Pupillary Dilation Reflex Assessment for Intraoperative Analgesic Titration. (PUP-AIT)

May 12, 2023 updated by: Davina Wildemeersch, University Hospital, Antwerp

Pupillary Dilation Reflex Assessment for Intraoperative Analgesic Titration [PUP-AIT]. A Double Blinded Randomized Trial.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Guy Hans, MD, PhD
  • Phone Number: 0032 03 821 35 86
  • Email: guy.hans@uza.be

Study Locations

  • Belgium
    • Antwerp
      • Edegem, Antwerp, Belgium, 2650
        • University Hospital Antwerp

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention 1
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.
Diagnostic test: Pupillary dilation reflex
Perioperative pupillary dilation reflex assessment is executed every 10 minutes from start sedation until extubation in patients allocated to study arm Intervention 1 and Intervention 3
Active Comparator: Intervention 2
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.
Other: Standard of care
Perioperative opioid administration based on the attending anesthesiologist decision (mainly including assessment of heart rate, blood pressure, and limb movement)
Experimental: Intervention 3
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.
Diagnostic test: Pupillary dilation reflex
Perioperative pupillary dilation reflex assessment is executed every 10 minutes from start sedation until extubation in patients allocated to study arm Intervention 1 and Intervention 3
Active Comparator: Intervention 4
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.
Other: Standard of care
Perioperative opioid administration based on the attending anesthesiologist decision (mainly including assessment of heart rate, blood pressure, and limb movement)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative pain
Time Frame: From patient extubation until postoperative day 5
Numeric rating scale (NRS) pain assessment
From patient extubation until postoperative day 5
Postoperative analgesia
Time Frame: From patient extubation until postoperative day 5
Analgetic consumption
From patient extubation until postoperative day 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stimulation intensity to elicit PDR
Time Frame: 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
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
Baseline pupil diameter
Time Frame: 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
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
Pupillary dilation reflex amplitude
Time Frame: 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
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
Pupillary pain index (PPI)
Time Frame: 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
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
Opioid usage during surgery
Time Frame: 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
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
Extubation time
Time Frame: 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
From the day of surgery at the termination of propofol infusion until patient extubation, assessed up to 2 hours
Postoperative nausea and vomiting
Time Frame: From patient extubation until postoperative day 5
Frequency of nausea or vomiting after surgery, in numbers of events
From patient extubation until postoperative day 5
Length of stay at the postanesthesia care unit
Time Frame: 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
From admission at the postanesthesia care unit until discharge to the nursing ward, assessed up to 24 hours
Length of hospital stay
Time Frame: From the day of the planned surgery until hospital discharge, assessed up to 5 days
Length of hospital stay, in days
From the day of the planned surgery until hospital discharge, assessed up to 5 days
Postoperative health status
Time Frame: From extubation until 1 month after surgery
Assessed by 5-level EQ-5D version (EQ-5D-5L), quality of life and health status questionnaire
From extubation until 1 month after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Antwerp

Collaborators

Universiteit Antwerpen

Investigators

  • Principal Investigator: Davina Wildemeersch, MD, University Hospital, Antwerp

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2017

Primary Completion (Actual)

September 6, 2021

Study Completion (Actual)

January 31, 2022

Study Registration Dates

First Submitted

August 1, 2017

First Submitted That Met QC Criteria

August 9, 2017

First Posted (Actual)

August 15, 2017

Study Record Updates

Last Update Posted (Actual)

May 15, 2023

Last Update Submitted That Met QC Criteria

May 12, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17/28/319

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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