Overview

Hyperglycemia is a common finding among medical and surgical inpatients with and without known diabetes, and is associated with poor outcomes across a variety of inpatient subpopulations. The relationship between hyperglycemia and inpatient outcomes may be weaker in patients with diabetes than in patients without diabetes. Hyperglycemia may be a marker of severe, acute illness, one of many physiological derangements associated with an abundance of counter-regulatory hormones, insulin resistance, and suppression of anabolic pathways. On the other hand, many investigators believe that hyperglycemia itself may worsen outcomes by contributing to inflammation, oxidative stress, poor immune function, and endothelial dysfunction. Interventions to control hyperglycemia in inpatients have largely centered on the use of adjustable insulin infusions to lower blood glucose. An early trial in myocardial infarction patients found that lowering blood glucose using intensive insulin therapy (IIT) reduced long-term mortality, though it remains unclear whether the inpatient or outpatient components of the intervention were responsible for the benefit. An influential single-center observational study of cardiac surgery patients reported reduced wound infection and mortality rates after the introduction of an intensive care unit IIT protocol. Subsequently a single-center trial in critically ill surgical patients suggested a mortality benefit from IIT used to achieve normoglycemia. These findings have fueled widespread interest in inpatient glycemic control strategies, and organizations have called for strict glycemic control strategies to be implemented in a variety of intensive care unit settings. More recently, new trials have been completed that may help clarify the balance of benefits and harms of widespread IIT implementation in intensive care units. We conducted a systematic review of trials and a critical appraisal of frequently cited observational studies to identify strengths of-and gaps in-the evidence supporting broad use of IIT to achieve glycemic control in inpatients. The objectives of this review are to address the following questions: 1. Does the use of intensive insulin therapy (IIT) to achieve tight glycemic control compared to less tight glycemic control improve final health outcomes in the following patients? patients in the surgical intensive care unit, patients in the medical intensive care unit, patients in the perioperative setting, acute myocardial infarction patients, acute stroke patients, general surgical ward patients, general medicine ward patients.2. What are the harms of strict glycemic control in the above subpopulations? 3. What are the most effective and safest means of lowering blood glucose in the above subpopulations?

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