Haemodynamic, metabolic, and biochemical derangements in critically ill patients affect drug pharmacokinetics and pharmacodynamics making dose optimisation particularly challenging. Appropriate therapeutic dosing depends on the knowledge of the physiologic changes caused by the patient’s comorbidities, underlying disease, resuscitation strategies, and polypharmacy. Critical illness will result in altered drug protein binding, ionisation, and volume of distribution; it will also decrease oral drug absorption, intestinal and hepatic metabolism, and renal clearance. In contrast, the resuscitation strategies and the use of vasoactive drugs may oppose these effects by leading to a hyperdynamic state that will increase blood flow towards the major organs including the brain, heart, kidneys, and liver, with the subsequent increase of drug hepatic metabolism and renal excretion. Metabolism is the main mechanism for drug clearance and is one of the main pharmacokinetic processes affected; it is influenced by patient-specific factors, such as comorbidities and genetics; therapeutic-specific factors, including drug characteristics and interactions; and disease-specific factors, like organ dysfunction. Moreover, organ support such as mechanical ventilation, renal replacement therapy, and extracorporeal membrane oxygenation may contribute to both inter- and intra-patient variability of drug pharmacokinetics. The combination of these competing factors makes it difficult to predict drug response in critically ill patients. Pharmacotherapy targeted to therapeutic goals and therapeutic drug monitoring is currently the best option for the safe care of the critically ill. The aim of this paper is to review the alterations in drug pharmacokinetics associated with critical illness and to summarise the available evidence.

Purpose of reviewExtracorporeal membrane oxygenation (ECMO) offers advanced mechanical support to patients with severe acute respiratory and/or cardiac failure. Ensuring an adequate therapeutic approach as well as prevention of ECMO-associated complications, by means of timely liberation, forms an essential part of standard ECMO care and is only achievable through continuous monitoring and evaluation. This review focus on the cardiorespiratory monitoring tools that can be used to assess and titrate adequacy of ECMO therapy; as well as methods to assess readiness to wean and/or discontinue ECMO support. Recent findingsSurrogates of tissue perfusion and near infrared spectroscopy are not standards of care but may provide useful information in select patients. Echocardiography allows to determine cannulas position, evaluate cardiac structures, and function, and diagnose complications. Respiratory monitoring is mandatory to achieve lung protective ventilation and identify early lung recovery, surrogate measurements of respiratory effort and ECMO derived parameters are invaluable in optimally managing ECMO patients. SummaryNovel applications of existing monitoring modalities alongside evolving technological advances enable the advanced monitoring required for safe delivery of ECMO. Liberation trials are necessary to minimize time sensitive ECMO related complications; however, these have yet to be standardized.

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