editor:

We are concerned that Dr. Marik's recommendations in a recent CHEST article (January 2009)1 on managing critical illness-related corticosteroid insufficiency contain inaccuracies, diverge from recent expert consensus statements, and may potentially compromise patient outcomes.

As authors of the Corticosteroid Therapy of Septic Shock (CORTICUS) study,2 we readily acknowledge its limitations, especially underpowering. However, as the largest study in this field, the results cannot be simply dismissed because of their direction. Despite many patients being ineligible for the study due to concomitant steroid treatment, the research team retained clinical equipoise during patient enrollment.3 Although our cohort was not as severely ill as the population of Annane et al,4 they were more representative of the “typical” septic shock patient and significantly sicker than those Dr. Marik1 has suggested should receive steroids. Indeed, he suggested giving hydrocortisone with norepinephrine doses of > 0.05 to 0.1 μg/kg/min, while in the CORTICUS study2 the mean dose at randomization for norepinephrine was 0.4 μg/kg/min.

An increased death rate was found in patients receiving etomidate in the CORTICUS study2 but etomidate was not identified as an independent risk factor for death. Notwithstanding more superinfections (including new septic shock) occurring in the hydrocortisone group, repeat shock episodes were similar to the placebo group. Although reducing the dose or ceasing hydrocortisone therapy led to an increase of interleukin-6 levels on day 12, interleukin-6 levels were similar to those of the control group on day 12. Thus, these data alone are insufficient to support the prolonged application of steroids.

We have witnessed many negative outcome studies of immunomodulatory agents in cases of sepsis. An important reason for this lack of success may be the enrollment of heterogeneous populations of patients with syndromes rather than specific diseases.5 While it would be convenient to have a unifying theory regarding the roles of systemic inflammation and immune dysregulation in patients with various sepsis syndromes,1 it is perhaps oversimplistic to believe that one therapy will be effective for all. Marik1 also implies that steroids should be used in patients receiving etomidate, with severe community-acquired pneumonia, during ventilatory weaning, undergoing cardiac surgery, and in critically ill patients with liver disease.

Two recent consensus statements6,7 developed by many expert panels (including the one Dr. Marik chaired) provided evidence-based guidelines for the use of corticosteroids in septic patients. Dr. Marik's opinions diverge from these guidelines, which are more conservative in nature regarding concerns surrounding harm. Thus, specific recommendations such as starting steroid therapy based on vasopressor dose and time from presentation, tapering, and longer duration of treatment (16 to 19 days) cannot be endorsed from current data. Steroid use in septic patients without shock is counter to one of the consensus guidelines.6 Dr. Marik acknowledged the need for careful infection surveillance to limit the complications of corticosteroid treatment, yet, arguably, the avoidance of drug treatment (or a more limited duration of treatment) would prove far more effective in nonproven indications. It is important to provide a balanced perspective to the debate and primum non nocere.

Marik PE. Critical illness-related corticosteroid insufficiency. Chest. 2009;135:181-193. [PubMed] [CrossRef]
 
Sprung CL, Annane D, Keh D, et al. The CORTICUS randomized, double-blind, placebo-controlled study of hydrocortisone therapy in patients with septic shock. N Engl J Med. 2008;358:111-124. [PubMed]
 
Sprung CL, Singer M, Annane D, et al. Corticosteroids for septic shock. N Engl J Med. 2008;358:2070-2071. [PubMed]
 
Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-870. [PubMed]
 
Eidelman LA, Sprung CL. Why have new effective therapies for sepsis not been developed? Crit Care Med. 1994;22:1330-1334. [PubMed]
 
Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock; 2008. Crit Care Med. 2008;36:296-327. [PubMed]
 
Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36:1937-1949. [PubMed]
 

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References

Marik PE. Critical illness-related corticosteroid insufficiency. Chest. 2009;135:181-193. [PubMed] [CrossRef]
 
Sprung CL, Annane D, Keh D, et al. The CORTICUS randomized, double-blind, placebo-controlled study of hydrocortisone therapy in patients with septic shock. N Engl J Med. 2008;358:111-124. [PubMed]
 
Sprung CL, Singer M, Annane D, et al. Corticosteroids for septic shock. N Engl J Med. 2008;358:2070-2071. [PubMed]
 
Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-870. [PubMed]
 
Eidelman LA, Sprung CL. Why have new effective therapies for sepsis not been developed? Crit Care Med. 1994;22:1330-1334. [PubMed]
 
Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock; 2008. Crit Care Med. 2008;36:296-327. [PubMed]
 
Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36:1937-1949. [PubMed]
 
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