Ill Adults: A Meta-analysis Benefits and Risks of Tight Glucose Control in Critically

CONTEXT The American Diabetes Association and Surviving Sepsis Campaign recommend tight glucose control in critically ill patients based largely on 1 trial that shows decreased mortality in a surgical intensive care unit. Because similar studies report conflicting results and tight glucose control can cause dangerous hypoglycemia, the data underlying this recommendation should be critically evaluated. OBJECTIVE To evaluate benefits and risks of tight glucose control vs usual care in critically ill adult patients. DATA SOURCES MEDLINE (1950-2008), the Cochrane Library, clinical trial registries, reference lists, and abstracts from conferences from both the American Thoracic Society (2001-2008) and the Society of Critical Care Medicine (2004-2008). STUDY SELECTION We searched for studies in any language in which adult intensive care patients were randomly assigned to tight vs usual glucose control. Of 1358 identified studies, 34 randomized trials (23 full publications, 9 abstracts, 2 unpublished studies) met inclusion criteria. DATA EXTRACTION AND ANALYSIS Two reviewers independently extracted information using a prespecified protocol and evaluated methodological quality with a standardized scale. Study investigators were contacted for missing details. We used both random- and fixed-effects models to estimate relative risks (RRs). RESULTS Twenty-nine randomized controlled trials totaling 8432 patients contributed data for this meta-analysis. Hospital mortality did not differ between tight glucose control and usual care overall (21.6% vs 23.3%; RR, 0.93; 95% confidence interval [CI], 0.85-1.03). There was also no significant difference in mortality when stratified by glucose goal ([1] very tight: < or = 110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2] moderately tight: < 150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or intensive care unit setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI, 0.63-1.22; [2] medical: 26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3] medical-surgical: 26.1% vs 27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose control was not associated with significantly decreased risk for new need for dialysis (11.2% vs 12.1%; RR, 0.96; 95% CI, 0.76-1.20), but was associated with significantly decreased risk of septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI, 0.59-0.97), and significantly increased risk of hypoglycemia (glucose < or= 40 mg/dL; 13.7% vs 2.5%; RR, 5.13; 95% CI, 4.09-6.43). CONCLUSION In critically ill adult patients, tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia.

[1]  R. Farah,et al.  Insulin therapy of hyperglycemia in intensive care. , 2007, The Israel Medical Association journal : IMAJ.

[2]  Z. Memish,et al.  Intensive Versus Standard Insulin Therapy: A Randomized Controlled Trial In Medical Surgical Critically Ill Patients.: 246 , 2006 .

[3]  R. Newton,et al.  Metabolic Control in Diabetic Subjects following Myocardial Infarction: Difficulties in Improving Blood Glucose Levels by Intravenous Insulin Infusion , 1991, Scottish medical journal.

[4]  M. Levy,et al.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 , 2007, Intensive Care Medicine.

[5]  F. Bilotta,et al.  The Effect of Intensive Insulin Therapy on Infection Rate, Vasospasm, Neurologic Outcome, and Mortality in Neurointensive Care Unit After Intracranial Aneurysm Clipping in Patients With Acute Subarachnoid Hemorrhage: A Randomized Prospective Pilot Trial , 2007, Journal of neurosurgical anesthesiology.

[6]  Stephen Daniel,et al.  Intensive insulin therapy and mortality in critically ill patients , 2008, Critical care.

[7]  Karen A Robinson,et al.  Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed. , 2002, International journal of epidemiology.

[8]  R. Bellomo,et al.  A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients. , 2006, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[9]  Daleen Aragon,et al.  Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control. , 2006, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[10]  J. Mechanick,et al.  Hypoglycemia in the intensive care unit , 2007, Current opinion in clinical nutrition and metabolic care.

[11]  F. Bilotta,et al.  Intensive Insulin Therapy After Severe Traumatic Brain Injury: A Randomized Clinical Trial , 2008, Neurocritical care.

[12]  M. Malesker,et al.  An efficiency evaluation of protocols for tight glycemic control in intensive care units. , 2007, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[13]  Neil J Grey,et al.  Reduction of nosocomial infections in the surgical intensive-care unit by strict glycemic control. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[14]  Aesha Drozdowski,et al.  Standards of medical care in diabetes. , 2004, Diabetes care.

[15]  D. Cook,et al.  Glycemic control in the ICU: a multicenter survey , 2004, Intensive Care Medicine.

[16]  Askiel Bruno,et al.  Treatment of Hyperglycemia In Ischemic Stroke (THIS): A Randomized Pilot Trial , 2008, Stroke.

[17]  Scott K Aberegg,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[18]  Anthony Delaney,et al.  Benefits and Risks of Tight Glucose Control in Critically Ill Adults: A Metaanalysis , 2009 .

[19]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[20]  A. Pesenti,et al.  Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients , 2008, Intensive Care Medicine.

[21]  Atul Malhotra,et al.  Intensive insulin in intensive care. , 2006, The New England journal of medicine.

[22]  P. Kvale,et al.  Intensive Insulin Therapy in Critical Illness , 2005 .

[23]  A. Melidonis,et al.  Intensive insulin treatment reduces transient ischaemic episodes during acute coronary events in diabetic patients. , 2002, Acta cardiologica.

[24]  M. Walters,et al.  A Randomised, Controlled Pilot Study to Investigate the Potential Benefit of Intervention with Insulin in Hyperglycaemic Acute Ischaemic Stroke Patients , 2006, Cerebrovascular Diseases.

[25]  Rolf Rossaint,et al.  Intensive insulin therapy and pentastarch resuscitation in severe sepsis. , 2008, The New England journal of medicine.

[26]  J. Dora,et al.  Standards of Medical Care in Diabetes—2008 , 2008, Diabetes Care.

[27]  Ning Li,et al.  [Influence and mechanism of a tight control of blood glucose by intensive insulin therapy on human sepsis]. , 2005, Zhonghua wai ke za zhi [Chinese journal of surgery].

[28]  P. Spronk,et al.  Intensive Insulin Therapy in Intensive Care: An Example of the Struggle to Implement Evidence-Based Medicine , 2006, PLoS medicine.

[29]  P. Sandercock,et al.  Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK) , 2007, The Lancet Neurology.

[30]  Iain Mackenzie,et al.  Tight glycaemic control: a survey of intensive care practice in large English hospitals , 2005, Intensive Care Medicine.

[31]  M. Enriquez-Sarano,et al.  Natural History of Asymptomatic Patients With Normally Functioning or Minimally Dysfunctional Bicuspid Aortic Valve in the Community , 2008, Circulation.

[32]  Mitchell M. Levy,et al.  Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock , 2004, Critical care medicine.

[33]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[34]  V. Pettilä,et al.  Strict versus moderate glucose control after resuscitation from ventricular fibrillation , 2007, Intensive Care Medicine.

[35]  R. Bellomo,et al.  Management of blood glucose in the critically ill in Australia and New Zealand: a practice survey and inception cohort study , 2006, Intensive Care Medicine.

[36]  Rinaldo Bellomo,et al.  Glycemic control in the intensive care unit: why we should wait for NICE-SUGAR. , 2005, Mayo Clinic proceedings.

[37]  H. Rodbard,et al.  American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. , 2007, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[38]  G. Carvalho,et al.  Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery. , 2007, Annals of internal medicine.

[39]  D. Cook,et al.  Lowering of glucose in critical care: a randomized pilot trial. , 2007, Journal of critical care.

[40]  Scott W. Lee,et al.  Intensive versus modified conventional control of blood glucose level in medical intensive care patients: a pilot study. , 2005, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[41]  M. Levy,et al.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 , 2007, Intensive Care Medicine.

[42]  M. Netea,et al.  Intensive insulin therapy does not alter the inflammatory response in patients undergoing coronary artery bypass grafting: a randomized controlled trial [ISRCTN95608630] , 2005, Critical care.

[43]  Liu Xinbing,et al.  Intensive insulin therapy for the critically ill patients with stress hyperglycemia , 2008 .

[44]  E. de Jonge,et al.  Evaluation of short-term consequences of hypoglycemia in an intensive care unit* , 2006, Critical care medicine.

[45]  Marcus J. Schultz,et al.  Tight glycaemic control: a survey of intensive care practice in the Netherlands , 2006, Intensive Care Medicine.

[46]  E. Fliers,et al.  Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during coronary artery surgery. , 2006, The Journal of clinical endocrinology and metabolism.

[47]  Eliotte Hirshberg,et al.  Blood glucose control in critically ill adults and children: a survey on stated practice. , 2008, Chest.

[48]  Yuan Xu,et al.  [Impact of intensive insulin therapy on surgical critically ill patients]. , 2007, Zhonghua wai ke za zhi [Chinese journal of surgery].