Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients

ABSTRACT

Introduction: One major challenge to achieving optimal patient outcome in extracorporeal membrane oxygenation (ECMO) is the development of effective dosing strategies in this critically ill patient population. Suboptimal drug dosing impacts on patient outcome as patients on ECMO often require reversal of the underlying pathology with effective pharmacotherapy in order to be liberated of the life-support device.

Areas covered: This article provides a concise review of the effective use of antibiotics, analgesics, and sedative by characterizing the specific changes in PK secondary to the introduction of the ECMO support. We also discuss the barriers to achieving optimal pharmacotherapy in patients on ECMO and also the current and potential research that can be undertaken to address these clinical challenges.

Expert opinion: Decreased bioavailability due to sequestration of drugs in the ECMO circuit and ECMO induced PK alterations are both significant barriers to optimal drug dosing. Evidence-based drug choices may minimize sequestration in the circuit and would enable safety and efficacy to be maintained. More work to characterize ECMO related pharmacodynamic alterations such as effects of ECMO on hepatic cytochrome system are still needed. Novel techniques to increase target site concentrations should also be explored.

KEYWORDS:

• Critical illness
• ECMO
• pharmacokinetics
• pharmacodynamics
• antibiotics
• sedatives
• analgesics

Article highlights

• ECMO is being increasingly adopted into adult intensive care units

• Dosing of sedatives, analgesics, and antibiotics remain empirical with little data available to guide optimized dosing

• Drug physicochemical properties can be used to guide drug and dose choices during ECMO

• Lipophilicity and degree of protein binding are important properties that could inform pharmacokinetic changes in the setting of ECMO

• More robust mechanistic and pharmacokinetic studies are required to measure the degree or absence of a change of drug and pharmacokinetic factors.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.