Medicating Patients During Extracorporeal Membrane Oxygenation: The Evidence is Building

Abstract

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at

Ventilatory and Pharmacotherapeutic Strategies for Management of Adult Patients on Extracorporeal Life Support

“…Most β‐lactams are hydrophilic molecules, primarily eliminated by the kidneys, and have low to moderate protein binding (exception ceftriaxone), making these agents highly susceptible to pharmacokinetic changes from critical illness and, potentially, from the addition of an extracorporeal circuit. Significant losses of meropenem, a highly lipophilic carbapenem, were observed in some studies, whereas more recent ex vivo studies noted minimal loss of cephalosporins and carbapenems in the ECLS circuit . A retrospective case‐control study observed no significant differences in pharmacokinetics with either piperacillin‐tazobactam or meropenem in patients managed with or without ECLS .…”

“…If lower ventilator settings confer a lesser risk of VILI, then removal of the ventilator would eliminate the risk of the ventilator altogether. In practice, endotracheal extubation is the preferred approach for those awaiting lung transplantation, where being awake, mobile, and free of ventilator‐associated complications are all vital to maintaining transplant candidacy . In patients with ARDS, an awake extubated strategy would certainly be preferred from the perspective of avoiding ventilator complications, but it is often difficult to identify those patients in whom such a strategy will be tolerated while still maintaining sufficient gas exchange.…”

“…Clinicians often develop dosing regimens in this patient population based on extrapolations of results from pharmacokinetic studies in healthy individuals. However, pharmacokinetic changes resulting from critical illness and the extracorporeal circuit can lead to significant and unpredictable alterations in the relationship between the dose of a drug and the intended response . Inappropriate dosing may result in either therapeutic failure or toxicity and may vacillate during the patient's continuum of critical illness.…”

“…Drugs that are highly protein bound and lipophilic have greater potential for sequestration within the ECLS circuit, resulting in low serum concentrations and therapeutic failure (Figures and ) . Hydrophilic drugs may have an increase in Vd, as a consequence of the ECLS circuit, from either the increased volume from the priming solution or activation of an inflammatory response . Changes in blood flow to the kidneys and liver, as a consequence of the critical illness, may lead to increased or decreased clearance of drugs; however, the contribution of ECLS on organ perfusion remains elusive …”

“…Vancomycin, a moderately protein‐bound hydrophilic glycopeptide antimicrobial, was not shown to have altered clearance or Vd in patients receiving ECLS in three cohort studies . Vancomycin should be dosed during ECLS support with the same approach used for critically ill patients not receiving ECLS.…”