The analgesic effect of combined treatment with intranasal S-ketamine and intranasal midazolam compared with morphine patient-controlled analgesia in spinal surgery patients: a pilot study

Abstract

Christine Riediger,1,* Manuel Haschke,2,* Christoph Bitter,3 Thomas Fabbro,4 Stefan Schaeren,5 Albert Urwyler,1 Wilhelm Ruppen1 1Department for Anesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, 2Clinical Pharmacology, 3Hospital Pharmacy, 4Clinical Trial Unit, 5Orthopedic Department, University Hospital Basel, University of Basel, Basel, Switzerland *These authors contributed equally to this work Objectives: Ketamine is a well-known analgesic and dose-dependent anesthetic used in emergency and disaster medicine. Recently, a new formulation of S-ketamine, as an intranasal spray, was developed and tested in our institution in healthy volunteers. The authors investigated the effect of intranasal S-ketamine spray combined with midazolam intranasal spray in postoperative spinal surgery patients. Materials and methods: In this prospective, computer-randomized, double-blinded noninferiority study in spinal surgery patients, the effects of intranasal S-ketamine and midazolam were compared with standard morphine patient-controlled analgesia (PCA). The primary end point was the numeric rating scale pain score 24 hours after surgery. Results: Twenty-two patients finished this study, eleven in each group. There were similar numeric rating scale scores in the morphine PCA and the S-ketamine-PCA groups at 1, 2, 4, 24, 48, and 72 hours after surgery during rest as well as in motion. There were no differences in the satisfaction scores at any time between the groups. The number of bolus demands and deliveries was not significantly different. Discussion: In our study, we found that an S-ketamine intranasal spray combined with intranasal midazolam was similar in effectiveness, satisfaction, number of demands/deliveries of S-ketamine and morphine, and number/severity of adverse events compared with standard intravenous PCA with morphine. S-ketamine can be regarded as an effective alternative for a traditional intravenous morphine PCA in the postoperative setting. Keywords: S-ketamine, intranasal, patient-controlled analgesia, postoperative pain