Clinical and Economic Outcomes Associated With Use of Liposomal Bupivacaine Versus Standard of Care for Management of Postsurgical Pain in Pediatric Patients Undergoing Spine Surgery.

Background: Approximately 60% of hospitalized children undergoing surgery experience at least 1 day of moderate-to-severe pain after surgery. Pain following spine surgery may affect opioid exposure, length of stay (LOS), and costs in hospitalized pediatric patients. This is a retrospective cohort analysis of pediatric patients undergoing inpatient primary spine surgery. Objectives: To examine the association of opioid-related and economic outcomes with postsurgical liposomal bupivacaine (LB) or non-LB analgesia in pediatric patients who received spine surgery. Methods: Premier Healthcare Database records (January 2015-September 2019) for patients aged 1-17 years undergoing inpatient primary spine surgery were retrospectively analyzed. Outcomes included in-hospital postsurgical opioid consumption (morphine milligram equivalents [MMEs]), opioid-related adverse events (ORAEs), LOS (days), and total hospital costs. A generalized linear model adjusting for baseline characteristics was used. Results: Among 10 189 pediatric patients, the LB cohort (n=373) consumed significantly fewer postsurgical opioids than the non-LB cohort (n=9816; adjusted MME ratio, 0.53 [95% confidence interval (CI), 0.45-0.61]; P<0.0001). LOS was significantly shorter in the LB versus non-LB cohort (adjusted rate ratio, 0.86 [95% CI, 0.80-0.94]; P=0.0003). Hospital costs were significantly lower in the LB versus non-LB cohort overall (adjusted rate ratio, 0.92 [95% CI, 0.86-0.99]; P=0.0227) mostly because of decreased LOS and central supply costs. ORAEs were not significantly different between groups (adjusted rate ratio, 0.84 [95% CI, 0.65-1.08]; P=0.1791). Discussion: LB analgesia was associated with shorter LOS and lower hospital costs compared with non-LB analgesia in pediatric patients undergoing spine surgery. The LB cohort had lower adjusted room and board and central supply costs than the non-LB cohort. These data suggest that treatment with LB might reduce hospital LOS and subsequently health-care costs, and additional cost savings outside the hospital room may factor into overall health-care cost savings. LB may reduce pain and the need for supplemental postsurgical opioids, thus reducing pain and opioid-associated expenses while improving patient satisfaction with postsurgical care. Conclusions: Pediatric patients undergoing spine surgery who received LB had significantly reduced in-hospital postsurgical opioid consumption, LOS, and hospital costs compared with those who did not.

A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY).

STUDY OBJECTIVE: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. DESIGN: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). SETTING: Operating room. PATIENTS: Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery). INTERVENTION: Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2). MEASUREMENTS: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively. MAIN RESULTS: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths. CONCLUSIONS: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.

Liposomal Bupivacaine Is Both Safe and Effective in Controlling Postoperative Pain After Spinal Surgery in Children: A Controlled Cohort Study.

STUDY DESIGN: Retrospective comparative cohort study. OBJECTIVE: To evaluate: (1) pain relief efficacy; (2) opioid consumption; (3) length of stay (LOS); (4) discharge disposition (DD); and (5) safety and adverse effects of liposomal bupivacaine (LB) in pediatric patients who underwent spinal deformity correction. SUMMARY OF BACKGROUND DATA: LB is a long-acting, locally injectable anesthetic. Previous orthopedic studies investigating its use have been limited to adult patients. The use of LB as part of postoperative pain management in pediatric patients undergoing spine deformity correction surgery is yet to be evaluated. MATERIALS AND METHODS: A total of 195 patients that received LB as part of their postoperative pain management regimen were compared with 128 patients who received standard pain management without LB. Pain intensity, opioid consumption, LOS, and DD were recorded. Potential LB-related complications were reported as frequencies and statistically compared for superiority. Noninferiority tests were performed using the Farrington-Manning score test. Multivariate tests based on generalized estimating equations were performed to determine the common and average treatment effects. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: The LB cohort demonstrated lower pain scores [postoperative day 1 (POD 1)-median=2, interquartile range (IQR)=(0-5) vs. 5 (2.5-7); POD 2-3 (0-5) vs. 4 (3-6); P<0.001], lower overall opioid consumption (78.2 vs. 129 morphine milligram equivalents; P=0.0001) and consistently from POD 0 to 3 (mean differences; 7.47, 9.04, 17.2, and 17.3 morphine milligram equivalents, respectively; P<0.01), shorter LOS (median=3 d, IQR=3-4 vs. 4 d, IQR=4-6; P<0.001), and similar to-home DD (98% vs. 97%). Complications were similar among the cohorts in superiority and 10% noninferiority analyses. Patients in the LB cohort had lower odds for complications (odds ratio=0.77; 95% CI, 0.64-0.93; P=0.009 and 0.67; 95% CI, 0.50-0.90; P=0.008). CONCLUSIONS: This study demonstrated the safety and efficacy of LB when added to the current multimodal postoperative pain management regimens after pediatric spinal surgery. LEVEL OF EVIDENCE: Level III.

A comparison of early versus late conversion from intravenous to oral therapy in the treatment of septic arthritis.

BACKGROUND: Clinical outcomes of children with bacterial septic arthritis, common in the pediatric age group, are often satisfactory with early recognition, prompt surgical drainage, and appropriate antibiotic therapy. However, the optimal duration and route of antibiotic administration for treatment of septic arthritis continues to be debated, as traditional treatment favored longer intravenous (IV) therapies yet oral regimens are increasingly available that are more cost effective, safe and produce satisfactory disease resolution. METHODS: Records of 186 patients from two children's hospitals, one that was thought to convert from IV to oral antibiotic therapy considerably earlier than the other, treated between 1985 and 1995 for bacterial septic arthritis were reviewed. Patients with concurrent osteomyelitis were excluded. RESULTS: Patients at Hospital #1 were converted to oral antibiotics after 7.4+/-7.4 days of IV antibiotic therapy and at Hospital #2 after 18.6+/-13.6 (P<0.001) days of IV therapy. Both groups received an average of four weeks of total antibiotic treatment. There was similar time to defervescence (2.4+/-3.2 d vs. 2.4+/-3.8 d, P>0.05) and to normalization of erythrocyte sedimentation rate (35.7+/-19.7 d vs. 33.8+/-44.9 d, P>0.05) in the patients converted to oral therapy early compared to those converted late. One case of mild avascular necrosis with no clinical disability developed in a patient from Hospital #2. CONCLUSIONS: We conclude that the clinical outcome in patients with septic arthritis converted to oral antibiotic therapy early in their treatment based on defined criteria was similar to those converted late.