Studienprotokoll der VISEP-Studie (original) (raw)
Related papers
2013
Severe metabolic derangement is characteristic of systemic inflammatory response in septic conditions. Changes in blood glucose levels are often deleterious further impairing organ functioning. Thus they are a subject of strict and sometimes even too aggressive control. Its disadvantages demand and stimulate research of new strategies. In the present paper we systematically review the current therapeutic options and recent research advances in the field of hyperglycemia in sepsis. They include the pathogenesis of sepsis and the role of insulin in this pathology. A special attention is paid to the glycemic control in sepsis. The correct strategy of glycemic control is combined approach with computerized infusion, continuous blood glucose monitoring and proper feeding support. Scripta Scientifica Medica 2013; 45(1): 7-11.
The roles of insulin and hyperglycemia in sepsis pathogenesis
Journal of Leukocyte Biology, 2003
Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group. Whether this is true for a population of sepsis patients, as such, has not been investigated in clinical trials, but evidence from in vitro studies and experimental sepsis suggests that this may be the case. The endocrinology of septic patients is characterized by a shift in the balance between insulin and its counter-regulatory hormones favoring the latter. This leads to prominent metabolic derangements composed of high release and low use of glucose, amino acids, and free fatty acids (FFA), resulting in increased blood levels of these substrates. Circulating, proinflammatory mediators further enhance this state of global catabolism. Increased levels of glucose and FFA have distinct effects on inflammatory signaling leading to additional release of proinflammatory mediators and endothelial and neutrophil dysfunction. Insulin has the inherent capability to counteract the metabolic changes observed in septic patients. Concomitantly, insulin therapy may act as a modulator of inflammatory pathways inhibiting the unspecific, inflammatory activation caused by metabolic substrates. Given these properties, insulin could conceivably be serving a dual purpose for the benefit of septic patients. J. Leukoc. Biol. 75: 413-421; 2004.
The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability
Critical Care, 2008
Introduction The purpose of this study was to assess the relation between glycaemic control and the severity of sepsis in a cohort of patients treated with intensive insulin therapy (IIT). Methods In a prospective, observational study, all patients in the intensive care unit (ICU) (n = 191) with sepsis, severe sepsis or septic shock were treated with IIT (target blood glucose (BG) level 80 to 140 mg/dl instead of strict normoglycaemia). BG values were analysed by calculating mean values, rate of BG values within different ranges, rate of patients experiencing BG values within different levels and standard deviation (SD) of BG values as an index of glycaemic variability. Results The number of patients with hypoglycaemia and hyperglycaemia was highly dependent on the severity of sepsis (critical hypoglycaemia ≤ 40 mg/dl:
Blood insulin responses to blood glucose levels in high output sepsis and septic shock
The American Journal of Surgery, 1978
and reduced pancreatic insulin secretion are well known features of hypovolemic shock [I, 2]. More recently low blood insulin levels also have been recognized as characteristic of stress in septic shock [3-51. However, in the clinical course of the seriously septic patient, when the circulatory stress has been resolved and equilibrium has been established, it appears that the situation is different. Clinical and experimental observations by our group and others have indicated that blood insulin levels relative to blood glucose levels approach normal values in severely infected patients who are doing well with the high cardiac outputs typical of the recovery pattern [3-61. Because of the importance of blood insulin levels in the energy metabolism of glucose and other substrates, both in health [ 71 and disease, data are presented from a series of observations in thirty-eight patients with major infections whose circulatory status was determined by cardiac outputs, measured at the same times as blood samples were drawn. Since hepatic glucogenesis and the body glucose pool are known to be increased in sepsis [8-101, measurements of the principal glucogenic precursors in the blood, lactate and alanine ]11], were also made simultaneously. In addition to differentiating significantly the insulin responses of the patients with high and low cardiac outputs, the data from both groups are compared with blood glucose and insulin values obtained from thirty-five normal people during glucose tolerance tests. The results indicate that, in
Annals of The Royal College of Surgeons of England, 2004
Loss of the anabolic effect of insulin (insulin resistance) is a key component of the adverse metabolic consequences of sepsis and may contribute to the apparent lack of efficacy of feeding regimens in critically ill patients. The mechanisms which underlie the development of insulin resistance in stress remain unclear. In this series of studies, the locus of insulin resistance in the septic patient was shown to lie within the metabolic pathways of glucose storage (glycogen synthesis) within skeletal muscle, was noted to be unrelated to the actions of hormone mediators such as leptin and was shown not to be associated with altered nutrient-induced thermogenesis during total parenteral nutrition (TPN). Clinically applicable maximal rates of glucose-based TPN for septic patients were calculated. A technique was also developed in which insulin resistance could be induced and studied in healthy volunteers. These studies demonstrated that insulin resistance develops within 7 h of an inflammatory stimulus and, as in clinical sepsis, is characterised by selective impairment of glucose storage. Finally, a series of related studies indicated that the magnitude and nature of the inflammatory response in vivo could be enhanced by exogenous insulin infusion, indicating links between the hormone systems involved in intermediary metabolism and the inflammatory response. These findings have significant implications for the optimal design of feeding regimens for critically ill patients.
Insulin in sepsis and septic shock
The Journal of the Association of Physicians of India, 2003
NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.
Intensive insulin therapy and mortality in critically ill patients
Critical Care, 2008
Introduction Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients. Methods We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I. Results Insulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III. Conclusion A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.