PPAP, Spine Fusion
Conditions
Keywords
PPAP, Pediatric, Spine Fusion Surgery
Brief summary
The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and reduce serious immediate and long-term adverse outcomes of perioperative opioids in children undergoing painful surgery.
Detailed description
Aim 1. Develop and implement a perioperative precision analgesia platform (PPAP) by linking genomics to opioid metabolism, CPIC guidelines, precision dosing, clinical safety, and personalizing analgesia. Aim 2. Implement and evaluate PPAP in children undergoing major inpatient surgery, posterior spinal fusion (PSF) 1. Determine genetic factors predisposing children to immediate and long-term postoperative methadone and oxycodone related adverse effects including RD, PONV, opioid dependence, and CPSP The PI postulate that specific CYP2B6, ABCB1, OPRM1, FAAH, and CYP2D6 variants identify children at risk for poor pain relief, RD, PONV, opioid dependence, and CPSP in the postoperative period. 2. Determine genetic variants-based perioperative dosing and outpatient prescribing of opioids The PI hypothesize that CYP2B6 and CYP2D6 variants will explain pharmacokinetic variations of methadone and oxycodone, determine the right doses, and implement precision opioid use for optimal clinical outcomes
Interventions
DIAGNOSTIC_TESTPreoperative Genotyping
Genotype based risk prediction and personalized pain management
Sponsors
Senthil Sadhasivam
National Center for Advancing Translational Sciences (NCATS)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
PK sampling and genetic testing will determine the type of analgesia medication treatment the patient receives
Eligibility
Sex/Gender
ALL
Age
10 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Children ages 10 to 21 * ASA physical status 1 to 3 * Undergoing Posterior-Lateral Spinal Fusion * Receives in-patient opioids * Prescribed opioids at discharge
Exclusion criteria
* Serious illness * Preoperative severe pain * Preoperative opioid use or misuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV) | Immediately post-surgery up to 4 days in patient | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience RD and PONV in the immediate post-surgical period (4 days) in the hospital |
| Look at genetic factors predisposing children to postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV) at genetic factors predisposing children to inadequate surgical pain relief with oxycodone | At home up to 1 year post-surgery | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience RD and PONV in the post-surgical period at home up to 1-year |
| Look at genetic factors predisposing children to inadequate surgical pain relief with oxycodone | Immediately post-surgery | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience poor pain relief in the immediate post-surgical period (4 days) in the hospital. Poor pain relief will be determined using the Numerical Rating Scale (NRS) which runs on a 0-10 scale; 0 being no pain at all, 10 being the worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Look at the impact of CYP2D6 variants on oxycodone's clinical dosing in children to see if specific variants correlate with a need for lower or higher doses of analgesic | Pre-operative to post-operative day 2 | The investigators will look at CYP2D6 variants to find correlations in oxycodone's PK sampling and the need for dose adjustments that lead to desired clinical outcomes in children undergoing major inpatient surgeries. Oxycodone will be measured by the IU CTSI's Clinical Pharmacology Analytical Core (CPAC) laboratory using a validated LC/MS/MS as-say,201 and plasma alpha-1 acid glycoprotein (AAG) will be measured using a HPLC/UV assay. Study team will track the subjects choices from their signed consent form regarding PK collections. |
Countries
United States
Contacts
CONTACTSenthilkumar Sadhasivam, MD, MPH
CONTACTDayana Alsamsam, BSPS, MSc
PRINCIPAL_INVESTIGATORSenthilkumar Sadhasivam, MD, MPH
University of Pittsburgh
Outcome results
None listed