1、Intensive insulin therapy and mortality in critically ill patientsCritical Care 2008, 12:R29 (doi:10.1186/cc6807),Abstract,Introduction Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients widely adopted in practice throughout the
2、world.there is only one randomized controlled trial showing unequivocal benefit study population ：post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.,We conducted a cohort study comparing three consecutive t
3、ime periods in a Level 1 trauma center: period I ：(no protocol); period II：target glucose 80 to 130 mg/dL; Period III： target glucose 80 to 110 mg/dL. Subjects ：10,456patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. study endpoints ： ICU and hospital mortal
4、ity, 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.,Methods,Results,Insulin administration increased over time (9% period I,25% period II,
5、 and 42% period III). patients in period III ： higher adjusted hospital mortality ( OR 1.15, 95% CI 0.98, 1.35) than period I. Excess hospital mortality in period III ：patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93）an approximately fourfold increase in the incidenc
6、e of hypoglycemia from periods I to III.,Conclusion,IIT in ICUs was not associated with a decrease in hospital mortality.,Introduction,Stress-induced hyperglycemia occurs frequently in critically ill patients and has been associated with increased morbidity and mortalityThe mechanisms ： could be rel
7、ated to suppressive effects on immune function and an associated increased risk of infection ，endothelial damage, hepatocyte mitochondrial damage , and potentiation of tissue ischemia due to acidosis or inflammation,Although there is still debate, the tight glycemic control has increasingly become t
8、he standard of care for critically ill patientsThe objective of the present study was to investigate the effect of implementing a policy of tight glycemic control in a broaderpopulation of critically ill patients,Materials and methods,Source populationall patients admitted to the ICUs at Harborview
9、Medical Center, a Level I trauma center and county hospital in Seattle,a cohort of all patients admitted to these ICUs over the course of a 4-year period between 1 Marc 2001 and 28 February 2005 was selected,Study design,The cohort was divided into three periods period I, 1 March 2001 to 28 February
10、 2002; no specific glycemic control protocol, hyperglycemia was treated by subcutaneous and intravenous insulin, target blood glucose of 120 to 180 mg/dL; period II, 1 March 2002 to 30 June 2003 target blood glucose of 80 to 130 mg/dL； period III, 1 July 2003 to 28 February 2005 80 to 110 mg/dL,only
11、 the first ICU stay per hospitalization and the first hospital stay were included Exclude： ICU stay was shorter than 24 hours ICU stay was not completed before the end of the study Patients younger than 16 years of age,Statistical analysis,Multivariable regression analysisSeverity of illness was mea
12、sured by the Simplified Acute Physiology Score (SAPS) II and the Acute Physiologic Score (APS) of the APACHE (Acute Physiology and Chronic Health Evaluation) III score in the first 24 hours of ICU admission in all patients;Chronic disease defined according to SAPS II criteria. range from 0 to 162, w
13、ith higher scores indicating a higher risk of death. APS range from 0 to 251, with higher scores indicating a higher risk of death.,Results,Study population and baseline characteristics(table 1),The distributions of demographic and baseline characteristics of the patient population were broadly simi
14、lar across the three periods (Table 1).,Compared with period I, history of type I diabetes was less frequent in periods II and III, type II diabetes was more common in the latter periods (Table 1). Blood glucose at ICU admission was lower in period III compared with the other two periods.The average
15、 SAPS II and APS III scores were lower in period III than in periods I and II. Requirement for mechanical ventilation at ICU admission was less frequent over time. Except for gender, ethnic group, history of diabetes I or II, and weight, all variables in Table 1 were associated with hospital mortali
16、ty. In particular, the OR of hospital mortality for admission glucose was 1.0009 (95% confidence interval CI 1.0002, 1.0016; P = 0.014) for a 1 mg/dL increase in admission blood glucose.,Insulin use, glucose control, and hypoglycemia,Due to the lower threshold to initiate insulin treatment, and the
17、broadened exposure to insulin, patients received lower doses of insulin in period III Moderate (65 mg/dL) and severe (40 mg/dL) hypoglycemic events increased approximately threefold to fourfold from the first to the third study periods (Table 2).The OR of hospital mortality for mean blood glucose in
18、 period 1 was 1.0078 (95% CI 1.0043, 1.0112; P 10,000) and the availability of extensive clinical data that allowed adjustment for severity of illness across time periods.,Four prior published studies have observed at least some reduction in mortality associated with IIT in critically ill patients.,
19、1. Van den Berghe reported the results of a large randomized trial of IIT in patients admitted to a surgical ICU, approximately 60% of whom had undergone cardiac surgery.IIT (blood glucose 80 to 110 mg/dL) was associated with a reduction in mortality from 8.0% to 4.6%,2. In a subsequent study, van d
20、en Berghe randomly assigned patients admitted to a medical ICU to IIT or conventional blood glucose management. There was no clear mortality benefit for IIT in the intention-to-treat populationHowever, IIT was associated with reduced in-hospital mortality in those patients who remained in the ICU fo
21、r more than 3 days.,34. In two studies,mortality after implementation of the protocol was improved compared with prior to protocol implementation,There are several reasons that may explain why the results of our study differ from these previous investigations of IIT.we were unable to consistently ac
22、hieve blood glucose concentrations within the range of 80 to 110 mg/dL. It is possible that the benefits of IIT are not achieved unless glucose concentrations are lower than 110 mg/dL.,A major difference between our cohort and that included in the trials of van den Berghe is the form of nutritional
23、support used.Parenteral nutrition was administered early in the course of care and comprised the vast majority of non-protein calories during the first few days of ICU stay. VS:not instituted until 3 to 5 days after ICU admission.we examined a mixed population of critically ill patients,Several othe
24、r studies also did not observe evidence of benefit of ITT.1. multicenter RCT in 537 patients with severe sepsis found no difference in mortality or organ failure in IIT；incidence of severe hypoglycemia was increased2. patients undergoing cardiac surgery；higher mortality and higher occurrence of stro
25、kes in the IIT group.3. after cardiac arrest；no mortality benefit and a much higher incidence of hypoglycemia4. A prospective consecutive series of 818 patients admitted to a trauma ICU found no reduction in mortality or infectious complications,The reason that IIT may result in increased mortality
26、is unclear but may be related to a direct effect of insulin or to insulininduced hypoglycemia.might be related to anabolic effects, similar to growth hormone,Conclusion,We observed that IIT in a mixed cohort of critically ill patients was not associated with a reduction in hospital mortality, and wa
27、s associated with increased ICU and hospital mortality in some subgroups. These results, combined with data from the most recently concluded randomized trials, suggest that broad implementation of IIT may be premature and that additional randomized trials in diverse groups of critically ill patients are necessary.,
