Impact of Continuous Intraoperative Administration of Esmolol on Nociception Level-guided Control of Nociception. The EsmoNOL Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Intra operative remifentanil administration
研究概览
简要总结
This study aims to evaluate esmolol's perfusion impact during induction and maintenance of general anesthesia, using Nociception-Level-guided control of nociception, in adult patients undergoing laparoscopic and lower abdominal surgery, on intraoperative remifentanil consumption and postoperative pain in the Post-Anesthesia Care Unit.
详细描述
Opioids are currently the gold standard for perioperative pain control and allow for proper intraoperative hemodynamic stability. However, their use presents several major challenges, as demonstrated by the opioid crisis intensifying over the years in North America and increasingly in Europe. Besides commonly described adverse effects such as postoperative nausea, vomiting, respiratory depression, ileus, or pruritus, opioids are associated with induced hyperalgesia. In this context, several opioid-sparing strategies have been explored. The use of esmolol, a short-acting beta-blocker, can reduce sympathetic stimulation induced by perioperative nociceptive stimuli. Integrated into a multimodal strategy, it reduces the need for intraoperative opioid administration and postoperative analgesic consumption. Concurrently, multiparametric monitoring of nociception via the Nociception-Level Index (NOL index) also allows for a reduction in intraoperative opioids and decreased pain scores in the post anesthesia care unit (PACU).
The aim of this trial will be to explore the combination of these two strategies and assess the impact of continuous esmolol infusion on Nociception-Level-guided intraoperative remifentanil administration in patients under general anesthesia undergoing gynecological or general surgery via laparoscopy or lower abdominal laparotomy.
This single center randomized controlled trial will be conducted in a Canadian academic hospital. Participants aged between 18 and 65 years undergoing gynecological or general surgery by laparoscopy or lower abdominal laparotomy will be included in this study. Induction of general anesthesia will be achieved with propofol in combination with target-controlled infusion (TCI) remifentanil at 3 ng.ml-1 for intubation, then guided by the NOL Index during the procedure. Hypnosis will be maintained by the administration of sevoflurane with a target minimum alveolar concentration (MAC) between 0.7 and 1.2 to sustain a bispectral Index (BIS)between 40 and 60. Intervention group participants will receive esmolol as follows: an initial bolus of 0.5 mg.kg-1 at induction of anesthesia followed by a continuous infusion of 20mcg.kg-1.min-1 until the end of the intervention. A saline solution infusion will be administered to control group participants under the same conditions. The primary outcome will be the amount of remifentanil administered intraoperatively in mcg.kg-1.h-1. Secondary outcomes will include variations in the NOL Index during nociceptive stimuli, average heart rate and blood pressure, the intraoperative doses and time weighted average of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg), the total time and time weighted average of hypotension and or bradycardia during surgery, the time to first analgesic requirement, amount of morphine equivalent consumption for postoperative pain relief in PACU, intensity of pain at rest and under stress, using a verbal rating scale (VRS), from arrival to discharge from PACU.
The main objective of the study is to evaluate the impact of continuous intraoperative infusion of esmolol on intraoperative remifentanil administration in patients undergoing general anesthesia with NOL-guided nociception management.
Secondary objectives are listed below.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomization will be done prior to the entrance in the OR, the day of the surgery.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully consented, American Society of Anesthesiologists Classification Score 1-3 patients from 18yo to 65yo
- •Undergoing laparoscopic surgery associated with sub umbilical mini-laparotomy. Eligible surgeries will be hysterectomy (excluding vaginal approach) and left hemicolectomy, of duration time expected under 180 minutes, under general anesthesia
- •No allergy to one of the medications used in this study
排除标准
- •Contraindication to the use of the study drug (esmolol) is an exclusion criterion :
- •Hypotension
- •Sinus bradycardia
- •Sick sinus syndrome
- •Second and third degree A-V block
- •Pulmonary hypertension
- •Right ventricular failure secondary to pulmonary hypertension
- •Decompensated heart failure
- •Cardiogenic shock
- •Nontreated pheochromocytoma
- •Known hypersensitivity to esmolol or any of the inactive ingredients of the product
- •Allergy to esmolol or other beta blockers (cross-sensitivity is possible)
- •Renal dysfunction
- •Airway disease such as asthma or chronic obstructive pulmonary disease
- •Thyrotoxicosis
- •Myasthenia gravis
- •Raynaud's disease or peripheral circulatory disorder
- •Other situations leading to exclusion :
- •Severe mental impairment
- •Chronic use of opioids, β-adrenergic receptors antagonists
- •High risk of conversion to laparotomy according to the surgical team (>25%)
- •Patients will automatically be excluded after recruitment if they withdraw their consent, or if laparoscopy is converted to laparotomy.
研究组 & 干预措施
Esmolol
In the Esmolol group, intravenous esmolol will be given as a bolus (0.5mg.kg-1) over 5 minutes, and will be started simultaneously to the remifentanil initiation.
Once the bolus of esmolol is over, a perfusion of 20 mcg.kg-1.min-1 will be programmed and maintained until the end of the surgery and completion of skin sutures
干预措施: Esmolol Hydrochloride (Drug)
Standard of care
In the standard of care group, intravenous saline bolus, equivalent to an esmolol bolus (0.5mg.kg-1) will be given over 5 minutes, and will be started simultaneously to the remifentanil initiation.
Once the bolus of saline is over, a saline perfusion equivalent to an esmolol infusion of 20 mcg.kg-1.min-1 will be programmed and maintained until the end of the surgery and completion of skin sutures
干预措施: Saline (Drug)
结局指标
主要结局
Intra operative remifentanil administration
时间窗: intraoperative (from T0 = incision until Tend = end of dressing)
Quantity of remifentanil in mcg.kg-1.h-1, administered between the first surgical incision and its discontinuation at wound dressing
次要结局
- The mean intraoperative blood pressure and heart rate(intraoperative (from T0 = incision until Tend = end of dressing))
- The NOL Index variation before and after orotracheal intubation and first surgical incision(intraoperative (from T0 = nociceptive stimulation Tend = 3 minutes post stimulation))
- doses and time weighted of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg)(intraoperative (from T0 = incision until Tend = end of dressing))
- Total time with NOL value above > 25(intraoperative (from T0 = incision until Tend = end of dressing))
- Postoperative nausea and vomiting (PONV) and antiemetics use(postoperative (from T0 = PACU arrival until Tend = PACU discharge))
- The total time and time weighted average of hypotension and/or bradycardia(intraoperative (from T0 = incision until Tend = end of dressing))
- The time to first analgesic requirement in PACU(postoperative (from T0 = PACU arrival until Tend = PACU discharge))
- The amount of morphine equivalent consumption(postoperative (from T0 = PACU arrival until Tend = PACU discharge))
- The intensity of pain at rest and under stress(postoperative (from T0 = PACU arrival until Tend = PACU discharge))
- The time spent in PACU(postoperative (from T0 = PACU arrival until Tend = PACU discharge))
研究者
Pascal Laferrière-Langlois
MD, MSc, FRQS, Assistant Professor, Principal Investigator, Anesthesiologist
Ciusss de L'Est de l'Île de Montréal