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  • Medication dosages are typically titrated to the intended effect, with an intravenous administration strategy selected based on the medication properties and goals of therapy.

  • Drug volume of distribution is often increased in critically ill patients necessitating the use of initial loading doses to quickly achieve therapeutic drug concentrations.

  • Pharmacokinetic changes evolve throughout a patient’s illness course requiring frequent reassessment and refinement of dosage regimens.

  • Therapeutic drug monitoring can improve dosage optimization but should be reserved for patient populations with significant pharmacokinetic variability.

  • Patients with acute kidney injury should have initial normal (nonadjusted) medication dosage regimens with subsequent modification based on renal injury progression, including the initiation or cessation of continuous renal replacement therapy.

  • Clinicians should thoroughly evaluate each medication during transitions of care in order to stop unnecessary therapies.


Critically ill and injured patients have a high risk for medication errors.1 Therapeutic regimen errors are poorly tolerated by these patients; incorrect drug selection and/or suboptimal dosing can lead to therapeutic failure, but physiologic reserve may also be inadequate to withstand the effects of adverse drug reactions from supraoptimal dosing. As such, an individualized pharmacotherapeutic plan must be developed to ensure safe and effective medication use. Bedside clinicians must understand the goals of drug administration, potential pharmacokinetic and pharmacodynamic changes, and therapeutic drug monitoring plan for the medications they intend to use in order to optimize therapy in these vulnerable populations. Additionally, clinicians should be familiar with drug dosing strategies in patients with specific organ dysfunctions (eg, acute kidney injury [AKI] and hepatic failure) and those treated with extracorporeal support (eg, extracorporeal membrane oxygenation [ECMO] and continuous renal replacement therapy [CRRT]).


Ideally, a medication regimen should provide an effective concentration at the site of drug action without leading to an adverse event. Unfortunately, though, most drug dosing regimens described in product labeling and the literature were designed in noncritically ill patients. Additionally, “off label” medication use is common in critically ill adults and associated with a higher rate of adverse drug reactions.2,3 While publications specific to critically ill injured patients are increasing in number, many drug therapy regimens are based on pharmacokinetic knowledge and fundamental medication use principles to optimize therapy.4

Medications with reliable bioavailability, rapid onset, titratability, and a wide therapeutic index are desirable in critically ill patients. The intravenous route of drug administration is often preferred for a number of reasons. First, complete drug bioavailability is ensured because the gastrointestinal tract is bypassed; enteral absorption may be impaired in the setting of gut edema or hypoperfusion. Second, use of intravenous medications does not require patient coordination (which may be effected by altered consciousness) or access to the enteral route (which may be impaired due to injury). Lastly, intravenous administration leads to quicker onset and easier titration to the desired effect ...

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