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.

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 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
6. Serial blood draws for morphine pharmacokinetic modeling
7. Opioid adverse effects in PACU and at home.

Children, 6-15 years of age, undergoing tonsillectomy or adenotonsillectomy at the Cincinati Children's Hospital Medical Center (CCHMC), who have consented to participate in an observational clinical study as approved by the CCHMC IRB, protocol # 2008-0848.

• Sadhasivam S, Krekels EH, Chidambaran V, Esslinger HR, Ngamprasertwong P, Zhang K, Fukuda T, Vinks AA. Morphine clearance in children: does race or genetics matter? J Opioid Manag. 2012 Jul-Aug;8(4):217-26. doi: 10.5055/jom.2012.0119.
• Sadhasivam S, Chidambaran V, Ngamprasertwong P, Esslinger HR, Prows C, Zhang X, Martin LJ, McAuliffe J. Race and unequal burden of perioperative pain and opioid related adverse effects in children. Pediatrics. 2012 May;129(5):832-8. Epub 2012 Apr 23.

Inclusion Criteria:

• boys and girls,
• 6-15 years of age,
• all races,
• ASA physical status 1 and 2,
• children with history of significant snoring suggestive of OSA.

Exclusion Criteria:

• allergy to morphine, codeine,
• developmental delay,
• liver and renal diseases,
• preoperative pain requiring analgesics,
• non-English speaking participants and families.