Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation

Abstract

Extracorporeal membrane oxygenation (ECMO) is a life-support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965-July 2016), EMBASE (1965-July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.

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 …”

Continuous infusion chemotherapy, radiotherapy, and FDG‐PET are feasible during extracorporeal membrane oxygenation

“…We opted to treat the patient with DA‐EPOCH at dose level three to account for the potential of drug loss from ECMO as protein‐bound drugs are particularly prone to sequestration in the circuit 5,24,25 . Although cyclophosphamide is not significantly protein bound, doxorubicin and etoposide are both largely bound to plasma proteins.…”

Case report of massive hemoptysis in pregnancy requiring veno‐venous extracorporeal membrane oxygenation

“…Anticoagulation must be approached with caution, however, because ECMO causes thrombocytopenia from cell lysis and up to 12% of pregnant women are thrombocytopenic at baseline . ECMO additionally alters drug bioavailability from sequestration . When sequestration combines with pregnancy‐related changes such as protein binding, tissue uptake, volume expansion and renal function, medication dosing on ECMO becomes significantly more complicated .…”

“…ECMO additionally alters drug bioavailability from sequestration . When sequestration combines with pregnancy‐related changes such as protein binding, tissue uptake, volume expansion and renal function, medication dosing on ECMO becomes significantly more complicated . Lastly, delivery of the fetus in an acutely ill mother may not improve her cardiorespiratory status and must be weighed against the risks of significant blood loss in an unstable patient.…”