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Effect of Intravenous Acetaminophen on Postoperative Hypoxemia After Abdominal SurgeryThe FACTOR Randomized Clinical Trial

Educational Objective
To learn the effect of intravenous acetaminophen on respiratory, pain, and other short-term postoperative clinical outcomes among patients undergoing abdominal surgery.
1 Credit CME
Key Points

Question  What is the effect of postoperative administration of intravenous acetaminophen, which is hypothesized to reduce opioid consumption, on postoperative hypoxemia after abdominal surgery?

Findings  In this randomized clinical trial that included 570 patients, the median duration of postoperative hypoxemia (defined as hemoglobin oxygen saturation <90%) was 0.7 minutes per hour in the acetaminophen group and 1.1 minutes per hour in the control group, a difference that was not statistically significant.

Meaning  After abdominal surgery, intravenous acetaminophen did not significantly reduce the duration of postoperative hypoxemia over 48 hours.


Importance  Opioid-induced ventilatory depression and hypoxemia is common, severe, and often unrecognized in postoperative patients. To the extent that nonopioid analgesics reduce opioid consumption, they may decrease postoperative hypoxemia.

Objective  To test the hypothesis that duration of hypoxemia is less in patients given intravenous acetaminophen than those given placebo.

Design, Setting, and Participants  Randomized, placebo-controlled, double-blind trial conducted at 2 US academic hospitals among 570 patients who were undergoing abdominal surgery, enrolled from February 2015 through October 2018 and followed up until February 2019.

Interventions  Participants were randomized to receive either intravenous acetaminophen, 1 g (n = 289), or normal saline placebo (n = 291) starting at the beginning of surgery and repeated every 6 hours until 48 postoperative hours or hospital discharge, whichever occurred first.

Main Outcomes and Measures  The primary outcome was the total duration of hypoxemia (hemoglobin oxygen saturation [Spo2] <90%) per hour, with oxygen saturation measured continuously for 48 postoperative hours. Secondary outcomes were postoperative opioid consumption, pain (0- 10-point scale; 0: no pain; 10: the most pain imaginable), nausea and vomiting, sedation, minimal alveolar concentration of volatile anesthetic, fatigue, active time, and respiratory function.

Results  Among 580 patients randomized (mean age, 49 years; 48% women), 570 (98%) completed the trial. The primary outcome, median duration with Spo2 of less than 90%, was 0.7 (interquartile range [IQR], 0.1-5.1) minutes per hour among patients in the acetaminophen group and 1.1 (IQR, 0.1-6.6) minutes per hour among patients in the placebo group (P = .29), with an estimated median difference of −0.04 (95% CI,−0.18 to 0.11) minutes per hour. None of the 8 secondary end points differed significantly between the acetaminophen and placebo groups. Mean pain scores within initial 48 postoperative hours were 4.2 (SD, 1.8) in the acetaminophen group and 4.4 (SD, 1.8) in the placebo group (difference, −0.28; 95% CI, –0.71 to 0.15); median opioid use in morphine equivalents was 50 mg (IQR, 18-122 mg) and 58 mg (IQR, 24-151 mg) , respectively, with a ratio of geometric means of 0.86 (95% CI, 0.61-1.21).

Conclusions and Relevance  Among patients who underwent abdominal surgery, use of postoperative intravenous acetaminophen, compared with placebo, did not significantly reduce the duration of postoperative hypoxemia over 48 hours. The study findings do not support the use of intravenous acetaminophen for this purpose.

Trial Registration  ClinicalTrials.gov Identifier: NCT02156154

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Article Information

Corresponding Author: Alparslan Turan, MD, Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave, P-77, Cleveland, OH 44195 (turana@ccf.org).

Accepted for Publication: May 22, 2020.

Author Contributions: Dr Turan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Ms Makarova conducted and is responsible for the data analysis. Because of her maternity leave, the revision was done by Mr Yang and Dr Mascha, who are also responsible for the data analysis and manuscript writing.

Concept and design: Turan, Saasouh, Hovsepyan, Makarova, Ayad, Soliman, Maheshwari, Ali Sakr Esa, Delaney, Sessler.

Acquisition, analysis, or interpretation of data: Turan, Essber, Saasouh, Hovsepyan, Makarova, Ayad, Cohen, Ruetzler, Yang, Mascha, Kessler, Delaney, Sessler.

Drafting of the manuscript: Turan, Essber, Saasouh, Makarova, Ayad, Ruetzler, Soliman, Maheshwari, Mascha, Ali Sakr Esa, Sessler.

Critical revision of the manuscript for important intellectual content: Turan, Essber, Saasouh, Hovsepyan, Makarova, Ayad, Cohen, Ruetzler, Maheshwari, Yang, Mascha, Kessler, Delaney, Sessler.

Statistical analysis: Turan, Essber, Makarova, Ayad, Yang, Mascha.

Obtained funding: Turan.

Administrative, technical, or material support: Turan, Essber, Hovsepyan, Ayad, Cohen, Ruetzler, Soliman, Maheshwari, Ali Sakr Esa, Kessler, Delaney, Sessler.

Supervision: Turan, Saasouh, Hovsepyan, Ayad, Soliman, Mascha, Ali Sakr Esa, Kessler, Sessler.

Conflict of Interest Disclosures: None reported.

Funding/Support: The study was funded by an investigator-initiated research grant from Mallinckrodt Pharmaceuticals. Sotera and Respiratory Motion provided devices and disposables.

Role of the Funder/Sponsor: The study supporters had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The authors had sole authority for the data, analysis, write-up, and submission.

Group Information: The FACTOR Study Group: Cleveland Clinic Main Campus: Christine Chang, MD, Michael Walters, MD, Tatyana Kopyeva, MD, Emre Gorgun, MD, Scott R Steele, MD, Joseph Vitale, David Chelnick, Janet Adegboye, MD. Cleveland Clinic Fairview Hospital: Azfar Niazi, MD, Partha Saha, MD.

Data Sharing Statement: See Supplement 3.

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