Critical care medicine
-
Critical care medicine · Sep 2007
Proinflammatory cytokines cause down-regulation of renal chloride entry pathways during sepsis.
Sepsis is the most important trigger for acute renal failure, with tubular dysfunction and collapse in urine concentration. As chloride plays a major role in the urinary concentrating mechanisms, we aimed to investigate the regulation of renal chloride entry pathways, such as kidney-specific chloride channel 1, kidney-specific chloride channel 2, Barttin, thiazide-sensitive Na+-Cl- cotransporter, renal outer medullary potassium channel, and Na+/K+-adenosine triphosphatase during sepsis. ⋯ Our results demonstrate down-regulation of renal chloride transporters/channels during sepsis, which is probably mediated by proinflammatory cytokines and accounts for the development of LPS-induced tubular dysfunction. Our findings contribute to the understanding, on one hand, the failure of single-anticytokine strategies and, on the other hand, the beneficial effects of glucocorticoids in the therapy of septic patients.
-
Critical care medicine · Sep 2007
Multicenter StudyFacilitating clinician adherence to guidelines in the intensive care unit: A multicenter, qualitative study.
To determine perceived facilitators and barriers to guideline implementation and clinician adherence to guidelines in the intensive care unit (ICU). ⋯ Complex ICU practices and unique interprofessional team dynamics influence clinician adherence to guidelines. Initiatives that employ an approach addressing these issues may optimize guideline uptake and adherence. The optimal approach and its effectiveness may be guideline-dependent and requires further study.
-
Critical care medicine · Sep 2007
ReviewEffects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system.
Therapeutic hypothermia has been shown to decrease neurologic damage in patients experiencing out-of-hospital cardiac arrest. In addition to being treated with hypothermia, critically ill patients are treated with an extensive pharmacotherapeutic regimen. The effects of hypothermia on drug disposition increase the probability for unanticipated toxicity, which could limit its putative benefit. This review examines the effects of therapeutic hypothermia on the disposition, metabolism, and response of drugs commonly used in the intensive care unit, with a focus on the cytochrome P450 enzyme system. ⋯ This review provides evidence that the therapeutic index of drugs is narrowed during hypothermia. The magnitude of these alterations indicates that intensivists must be aware of these alterations in order to maximize the therapeutic efficacy of this modality. In addition to increased clinical attention, future research efforts are essential to delineate precise dosing guidelines and mechanisms of the effect of hypothermia on drug disposition and response.
-
Severe burns lead to insulin resistance, which is associated with hyperglycemia and muscle wasting. Investigators showed relatively recently that control of hyperglycemia with intensive insulin treatment is associated with improved outcomes for those in the intensive care unit, including patients with severe burns. In this article, we review the actions of insulin in terms of glycemic control and muscle metabolism, biochemical and clinical effects of insulin treatment in the severely burned, and the vagaries of glucose control.
-
There is still insufficient knowledge about in vivo glutamine metabolism and the regulation of glutamine homeostasis, particularly during metabolic stress. A shortage of glutamine is associated with a poor outcome, whereas for septic patients in the intensive care unit an increased availability of glutamine can prevent mortality and morbidity. Cellular defense mechanisms depend on normal glutamine availability to respond adequately to challenges presented. ⋯ Ordinary food is not a sufficient supply of glutamine for the patient with multiple organ failure in the intensive care unit, but that is also true for several other nutrients. It is, therefore, debatable whether an exogenous supply of glutamine should be regarded as a pharmacologic treatment or whether this just represents physiology in stressed states. If a glutamine shortage requires substitution, supplementation to the normal concentration is compensation of a shortage, and the effect is physiological.