Evaluation of the Pupil Dilation Reflex in Response to Noxious Stimulation in Anaesthetized Children. A Proof of Concept Trial

Study Overview
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Brief Summary
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After conduction a pilot study, pupillary dilation reflex (PDR) is measured in response to nociceptive stimulation perioperatively in infants, children and adolescents.

Detailed Description
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An infrared camera of the video pupillometer measures the pupillary dilation reflex (PDR) in response to incremental nociceptive stimuli. The PDR is a robust reflex, even in patients under general anesthesia, and may provide a potential evaluation of the autonomous nociceptive circuit. American Society of Anesthesiologists (ASA) classification I or II patients from the age of 28 days till 18 years undergoing elective surgery under general anesthesia are recruited. Enrolled patients perioperative undergo PDR measurement at 2 different standardized times (before and after opioid administration) generated by an inbuilt pupillary pain index (PPI) protocol. PPI, as a surrogate for nociception includes noxious stimulations from 10 up to 60 milli ampere (mA) until pupil dilation is larger than 13% from baseline diameter. Therefore, no inappropriate high stimulation is executed.

Official Title
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Evaluation of the Pupil Dilation Reflex (PDR) Using a Pupillary Pain Index (PPI) Stimulation Protocol in Response to Noxious Stimulation in Anaesthetized Children. A Proof of Concept Trial

Conditions
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Pain, Monitoring, Intraoperative

Intervention / Treatment
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* Device: PDR measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled abdominal, urological or otorhinolaryngology surgery under general anaesthesia ASA I-II Exclusion Criteria: History of eye deformity, invasive ophthalmologic surgery Known cranial nerve(s) deficit Infection of the eye Predicted difficult airway management (Paediatric Difficult Airway Guidelines - Difficult Airway Society) Chronic opioid use (>3 months) Ongoing treatment with beta-blockers, dopamine antagonists, topical atropine Preoperatively administrated benzodiazepins or antiemetics

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDR measurement group A<br>Two measurements of PDR perioperatively before and after opioid administration in toddlers (28 days until 23 months) | Device: PDR measurement<br>* PDR measurement at two standardized times perioperatively: Anesthetized subject by sevoflurane sedation until a minimum alveolar concentration (MAC) of at least 1,5 is reached Administration of fentanyl 2µg/kg, in the absence of adjustments in sedation depth<br>* Other names: PPI assessment;|
| Experimental: PDR measurement group B<br>Two measurements of PDR perioperatively before and after opioid administration in children (2 until 11 years) | Device: PDR measurement<br>* PDR measurement at two standardized times perioperatively: Anesthetized subject by sevoflurane sedation until a minimum alveolar concentration (MAC) of at least 1,5 is reached Administration of fentanyl 2µg/kg, in the absence of adjustments in sedation depth<br>* Other names: PPI assessment;|
| Experimental: PDR measurement group C<br>Two measurements of PDR perioperatively before and after opioid administration in adolescents (12 until 18 years) | Device: PDR measurement<br>* PDR measurement at two standardized times perioperatively: Anesthetized subject by sevoflurane sedation until a minimum alveolar concentration (MAC) of at least 1,5 is reached Administration of fentanyl 2µg/kg, in the absence of adjustments in sedation depth<br>* Other names: PPI assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulation Intensity | Necessary stimulation intensity to dilate the pupil more than 13% | During pupil measurements in the perioperative period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pupillary Pain Index score | Device specific PPI score defined in accordance to stimulation intensity necessary for pupil dilation more than 13% | During pupil measurements in the perioperative period | 
| Blood pressure | Hypertension as a common used parameter for perioperative nociceptive assessment defined as an increase in systolic blood pressure by >10% of the initial systolic blood pressure | During PDR measurements | 
| Heart rate | Tachycardia as a common used parameter for perioperative nociceptive assessment | During PDR measurements |