Increased Postoperative Opioid Consumption in the Presence of Coadministration of 5-Hydroxytryptamine Type 3 Antagonists with Acetaminophen: A Hospital Registry Study

Author:

Ratajczak Nikolai1,Munoz-Acuna Ricardo2ORCID,Redaelli Simone3ORCID,Suleiman Aiman4ORCID,Seibold Eva-Lotte5ORCID,von Wedel Dario6ORCID,Shay Denys7ORCID,Ashrafian Sarah8,Chen Guanqing9ORCID,Sundar Eswar10ORCID,Ahrens Elena11ORCID,Wachtendorf Luca J.12,Schaefer Maximilian S.13

Affiliation:

1. 1Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

2. 2Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

3. 3Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

4. 4Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Anesthesia and Intensive Care, Faculty of Medicine, University of Jordan, Amman, Jordan.

5. 5Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

6. 6Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

7. 7Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

8. 8Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

9. 9Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

10. 10Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

11. 11Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

12. 12Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

13. 13Department of Anesthesia, Critical Care and Pain Medicine, and Center for Anesthesia Research Excellence, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany.

Abstract

Background Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen’s analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting. Methods This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied. Results A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a –5.5% (95% CI, –9.6 to –1.4%; P = 0.009; adjusted absolute difference, –0.19 mg OME; 95% CI, –0.33 to –0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, –0.06 to 0.05; P = 0.93; P for interaction = 0.013). Conclusions A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Publisher

Ovid Technologies (Wolters Kluwer Health)

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