Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Feb 2001
ReviewEffects of genomic polymorphisms on the course of sepsis: is there a concept for gene therapy?
Sepsis and its sequelae are still a major cause of morbidity and mortality on today's intensive care units. The evidence that endogenous mediators actually mediate the individual's response to infection has led to various approaches to assess the individual's contribution to the course of the disease. The role of an individual's genetic background and predisposition for the extent of inflammatory responses is determined by variabilities of genes encoding endogenous mediators that constitute the pathways of inflammation. ⋯ Therefore, all genes encoding proteins involved in the transduction of inflammatory processes are candidate genes to determine the human genetic background that is responsible for interindividual differences in systemic inflammatory responses to injury. The genetically determined capacity of cytokine production and release, heat shock protein expression, nitric oxide synthase activity, gene polymorphisms of coagulation factors or factors of the innate immune system-like defensins, and other genes involved in inflammation may contribute to a wide range of clinical manifestations of an inflammatory disease. Genomic information may be used to identify groups of patients with a high risk of developing severe sepsis and multiple organ dysfunction, and determining which patients will benefit from antimediator strategies because of their genetic determination to high cytokine release in the inflammatory response will be the subject of future trials.
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J. Am. Soc. Nephrol. · Feb 2001
ReviewVolume replacement in critically ill patients with acute renal failure.
Maintenance and restoration of intravascular volume are essential tasks of critical care management to achieve sufficient organ function and to avoid multiple organ failure in critically ill patients. Inadequate intravascular volume followed by impaired renal perfusion is the predominate cause of acute renal failure. Crystalloid solutions are the first choice to correct fluid and electrolyte deficits in these patients. ⋯ In these patients, measurement of the colloidal osmotic pressure and adequate amounts of crystalloid solutions will reduce the risk of hyperoncotic renal failure. Of all colloids, gelatin and HES solutions with low in vivo molecular weight are preferred in these cases. In the very specific situation of kidney transplantation, colloid solutions should be administered in a restricted manner to organ donors and kidney recipients.
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J. Am. Soc. Nephrol. · Feb 2001
Randomized Controlled Trial Clinical TrialImmunomodulation in septic shock: hydrocortisone differentially regulates cytokine responses.
Cortisol is known to be an immunomodulatory hormone that exerts suppressive and permissive effects on the immune response. Little is known regarding the evolution of the cytokine response in human septic shock in the presence of hypercortisolemia induced by infusion of stress doses of hydrocortisone. Twenty-four consecutive patients with high-out-put circulatory failure (cardiac index, >4 liters/min per m(2)) who met the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee criteria for septic shock were enrolled in a prospective, double-blind study. ⋯ Hydrocortisone infusion in septic shock differentially regulated the cytokine responses. IL-6 and IL-8 levels decreased significantly and IL-6 levels differed between the groups, whereas TNF and IL-10 levels were not affected by hydrocortisone. Stress doses of hydrocortisone may be a valuable immunomodulatory therapy for septic shock.
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J. Am. Soc. Nephrol. · Feb 2001
ReviewMonitoring of organ dysfunction in sepsis/systemic inflammatory response syndrome: novel strategies.
Sepsis and systemic inflammatory response syndrome-induced severe disruption of microcirculation and consecutive tissue hypoxia is considered a key factor in the development of organ dysfunction and multiple organ failure. The conventionally measured global variables such as lactate or macrohemodynamic parameters using a pulmonary artery catheter do not adequately mirror microcirculatory disturbances. Evaluation of the severity of microcirculatory distress and the effectiveness of resuscitation strategies requires new clinical technologies aimed at the microcirculation. ⋯ Techniques for the assessment of regional perfusion and microcirculatory bioenergetics to direct therapeutic procedures are expected to refine and optimize clinical treatment of critically ill patients in the future. This article addresses the question of which variables should be monitored, what is feasible, and what is valid for therapeutic consequences. Recent developments in monitoring of macro- and microcirculation and organ-specific dysfunction, e.g., lung, kidney, are described with respect to their advantages and limitations, and future directions are outlined.
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J. Am. Soc. Nephrol. · Feb 2001
ReviewTherapeutic options for the treatment of impaired gut function.
Tissue hypoxia, especially in the splanchnic area, is still considered to be an important cofactor in the pathogenesis of multiple organ failure. Therefore, the specific effects of the various therapeutic interventions on splanchnic perfusion and oxygenation are of particular interest. Restoring and maintaining oxygen transport and tissue oxygenation is the most important step in the supportive treatment of patients with sepsis and impaired gut perfusion. ⋯ There are no convincing data yet to support the routine use of low-dose dopamine or dopexamine to improve an impaired gut perfusion. There is even evidence that low-dose dopamine may reduce the mucosal perfusion in the gut in some patients. It has been suggested that dopexamine can improve splanchnic perfusion, but because these effects remain somewhat controversial, a general recommendation for dopexamine to improve gut perfusion is not justified.