Nociception Level Index as a Verbal Tool of Pain in Children

Study Overview
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Brief Summary
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60 children under 6 years old, scheduled for orthopedic surgery for limb fracture or neuromuscular and bone deformities will be randomized by closed envelope method into two groups (n=30) either receiving standard pain management protocol or intraoperative NOL guided analgesia. Our study aims to evaluate the nociception monitor's effectiveness in providing adequate postoperative analgesia in pediatric patients. Besides, the difference between the amount of analgesic medication will be recorded. Data to be recorded are total intraoperative morphine and postoperative rescue analgesic consumption, NOL values, and FLACC scores.

Detailed Description
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The nociception level index (NOL) is one of the nociception monitors and stands out from the others with its multi-parameter evaluation. It is generated from five different parameters (heart rate, heart rate variability, skin conductance level, photo-plethysmography waveform amplitude, number of skin conductance fluctuations, and their time derivatives). Moreover, its design as a finger probe connected to a non-invasive continuous nociception monitor makes it more suitable, especially for pediatric patients. Although this monitor has been validated for discrimination of a noxious stimulus with high accuracy, its effects on perioperative pain management have recently started to be shown in clinical practice. More importantly, no study has yet been conducted on the use of NOL monitoring in pain management in pediatric patients. The study is designed as a single-blind, prospective study after approval of our Institutional ethics committee (dossier no:211-2022) and planned to allocate 60 patients (2 groups; 1:1 allocation; n=30) after obtaining written informed parental consent. Children aged under 6 who are scheduled for orthopedic surgery for limb fracture or neuromuscular and bone deformities are eligible for this study. Exclusion criteria are refusal to participate in the study; history of premature birth; known metabolic syndrome; allergies to drugs used within the study protocol; decreased liver or renal function; diagnosed mental retardation. Patient randomization Randomization is designed with concealed opaque envelope in a 1:1 ratio into 2 groups (n= 30): the control group (Group A) and the study group (Group B). Before the start of the study, an independent anesthetist will prepare 60 envelopes each containing the name of one group. When the inclusion/exclusion criteria are met, on the day of the surgery the anesthetist will choose one envelope in the operating room to apply the designed protocol for each group. Data obtained at the clinical follow-up will be gathered by an independent anesthetist who is blinded to the groups and protocol used in the operating room. Anesthesia, intervention, and post-interventional follow-up After standard monitorization, general anesthesia induction will start with sevoflurane 4-6% administered via a face mask. Subsequently, after intravenous (IV) cannulation 2 mcg/kg fentanyl; 0,05 mg/kg midazolam; 1-2,5 mg/kg propofol; 0,6 mg/kg rocuronium will be administered and orotracheal intubation will be performed. Once the randomization is concluded to decide the group of the patient, Group A will receive 15 mg/kg (IV) paracetamol and 0,05 mg/kg morphine (IV). For once, NOL monitorization will be applied 30 minutes before waking up the patient to assess standard pain management and if the NOL value is higher than 25; 0,025 mg/kg morphine (IV) bolus doses (the maximum total intraoperative dose is concluded to be 0,5 mg/kg (IV)) will be added to ensure adequate analgesia for all patients within the study. On the contrary, patients within Group B will receive NOL monitorization from the beginning, all along the surgery. As pain management protocol, other than standard 15 mg/kg (IV) paracetamol, 0,025 mg/kg morphine (IV) bolus doses will be applied if only intraoperative NOL values are over 25 (concluded to be valuable only if it remains over 25 for at least one minute). Postoperative pain was assessed by FLACC (Face, Legs, Activity, Cry, Consolability) behavioral pain assessment score at the postoperative care unit, 6th 12th, and 24th hour postoperatively. The same anesthetist who is blind to study groups will make all assessments to precise standardization. All children will be prescribed paracetamol 15 mg/kg (IV) four times per day. If the pain score was equal to or more than 4, tramadol 1 mg/kg will be administered intravenously as a rescue analgesic. The amount of total intraoperative morphine and postoperative rescue analgesic consumption along with NOL values and FLACC scores will be recorded.

Official Title
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Effect of Nociception Level Index on Postoperative Pain Management in Pediatric Patients

Conditions
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Pediatric Patients, Orthopedic Surgery, Extremity Fractures Lower, Extremity Fractures Upper, Deformity; Congenital

Intervention / Treatment
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* Device: The nociception level index monitorization
* Device: The nociception level index measurement;postoperative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anaesthesiologists (ASA) Physical Status classification I to II Patients whose parents will give informed consent for the study Exclusion Criteria: Refusal to take part in the study History of allergies to drugs used in the study protocol History of premature birth Diagnosed metabolic syndrome Known hepatic insufficiency or decreased function Known renal insufficiency or decreased function Diagnosed with mental retardation

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 6 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After standard monitorization, general anesthesia will be applied. Once the randomization is concluded to decide the group of the patient, Group A will receive 15 mg/kg (IV) paracetamol and 0,05 mg/kg morphine (IV). For once, NOL monitorization will be applied 30 minutes before waking up the patient to assess standard pain management and if the NOL value is higher than 25; 0,025 mg/kg morphine (IV) bolus doses (the maximum total intraoperative dose is concluded to be 0,5 mg/kg (IV)) will be added to ensure adequate analgesia for all patients within the study. On the contrary, patients within Group B will receive NOL monitorization from the beginning, all along the surgery.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Group A will receive a standard intraoperative analgesia protocol | Device: The nociception level index measurement;postoperative<br>* The nociception level index (NOL) will be used postoperatively<br>|
| Experimental: Group B<br>Group B will receive a NOL-guided analgesia protocol | Device: The nociception level index monitorization<br>* The nociception level index (NOL) is one of the nociception monitors and stands out from the others with its multi-parameter evaluation. It is generated from five different parameters (heart rate, heart rate variability, skin conductance level, photo-plethysmography waveform amplitude, number of skin conductance fluctuations, and their time derivatives).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores | Face, Legs, Activity, Cry, Consolability (FLACC) behavioral pain assessment score : range 0-10; 0 = Relaxed and comfortable;1-3 = Mild discomfort; 4-6 = Moderate. pain. 7-10 = Severe discomfort/pain. | postoperative 24 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The total amount of analgesic drug | morphine(mg) used intraoperatively and tramadol(mg) at postoperative follow-up | Intraoperative and postoperative 24 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative pain, nociception level index, behavioral pain scores, general anesthesia, pain monitorization