Retrospective study comparing outcomes of multimodal epidural and erector spinae catheter pain protocols after pectus surgery.

INTRODUCTION: There are no optimal postoperative analgesia regimens for Nuss procedures. We compared the effectiveness of thoracic epidurals (EPI) and novel ambulatory erector spinae plane (ESP) catheters as part of multimodal pain protocols after Nuss surgery. METHODS: Data on demographics, comorbidities, perioperative details, length of stay (LOS), in hospital and post discharge pain/opioid use, side effects, and emergency department (ED) visits were collected retrospectively in children who underwent Nuss repair with EPI (N = 114) and ESP protocols (N = 97). Association of the group with length of stay (LOS), in hospital opioid use (intravenous morphine equivalents (MEq)/kg over postoperative day (POD) 0-2), and oral opioid use beyond POD7 was analyzed using inverse probability of treatment weighting (IPTW) with propensity scores, followed by multivariable regression. RESULTS: Groups had similar demographics. Compared to EPI, ESP had longer block time and higher rate of ketamine and dexmedetomidine use. LOS for ESP was 2 days IQR (2, 2) compared to 3 days IQR (3, 4) for EPI (p < 0.01). Compared to EPI, ESP group had higher opioid use (in MEq/kg) intraoperatively (0.32 (IQR 0.27, 0.36) vs. 0.28 (0.24, 0.32); p < 0.01) but lower opioid use on POD 0 (0.09 (IQR 0.04, 0.17) vs. 0.11 (0.08, 0.17); p = 0.03) and POD2 (0.00 (IQR 0.00, 0.00) vs. 0.04 (0.00, 0.06) ; p < 0.01). ESP group also had lower total in hospital opioid use (0.57 (IQR 0.42, 0.73) vs.0.82 (0.71, 0.91); p < 0.01), and shorter duration of post discharge opioid use (6 days (IQR 5,8) vs. 9 days (IQR 7,12) (p < 0.01). After IPTW adjustment, ESP continued to be associated with shorter LOS (difference -1.20, 95% CI: -1.38, -1.01, p < 0.01) and decreased odds for opioid use beyond POD7 (OR 0.11, 95% CI: 0.05, 0.24); p < 0.01). However, total in hospital opioid use in MEq/kg (POD0-2) was now similar between groups (difference -0.02 (95% CI: -0.09, -0.04); p = 0.50). The EPI group had higher incidence of emesis (29% v 4%, p < 0.01), while ESP had higher catheter malfunction rates (23% v 0%; p < 0.01) but both groups had comparable ED visits/readmissions. DISCUSSION/CONCLUSION: Compared to EPI, multimodal ambulatory ESP protocol decreased LOS and postoperative opioid use, with comparable ED visits/readmissions. Disadvantages included higher postoperative pain scores, longer block times and higher catheter leakage/malfunction. LEVELS OF EVIDENCE: Level III.

CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients.

AIM: Oxycodone is partly metabolized to the active metabolite oxymorphone by hepatic CYP2D6 in the liver. Significant genetic variability in CYP2D6 activity affects oxymorphone formation. This study aimed to associate CYP2D6 genotype and oxycodone's metabolism. METHODS: 30 children were administered oral oxycodone postoperatively. Plasma levels of oxycodone and oxymorphone, and CYP2D6 genotype were analyzed. CYP2D6 genotype and oxycodone metabolism phenotype were determined based on CYP2D6 total activity score (TAS) and metabolism phenotype: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM) or ultrarapid metabolizer (UM). RESULTS: Compared with PM/IM subjects, significantly greater oxymorphone exposure was seen in EM subjects (p = 0.02 for Cmax, p = 0.016 for AUC0-6 and p = 0.026 for AUC0-24). Similarly, higher TAS value was found to be associated with greater oxymorphone exposure. Higher conversion of oxycodone to oxymorphone was observed in EM subjects compared with PM/IM subjects (p = 0.0007 for Cmax, p = 0.001 for AUC0-6 and p = 0.004 for AUC0-24). CONCLUSION: CYP2D6 phenotypes explain metabolism of oxycodone in children, and oxymorphone exposure is higher in CYP2D6 EM phenotype. Further studies are needed to predict the occurrence of adverse event and tailor oxycodone dose for a specific CYP2D6 phenotype.

Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids.

OBJECTIVE: Unpredictable interindividual variability in response to opioids results in inadequate analgesia and opioid-related adverse effects. The effects of the child's sex on opioid response have not been well studied. The aim of this study is to determine the effects of sex on opioid-related adverse effects in children undergoing tonsillectomy. DESIGN: Prospective observational clinical study. SETTING: Outpatient pediatric surgery. SUBJECTS: Two hundred and seventy five children between 6 and 15 years of age undergoing outpatient tonsillectomy. METHODS: All children received standard perioperative care with a standard intraoperative dose of morphine. Opioid-related analgesia and safety outcomes included incidences of respiratory depression (RD), postoperative nausea and vomiting (PONV) and incidence of prolonged stay in the, post-anesthesia recovery unit (PACU) due to opioid related adverse effects. RESULTS: Given the small sample of minority population, we focused our study on 219 white children. Significant morphine effect was observed in girls but not boys for PONV (P = 0.001) and prolonged PACU stay due to PONV (P = 0.010). Although the overall incidence of RD is not statistically different between boys and girls, the incidence of RD (52% vs 32%) and PONV (43% vs 4%) tended to be more in white girls than boys as the total perioperative morphine dose increased to 0.3 mg/kg or more. CONCLUSIONS: This study demonstrates that child's sex influences morphine's dose response and adverse effects. White girls have an unequal burden with higher incidences of PONV, RD, and prolonged PACU stays following tonsillectomy from PONV and RD as total morphine doses are increased.