scholarly journals Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic Drug Serum Concentrations in Pediatric Patients

2017 ◽  
Vol 22 (5) ◽  
pp. 352-357 ◽  
Author(s):  
Nicholas O. Dillman ◽  
Mindl M. Messinger ◽  
Kimberly N. Dinh ◽  
Jennifer L. Placencia ◽  
Brady S. Moffett ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Extracorporeal Membrane Oxygenation ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Volume Of Distribution ◽  
Serum Concentrations ◽  
Inclusion Criteria ◽  
Lower Serum ◽  
Membrane Oxygenation ◽  
Dosing Strategies

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.

scholarly journals Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation

Perfusion ◽  
2018 ◽  
Vol 33 (1_suppl) ◽  
pp. 80-86 ◽  
Author(s):  
Pavla Pokorná ◽  
Martin Šíma ◽  
Václav Vobruba ◽  
Dick Tibboel ◽  
Ondřej Slanař
Keyword(s):  
Body Weight ◽  
Extracorporeal Membrane Oxygenation ◽  
Volume Of Distribution ◽  
Individual Variability ◽  
Therapeutic Drug ◽  
Pharmacokinetic Data ◽  
Serum Concentrations ◽  
Linear Regression Models ◽  
Membrane Oxygenation ◽  
Neonates And Infants

Introduction: The disposition of drugs is potentially changed due to extracorporeal membrane oxygenation (ECMO) in neonates and infants. Methods: The aim of the study was to evaluate the individual pharmacokinetics (PK) of phenobarbital and the effect of PK covariates in neonates and infants undergoing ECMO. Sixteen patients (7 neonates, 9 infants) treated with phenobarbital during ECMO (centrifugal-flow pump circuits) were enrolled in the PK study. Phenobarbital serum concentrations were measured using a fluorescence polarization immunoassay. Individual PK parameters - volume of distribution (Vd) and clearance (CL) were calculated in a one-compartmental pharmacokinetic model. Results: The mean (SD) Vd and CL values in neonates were 0.46 (0.24) L/kg and 8.0 (4.5) mL/h/kg, respectively. Respective values in infants were 0.56 (0.23) L/kg and 8.5 (3.1) mL/h/kg. PK parameters in neonates and infants were not significantly different. We observed high inter-individual variability in PK parameters (coefficients of variation [CV] were 52% and 53% for CL and Vd, respectively). Doses were adjusted based on therapeutic drug monitoring (TDM) in 87.5% patients. Only 50% of the first measured phenobarbital serum concentrations in each patient were within the therapeutic range of 10-40 mg/L, in comparison with 88.6% concentration measured after TDM implementation. Linear regression models showed that both Vd and CL are significantly related with body weight (BW) and length. Median optimal phenobarbital loading dose (LD) and maintenance dose (MD), calculated from pharmacokinetic data, were 15 mg/kg and 4 mg/kg/day, respectively. Conclusions: Body weight was shown to be the main PK covariate of phenobarbital disposition. Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO.

Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

2019 ◽  
Author(s):  
Natalia Sutiman ◽  
Janine Cynthia Koh ◽  
Kevin Watt ◽  
Christoph Hornik ◽  
Beverly Murphy ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Drug Disposition ◽  
Ex Vivo ◽  
Volume Of Distribution ◽  
Controlled Vocabulary ◽  
Systematic Evaluation ◽  
Inclusion Criteria ◽  
Membrane Oxygenation ◽  
Drug Classes ◽  
Dose Recommendations

Abstract BACKGROUNDTo identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps and inform future clinical pharmacology studies.METHODSWe systematically searched the following databases from earliest publication until November 2018: MEDLINE, CINAHL and EMBASE, using a controlled vocabulary and keywords related to: “ECMO”, and “pharmacokinetics”, “pharmacology”, “drug disposition”, “dosing” and “pediatrics”. Inclusion criteria were: study population aged <18 years, supported on ECMO for any indications, receiving any medications while on ECMO and reported pharmacokinetics data. Clearance and/or volume of distribution (Vd) values were extracted from the included studies.RESULTS41 studies (total patients=574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were anti-microbials (n=13), and anticonvulsants (n=3). 28 studies (68%) were conducted in children < 1 year of age. 33 studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in Vd attributable to ECMO was demonstrated for 9 (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased Vd was reported for 2 drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine and sildenafil (range: 25-455% increase relative to non-ECMO controls).CONCLUSIONSThere were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes, and those that allow direct comparisons between ECMO and non-ECMO patients, are still lacking. Systematic evaluation of pharmacokinetic alterations of drugs on ECMO that incorporate multi-drug opportunistic trials, physiologically based pharmacokinetic modeling, ex-vivo studies and other methods are necessary for definitive dose recommendations.

Treatment of hyperammonemia using in-line renal replacement and hyperosmolar therapies within an extracorporeal membrane oxygenation circuit

Perfusion ◽  
2021 ◽  
pp. 026765912110359
Author(s):  
Alison Grazioli ◽  
Jamie E Podell ◽  
Aldo Iacono ◽  
Alexander Sasha Krupnik ◽  
Ronson J Madathil ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Cerebral Edema ◽  
Urea Cycle ◽  
Rare Complication ◽  
Volume Of Distribution ◽  
Intermittent Hemodialysis ◽  
Treatment Goals ◽  
Continuous Venovenous Hemofiltration ◽  
Small Molecular Weight ◽  
Membrane Oxygenation

After orthotopic lung transplantation, hyperammonemia can be a rare complication secondary to infection by organisms that produce urease or inhibit the urea cycle. This can cause neurotoxicity, cerebral edema, and seizures. Ammonia is unique in that it has a large volume of distribution. However, it is also readily dialyzable given its small molecular weight. As such, removal of ammonia requires renal replacement modalities that can both rapidly remove ammonia from the plasma space and allow for continuous removal to prevent rebound accumulation from intracellular stores. Prevention of iatrogenic osmotic lowering in this setting is required to prevent worsening of cerebral edema. Herein, we describe use of sequential in-line renal replacement therapy using both intermittent hemodialysis and continuous venovenous hemofiltration within an extracorporeal membrane oxygenation circuit in conjunction with higher sodium dialysate and 7.5% hypertonic saline to achieve these treatment goals.

Extracorporeal membrane oxygenation outcomes in children with hemophagocytic lymphohistiocytosis

Perfusion ◽  
2016 ◽  
Vol 32 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Katherine Cashen ◽  
Roland L Chu ◽  
Justin Klein ◽  
Peter T Rycus ◽  
John M Costello
Keyword(s):  
Risk Factors ◽  
Extracorporeal Membrane Oxygenation ◽  
Cardiac Failure ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Pediatric Patients ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Hemorrhagic Complication ◽  
Membrane Oxygenation ◽  
Va Ecmo

Introduction: Pediatric patients with hemophagocytic lymphohistiocytosis (HLH) may develop refractory respiratory or cardiac failure that warrants consideration for extracorporeal membrane oxygenation (ECMO) support. The purposes of this study were to describe the use and outcomes of ECMO in pediatric HLH patients, to identify risk factors for hospital mortality and to compare their ECMO use and outcomes to the ECMO population as a whole. Methods: Pediatric patients (⩽ 18 years) with a diagnosis of HLH in the Extracorporeal Life Support Organization (ELSO) Registry were included. Results: Between 1983 and 2014, data for 30 children with HLH were available in the ELSO registry and all were included in this study. All cases occurred in the last decade. Of the 30 HLH patients, 24 (80%) had a respiratory indication for ECMO and six (20%) had a cardiac indication (of which 4 were E-CPR and 2 cardiac failure). Of the 24 respiratory ECMO patients, 63% were placed on VA ECMO. Compared with all pediatric patients in the ELSO registry during the study period (n=17,007), HLH patients had worse hospital survival (non-HLH 59% vs HLH 30%, p=0.001). In pediatric HLH patients, no pre-ECMO risk factors for mortality were identified. The development of a hemorrhagic complication on ECMO was associated with decreased mortality (p=0.01). Comparing HLH patients with respiratory failure to patients with other immune compromised conditions, the overall survival rate is similar (HLH 38% vs. non-HLH immune compromised 31%, p=0.64). Conclusions: HLH is an uncommon indication for ECMO and these patients have increased mortality compared to the overall pediatric ECMO population. These data should be factored into decision-making when considering ECMO for pediatric HLH patients.

Procainamide pharmacokinetics during extracorporeal membrane oxygenation

Perfusion ◽  
2021 ◽  
pp. 026765912110506
Author(s):  
Nicholas J Vollmer ◽  
Erica D Wittwer ◽  
Andrew N Rosenbaum ◽  
Patrick M Wieruszewski
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Elevated Serum ◽  
Stable Condition ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Therapeutic Drug ◽  
Slow Acetylator ◽  
Membrane Oxygenation ◽  
Serum And Urine

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

scholarly journals Kinetics of Procalcitonin in Pediatric Patients on Extracorporeal Membrane Oxygenation

2018 ◽  
Vol 13 ◽  
pp. 117727191775190 ◽  
Author(s):  
Sara Bobillo ◽  
Javier Rodríguez-Fanjul ◽  
Anna Solé ◽  
Julio Moreno ◽  
Mònica Balaguer ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Prospective Observational Study ◽  
Pediatric Patients ◽  
Clinical Situation ◽  
Multiple Organ ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Membrane Oxygenation ◽  
Neurologic Sequelae ◽  
Kinetics Of

Objectives: To assess the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) in pediatric patients who required extracorporeal membrane oxygenation (ECMO) and to analyze its relationship with morbidity and mortality. Patients and methods: Prospective observational study including pediatric patients who required ECMO. Both PCT and CRP were sequentially drawn before ECMO (P0) and until 72 hours after ECMO. Results: A total of 40 patients were recruited. Two cohorts were established based on the value of the P0 PCT (>10 ng/mL). Comparing the kinetics of PCT and CRP in these cohorts, the described curves were the expected for each clinical situation. The cutoff for P0 PCT to predict multiple organ dysfunction syndrome was 2.55 ng/mL (sensibility 83%, specificity 100%). Both PCT and CRP did not predict risk of neurologic sequelae or mortality in any group. Conclusions: Procalcitonin does not seem to be modified by ECMO and could be a good biomarker of evolution.

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