# Implementing and Personalizing Best-In-Class Opioid-sparing Pain Management for Major Inpatient Surgeries in Children

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $3,404,830

## Abstract

PROJECT SUMMARY: The multicenter PRECISE Analgesia (Prospective Randomized Evaluation of Analgesia
for Cardiac and Idiopathic Scoliosis Spine Fusion Elective Surgery in Children) trials will a) implement and in-
vestigate the efficacy and safety of multidose methadone-based standardized enhanced recovery after surgery
(ERAS) protocol, and b) develop personalized ERAS protocols including precision methadone and oxycodone
dosing and personalized analgesia for the safe and effective opioid-sparing management of surgical pain after
posterior spine fusion (PSF) and cardiac surgery (CS) in children. PSF and CS are both extremely painful sur-
geries in children requiring long hospital stays and high opioid use associated with adverse effects (AEs), high
incidence of opioid dependence (OD), and chronic post-surgical pain (CPSP). Post-discharge prescribed oxyco-
done is used for >1-2 weeks, and opioid dependence occurs within 5 days in children. 20-50% of children develop
CPSP, largely due to severe uncontrolled acute surgical pain, contributing to life-long risks for opioid use/misuse
and the ongoing opioid epidemic. There is an urgent need for safe, effective opioid-sparing analgesia as well as
proactive risk predictions and personalized analgesia to provide best-in-class immediate surgical pain relief while
minimizing the risk of opioid-induced respiratory depression (RD), sedation, postoperative nausea and vomiting
(PONV), CPSP and persistent opioid use/misuse. Recently, we showed that a methadone- based standardized
ERAS protocol shortened hospital stays (2-4 days), reduced prescribed opioid use (5-7 vs. 7-18 days), and the
risks of CPSP. Despite this improvement, with standardized methadone ERAS, 30-40% of children still experi-
enced uncontrolled severe pain, PONV, and sedation from methadone and oxycodone. Our preliminary data
show that CYP2B6 and ORM1 genotypes and alpha acid glycoprotein (AAG) contribute to the variation in phar-
macokinetics (PK), analgesia, and adverse outcomes. Our preliminary data in children undergoing CS with car-
dio-pulmonary bypass (CPB) reveal opioid-sparing and safe postoperative analgesia with methadone. We will
now study the effect of CPB on intraoperative methadone dosing with robust PK modeling to enable precision
methadone dosing for the first time in children. Our expert multidisciplinary team will enroll a total of 1000
children to conduct two parallel randomized clinical trials for PSF (500 children 12-<18 yrs from 4 clinical sites)
and CS (500 children 1 month-10 yrs from 5 clinical sites). Specifically, we will 1. Conduct two randomized clinical
trials in PSF and CS to compare acute pain relief, opioid-sparing efficacy, and safety of standardized periopera-
tive multidose methadone-based ERAS vs. standard-of-care non-methadone-based analgesia. 2. Develop pre-
cision methadone dosing based on age, CYP2B6 and ORM1 variants, AAG, and CPB, and 3. Identify patient
profiles that predict benefit from the assigned a...

## Key facts

- **NIH application ID:** 10990745
- **Project number:** 1U01HD116257-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Vidya Chidambaran
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,404,830
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990745

## Citation

> US National Institutes of Health, RePORTER application 10990745, Implementing and Personalizing Best-In-Class Opioid-sparing Pain Management for Major Inpatient Surgeries in Children (1U01HD116257-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10990745. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*