Intensive insulin therapy

Acute stress-related hyperglycemia is a condition, commonly observed in patients following major surgical procedures, trauma as well as life-threatening illness. This may result in organic dysfunction in the critically ill. Intensive Insulin Therapy (IIT) describes intravenous application of insulin to sustain a defined level of blood glucose to reduce negative effects of hyperglycemia. IIT requires close monitoring regimes.     

危重病人的强化胰岛素治疗

合理控制危重病人的血糖是临床医生常规工作之一，但是如何有效控制血糖至今仍有争论。长期以来普遍认为将危重病人的血糖控制在稍高于正常水平（10．0～11．1mmol／L），对于机体是有利的。然而，多年来高血糖对免疫功能的抑制，导致感染机会增加，或使感染难以控制的证据在不断增加。特别是近年来，国内外多项研究均表明强化胰岛素治疗能改善危重病人的预后，使得如何控制危重病人的血糖开始备受重视。本文就危重病人强化胰岛素治疗的有效性、安全性、可行性，以及可能的机制等进行讨论。     

Intensive insulin therapy in brain injury: a meta-analysis

Many studies have addressed the question of whether intensive insulin therapy (IIT) provides better outcomes for brain-injured patients than does conventional insulin therapy (CIT), with conflicting results. We performed a systematic review and meta-analysis of the literature to estimate the effect of IIT on patients with brain injury. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and citations of key articles and selected "all randomized controlled trials" (RCTs) comparing the effect of IIT to CIT among adult patients with acute brain injury (traumatic brain injury, stroke, subarachnoid hemorrhage, and encephalitis). Of the 2807 studies, we identified 9 RCTs with a total of 1160 patients for analysis. IIT did not appear to decrease the risk of in-hospital or late mortality (RR=1.04, 95% CI=0.75, 1.43 and RR=1.07, 95%CI=0.91, 1.27 respectively). No significant heterogeneity was found (I(2)=0.0%). IIT also did not have a protective effect on long-term neurological outcomes (LTNO) (RR=1.10, 95% CI=0.96, 1.27). IIT, however, did decrease the rate of infections (RR=0.76, 95% CI=0.58, 0.98). Heterogeneity was present (I(2)=64%), which was eliminated upon sensitivity analysis bringing the RR to 0.66 (95% CI=0.55, 0.80, I(2)=0%). IIT increased the rate of hypoglycemic episodes (RR=1.72, 95% CI=1.20, 2.46) however there was intractable heterogeneity present (I(2)=89%), which did not resolve upon sensitivity analysis. We found no evidence of publication bias by Egger's test (p=0.50). To conclude, IIT has no mortality or LTNO benefit to patients with brain injury, but is beneficial at decreasing infection rates.     

Intensive insulin therapy,insulin sensitisers and insulin secretagogues for burns: A systematic review of effectiveness and safety

This systematic review investigated the effectiveness and safety of intensive insulin therapy (IIT), insulin secretagogues and sensitisers in burn patients. PubMed, Embase, clinicaltrials.gov and Cochrane central were searched from 1990 to 2016. Title/abstract screening, full-text review, critical appraisal and data extraction were carried out by two independent reviewers. Inclusion criteria were hospitalised burn patients, IIT, insulin sensitisers or secretagogues and the outcomes mortality, length of stay, resting energy expenditure, blood glucose, catabolism, or complications. We identified 594 potential studies of which 13 were included. Five studies investigated IIT in paediatric patients, 3 investigated IIT in adults and 5 investigated sensitisers or secretagogues. Glycaemic targets differed with age group — paediatric studies compared IIT to loose glycaemic control while adult studies compared IIT to more moderate control. Meta-analyses were limited by differences in outcome reporting, however mortality was increased in children by loose glycaemic control (OR = 3.78, 95%CI 1.19–12.02) but not significantly affected in adults by moderate compared to tight control. Meta-analyses could not be performed for sensitisers or secretagogues. These findings support recommendations that moderate insulin administration (130–150 mg/dL) is the prudent approach in burn patients. The evidence is relatively sparse and further research is warranted.     

Intensive insulin therapy to non-cardiac ICU patients: a prospective study

OBJECTIVE: Intensive insulin therapy reduced mortality in patients admitted to an intensive care unit following mainly cardiac surgery. The aim of this prospective study was to evaluate, if intensive insulin therapy could reduce mortality in medical and non-cardiac surgical patients admitted to a multidisciplinary intensive care unit. PATIENTS AND METHODS: For 6 months all adult patients, admitted to the intensive care unit, were included. Insulin was administered, if blood glucose 12 mmol L-1. For the next 6 months blood glucose level was reduced with intensive insulin therapy (aim 4.4 < BG < 6.1 mmol L-1); 271 patients were included. Patient characteristics data, APACHE II score, morbidity and mortality were recorded. RESULTS: At admission the two groups were comparable. The overall relative mortality was reduced 20% in the intensive insulin treated group (n.s.). In the intensive insulin treated group mortality was 13.1% in the medical patients and 11.2% in the surgical patients compared to 15.8% and 14.4%, respectively, in the conventional treated group (n.s.). The frequency of secondary infections was 21.5% in the intensive insulin treated group and 16.0% in the conventional treated group (n.s.). The proportion of hypoglycaemia increased from 4% to 14% (P < 0.05). CONCLUSIONS: Following intensive insulin therapy there was a trend towards reduced mortality in medical and non-cardiac surgical patients but less pronounced as in cardiac surgical patients. Intensive insulin therapy increased the frequency of hypoglycaemia. Around 4400 patients would have to be included in any future randomized study to reach significance.     

Intensive insulin protocol improves glucose control and is associated with a reduction in intensive care unit mortality

BACKGROUND: Intensive insulin therapy to maintain serum glucose levels between 80 and 110 mg/dL has previously been shown to reduce mortality in the critically ill; recent data, however, have called this benefit into question. In addition, maintaining uniform, tight glucose control is challenging and resource demanding. We hypothesized that, by use of a protocol, tight glucose control could be achieved in the surgical trauma intensive care unit (STICU), and that improved glucose control would be beneficial. STUDY DESIGN: During the study period, a progressively more rigorous approach to glucose control was used, culminating in an implemented protocol in 2005. We reviewed STICU patients' blood glucose levels, measured by point-of-care testing, from 2003 to 2006. Mortality was tracked over the course of the study, and patient charts were retrospectively reviewed to measure illness and injury severity. RESULTS: Mean blood glucose levels steadily improved (p < 0.01). In addition to absolute improvements in glucose control, total variability of glucose ranges in the STICU steadily diminished. A reduction in STICU mortality was temporally associated with implementation of the protocol (p < 0.01). There were fewer intraabdominal abscesses and fewer postinjury ventilator days after implementation of the protocol. There was a small increase in the incidence of clinically relevant hypoglycemia. CONCLUSIONS: Improvements in glucose control in the ICU can be achieved by using a protocol for intensive insulin therapy. In our ICU, this was temporally associated with a significant reduction in mortality.     

Intensive insulin therapy in high-risk cardiac surgery patients: evidence from the Leuven randomized study

Mortality and morbidity of critically ill diabetic as well as nondiabetic patients are improved when blood glucose levels are tightly controlled to normoglycemia with intensive insulin therapy during their stay in the intensive care unit (ICU). This has been demonstrated in large prospective, randomized, controlled clinical studies for adult patients admitted to surgical and medical ICUs. Particularly for cardiac surgery patients, the hospital survival benefit with insulin therapy is most pronounced and maintained up to 4 years after hospital discharge, without inducing a substantial burden for the patients, their relatives, or society. Mechanistic studies exploring the molecular pathways involved suggest that intensive insulin therapy exerts its beneficial effects mainly through the maintenance of normal blood glucose levels.     

慢性阻塞性肺疾病急性加重期胰岛素强化治疗的临床研究

目的:观察胰岛素强化治疗在慢性阻塞性肺疾病(COPD)急性加重期的治疗作用及预后.方法:106例COPD急性发作期患者随机分为常规治疗组(CT组)及胰岛素强化治疗组(IT组),每4 h监测1次床旁血糖.当CT组血糖>11.1 mmol/L时,皮下注射中性可溶性胰岛素控制血糖在11.1 mmo l/L以下;当IT组血糖>6.1 mmol/L时,皮下注射胰岛素控制血糖在4.4～6.1mmo l/L.观察两组肝肾功能异常、有创通气患者例敷及死亡例教.并用酶联免疫吸附试验(ELISA)检测两组治疗前、1、3、7天血清C反应蛋白(CRP)值.结果:强化组肝肾功能异常例数显著少于常规组(P<0.05),两组死亡例数差异无显著(P>0.05).强化组治疗7天后血清CRP含量较常规组显著降低(P<0.05或0.01).结论:胰岛素强化治疗在COPD急性加重期伴有应激性高血糖患者中有较好应用价值.     

Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm

Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110-150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10-1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61-0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.     

Intensive care support therapy

Patients with small-for-size syndrome (SFSS) and acute liver failure share some important clinical features that are paralleled by common approaches to their intensive care unit management. Both are characterized by a period of acute hepatic insufficiency, with clinical features reflecting the impairment of metabolic and immunologic function that results. The basic principles of management of the two conditions remain essentially the same: to support hepatic regeneration, to anticipate and prevent the development of complications, and to identify patients unlikely to survive early in their clinical course so that retransplantation may be considered. Many treatments are available in the intensive care unit to overcome biochemical and metabolic disturbances in acute liver failure. Optimal pharmacologic management of SFSS complicated by portal hypertension and variceal hemorrhage is currently uncertain. Extracorporeal liver support has several theoretical attractions in the critically ill patient with SFSS, through its ability by removal of hepatotoxins to provide an environment more conducive to hepatic regeneration and recovery, or to support and bridge the patient to transplantation. The molecular adsorbent recycling system has been proposed to remove both water-soluble and protein-bound toxins. This system is particularly attractive in the treatment of SFSS, however, despite its current clinical application, there are presently limited published data to support its use.