Increased Postoperative Opioid Consumption in the Presence of Co-administration of 5-HT3 Antagonists with Acetaminophen: A Hospital Registry Study

Nikolai Ratajczak; Ricardo Munoz-Acuna; Simone Redaelli; Aiman Suleiman; Eva-Lotte Seibold; Dario von Wedel; Denys Shay; Sarah Ashrafian; Guanqing Chen; Eswar Sundar; Elena Ahrens; Luca J Wachtendorf; Maximilian S Schaefer

doi:10.1097/ALN.0000000000005033

Increased Postoperative Opioid Consumption in the Presence of Co-administration of 5-HT3 Antagonists with Acetaminophen: A Hospital Registry Study

Anesthesiology. 2024 May 3. doi: 10.1097/ALN.0000000000005033. Online ahead of print.

Authors

Nikolai Ratajczak^{1

2}, Ricardo Munoz-Acuna^{1

2}, Simone Redaelli^{1

2

3}, Aiman Suleiman^{1

2

4}, Eva-Lotte Seibold^{1

2}, Dario von Wedel^{1

2}, Denys Shay^{1

2

5}, Sarah Ashrafian^{1

2}, Guanqing Chen^{1

2}, Eswar Sundar¹, Elena Ahrens^{1

2}, Luca J Wachtendorf^{1

2}, Maximilian S Schaefer^{1

2

6}

Affiliations

¹ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
² Center for Anesthesia Research Excellence (CARE), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³ School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
⁴ Department of Anesthesia and Intensive Care, Faculty of Medicine, University of Jordan, Amman, Jordan.
⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁶ Department of Anesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany.

PMID: 38700445
DOI: 10.1097/ALN.0000000000005033

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, United States of America, from 2015 to 2022. Using binary exposure variables and a comprehensive selection of pre-planned patient- and procedure-related covariates for confounder control, we investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in mg oral morphine equivalents (OME) administered in the post-anesthesia care unit (PACU). A multivariable, zero-inflated negative binomial regression model was applied.

Results: 3,166 (5.8%) patients 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 PACU opioid dose was 7.5 mg OME (interquartile range 7.5 to 14.3 mg OME) among 16,640/55,016 (30.3%) patients who received opioids and the average 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=0.012).

Conclusion: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were co-administered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis.