"Remarkable" 20% Drop in Post-Surgery Opioids With Simple, Safe Supplement

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Giving the antioxidant NAC during spine surgery was demonstrated to lower patients' postoperative pain and reduce their need for dangerous opioid drugs

Acute post-surgical pain afflicts over 80% of patients who undergo invasive operations.1 Though opioid medications effectively treat pain, they come with concerning side effects like nausea, constipation, physical dependence, and even mortality from overdose.2 Thus, surgeons aim to minimize opioid use where possible. New research investigates whether an antioxidant drug called N-acetylcysteine (NAC) could reduce patients' pain after spine surgery, lowering their need for opioid painkillers.3

NAC is best known as an antidote for acetaminophen poisoning, but evidence suggests it also holds anti-inflammatory properties.4 Researchers hypothesized NAC could dampen inflammation driving acute post-surgical pain, allowing patients to use fewer opioid pain medications.

The team conducted a two-part pilot randomized controlled trial on patients undergoing posterior spine fusion surgery.5 This invasive spinal procedure often causes significant postoperative pain managed with opioid painkillers.6 In phase I, researchers assigned 20 patients randomly to receive intravenous NAC at doses of 0 mg/kg (placebo), 50 mg/kg, 100 mg/kg, or 150 mg/kg during their operation. The phase aimed to determine the optimal NAC dose to test further.

Researchers then selected the highest dose of 150 mg/kg NAC for a larger phase II trial. They randomly assigned 30 additional patients to receive either intraoperative 150 mg/kg NAC or placebo, monitoring everyone's postoperative pain and opioid use.   

The results showed that patients receiving intraoperative 150 mg/kg NAC consumed 19.3% less opioid pain medication at 12 hours post-surgery compared to the placebo group. This difference held at 18 and 36 hours, with the NAC group using 20% less opioids than placebo subjects at both later times.

Accounting for any intraoperative opioids patients received, the NAC group used 22-24% less postoperative opioids overall across the first 36 hours.7 Individuals receiving NAC during surgery also took longer before needing opioid rescue medications for breakthrough pain and reported lower pain intensity scores.

The researchers conclude that intraoperative NAC appears to provide small but meaningful pain and opioid-sparing effects after invasive spine surgery. They call for larger randomized placebo-controlled trials to confirm the positive impact of this safe, inexpensive intervention. If validated, administering NAC during surgery could benefit countless back surgery patients at risk of prolonged opioid use.8 The simple antioxidant may offer a novel way to enhance recovery and limit pain after this major operation.

Learn more NAC's wide range of therapeutic properties here.


1. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367(9522):1618-1625. doi:10.1016/S0140-6736(06)68700-X

2. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain physician. 2008;11(2 Suppl):S105–S120.

3. Wilson SH, Sirianni JM, Bridges KH, Wolf BJ, Valente IE, Scofield MD. The impact of intraoperative N-acetylcysteine on opioid consumption following spine surgery: a randomized pilot trial. Pain Manag. 2023;13(10):593-602. doi:10.2217/pmt-2023-0061

4. Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 2003;60(1):6-20. doi:10.1007/s000180300001

5. Wilson SH, Sirianni JM, Bridges KH, et al. Pain Manag. 2023;13(10):593-602.

6. Lee DG, Lee SJ, Park SY, Kim DH, Kim DH, Park HS. Comparative efficacy of different postoperative pain management methods for spinal surgery: A network meta-analysis of randomized controlled trials. Medicine (Baltimore). 2020;99(32):e21575. doi:10.1097/MD.0000000000021575

7. Wilson SH, Sirianni JM, Bridges KH, et al. Pain Manag. 2023;13(10):593-602.

8. Clarke H, Soneji N, Ko DT, Yun L, Wijeysundera DN. Rates and risk factors for prolonged opioid use after major surgery: population based cohort study. BMJ. 2014;348:g1251. Published 2014 Feb 11. doi:10.1136/bmj.g1251

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