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Postoperative pain reduction by pre-emptive N-acetylcysteine: an exploratory randomized controlled clinical trial
  1. Chantal Elise Mulkens1,
  2. Marieke Staatsen2,
  3. Lucie van Genugten3,
  4. Barbara A M Snoeker4,
  5. Kris C P Vissers1,
  6. Jörgen Bruhn1 and
  7. Martin J L Bucx1
  1. 1Department of Anesthesiology, Pain and Palliative Medicine, Radboudumc, Nijmegen, Gelderland, The Netherlands
  2. 2Department of Anesthesiology, Máxima Medical Centre, Eindhoven, Noord-Brabant, The Netherlands
  3. 3Department of Anesthesiology, Slingeland Hospital, Doetinchem, The Netherlands
  4. 4Department of Clinical Epidemiology, Biostatistics and Bioinformatics, University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Chantal Elise Mulkens, Department of Anesthesiology, Pain and Palliative Medicine, Radboudumc, Nijmegen, Gelderland, Netherlands; chantal.mulkens{at}


Background A new potential target for multimodal pain management is the group-II metabotropic glutamate receptor subtypes, which can be activated by N-acetylcysteine. We investigated whether pre-emptive administration of N-acetylcysteine leads to a reduction in postoperative pain after laparoscopic inguinal hernia repair.

Methods Sixty American Society of Anesthesiologists I-II patients scheduled for elective inguinal hernia repair were randomized to receive either N-acetylcysteine (150 mg/kg) or placebo intravenously 1 hour before surgery. The primary outcome was the visual analogue score during movement in the morning (approximately 24 hours) after surgery. Among secondary outcomes were postoperative opioid consumption and safety of intravenous N-acetylcysteine.

Results In total, 23 patients were analyzed per group. Pain scores were similar at all timepoints with a 24 hours median score of 34 (IQR of 19.0 to 42.5) in the N-acetylcysteine group and a median score of 26 (16.0 to 50.0) in the placebo group. The percentage of patients using opioids after surgery was 22% versus 39% day 1 (p=0.63); 9% versus 26% day 2 (p=0.14); 9% versus 17% day 3 (p=0.35) in the N-acetylcysteine group compared with placebo group. Side effects resembling anaphylactoid reactions in response to the administration of N-acetylcysteine were present in more than half of the patients.

Conclusions Without finding important differences between N-acetylcysteine and placebo group in pain scores postoperatively, but with a high percentage of bothersome side effects for the N-acetylcysteine group, we would not recommend the use of pre-emptive intravenous N-acetylcysteine to reduce postoperative pain in laparoscopic inguinal hernia repair patients based on this study.

Trial registration number NCT03354572.

  • ambulatory care
  • analgesia
  • pain
  • postoperative

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Contributors All authors contributed to this manuscript accordingly.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.