Nociception Level-guided Remifentanil Dosing in Children During General Anesthesia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Surgical Procedure, Unspecified
• Intervention / Treatment: Device: The NOL monitor (Pain Monitoring Device monitor-PMD200™)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mette Lea Mortensen, MD; Phone Number: 0045 35452227; Email: mette.lea.mortensen@regionh.dk
• Study Contact Backup: Name: Pia Jæger, MD, PhD; Phone Number: 0045 35454016; Email: pia.therese.jaeger@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Anaesthesia, The Center of Head and Orthopaedics, Rigshospitalet
    • Contact: Morten Bøttger, MD, MMD; Email: morten.boettger@regionh.dk
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Anaesthesia, The Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet
    • Contact: Mette Lea Mortensen, MD; Email: mette.lea.mortensen@regionh.dk
    • Principal Investigator: Arash Afshari, MD, PhD
  • Køge, Denmark, 4600
    • Not yet recruiting
    • Department of Anaesthesia, Sjællands Universitetshospital, Køge
    • Contact: Casper H Jørgensen, MD, PhD; Email: chj@regionsjaelland.dk
  • Vejle, Denmark, 7100
    • Not yet recruiting
    • Department of Anaesthesia, Vejle Sygehus
    • Contact: Nick P Steen, MD; Email: nick.phaff.steen@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NOL-guided remifentanil dosing; 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™); NOL-guided perioperative remifentanil administration; Other Names: NOL-guided remifentanil dosing
No Intervention: Standard care remifentanil dosing; Remifentanil dosing will be administered according to standard care per institutional practice.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PACU length of stay.	PACU length of stay.	Assessed as time from extubation (in case there is a wait for a PACU bay) and until PACU discharge readiness, defined as the time the participant fulfils local discharge criteria
Postoperative nausea or vomiting	Assessed as a dichotomous endpoint, as either presence or absence of nausea or vomiting at any time point, during the period.	Will be assessed twice; 1) at the PACU and 2) from PACU discharge and until the 48-hour follow up.
Number of events of hemodynamic instability	Number of events of hemodynamic instability requiring drug or fluid administration perioperatively.	Perioperatively
Time to extubation	The time from anesthesia maintenance is stopped until the patient is extubated/LMA is removed	From anesthesia maintenance is stopped until the patient is extubated/LMA is removed
Parental satisfaction.	Parental satisfaction with anesthesia assessed on a numeric rating scale from 0 to 10.	Assessed at 48 hours postoperatively, for the entire period 0-48 hours postoperatively
Time where the NOL index value is > 25	Time (minutes) where the NOL index value is > 25	From the start of induction and until the time of extubation
Maximum NOL index	The highest NOL index during a 5-minute period at any time perioperatively	From the start of induction and until the time of extubation
Mean NOL index	The mean NOL index during surgery	From the start of induction and until the time of extubation

Collaborators and Investigators

• Sponsor: Pia Jaeger, MD, PhD
• Investigators: Study Chair: Pia Jæger, MD, PhD, Department of Anaesthesia, The Juliane Marie Center, Rigshospitalet

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: February 9, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Pediatric
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: NOL1-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No