Perioperative Methadone for Ameliorating Postoperative Pain and Reduction in Postoperative Opioid Consumption in Hip Fracture Patients - Dosage Adjusting Pilot-study

A multimodal approach and the use of peripheral nerve blocks have improved the treatment of postoperative pain. However, supplemental opioids are predominantly necessary and often continued for months or years after surgery. In fact, continued use of opioids after surgery is an increasing challenge. Consequently, patients undergoing surgery are at risk of experiencing side effects and developing physical as well as psychological addiction to opioids. The most common opioid-related side effects include obstipation, nausea, itchy skin, dry mouth, vertigo, and sedation. The means to decrease the need for opioids in the postoperative phase are in high demand, and therefore the investigation of perioperative Methadone is highly relevant. Methadone is a lipophilic opioid agonist with a large distribution volume and a very long elimination half-life of 15 - 60 hours. It is also an N-methyl D-aspartate (NMDA) receptor antagonist, which attenuates opioid-induced tolerance and hyperalgesia. Furthermore, Methadone inhibits the reuptake of Serotonin and Noradrenalin, which could positively affect the experience of pain in the postoperative phase. Methadone is mostly excreted through the bile and can, therefore, even be used in patients with reduced kidney function. Methadone's analgesic effects occur only eight minutes after intravenous administration. In most studies, methadone is given perioperatively in dosages of 0.10-0.30 mg/kg and is commenced at the induction of anaesthesia or the initiation of surgery. Studies investigating the optimal dosage and time for administration found that patients receiving methadone after the procedure needed twice as much opioid pain medication on postoperative day one compared to patients receiving methadone at anaesthetic induction. These studies also indicate that using smaller dosages such as 5-10 mg, the analgesic duration is only 3-4 hours, whereas doses of 20 mg or more have a clinical effect closely related to the elimination half-life of 15-60 hours without any increased risk for respiratory depression. The aim of this study is to determine the optimal dose of methadone for a future randomized controlled trial (RCT). The objective is to investigate whether doses greater than 0.10 mg/kg are tolerated with no increased risk to respiratory depression, side effects, or prolonged stay in the post-anaesthesia care units (PACU).