Clinical pharmacology and drug therapy in the burned patient

Abstract

Multiple factors, including alterations in blood flow, plasma protein binding, and organ function can affect the pharmacokinetics of drugs administered after burn injury. This situation is confounded by the co-administration of drugs that can induce or inhibit the metabolism and excretion of other drugs. The pharmacology of this population is further complicated by changes in target-organ sensitivity induced my multiple endogenous substances released in response to, or as a consequence of, the burn injury, as well as from malnutrition, physical immobilization, and various iatrogenic factors. There is some evidence to indicate that the patient with minor burns (<15% body surface area) responds differently to a drug than the patient with major burns (>30%). Although a number of studies have been conducted on the antibiotics and muscle relaxants, the mechanisms underlying the altered pharmacokinetics and pharmacodynamics of these agents in association with burn injury require more complete characterization. Further studies are needed to examine the relationship between particular drugs and the type of burn injury (e.g., scald vs. electrical vs. flame); time elapsed since injury when the drug is administered, and magnitude of the burn. Although additional research using animal modes will undoubtedly assist in defining the mechanisms responsible for these altered responses, clinical research in humans is urgently required. If we are to improve the care of patients with burn and other traumatic injury, we must begin to conduct definitive clinical studies in these patients. Nutritional status and the effects of malnutrition appear to have important implications for the pharmacologic action and metabolism of drugs, yet very little information is available concerning the combined effects of malnutrition, parenteral nutrition, and critical illness on the disposition and pharmacologic effect of drugs. With the current move to centralize trauma and burn care in many centers across the country, these studies should be forthcoming. Their need cannot be overemphasized.