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.

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 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.

Sufentanil pharmacokinetics in a full-term neonate treated with extracorporeal membrane oxygenation: a case report

Perfusion ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 433-436 ◽  
Author(s):  
Pavla Pokorná ◽  
Martin Šíma ◽  
Václav Vobruba ◽  
Martina Bašková ◽  
Lenka Posch ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Case Report ◽  
Extracorporeal Membrane Oxygenation ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Analgesic Drug ◽  
Membrane Oxygenation ◽  
Ischemic Encephalopathy

Introduction: Sufentanil is a potent analgesic drug used for pain management. A few studies describe the pharmacokinetics of sufentanil in neonates; however, no pharmacokinetic data about sufentanil during extracorporeal membrane oxygenation have been published yet. Case report: A 1-day-old neonate with moderate hypoxic–ischemic encephalopathy received veno-arterial extracorporeal membrane oxygenation support for refractory respiratory and circulatory failure. Sufentanil plasma concentrations were determined during both extracorporeal membrane oxygenation (n = 14) and non–extracorporeal membrane oxygenation (n = 17) period. Based on these measurements, individual sufentanil pharmacokinetic parameters were calculated. Discussion: We observed increased sufentanil volume of distribution (11.6 vs 5.6 L/kg) and decreased sufentanil clearance (0.535 vs 0.746 L/h/kg) in extracorporeal membrane oxygenation period. The increment of volume of distribution was attributed to ECMO influence, while difference in clearance was probably due to drug interaction. Conclusions: This is the first description of sufentanil pharmacokinetics in neonate treated with extracorporeal membrane oxygenation. We observed considerably larger volume of distribution during extracorporeal membrane oxygenation period in comparison with non–extracorporeal membrane oxygenation period.

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.

Factors affecting the outcome of extracorporeal membrane oxygenation following paediatric cardiac surgery

2019 ◽  
Vol 29 (12) ◽  
pp. 1501-1509 ◽  
Author(s):  
Ahmed M. Dohain ◽  
Gaser Abdelmohsen ◽  
Ahmed A. Elassal ◽  
Ahmed F. ElMahrouk ◽  
Osman O. Al-Radi
Keyword(s):  
Cardiac Surgery ◽  
Extracorporeal Membrane Oxygenation ◽  
Hospital Discharge ◽  
University Hospital ◽  
P Value ◽  
Biventricular Repair ◽  
Factors Affecting ◽  
Membrane Oxygenation ◽  
Paediatric Cardiac Surgery ◽  
Neonates And Infants

AbstractBackground:Extracorporeal membrane oxygenation has been widely used after paediatric cardiac surgery due to increasing complex surgical repairs in neonates and infants having complex CHDs.Materials and methods:We reviewed retrospectively the medical records of all patients with CHD requiring corrective or palliative cardiac surgery at King Abdulaziz University Hospital that needed extracorporeal membrane oxygenation support between November 2015 and November 2018.Results:The extracorporeal membrane oxygenation population was 30 patients, which represented 4% of 746 children who had cardiac surgery during this period. The patients’ age range was from 1 day to 20.33 years, with a median age of 6.5 months. Median weight was 5 kg (range from 2 to 53 kg). Twenty patients were successfully decannulated (66.67%), and 12 patients (40%) were survived to hospital discharge. Patients with biventricular repair tended to have better survival rate compared with those with single ventricle palliation (55.55 versus 16.66%, p-value 0.058). During the first 24 hours of extracorporeal membrane oxygenation support, the flow rate was significantly reduced after 4 hours of extracorporeal membrane oxygenation connection in successfully decannulated patients.Conclusion:Survival to hospital discharge in patients requiring extracorporeal membrane oxygenation support after paediatric cardiac surgery was better in those who underwent biventricular repair than in those who had univentricular palliation. Capillary leak on extracorporeal membrane oxygenation could be a risk of mortality in patients after paediatric cardiac surgery.

scholarly journals Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Dennis Kühn ◽  
Carlos Metz ◽  
Frederik Seiler ◽  
Holger Wehrfritz ◽  
Sophie Roth ◽  
...  
Keyword(s):  
Intensive Care ◽  
Renal Replacement Therapy ◽  
Therapeutic Drug Monitoring ◽  
Extracorporeal Membrane Oxygenation ◽  
Replacement Therapy ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Icu Patients ◽  
Intensive Care Patients

Abstract Background Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

Pharmacokinetics of linezolid for methicillin-resistant Staphylococcus aureus pneumonia in an adult receiving extracorporeal membrane oxygenation

2020 ◽  
Vol 77 (11) ◽  
pp. 877-881 ◽  
Author(s):  
Peter Nikolos ◽  
Justin Osorio ◽  
Kerry Mohrien ◽  
Christina Rose
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Failure ◽  
Extracorporeal Membrane Oxygenation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Minimum Concentration ◽  
Methicillin Resistant ◽  
Membrane Oxygenation

Abstract Purpose We present a case of a 55-year-old man post right lung transplantation receiving ECMO for treatment of respiratory failure secondary to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Summary Extracorporeal membrane oxygenation (ECMO) is a frequently utilized support therapy for patients with cardiac and/or respiratory failure. Dosing of medications during ECMO can be challenging due to several factors, including sequestration of medications within ECMO circuits, alterations in volume of distribution, and changes in drug clearance. The patient was initiated on empiric antibiotics, then switched to linezolid at a dose of 600 mg every 8 hours. Linezolid plasma concentrations were collected 30 minutes prior to the sixth administered dose and 30 minutes following the 1-hour infusion of the sixth dose, which resulted in values of 0.4 and 1.7 μg/mL, respectively. The ratio of 24-hour area under the curve (AUC0-24) to minimum inhibitory concentration (MIC), assuming a MIC of 2 μg/mL, was calculated using the extrapolated maximum concentration (1.9 μg/mL) and minimum concentration (0.35 μg/mL), resulting in an AUC0-24/MIC value of 10.8. Due to subtherapeutic linezolid plasma concentrations, ceftaroline was initiated and continued for a total of 18 days. To our knowledge, this is the second report to describe inadequate plasma concentrations of linezolid during ECMO. Conclusion In the case described here, linezolid at a dose of 600 mg every 8 hours did not achieve target plasma concentrations in a patient receiving concomitant venovenous ECMO support.

scholarly journals Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Jin Wi ◽  
Hayeon Noh ◽  
Kyoung Lok Min ◽  
Seungwon Yang ◽  
Byung Hak Jin ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Trough Concentration ◽  
Optimal Dose ◽  
Volume Of Distribution ◽  
Membrane Oxygenation ◽  
Venoarterial Extracorporeal Membrane Oxygenation ◽  
Optimal Dosing ◽  
Population Pk ◽  
Severe Infections ◽  
Central Volume

ABSTRACT The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

Thyroid function in neonates with severe respiratory failure on extracorporeal membrane oxygenation

Perfusion ◽  
2001 ◽  
Vol 16 (6) ◽  
pp. 469-475 ◽  
Author(s):  
Dan L Stewart ◽  
Noah Ssemakula ◽  
Duncan R MacMillan ◽  
L Jane Goldsmith ◽  
Larry N Cook
Keyword(s):  
Respiratory Failure ◽  
Extracorporeal Membrane Oxygenation ◽  
Thyroid Function ◽  
Newborn Infants ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Function Tests ◽  
Severe Respiratory Failure ◽  
Serum Concentrations ◽  
Free Triiodothyronine ◽  
Membrane Oxygenation

The object was to study thyroid function in neonates with severe respiratory failure on extracorporeal membrane oxygenation (ECMO) and determine whether abnormal thyroid function correlates with prognosis. Total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), reverse triiodothyronine (rT3), thyroid-stimulating hormone, and thyroxine binding globulin were measured in 14 newborn infants with severe respiratory failure (age 1-30 days) from samples collected before anesthesia for cannula placement, at 30, 60, and 360 min after initiation of ECMO, and on days 2, 4, 6, and 8. The patients were divided into survivors and non-survivors for statistical analyses. No differences were noted between survivors and non-survivors in the pre-ECMO mean serum concentrations of the thyroid function tests analyzed. In nine survivors, mean serum T4, FT4, T3, FT3, and rT3 all declined significantly within 30-60 min after initiation of ECMO, compared to baseline values. The values for all mean serum concentrations recovered completely and exceeded baseline between days 2 and 8. In five non-survivors, the decline of all mean serum values was not statistically significant and recovery to baseline was not achieved. The ratios of mean serum concentration of rT3/FT3were significantly different between survivors and non-survivors across all times during the ECMO course ( p λ 0.0005). These findings indicate that abnormalities in thyroid function occur in neonates with severe respiratory failure on ECMO and that the rT3/FT3 ratio correlates with prognosis over the ECMO course. Survival was associated with a significant reduction of serum thyroid hormone concentrations followed by recovery. We speculate that, in neonates with respiratory failure on ECMO, adaptive mechanisms which enhance survival include the capacity to down-regulate the pituitary-thyroid axis.

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