Volume of distribution (Vd) is a nebulous pharmacokinetic principle that describes the hypothetical volume of plasma into which a drug distributes. While this is not an actual physiologic parameter like cardiac output or clearance, it is an extremely useful tool that describes how widely a drug distributes throughout body fluids and tissues.

Vd is often reported in either liters or liters per kg to help normalize a particular drug’s Vd to a patient’s weight. As the Vd increases, so does the drug’s ability to distribute into various body tissues. The body tissues that the drug distributes into will be based on drug characteristics in addition to the Vd. This is important to understand when determining the dose of a medication to administer to a patient. Dose is related to Vd by the following equation:

This shows that as Vd increases, the dose must increase to achieve the same concentration; the converse is also true. As a patient’s weight changes through his or her stay in an intensive care unit (ICU) (early on, weight gain due to fluid resuscitation; later, weight loss due to diuresis), Vd will change as well and may affect how doses result in the therapeutic levels that are achieved. Vd can be affected by various physiologic aberrations that occur in the ICU patient because of deranged organ function. These include decreased plasma proteins (and plasma protein binding), pH differences, and fluid balance abnormalities.

These issues with Vd can be related to the weight changes and the various weight definitions that are used in critically ill patients. In drugs with a larger Vd that will distribute widely within the body, doses based on actual weight are used. To briefly review, the various weight definitions are

IBW (male) = (height in inches >60 × 2.3) + 50

IBW (female) = (height in inches >60 × 2.3) + 45.5