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Biologic, Demographic and Clinical Factors Associated with Acute Postsurgical Pain in Racially Diverse Pediatric Cohorts Undergoing Major Surgery

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      Despite postoperative pain being a predictor for chronic postsurgical pain, postoperative pain remains undertreated in children. Pediatric studies examining disparities in acute pain outcomes are mostly limited to ambulatory surgeries. We evaluated risk for severe post-surgical pain after major surgeries in children. In Cohort 1 (retrospective, N=2788; 5 surgeries) and Cohort 2 (Prospective; N=360; spine/pectus surgery), surgical, pain, opioid use, analgesia, demographics, Area deprivation index (ADI) data were analyzed for association with outcomes sing Wilcoxon/Chi-square tests and linear regression Outcomes: Pain score AUC and opioid use on postoperative days 0-2, regional analgesia. Compositional analysis was conducted for %AUC for pain score<4, 4-7, and >7/10 using Aitchison compositional scale. Genotyping and association of 355 variants (21 genes in HPA/immune pathways) were studied (cohort 2). Cohort 1: Pain AUC was associated with age (p=0.002), sex (p=0.004), surgery (p<0.001). ADI was higher in African Americans (AA) (p<0.001). Opioid use was higher for abdominal surgery, lower with age and regional use. Pain AUC and opioid use were not different between races, though NRS AUC% for severe pain (POD2) and use of regional analgesia was higher in Whites (p<0.001). FLACC and NRS were negatively correlated in AA but not Whites. Cohort 2: AUC POD0-2 was higher among Whites compared to AA (p=0.002). Female sex (p=0.006), White race (p=0.026), surgery type (p=0.001), age (p<0.001), weight (p<0.001) and preoperative pain (p<0.001) were associated with AUC. 9 SNPs from stress genes: ANXA2, CRHR2, FKBP5, IGF2, MC2R were associated with AUC (p<0.05). Both cohorts showed associations for age, sex, race, preoperative pain and surgery type with acute post-surgical pain. Underlying socioeconomic disparities and stress genomics need consideration in racially diverse pain cohorts. Differences in education/understanding might influence regional analgesia use. Potential provider bias in objective pain assessments in AA children needs to be ruled out. Grant support from 1R01AR075857 (NIAMS).
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