Personalizing Perioperative 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 Design:||Time Perspective: Prospective|
|Official Title:||Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children|
- 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) ] [ Designated as safety issue: No ]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.
- 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) ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]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
- 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 ] [ Designated as safety issue: No ]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
Biospecimen Retention: Samples With DNA
DNA from blood is obtained and analyzed for genetic varaiations
|Study Start Date:||April 2008|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||April 2018 (Final data collection date for primary outcome measure)|
Measures and Procedures: Participants will receive standard care, standard anesthetic and an intraoperative dose of morphine per the clinical team.
Research procedures will include:
- Blood draws for genotyping candidate genes and exploratory genes
- Standardized PACU 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.
- 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
- Effects of opioids on pupil measures
- 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.
- Serial blood draws for morphine pharmacokinetic modeling (through subject #351).
- Opioid adverse effects in PACU and at home.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01140724
|Contact: Senthilkumar Sadhasivam, MD, MPHemail@example.com|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Senthilkumar Sadhasivam, MD, MPH 513-636-4408 firstname.lastname@example.org|
|Contact: Marietta Labbato, BS 5136365983 email@example.com|
|Principal Investigator: Senthilkumar Sadhasivam, MD, MPH|
|Principal Investigator:||Senthilkumar Sadhasivam, MD, MPH||Children's Hospital Medical Center, Cincinnati|