Effect Of Intensive Insulin Therapy Research Articles

Effect of early intensive insulin therapy on high mobility group box 1 protein levels and prognosis of patients with severe trauma

To study the effect of intensive insulin therapy on serum high mobility group box 1 (HMGB1) levels and its relationship with the prognosis in early phase of severe trauma. Eighty severe trauma patients [injury severity score (ISS)≥ 16] were divided into groups according to injury to matched anatomical regions. Forty patients of intensive therapy group were given early intensive insulin therapy, while another 40 patients of the conventional treatment group received routine treatment based on clinical experience with insulin treatment. The insulin dose and the blood glucose levels were recorded within 72 hours after treatment. The relationship between HMGB1 levels and prognosis was analyzed by testing serum HMGB1 levels at 24, 36, 48, 60 or 72 hours after treatment, and clinical terminal events such as multiple organ dysfunction syndrome (MODS) and death rate within 1 week were recorded. Results The insulin dose of intensive therapy group was significantly greater than that of conventional treatment group following the blood glucose levels were significantly lower than those of the conventional treatment group after treatment for 72 hours. The levels of HMGB1 (μg/L) lowered after intensive insulin therapy for 36 hours , and were significantly lower than those of conventional treatment group at 36, 48, 60 and 72 hours after intensive treatment (36 hours: 41.3 ± 9.5 vs. 52.7 ± 11.5, 48 hours: 48.6 ± 17.6 vs. 124.1 ± 22.9, 60 hours: 47.7 ± 23.3 vs. 132.9 ± 33.4, 72 hours: 54.3 ± 26.3 vs. 140.6 ± 16.5, P <0.05 or P <0.01). The incidence of MODS and mortality in intensive therapy group was respectively significantly lower than that of the conventional treatment group (20.0% vs. 55.0%, 10.0% vs. 30.0%, both P <0.05). In conventional treatment group the patients with HMGB1 ≥ 132.26 μg/L ( n =22) occurred MODS, and those with HMGB1<132.26 μg/L ( n =18) did not occur MODS. The HMGB1 levels in death patients ( n =12) were ≥ 132.26 μg/L. Early intensive insulin treatment could probably reduce MODS and mortality by inhibiting stress hyperglycemia and serum HMGB1 levels effectively. Serum HMGB1 of severe trauma patients can be used for the clinical indicator of prognosis.

SRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy

IntroductionHyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE).MethodsA predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls.ResultsBoth diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality.ConclusionsThese findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.

What is the optimal blood glucose target in critically ill patients? A nested cohort study

AIMS:There is an uncertainty about what constitutes an optimal level of blood glucose (BG) in critically ill patients. The objective of this study is to identify the optimal BG target for glycemic control in critically ill patients that is associated with survival benefit with the least hypoglycemia risk.SETTING AND DESIGN:This is a nested cohort study within a randomized control trial conducted in a tertiary care center in King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia.METHODS:The study was carried out in a single center to assess the effect of intensive insulin therapy [IIT; target BG 4.4-6.1 mmol/L (80-110 mg/dL)] versus conventional insulin therapy [CIT; target BG 10-11.1 mmol/L (180-200 mg/dL)] in a medical/surgical ICU. All patients were divided into six groups based on the mean daily BG levels. A logistic regression model was used to determine the association of BG and ICU mortality. We compared different outcomes below and above different BG thresholds of 0.1 mmol/L (2 mg/dL) increments using multivariate analyses.STATISTICAL ANALYSIS:Data are presented as mean ± SD or median with interquartile ranges, unless otherwise indicated. Differences between the six groups were assessed using the χ2 test. A P-value equal or less than 0.05 was considered to indicate statistical significance. The results were expressed as adjusted odds ratio (aOR) and 95% confidence intervals (CI). Statistical analyses were carried out using the Statistical Analysis Software (SAS, release 8, SAS Institute Inc., Cary, NC, USA).RESULTS:Among six groups, the ICU mortality was least in patients with BG <8.7 mmol/L (<157 mg/dL) compared with patients with BG ≥8.7 mmol/L (≥157 mg/dL) [11.5% vs. 21.5%, P = 0.002]. When analyzed using 0.1 mmol increments in average BG, we found that mortality remained unchanged by increasing thresholds of BG up to 8.0 mmol/L (144 mg/dL) and started to rise with thresholds of BG of 8.1 mmol/L (146 mg/dL) and above. The risk of hypoglycemia was the highest with a BG threshold of 6.1 mmol/L (110 mg/dL) and gradually decreased with increasing BG levels to plateau with a BG level of 7.2 mmol/L (130 mg/dL) and higher.CONCLUSION:Our study suggests that a BG level of 8.1 mmol/L (146 mg/dL) and below represents an optimal level in critically ill patients.

Blood glucose monitoring and nursing of intensive care patients with intensive insulin therapy

Objective To investigate the practical effects of intensive insulin therapy in intensive care patients. Methods A retrospective study was performed, 51 intensive care patients received intensive insulin therapy as observation group;and 51 intensive care patients received routine insulin therapy as control group. nosocomial infection rate, hypoglycemia rate and mortality were compared between the two groups. Results Intensive insulin therapy reduces the incidence of nosocomial infection and hospital mortality (P ＜ 0. 05). Conclusions Intensive insulin therapy plays an important role in the treatment of intensive care patients. Key words: Intensive care; Intensive insulin therapy; Blood glucose monitoring; Nursing

Impacts of Intensive Insulin Therapy in Patients Undergoing Heart Valve Replacement

Cardiac surgery with cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) is associated with severe stress response, systemic inflammatory response, and injury. This study was designed to investigate the effects of intensive insulin therapy on patients undergoing valve replacement with CPB. One hundred nondiabetic inpatients undergoing valve replacement were randomly assigned to a control group or an intensive insulin therapy (IT) group. Plasma cytokine and cardiac troponin I (cTnI) levels were monitored perioperatively. Compared with the control group, the IT group had smaller increases in plasma concentrations of tumor necrosis factor α, interleukin 1β (IL-1β), IL-6, and cTnI, and had a more pronounced increase in IL-10 levels after the initiation of CPB. After surgery, the required inotropes were reduced in the IT group. In the IT group, the time of artificial ventilation and the postoperative length of stay in the hospital were markedly shortened; however, there were no significant differences between the IT and control groups in mortality and the rate of nosocomial infections of deep sternal wounds. IT can significantly attenuate the systemic inflammatory response and improve a damaged cardiac function, but it does not reduce the in-hospital mortality rate.

Intensive Versus Conventional Insulin Therapy in Type 2 Diabetes Patients Undergoing D2 Gastrectomy for Gastric Cancer: A Randomized Controlled Trial

This study was to compare the effect of intensive insulin therapy (IIT) to conventional insulin therapy (CIT) on postoperative outcomes among type 2 diabetes mellitus (DM) patients who underwent D2 gastrectomy for gastric cancer. We randomly assigned gastric cancer patients with type 2 DM who underwent radical gastrectomy to receive IIT (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/l) with insulin infusion or CIT (maintenance of blood glucose at a level between 10 and 11.1 mmol/l) during the postoperative period. Of the 179 eligible patients, 92 patients were assigned to receive IIT and 87 patients to receive CIT. Mean blood glucose concentrations were lower in the intensive group (IG) than in the conventional group (CG) (5.5 ± 0.8 vs. 9.9 ± 1.0 mmol/l, P < 0.001). Hypoglycemia occurred in 6 patients (6.5%) in the IG (P = 0.029) versus in 1 patient (1.1%) in the CG. Hospital mortality did not differ significantly between two groups (4.3% vs. 5.7%, P = 0.742). However, IIT significantly reduced morbidity (from 18.4 to 7.6%, P = 0.031). Also, IIT shortened the days to suture removal, postoperative hospital stay, and postoperative duration of antibiotic use. The HOMA-IR score was lower at all time points in IG. Moreover, IIT increased the postoperative HLA-DR expression on monocytes on postoperative days 3 and 5. IIT significantly reduced short-term morbidity but not mortality among type 2 DM patients who underwent D2 gastrectomy for gastric cancer. Furthermore, a possible mechanism of suppression of the insulin resistance and improvement of HLA-DR expression may partially explain the benefits of IIT.

Effect of intensive insulin therapy on macular biometrics, plasma VEGF and its soluble receptor in newly diagnosed diabetic patients

To evaluate whether intensive insulin therapy leads to changes in macular biometrics (volume and thickness) in newly diagnosed diabetic patients with acute hyperglycaemia and its relationship with serum levels of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). Twenty-six newly diagnosed diabetic patients admitted to our hospital to initiate intensive insulin treatment were prospectively recruited. Examinations were performed on admission (day 1) and during follow-up (days 3, 10 and 21) and included a questionnaire regarding the presence of blurred vision, standardized refraction measurements and optical coherence tomography. Plasma VEGF and sFlt-1 were assessed by ELISA at baseline and during follow-up. At study entry seven patients (26.9%) complained of blurred vision and five (19.2%) developed burred vision during follow-up. Macular volume and thickness increased significantly (p = 0.008 and p = 0.04, respectively) in the group with blurred vision at day 3 and returned to the baseline value at 10 days. This pattern was present in 18 out of the 24 eyes from patients with blurred vision. By contrast, macular biometrics remained unchanged in the group without blurred vision. We did not detect any significant changes in VEGF levels during follow-up. By contrast, a significant reduction of sFlt-1 was observed in those patients with blurred vision at day 3 (p = 0.03) with normalization by day 10. Diabetic patients with blurred vision after starting insulin therapy present a significant transient increase in macular biometrics which is associated with a decrease in circulating sFlt-1.

Effects of intensive insulin therapy on IL-10 level and NF-ΚB activity in patients undergoing cardiopulmonary bypass

Objective To observe the effects of intensive insulin therapy on IL-10 level and NF-ΚB activity in peripheral blood mononuclear cells in patients undergoing cardiopulmonary bypass.Methods The non-diabetic patients undergoing cardiopulmonary bypass in our department were selected and assigned to intensive therapy group (group A,n=40) and received strict glycemic control after the initiation of surgery.And those who undergoing cardiac surgery but without strict glycemic control were assigned to routine therapy group (group B,n=40) as controls.The blood glucose in group A was maintained at 4.4～8.3mmol/L,whereas the glucose in group B was below 11.lmmol/L.The concentration of serum IL-10 and NF-ΚB activity in peripheral blood mononuclear cells was measured at different time points.Results There were no significant differences in general data between two groups.The concentration of IL-10 in group B was significantly lower than that in group A(P<0.05).compared with group B,strict glycemic control markedly suppressed NF-KB activation (P<0.05).Conclusion Intensive insulin therapy could reduce the activity of NF-ΚB and then reduce the expression of IL-10.Strict glycemic control could significantly mitigate the systemic inflammatory response. Key words: Cardiopulmonary bypass; Blood glucose; Insulin; Interleukin-10; Nuclear factor-κB

Effect of intensive insulin therapy on glutathione synthesis rate in cancer patients with stress hyperglycemia after major surgery.

e19593 Background: The glutathione system plays an essential role in antioxidant defense. We assessed the effects of intensive insulin treatment on glutathione synthesis rate and redox balance in n...

Dynamic characteristics of blood glucose time series during the course of critical illness: Effects of intensive insulin therapy and relative association with mortality*

To assess the effect of intensive insulin therapy on blood glucose amplitude variation and pattern irregularity in critically ill patients. To assess the association of these blood glucose signal characteristics with hospital mortality, independent of blood glucose level. Retrospective analysis of the databases of two previously published randomized controlled trials. University hospital, 56-bed adult surgical intensive care unit and 17-bed medical intensive care unit. One thousand five-hundred forty-eight surgical intensive care unit patients, admitted between February 2000 and January 2001, and 1200 medical intensive care unit patients, admitted between March 2002 and May 2005. In the two randomized controlled trials, patients were randomized to receive either intensive insulin therapy (targeting normoglycemia, between 4.4 and 6.1 mmol/L) or conventional insulin therapy (infusing insulin when blood glucose levels were >12 mmol/L and stopping at 10 mmol/L). Intensive insulin therapy significantly lowered mean blood glucose (5.8 vs. 8.4 mmol/L), hyperglycemic index (0.8 vs. 3.2 mmol/L), and glycemic penalty index (26 vs. 53), but it increased the mean daily difference between minimum and maximum blood glucose (mean daily delta blood glucose; 4.0 vs. 3.3 mmol/L). There was no significant effect on the standard deviation of the blood glucose measurements or on jack-knifed approximate entropy. In multivariable logistic regression analysis, corrected for baseline risk factors, blood glucose levels outside the normoglycemic range, higher mean daily delta blood glucose, higher standard deviation blood glucose, and higher jack-knifed approximate entropy were independently associated with hospital mortality. The Leuven intensive insulin therapy strategy increased mean daily delta blood glucose while not affecting standard deviation blood glucose and jack-knifed approximate entropy. Increased blood glucose amplitude variation and pattern irregularity were associated with mortality, irrespective of blood glucose level. The reduced mortality observed with intensive insulin therapy in the Leuven trials cannot be attributed to an effect on blood glucose amplitude variation or entropy. Reducing amplitude variation and entropy of the blood glucose signal, irrespective of blood glucose concentration, may produce clinical benefits.

Clinical effects of intensive insulin therapy on diabetes with acute obstructive suppurative cholangitis in elderly patients

Objective To study the clinical effects of the intensive insulin therapy on diabetes with acute obstructive suppurative cholangitis in elderly patients.Methods Sixty-four patients aged over 70 were divided into two groups:group A(maintenance of blood glucose at a level between 4.4 and 6.1lmmol/L)and group B(maintenance of blood glucose at a level between 10.0 and 11.1mmol/L).Insulin was infused by micro-injection pump.The changes of APACHEII score postoperative complications,average length of stay in hospital and prognosis were observed.Results The average APACHEII score of group A was significantly decreased after 3rd day postoperation(P＜0.01).The average length of stay in hospital of group A was significantly shorter than that of group B(P＜0.05).The postoperative complications of group A were significantly decreased(P＜0.05).Conclusion Intensive insulin therapy contributes to the outcome of the elderly patients with acute obstructive suppurative cholangitis. Key words: Cholangitis; Insulin infusion; Aged

Blood glucose amplitude variation: effects of intensive insulin therapy and relative association with mortality

There is growing evidence that not only blood glucose (BG) level but also BG amplitude variation (BGAV) is associated with mortality in critically ill patients [1].

P108 Effect of intensive insulin therapy on the somatotropic axis in critically ill children

P108 Effect of intensive insulin therapy on the somatotropic axis in critically ill children

Effects of intensive insulin therapy alone and with added pioglitazone on renal salt/water balance and fluid compartment shifts in type 2 diabetes

To evaluate the effects of intensive insulin therapy alone or with added pioglitazone on renal salt/water balance and body fluid compartment shifts in type 2 diabetes. A total of 25 insulin-treated, obese patients with type 2 diabetes were randomized to pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks to achieve equivalent glycaemic control. We measured total body water (TBW) and extracellular/intracellular fluid by bioimpedance analysis; plasma/RBC volume with I(131)albumin; sodium handling by fractional excretion of sodium/lithium (FeNa/FeLi) and other renal/hormonal parameters. Intensification of insulin therapy and the addition of pioglitazone significantly improved glycaemia (HbA1C 7.8-7.2% and 7.6-7.1%) and increased body weight (1.7 and 4.9 kg) respectively. TBW increased 1.7 l with insulin alone (65% intracellular) and 1.6 l with added pioglitazone (75% extracellular) (p = 0.06 and 0.09 respectively). Plasma volume increased 0.2 +/- 0.1 l with insulin alone (p = 0.05) and 0.4 +/- 0.1 l with added pioglitazone (p < 0.05). Extravascular, extracellular (interstitial) fluid increased significantly and more with added pioglitazone (0.8 +/- 0.2 l, p < 0.01) than with insulin alone (0.4 +/- 0.2 l, p = ns). At steady-state, FeLi (marker of proximal-tubular sodium delivery to the distal nephron) increased significantly with added pioglitazone (12.4 +/- 1.3 to 18.0 +/- 3.2%) vs. no significant change with insulin alone (15.4 +/- 1.2 to 14.5 +/- 2.3%). There were no significant changes in the other parameters. In intensively insulin-treated obese type 2 diabetic patients, at equivalent glycaemic control, the addition of pioglitazone causes greater weight gain, but a similar increase in body water that is mainly extracellular and interstitial compared with intracellular increase with insulin therapy alone. Pioglitazone also increases the filtered load of sodium reabsorbed at the distal nephron with no net change in FeNa.

Metabolic effects of intensive insulin therapy in critically ill patients

Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.

Reducing Glycemic Variability in Intensive Care Unit Patients: A New Therapeutic Target?

Acute hyperglycemia is common in critically ill patients. Strict control of blood glucose (BG) concentration has been considered important because hyperglycemia is associated independently with increased intensive care unit mortality. After intensive insulin therapy was reported to reduce mortality in selected surgical critically ill patients, lowering of BG levels was recommended as a means of improving patient outcomes. However, a large multicenter multination study has found that intensive insulin therapy increased mortality significantly. A difference in variability of BG control may be one possible explanation why the effect of intensive insulin therapy varied from beneficial to harmful. Several studies have confirmed significant associations between variability of BG levels and patient outcomes. Decreasing the variability of the BG concentration may be an important dimension of glucose management. If reducing swings in the BG concentration is a major biologic mechanism behind the putative benefits of glucose control, it may not be necessary to pursue lower glucose levels with their attendant risk of hypoglycemia.

Curative effect of intensive insulin therapy in critical old patients with stress hyperglycemia

Objective To observe the clinical curative effect of early intensive insulin therapy for critical old patients with stress hyperglycemia. Methods Fifty-six (> 60 years) patients in critical conditions with stress hyperglycemia were divided into two groups randomly, the intensive ins lin-therapy (IIT) group (n = 28) and traditional insulin-therapy (TIT) group (n = 28). The serum C-reactive protein (CRP) level, the time of the usage of insulin-infusion, the days in the ICU, the incidence of infection in hospital, mortality and the complications of hypoglycemia and hypokalemia were recorded. Results In IIT group, the serum CRP level, the time of usage of insulin, the days in the ICU, the incidence of infection in hospital and mortality were significandy lower than that in TIT group. (P < 0.05), but the wound healing rate was elevated obviously. As to complications, the incidence of hypoglycemia and hypokalemia was higher in IIT group than that in TIT group, even though there was no statistical significance on incidences of hypokalemia. Conclusions For critical old patients with stress hyperglycemia, early intensive insulin therapy can control blood glucose more effectively and promptly and improve the clinical curative effect. But the targeted nursing care for hypoglycemia and hypokalemia should be reinforced for the patients with intensive insulin-therapy. Key words: Hyperglycemia; Insulin; Therapy; Aged; Critical illness

Other complications and associated conditions with diabetes in children and adolescents

aChildren’s Hospital auf der Bult, Hannover, Germany; bthe Children’s Hospital at Westmead, NSW, Australia; cUniversity of Helsinki, Finland; dMedical University Vienna, Austria; eUniversity of Genova, Italy; fUniversitat Ulm, Uni West, Germany; gUniversity of Sydney, Australia Corresponding author: Prof. Dr. med. Olga Kordonouri Diabetes Center for Children and Adolescents Children’s Hospital auf der Bult Hannover, Germany Tel: +49 511/8115-3340; fax: +49 511/8115-3334; e-mail: kordonouri@hka.de

The influence of intensive insulin therapy on hemodynamics in patients with septic shock

To elucidate effects of intensive insulin therapy and target glucose control on hemodynamics and cardiac function in patients with septic shock. Twenty-seven patients of septic shock with myocardial depression were divided into routine group (14 cases, level of blood glucose was 4.1 to 6.1 mmol/L) and target group (13 cases, level of blood glucose was 6.2 to 8.3 mmol/L). Hemodynamics and cardiac function parameters were obtained via pulmonary artery catheter after 48 hours. Mean blood glucose level in target group was lower than that in routine group [(6.0+/-1.5) mmol/L vs. (8.2+/-1.9) mmol/L, P<0.05], with dosage of insulin infusion in target group increased as compared with that of routine group [(10.3+/-3.7) U/h vs. (7.5+/-3.0) U/h, P<0.05]. Furthermore, oxygenation index (PaO(2)/FiO(2)), stroke volume index (SVI), cardiac index (CI) and oxygen delivery index (DO(2)I) were increased 20.2%, 23.3%, 15.1% and 11.7%, respectively (all P<0.05). On the other hands, there was no significant difference between target and routine group in mean artery pressure, acute physiology and chronic health evaluation II (APACHEII) score, blood lactic acid (all P>0.05), although the incidence of severe hypoglycemia was higher in target group than the routine group (38.5% vs. 28.6%, P>0.05). Intensive insulin therapy and blood glucose control may improve hemodynamic status and enhance cardiac function in patients with septic shock and myocardial depression.

Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients

Intensive insulin therapy to maintain blood glucose at or below 6.11 mM reduces morbidity and mortality after cardiac surgery and morbidity in medical intensive care unit (ICU) patients. The authors investigated the clinical safety and outcome effects of intensive insulin therapy compared to conventional insulin therapy in patients receiving postoperative intensive care after neurosurgical procedures. In this prospective randomized controlled trial, 483 patients undergoing elective or emergency brain surgery were prospectively and randomly assigned either to intensive insulin therapy (241 patients), receiving insulin titrated to maintain blood glucose levels within the range of 4.44-6.11 mM, or to conventional insulin therapy (242 patients), receiving insulin to maintain blood glucose levels below 11.94 mM. Primary endpoint was incidence of hypoglycemia (defined as blood glucose < 2.78 mM). Efficacy measures included the length of ICU stay, infection rate, and 6 months follow-up Glasgow outcome scale score and overall survival. Hypoglycemia episodes were more frequent in patients receiving intensive insulin therapy, median (min-max): 8 (0-23) versus 3 (0-4); P < 0.0001. The length of stay in the ICU was shorter (6 vs. 8 days; P = 0.0001), and the infection rate was lower (25.7% vs. 39.3%; P = 0.0018). Glasgow outcome scale score and overall survival at 6 months were similar in the two groups. Intensive insulin therapy in patients admitted to a postoperative neurosurgical ICU after brain surgery is associated with iatrogenic hypoglycemia, but it can also reduce the infection rate and shorten the ICU stay.