Gabapentin as a novel adjunct for postoperative irritability after superior cavopulmonary connection operation in children.

OBJECTIVES: Describing our institution's off-label use of gabapentin to treat irritability after superior cavopulmonary connection surgery and its impact on subsequent opiate and benzodiazepine requirements. METHODS: This is a single-center retrospective cohort study including infants who underwent superior cavopulmonary connection operation between 2011 and 2019. RESULTS: Gabapentin was administered in 74 subjects (74/323, 22.9%) during the observation period, with a median (IQR) starting dose of 5.7 (3.3, 15.0) mg/kg/day and a maximum dose of 10.7 (5.5, 23.4) mg/kg/day. Infants who underwent surgery in 2015-19 were more likely to receive gabapentin compared with those who underwent surgery in 2011-14 (p < 0.0001). Infants prescribed gabapentin were younger at surgery (137 versus 146 days, p = 0.007) and had longer chest tube durations (1.8 versus 0.9 days, p < 0.001), as well as longer postoperative intensive care (5.8 versus 3.1 days, p < 0.0001) and hospital (11.5 versus 7.0 days, p < 0.0001) lengths of stays. The year of surgery was the only predisposing factor associated with gabapentin administration in multivariate analysis. In adjusted linear regression, infants prescribed gabapentin on postoperative day 0-4 (n = 64) had reduced benzodiazepine exposure in the following 3 days (-0.29 mg/kg, 95% CI -0.52 - -0.06, p = 0.01) compared with those not prescribed gabapentin, while no difference was seen in opioid exposure (p = 0.59). CONCLUSIONS: Gabapentin was used with increasing frequency during the study period. There was a modest reduction in benzodiazepine requirements associated with gabapentin administration and no reduction in opioid requirements. A randomised controlled trial could better assess gabapentin's benefits postoperatively in children with congenital heart disease.

Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery.

OBJECTIVE: Volatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic. Safe limits of exposure are not known for neonates. This study examined determinants of exposure in newborns undergoing cardiac surgery. METHODS: Twenty metabolites of 16 VOCs (eg, xylene, cyanide, acrolein, acrylonitrile, N, N-dimethylformamide, 1,3-butadiene, styrene, and benzene) were measured as metabolites in daily urine samples collected from 10 neonates undergoing cardiac operations (n = 150 samples). Metabolites were quantified using reversed-phase ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry. Repeated measures analysis of covariance was performed for each metabolite to examine associations with use of medical devices. RESULTS: At least 3 metabolites were detected in every sample. The median number of metabolites detected in each sample was 14 (range, 3-15). In a model controlling for other factors, the use of extracorporeal membrane oxygenation was associated with significantly (P ≤ .05) greater metabolite levels of acrolein, acrylonitrile, ethylene oxide, propylene oxide, styrene, and ethylbenzene. Patients breathing ambient air had greater levels of metabolites of acrolein, xylene, N,N-dimethylformamide, methyl isocyanate, cyanide, 1,3-butadiene (all P ≤ .05). CONCLUSIONS: Exposure to volatile organic compounds is pervasive in newborns undergoing cardiac surgery. Sources of exposure likely include medical devices and inhalation from the air in the intensive care unit. The contribution of VOC exposure during cardiac surgery in newborns to adverse outcomes warrants further evaluation.

Improvement in Palivizumab Administration Prior to Discharge for Hospitalized Infants with Hemodynamically Significant Congenital Heart Disease: A Quality Improvement Initiative.

In this quality improvement initiative, we aimed to increase provider adherence with palivizumab administration guidelines for hospitalized infants with hemodynamically significant congenital heart disease. We included 470 infants over four respiratory syncytial virus (RSV) seasons from 11/2017 to 03/2021 (baseline season: 11/2017-03/2018). Interventions included the following: education, including palivizumab in the sign-out template, identifying a pharmacy expert, and a text alert (seasons 1 and 2: 11/2018-03/2020) that was replaced by an electronic health record (EHR) best practice alert (BPA) in season 3 (11/2020-03/2021). The text alert and BPA prompted providers to add "Need for RSV immunoprophylaxis" to the EHR problem list. The outcome metric was the percentage of eligible patients administered palivizumab prior to discharge. The process metric was the percentage of eligible patients with "Need for RSV immunoprophylaxis" on the EHR problem list. The balancing metric was the percentage of palivizumab doses administered to ineligible patients. A statistical process control P-chart was used to analyze the outcome metric. The mean percentage of eligible patients who received palivizumab prior to hospital discharge increased significantly from 70.1% (82/117) to 90.0% (86/96) in season 1 and to 97.9% (140/143) in season 3. Palivizumab guideline adherence was as high or higher for those with "Need for RSV immunoprophylaxis" on the problem list than for those without it in most time periods. The percentage of inappropriate palivizumab doses decreased from 5.7% (n = 5) at baseline to 4.4% (n = 4) in season 1 and 0.0% (n = 0) in season 3. Through this initiative, we improved adherence with palivizumab administration guidelines for eligible infants prior to hospital discharge.

Evaluation of Sirolimus Dosing in Neonates and Infants With Lymphatic Disorders: A Case Series.

OBJECTIVE: Literature in pediatric patients suggests dosing sirolimus 1.6 mg/m2/day divided twice daily for lymphatic disorders with limited evidence available for dosing in neonates and infants. The objective of this research was to determine the sirolimus dose required to achieve therapeutic trough concentrations in infants with lymphatic disorders at Children's Hospital of Philadelphia. METHODS: This retrospective review included patients <1 year of age at Children's Hospital of Philadelphia who were initiated on sirolimus for lymphatic disorder. Patients were included if they received at least 5 days of consecutive sirolimus therapy prior to trough concentration monitoring. Measures of central tendency and variability were used for statistical analysis. RESULTS: A total of 16 patients met criteria for inclusion. The median initial sirolimus dose was 1 mg/m2/day (IQR, 0.5-1.6 mg/m2/day). Fourteen patients (87.5%) achieved therapeutic trough concentrations on a median sirolimus dose of 0.5 mg/m2/day. Dosing frequency to achieve therapeutic trough concentrations included 1 patient (6.25%) on twice daily dosing, 12 patients (75%) on once daily dosing, and 1 patient (6.25%) requiring every 48-hour dosing. The median time to first therapeutic trough was 15.5 days (IQR, 5.5-18.5 days), and patients required a median of 1 dose adjustment. CONCLUSIONS: A median sirolimus dose to achieve therapeutic sirolimus trough concentrations in infants with lymphatic disorders was 0.5 mg/m2/day with a median of 1 dose adjustment. Sirolimus was well tolerated in the study population.

Patterns of Medication Exposure in Children on Extracorporeal Membrane Oxygenation: A Step in Prioritizing Future Pharmacologic Studies.

To identify medications administered to pediatric patients on extracorporeal membrane oxygenation and to review the available pharmacokinetics and pharmacodynamics literature for the most commonly administered medications. DESIGN: Retrospective single-center study. SETTING: ICUs at Children's Hospital of Philadelphia. PATIENTS: Pediatric patients supported by extracorporeal membrane oxygenation between October 1, 2014, and September 30, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Drug exposure was described according to age group (< 1 mo, 1 mo to < 2 yr, 2 to < 12 yr, and > 12 yr) and ICU (cardiac, neonatal, pediatric). The association of drug exposure with patient's characteristics was examined using one-way analysis of variance for categorical variables and linear regression for continuous variables. All pharmacokinetics and pharmacodynamics literature for the 50 most commonly administered medications on extracorporeal membrane oxygenation was reviewed, with inclusion of studies that reported dosing regimens in conjunction with pharmacokinetics or pharmacodynamics data. A total of 179 different medications were administered to 254 children. Cumulative drug exposure increased with the duration of extracorporeal membrane oxygenation from a median (interquartile) of 10 drugs (6-14) at 1 week to 31 drugs (21-45) at 5 weeks following cannulation. There were significant differences in total drug exposure between age groups and ICUs. With exclusion of in vitro studies, published literature was available to support the use of 40% (20/50) of the most commonly administered medications. Dosing guidance was available for 20% (10/50) of medications and was primarily based on simulations and retrospective studies focusing on neonates and infants. CONCLUSIONS: This study highlights specific needs for future pharmacokinetics and pharmacodynamics studies. Dosing guidelines are essential to optimize the care of critically ill children supported by extracorporeal membrane oxygenation.

Evaluation of IV to Enteral Benzodiazepine Conversion Calculations in a Pediatric Intensive Care Setting.

OBJECTIVES: To evaluate if institutionally established calculations for transitioning continuous IV midazolam to enteral benzodiazepines maintain Withdrawal Assessment Tool-Version 1 scores equal to or less than preconversion values. DESIGN: Retrospective cohort study evaluating the effectiveness and safety of benzodiazepine conversion calculations embedded within an institution-specific clinical pathway for sedation and weaning of mechanically ventilated pediatric patients. SETTING: A 55-bed, mixed-medical, noncardiac surgical PICU in a tertiary care children's hospital. PATIENTS: All patients age 6 months to 18 years who received continuous midazolam for 5 days or longer while mechanically ventilated for 5-21 days and were then converted to either enteral diazepam or lorazepam following extubation (or return to baseline ventilator settings in tracheostomy-dependent patients) between January 1, 2015, and June 30, 2016. INTERVENTIONS: Benzodiazepine conversion calculations were applied according to institutional clinical pathway guidance. MEASUREMENTS AND MAIN RESULTS: Withdrawal Assessment Tool-Version 1 scores were compared pre and post benzodiazepine conversion. Patient demographics, benzodiazepine dose escalations, as needed benzodiazepine requirements, and severe adverse events within 48 hours of conversion were assessed. Seventy-one patient encounters were analyzed (median age, 2.5 yr; interquartile range, 1.2-5.3). The median Withdrawal Assessment Tool-Version 1 scores pre conversion and post conversion were not significantly different (1 [interquartile range, 0.75-2] and 1 [interquartile range, 0.25-2], respectively, p = 0.1). As needed benzodiazepine doses were administered in 38% of encounters post conversion, but escalation of a scheduled enteral benzodiazepine regimen was only required in 2.8% of encounters. Post conversion, one patient (1.4%) had increased seizure activity, and four patients (5.6%) required fluid boluses secondary to tachycardia or dehydration, but not hypotension. CONCLUSIONS: These findings suggest that standardized benzodiazepine conversions successfully achieved consistent Withdrawal Assessment Tool-Version 1 scores compared with preconversion values. Severe adverse events associated with oversedation and/or withdrawal were minimal and confounded by underlying disease states.

Ethanol lock therapy: a pilot infusion study in infants.

BACKGROUND: Ethanol lock therapy (ELT) has emerged as an effective method for the prevention and treatment of central line-associated bloodstream infections (CLABSIs), but the safety of ELT in infants has not been established. OBJECTIVE: The objective of this study was to determine blood alcohol concentration (BAC) and evidence of hepatic injury in infants after infusing a small one-time dose of ethanol, equivalent to the volume that would be flushed through the central venous catheter (CVC) after ELT is completed. METHODS: This was a prospective pilot study in infants weighing ≤6 kg with and without liver dysfunction who had a CVC. The primary end points were 5-minute and 1-hour BACs after a 0.4-mL dose of 70% ethanol was flushed through the CVC. Acceptable BACs were defined as <0.025% at 5 minutes and <0.01% at 1 hour. The secondary end point was evidence of hepatic injury, defined as a change of greater than 2 times the upper limit of normal of any component in the hepatic panel in patients with a normal baseline panel or doubling of any component in the hepatic panel in patients with an abnormal baseline panel (aspartate aminotransferase, alanine transaminase, total or direct bilirubin, gamma-glutamyl transferase, or alkaline phosphatase). RESULTS: A total of 10 patients were included for analysis, with a mean age and weight of 3.5 ± 2.4 months and 4.5 ± 0.9 kg, respectively. All patients had acceptable BACs and no evidence of hepatic injury. In 8 patients, 5-minute BACs were undetectable; BACs of the other 2 patients were 0.011%. One-hour BACs in all patients were undetectable. CONCLUSIONS: Flushing ELT resulted in acceptable BACs and no evidence of hepatic injury in this patient cohort. Further studies are needed to investigate the long-term safety and efficacy of ethanol infusion after ELT in this patient population for the prevention and treatment of CLABSIs.