Effect of Dexmedetomidine on Nol-Index Guided Remifentanil Analgesia

Effect of Dexmedetomidine vs 0.9% Sodium Chloride on Nol-Index Guided Remifentanil Analgesia: a Double-blinded Bicenter Randomized Controlled Trial

Background:

Analgesia remains to this day a challenge for anesthesiologists. Dexmedetomidine, a potent central alpha-2 agonist, has been shown to have analgesic and opioid sparing effects. The classic analgesic strategy focuses on opioid administration guided by estimated time of elimination and hemodynamic response (increase in blood pressure and heart rate). This technique is not sensitive and forces the anesthesiologist to be one step behind nociception, the patient's unconscious response to pain.

PMD-200 (Medasense, Israel) displays the Nociceptive level (NOL)-Index as marker of nociception. The NOL-Index ranges from 0 (no nociception) to 100 (intense nociception) and the recommended analgesic range during surgery is from 10 to 25 (Medasense recommendations).

The goal of this study is to compare two analgesia strategies guided by the NOL Index (range 10-25) using either remifentanil TCI (target controlled infusion) alone or remifentanil TCI associated with a continuous dexmedetomidine infusion.

Methods:

A total of 100 patients will be included and informed consent will be acquired. This bi-center study will take place at Erasme University Hospital (primary center) and Saint-Pierre University Hospital. Patients will be randomized into either two groups: remifentanil and placebo versus remifentanil and dexmedetomidine. Both groups will be monitored using the PMD-200 that will guide the analgesic therapy strategy. Investigators and patients will be blinded to dexmedetomidine and placebo administration. The primary outcome will be intraoperative remifentanil consumption. Secondary outcomes will include postoperative opioid administration, opioid associated complications, hemodynamics, and hospital length of stay.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Opioid Use; Perioperative/Postoperative Complications; Nociceptive Pain
• Intervention / Treatment: Drug: sodium chloride; Drug: Remifentanil; Drug: Dexmedetomidine

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Erasme University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- American Society of Anesthesiologists (ASA) grades 1-2 undergoing scheduled stomatological, cervical, and thyroid surgery anticipated to last at least two hours

Exclusion Criteria:

• ASA score >2
• Preoperative organ dysfunction
• Patients with non-regular cardiac rhythm
• Implanted pacemakers
• Emergent surgery
• Pregnancy or lactation
• Allergy or intolerance to any of the study drugs
• Participation in another interventional study
• Patient refusal

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remifentanil Analgesia; Continuous intraoperative analgesia with remifenanil + 0.9% sodium chloride	Drug: sodium chloride; Patients in the remifentanil group will receive an infusion of 0.9% sodium chloride instead of dexmedetomidine (identical infusion rate); Other Names: normal saline 0.9%; Drug: Remifentanil; Both groups will have remifentanil analgesia guided by the Nol-Index; Other Names: Ultiva
Active Comparator: Remifentanil and Dexmedetomidine Analgesia; Continuous intraoperative analgesia with remifenanil + dexmedetomidine	Drug: Remifentanil; Both groups will have remifentanil analgesia guided by the Nol-Index; Other Names: Ultiva; Drug: Dexmedetomidine; Patients in the dexmedetomidine-remifentanil group will receive an infusion of 0.6 mcg/kg in half an hour followed by an infusion of 0.6 mcg/kg/hour.; Other Names: Dexdor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remifentanil consumption measured as the amount (µg) of remifentanil administered during the anesthestic	Intraoperative remifentanil consumption	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Propofol Consumption measured as the amount of propofol (mg) administered during the anesthestic	Intraoperative propofol consumption	6 hours
Use of vasoactive drugs	Use and amount of vasoactive drugs used (ephedrine/phenylephrine/noradrenaline)	6 hours
Use of hypotensive drugs	Use and amount of hypotensive drugs used (nicardipine/esmolol)	6 hours
Net fluid balance	Sum of in (infused fluids) and out (net blood loss, diuresis, other losses)	6 hours
Time to extubation	Time from end of surgery to extubation of patient	6 hours
Number of patients with intraoperative hypotension	Intraoperative MAP (mean arterial pressure) <65 mmHg*; Patients that have chronic hypertension or that are 65 years of age or older will have a MAP threshold of 75mmHg (and not 65mmHg).	6 hours
Number of patients with intraoperative hypertension	Intraoperative MAP≥100 or surgical need to decrease blood pressure	6 hours
Number of patients with hemodynamic instability	MAP<65 mmHg*, HR<45, MAP≥100, HR>90 * Patients that have chronic hypertension or that are 65 years of age or older will have a MAP threshold of 75mmHg for hypotension (and not 65mmHg).	6 hours
Intraoperative heart rate	Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia)	6 hours
Intraoperative blood pressure	Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia)	6 hours
Intraoperative Nol-Index	Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia)	6 hours
Intraoperative remifentanil target cite concentration	Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia)	6 hours
Postoperative morphine consumption	mg of morphine administered postoperatively	24 hours
Number of patients with postoperative opioid-related side effect (composite and individual complications)	Post-operative nausea or vomiting within the first 24 h, postoperative hypoxemia (need within 24h postop to have supplemental oxygen (to maintain sat >94%), and pruritus.	72 hours
PACU length of stay (LOS)	hours spent at PACU	48 hours
Hospital LOS	days spents hospitalized	28 days

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Collaborators: Saint-Pierre University Hospital
• Investigators: Principal Investigator: Sean Coeckelenbergh, M.D., Université Libre de Bruxelles

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 (Actual): April 11, 2019
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: April 10, 2019
• First Posted (Actual): April 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Postoperative Complications; Nociceptive Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Remifentanil; Dexmedetomidine
• Other Study ID Numbers: P2018/568

Drug and device information, study documents

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