Perioperative Intravenous Nimodipine Trial

Background with aim: Acute postoperative pain is still of major clinical concern for a large number of patients undergoing surgery worldwide. Despite advances in pain management strategies, many patients continue to suffer from moderate-to-severe pain during the early postoperative period, while opioids are still largely over-prescribed. Not effectively and especially unrelieved pain can result in decreased patient satisfaction, increased morbidity, prolonged hospital length-of-stay and increased risk of persistent pain. Furthermore, effective treatment of acute postoperative pain using opioid analgesics remains the core treatment for postoperative pain. Although the potential benefits of opioid therapy for acute pain lead to a short-term pain control there are several potential severe side-effects associated with opioid use which may outweigh the benefits including sedation, nausea, vomiting, constipation especially in bowel surgery, and the risk of long-term use. Although various non-opioid drugs have been investigated over the past decades, information regarding L-type calcium channel blockers in acute postoperative pain is limited. In this respect, the perioperative use of nimodipine, a drug which furthermore crosses the blood-brain barrier and has direct effects on the Central Nernous System (CNS) could potentiate the effects of opioid analgesia and intraoperative anesthetic requirements, providing improved analgesia and potentially reduce for opioids in the perioperative period. Therefore, the investigators decided to carry out the present study with the aim to examine the analgesic efficacy and safety of perioperatively administered IV nimodipine in patients undergoing open colectomy on perioperative opioid and anesthetic consumption, pain intensity, opioid-related side effects and early postoperative bowel mobility.

Method: A power analysis based on a previous preliminary study using IV nimodipine for medium risk general surgery (open cholecystectomy) showed that 9 patients would provide a power greater than 0.9 (α = 0.05) for detection of differences of pain scores and cumulative opioid consumption over time (up to 48 h). Therefore, 40 patients undergoing open colectomy will be included in this prospective, randomized, double-blind, controlled trial with two arms: an intervention arm (IV nimodipine 4 mg/h starting 1h prior to surgery until one h after the start of surgery, followed by 2 mg/h until 24 h post-operation) and a control arm (isotonic saline 20 ml/ h 1h prior to and until one h after start of surgery, followed by 10 ml/h until 24 h post-operation). The study is approved by the local hospital scientific board (#18-4\_2024-12-05).

Hypothesis: The investigators hypothesize that perioperative intravenous administration of nimodipine, an L-type calcium channel antagonist, will be effective in reducing intraoperative anesthetic requirements, as well as intra- and postoperative opioid requirements, as well as postoperative pain intensity and opioid-related side effects.

• Pain intensity at rest [Срок оценки: From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.]
• Pain intensity during coughing [Срок оценки: From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.]
• Opioid related sedation [Срок оценки: From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.]
• Opioid related pruritus [Срок оценки: From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.]
• Postoperative nausea and/or vomiting (PONV) [Срок оценки: From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.]
• Time to first signs of bowel mobilization [Срок оценки: From end of surgery to 90 hours postoperatively or until hospital discharge, whichever comes first.]
• Length of stay (LOS) [Срок оценки: Duration of hospitalization, from the day of admission to the day of discharge (up to 30 days).]