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Active, not recruitingNCT01140724Updated Sep 17, 2026

Personalizing Perioperative Analgesia in Children

An observational study in Postoperative Pain, sponsored by Senthil Sadhasivam. Active, not recruiting at 1 site in United States. Open to participants aged 3 Years to 15 Years. Per ClinicalTrials.gov, last updated 2026-09-17.

Sponsored by Senthil Sadhasivam · Observational

Study type
Observational
Model
Other
Time perspective
Prospective
Enrollment
1,200
Ages
3 Years to 15 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • Postoperative Pain

Keywords

  • pain
  • genes
  • morphine
  • respiratory depression
  • tonsillectomy
  • children
  • Opioid adverse effects
  • Pharmacogenetics of morphine
  • Pharmacokinetics of morphine
  • Personalizing analgesia
03

Who can participate

Ages eligible
3 Years to 15 Years
Sexes eligible
All
Accepts healthy volunteers
No
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.

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

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
04

Study design

Observational model
Other
Time perspective
Prospective
Enrollment
1,200 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna
05

What researchers measure

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.

    Time frame: 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

    Time frame: After tonsillectomy surgery (duration of post anesthesia care unit stay)

Other outcomes

  1. 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

    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

    Time frame: During tonsilectomies

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

    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

    Time frame: After tonsilectomy surgery data collection

06

Study locations

1 site
  • UPMC Children's Hospital
    Pittsburgh, Pennsylvania 15224, United States
07

References and documents

Publications

  • 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. PubMed 34029273 ↗
  • 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. PubMed 32090339 ↗
  • 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. PubMed 26810133 ↗
  • 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. PubMed 25558980 ↗
  • 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. PubMed 25521773 ↗
  • 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. PubMed 24533707 ↗
  • 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. PubMed 24122716 ↗
  • 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. PubMed 22941849 ↗
  • 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. PubMed 22529273 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT01140724
Lead sponsor
Senthil Sadhasivam
Collaborators
Children's Hospital Medical Center, Cincinnati, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Senthil Sadhasivam (Professor, University of Pittsburgh) — Sponsor-investigator
First posted
Jun 9, 2010
Start date
Feb 7, 2022
Primary completion
Aug 16, 2027 (estimated)
Completion
Dec 25, 2027 (estimated)
Last update
Sep 17, 2026

Study contacts

Senthilkumar Sadhasivam, MD, MPH
principal investigator · University of Pittsburgh, UPMC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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