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

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.

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.

The patient, the performer of the pupillary reflex measurement, and the postoperative health care provider are masked for the study arms.

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.

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.

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.

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.

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

Perioperative opioid administration based on the attending anesthesiologist decision (mainly including assessment of heart rate, blood pressure, and limb movement)

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

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

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

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

From the day of surgery at the termination of propofol infusion until patient extubation, assessed up to 2 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

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

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.