Effects of Glucose-Insulin-Potassium Infusion on ST-Elevation Myocardial Infarction in Patients Treated With Thrombolytic Therapy

doi:10.1016/j.amjcard.2005.05.068

The American Journal of Cardiology

Volume 96, Issue 8, 15 October 2005, Pages 1053-1058

https://doi.org/10.1016/j.amjcard.2005.05.068 Get rights and content

The role of glucose-insulin-potassium (GIK) infusion in the management of acute myocardial infarction is not well established. This prospective, randomized study comprised 120 patients who had ST-elevation myocardial infarction that was treated within 12 hours from symptom onset with a high dose of GIK (25% glucose, 50 IU of soluble insulin per liter, and 80 mmol of potassium chloride per liter at 1 ml/kg/hour over 24 hours) as adjunct to thrombolytic therapy (1.5 MU of streptokinase/30 to 60 minutes; GIK group) or thrombolytic therapy alone (control group). The primary end point of the study was the rate of major adverse cardiac events (MACEs) at 1 month, defined as a composite of cardiac death, reinfarction, serious arrhythmias (ventricular fibrillation and/or tachycardia), and severe heart failure. The secondary end points were the rate of MACEs at 1 year and improvement in left ventricular systolic function. The incidence of MACEs at 1 month was significantly lower in the GIK group (10% vs 32.5%, relative risk 0.24, 95% confidence interval 0.09 to 0.63, p = 0.0043). Patients in the GIK group had significant decreases in ventricular tachycardia and/or fibrillation (1.3% vs 15.0%, p = 0.003) and severe heart failure (3% vs 12.5%, p = 0.031). The rate of MACEs at 1 year was also significantly lower in the GIK group (13% vs 40.0%, relative risk 0.22, 95% confidence interval 0.09 to 0.55, p = 0.0012). After 1 year, there was a significant improvement in left ventricular ejection fraction in the GIK group (from 48 ± 8% to 51 ± 10%, p <0.01), which was not observed in the control group. In conclusion, high-dose GIK, used as an adjunct to thrombolytic therapy, was safe and improved clinical outcome at 1 month. The beneficial effect of GIK infusion was maintained up to 1 year.

Section snippets

Selection of patients

All consecutive patients who had symptoms consistent with AMI >20 minutes in duration, presented within 12 hours of symptom onset, and had ST elevation in ≥1 mm in ≥2 contiguous electrocardiographic leads when admitted to the Coronary Care Unit of the University Institute of Cardiovascular Disease (Belgrade, Serbia) were evaluated for inclusion in this study.6, 7 Exclusion criteria for GIK therapy were renal insufficiency (serum creatinine >3 mg/dl, oliguria, or anuria), hyperkalemia (>5.0

Study population

One hundred twenty patients who had ST-elevation AMI were enrolled from August 2000 to September 2001. There were 80 patients in the GIK group (40 patients received intravenous metoprolol and 40 did not) and 40 patients in the control group. Two patients in the GIK group were lost to follow-up. Except for higher diastolic blood pressure in the control group, there were no differences in the other demographic and clinical characteristics among the groups (Table 1). The mean infused volume of GIK

Discussion

The main finding of our study was that the high-dose GIK infusion as an adjunct to thrombolytic therapy in patients who had AMI significantly decreased the 1-month rate of MACEs compared with thrombolytic therapy alone. This beneficial effect was maintained up to 1 year, but because the difference between groups from 1 month to 1 year was not significant, it was mainly attributed to the decrease in MACEs observed during the first 30 days after AMI. That beneficial effect was based dominantly on

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Hyperglycemia in nondiabetic patients presenting with acute myocardial infarction
2012, American Journal of the Medical Sciences
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The associated increase in mortality and heart failure in the first 3 days was attributed to the glucose-insulin-potassium infusion. In contrast, a smaller study analyzing early initiation of lower infusion rate of glucose-insulin-potassium in 120 AMI patients demonstrated an 88% reduction in major cardiovascular events at 1 year follow-up.61 The majority of the patients studied in this trial had no history of diabetes.
Hyperglycemia is common in nondiabetic patients with acute myocardial infarction (AMI). Elevated blood glucose level may reflect a response to stress, an underlying abnormal glucometabolic state or both. Regardless of mechanism, hyperglycemia complicating AMI is associated with an inflammatory and prothrombotic state, depressed myocardial contractility and increased short- and long-term mortality. Studies are needed to define optimal monitoring and management of hyperglycemia in nondiabetic patients with AMI.
The need for increased vigilance in managing hyperglycaemia during acute coronary syndrome in the emergency department: An introduction to the evidence
2011, Australasian Emergency Nursing Journal
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A number of large studies have tested two methods of delivering insulin in ACS: these are known as the glucose-insulin-potassium (GIK) and insulin only (intensive insulin therapy, IIT) regimens. After promising early findings,42–44 two large trials failed to demonstrate improved outcomes in patients with ACS treated with GIK,41,45 leading others to discredit this approach.27 Cheung37 has criticised these appraisals, arguing the relevant trials focussed on insulin-only, with little regard for glucose levels.
Until recently, increased blood glucose levels in those with and without diabetes with critical illnesses were perceived to be adaptive and benign responses to physiological stress in the critical care environment. In a landmark study published in 2001, Van den Berghe and colleagues demonstrated stress hyperglycaemia was not beneficial for patients who were experiencing critical illness. Instead, they found it resulted in significant increases in mortality. Several clinical trials and meta-analyses have since reported early management of hyperglycaemia in acute coronary syndrome (ACS), and many other critical illnesses to be advantageous. Not all evidence supports tight glycaemic control however. In this paper, we examine possible mechanisms by which increased blood glucose may harm patients with ACS and explain how insulin may be protective. We introduce evidence for and against increased glucose control in the emergency department. Given the increased mortality and morbidity associated with high blood glucose in ACS, we recommend increased diligence in the management of hyperglycaemic patients with ACS upon presentation to emergency departments.
Acute Myocardial Infarction, Hyperglycemia, and Insulin
2009, Journal of the American College of Cardiology
Insulin as an Anti-Inflammatory and Antiatherogenic Modulator
2009, Journal of the American College of Cardiology
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Another possible reason for the lack of benefit of GIK in CREATE-ECLA may have been the time of initiation of GIK after reperfusion therapy in the majority of patients. A recent study of GIK infusion at the time of reperfusion with thrombolytic agents (mean of 3 h following chest pain) demonstrated an impressive 88% reduction in major cardiovascular events at 1 year (61). The first evidence on the outcomes of glycemic control with low-dose insulin infusions came from a study by Van den Berghe et al. in 2001 (62).
Data demonstrate the anti-inflammatory effects of insulin and proinflammatory effects of glucose. These data provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in hospitalized patients. Regimens that infuse fixed doses of insulin with high rates of glucose are usually associated with hyperglycemia, which may neutralize the beneficial effects of insulin. Therefore, we propose that such regimens should be avoided and instead replaced by insulin infusions that normalize and maintain blood glucose at a reasonably low level and ensure that plasma insulin is maintained at levels high enough to provide clinically relevant anti-inflammatory and cardioprotective effects. Trials to test this hypothesis are in progress.
Lowering Glucose to Prevent Adverse Cardiovascular Outcomes in a Critical Care Setting
2009, Journal of the American College of Cardiology
High admission blood glucose levels after acute myocardial infarction are common and associated with an increased risk of death in patients with or without diabetes. Hyperglycemia is associated with altered myocardial blood flow and energetics and can lead to a pro-oxidative/proinflammatory state. The use of intensive insulin treatment has shown superior benefits in the treatment of hyperglycemia versus glucose-insulin-potassium infusion, particularly in critical care settings.
Effect of Hyperglycemia and Insulin in Acute Coronary Syndromes
2007, American Journal of Cardiology
Citation Excerpt :
Another reason for the lack of benefit from GIK infusion in CREATE-ECLA may have been the initiation of infusion after reperfusion therapy in most patients.62 A recent study of GIK infusion at the time of reperfusion with thrombolytic agents (a mean of 3 hours after chest pain) demonstrated an 88% reduction in major cardiovascular events at 1 year.63 Subjects with hyperglycemia in the HI-5 study64 demonstrated a reduction in reinfarction and heart failure with an insulin regimen that was designed to control glucose between 4.0–9.99 mmol/L (72–180 mg/dL).
Previously published data clearly demonstrate that hyperglycemia worsens morbidity and mortality in patients in intensive care, those with acute myocardial infarction and stroke, and those undergoing coronary artery bypass grafting. The control of hyperglycemia with insulin infusion improves clinical outcomes in these patients. In this article, we discuss data that demonstrate a proinflammatory effect of glucose and free fatty acids and an anti-inflammatory effect of insulin. We also provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusion in hospitalized patients.

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Coronary artery diseaseEffects of Glucose-Insulin-Potassium Infusion on ST-Elevation Myocardial Infarction in Patients Treated With Thrombolytic Therapy

Section snippets

Selection of patients

Study population

Discussion

Am J Cardiol

J Am Coll Cardiol

Lancet

Glucose-insulin-potassium therapy for treatment of acute myocardial infarctionan overview of randomized placebo-controlled trials

Circulation

Metabolic modulation of acute myocardial infarctionThe ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group

Circulation

Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarctionresults of randomized multicenter Pol-GIK trial

Cardiovasc Drugs Ther

Management of acute myocardial infarction in patients presenting with ST-segment elevationThe Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology

Eur Heart J

Circulation

A randomized evaluation of effects of glucose-insulin-potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy

Am Heart J

Oxidative stress after reperfusion with primary coronary angioplastylack of effect of glucose-insulin-potassium infusion

Crit Care Med

Coronary artery disease
Effects of Glucose-Insulin-Potassium Infusion on ST-Elevation Myocardial Infarction in Patients Treated With Thrombolytic Therapy