Nociception Level-guided Remifentanil Dosing in Children During General Anesthesia

Study Overview
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Brief Summary
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The investigators aim to investigate whether administration of a short-acting opioid (remifentanil) guided by a pain monitor (nociceptive level monitor) during anesthesia, can reduce pain in children after surgery. The investigators hypothesize that pain monitor-guided administration of remifentanil can reduce pain postoperatively compared with standard care.

Detailed Description
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NOL-guided analgesia has not previously been assessed in children, and it is unknown whether this additional monitoring has any clinical benefits in a pediatric population. In the present study the investigators aim to investigate whether administration of perioperative remifentanil guided by the CE-certified Pain Monitoring Device monitor-PMD200™, also called NOL-monitor, can reduce pain (primary endpoint), opioid consumption and agitation in children aged 3-16 years undergoing surgery with intravenous anesthesia. The investigators hypothesize that NOL-guided perioperative remifentanil administration can reduce postoperative pain compared with standard clinical care (remifentanil dosing based on hemodynamic variables). All patients will receive standard analgesia and antiemetic administered perioperatively: IV paracetamol 15 mg/kg IV Ibuprofen 10 mg/kg, unless contraindicated IV Morphine 25-100 μg/kg according to the extent of surgery and the departments' standard, administered 30 minutes before end of surgery (will not be included in the total perioperative or postoperative opioid consumption) In case of minor surgery, 1-2 μg/kg fentanyl, according to the department's standard, may be administered instead of morphine at the discretion of the anesthetist (will not be included in the total perioperative or postoperative opioid consumption) Regional anesthesia may be provided at the discretion of the anesthetist IV ondansetron 100 μg/kg

Official Title
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Can Nociception Level-guided Remifentanil Dosing Reduce Postoperative Pain in Children During General Anesthesia: A Blinded, Randomized Controlled Trial

Conditions
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Surgical Procedure, Unspecified

Intervention / Treatment
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* Device: The NOL monitor (Pain Monitoring Device monitor-PMD200™)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiology (ASA) class of 1-3 Scheduled surgery requiring intraoperative opioid administration Planned maintenance anesthesia with propofol and remifentanil The trial subject's custody holders' must be able to understand the trial protocol, risks, and benefits, and provide signed informed consent Exclusion Criteria: Inability of the trial subject's custody holder to read or write Danish Children who cannot cooperate to the study assessments based on the investigators' evaluation. This may be children with mental disorders, visual disturbances, hearing or speech impairment etc. interfering with assessments. Arrythmias, either known arrythmias preoperatively or arrythmias detected within the first minutes perioperatively (in which case the patient will be excluded post- randomization). Allergy to the medicines used in the study Daily intake of opioids (morphine, oxycodone, ketobemidone, methadone, fentanyl) during the last 4 weeks Weight < 10 kg

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 16 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Blinded, randomized, controlled multicenter trial with two parallel groups and a superiority design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOL-guided remifentanil dosing<br>Remifentanil dosing will preferentially be guided by the NOL index, but blood pressure and heart rate will be monitored and considered concurrently. If the NOL index is > 25, remifentanil infusion will be increased. If the NOL index is < 10 the remifentanil infusion rate will be reduced | Device: The NOL monitor (Pain Monitoring Device monitor-PMD200™)<br>* NOL-guided perioperative remifentanil administration<br>* Other names: NOL-guided remifentanil dosing;|
| No Intervention: Standard care remifentanil dosing<br>Remifentanil dosing will be administered according to standard care per institutional practice. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First pain score assessed at the PACU | Pain at rest assessed using the Faces Pain Scale - Revised (0-100 mm). | Assessed at the first time the child is awake at the PACU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid consumption at the PACU | Total, cumulative, opioid consumption, calculated as IV fentanyl equivalents | From extubation until discharge from PACU | 
| Perioperative opioid consumption | Total, cumulative, perioperative opioid consumption, calculated as IV remifentanil equivalents. The planned administration of morphine/fentanyl at the end of surgery will NOT be included. | From induction until extubation | 
| Opioid consumption after discharge from PACU and until the 48-h anesthesia followup | Total, cumulative, opioid consumption, calculated as IV morphine equivalents | From PACU discharge and until the 48-hours anesthesia followup | 
| Faces Pain Scale - Revised scores at rest during the PACU stay | Pain at rest, assessed using the Faces Pain Scale - Revised (Revised (0-100 mm), calculated as the area under the curve. If the child is sleeping, a pain score of 0 will be assigned. | Assessed at 15, 30, 45 and 60 minutes after arrival at the PACU, and thereafter every 30 minutes until discharge. | 
| FLACC pain scores at rest during the PACU stay | Pain at rest assessed using the Face Legs, Activity, Cry and Consolability scale (FLACC, 0-10 points), calculated as area under the curve. | Assessed at 15, 30, 45 and 60 minutes after arrival at the PACU, and thereafter every 30 minutes until discharge. | 
| Postoperative agitation | Postoperative agitation assessed using the WATCHA scale (0-4). The highest score at any time point will be used for the comparison between groups. | Assessed at 15, 30, 45 and 60 minutes after arrival at the PACU, and thereafter every 30 minutes until discharge. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Pain