Comparison of Time Within Therapeutic Range Using Anti-Factor Xa Versus Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin in Children.

OBJECTIVE: To compare unfractionated heparin (UFH) monitoring using time in therapeutic range of activated partial thromboplastin time (aPTT) versus anti-factor Xa activity (anti-Xa) in children. METHODS: This retrospective chart review, with data between October 2015 and October 2019, included pediatric patients younger than 18 years on therapeutic UFH infusion with aPTT or anti-Xa monitoring. Patients receiving extracorporeal membrane oxygenation, dialysis, concomitant anticoagulants, prophylactic UFH, no stated goal, and UFH administered for less than 12 hours were excluded. The primary outcome compared the percentage of time in therapeutic range between aPTT and anti-Xa. Secondary outcomes included time to first therapeutic value, UFH infusion rates, mean rate adjustments, and adverse events. RESULTS: A total of 65 patients were included, with 33 aPTT patients and 32 anti-Xa patients, representing 39 UFH orders in each group. Baseline characteristics were similar between groups, with an overall mean age of 1.4 years and mean weight of 6.7 kg. The anti-Xa cohort demonstrated a statistically significantly higher percentage of time in therapeutic range compared with the aPTT group (50.3% vs 26.9%, p = 0.002). The anti-Xa group also demonstrated a trend toward decreased time to first therapeutic value compared with aPTT (14 vs 23.2 hours, p = 0.12). Two patients in each group experienced new or worsening thrombosis. Six patients in the aPTT cohort experienced bleeding. CONCLUSIONS: This study demonstrated greater time was spent within therapeutic range for children receiving UFH monitored with anti-Xa compared with aPTT. Future studies should assess clinical outcomes in a larger population.

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.

Dexmedetomidine Use in Critically Ill Children With Acute Respiratory Failure.

OBJECTIVE: Care of critically ill children includes sedation but current therapies are suboptimal. To describe dexmedetomidine use in children supported on mechanical ventilation for acute respiratory failure. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. SETTING: Thirty-one PICUs. PATIENTS: Data from 2,449 children; 2 weeks to 17 years old. INTERVENTIONS: Sedation practices were unrestrained in the usual care arm. Patients were categorized as receiving dexmedetomidine as a primary sedative, secondary sedative, periextubation agent, or never prescribed. Dexmedetomidine exposure and sedation and clinical profiles are described. MEASUREMENTS AND MAIN RESULTS: Of 1,224 usual care patients, 596 (49%) received dexmedetomidine. Dexmedetomidine as a primary sedative patients (n = 138; 11%) were less critically ill (Pediatric Risk of Mortality III-12 score median, 6 [interquartile range, 3-11]) and when compared with all other cohorts, experienced more episodic agitation. In the intervention group, time in sedation target improved from 28% to 50% within 1 day of initiating dexmedetomidine as a primary sedative. Dexmedetomidine as a secondary sedative usual care patients (n = 280; 23%) included more children with severe pediatric acute respiratory distress syndrome or organ failure. Dexmedetomidine as a secondary sedative patients experienced more inadequate pain (22% vs 11%) and sedation (31% vs 16%) events. Dexmedetomidine as a periextubation agent patients (n = 178; 15%) were those known to not tolerate an awake, intubated state and experienced a shorter ventilator weaning process (2.1 vs 2.3 d). CONCLUSIONS: Our data support the use of dexmedetomidine as a primary agent in low criticality patients offering the benefit of rapid achievement of targeted sedation levels. Dexmedetomidine as a secondary agent does not appear to add benefit. The use of dexmedetomidine to facilitate extubation in children intolerant of an awake, intubated state may abbreviate ventilator weaning. These data support a broader armamentarium of pediatric critical care sedation.

Contamination of patient blood samples by avian RBCs from control material during automated hematology analysis.

OBJECTIVES: Atypical nucleated RBCs (NRBCs) found on several patient blood smears between 2010 and 2012 were noted to resemble avian RBCs. NRBCs are not normally found in the circulation beyond the neonatal period and may indicate hematologic disease, malignancy in the bone marrow, or other severe conditions. Our blood smears with unusual NRBCs did not contain other abnormalities that typically accompany NRBCs, such as immature cells or dysplastic granulocytes. To investigate this anomaly, we considered possibilities such as contaminated collection tubes and instrument problems. The Retic-C Cell Control used with the LH 750 Hematology Analyzer contains a mixture of human and avian RBCs. METHODS: CBC count with differential tests were performed on blanks and routine laboratory samples run immediately after the Retic-C Cell Control on the LH 750 and LH 780 analyzers to recreate the conditions that might cause spillage into the next tube. RESULTS: We experimentally reproduced the phenomenon of contamination of a subsequent tube with avian cells from a multiply punctured reticulocyte control tube. CONCLUSIONS: We concluded that the NRBCs likely represented avian RBCs from the Retic-C Cell Control that had been introduced into the patient tubes.