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

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.

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)