Treatment of endotoxic shock: glucocorticoids, lazaroids, nonsteroidals, others

Review of the literature would indicate that a therapy inhibiting a single step in the inflammatory mediator cascade, although potentially beneficial, cannot serve as the "magic bullet" in endotoxic shock. Thus, combination therapy using drugs that target multiple steps in the mediator cascade may prove useful in the future. Until controlled clinical studies have been performed in veterinary medicine using the agents discussed in this manuscript (or others), many questions will remain regarding the best possible pharmacologic therapies to use in supplementing traditional supportive care (e.g., fluids, broad-spectrum antimicrobials) measures. Many of the therapies discussed in this manuscript hold tremendous potential, but must be administered before endotoxic shock occurs or early in the course of endotoxic shock to elicit a beneficial response. Unfortunately this is not usually possible in the clinical situation. Further, the possibility of eliciting a detrimental response by use of drugs at inappropriate dosages or too late in the course of the disease must be considered. In time, therapies may be grouped into those that hold promise for being beneficial in the patient at risk for endotoxic shock and those that are beneficial for treatment of established endotoxic shock. Therapies that may hold promise for the patient with established endotoxic shock possibly include the lazaroids, certain NSAIDs, pentoxifylline, and selective inhibitors of iNOS activity. Although still controversial, methylprednisolone and other glucocorticoids are probably best reserved for the patient at risk for endotoxic shock, or those identified very early in the course of endotoxemia and endotoxic shock, and should never be used in conjunction with NSAIDs. Since no one therapy is likely to provide the "magic bullet" for the patient in endotoxic shock, treatment may ultimately involve combination therapy using some of these drugs that target different pathways and mediators and may also include antibodies against endotoxin or its mediators.