Table 2.

Overview of pharmacokinetic alterations in sepsis, with examples of potential clinical effects

Pharmacokinetic process	Alteration in sepsis	Potential clinical effect
Absorption	•Decreased for most routes •Potentially increased transdermal absorption	•Potential for subtherapeutic effects of all enterally administered medications •Potential increased absorption of transdermal preparations (fentanyl)
Distribution	•Lipophilic medications—decreased VD •Hydrophilic medication—increased VD •Hypoalbuminaemia—increased free drug concentration of acidic protein bound drugs •Increased α1 acid glycoprotein—decreased free drug concentration of basic protein bound drugs •Acidaemia—decreased VD of weak bases	•Increased plasma concentration of intravenous anaesthetic agents, opioids and sedatives leading to adverse effects (e.g. cardiovascular depression) •Potential for subtherapeutic levels of commonly used hydrophilic antimicrobial agents such as beta-lactams and aminoglycosides •Midazolam may have a more rapid onset because of decreased protein binding in hypoalbuminaemia •Decreased clinical effect of opioids because of increased binding by the acute phase reactant α1 acid glycoprotein
Metabolism	•Generally decreased	•Prolonged clinical effect and risk of toxicity
Excretion	•Generally decreased	•Prolonged clinical effect and risk of toxicity