Dataset Information

Impaired Pharmacokinetics of Amiodarone under Veno-Venous Extracorporeal Membrane Oxygenation: From Bench to Bedside.

ABSTRACT:

Background

Adjusting drug therapy under veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging. Although impaired pharmacokinetics (PK) under VV ECMO have been reported for sedative drugs and antibiotics, data about amiodarone are lacking. We evaluated the pharmacokinetics of amiodarone under VV ECMO both in vitro and in vivo.

Methods

In vitro: Amiodarone concentration decays were compared between closed-loop ECMO and control stirring containers over a 24 h period. In vivo: Potassium-induced cardiac arrest in 10 pigs with ARDS, assigned to either control or VV ECMO groups, was treated with 300 mg amiodarone injection under continuous cardiopulmonary resuscitation. Pharmacokinetic parameters C_max, T_max AUC and F were determined from both direct amiodarone plasma concentrations observation and non-linear mixed effects modeling estimation.

Results

An in vitro study revealed a rapid and significant decrease in amiodarone concentrations in the closed-loop ECMO circuitry whereas it remained stable in control experiment. In vivo study revealed a 32% decrease in the AUC and a significant 42% drop of C_max in the VV ECMO group as compared to controls. No difference in T_max was observed. VV ECMO significantly modified both central distribution volume and amiodarone clearance. Monte Carlo simulations predicted that a 600 mg bolus of amiodarone under VV ECMO would achieve the amiodarone bioavailability observed in the control group.

Conclusions

This is the first study to report decreased amiodarone bioavailability under VV ECMO. Higher doses of amiodarone should be considered for effective amiodarone exposure under VV ECMO.

SUBMITTER: Lescroart M

PROVIDER: S-EPMC9147299 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Impaired Pharmacokinetics of Amiodarone under Veno-Venous Extracorporeal Membrane Oxygenation: From Bench to Bedside.

Lescroart Mickaël M Pressiat Claire C Péquignot Benjamin B Tran N'Guyen N Hébert Jean-Louis JL Alsagheer Nassib N Gambier Nicolas N Ghaleh Bijan B Scala-Bertola Julien J Levy Bruno B

Pharmaceutics 20220430 5

<h4>Background</h4>Adjusting drug therapy under veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging. Although impaired pharmacokinetics (PK) under VV ECMO have been reported for sedative drugs and antibiotics, data about amiodarone are lacking. We evaluated the pharmacokinetics of amiodarone under VV ECMO both in vitro and in vivo.<h4>Methods</h4>In vitro: Amiodarone concentration decays were compared between closed-loop ECMO and control stirring containers over a 24 h perio ...[more]

PMID: 35631560

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Project description:ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28-57) years and SOFA score was 14 (12-17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12-123) at V-VA ECMO upgrade to 9 (3-37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6-22) days and ICU length of stay was 32 (16-46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

Project description:BackgroundWe tested the effect of different blood flow levels in the extracorporeal circuit on the measurements of cardiac stroke volume (SV), global end-diastolic volume index (GEDVI) and extravascular lung water index derived from transpulmonary thermodilution (TPTD) in 20 patients with severe acute respiratory distress syndrome (ARDS) treated with veno-venous extracorporeal membrane oxygenation (ECMO).MethodsComparative SV measurements with transesophageal echocardiography and TPTD were performed at least 5 times during the treatment of the patients. The data were interpreted with a Bland-Altman analysis corrected for repeated measurements. The interchangeability between both measurement modalities was calculated and the effects of extracorporeal blood flow on SV measurements with TPTD was analysed with a linear mixed effect model. GEDVI and EVLWI measurements were performed immediately before the termination of the ECMO therapy at a blood flow of 6 l/min, 4 l/min and 2 l/min and after the disconnection of the circuit in 7 patients.Results170 pairs of comparative SV measurements were analysed. Average difference between the two modalities (bias) was 0.28 ml with an upper level of agreement of 40 ml and a lower level of agreement of -39 ml within a 95% confidence interval and an overall interchangeability rate between TPTD and Echo of 64%. ECMO blood flow did not influence the mean bias between Echo and TPTD (0.03 ml per l/min of ECMO blood flow; p = 0.992; CI - 6.74 to 6.81). GEDVI measurement was not significantly influenced by the blood flow in the ECMO circuit, whereas EVLWI differed at a blood flow of 6 l/min compared to no ECMO flow (25.9 ± 10.1 vs. 11.0 ± 4.2 ml/kg, p = 0.0035).ConclusionsIrrespectively of an established ECMO therapy, comparative SV measurements with Echo and TPTD are not interchangeable. Such caveats also apply to the interpretation of EVLWI, especially with a high blood flow in the extracorporeal circulation. In such situations, the clinician should rely on other methods of evaluation of the amount of lung oedema with the haemodynamic situation, vasopressor support and cumulative fluid balance in mind.Trial registrationGerman Clinical Trials Register (DRKS00021050). Registered 03/30/2020 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017237.

Project description:Background The use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) has rapidly increased in recent years. Today, applications of V-V ECMO include a variety of clinical conditions such as acute respiratory distress syndrome (ARDS), bridge to lung transplantation and primary graft dysfunction after lung transplantation. The purpose of the present study was to investigate in-hospital mortality of adult patients undergoing V-V ECMO therapy and to determine independent predictors associated with mortality. Methods This retrospective study was conducted at the University Hospital Zurich, a designated ECMO center in Switzerland. Data was analyzed of all adult V-V ECMO cases from 2007 to 2019. Results In total, 221 patients required V-V ECMO support (median age 50 years, 38.9% female). In-hospital mortality was 37.6% and did not statistically vary significantly between indications (P=0.61): 25.0% (1/4) for primary graft dysfunction after lung transplantation, 29.4% (5/17) for bridge to lung transplantation, 36.2% (50/138) for ARDS and 43.5% (27/62) for other pulmonary disease indications. Cubic spline interpolation showed no effect of time on mortality over the study period of 13 years. Multiple logistic regression modelling identified significant predictor variables associated with mortality: age [odds ratio (OR), 1.05; 95% confidence interval (CI): 1.02–1.07; P=0.001], newly detected liver failure (OR, 4.83; 95% CI: 1.27–20.3; P=0.02), red blood cell transfusion (OR, 1.91; 95% CI: 1.39–2.74; P<0.001) and platelet concentrate transfusion (OR, 1.93; 95% CI: 1.28–3.15; P=0.004). Conclusions In-hospital mortality of patients receiving V-V ECMO therapy remains relatively high. Patients’ outcomes have not improved significantly in the observed period. We identified age, newly detected liver failure, red blood cell transfusion and platelet concentrate transfusion as independent predictors associated with in-hospital mortality. Incorporating such mortality predictors into decision making with regards to V-V ECMO use may increase its effectiveness and safety and may translate into better outcomes.

Dataset Information

Impaired Pharmacokinetics of Amiodarone under Veno-Venous Extracorporeal Membrane Oxygenation: From Bench to Bedside.

Background

Methods

Results

Conclusions

Publications

Impaired Pharmacokinetics of Amiodarone under Veno-Venous Extracorporeal Membrane Oxygenation: From Bench to Bedside.

Similar Datasets

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