Pain, AcutePUP-AITNCT03248908
Pupillary Dilation Reflex Assessment for Intraoperative Analgesic Titration.
A study testing Pupillary dilation reflex in people with Pain, Acute and Anesthesia, run by University Hospital, Antwerp at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Acute, Anesthesia
- What is being tested?
- Pupillary dilation reflex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteBelgium
- Study dates
- 12 Oct 2017to 31 Jan 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > 18 jaar
- Elective abdominal or gynaecological operation
- ASA (American Society of Anesthesiologists classification): I - II - III
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Pain, Acute, Anesthesia
- Being tested
- Pupillary dilation reflex, Standard of care
- Keywords
- pupillary reflex, nociception, heart rate, intraoperative monitoring
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pupillary dilation reflexDiagnostic test
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
Standard of careOther
Perioperative opioid administration based on the attending anesthesiologist decision (mainly including assessment of heart rate, blood pressure, and limb movement)
| Study group | Role | What they receive |
|---|---|---|
| Intervention 1 | Experimental | 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. Receives: Diagnostic Test: Pupillary dilation reflex |
| Intervention 2 | Active comparator | 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. Receives: Other: Standard of care |
| Intervention 3 | Experimental | 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. Receives: Diagnostic Test: Pupillary dilation reflex |
| Intervention 4 | Active comparator | 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. Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative pain
Numeric rating scale (NRS) pain assessment
Measured: From patient extubation until postoperative day 5
Postoperative analgesia
Analgetic consumption
Measured: From patient extubation until postoperative day 5
Secondary outcomes (10)
Stimulation intensity to elicit PDR
Necessary stimulation intensity generated by the pupillometer to elicit a PDR
Measured: 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
Pupil size before stimulation
Measured: 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
The amplitude of the pupil enlargement after nociceptive stimulation
Measured: 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)
Generated PPI score by the pupillometer in accordance to given stimulation and pupillary dilation reflex amplitude
Measured: 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
Total dose remifentanil or sufentanil administrated during surgery, in microgram
Measured: 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
The time between stop of propofol administration and patient extubation, in minutes
Measured: From the day of surgery at the termination of propofol infusion until patient extubation, assessed up to 2 hours
Postoperative nausea and vomiting
Frequency of nausea or vomiting after surgery, in numbers of events
Measured: From patient extubation until postoperative day 5
Length of stay at the postanesthesia care unit
Hours of admission at the postanesthesia care unit after surgery until discharge to the nursing ward, in minutes
Measured: From admission at the postanesthesia care unit until discharge to the nursing ward, assessed up to 24 hours
Length of hospital stay
Length of hospital stay, in days
Measured: From the day of the planned surgery until hospital discharge, assessed up to 5 days
Postoperative health status
Assessed by 5-level EQ-5D version (EQ-5D-5L), quality of life and health status questionnaire
Measured: From extubation until 1 month after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2017
- Study start12 Oct 2017
- Primary completion6 Sep 2021
- Study completion31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blinded randomized controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Universiteit Antwerpen
- Responsible party
- Principal investigator, Davina Wildemeersch, University Hospital, Antwerp
- Investigators
- Davina Wildemeersch, MD, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03248908
- Sponsor's protocol ID
- 17/28/319
- Acronym
- PUP-AIT
- Status last verified
- May 2023
- First submitted
- 1 Aug 2017
- Last updated
- 15 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vlaenderen DV, Hans G, Saldien V, Wildemeersch D. Pupillary reflex dilation and pain index evaluation during general anesthesia using sufentanil: a double-blind randomized controlled trial. Pain Manag. 2022 Nov;12(8):931-941. doi: 10.2217/pmt-2022-0027. Epub 2022 Oct 3.
PubMed 36189668
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pupillary Dilation Reflex Assessment for Intraoperative Analgesic Titration [PUP-AIT]. A Double Blinded Randomized Trial.
- ClinicalTrials.gov ID
- NCT03248908
- Acronym / sponsor ID
- PUP-AIT / 17/28/319
- Conditions
- Pain, Acute, Anesthesia
- Keywords
- pupillary reflex, nociception, heart rate, intraoperative monitoring
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Universiteit Antwerpen
- Study start
- 12 Oct 2017 (actual)
- Primary completion
- 6 Sep 2021 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 15 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
- Model description
- Double blinded randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Intervention 1 | Experimental | Diagnostic Test: Pupillary dilation reflexPupillary 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 | Active comparator | Other: Standard of careAnesthesiologist 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 | Experimental | Diagnostic Test: Pupillary dilation reflexPupillary 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 | Active comparator | Other: Standard of careAnesthesiologist 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- > 18 jaar
- Elective abdominal or gynaecological operation
- ASA (American Society of Anesthesiologists classification): I - II - III
Key exclusion criteria (11 listed)
- History of invasive ophthalmological surgery
- Known bilateral eye disease
- Known optical of oculomotor nerve deficit
- Active psychiatrical disease
- Proven active pheochromocytoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pupillary dilation reflexPerioperative 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 | Diagnostic test | Intervention 1, Intervention 3 |
| Standard of carePerioperative opioid administration based on the attending anesthesiologist decision (mainly including assessment of heart rate, blood pressure, and limb movement) | Other | Intervention 2, Intervention 4 |
Primary outcome
Postoperative pain
Time frame: From patient extubation until postoperative day 5
Numeric rating scale (NRS) pain assessment
Postoperative analgesia
Time frame: From patient extubation until postoperative day 5
Analgetic consumption
10 secondary outcomes
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
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
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
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
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
Extubation time
Time frame: 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
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
Length of hospital stay
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
- Derived from this study: PubMed 36189668Vlaenderen DV, Hans G, Saldien V, Wildemeersch D. Pupillary reflex dilation and pain index evaluation during general anesthesia using sufentanil: a double-blind randomized controlled trial. Pain Manag. 2022 Nov;12(8):931-941. doi: 10.2217/pmt-2022-0027. Epub 2022 Oct 3.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Davina Wildemeersch, MD principal investigator
University Hospital, Antwerp
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pupillary dilation reflex in people with Pain, Acute and Anesthesia, run by University Hospital, Antwerp at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative pain (time frame: From patient extubation until postoperative day 5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03248908, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.