Personalizing Perioperative Analgesia in Children

Active, not recruiting

• Conditions: Postoperative Pain

• Registration Number: NCT01140724
• Lead Sponsor: Senthil Sadhasivam

Brief 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.

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 Timeline

• Study First Submitted: 2010-06-08
• Study First Submitted QC: 2010-06-08
• Study First Posted: 2010-06-09
• Study Start: 2022-02-07
• Primary Completion: 2022-08-16
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-15
• Study Completion: 2025-12-25

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

• boys and girls,
• 3-15 years of age,
• all races,
• American Society of Anesthesiologists (ASA) physical status 1,2, and 3,
• children with history of significant snoring suggestive of obstructive sleep apnea (OSA),
• Scheduled for tonsillectomy (T) or tonsillectomy and adenoidectomy (T and A).

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.	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.

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

UPMC Children's Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States