Personalizing Perioperative Analgesia in Children

Postoperative Pain Clinical Trial

Official title:

Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01140724
• Other study ID #: STUDY21070173
• Secondary ID: 7R01HD089458-02
• Status: Active, not recruiting
• Start date: February 7, 2022
• Est. completion date: October 2024

Study information

• Verified date: February 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In the United States alone, each year approximately 5 million children undergo painful surgery, many of them experience serious side-effects with opioids and inadequate pain relief. Safe and effective analgesia is an important unmet critical medical need in children and its continued existence is an important perioperative safety and economic problem. Inadequate pain relief and serious side effects from perioperative opioids occur frequently in up to 50% of children. Morphine, the most commonly used perioperative opioid, has a narrow therapeutic index and large inter-patient variations in analgesic response and serious side effects. Frequent inter-individual variations in responses to morphine have significant clinical and economic impact with inadequate pain relief at one end of the spectrum of responses and serious adverse effects such as respiratory depression at the other end. Much of the inter-individual variability in response to a dose of morphine following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a subset of the genes that encode proteins involved in pain mechanisms and opioid pathway.

Description:

Measures and Procedures: Participants will receive standard care, standard anesthetic and an intraoperative dose of morphine per the clinical team.

Research procedures will include:

1. Blood draws for genotyping candidate genes and exploratory genes

2. Standardized PACU (post anesthesia care unit) Protocol: Subjective pain assessments:

Numerical Rating Scale (NRS) 0 to 10. Objective assessment with FLACC (facial expression; leg movement; activity; cry; and consolability) scale, 0-10.

3. Significant postoperative pain will be managed in the PACU with rescue doses of morphine and opioids by the clinical team. Analgesic interventions and morphine requirements are collected

4. Effects of opioids on pupil measures

5. Respiratory response to 5% carbon dioxide preoperatively and postoperatively (first 350 patients only). Another measure of end tidal carbon dioxide will be implemented when the device is clinically available.

6. Serial blood draws for morphine pharmacokinetic modeling (through subject #351).

7. Opioid adverse effects in PACU and at home.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: October 2024
• Est. primary completion date: August 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 15 Years

Eligibility

Inclusion Criteria:

• boys and girls,

• 6-15 years of age,

• all races,

• American Society of Anesthesiologists (ASA) physical status 1 and 2,

• children with history of significant snoring suggestive of obstructive sleep apnea (OSA.)

Exclusion Criteria:

• allergic to study medications

• developmental delay,

• liver and renal diseases,

• preoperative pain requiring analgesics,

• children who have problems with pupil or pupillary reaction due to disease

• preoperative medications influencing pupillary size

• non-English speaking participants and families

• Body Mass Index =30

• Participants undergoing additional procedures during surgery

• Children with certain cardiac conditions

• Children with severe lung disease

• Children with a history of seizures currently treated on medication

• Children with psychiatric/psychological conditions for which patient currently takes medication

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Locations

Country	Name	City	State
United States	UPMC Children's Hospital	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Senthil Sadhasivam	Children's Hospital Medical Center, Cincinnati, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate contribution of polymorphisms in genes to variability in codeine response in children with CYP2D6 genotypes predictive of extensive metabolizer or ultra-extensive metabolizer phenotypes	Evaluate contribution of polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to variability in codeine response in children with CYP2D6 genotypes predictive of extensive metabolizer or ultra-extensive metabolizer phenotypes	During tonsilectomies
Other	Evaluate whether machine learning techniques can be used to predict pain response, opioid responses and morphine usage requirements in patients	Evaluate whether machine learning techniques can be used to predict pain response, opioid responses and morphine usage requirements in patients solely using information extracted from the medical record as well as in combination with other genetic information	After tonsilectomy surgery data collection
Primary	Look at polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to see if there is a higher susceptibility to pain and morphine requirement.	Look at polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to see if there is a relationship to more pain and need for a higher morphine requirement.	After tonsillectomy surgery (duration of post anesthesia care unit stay)
Secondary	Evaluate relationship of pupil reaction and response to 5% carbon dioxide to adverse effects of morphine		After tonsillectomy surgery (duration of post anesthesia care unit stay)