Structured abstract
Question
In patients with septic shock and relative adrenal insufficiency, does adrenal replacement therapy improve survival compared to placebo?
Design
Blinded (patients, investigators, and outcome assessors), randomized placebo-controlled trial.
Setting
Nineteen intensive care units across France between September 1995 and March 1999.
Patients
Three hundred thirty men and women > 18 yr of age, who met standard criteria for septic shock. There were no differences in baseline characteristics.
Intervention
After undergoing a 250 μg synthetic adrenocorticotropin (ACTH) stimulation test, patients were allocated to receive hydrocortisone 50 mg iv Q6H and fludrocortisone 50 μg tablet once daily or matching placebos for seven days.
Main outcome measures
The primary outcome was 28-day survival in patients with sepsis and relative adrenal insufficiency (designated as nonresponders to the corticotropin test on the basis of less than a 248 nmol·L−1 incremental change in cortisol following a 250 μg ACTH stimulation test). Secondary outcomes included time to withdrawal of vasopressor therapy. All patients were evaluated on an intention-to-treat basis (one patient was excluded due to consent withdrawal; one patient who died prior to placebo administration was included).
Results
Seventy-six percent (229 of the 330 patients) were nonresponders to the ACTH stimulation test (115 in the placebo group; 114 in the treatment group).
For the primary outcome, mortality in the nonresponder treatment group was 53% (60 out of 114) vs 63% (73 out of 115) amongst the nonresponder placebo group [hazard ratio 0.67; 95% confidence interval (CI) 0.47–0.95;P = 0.02].
For the secondary outcome, vasopressor therapy was withdrawn more often within 28 days in the nonresponder treatment group vs the nonresponder placebo group (57% vs 40% of patients; hazard ratio, 1.91; 95% CI, 1.29–2.84;P = 0.001).
Amongst responders, there were no significant differences between treatment and placebo groups. Adverse event rates were similar in groups of responders and nonresponders.
Conclusion
Adrenal replacement therapy in patients with relative adrenal insufficiency and sepsis improves 28-day survival without increasing adverse events.
Author’s recommendation
After performing a 250 μg ACTH stimulation test, adrenal replacement therapy should be instituted in all patients with sepsis requiring inotropic support until results are made available.
Funding
Groupe d’Étude et de Recherche sur le Médicament (GERMED).
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References
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Meggison, H., Jones, G. Best evidence in critical care medicine. Can J Anesth 51, 264–265 (2004). https://doi.org/10.1007/BF03019108
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DOI: https://doi.org/10.1007/BF03019108