Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

BACKGROUND: Acetaminophen is a frequently used adjunct analgesic in pediatric patients undergoing tonsillectomy and adenoidectomy. We compared opioid administration following preoperative intravenous (IV) or oral acetaminophen in addition to a standard multimodal regimen to test the hypothesis that 1 loading dose approach would provide superior opioid sparing effects among pediatric surgical patients undergoing tonsillectomy and adenoidectomy. METHODS: This single-center, double-blind, double-dummy prospective randomized study was conducted in patients ages 3 to 15 years undergoing tonsillectomy and adenoidectomy with or without myringotomy and tube placement between September 2017 and July 2019. Subjects received 1 dose of either oral acetaminophen 30 mg/kg with IV placebo (oral group) or IV acetaminophen 15 mg/kg with oral placebo (IV group). Acetaminophen plasma levels were measured at 2 timepoints to evaluate safety and determine plasma levels attained by each dosing regimen. Intraoperative opioid administration and postoperative analgesia were standardized. Standardized postoperative multimodal analgesia included opioid if needed to control pain assessed by standardized validated pediatric pain scales. The primary outcome measure was total opioid administration in the first 24 hours after surgery. Continuous data were not normally distributed and were analyzed using the Wilcoxon rank sum test and the Hodges-Lehman estimator of the median difference. Clinical significance was defined as a 100 µg/kg IV morphine equivalents per day difference. RESULTS: Sixty-six subjects were randomized into and completed the study (29 women, 37 men; age 5.9 ± 3.0 years; percentile weight for age 49.5 ± 30.2; no differences between groups). There was no opioid dose difference between oral (median 147.6; interquartile range [IQR], 119.6-193.0 µg/kg) and IV groups (median 125.4; IQR, 102.8-150.9 µg/kg; median difference 21.3; 95% confidence interval [CI] -2.5 to 44.2 µg/kg IV morphine equivalents; P = .13). No acetaminophen levels exceeded the predefined safety threshold (40 mg/L). No difference was found in the percentage of patients with severe pain: 50.0% oral group, 47.2% IV group; relative risk of severe pain in IV 0.94; 95% CI, 0.57-1.6; P = .82. Postoperative plasma acetaminophen levels were higher in oral (22; IQR, 16-28 mg/L) than IV (20; IQR, 17-22 mg/L) group (median difference 7.0; 4.0-8.0 mg/L; P = .0001). CONCLUSIONS: Opioid-sparing effects did not differ following an oral or standard IV acetaminophen loading dose with no identified acetaminophen toxicity in pediatric patients undergoing tonsillectomy and adenoidectomy who received standardized multimodal postoperative analgesia. An oral loading dose may provide more consistent serum acetaminophen levels at lower cost compared to a standard IV dose.

Corrected QT Interval Prolongation in Hospitalized Pediatric Patients Receiving Methadone.

OBJECTIVES: Methadone is often used in pediatric patients to prevent or treat opioid withdrawal after prolonged sedation. Prolonged corrected QT interval is an important adverse effect of methadone because it can progress to torsades de pointes, a potentially fatal dysrhythmia. The prevalence of corrected QT interval prolongation and contributing risk factors are not well defined in hospitalized pediatric patients receiving methadone. The study purpose was to identify the frequency and risk factors of corrected QT interval prolongation in hospitalized pediatric patients receiving methadone. DESIGN: Retrospective cohort study. SETTING: Tertiary academic pediatric hospital, University of California Davis Children's Hospital, Sacramento, CA. PATIENTS: Cohort of 89 pediatric patients (birth to 18 yr) who received at least one dose of methadone while hospitalized. INTERVENTIONS: Retrospective data over 7.5 years were obtained from the electronic health record. MEASUREMENTS AND MAIN RESULTS: From the cohort, 45 patients (50.6%) had documented corrected QT interval prolongation (≥ 450 ms) during the study period. No episodes of torsades de pointes were identified. In univariate analyses, higher maximum methadone doses were associated with a prolonged corrected QT interval (0.98 vs 0.59 mg/kg/d; odds ratio, 2.56; 1.15-5.70). Corrected QT interval prolongation occurred more frequently in patients with cardiac disease (63% vs 41%; p = 0.10). No factors were statistically significant in the multivariate analysis. CONCLUSIONS: In hospitalized pediatric patients receiving methadone, corrected QT interval prolongation was common, but no episodes of torsades de pointes were documented. Risk factors that have been identified in adults were not associated with prolongation in our study population.

Continuous Infusion Ketorolac for Postoperative Analgesia Following Unilateral Total Knee Arthroplasty.

BACKGROUND: Previous clinical trials have demonstrated benefit with the addition of continuous infusion (CI) ketorolac to a multimodal pain regimen in surgical patients. Data following major orthopedic surgery are minimal and conflicting. OBJECTIVES: To evaluate CI ketorolac use following unilateral total knee arthroplasty (TKA) through assessment of patient-reported pain scores, opioid consumption, and safety outcomes. METHODS: This was a retrospective, open-label cohort study that included patients undergoing unilateral TKA at a single-center teaching hospital. Participants were categorized into 2 study groups based on postoperative management: CI ketorolac or opioid protocol (OP). The first group received a ketorolac 30-mg bolus followed by CI 3.6 mg/h plus as-needed (PRN) opioids. The OP group received PRN narcotics in a tiered protocol. The primary end point was comparison of median pain scores. Secondary end points included opioid consumption (morphine equivalent units [MEUs]) in the first 48 hours postoperatively, length of stay, and adverse effects. RESULTS: Of 447 patients screened, 191 were analyzed (CI ketorolac, n = 116; OP, n = 75). Median pain scores were significantly lower in the CI ketorolac group at 48 hours postoperatively (3 [2-4] vs 3.5 [2.5-5], P = 0.033). Cumulative MEUs at 48 hours were significantly lower in the CI ketorolac group (33.9 ± 38.5 mg vs 301.6 ± 36.6 mg, P < 0.001). Patients in the CI ketorolac group experienced less respiratory depression (5.2% vs 25.3%, P < 0.001) and less naloxone administration (0% vs 8%, P = 0.002) compared with the OP group. Other adverse effects were similar among groups. CONCLUSIONS: Postoperative CI ketorolac improved pain control while reducing opioid consumption and adverse effects.