Tolerability and efficacy profile of S-ketamine compared with racemic ketamine in surgical patients, a prospective observational before-and-after study in the perioperative settingEditor's key points

Background: While the S-enantiomer of Ketamine (S-Ketamine) is described to be more potent than the racemic form (Ra-Ketamine), with a shorter half-life and almost no side effects, both forms have never been compared in real life. This before-after observational study leverages an institutional switch across multiple hospitals from Ra- to S-Ketamine to compare their efficacy and tolerance profile. The primary aim was to assess the occurrence of hallucination in patients receiving racemic Ketamine compared with S-Ketamine, as a proxy for ketamine's tolerance, as it is the most specific adverse effect. Methods: This is a prospective, observational, before-aafter, multicentre study conducted in the four centres of the APHP Sorbonne Universite hospitals consortium (GHU Sorbonne Universite), Paris, from 19 February to 22 March 2024. All patients requiring anaesthesia for any type of surgery and receiving Ketamine during the study period were included. Exclusion criteria included persistent sedation after surgery. Hallucinations, PACU length of stay, analgesic strategies, and postoperative adverse events were prospectively recorded. Results: Among 5578 surgical patients, 1426 (25%) received Ketamine and 783 (55%) were included in the study (447 Ra-Ketamine, 339 S-Ketamine). Infusion strategy was similar in both groups. Patients in the Ra-Ketamine group had more hallucinations (1.4% vs 0%, risk difference of 1.34%, 95% confidence interval (CI) (−0.50 to 2.90), P=0.04) and received higher morphine doses in the PACU (10 mg inter-quartile range [IQR] [6–12] vs 8 mg [6–10]; median difference 1.00 [95% CI, 0.00–3.00; P=0.02]). PACU length of stay was comparable in both groups (Ra-Ketamine: 105 min IQR [65–150] vs S-Ketamine: 100 min IQR [70–153], median difference −1.0 (95% CI, −10.0 to 6.0; P=0.70). Conclusions: S-Ketamine demonstrated a safer profile compared with Ra-Ketamine, including fewer psychodysleptic side effects and possible superior analgesic efficacy, supporting its potential to enhance the quality of perioperative care. Clinical trial registration: researchregistry11703