Pharmacokinetics/Pharmacodynamics

first-pass metabolism by the liver and can increase the bioavailability of a drug. However, these routes still

require the drug to be absorbed into the blood. Therefore, these routes are potentially affected by changes in

absorption. Unlike with the enteral or oral route, clinicians do not routinely abandon the use of subcutaneously

or intramuscularly administered medications. Examples include the continued use of low-molecular-weight

heparins, insulin, and antipsychotics in patients with obesity for whom the absorption may be altered. In

addition, clinicians should be aware of similar concerns for altered absorption in critically ill patients with

sepsis or shock states because of changes in perfusion. Use of the sublingual route of administration in

critically ill patients has not been thoroughly researched. However, one could expect that alterations in blood

flow and absorption would cause similar concerns as for subcutaneous and intramuscular routes. Critical care

clinicians should understand that the subcutaneous route may be used; however, little to no data are available

in critically ill patients to determine if any pharmacokinetic changes will occur.

systemic exposure and/or achieve a high concentration in the pulmonary tissue. The high local concentration

is intended to maximize the therapeutic effect while reducing any adverse or unwanted effects. For example,

the use of inhaled bronchodilators reduces unwanted systemic effects such as tachycardia. Antibiotics such

as colistin and aminoglycosides are administered via inhalation to improve the antibiotic concentrations

in the lungs and reduce exposure to the kidneys. Studies have demonstrated varying serum concentrations

following inhaled administration of amikacin in critically ill patients, but these concentrations were much

lower than when administered intravenously (J Antimicrob Chemotherapy 2016;71:3482-6). Additional

research found that older age and higher positive end expiratory pressure (PEEP) independently predicted

detectable serum tobramycin concentrations (Respir Care 2022;67:16-23). While inhaled antibiotics are used

to reduce the likelihood of systemic adverse effects, the efficacy of this route of antibiotic administration is

not well established. Drug particles of 1–5 micrometers have the best opportunity to be delivered to all areas

of the lungs. Smaller particles will be exhaled without being deposited in the lower airways, whereas larger

particles will be deposited in the large bronchi or the oropharynx. Several models of nebulizers are on the

market that use different methods to achieve the desired particle sizes.

and reduce systemic concentrations. Data evaluating the efficacy of this route of administration are lacking

in the general population limited to case series. Despite the lack of data, clinicians use this route when

treating multidrug-resistant meningitis with antibiotics, or for the administration of analgesics in patients

with chronic pain.

Patient Case

M.J. is a 70-year-old man admitted to the neurosurgical ICU for an aneurysmal subarachnoid hemorrhage.

His initial treatment included placement of an external ventricular drain. Subsequently, he had a maximum

temperature of 101.5°F, a WBC of 15 × 103 cells/mm3, and a cerebrospinal fluid culture positive for methi-

cillin-resistant S. aureus. Intraventricular vancomycin 20 mg is used for therapy. Which is the best rationale

for this approach?