Perioperative Nimodipine for Intra- and Postoperative Pain Management and Reduction of Anesthetic Requirements in Patients Undergoing Open Colectomy: a Prospective, Double-blind, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Intraoperative Remifentanil Consumption
研究概览
简要总结
The role of perioperative IV administration of nimodipine, an L-type calcium channel antagonist which is capable of crossing the blood-brain barrier, on peri-operative opioid and anesthetics requirements, pain intensity, opioid-related side effects and early postoperative bowel mobility in patients undergoing surgical treatment for bowel cancer with open radical colectomy remains scarcely explored. A prospective double-blind, randomized controlled trial investigating the effect of perioperative IV administration of nimodipine in patients undergoing open colectomy for cancer treatment is therefore conducted.
详细描述
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 2 mg/h [10 ml/h] starting 1 h prior to surgery and continuing until 24 h after the end of the procedure) and a control arm (isotonic saline 10 ml/h starting 1 h prior to surgery and continuing until 24 h after the end of the procedure). 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Randomization and study medication will be handled by the hospital pharmacy. All research team members, caregiving clinicians and enrolled patients will be blinded to the study allocation arms and the randomization list will be concealed until all statistical analyses are made.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients scheduled for open surgical treatment of bowel cancer at the General Hospital of Patra
排除标准
- •Age < 18 years, > 75 years
- •American Society of Anesthesiologists (ASA) physical status > III
- •Allergy to nimodipine
- •Inability to provide informed consent
- •Known severe renal insufficiency
- •Known severe bradyarrhythmia
- •Daily opioid consumption the last 7 days before surgery
- •Pain intensity assessed using the Numerical Rating Scale (NRS; 0-10), with scores greater than 5 reported on more than half of the days during the past month.
研究组 & 干预措施
Isotonic saline
Prepared (coded) by the pharmacy 50 ml solutions with blinded 50 ml syringes of isotonic saline will be used in each patient.
干预措施: Isotonic Saline (Drug)
Nimodipine
Prepared (coded) by the pharmacy 50 ml solutions of nimodipine (2 mg/10 ml) with blinded 50 ml syringes will be used in each patient.
干预措施: Nimodipine (Drug)
结局指标
主要结局
Intraoperative Remifentanil Consumption
时间窗: Intraoperative period, defined as the time (in minutes) from induction of general anesthesia to extubation.
Remifentanil will be administered intraoperatively based on qNOX (quantum NOXious stimulus index) levels, which will be maintained between 40 and 60. qNOX values below 40 will prompt a reduction in remifentanil dosing, while values above 60 will prompt an increase, in order to optimize analgesia.
Cumulative opioid consumption within 0 to 72 hours postoperatively
时间窗: From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.
Cumulative morphine consumption (mg) during the first 72 hours after arrival at the Post Anesthesia Care Unit (PACU). During the first hour in the PACU, morphine will be administered using a titration method. Following transfer to the surgical ward, a patient-controlled analgesia (PCA) device will be used to monitor morphine consumption. Cumulative opioid use will be recorded at specific time points: 3, 6, 12, 18, 24, 30, 36, 48, 60, and 72 hours postoperatively.
Intraoperative propofol consumption
时间窗: Intraoperative period, defined as the time (in minutes) from induction of general anesthesia to extubation.
Propofol will be administered intraoperatively based on BIS (Bispectral Index) and qCON (quantum Consciousness Index) values, which will be maintained between 40 and 60. BIS or qCON values below 40 will prompt a reduction in propofol dosing, while values above 60 will prompt an increase, in order to maintain appropriate depth of anesthesia.
次要结局
- Pain intensity at rest(From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.)
- Pain intensity during coughing(From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.)
- Opioid related sedation(From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.)
- Opioid related pruritus(From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.)
- Postoperative nausea and/or vomiting (PONV)(From Post Anesthesia Care Unit (PACU) admission (time zero) to 72 hours postoperatively.)
- Length of stay (LOS)(Duration of hospitalization, from the day of admission to the day of discharge (up to 30 days).)
- Time to first signs of bowel mobilization(From end of surgery to 90 hours postoperatively or until hospital discharge, whichever comes first.)
研究者
Petros Tzimas
Professor of Anesthesiology
University of Ioannina