The Impact of a Dexmedetomidine Perfusion on Intraoperative Remifentanil Consumption (DEXREM)

The Impact of a Dexmedetomidine Perfusion on Intraoperative Remifentanil Consumption: a Randomized Controlled Trial

Opioids analgesic are the gold standard for intraoperative pain management. Their short- and long-term adverse effect motivate anesthesiologists to explore opioid sparing strategies. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist that could help minimize opioid consumption both intraoperative and postoperative due to its sedative, analgesic and sympatholytic properties. This new randomized controlled trial (RCT) will answer the question whether an intraoperative dexmedetomidine infusion compared to placebo has a clinically significant impact on intraoperative remifentanil consumption during a laparoscopic abdominal elective surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Dexmedetomidine; Remifentanil; Total Intravenous Anesthesia; Laparoscopic Abdominal Surgery; Remifentanil Consumption
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

Detailed Description

Opioids analgesic have been used for intraoperative pain management for decades. They are the gold standard for pain relief due to their high efficacy. However, the short- and long-term adverse effects of opioids motivate anesthesia teams to explore opioid sparing strategies employing a combination of analgesics and adjuvants via continuous infusions. Opioid tolerance and opioid-induced hyperalgesia can lead to dose escalation of prescribed opioids and poor pain control.

Dexmedetomidine is a highly selective α2 adrenergic receptor agonist that could help minimize opioid consumption both intraoperative and postoperative due to its sedative, analgesic and sympatholytic properties. Other post-procedure applications such as reduction of cough, agitation and shivering have been described.

Many trials have studied the impact of intraoperative dexmedetomidine on post-operative pain scores, post-operative opioids consumption and common side effects compared with a remifentanil intraoperative infusion. One randomized controlled trial studied the impact of a 30 min dexmedetomidine infusion on intraoperative remifentanil consumption in ASA 1-2 patients undergoing maxillofacial or cervicofacial surgeries. They found a clinically meaningful reduction of 33% of remifentanil consumption at 120 minutes in the dexmedetomidine group. This trial aims to demonstrate a similar reduction when extending to ASA 3 patients undergoing laparoscopic surgery. Furthermore, the investigators aim to evaluate patients' recovery and pain status 24h after the surgery which hasn't been done before in the context of joint dexmedetomidine and remifentanil infusion. The investigators hypothesize that patients of the dexmedetomidine infusion group will require less intraoperative remifentanil to keep the NOL-index into the prespecified range. In the PACU, lower pain score et less opioids requirements are anticipated.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olivier Verdonck; Phone Number: +15142523426; Email: overdonck@gmail.com
• Study Contact Backup: Name: Nadia Godin; Phone Number: 3193 +15142523400; Email: ngodin.hmr@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H1T2M4
      • Hôpital Maisonneuve-Rosemont
      • Contact: Olivier Verdonck; Phone Number: +15142523426; Email: overdonck@gmail.com
      • Contact: Nadia Godin; Phone Number: 3193 +15142523400; Email: ngodin.hmr@ssss.gouv.qc.ca
      • Principal Investigator: Olivier Verdonck

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• ASA 1-3
• Laparascopic surgery (including general surgery, gynecology, urology) a small abdominal incision (less than 5 cm) will be tolerated.

Exclusion Criteria:

• Patient refusal
• Chronic use of opioids
• Allergy to medication used in the trial
• Pregnant or breastfeeding women
• Contraindications to dexmedetomidine (Bradycardia, arrythmia or pace- maker, severe ventricular dysfunction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexmedetomidine; Dexmedetomidine 0.5 mcg/kg (adjusted body weight) ; Administered via infusion pump (Smith Medical Medfusion® 4000 Syringe Infusion Pump) delivered over 10 minutes during induction of general anesthesia, followed by dexmedetomidine 0.5 mcg.kg-1.h-1 (maximum dose: 2.5mcg.kg-1)	Drug: Dexmedetomidine; Intravenous dexmedetomidine will be given as a bolus (0.5 μg.kg-1) over 10 minutes. A perfusion of 0.5 mcg.kg-1.h-1 of dexmedetomidine will be programmed and maintained up until the pneumoperitoneum is deflated or up until a total dose of 2.5μg.kg-1 has been administered.
Placebo Comparator: Placebo - Normal Saline; Normal saline in volume equivalent of dexmedetomidine dose according to patient weight ; Administered via infusion pump (Smith Medical Medfusion® 4000 Syringe Infusion Pump) so that the full dose is delivered is equivalent to a maximum dose of 2.5mcg.kg-1 of dexemedetomidine	Drug: Placebo; Saline will be used instead of dexmedetomidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remifentanil consumption expressed in mcg.kg-1.h-1	Compare remifentanil consumption when using an intraoperative dexmedetomidine infusion (bolus of 0.5mcg.kg-1, than infusion of 0.5 mcg.kg-1.h-1, with a maximum dose of 2.5 mcg.kg-1) versus placebo (normal saline)	From induction of anesthesia to end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total intraoperative propofol consumption (mg.kg-1.h-1)	Compare the total intraoperative propofol consumption during anesthesia, to maintien BIS values between 40-60	From induction of anesthesia to end of surgery
Mean intraoperative blood pressure	Compare intraoperative blood pressure in both groups (mmHg)	From induction of anesthesia to end of surgery
Number of intraoperative episodes of high/low blood pressure	Compare episodes of high blood pressure (defined as + 20% of patient's baseline) ans episodes of low blood pressure (defined as - 20% of patient's baseline) between both groups	From induction of anesthesia to end of surgery
Number of episodes of intraoperative tachy-/bradycardia	Compare episodes of tachycardia (defined as > 100 bpm) and episodes of bradycardia (defined as < 45 bpm) between both groups	From induction of anesthesia to end of surgery
Total intraoperative dose of vasopressors	Compare the intraoperative requirements of norepinephrine, ephedrine, glycopyrrolate and atropine.	From induction of anesthesia to end of surgery
intraoperative NOL index	compare the percentage of time during the intraoperative period for which the NOL index will be above the pain threshold of 25	From intubation to end of surgery
Time for extubation (in minutes)	Compare the time for extubation	From end of surgery to extubation
Morphine equivalent consumption in the post anesthesia care unit (PACU)	Compare total amount of morphine equivalent given in the post anesthesia care unit (mesured in mg)	From PACU admission to discharge from PACU (Aldrete Score >=9 / 10)
Pain scores using visual analogue scale (VAS) in PACU	Compare pain scores using VAS in PACU	From PACU admission to discharge from PACU (Aldrete Score >=9 / 10)
Adverse events in PACU	Compare adverse events in PACU: hypotension, bradycardia and post-operative nausea and vomiting (PONV)	From PACU admission to discharge from PACU (Aldrete Score >=9 / 10)
Lenght of stay in PACU (in minutes)	Compare total time for readiness for discharge from PACU between groups assessed by recovery scores (Aldrete's modified score and Maisonneuve-Rosemont PACU score)	From PACU admission to discharge
Pain scores using numeric rating scale (NRS) 24h post-op	Compare pain score between both groups 24h post-op	post-op day 1
Quality of recovery (QoR) index 24h post-op	Compare Quality of recovery (QoR) index 24h post-op	post-op day 1
Mean intraoperative heart rate	Compare intraoperative heart rate in both groups (beats per minute)	From induction of anesthesia to end of surgery

Collaborators and Investigators

• Sponsor: Ciusss de L'Est de l'Île de Montréal

Publications and helpful links

General Publications

• Coeckelenbergh S, Doria S, Patricio D, Perrin L, Engelman E, Rodriguez A, Di Marco L, Van Obbergh L, Estebe JP, Barvais L, Kapessidou P. Effect of dexmedetomidine on Nociception Level Index-guided remifentanil antinociception: A randomised controlled trial. Eur J Anaesthesiol. 2021 May 1;38(5):524-533. doi: 10.1097/EJA.0000000000001402.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: November 8, 2024
• First Posted (Estimated): November 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: CAR 2025-3856

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No