Evaluation of the Nociception Guided by NoL Index and PK of Fentanyl in Pediatric Patients Under General Anesthesia

NCT04786275 | Completed DMC FDA Drug

• 1 other identifier: 190416008
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Fentanyl is one of the most common used opioids for analgesia during general anesthesia, however there are few studies that describe the relationship between its pharmacokinetics and pharmacodynamics, especially in the pediatric population. The monitoring of the analgesia component during general anesthesia has been traditionally by changes in patient's vital signs, with new devices that measure nociceptive indexes like the Nociception level (NoL) index currently being validated for adults. There is still lacking evidence with nociceptive indexes in the pediatric population. Insufficient dose of opioids may cause sympathetic response, respiratory complications, development of persistent post-surgical pain and even prolonged hospitalization. In the other hand, and overdose of opioids may cause over sedation, postoperatory nausea and vomiting, respiratory depression, hyperalgesia and tolerance. Given the lack of evidence on the Pharmacokinetic and pharmacodynamic (PK/PD) of fentanyl in this group of patients, has led to raise the development of this observational prospective study; which is to describe a PK/PD model of fentanyl in pediatric population, through evaluation of the NoL index, in patients submitted to elective general non-cardiac surgery.

Conditions

Pain; Anesthesia; Pediatric ALL

Keywords

NoL; Nociception level; Fentanyl; Pediatric anesthesia; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• NoL index.

  Variations in the NoL index (0-100). NoL has a range from 0-100, with 0 indicates no pain and 100 indicates worst pain. Data will also be analyzed using nonlinear mixed effect modeling (NONMEM)

  Since induction of anesthesia until emergence of anesthesia (one hour in average)

• Change of the plasmatic levels of fentanyl

  Describe the change of the levels of fentanyl plasmatic levels (ng/mL) measured by high pressure liquid chromatography (HPLC).

  5, 15, 30, 45, 75 until 120 minutes after one dose of fentanyl.

• Peak Plasma Concentration (Cmax)

  Calculate maximum plasma concentration (Cmax) fentanyl plasma levels measured with high pressure fluid (HPLC) after a single bolus of fentanyl in enrolled pediatric patients.

  5, 15, 30, 45, 75 until 120 minutes after one dose of fentanyl.

Secondary Outcomes (5)

• Hemodynamics

  At time of surgery, up to 120 minutes.

• Heart rate (bpm)

  At time of surgery, up to 120 minutes

• Pulse oximetry

  At time of surgery, up to 120 minutes.

• Bispectral index

  At time of surgery, up to 120 minutes

• Pain in Visual analogue scale (0-10)

  Every 15 minutes in the PACU, up to 120 minutes

Study Arms (1)

Tetanic stimulation

Single arm study

Drug: Fentanyl; Other: Tetanic stimulation

Interventions

Fentanyl DRUG

Standard dose of 2 ug/kg after tetanic stimulation.

Tetanic stimulation

Tetanic stimulation OTHER

Standard tetanic stimulation will be used as the stimulus to evaluate response of the intraoperative pain index (NoL) at a standard fentanyl dose.

Tetanic stimulation

Eligibility Criteria

• Age: 3 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

ASA I or II children from 3 up to 10 years requiring elective non-cardiac surgery, under general anesthesia and caudal block.

You may qualify if:

• Children 3-10 years old
• ASA I - II
• Lower abdominal or urological surgery, requiring general anesthesia and caudal block

You may not qualify if:

• Obese patients
• ASA III - IV - V
• Allergy to fentanyl
• Emergency surgery
• Patients with sleep apnea
• Surgeries anticipated to have an increased volume exchange or transfusion

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, Chile

Location

Related Publications (3)

• Ziesenitz VC, Vaughns JD, Koch G, Mikus G, van den Anker JN. Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review. Clin Pharmacokinet. 2018 Feb;57(2):125-149. doi: 10.1007/s40262-017-0569-6.

  PMID: 28688027 BACKGROUND

• Lotsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. J Pain Symptom Manage. 2005 May;29(5 Suppl):S90-103. doi: 10.1016/j.jpainsymman.2005.01.012.

  PMID: 15907650 BACKGROUND

• Renaud-Roy E, Stockle PA, Maximos S, Brulotte V, Sideris L, Dube P, Drolet P, Tanoubi I, Issa R, Verdonck O, Fortier LP, Richebe P. Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli. Can J Anaesth. 2019 Sep;66(9):1049-1061. doi: 10.1007/s12630-019-01372-1. Epub 2019 Apr 17.

  PMID: 30997633 BACKGROUND

MeSH Terms

Conditions

Pain; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Fentanyl

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Juan C Pedemonte, MSc, MD

  Pontificia Universidad Catolica de Chile

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 27, 2021
• First Posted: March 8, 2021
• Study Start: December 1, 2020
• Primary Completion: December 31, 2022
• Study Completion: March 31, 2023
• Last Updated: November 27, 2023

Record last verified: 2023-11

Locations

CL (1)