RESUMO
OBJECTIVES: Patients supported on extracorporeal membrane oxygenation (ECMO) have an increased incidence of seizures. Phenobarbital (PB) and fosphenytoin (fos-PHT) are common antiepileptic drugs (AEDs) used to manage seizures in the pediatric population; however, it is unknown what effect ECMO has on the serum concentrations of AEDs. The purpose of this study is to evaluate the effect of ECMO on AED serum concentrations. METHODS: A retrospective, matched-cohort study was performed in patients younger than 18 years who received ECMO and were treated with intravenous (IV) PB or fos-PHT at Texas Children's Hospital between 2004 and 2014. Patients receiving IV AED therapy and ECMO were matched, based on age, sex, and weight, with patients receiving IV AED therapy without ECMO. The 24-hour cumulative AED dose, serum concentrations, number of doses per serum concentration drawn ratio, volume of distribution, therapeutic serum concentrations, and time to therapeutic serum concentration were compared between both groups. The fos-PHT and PB groups were analyzed in all patients and in neonates only. RESULTS: Fourteen patients met inclusion criteria. The fos-PHT neonatal (20.1 vs 11.3 mg/kg/day, p = 0.044), PB composite (33.9 vs 21.6 mg/kg/day, p = 0.012), and PB neonatal (40.3 vs 20 mg/kg/day, p = 0.04) had larger 24-hour cumulative doses compared with non-ECMO patients. Lower serum concentrations were observed in the PB composite ECMO group (19.1 vs 35.4 mg/L, p < 0.001) and the PB neonatal ECMO group (20.5 vs 27.8 mg/L, p = 0.01) compared with non-ECMO patients. CONCLUSION: Pediatric patients receiving PB on ECMO and neonatal patients receiving fos-PHT on ECMO required larger doses, and in pediatric patients achieved lower serum concentrations, suggesting the necessity for alternative dosing strategies in these populations.
RESUMO
OBJECTIVE: Pediatric patients often require larger doses of antiepileptic drug (AED) than adults in order to attain therapeutic serum concentrations and/or achieve seizure control. Safety and efficacy data are often extrapolated from adult literature; hence, optimal dosage may only be determined anecdotally or based on expert opinion. With limited pediatric dosing guidelines, milligrams per day that are based on weight may exceed the maximum adult dose. The primary objective of this study is to evaluate the safety of exceeding maximum doses as specified by the US Food and Drug Administration or manufacturers of commonly used AEDs in pediatric patients. METHODS: This study is a single-center, retrospective analysis of all pediatric patients seen in the outpatient clinic between October 2010 and October 2014 who were prescribed a dose that exceeds the maximum approved dose of oxcarbazepine, zonisamide, topiramate, levetiracetam, lamotrigine, or clobazam. Baseline demographics (ie, sex, age, race/ethnicity, weight, height, diagnosis), serum drug concentrations, and appropriate laboratory tests were collected. Side effects were reviewed. RESULTS: During the 4-year study period, 41,137 prescriptions were included. A total of 2% of prescriptions exceeded the maximum dose of 1 of the included AEDs. The most common AED prescribed above the maximum dose was levetiracetam (53%), whereas lamotrigine was the least common (6%). The largest doses prescribed exceeded the maximum by 3-fold (i.e., levetiracetam dose of 9000 mg/day). CONCLUSION: It appears safe to use doses exceeding the maximum approved dose of the evaluated AEDs in pediatric patients, with appropriate counseling and monitoring for adverse effects.
RESUMO
BACKGROUND: Advances in cardiac operations over the last few decades, including corrective operations in early life, have dramatically increased the survival of children with congenital heart disease. However, postoperative care has been associated with neurologic complications, with seizures being the most common manifestation. The primary objective of this study is to describe the outcomes in pediatric patients who received an antiepileptic drug (AED) post-cardiac surgery. METHOD: A retrospective cohort study was performed in all patients less than 18 years of age who received an AED in the cardiovascular intensive care unit at Texas Children's Hospital from June 2002 until June 2012. Cardiac surgical patients initiated on phenobarbital, phenytoin, and levetiracetam were queried. Patients were excluded if the AED was not initiated on the admission for surgery. Patients who received 1 AED were compared to patients who received 2 AED, and differences in outcomes examined between the 3 AEDs used were evaluated. RESULTS: A total of 37 patients met the study criteria. Patients were initiated on an AED a median of 4 days following surgery and became seizure free a median of 1 day after initiation, with 65% remaining seizure free after the first dose. Half of all patients required 2 AEDs for seizure control, with a higher proportion of adolescents requiring 2 AEDs (p = 0.04). No differences were found when comparing the collected outcomes between phenobarbital, fosphenytoin, or levetiracetam. CONCLUSION: No adverse events were reported with the AEDs reviewed. Further work is necessary to evaluate long-term neurodevelopmental outcomes in this population and whether outcomes are a result of the AED or of other clinical sequelae.
RESUMO
BACKGROUND: Obesity has been shown to affect the disposition of water-soluble medications in pediatric patients. There are no published data describing serum phenytoin concentrations in obese pediatric patients. METHODS: A retrospective descriptive study was designed that included patients from 2011 to 2013 between 2 and 19 years of age who received a dose of fosphenytoin with a subsequent serum phenytoin concentration, drawn 2-4 hours postloading dose. Body mass index (BMI) was calculated and patients were categorized by BMI percentiles into underweight (<5th percentile), normal weight (5th-84th percentile), overweight (85th-94th percentile), and obese (≥95th percentile). Descriptive statistical analysis and comparisons between groups occurred to determine differences in serum phenytoin concentrations. Multivariable linear regression analysis was performed to determine the effect of body habitus on serum phenytoin concentrations. RESULTS: One hundred ten patients met study criteria (male 51.8%, mean age: 8.3 ± 4.9 years). Patients were normal weight (47.3%), underweight (20.9%), overweight (14.6%), and obese (17.3%). No significant differences were identified between groups in regard to patient demographics, with the exception of weight (P < 0.05). The mean fosphenytoin dose was 23.4 ± 5.7 mg Phenytoin Equivalents (PE)/kg and the serum phenytoin concentration was 22.4 ± 6.8 mg/L measured at 2.9 ± 0.6 hours after dose, and this did not vary significantly across groups (P > 0.05). Multivariable linear regression identified body habitus as a nonsignificant predictor of serum phenytoin concentrations (P > 0.05). Patients of higher BMI did not require further antiepileptic therapy as compared with patients with lower BMI (P > 0.05). CONCLUSION: Contrary to the adult population, loading dose adjustments do not seem to be required in pediatric patients. Obesity does not affect serum phenytoin concentrations in pediatric patients after intravenous bolus fosphenytoin administration.
