Effect of implementing an enhanced recovery protocol for pediatric colorectal surgery on complication rate, length of stay, and opioid use in children.

Introduction In the past two decades, Enhanced Recovery After Surgery (ERAS) pathways for adults have improved efficiency of care and decreased length of stay (LOS) without increasing postoperative complications. The effects of enhanced recovery pathways for children are less well known. In this retrospective cohort study, we evaluated the effects of an enhanced recovery protocol (ERP) implementation in children undergoing colorectal surgery. Methods We introduced a colorectal ERP in 2017. Children and young adults (ages 2-22 years) were divided into pre-intervention (2014-2016) and post-intervention groups (2017-2019) for analysis. We abstracted data, including demographics, primary surgery, LOS, postoperative pain scores, and postoperative complications. Results A total of 432 patients were included. Of those,148 (34%) were pre-ERP implementation and 284 (66%) were post-ERP implementation. Post-ERP patients experienced significantly shorter LOS (5.7 vs. 8.3 days, p<0.01); required less intraoperative local anesthetic (9.5% vs. 38.5%, p<0.01) because 55% of patients received an epidural and 18% received an abdominal plane block; and used less postoperative opioid (62.5% vs. 98.7%, p<0.01) than did pre-ERAS patients. After protocol implementation, average pain scores were lower on postoperative day 1 (3.6 vs. 4.5, p<0.05) and across the hospitalization (3.0 vs. 4.0, p<0.01). Conclusion Enhanced recovery pathways decrease LOS, opioid use, and postoperative pain scores for children undergoing colorectal surgery and should be considered for this patient population.

Process measures facilitate maturation of pediatric enhanced recovery protocols.

BACKGROUND/PURPOSE: The role of process measures used to predict quality in pediatric colorectal surgery enhanced recovery protocols has not been described. The purpose of this study was to demonstrate the feasibility of abstracting and monitoring process measures over protocol improvement iteration. METHODS: Patients enrolled in the Pediatric Colorectal Enhanced Recovery After Surgery pathway at our institution were grouped by stage of implementation. We used a quality improvement database to compare multistage enhanced recovery process measures and 30-day patient outcomes. RESULTS: We identified 58 surgical patients with 28(48%) cases enrolled in the pathway. There was increased use of regional anesthesia techniques in pathway patients (83% versus 20%, p < 0.001). All preoperative process measures clinically improved between early and full implementation. Improvements included a dramatic increase in formal preoperative education (56% versus 0%, p = 0.004) and administration of preoperative medication (p = 0.025). Overall, 12 (21%) patients experienced postoperative complications, which were similarly distributed between implementation groups. Readmissions were highest during the early implementation phase (40%, p = 0.029). Children in the late implementation group experienced fewer complications, which clinically correlated with process measure adherence. CONCLUSIONS: Process measures complement outcome measures in assessing quality and effectiveness of a pediatric colorectal recovery protocol. Adherence to processes may reduce complications. LEVEL OF EVIDENCE: Treatment study, Level III.

Review of the enhanced recovery pathway for children: perioperative anesthetic considerations.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways have been used for two decades to improve perioperative recovery in adults. Nevertheless, little is known about their effectiveness in children. The purpose of this review was to consider pediatric ERAS pathways, review the literature concerned with their potential benefit, and compare them with adult ERAS pathways. SOURCE: A PubMed literature search was performed for articles that included the terms enhanced recovery and/or fast track in the pediatric perioperative period. Pediatric patients included those from the neonatal period through teenagers and/or youths. PRINCIPAL FINDINGS: The literature search revealed a paucity of articles about pediatric ERAS. This lack of academic investigation is likely due in part to the delayed acceptance of ERAS in the pediatric surgical arena. Several pediatric studies examined individual components of adult-based ERAS pathways, but the overall study of a comprehensive multidisciplinary ERAS protocol in pediatric patients is lacking. CONCLUSION: Although adult ERAS pathways have been successful at reducing patient morbidity, the translation, creation, and utility of instituting pediatric ERAS pathways have yet to be realized.

Opioid Prescribing for the Treatment of Acute Pain in Children on Hospital Discharge.

BACKGROUND: The epidemic of nonmedical use of prescription opioids has been fueled by the availability of legitimately prescribed unconsumed opioids. The aim of this study was to better understand the contribution of prescriptions written for pediatric patients to this problem by quantifying how much opioid is dispensed and consumed to manage pain after hospital discharge, and whether leftover opioid is appropriately disposed of. Our secondary aim was to explore the association of patient factors with opioid dispensing, consumption, and medication remaining on completion of therapy. METHODS: Using a scripted 10-minute interview, parents of 343 pediatric inpatients (98% postoperative) treated at a university children's hospital were questioned within 48 hours and 10 to 14 days after discharge to determine amount of opioid prescribed and consumed, duration of treatment, and disposition of unconsumed opioid. Multivariable linear regression was used to examine predictors of opioid prescribing, consumption, and doses remaining. RESULTS: Median number of opioid doses dispensed was 43 (interquartile range, 30-85 doses), and median duration of therapy was 4 days (interquartile range, 1-8 days). Children who underwent orthopedic or Nuss surgery consumed 25.42 (95% confidence interval, 19.16-31.68) more doses than those who underwent other types of surgery (P < .001), and number of doses consumed was positively associated with higher discharge pain scores (P = .032). Overall, 58% (95% confidence interval, 54%-63%) of doses dispensed were not consumed, and the strongest predictor of number of doses remaining was doses dispensed (P < .001). Nineteen percent of families were informed how to dispose of leftover opioid, but only 4% (8 of 211) did so. CONCLUSIONS: Pediatric providers frequently prescribed more opioid than needed to treat pain. This unconsumed opioid may contribute to the epidemic of nonmedical use of prescription opioids. Our findings underscore the need for further research to develop evidence-based opioid prescribing guidelines for physicians treating acute pain in children.

Preparing enhanced recovery after surgery for implementation in pediatric populations.

Standardization in perioperative care has led to major improvements in surgical outcomes during the last two decades. Enhanced recovery after surgery (ERAS) programs are one example of a clinical pathway impacting both surgical outcomes and efficiency of care, but these programs have not yet been widely adapted for surgery in children. In adults, ERAS pathways have been shown to reduce length of stay, reduce complication rates, and improve patient satisfaction. These pathways improve outcomes through standardization of existing evidence-based best practices. Currently, the direct evidence for adapting ERAS pathways to pediatric surgery patients is limited. Challenges for implementation of ERAS programs for children include lack of direct translatability of adult evidence as well as varying levels acceptability of ERAS principles among pediatric providers and patients' families. We describe our newly implemented ERAS program for pediatric colorectal surgery patients in an era of limited direct evidence and discuss what further issues need to be addressed for broader implementation of pediatric ERAS pathways. LEVEL OF EVIDENCE: Level 5.

Src tyrosine kinase as a chemotherapeutic target: is there a clinical case?

Src tyrosine kinase was the first protooncogene described. It has been found to be overexpressed and activated in a large number of different cancers. Cellular Src has been shown to activate a number of different effectors that are involved in different aspects of cancer biology such as metastasis, cell cycle regulation and cell survival. Despite this, Src inhibitors have not entered the regular arsenal of chemotherapeutics. This article reviews some of the biology, rationale, in vitro and in vivo preclinical evidence, and some very early clinical trials demonstrating efficacy of Src inhibitors.

SRC tyrosine kinase and multidrug resistance protein-1 inhibitions act independently but cooperatively to restore paclitaxel sensitivity to paclitaxel-resistant ovarian cancer cells.

Src tyrosine kinase has been found to be overexpressed in both mouse and human ovarian cancer cells as well as in human primary ovarian cancers. Furthermore, Src inhibition sensitizes ovarian cancer cells to chemotherapeutic agents such as paclitaxel and cisplatin. Interestingly, Src inhibition has also been shown to resensitize paclitaxel-resistant cells to the cytotoxic effects of paclitaxel. The current study was undertaken in an effort to determine the mechanism by which Src resensitizes drug-resistant ovarian cancer cells. The paclitaxel-resistant human (CaOV3TaxR) and mouse (ID8TaxR) ovarian cancer cell lines express large amounts of the multidrug resistance-1 (MDR-1) protein compared with the paclitaxel-sensitive parent cell lines. Src inhibition had no effect on MDR-1 protein expression. Furthermore, Src inhibition did not affect MDR-1 function as determined by rhodamine 123 and paclitaxel uptake or retention. Coinhibition of both Src and MDR-1 synergistically enhanced paclitaxel-induced cytotoxicity in paclitaxel-resistant ovarian cancer cell lines. Inhibition of Src enhanced microtubule stabilization in paclitaxel-resistant ovarian cancer cells treated with paclitaxel without affecting expression of beta-tubulin isotypes and resulted in multipolar spindle formation and apoptosis. These results show that Src inhibition restores paclitaxel sensitivity to paclitaxel-resistant ovarian cancer cells by an MDR-independent mechanism, possibly by decreasing the critical intracellular concentration at which paclitaxel induces tubulin stabilization and bundling. Src tyrosine kinase may provide a viable target for therapeutic intervention in drug-resistant ovarian cancer.