American Heart Journal
Volume 150, Issue 6 , Page e1, December 2005

Internal Medicine, University of California Davis Medical School, Redding, CA

Article Outline

 

To the Editor:

Opioid-induced cortisol deficiency may explain much of the increased mortality after the use of morphine during treatment of acute myocardial infarction documented by Meine et al.1 A single 5-mg intravenous dose of morphine sulfate quickly paralyzes cortisol production in opioid-naive men and women2, 3 with a drop of more than 75% from baseline within 3 hours. This drop may be equally profound but slower to develop during oral4 or intrathecal5 therapy and may be universal in opioid-naive subjects but is less commonly found in opioid-tolerant long-term opioid consumers. Occasional episodes of Addisonian crises have been reported to be opioid-induced.5 We have repeatedly documented depressed cortisol levels induced by opioids in opioid-naive patients in our cardiac care unit and intensive care unit, some of these values being less than 2.0 μg/dL but have often been uncertain when and whether to begin replacement corticosteroid therapy.

Reports of improved survival in populations of patients with myocardial infarctions treated with systemic corticosteroids6, 7 may represent inadvertent corticosteroid replacement in cortisol-deficient patients receiving morphine sulfate, rather than reflecting benefit secondary to the anti-inflammatory activity of these steroids, as suggested by other investigators.

The randomized trial proposed by Dr Meine et al should receive high priority but should also include measurement of cortisol levels before and after morphine sulfate administration. Additional studies examining the effectiveness of replacement corticosteroids, perhaps beginning concurrently with morphine administration in patients with acute myocardial infarctions, are also warranted.

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References 

  1. Meine T, Roe M, Chen A, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the crusade quality improvement initiative. Am Heart J. 2005;1–7
  2. Zis A, Haskett R, Albala A, et al. Morphine inhibits cortisol and stimulates prolactin secretion in man. Psychoneuroendocrinology. 1984;9:423–427
  3. Rittmaster RS, Cutler GB, Sobel DO, et al. Morphine inhibits the pituitary-adrenal response to ovine corticotropin-releasing hormone in normal subjects. J Clin Endocrinol Metab. 1985;60:891–895
  4. Woody G, McLellan T, O'Brien C, et al. Hormone secretion in methadone-dependent and abstinent patients. NIDA Res Monogr. 1988;81:216–223
  5. Abs R, Verhelst J, Maeyaert J, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000;85:2215–2222
  6. Giugliano G, Giugliano R, Gibson C, et al. Meta-analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol. 2003;91:1055–1059
  7. Hafezi-Moghdam A, Simoncini T, Yang Z, et al. Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat Med. 2002;8:473–479

PII: S0002-8703(05)00803-3

doi:10.1016/j.ahj.2005.08.014

Refers to article:

  • Association of intravenous morphine use and outcomes in acute coronary syndromes: Results from the CRUSADE Quality Improvement Initiative

    Trip J. Meine, Matthew T. Roe, Anita Y. Chen, Manesh R. Patel, Jeffrey B. Washam, E. Magnus Ohman, W. Frank Peacock, Charles V. Pollack, W. Brian Gibler, Eric D. Peterson, for the CRUSADE Investigators
    American Heart Journal June 2005 (Vol. 149, Issue 6, Pages 1043-1049)

American Heart Journal
Volume 150, Issue 6 , Page e1, December 2005

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