Pupillary Dilation Reflex Assessment for Intraoperative Analgesic Titration.

Not Applicable

Completed

• Conditions: Anesthesia; Pain, Acute
• Interventions: Diagnostic Test: Pupillary dilation reflex; Other: Standard of care

• Registration Number: NCT03248908
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

In this double blinded randomized controlled study, the pupillary dilation reflex is used for as a nociceptive indicator for opioid administration during elective surgery under general anesthesia.

Detailed Description

An infrared camera of the video pupillometer measures the pupillary dilation reflex (PDR) in response of a nociceptive stimulus. This autonomic reflex, parasympathetic mediated in sedated patients, can be generated by various pain stimuli (built in standardized protocol, surgical incision, ...) The PDR is a robust reflex, even in patients under general anesthesia, and provides a potential evaluation of the autonomous circuit within the nociceptive evaluation based on pupil dilation upon A-delta and C fibers in both electrical or mechanic stimulation. This double blind randomized controlled trial involving American Society of Anesthesiologists (ASA) classification I-III patients undergoing elective surgery under general anesthesia are recruited. Enrolled patients are randomized in four groups: (1) remifentanil administration depending on PDR results, (2) remifentanil administration depending on decision attending anesthesiologist, (3) sufentanil administration depending on PDR results, (4) sufentanil administration depending on decision attending anesthesiologist.

Study Timeline

• Study First Submitted: 2017-08-01
• Study First Submitted QC: 2017-08-09
• Study First Posted: 2017-08-15
• Study Start: 2017-10-12
• Primary Completion: 2021-09-06
• Study Completion: 2022-01-31
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-12
• Last Update Posted: 2023-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• > 18 jaar
• Elective abdominal or gynaecological operation
• ASA (American Society of Anesthesiologists classification): I - II - III

Exclusion Criteria

• History of invasive ophthalmological surgery
• Known bilateral eye disease
• Known optical of oculomotor nerve deficit
• Active psychiatrical disease
• Proven active pheochromocytoma
• Opioid usage > 7 days preoperative
• Ongoing oncological treatment with chemotherapeutic agents
• Usage of A-1 adrenergic of beta-blocking agents
• Preoperative usage of benzodiazepines
• Topical atropine or phenylephrine (eye droplets)
• Planned perioperative usage of dopamine antagonists

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention 1	Pupillary dilation reflex	Pupillary dilation reflex based perioperative intravenous remifentanil administration. Starting dose 5 ng/ml by continous infusion, dosage adjustments are made after pupillary dilation reflex assessment every 10 minutes. When PPI score is 1, the dosage is decreased with 0.2 ng/ml. When PPI score is greater than 1, the dosage is increased with 0.2 ng/ml.
Intervention 2	Standard of care	Anesthesiologist based perioperative intravenous remifentanil administration (daily practice, standard of care). Starting dose 5 ng/ml, dosage adjustments are made when deemed necessary by attending anesthesiologist.
Intervention 3	Pupillary dilation reflex	Pupillary dilation reflex based perioperative intravenous sufentanil administration. Starting dose 0.1 mcg/kg bolus, dosage adjustments are made after pupillary dilation reflex assessment every 10 minutes. When PPI score is 1, no supplementary administration is executed. When PPI score is greater than 1, a supplementary bolus of 0.1 mcg/kg is given.
Intervention 4	Standard of care	Anesthesiologist based perioperative intravenous sufentanil administration (daily practice, standard of care). Starting dose 0.1 mcg/kg bolus, dosage adjustments are made when deemed necessary by attending anesthesiologist.

Primary Outcome Measures

Name	Time	Method
Postoperative pain	From patient extubation until postoperative day 5	Numeric rating scale (NRS) pain assessment
Postoperative analgesia	From patient extubation until postoperative day 5	Analgetic consumption

Secondary Outcome Measures

Name	Time	Method
Stimulation intensity to elicit PDR	From the day of surgery at the start of general anesthesia, assessed every 10 minutes until the end of surgery or extubation, whichever came first, assessed up to 4 hours	Necessary stimulation intensity generated by the pupillometer to elicit a PDR
Baseline pupil diameter	From the day of surgery at the start of general anesthesia, assessed every 10 minutes until the end of surgery or extubation, whichever came first, assessed up to 4 hours	Pupil size before stimulation
Pupillary dilation reflex amplitude	From the day of surgery at the start of general anesthesia, assessed every 10 minutes until the end of surgery or extubation, whichever came first, assessed up to 4 hours	The amplitude of the pupil enlargement after nociceptive stimulation
Pupillary pain index (PPI)	From the day of surgery at the start of general anesthesia, assessed every 10 minutes until the end of surgery or extubation, whichever came first, assessed up to 4 hours	Generated PPI score by the pupillometer in accordance to given stimulation and pupillary dilation reflex amplitude
Opioid usage during surgery	From the day of surgery at the start of general anesthesia, assessed every 10 minutes until the end of surgery or extubation, whichever came first, assessed up to 4 hours	Total dose remifentanil or sufentanil administrated during surgery, in microgram
Extubation time	From the day of surgery at the termination of propofol infusion until patient extubation, assessed up to 2 hours	The time between stop of propofol administration and patient extubation, in minutes
Postoperative nausea and vomiting	From patient extubation until postoperative day 5	Frequency of nausea or vomiting after surgery, in numbers of events
Length of stay at the postanesthesia care unit	From admission at the postanesthesia care unit until discharge to the nursing ward, assessed up to 24 hours	Hours of admission at the postanesthesia care unit after surgery until discharge to the nursing ward, in minutes
Length of hospital stay	From the day of the planned surgery until hospital discharge, assessed up to 5 days	Length of hospital stay, in days
Postoperative health status	From extubation until 1 month after surgery	Assessed by 5-level EQ-5D version (EQ-5D-5L), quality of life and health status questionnaire

Trial Locations

Locations (1)

University hospital Antwerp; 🇧🇪 Edegem, Antwerp, Belgium