NOL Index to Compare the Intraoperative Analgesic Effect of Propofol Versus Sevoflurane

NCT ID: NCT04567160

Last Updated: 2023-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-01

Study Completion Date

2022-03-17

Brief Summary

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The purpose of this prospective randomized controlled study is to compare the analgesic properties of propofol and sevoflurane using variation of the NOL index and standard monitoring (Heart Rate and Mean Arterial Blood Pressure) when patients under general anaesthesia with either agents are subjected to a standardized painful stimulus (a tetanic stimulation over the ulnar nerve at 70 mA, 100 Hz for 30 seconds).

Detailed Description

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This study proposes a research design that compare the analgesic properties of two commonly used agents for induction and maintenance of the hypnotic component of anesthesia: propofol versus sevoflurane. Using the NOL index to quantitatively monitor nociception, it is expected to see a difference in response to a standardized electrical and tetanic stimulus during general anesthesia maintained with either agents.

Hypothesis is that magnitude of the variation and/or the value of the NOL Index following a standardized nociceptive stimulus is lower when general anesthesia is based on propofol rather than on sevoflurane.

Induction of general anesthesia will differ depending in which group the patient belongs.

In the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil.

In the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane.

At this point, noxious stimulation will be delayed at least 10 minutes after TCI remifentanil is paused to allow for the remifentanil to be cleared out and to ensure brain-alveolar equilibration of sevoflurane (sevoflurane group).

Measurements of the NOL Index, BIS, HR and MAP start 1 minute before applying noxious stimulus (prestimulation period). Means of the data collected during that period will constitute the basal values for NOL and HR before stimulation. After this stand-by period, electric stimulation is applied. This will consist in a standardized tetanic stimulation to the ulnar nerve of the non-dominant forearm delivered by a routine nerve stimulator at a frequency of 100 Hz and a current of 70 mA for a duration of 30 seconds. Measurements of the NOL Index, BIS, HR and MAP will continue during 3 minutes after (poststimulation period). This window of recording has to be free of any other external stimulation as it could produce noise disturbance on recorded values.

After the stimulation, all the monitors will be used to guide intraoperative administration of hypnotic agents and analgesics. Total consumption of hypnotics and opioids will be recorded for the duration of surgery. Postoperative assessment of pain and opioid consumption will be done in post anesthesia care unit as exploratory outcomes.

Conditions

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Nociceptive Pain Anesthesia

Keywords

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NOL index

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized controlled parallel open label study
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Propofol group

Induction and maintenance of general anesthesia using propofol

Group Type ACTIVE_COMPARATOR

Propofol

Intervention Type DRUG

In the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil. Marsh pharmacokinetic model will be used to set the initial target predicted effect-site concentration of propofol at 3.0 mcg/ml in flash mode. Simultaneously, target-controlled infusion of remifentanil will be started to reach an initial target predicted effect-site concentration of 3 ng/mL using the Minto pharmacokinetic model.

After tracheal intubation, TCI of remifentanil is paused.

Sevoflurane group

Induction and maintenance of general anesthesia using sevoflurane

Group Type ACTIVE_COMPARATOR

Sevoflurane

Intervention Type DRUG

In the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane. After tracheal intubation, TCI of remifentanil is paused.

Interventions

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Propofol

In the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil. Marsh pharmacokinetic model will be used to set the initial target predicted effect-site concentration of propofol at 3.0 mcg/ml in flash mode. Simultaneously, target-controlled infusion of remifentanil will be started to reach an initial target predicted effect-site concentration of 3 ng/mL using the Minto pharmacokinetic model.

After tracheal intubation, TCI of remifentanil is paused.

Intervention Type DRUG

Sevoflurane

In the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane. After tracheal intubation, TCI of remifentanil is paused.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* ASA status I, II or III
* Age 18 years or older
* Elective surgery under general anesthesia.
* Good understanding of English or French language


* Ongoing Coronary artery disease
* Patients with non-regular sinus cardiac rhythm, implanted pacemakers, prescribed antimuscarinic agents, α2-adrenergic agonists, β1-adrenergic antagonists and antiarrhythmic agents
* Emergent surgery
* Pregnancy/lactation
* Preoperative hemodynamic disturbance
* Central nervous system disorder (neurologic/head trauma/uncontrolled epileptic seizures)
* Patient refusal
* Drug or alcohol abuse within the last 6 months
* Chronic use of psychoactive drugs
* Pre-operative chronic opioid use or chronic pain, equivalent to oxycodone 20mg per oral, per day for more than 6 weeks
* History of psychiatric diseases or psychological problems
* Allergy or intolerance to any of the study drugs

Exclusion Criteria

* Unexpected difficult airway requesting excessive, possibly painful airway manipulations.
* Intraoperative unexpected complications requiring strong hemodynamic support (transfusions, vasopressors, inotropes)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ciusss de L'Est de l'Île de Montréal

OTHER

Sponsor Role lead

Responsible Party

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Philippe Richebe

Professor, MD, PhD, DESAR, Chair of Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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CIUSSS de l'Est de l'Ile de Montreal

Montreal, Quebec, Canada

Site Status

Countries

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Canada

Other Identifiers

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2021-2343

Identifier Type: -

Identifier Source: org_study_id