Optimising drug dosing in patients receiving extracorporeal membrane oxygenation

Abstract

Optimal pharmacological management during extracorporeal membrane oxygenation (ECMO) involves more than administering drugs to reverse underlying disease. ECMO is a complex therapy that should be administered in a goal-directed manner to achieve therapeutic endpoints that allow reversal of disease and ECMO wean, minimisation of complications (treatment of complications when they do occur), early interruption of sedation and rehabilitation, maximising patient comfort and minimising risks of delirium. ECMO can alter both the pharmacokinetics (PK) and pharmacodynamics (PD) of administered drugs and our understanding of these alterations is still evolving. Based on available data it appears that modern ECMO circuitry probably has a less significant impact on PK when compared with critical illness itself. However, these findings need further confirmation in clinical population PK studies and such studies are underway. The altered PD associated with ECMO is less understood and more research is indicated. Until robust dosing guidelines become available, clinicians will have to rely on the principles of drug dosing in critically ill and known PK alterations induced by ECMO itself. This article summarises the PK alterations and makes preliminary recommendations on possible dosing approaches.

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

“…Venoarterial ECMO (VA-ECMO) provides support for both the heart and the lungs, while venovenous ECMO (VV-ECMO) only provides respiratory support. An increasing number of studies have shown that ECMO is associated with significant pharmacokinetic (PK) alterations, including an increased volume of distribution and reduced clearance ( 10 – 13 ). Studies on whether the PK of caspofungin will change in patients receiving ECMO are very limited and controversial.…”

Comparison of Hydromorphone versus Fentanyl‐based Sedation in Extracorporeal Membrane Oxygenation: A Propensity‐Matched Analysis

“…Consensus guidelines recommend the use of sedation for patients receiving ECMO cannulation during the first 12–24 hours post‐cannulation, followed by minimal sedation thereafter to maintain patient comfort and prevent complications 1 . Optimization of sedation in these patients is crucial; however, altered drug pharmacokinetics (PK) in patients receiving ECMO may contribute to therapeutic failure of these agents 2‐5 …”

Perspectives on adjunctive use of ketamine for analgosedation during extracorporeal membrane oxygenation

“…Degradation of drugs may further worsen PK derangements. ECMO has also been shown to exacerbate the PK alterations of some drugs and may lead to either therapeutic failure or toxicity [7].…”