Insulin‐based regimens decrease mortality rates in critically ill patients: a systematic review

To determine whether treatment with glucose‐insulin‐potassium (GIK), insulin and glucose, or insulin by itself is beneficial in limiting organ damage after acute myocardial infarction (AMI) and reducing mortality and morbidity among critically ill hyperglycaemic patients.

Abstract

Abstract Objectives To determine whether treatment with glucose‐insulin‐potassium (GIK), insulin and glucose, or insulin by itself is beneficial in limiting organ damage after acute myocardial infarction (AMI) and reducing mortality and morbidity among critically ill hyperglycaemic patients. Methods Systematic review of randomized controlled trials. Main outcome measure To assess whether tight glycaemic control reduces morbidity and mortality. Studies reviewed Randomized controlled trials of insulin‐based regimens in the treatment of critically ill patients. Results Nine hundred and twenty‐four potentially relevant studies were identified and screened for retrieval. Of these, 16 randomized controlled trials met the inclusion criteria (Table 1 ). Ten studies examined the effects of GIK, and six of these studies reported a mortality reduction with GIK treatment in addition to enhanced myocardial performance. Five studies examined the administration of insulin. Among these studies, tight glycaemic control of blood glucose in one study was shown to reduce morbidity and mortality of patients in intensive care. Only one study examined insulin/glucose therapy, and it showed a post‐myocardial infarction mortality reduction of one year. Description of Studies in Order of Treatment (Glucose‐Insulin‐Potassium‐GIK) Study No. Source Year Study title Study design/description Study findings—whether tight glycaemic control improves morbidity and mortality 2 Lazar et al. 1997 GIK solutions enhance recovery after urgent coronary artery bypass grafting Study undertaken to determine whether GIK solutions would benefit patients undergoing coronary artery bypass grafting. Although no mortality was evident in either group. GIK therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting. The study group consisted of 30 patients with unstableangina who required coronary artery bypass surgery: 15 patients randomized to treatment with GIK solution administered intravenously after induction of anaesthesia and continued for 12 h after aortic unclamping, the remaining 15 patients received intravenous 5% dextrose in water. 3 Diaz et al. 1998 Metabolic modulation of AMI: The ECLA GIK pilot trial Study conducted to evaluate the impact of a GIK infusion administered during the first few hours of AMI. A trend toward a non‐significant reduction in major and minor in‐hospital events was observed in patients allocated to GIK. However, in the patients treated with reperfusion strategies, a statistically significant reduction in mortality and a consistent trend toward fewer in‐hospital events in the GIK group was observed. A total of 407 patients with suspected AMI were studied. In a ratio of 2 : 1 patients, 268 were randomized to receive GIK (high or low dose) and 139 to receive control. 4 Scott et al. 1999 GIK infusions in the treatment of acute stroke patients with mild to moderate hyperglycaemia. The glucose–insulin in stroke trial (GIST) Study designed to determine whether glucose/insulin induced and maintained euglycaemia in acute stroke patients with mild to moderate hyperglycaemia can improve outcome after stroke. Fiftythree acute stroke patients with mild to moderate hyperglycaemia (7–17 mmol/L) were studied: 25 randomized to treatment with a GIK infusion (insulin concentration in the GIK was altered according to BM glucose values) and 28 to the control, which were administered as sodium chloride infusion. Results confirm that GKI infusion in mild to moderate hyperglycaemia following acute stroke is a safe, practical, and pragmatic intervention that effectively lowers the plasma glucose levels to within normal range; however, the beneficial effects of this treatment remain to be elucidated. 5 Ceremuzynski et al. 1999 Low‐dose GIK is ineffective in AMI: results of a randomized multi‐centre Pol‐GIK trial Study designed to assess the clinical efficacy of GIK infusion in AMI. Low‐dose GIK treatment does not improve the survival and clinical course in AMI. The study consisted of 954 patients: 494 randomized to treatment with low‐dose GIK infusion and 460 to the control group, which was administered sodium chloride by IV infusion. Total mortality at 35 days was significantly higher in the GIK infusion group than in the control group. 6 Besogul et al. 1999 Chemical, biochemical and histochemical assessment of pre‐treatment with GIK for patients undergoing mitral valve replacement in the third and forth functional groups of the New York Heart Association. A study designed to investigate the potentially beneficial effects of pre‐operative treatment with GIK for patients undergoing mitral valve replacement. No significant reduction in mortality was evident throughout the period of the trial; however, the patients receiving GIK required less inotropic support, had fewer ventricular arrhythmias, and exhibited improved haemodynamic indices: cardiac output increased & systemic vascular resistance decreased. A total of 30 patients were studied: 15 randomly assigned to treatment with GIK infusion and 15 to the control group, which was administered an equivalent volume of sodium chloride. 7 Lazar et al. 2000 GIK solutions improve outcomes in diabetic patients who have coronary artery operations. Study undertaken to determine whether GIK would improve myocardial performance and limit morbidity after coronary artery bypass grafting in diabetic patients. Although no mortality was evident in either group. GIK therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting. A total of 40 patients were studied: 20 randomized to receive a GIK infusion and 20 to the control group, which received 5% dextrose in water. 9 Ulgen et al. 2001 The effect of GIK solution on ventricular late potentials and heart rate variability in AMI. Study designed to investigate the effects of GIK solution on ventricular late potentials (VLP) and high rate variability (HRV) during the early period of AMI. Although treatment with GIK solution did not find a statistically significant reduction in mortality, the results suggest that GIK therapy in the early periods of AMI shows beneficial effects: decreased post‐myocardial infarction angina and ischaemia. (High rate variability and presence of VLP are known to correlate with an increased risk of ventricular tachycardia and sudden death in AMI.) A total of 72 patients were studied: 34 randomized to treatment with GIK and 38 to the placebo. 10 Szabo et al. 2001 Effects of high‐dose GIK on myocardial metabolism after coronary surgery in patients with type 2 diabetes. Study designed to investigate the effects of high‐dose GIK on myocardial substrate utilization after coronary surgery in patients with type 2 diabetes. Although no mortality was evident in either group, it can be concluded that high‐dose GIK significantly enhances myocardial performance. A total of 20 patients were randomly allocated: 10 received high‐dose GIK infusion post‐operatively and the remaining 10 in the control group received standard post‐operative care, including insulin infusion if required, to maintain blood glucose below 10 mmol/L. 11 Smith et al. 2002 Coronary revascularisation: a procedure in transition from on‐pump to