scholarly journals Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation.

1996 ◽  
Vol 40 (5) ◽  
pp. 1139-1142 ◽  
Author(s):  
R D Amaker ◽  
J T DiPiro ◽  
J Bhatia
Keyword(s):  
Renal Impairment ◽  
Extracorporeal Membrane Oxygenation ◽  
Half Life ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Published Data ◽  
Term Infants ◽  
Circulating Blood Volume ◽  
Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a widely used therapy for neonates with respiratory failure. Because of sepsis, many of these infants require antibiotics like vancomycin during ECMO treatment. ECMO transiently alters renal function and increases the circulating blood volume by 75%. Initial vancomycin pharmacokinetics were determined in 12 infants undergoing ECMO to determine an adequate drug administration regimen. Vancomycin dosage was based on current recommendations for weight and gestational age. Pharmacokinetic parameters were determined by fitting the data to a two compartment model. This study yielded a mean steady-state volume of distribution of 1.1 +/- 0.5 (range, 0.6 to 2.1) liters/kg and a mean vancomycin clearance of 0.78 +/- 0.19 (range, 0.49 to 1.07) ml/min/kg. The mean vancomycin half-life was 16.9 +/- 9.5 (range, 8.8 to 42.9) h. Nomogram-calculated creatinine clearance was a significant predictor of vancomycin terminal rate constant and clearance. These data suggest alterations in the pharmacokinetics of vancomycin in infants on ECMO. With the goal of achieving vancomycin concentrations in serum above the MIC for the offending pathogen while using the least amount of the drug necessary, new administration guidelines for term infants without renal impairment undergoing ECMO should be 20 mg of vancomycin per kg at an interval of 24 h. With significant renal impairment, the interval should be extended on the basis of concentrations in serum. In comparison with previously published data, the neonates undergoing ECMO in our study demonstrated a much larger volume of distribution, a lower clearance, and consequently a longer vancomycin half-life.

scholarly journals Fluconazole Population Pharmacokinetics and Dosing for Prevention and Treatment of Invasive Candidiasis in Children Supported with Extracorporeal Membrane Oxygenation

2015 ◽  
Vol 59 (7) ◽  
pp. 3935-3943 ◽  
Author(s):  
Kevin M. Watt ◽  
Daniel Gonzalez ◽  
Daniel K. Benjamin ◽  
Kim L. R. Brouwer ◽  
Kelly C. Wade ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Mixed Effect ◽  
Final Model ◽  
Content Type ◽  
Membrane Oxygenation ◽  
Nonlinear Mixed Effect ◽  
Nonlinear Mixed Effect Modeling ◽  
Drug Pharmacokinetics

ABSTRACTCandidainfections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal drug exposures. The objective of our study was to determine the PK of fluconazole in children on ECMO. Forty children with 367 PK samples were included in the analysis. The PK data were analyzed using nonlinear mixed-effect modeling (NONMEM). A one-compartment model best described the data. Weight was included in the base model for clearance (CL) and volume of distribution (V). The final model included the effect of serum creatinine (SCR) level on CL and the effect of ECMO onVas follows: CL (in liters per hour) = 0.019 × weight × (SCR/0.4)−0.29× exp(ηCL) andV(in liters) = 0.93 × weight × 1.4ECMO× exp(ηV). The fluconazoleVwas increased in children supported by ECMO. Consequently, children on ECMO require a higher fluconazole loading dose for prophylaxis (12 mg/kg of body weight) and treatment (35 mg/kg) paired with standard maintenance doses to achieve exposures similar to those of children not on ECMO.

Population Pharmacokinetics and Dose Optimization of Piperacillin/tazobactam in Critically Ill Patients During Extracorporeal Membrane Oxygenation (ECMO) and Weaned from ECMO

2021 ◽  
Author(s):  
Jongsung Hahn ◽  
Kyoung Lok Min ◽  
Soyoung Kang ◽  
Seungwon Yang ◽  
Byung Hak Jin ◽  
...  
Keyword(s):  
Critical Illness ◽  
Extracorporeal Membrane Oxygenation ◽  
Volume Overload ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Optimal Dosage ◽  
Close Monitoring ◽  
Membrane Oxygenation ◽  
Extended Infusion

Abstract Background: Piperacillin/tazobactam is commonly used for empirical or directed treatment of infections during extracorporeal membrane oxygenation therapy (ECMO). Critical illness and extracorporeal circulation, such as ECMO and continuous renal replacement therapy may alter the pharmacokinetic parameters. We aimed to develop a population pharmacokinetic model of piperacillin/tazobactam in ECMO patients and investigate the optimal dosage regimen to achieve a pharmacodynamics target.Methods: This was a prospective observational study of 26 ECMO patients who received piperacillin/tazobactam. A population PK model was developed using non-linear mixed-effects models and simulations were performed to evaluate patient variables, MIC levels, and dosage regimens in relation to the probability of target attainment (PTA). The acceptable piperacillin PTA was set at ≥90% for 50%ƒT >16 mg/L.Results: A total of 244 samples were collected (163 during ECMO and 81 weaned from ECMO). Thirteen patients (50%) underwent continuous venovenous hemodiafiltration (CVVHDF). In a 2-compartment model, clearance increased by 10.1% when patients weaned from ECMO. Because patients on CVVHDF had a significant residual renal function, CVVHDF was found non-relevant to clearance. Instead, volume overload which was main cause of CVVHDF and membrane adsorption might contribute to the increased volume of distribution. Creatinine clearance (CrCL) calculated by Cockcroft-Gault equation had a significant impact on clearance. Simulation demonstrated that extended infusion should be considered in ECMO patients with CrCL >60 mL/min. Our proposed regimen was extended infusion of 2/0.25 g q8h, 2/0.25 g 6h, 3/0.375 g q 6h, and 4/0.5g q6h for CrCL ≤40, 40–60, 60–130, and >130 mL/min, respectively. Furthermore, even a higher dose would be required when patients did not receive CVVHDF after weaning from ECMO, which was 4/0.5g q6h for CrCL >110 mL/minConclusions: Piperacillin/tazobactam PK changes observed in ECMO patients were associated with critical illness rather than ECMO itself. A recent guideline dose may result in underexposure against P.aeruginosa when ECMO patients have CrCL > 110 mL/min; therefore, close monitoring of renal clearance is crucial in ECMO patients who received piperacillin/tazobactam regardless of CVVHDF use to provide effective treatment of infections and promote recovery. Overall, this study provides preliminary insights into the incremental effects of critical illness, ECMO and CVVHDF on piperacillin/tazobactam PK.Trial Registration: Clinicaltrials.gov NCT02581280, December 1st, 2014.

Pharmacokinetics of Midazolam in Neonates Undergoing Extracorporeal Membrane Oxygenation

2003 ◽  
Vol 99 (2) ◽  
pp. 275-282 ◽  
Author(s):  
Hussain Mulla ◽  
Peter McCormack ◽  
Graham Lawson ◽  
Richard K. Firmin ◽  
David Robert Upton
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Standard Error ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Ratio ◽  
Critically Ill Children ◽  
Pharmacokinetic Analysis ◽  
Parameter Estimates ◽  
Membrane Oxygenation ◽  
Plasma Half Life

Background Although the pharmacokinetics of midazolam in critically ill children has been described, there are no such reports in extracorporeal membrane oxygenation. Methods The pharmacokinetics of midazolam and 1-hydroxy midazolam after continuous infusion (50-250 microg. kg(-1). h(-1)) were determined in 20 neonates undergoing extracorporeal membrane oxygenation. Patients were randomized into two groups: group 1 (n = 10) received midazolam extracorporeally (into the circuit), and group 2 received drug via central or peripheral access. Blood samples for determination of plasma concentrations were taken at baseline, 2, 4, 6, 12, 18, and 24 h, then every 12 h. Population pharmacokinetic analysis and model building was conducted using WinNonMix (Pharsight Corporation, Mountain View, CA). The 1-hydroxy midazolam/midazolam metabolic ratio was determined as a surrogate marker of cytochrome P450 3A activity. Results The parameter estimates (n = 19) were based on a one-compartment model with time-dependent change in volume of distribution. Volume (mean +/- standard error) expanded monoexponentially from the onset of extracorporeal membrane oxygenation to a maximum value, 0.8 l +/- 0.5 and 4.1 +/- 0.5 l/kg, respectively. Consequently, plasma half-life was substantially prolonged (median [range]) from onset to steady-state: 6.8 (2.2-39.8) and 33.3 (7.4-178) h, respectively. Total body clearance was determined as (mean +/- standard error) 1.4 +/- 0.15 ml. kg-1. min-1. The median metabolic ratio was 0.17 (0.03-0.9). No significant differences were observed between the two groups with respect to parameter estimates. Simulations of plasma concentration profiles revealed excess levels at conventional doses. Conclusions These results reveal significantly increased volume of distribution and plasma half-life in neonates receiving extracorporeal membrane oxygenation. Altered kinetics may reflect sequestration of midazolam by components of the extracorporeal membrane oxygenation circuit.

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.

scholarly journals 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S562-S562
Author(s):  
Younghee Jung ◽  
Dong-Hwan Lee ◽  
Hyoung Soo Kim
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Creatinine Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Test Model ◽  
Mixed Effect ◽  
Korean Patients ◽  
Membrane Oxygenation ◽  
Population Pk

Abstract Background There is no literature on population pharmacokinetics (PK) of vancomycin in Korean patients receiving extracorporeal membrane oxygenation (ECMO) therapy. The aim of this study was to develop a population PK model for vancomycin in Korean ECMO patients. Methods We prospectively enrolled adult patients who were undergoing ECMO and receiving vancomycin from July 2018 to April 2019. After initial dose of vancomycin was administrated, serial blood samples (seven to nine times per patient) were drawn before the next dose. A population PK model for vancomycin was developed using a nonlinear mixed-effect modeling. Age, sex, creatinine clearance, and body weight were tested as potential covariates in the model. Model selection was based on log-likelihood test, model diagnostic plots, and clinical plausibility. Results Fourteen patients were included over the period. Ten received venovenous, three venoarterial, and one both type ECMO. Eleven were men and the median age was 54 (interquartile range 45–66.3). Mean estimated glomerular filtration rate (eGFR) was 69 ± 46 mL/minute/1.73m2 by the modification of diet in renal disease equation. A total of 123 vancomycin concentrations from the patients were included in the analysis. The population PK of vancomycin was best described by a two-compartment model with a proportional residual error model. The typical value (%between-subject variability) for total clearance was estimated to be 4.33 L/h (21.6%), central volume of distribution was 9.22 L, the intercompartmental clearance was 10.75 L/hr (34.9%) and the peripheral volume of distribution was 19.6 L (26.6%). The proportional residual variability was 8.81%. Creatinine clearance significantly influenced vancomycin clearance (CL). The proposed equation to estimate vancomycin clearance in Korean ECMO patients was CL = 4.33 + 0.199 × (eGFR – 56). Conclusion A two-compartment population PK model successfully describes vancomycin PK profiles in Korean ECMO patients. The model could be used to optimize the dosing regimen if more data become available from currently ongoing clinical study. Disclosures All authors: No reported disclosures.

scholarly journals Zidovudine Pharmacokinetics in Premature Infants Exposed to Human Immunodeficiency Virus

1998 ◽  
Vol 42 (4) ◽  
pp. 808-812 ◽  
Author(s):  
Mark Mirochnick ◽  
Edmund Capparelli ◽  
Wayne Dankner ◽  
Rhoda S. Sperling ◽  
Russ van Dyke ◽  
...  
Keyword(s):  
Half Life ◽  
Population Analysis ◽  
Volume Of Distribution ◽  
Preterm Neonates ◽  
Pharmacokinetic Parameters ◽  
Term Infants ◽  
Standard Dosage ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Toxic Concentrations

ABSTRACT We used population analysis techniques to determine zidovudine (ZDV) pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4 weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the pharmacokinetic parameters were as follows: clearance, 2.53 ± 0.44 ml/min/kg; volume of distribution, 1.59 ± 0.51 liters/kg; and half-life, 7.2 ± 1.5 h. For seven infants studied a second time, at a mean age of 17.7 days, an increase in the mean clearance (2.33 versus 4.35 ml/min/kg; P = 0.024) and a decrease in the half-life (7.3 versus 4.4 h; P = 0.003) were found. The ZDV clearance is low and the half-life is prolonged in premature neonates, but the clearance increases and the half-life decreases with postnatal age. Potentially toxic concentrations may accumulate in serum if the standard dosage for full-term infants is used. We suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for preterm neonates.

scholarly journals Population Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung Transplantation

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Qianlin Wang ◽  
Zhu Zhang ◽  
Donglin Liu ◽  
Wenqian Chen ◽  
Gang Cui ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Lung Transplantation ◽  
Postoperative Period ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Self Control ◽  
Control Group ◽  
Membrane Oxygenation ◽  
Population Pk ◽  
Before And After

ABSTRACT Little is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and to investigate covariates influencing caspofungin PK. We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning as self-controls, to analyzed changes in caspofungin PK. Eight serial blood samples were collected from each patient for PK analysis. The population PK of caspofungin was described using nonlinear mixed-effects modeling. Twelve ECMO and 7 non-ECMO lung transplant recipients were enrolled in this study. None of the patients received renal replacement therapy during any part of the study period. The PK of caspofungin was best described by a two-compartment model. There were no significant differences in the PK parameters and concentrations of caspofungin among the ECMO, non-ECMO, and self-control group. In the final covariate model, we found that there was a significant association between the male gender and increased distribution volume, that a higher sequential organ failure assessment score was related to an increase in intercompartmental clearance, and that a longer operative time was related to an increase in clearance and the volume of distribution. ECMO did not have a significant impact on the PK of caspofungin in patients after LTx. Some factors were identified as statistically significant covariates related to the PK of caspofungin; however, their impact on clinical practice of caspofungin needs to be investigated further in more studies. (This study has been registered at ClinicalTrials.gov under identifier NCT03766282.)

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.

Adenosine Infusion Improves Oxygenation in Term Infants With Respiratory Failure

PEDIATRICS ◽  
1996 ◽  
Vol 97 (3) ◽  
pp. 295-300
Author(s):  
G. Ganesh Konduri ◽  
Daisy C. Garcia ◽  
Nadya J. Kazzi ◽  
Seetha Shankaran
Keyword(s):  
Pulmonary Hypertension ◽  
Placebo Group ◽  
Extracorporeal Membrane Oxygenation ◽  
Normal Saline ◽  
Medical Center ◽  
Blood Gases ◽  
Adenosine Infusion ◽  
Term Infants ◽  
Membrane Oxygenation ◽  
Arterial Blood

Objective. Adenosine infusion causes selective pulmonary vasodilation in fetal and neonatal lambs with pulmonary hypertension. We investigated the effects of a continuous infusion of adenosine on oxygenation in term infants with persistent pulmonary hypertension of newborn (PPHN). Design. A randomized, placebo-controlled, masked trial comparing the efficacy of intravenous infusion of adenosine to normal saline infusion over a 24-hour period. Setting. Inborn and outborn level III neonatal intensive care units at a university medical center. Participants. Eighteen term infants with PPHN and arterial postductal Po2 of 60 to 100 Torr on inspired O2 concentration of 100% and optimal hyperventilation (PaCo2 <30 Torr) were enrolled into the study. Study infants were randomly assigned to receive a placebo infusion of normal saline, or adenosine infusion in doses of 25 to 50 µg/kg/min over a 24-hour period. Results. Nine infants each received adenosine or placebo. The two groups did not differ in birth weight, gestational age, or blood gases and ventilator requirements at the time of entry into the study. Four of nine infants in the adenosine group and none of the placebo group had a significant improvement in oxygenation, defined as an increase in postductal PaO2 of ≥20 Torr from preinfusion baseline. The mean PaO2 in the adenosine group increased from 69 ± 19 at baseline to 94 ± 15 during 50 µg/kg/min infusion rate of adenosine and did not change significantly in the placebo group. Arterial blood pressure and heart rate did not change during the study in either group. The need for extracorporeal membrane oxygenation, incidence of bronchopulmonary dysplasia, and mortality were not different in the two groups. Conclusion. Data from this pilot study indicate that adenosine infusion at a dose of 50 µg/kg/min improves PaO2 in infants with PPHN without causing hypotension or tachycardia. Larger trials are needed to determine its effects on mortality and/or need for extracorporeal membrane oxygenation in infants with PPHN.

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.

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