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Methylprednisolone Does Not Reduce Acute Postoperative Pain After Cardiac Surgery: Subanalysis of a Randomized Clinical Trial

Turan, Alparslan MD*,†; Cohen, Barak MD*,‡; Whitlock, Richard P. MD§; Essber, Hani MD*; Niazi, Azfar MD*; Makarova, Natalya MSc*‖; Saasouh, Wael MD; Alfirevic, Andrej MD#; Marciniak, Donn MD#; Sessler, Daniel I. MD*

doi: 10.1213/ANE.0000000000004061
Cardiovascular and Thoracic Anesthesiology: Original Clinical Research Report

BACKGROUND: Pain after cardiac surgery is largely treated with opioids, but their poor safety profile makes nonopioid medications attractive as part of multimodal pathways. Anti-inflammatory drugs reduce acute postoperative pain, but the role of steroids in reducing acute poststernotomy pain is unclear. We evaluated the association between the intraoperative administration of methylprednisolone and postoperative analgesia, defined as a composite of pain scores and opioid consumption, during the initial 24 hours after cardiac surgery.

METHODS: We conducted a post hoc retrospective analysis of a large clinical trial in which adults having cardiac surgery were randomized 1:1 to receive 2 intraoperative doses of 250 mg IV methylprednisolone or placebo. Pain scores and opioid consumption were collected during the initial 24 hours after surgery. Methylprednisolone was considered to be associated with better pain control than placebo if proven noninferior (not worse) on both pain scores (defined a priori with delta of 1 point) and opioid consumption (delta of 20%) and superior to placebo in at least 1 of the 2 outcomes. This test was repeated in the opposite direction (testing whether placebo is better than methylprednisolone on postoperative pain management).

RESULTS: Of 251 eligible patients, 127 received methylprednisolone and 124 received placebo. Methylprednisolone was noninferior to placebo on pain with difference in mean (CI) pain scores of −0.25 (−0.71 to 0.21); P < .001. However, methylprednisolone was not noninferior to placebo on opioid consumption (ratio of geometric means [CI]: 1.11 [0.64–1.91]; P = .37). Because methylprednisolone was not noninferior to placebo on both outcomes, we did not proceed to superiority testing based on the a priori stopping rules. Similar results were found when testing the opposite direction.

CONCLUSIONS: In this post hoc analysis, we could not identify a beneficial analgesic effect after cardiac surgery associated with methylprednisolone administration. There are currently no data to suggest that methylprednisolone has significant analgesic benefit in adults having cardiac surgery.

From the Departments of *Outcomes Research

General Anesthesia, Cleveland Clinic, Cleveland, Ohio

Division of Anesthesia, Critical Care and Pain Management, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel

§Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada

Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio

Department of Anesthesiology, Detroit Medical Center, Detroit, Michigan

#Department of Cardiothoracic Anesthesia Cleveland Clinic, Cleveland, Ohio.

Published ahead of print 18 February 2019.

Accepted for publication January 4, 2019.

Funding: This work received internal funding. B.C. is a recipient of a Fellowship Grant from the American Physicians Fellowship for Medicine in Israel.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Alparslan Turan, MD, Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave, P77, Cleveland, OH 44195. Address e-mail to

Copyright © 2019 International Anesthesia Research Society
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