Personalizing Perioperative Analgesia in Children

February 8, 2024 updated by: Senthil Sadhasivam

Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children

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.

Study Overview

Status

Active, not recruiting

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Estimated)

1200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • UPMC Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 15 years (Child)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Children, 6-15 years of age, undergoing tonsillectomy or adenotonsillectomy at the Riley Hospital for Children, who have consented to participate in an observational clinical study as approved by the IU IRB, protocol # 1707325115.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: After tonsillectomy surgery (duration of post anesthesia care unit stay)
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 Outcome Measures

Outcome Measure
Time Frame
Evaluate relationship of pupil reaction and response to 5% carbon dioxide to adverse effects of morphine
Time Frame: After tonsillectomy surgery (duration of post anesthesia care unit stay)
After tonsillectomy surgery (duration of post anesthesia care unit stay)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: During tonsilectomies
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
Evaluate whether machine learning techniques can be used to predict pain response, opioid responses and morphine usage requirements in patients
Time Frame: After tonsilectomy surgery data collection
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Senthil Sadhasivam

Collaborators

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

Investigators

  • Principal Investigator: Senthilkumar Sadhasivam, MD, MPH, University of Pittsburgh, UPMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2022

Primary Completion (Actual)

August 16, 2022

Study Completion (Estimated)

October 1, 2024

Study Registration Dates

First Submitted

June 8, 2010

First Submitted That Met QC Criteria

June 8, 2010

First Posted (Estimated)

June 9, 2010

Study Record Updates

Last Update Posted (Actual)

February 12, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY21070173
  • 7R01HD089458-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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