Pharmacokinetic considerations

Limited studies of the pharmacokinetics of pain medication suggest altered serum elimination when the liver is hypoperfused or affected by severe cirrhosis. Drugs that are eliminated by Phase I oxidation reactions are sensitive to changes in hepatic blood flow, while drugs eliminated by Phase II glucuronidation are more affected by diseased hepatocytes. Additionally, alterations in renal function decrease elimination of both parent drugs and metabolites, resulting in toxicity for selected opioids such as meperidine and morphine. Caution is suggested in drawing general conclusions from pharmacokinetic patterns of opioid elimination discussed in this review. Practitioners should be aware that drugs with short duration of action may have long half-lives and accumulate in end-stage liver and renal disease. While pharmacokinetic differences have been described in various populations, the clinical effects and adverse outcomes are greatly influenced by numerous independent physiologic alterations seen in critical care patients. Patients with severe alterations in liver and renal function should be administered pain medications judiciously because these patients are predisposed to metabolic disarrays. These patients should not be denied pain care, but they may benefit from smaller, less frequently administered doses, rather than continuous infusion of opioid drugs. Titration of doses to clinical effects with careful patient assessment for adverse effects is crucial for achieving desired therapeutic outcomes with analgesic agents in the ICU.