To Assess the Impact of Glucose, Insulin, and Potassium Chloride Infusions in Patients after Cardiothoracic Surgery on Arrhythmias and Outcome

INTRODUCTION

For many years, cardiac protection has been accomplished through the usage of glucose, insulin, and potassium (GIK) solution during cardiac surgery. Few studies showed that when GIK infusion was started early in patients who were presented with acute myocardial infarction it resulted in reduced morbidity and mortality.^[1,2] Improved ventricular performance and a smaller infarct size are associated with GIK infusion. Few studies evaluated the use of GIK solution in cardiac surgery patients and demonstrated its effectiveness in lowering mortality and improving post-operative morbidity, but some studies concluded that perioperative GIK usage does not significantly lower death and arrhythmias in patients undergoing cardiac surgeries.^[3-5]

Following cardiac surgery, GIK administration was linked to better post-operative contractile function and a lower risk of atrial arrhythmias according to a study done by Ranucci et al.⁶ Therefore, the use of GIK solution to prevent arrhythmias in patients who are undergoing cardiac surgery is still debatable, necessitating the completion of more research before a conclusion can be drawn. Most of the research was conducted in settings where GIK infusions were initiated during surgery. Considering this, I intended to carry out a prospective randomized controlled study to determine how post-operative infusions of GIK affect the course of rhythm issues and outcome after cardiothoracic surgery.

MATERIAL AND METHODS

This prospective randomized clinical trial which lasted for 9 months. Total number of patients included was 100 in number who were randomly allocated to two groups equally. Randomization was done by computerized method. The study was not blinded.

Study group (GIK group); once the patient is shifted to post-operative cardiothoracic unit after cardiac surgery, GIK infusion (40 IU/L of human actrapid and 40 meq/L potassium chloride was added to 10% dextrose solution) given to the GIK group, with flow rate of 30 mL/hr. The infusion continued for 48 h following surgery.

Control group (non-GIK group); in non-GIK group, normal saline or other intravenous fluid was started as per requirement. Patients aged 20–60 years who underwent cardiac surgery and met the inclusion criteria were included in the study.

RESULTS

The demographic characteristics of the study group (GIK group) and control group (non-GIK group) are similar [Table 1]. A significant difference was observed between the GIK and non-GIK group with respect to incidence of arrhythmias (P < 0.001), a greater number of arrhythmias are seen in control group Figure 1, Table 2. The odds ratio is 0.1976 and confidence interval 95% between the two groups is 0.084–0.465. The incidence of AF was high among all arrhythmias in non GIK (control) group, while the GIK (study) group had a higher incidence of ectopics PVCs Figure 2, Table 3. The non-GIK group experienced longer ionotropic support than the study group (GIK group) with significant P < 0.002 Figure 3, Table 4. The non-GIK group had higher rates of mechanical ventilation hours and increased duration of ICU stay (P = 0.002 and < 0.001) Figures 4 and 5, Tables 5 and 6.

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Figure 1:

Incidence of arrhythmias among GIK and Non GIK groups. GIK: Glucose-Insulin- Potassium, Non GIK: Non- Glucose-Insulin- Potassium.

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Figure 2:

Shows comparison of incidence of various Arrhythmias between GIK and Non GIK group. GIK: Glucose-Insulin-Potassium.

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Figure 3:

Comparison of the duration of ionotropic requirement between GIK and Non GIK groups. GIK:Glucose-Insulin-Potassium, Non GIK: Non- Glucose-Insulin- Potassium.

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Figure 4:

Graph depicting that duration of mechanical ventilation is more in Non-GIK group when compared to GIK group.GIK: Glucose-Insulin- Potassium, Non GIK: Non- Glucose-Insulin-Potassium.

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Figure 5:

Comparison of ICU length of stay between GIK and Non GIK group. GIK: Glucose-Insulin- Potassium, Non-GIK: Non-Glucose-Insulin- Potassium.

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DISCUSSION

Fatty acids are the main source of energy for non-ischemic cardiac tissue, providing 60–70% of the overall energy requirements of the heart. These fatty acids are harmful during ischemia because they raise oxygen demand, decrease glucose consumption, and increase the risk of O₂ free radical production in the heart, which can lead to arrhythmias.^[6,7] Therefore, myocardium may benefit from the supply of exogenous glucose substrate during ischemia. GIK infusion can cause metabolic changes during ischemia and reperfusion, such as decreased oxidation of free fatty acids, enhanced oxidation of glucose, increased glycolysis, and increased absorption of oxygen for the synthesis of adenosine triphosphate (ATP) and its use for enhanced cardiac contractility.^[8] In addition, GIK contributes to the activation of K-ATP channels that are signaled by insulin. These channels are crucial ischemic pre-conditioning mediators that provide strong defense against myocardial ischemia (ischemia reperfusion damage). By raising the open state probability and lowering the ATP sensitivity of K-ATP channels, insulin plays a crucial part in controlling these channels.

In addition, GIK infusion has been shown to possess inotropic and vasodilator qualities. In 2004, Bothe et al. carried out an analysis to assess the function of GIK infusion in cardiothoracic surgery. The results suggest that GIK may significantly lessen atrial arrhythmias incidence during cardiothoracic surgery and increase recovery of contractile function postoperatively. To properly evaluate the effectiveness of GIK following heart surgery, large-scale randomized multicenter trials are necessary, as a number of factors restrict the power of this analysis.^[9]

To determine the impact of GIK infusion on arrhythmias and mortality after cardiac surgery, Rabi et al. conducted a systematic meta-analysis in 2010. They concluded patients who have undergone cardiothoracic surgery, perioperative use of GIK infusion does decrease mortality or arrhythmias.^[10] The usage of GIK infusion in patients undergoing cardiothoracic surgery should be avoided until future trials results supporting GIK infusions are published, as the safety of these infusions has not been well investigated.^[11]

In 2015, Ahmad et al. studied how GIK chloride infusion during adult cardiothoracic surgery protected the myocardium. Patients were randomly allocated equal groups equally: Study group or control group. A dextrose solution containing human actrapid and potassium chloride was given to the GIK group.^[12] After the anesthesia was induced but before cardiopulmonary bypass began, flow rate of the infusion was 30 mL/h. When the clamp was removed from aorta, the infusion was resumed and maintained for 6 h. According to study findings, GIK infusion improves post-operative outcomes and plays a positive role in myocardial protection without raising the risk of non-cardiac complications.^[13,14]

In 2016, Zhao et al. conducted research to determine if patients undergoing cardiopulmonary bypass surgery benefit from modified GIK regimens in terms of improved tissue perfusion and cardio-protection. They concluded that patients undergoing cardiopulmonary bypass surgery have a lesser significant adverse cardiac event in the hospital when they are offered a modified GIK regimen perioperatively.^[15,16] These advantages most likely come from improved myocardial metabolism and increased systemic tissue perfusion brought on by GIK^[17,18] activating insulin signaling.

In our study, we discovered that the GIK (study) group had a lesser incidence of arrhythmias than the control (non-GIK) group (P < 0.002 and confidence interval 95% 0.074–0.565). The GIK group also had shorter ventilatory and ionotropic support durations, which reduced morbidity and ICU stay after surgery. Non-GIK group showed longer duration of mechanical ventilation due to increase in incidence of arrhythmias and hemodynamic instability. The type of surgeries between GIK and Non GIK groups are also comparable [Figure 6, Table 7].

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Figure 6:

Graph projecting the comparison of type of surgery between GIK and Non-GIK group. GIK:Glucose-Insulin- Potassium, Non GIK: Non- Glucose-Insulin- Potassium, AVR: Aortic valve repalcement, CABG: Coronary Artery Bypass Graft, DVR: Double valve repalcement, MVR: Mitral valve replacement, TV repair: Tricuspid valve repair..

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The supplementary table depicts the data collected in both GIK and Non GIK groups with respect to various parameters. Side effects observed with GIK infusion are hyperkalemia and hyperglycemia which was manageable.

CONCLUSION

GIK chloride infusion after cardiothoracic surgery helps to minimize post-operative arrhythmias and is linked to better post-operative outcomes, such as lower requirement of ionotropic support and early extubation, leading to reduced stay in the intensive care unit after surgery. There are no noteworthy non-cardiac problems linked to the use of GIK infusion.

Therefore, we advise using GIK infusion to prevent and lessen arrhythmias in suitable patients after cardiac surgery in the ICU, thereby reducing the duration of ICU stay.