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

Phase 4
Completed
Conditions
Nociceptive Pain
Anesthesia
Interventions
Registration Number
NCT04567160
Lead Sponsor
Ciusss de L'Est de l'Île de Montréal
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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

Non-inclusion Criteria

  • 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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sevoflurane groupSevofluraneInduction and maintenance of general anesthesia using sevoflurane
Propofol groupPropofolInduction and maintenance of general anesthesia using propofol
Primary Outcome Measures
NameTimeMethod
Delta NOL (no unit for the NOL index)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the variation of NOL (delta NOL) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Secondary Outcome Measures
NameTimeMethod
Delta Mean Arterial Blood Pressure (unit: mmHg)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the variation of mean arterial blood pressure (MABP) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Delta BIS (no unit for BIS index)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the variation of bispectral index (BIS) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Peak value of NOL (no unit)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the peak value of NOL after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Peak value of BIS (no unit)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the peak value of bispectral index (BIS) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Area Under the Curve for NOL for Propofol Versus Sevoflurane (no unit)From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient

To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation

Peak value of Heart Rate (unit: beat per minute)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the peak value of heart rate after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Area Under the Curve for Mean Arterial Blood Pressure for Propofol Versus Sevoflurane (no unit)From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient

To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation

Area Under the Curve for BIS for Propofol Versus Sevoflurane (no unit)From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient

To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation

post-anesthesia care unit (PACU) Pain Scores at Rest (scale from 0 to 10)From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours

Pain scores on a scale from 0 to 10 at rest in post-anesthesia care unit

Delta Heart Rate (beat per minute)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the variation of heart rate after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Peak value of Mean Arterial Blood Pressure (unit: mmHg)From 1 minute before to 3 minutes after tetanic stimulation for each patient

To compare the peak value of mean arterial blood pressure (MABP) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane

Area Under the Curve for Heart Rate for Propofol Versus Sevoflurane (no unit)From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient

To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation

Total Dose of Sevoflurane (unit: mL)Intraoperative

Total dose of sevoflurane in mL from induction of anesthesia until tracheal extubation in Sevoflurane group

Total Dose of Hydromorphone in post-anesthesia care unit (PACU) (unit: mg)From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours

Total dose of hydromorphone in mg in post-anesthesia care unit

post-anesthesia care unit (PACU) Pain Scores during Cough (scale from 0 to 10)From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours

Pain scores on a scale from 0 to 10 during cough effort in post-anesthesia care unit

Total Dose of Remifentanil (unit: mcg)Intraoperative

Total dose of remifentanil in mcg from induction of anesthesia until tracheal extubation

Total Dose of Propofol (unit: mg)Intraoperative

Total dose of propofol in mg from induction of anesthesia until tracheal extubation in Propofol group

Trial Locations

Locations (1)

CIUSSS de l'Est de l'Ile de Montreal

🇨🇦

Montreal, Quebec, Canada

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