The Impact of Intraoperative N-Acetylcysteine on Opioid Consumption Following Spine Surgery: a Randomized Pilot Trial

Abstract

Aim: N-acetylcysteine (NAC) decreases inflammation and could augment perioperative analgesia. Materials & methods: This prospective pilot trial examined postoperative opioid consumption at 12 h following intraoperative NAC. In phase I, 20 adults scheduled for posterior spine surgery were randomized to NAC (0, 50, 100 and 150 mg/kg) to determine the optimal dose. In phase II, 30 patients were randomized to placebo or NAC (150 mg/kg). Opioid consumption, pain ratings and time to opioid rescue were recorded. Results: Postoperative opioid consumption was reduced in the NAC group 19.3% at 12 h and 20% at 18 and 36 h. Opioid consumption was reduced 22–24% in the NAC group at all times after adjusting for intraoperative opioid administration. NAC subjects reported lower pain scores relative to placebo. Conclusion: Subjects randomized to NAC consumed less postoperative opioids and reported less pain versus placebo. Larger randomized controlled trials are needed to further evaluate NAC for analgesia.

Clinical Trial Registration: NCT04562597 (ClinicalTrials.gov)

Plain language summary

N-acetylcysteine (NAC) is a powerful anti-inflammatory drug used to treat some types of poisoning. It could help pain for patients after surgery. This study looked at how much pain medicine patients needed after back surgery when they received NAC or no drug (placebo). In the first 20 patients, people randomly received placebo or a small, medium or large dose of NAC (0, 50, 100, and 150 mg/kg) with five patients in each group. Since there were only a small number of patients, it was difficult to see any definite differences, and the next 30 patient patients randomly received placebo or the large dose of NAC (150 mg/kg). Patients that were given NAC received 16–22% less opioids in the first 2 days after surgery compared with those that were given placebo. NAC patients also took longer to request pain medications after surgery and reported lower pain scores in the first 2 days after surgery relative to placebo.

Tweetable abstract

N-acetylcysteine (NAC) decreases inflammation and could augment analgesia. Patients undergoing spine surgery received NAC (150 mg/kg) or placebo. NAC reduced postoperative opioid consumption by 16–22% in the first 6–48 h versus placebo.

Keywords::

• acetylcysteine
• analgesia
• anti-inflammatory agents
• neurosurgical procedures
• orthopedic procedures
• pain management

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pmt-2023-0061

Author contributions

SH Wilson. Conflicts of interest: none. This author helped with study conception, study procedures, interpretation of the results, and manuscript writing and editing. JM Sirianni. This author helped with data collection, interpretation of the results, and manuscript writing and editing. KH Bridges. This author helped with data collection, interpretation of the results, and manuscript writing and editing. BJ Wolf. Conflicts of interest: none. This author helped with study design, data interpretation, statistical analysis and manuscript writing and editing. IE Valente. This author helped with data collection and manuscript writing and editing. MD Scofield. Conflicts of interest: none. This author helped with study conception, interpretation of the results, and manuscript writing and editing.

Acknowledgments

We would like to thank the Department of Anesthesia and Perioperative Medicine at the Medical University of South Carolina for financial support and especially thank K Massman, R McFadden and H Nitchie in our research office for their assistance. This work was partially supported by the South Carolina Clinical and Translational Research Institute NIH/NCATS Grant (UL1TR001450).

Financial disclosure

This work was supported by internal departmental support (Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina). This project was also supported by the South Carolina Clinical & Translational Research Institute, Medical University of South Carolina’s CTSA, NIH/NCRR Grant Number 1UL1TR001450. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interest disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The authors certify that this manuscript reports original clinical trial data. Deidentified, individual data that underlie the results reported in this article (text, tables, figures and appendices), along with the study protocol will be available after publication for five years to researchers.

Additional information

Funding

This work was supported by internal departmental support (Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina). This project was also supported by the South Carolina Clinical Translational Research Institute, Medical University of South Carolina CTSA, NIH/NCRR Grant Number 1UL1TR001450. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed