## KEY CONCEPTS

KEY CONCEPTS

• Intensive care units are designed to support the complex needs of critically ill patients with acute organ dysfunction in need of a higher level of monitoring and treatment.

• The four phases of critical illness include rescue, optimization, stabilization, and de-escalation, each of which can affect drug selection, dosing, and monitoring.

• Ideal medications for use in the ICU have predictable bioavailability, fast onset, rapid titratability, and a wide therapeutic window.

• Critically ill patients exhibit a uniquely complex pharmacokinetic profile and response to therapies that needs to be considered when individualizing drug regimens.

• Acute changes to end-organ function occur more commonly in the ICU and affect drugs in a dynamic way.

• Perfusion deficits and iatrogenic exposures can decrease enteral, subcutaneous, and intramuscular drug bioavailability which makes the intravenous route preferred in acutely ill unstable patients in the ICU.

• The use of advanced organ support devices is common in the ICU and each device differentially affects the pharmacokinetics and pharmacodynamics of medications.

• Key properties of drugs susceptible to sequestration in the ECMO circuit include high percentage of protein binding and high degree of lipophilicity.

• Highly protein bound drugs are readily cleared by MARS and TPE, but not efficiently cleared by renal replacement therapies.

• Many patient, provider, and environmental factors increase an ICU patient’s vulnerability to medical errors, adverse drug events, and their related consequences, relative to their noncritically ill counterparts.

## PRECLASS ACTIVITY

Preclass Engaged Learning Activity

Watch the first 12-minutes of the video “Right dose, right now: customizing drug dosing for the critically ill patient”. This video briefly overviews some of the key pharmacokinetic and pharmacodynamic changes present in critically ill patients and the potential impact on anti-infective effectiveness and safety in the ICU.

## INTRODUCTION

### Epidemiology of Critical Illness

Since the poliomyelitis epidemic of the 1950s when mechanical ventilation was first introduced, significant advancements have been made in our understanding of the pathophysiology of syndromes of critical illness and the interventions needed to improve patient outcomes.1 Only recently, however, have we begun to quantify the true global burden of critical illness. In the United States, 27% of all hospitalizations or 4.6 million stays annually include an intensive care unit (ICU) admission.2 Short-term mortality for ICU patients is 8% to 22%, but can be much higher in patients with sepsis, acute respiratory distress syndrome, shock, or those in the developing world, where mortality still reaches 50% to 60% in some studies.3 Although surviving critical illness is a short-term goal, survivors can experience long-term physical, psychological, and cognitive consequences, collectively termed “post-intensive care syndrome.” When considering these sequelae, care of critically ill patients is estimated to cost $121 to$263 billion annually in the United States, on par with the financial burden of cancer care or cardiovascular disease.4 It is essential that clinicians and scientists seek ...

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