Personalizing Perioperative Analgesia in Children

NCT01140724 | Active Not Recruiting

• 2 other identifiers: STUDY21070173R01HD089458
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Pain

Keywords

pain; genes; morphine; respiratory depression; tonsillectomy; children; Opioid adverse effects; Pharmacogenetics of morphine; Pharmacokinetics of morphine; Personalizing analgesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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)

Other Outcomes (2)

• 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

  During tonsilectomies

• Evaluate whether machine learning techniques can be used to predict pain response, opioid responses and morphine usage requirements in patients

  After tonsilectomy surgery data collection

Eligibility Criteria

• Age: 3 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children, 3-15 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.

You may qualify if:

• boys and girls,
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Senthil Sadhasivam: lead
• Children's Hospital Medical Center, Cincinnati: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

UPMC Children's Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Publications (9)

• Packiasabapathy S, Zhang X, Ding L, Aruldhas BW, Pawale D, Sadhasivam S. Quantitative Pupillometry as a Predictor of Pediatric Postoperative Opioid-Induced Respiratory Depression. Anesth Analg. 2021 Oct 1;133(4):991-999. doi: 10.1213/ANE.0000000000005579.

  PMID: 34029273 DERIVED

• Hahn D, Fukuda T, Euteneuer JC, Mizuno T, Vinks AA, Sadhasivam S, Emoto C. Influence of MRP3 Genetics and Hepatic Expression Ontogeny for Morphine Disposition in Neonatal and Pediatric Patients. J Clin Pharmacol. 2020 Aug;60(8):992-998. doi: 10.1002/jcph.1592. Epub 2020 Feb 24.

  PMID: 32090339 DERIVED

• Chidambaran V, Venkatasubramanian R, Zhang X, Martin LJ, Niu J, Mizuno T, Fukuda T, Meller J, Vinks AA, Sadhasivam S. ABCC3 genetic variants are associated with postoperative morphine-induced respiratory depression and morphine pharmacokinetics in children. Pharmacogenomics J. 2017 Mar;17(2):162-169. doi: 10.1038/tpj.2015.98. Epub 2016 Jan 26.

  PMID: 26810133 DERIVED

• Sadhasivam S, Zhang X, Chidambaran V, Mavi J, Pilipenko V, Mersha TB, Meller J, Kaufman KM, Martin LJ, McAuliffe J. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects. Pharmacogenomics J. 2015 Oct;15(5):436-42. doi: 10.1038/tpj.2014.79. Epub 2015 Jan 6.

  PMID: 25558980 DERIVED

• Sadhasivam S, Chidambaran V, Olbrecht VA, Costandi A, Clay S, Prows CA, Zhang X, Martin LJ. Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids. Pain Med. 2015 May;16(5):985-97. doi: 10.1111/pme.12660. Epub 2014 Dec 17.

  PMID: 25521773 DERIVED

• Sadhasivam S, Chidambaran V, Olbrecht VA, Esslinger HR, Zhang K, Zhang X, Martin LJ. Genetics of pain perception, COMT and postoperative pain management in children. Pharmacogenomics. 2014 Feb;15(3):277-84. doi: 10.2217/pgs.13.248.

  PMID: 24533707 DERIVED

• Prows CA, Zhang X, Huth MM, Zhang K, Saldana SN, Daraiseh NM, Esslinger HR, Freeman E, Greinwald JH, Martin LJ, Sadhasivam S. Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study. Laryngoscope. 2014 May;124(5):1242-50. doi: 10.1002/lary.24455. Epub 2013 Nov 13.

  PMID: 24122716 DERIVED

• 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.

  PMID: 22941849 DERIVED

• 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. doi: 10.1542/peds.2011-2607. Epub 2012 Apr 23.

  PMID: 22529273 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA from blood is obtained and analyzed for genetic varaiations

MeSH Terms

Conditions

Pain, Postoperative; Pain; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Senthilkumar Sadhasivam, MD, MPH

  University of Pittsburgh, UPMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 8, 2010
• First Posted: June 9, 2010
• Study Start: February 7, 2022
• Primary Completion: August 16, 2022
• Study Completion (Estimated): December 25, 2026
• Last Updated: February 2, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)