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Tolerance and efficacy profile of s-ketamine compared to racemic ketamine, a prospective observational before-and-after study. the ketalert study
Position du problème et objectif(s) de l’étude
The S enantiomer of Ketamine (S-Ketamine) is 3 to 4 times more potent than the racemic form with a shorter half-life and almost no side effects such as hallucinations, postoperative nausea and vomiting (PONV). However, its use and side effects in real life have never been compared to Racemic Ketamine (Ra-Ketamine). This before-after observational study leverages an institutional switch across multiple university hospitals from Ra- to S-Ketamine to compare their real-life efficacy, tolerance, and impact on post-operative care unit (PACU) stay.
Matériel et méthodes
Between February 19 and March 3, 2024, any patient requiring anesthesia for any surgery type and receiving Ketamine was included. Exclusion criteria included opposition to data collection, and persistent sedation after surgery. Perioperative management was left at the discretion of the physician. PACU length of stay, pain numerical rating scale (NRS), analgesic strategies, and postoperative adverse events such as PONV, vertigo, headache, hallucination, delirium, and respiratory depression were prospectively recorded.
Résultats & Discussion
During the study period, 5578 patients underwent surgery, 1426 (25%) received Ketamine and 783 were included in the study (447 Ra-Ketamine, 339 S-Ketamine). Demographic parameters were not significantly different between both groups. Ketamine was administered as a single initial bolus for 90% of patients, and only 36 patients (5%) received Ketamine for postoperative analgesia. Patients’ characteristics and infusion strategy were similar across groups. Time to PACU discharge did not differ between both group (Ra-Ketamine: 105 min [65, 150] vs S-Ketamine: 100 min [70, 153], p=0.70). Cumulative median morphine dose was higher in the Ra-Ketamine group (10 mg [6, 12] vs 8mg [6, 10]; p=0,019)). Patients presented more hallucinations in the Ra-Ketamine group (n=6/437 (1.4%) vs n=0/329 (0%); p=0.04). There was no significant difference in terms of PONV, vertigo, headache, delirium, or respiratory depression between the two groups.
Conclusion
S-Ketamine demonstrated superior analgesic efficacy, and a safer tolerance profile compared to Ra-Ketamine, with fewer psychodysleptic side effects. These findings support its potential to enhance the quality of perioperative care. S-Ketamine's safety profile may also allow the use of higher doses to reach systemic immunomodulatory effects to prevent chronic pain, postoperative neurocognitive decline, or postoperative depression.
Auteurs
Daniel EL KHOURY (1) , Amelie CAMBRIEL (2), Emmanuel PARDO (1), Adrien BOUGLE (3), Souad FELLOUS (1), Vincent DEGOS (4), James ARTHUR (5), Jean-Michel CONSTANTIN (6), Consortium GRC29 (7), Franck VERDONK (2) - (1)Department Of Anesthesiology And Intensive Care, Hôpital Saint-Antoine, & Sorbonne University, Grc 29, Dmu Dream, Assistance Publique-Hôpitaux De Paris, Paris, France, (2)Department Of Anesthesiology And Intensive Care, Hôpital Saint-Antoine, & Sorbonne University, Grc 29, Dmu Dream, Assistance Publique-Hôpitaux De Paris & Umrs_938, Centre De Recherche Saint-Antoine (crsa), Sorbonne Université-Inserm & Department Of Anesthesiology, Perioperative And Pain Medicine, St, Paris, France, (3)Department Of Anesthesiology And Critical Care Medicine, Institute Of Cardiology, Pitié-Salpêtrière University Hospital, Sorbonne University, Public Hospitals Of Paris, Paris, France, (4)Anesthésie Et Neuro-Réanimation Chirurgicale Babinski, Département D’anesthésie-Réanimation, Assistance Publique Hôpitaux De Paris (ap-Hp), Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, France, Paris, France, (5)Service De Réanimation Chirurgicale Polyvalente, Department Of Anaesthesiology And Critical Care, Sorbonne University, Grc 29, Ap-Hp, Dmu Dream, Pitié-Salpêtrière Hospital, 47-83 Bd De L’hôpital, 75013, Paris, France, Paris, France, (6)Orbonne University, Grc 29, Groupe De Recherche Clinique Arpe, Ap-Hp, Dmu Dream, Pitié-Salpêtrière Hospital, 75013, Paris, France, Paris, France, (7)Sorbonne University, Grc 29, Groupe De Recherche Clinique Arpe, Ap-Hp, Dmu Dream, Pitié-Salpêtrière Hospital, 75013, Paris, Paris, France