GIK Group Research Articles

Inhibitory Effect and Mechanism upon Glucose-Insulin-Potassium Administration on Postpartum Mice with Uterine Cramping Pain

This study aimed to explore the effect of glucose-insulin-potassium (GIK) on postpartum uterine cramping pain(UCP) in mice and the possible underlying mechanisms. Thirty full-term pregnancy C57BL/6 mice, within 6 h after spontaneous labor, the mice were randomly assigned into the following three groups: the control group (group C), the oxytocin group (group O), and the GIK plus oxytocin group (group G). Group G and group O were administered GIK and normal saline, respectively, and 10 min later, oxytocin was injected intraperitoneally; group C received normal saline twice. The pain scores of the mice were assessed after establishment of the postpartum UCP model. The differential expressions of energy metabolism and oxidized lipid metabolites in the uterus were analyzed. The behavioral scores in group G were significantly lower than those in group O (P < 0.05).When compared to group O, group G showed a significant increase in ATP levels (P = 0.046), and group G exhibited elevated levels of amino acids, including L-glutamine, L-aspartic acid, and ornithine. Additionally, phosphate compounds (2-phosphoglyceric acid and 3-phosphoglyceric acid) showed elevated levels. When compared to group O, group G exhibited a decrease in 19R-hydroxy PGF2α, an increase in 9,10-EpOME and 12,13-EpOME, and a decrease in trans-EKODE-E-Ib. Additionally, group G showed an elevation in 16,17-EpDPE and 8-HDoHE. This study confirms the analgesic effect of GIK during postpartum oxytocin infusion. Metabolomics and glycolysis product analysis suggest that GIK’s alleviation of UCP is associated with its enhancement of glycolysis and the influence of phenylalanine synthesis, aspartate metabolism, and arginine synthesis pathways. Additionally, the effects of GIK appears to be linked to its influence on the linoleic acid metabolic pathway.

Glucose-insulin-potassium alleviates uterine cramping pain following cesarean delivery: A randomized, controlled trial.

To explore the effect of glucose-insulin-potassium (GIK) therapy on uterine cramping pain (UCP) following cesarean delivery (CD). Single-center, randomized controlled study. Second Affiliated Hospital of Army Medical University, Chongqing, China. A total of 140 women, aged 20-40 years, who underwent CD with a transverse incision were randomly assigned to the GIK (P) or control (C) groups in a 1:1 ratio. GIK was intravenously administered to patients in Group P. Patients in Group C received normal saline (NS). After umbilical cord clamping, oxytocin was administered intravenously. The same GIK and NS regimens were administered on postoperative days 1 and 2, followed by oxytocin 10 min later. Following oxytocin administration, UCP was assessed using the visual analog scale (VAS), and the maximum VAS score (primary outcome) was recorded. Patients in Group P had significantly lower maximum VAS scores than those in Group C on postoperative days 1 (38.4 ± 21.1 vs. 52.3 ± 20.8, p < 0.001) and 2 (10 [0,30] vs. 30.5 [8.75,50], p < 0.001). Group P patients also had shorter pain duration on postoperative day 1 (39.6 ± 19.5 min vs. 50.6 ± 18.2 min, p = 0.001). Group P patients had a lower incidence of inadequate analgesia of UCP than Group C on days 1 (45.5% vs. 74.2%, p < 0.001) and 2 (10.6% vs. 47.0%, p < 0.001); the RRs for experiencing inadequate analgesia for UCP postpartum in Group P patients was 0.612 (95% CI: 0.454-0.826, p < 0.001) on day 1 and 0.226 (95% CI: 0.107-0.476, p < 0.001) on day 2. The absolute risk reduction (ARR) was 28.7%; thus number needed to treat (NNT) was 3 after rounding up. A subgroup analysis demonstrated that Group P patients undergoing repeat CD had lower maximum VAS scores for UCP on both postoperative days 1 and 2. Our findings suggest that GIK can relieve UCP and shorten its duration. Our results provide information to facilitate the development of novel approaches for managing UCP.Clinical Trial Registration: This study was approved by the Medical Ethics Committee of Second Affiliated Hospital of Army Medical University (2020-109-01, 19/11/2020) and registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR2100041607,01/01/2021).

Effect of Glucose-Insulin-Potassium Infusion on Hemodynamics in Patients with Septic Shock

BACKGROUND: Glucose-insulin-potassium (GIK) demonstrates a cardioprotective effect by providing metabolic support and anti-inflammatory action, and may be useful in septic myocardial depression. AIM: The aim of this study was to assess role of GIK infusion in improving hemodynamics in patients with septic shock in addition to its role in myocardial protection and preventing occurrence of sepsis-induced myocardial dysfunction and sepsis-induced arrhythmias. METHODS: This study was conducted on 75 patients admitted to the Critical Care Department in Cairo University Hospital with the diagnosis of septic shock during the period from January 2019 to December 2019. Patients were divided into two groups; first group was managed according to the last guidelines of surviving sepsis campaign and was subjected to the GIK infusion protocol while second group was managed following the last guidelines of surviving sepsis campaign only without adding GIK infusion. RESULTS: Patients in the GIK group showed better lactate clearance (50% vs. 46.7%) and less time needed for successful weaning of vasopressors than the control group (3.57±1.16 vs. 3.6±1.45 days) thought not reaching statistical significance. There was no statistically significant difference between both groups regarding development of septic-induced cardiomyopathy (16.7% in the control group vs. 13.3% in the GIK group); however, patients with hypodynamic septic shock showed better improvement in hemodynamic profile in the GIK group. Sepsis-induced arrhythmias occurred more in patients of the control group than in patients of the GIK group with no statistically significant difference between both groups (33.3% vs. 20%, p = 0.243). Few side effects were developed as a result of using GIK infusion protocol. CONCLUSIONS: GIK may help in improving hemodynamics and weaning of vasopressors in patients with refractory septic shock and those with septic induced cardiomyopathy. The use of GIK was well tolerated with minimal adverse reactions.

Does Glucose–Insulin–Potassium Infusion during on-pump Coronary Revascularization Affect Perioperative Inotropic Requirements?

Background: During coronary artery bypass grafting (CABG), the myocardium is subjected to endure periods of ischemia and reperfusion, which may result in post-ischemic contractile dysfunction. That is a major contributor to early and late morbidity and mortality and increased requirement of pharmacologic and mechanical circulatory support.Glucose insulin potassium (GIK) infusion was thought to provide a cardioprotective effect. Objective: To investigate whether the use of GIK solution in patients undergoing on-pump CABG affects requirements of inotropes. Patients and Method: In this prospective, randomized placebo-controlled trial, 64 patients were assigned into two groups: the GIK group in which glucose-insulin and potassium infusion was given during CABG surgery, and the non-GIK group in which only saline infusion was given during the procedure. Results: In the GIK group, all patient needed not more than two inotropes with mean of 1.28 ± 0.46, while in the non-GIK group there were patients who need up to three inotropes with mean of 1.56 ± 0.56 (P. value of 0.032). Conclusion: GIK infusion during on-pump CABG reduces perioperative inotropic requirements.

Myocardial Protection with Glucose-Insulin-Potassium Infusion during Cardiopulmonary Bypass for Coronary Revascularization

Background: Sodi-Pallares and colleagues first time introduced use of glucose-insulin and potassium (GIK) solution for myocardial protection. They used this solution in patients with acute myocardial infarction and concluded that GIK solution limited electrocardiographic changes in these patients. Objective: To investigate the effectiveness of the GIK solution regarding myocardial protection evaluated by postoperative creatine kinase MB (CKMB) and cardiac troponin I levels. Method: In this prospective, randomized clinical trial, sixty-four patients were assigned into two groups: GIK group, in which glucose-insulin and potassium infusion were given during surgery, and non-GIK group in which only saline infusion was given during the procedure. Results: All CK-MB values were lower in the GIK group than the Non-GIK group in the postoperative period (6, 12 and 24 hours’ samples) with statistically significant results. Troponin values were lower in the GIK group versus the Non-GIK group after 6 and 12 hours with statistical significance (P < 0.001 and 0.022 respectively). Conclusion: The addition of GIK infusion throughout the operation to standard myocardial protective techniques in patients undergoing on-pump coronary artery bypass graft (CABG) surgery attenuates myocardial ischemic injury.

Effectiveness of glucose-insulin–potassium infusion for myocardial protection in non-diabetic patients during adult cardiac surgery

Background: Glucose-insulin-potassium (GIK) infusion is most commonly used in diabetic patients during cardiopulmonary bypass. Many studies suggest that the use of GIK infusion has beneficial outcomes mainly in myocardial protection, as myocardial protection is the main goal of Perfusionist during bypass surgery. In Pakistan, GIK is used normally in the diabetic patient as it has a good effect on insulin maintenance. Most surgeons use GIK in diabetic patients but many of the studies suggest that it has good post-op outcomes especially in myocardial protection. Method: This was an observational cross-sectional study conducted for 6 months, from November 2019 to April 2020 at the Pakistan Institute of medical sciences department of Cardiac surgery. Ethical approval was taken from the hospital ethical committee. It was consisting of 80 patients, 40 from group A (GIK infused) and 40 from group B (GIK non-infused) by using the Non-probability convenient sampling technique. Data was collected through pre-structured Performa. Results: In the early postoperative period, peak CKMB levels were high in the Non-GIK group (62.7375± 19.75393IU/L) versus (54.0005±11.41493IU/L) in the GIK group (p-value 0.000). Mean ventilation time in the GIK group was (10.85 ±6.302) hours versus (12.15 ±7.814) hours in the non-GIK group (p&lt; 0.001). Similarly, ICU stay period was also shorter in the GIK group is (3.50 ±1.013) and in the non-GIK group is (3.50 ±0.906) (p&gt;0.001). Conclusion: Glucose-insulin-potassium (GIK) infusion has a beneficial role in myocardial protection and is associated with better post-operative outcomes without increasing the risk of non-cardiac complications.

Glucose—Insulin—potassium (GIK) Morbidity and mortality effects in cardiac surgery: a systematic review and meta-analysis of randomized trials

Introduction Although experimental studies strongly support the cardioprotective effects of glucose—insulin—potassium (GIK) infusion, clinical trials have yielded mixed results due to the heterogeneity of patient populations as well as varying GIK administration patterns. An updated systematic review and meta-analysis were conducted to assess the impact of GIK treatment on postoperative complications in patients undergoing on- or off-pump cardiac surgery. Methods We searched MEDLINE, Embase and the Cochrane Central Register without language restrictions for studies from inception to March, 2020. We included randomized controlled trials that compared GIK infusion as cardioprotective measure to conventional treatment or placebo in adults undergoing on- or off-pump cardiac surgery. Postoperative myocardial infarct (PMI) was the main study endpoint; secondary outcomes were in-hospital mortality, postoperative complications, as well as duration of mechanical ventilation, intensive care stay and hospital stay. Postoperative glycemia and cardiac index were also examined. The study was registered with PROSPERO (N°CRD42019117728). We computed risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) and heterogeneity was estimated using I2 statistic. Results From 47 studies, 5’872 participants were pooled for meta-analysis. The incidence of PMI was 5.9% and 8.3% in the GIK and Control groups, respectively (n = 20, RR [95% CI] = 0.83 [0.65 to 1.04] I2 = 0). Compared to control treatment, GIK infusion was associated with lower hospital mortality (n = 19, RR [95%CI] = 0.64 [0.43 to 0.97], I2 = 0), reduced acute kidney injury (n = 6, RR [95%CI] = 0.59 [0.4 to 0.87, I2 = 0), fewer atrial fibrillation (n = 23, RR [95%CI] = 0.75 [0.6 to 0.94], I2 = 0.58), as well as a shorter duration of mechanical ventilation (n = 14, MD [95%CI] = -1.77 [-3.04 to -0.49] hours, I2 = 0.96), shorter stay in intensive care (n = 20, MD [95%CI] = -5.39 [-9.34 to -1.44] hours, I2 = 0.99) and faster hospital discharge (n = 19, MD [95%CI] = -0.84 [-1.6 to -0.08] days, I2 = 0.95). Discussion A recent systematic review and meta-analysis restricted to part of the literature published on the topic since 2000 concluded to a strong effect of GIK on PMI [1]. While the analysis of our augmented corpus of literature did not find any such association in patients undergoing cardiac surgery, perioperative administration of GIK was associated with improved postoperative clinical outcomes as reflected by lower in-hospital mortality and morbidity as well as lesser utilization of hospital resources. Further clinical studies are warranted to ascertain the effectiveness of GIK in minimizing myocardial injuries and to explore the specific dosage and timing of GIK infusion.

104-LB: Glucose-Insulin-Potassium (GIK) as a Proposed Treatment for Normoglycemic Diabetic Ketoacidosis: An Old Friend for a New Foe?

Introduction: Glucose, Insulin, and potassium (GIK) infusions were introduced into medical practice to reduce myocardial injury during a heart attack in 1962. Euglycemic diabetic ketoacidosis (EDKA) is a clinical triad comprising increased anion gap metabolic acidosis, ketonemia or ketonuria and blood glucose levels &amp;lt;250mg/dL. Based on common treatment delays due lack of hyperglycemia, we decided to start a new proposed protocol for patients with confirmed EDKA that included the use of GIK and compared them with historical controls before the protocol was established. GIK solution was prepared with Dextrose 5% solution 500 cc, 10 UI of short acting insulin al 10 mmol KCl. At al initial rate of 100 ml/hr. Objectives: Describe general characteristics and compare time to remission, length of ICU stay and length of hospital time between patients with SGLT2i-associated EDKA in whom GIK was used compared to standard care. Design: A Cohort study was designed to compare objectives between EDKA patients treated with a GIK-adapted protocol versus previous patients treated with standard of care of DKA. Patients and Methods: 4 Patients with EDKA treated with new protocol were compared with 7 previous patients treated with ADA recommendations for DKA. Results: 41.66% of patients were male, type 2 diabetes was initially diagnosed in 66.66% of patients. No differences in ER characteristics between standard vs. GIK group. The use of GIK as an add-on treatment to standard care was associated with a significant lower time to resolution (1.5±0.5 vs. 3.57±1.61, p&amp;lt;0.01), fewer ICU days (2.5±0.57 vs. 5.57±1.98, p&amp;lt;0.01), in-hospital days (4.5±0.577 vs. 11.85±3.43, p&amp;lt;0.01). No differences in hypoglycemic or hipo/hyperkalemia were found. Conclusions: With the wide use of SLGT2 inhibitors there has been a similar increase in the number of SGLT2i-associated EDKA. Were propose a different way of management of these patients. More research is needed in this field and entity. Disclosure D. Espinoza-Peralta: None. J. Monjardin-Rochin: None. M.E. Búrquez-González: None. L.G. Mireles-Zavala: None.

Glucose-insulin-potassium infusion for the treatment of acute aluminum phosphide poisoning: an open-label pilot study

Introduction: Acute aluminum phosphide poisoning is common in low- and middle-income countries, and is associated with very high case fatality. The addition of glucose-insulin-potassium (GIK) infusion to the standard supportive care has been proposed to improve outcomes. We aimed to assess the effectiveness of GIK infusion in acute aluminum phosphide toxicity.Methods: We performed a prospective open-label pilot study in a tertiary care hospital in north India in patients over 13 years of age with acute aluminum phosphide poisoning, to determine whether the treatment with GIK infusion improved outcomes. The primary outcome was in-hospital case fatality, and the secondary outcomes were the duration of hospital stay, the requirement of mechanical ventilation, and the change in hemodynamic and metabolic parameters.Results: A total of 60 patients were randomly assigned to groups that received either GIK infusion with supportive care or supportive care alone. Baseline parameters in both groups were comparable. Treatment with GIK infusion was associated with significantly lower in-hospital case fatality compared with supportive care alone (46.7% versus 73.3%; p-value 0.03). It was associated with a longer duration of hospital stay (p-value < 0.01) and reduced requirement of mechanical ventilation (p-value < 0.01). The treatment improved blood pressure (systolic, diastolic, and mean arterial pressure) and Glasgow coma scale score at various time intervals; however, pulse rate and metabolic acidosis (blood pH and bicarbonate levels) remained comparable in both the groups. Hyperglycemia was significantly higher in the GIK group but was easily managed.Conclusion: Treatment with GIK infusion may improve survival and hemodynamics in patients with acute aluminum phosphide poisoning.

Plasma metabolomics of early parenteral nutrition followed with enteral nutrition in pancreatic surgery patients

Nutrition support is essential for surgical patients. Patients undergoing pancreaticoduodenectomy (PD) require tremendous nutrient support but also faced with risks of infection and gastrointestinal complications. Early parenteral nutrition has recently shown benefits while limited information provided about the influence on metabolism. This prospective single-center cohort study used plasma metabolomics to clarify metabolic alteration after early parenteral nutrition followed with enteral nutrition. Patients undergoing pancreaticoduodenectomy (n = 52) were enrolled. 36 patients received parenteral nutrition within 3 days postoperatively followed with EN (TPN group), 16 patients received standard fluids followed with EN (GIK group). We found that the weight loss is reduced in TPN group while the other clinical outcomes and inflammatory cytokines showed no statistical significance. The TPN group showed significance in amino acids, lipid, and phospholipids metabolism compared with the GIK group. Moreover, integration analysis indicated that early TPN could promote the metabolism of long-chain fatty acids, phospholipids, ketone bodies, and branched-chain amino acids. We conclude that early TPN support followed with EN for patients undergoing PD reduced the perioperative weight loss and promoted the metabolic transition to anabolic metabolism with the recovery of lipid metabolism, suggesting its benefits for the recovery of patients.

Intensive treatment of hyperglycemia in the acute phase of myocardial infarction: the tenuous balance between effectiveness and safety - a systematic review and meta-analysis of randomized clinical trials.

In acute myocardial infarction (AMI), each 18 mg/dl (1 mmol/L) increment is associated with a 3% increase in mortality rates. All strategies applied for reducing blood glucose to this date, however, have not presented encouraging results. We searched the Medline (PubMed) and Cochrane Library databases for randomized clinical trials (RCTs) from 1995 to 2017 that used the intensive strategy or GIK therapy for blood glucose control during the acute stage of the AMI. We included eight studies. In order to identify the effects of GIK or insulin therapy, we calculated a overall risk ratio (RR) with meta-analysis of fixed and random effects models. A two-tail p-value of < 0.05 was considered statistically significant. A total of 28,151 patients were included: 1,379 intensively treated with insulin, 13,031 in GIK group, and 13,741 in the control group. The total mortality was 10.5% (n=2,961) and the RR of 1.03 [95%CI 0.96-1.10]; I2 = 31%; p = 0.41 for the combined intensive insulin plus GIK groups in comparison with the control group. In meta-regression analyses, intense reductions in blood glucose (> 36 mg/dL) in relation to the estimated average blood glucose (estimated by HbA1c) were associated with higher mortality, whereas lower reductions in blood glucose (< 36 mg/dL) were not associated with mortality. The lowering of blood glucose in the acute phase of MI compared with the average blood glucose was more effective around 18 mg/dL. This meta-analysis suggests that there may be a tenuous line between the effectiveness and safety of reducing blood glucose in the acute phase of MI. The targets must not exceed a reduction greater than 36 mg/dL in relation to estimated average blood glucose.

Myocardial Protection by Glucose-Insulin-Potassium in Moderate- to High-Risk Patients Undergoing Elective On-Pump Cardiac Surgery: A Randomized Controlled Trial.

Low cardiac output syndrome is a main cause of death after cardiac surgery. We sought to assess the impact of glucose-insulin-potassium (GIK) to enhance myocardial protection in moderate- to high-risk patients undergoing on-pump heart surgery. A randomized controlled trial was performed in adult patients (Bernstein-Parsonnet score >7) scheduled for elective aortic valve replacement and/or coronary artery bypass surgery. Patients were randomized to GIK (20 IU of insulin, 10 mEq of potassium chloride in 50 mL of glucose 40%) or saline infusion given over 60 minutes on anesthetic induction. The primary end point was postcardiotomy ventricular dysfunction (PCVD), defined as new/worsening left ventricular dysfunction requiring inotropic support (≥120 minutes). Secondary end points were the intraoperative changes in left ventricular function as assessed by transoesophageal echocardiography, postoperative troponin levels, cardiovascular and respiratory complications, and intensive care unit and hospital length of stay. From 224 randomized patients, 222 were analyzed (112 and 110 in the placebo and GIK groups, respectively). GIK pretreatment was associated with a reduced occurrence of PCVD (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.25-0.66). In GIK-treated patients, the left systolic ventricular function was better preserved after weaning from bypass, plasma troponin levels were lower on the first postoperative day (2.9 ng·mL(-) [interquartile range {IQR}, 1.5-6.6] vs 4.3 ng·mL(-) [IQR, 2.4-8.2]), and cardiovascular (RR, 0.69; 95% CI, 0.50-0.89) and respiratory complications (RR, 0.5; 95% CI, 0.38-0.74) were reduced, along with a shorter length of stay in intensive care unit (3 days [IQR, 2-4] vs 3.5 days [IQR, 2-7]) and in hospital (14 days [IQR, 11-18.5] vs 16 days [IQR, 12.5-23.5]), compared with placebo-treated patients. GIK pretreatment was shown to attenuate PCVD and to improve clinical outcome in moderate- to high-risk patients undergoing on-pump cardiac surgery.

One-Year Outcome of Intensive Insulin Therapy Combined to Glucose-Insulin-Potassium in Acute Coronary Syndrome: A Randomized Controlled Study.

BackgroundA number of factors may offset the cardioprotective effects of glucose‐insulin‐potassium (GIK) on outcome of patients with acute coronary syndrome, such as hyperglycemia induced by this cocktail infusion. We performed a study to evaluate the effect of intensive insulin therapy in association with GIK on 1‐year outcome in patients hospitalized for acute coronary syndrome.Methods and ResultsIn a randomized prospective controlled trial we included 772 patients with non–ST‐segment elevation acute coronary syndrome. Patients were randomized into 3 groups: GIKI2 group, who received GIK with intensive insulin therapy for 24 hours; GIK group, who received GIK with nonintensive insulin therapy; and control group, who received usual care. The primary outcome criteria were the rates of major cardiovascular events combining death, reinfarction, and stroke rate at 1 year. In addition, we measured platelet function assay‐100 and plasminogen activator inhibitor‐1 at admission and 24 hours later. Based on an intention‐to‐treat analysis, major cardiovascular events at 1 year was 12.8% in the GIKI2 group, 15.5% in the GIK group, and 20.5% in the placebo group; the difference was significant between the GIK2 and control groups (P=0.01). Platelet function assay‐100 at 24 hours decreased significantly from baseline in the control group but not in the GIKI2 group. Plasminogen activator inhibitor‐1 decreased significantly in the GIKI2 group but significantly increased in the control group. Minor hypoglycemic events were more frequent in the GIKI2 group compared with other groups.ConclusionsGIKI2 led to improvement of 1‐year outcome rates in patients with non–ST‐segment elevation acute coronary syndrome. This beneficial effect was associated with a decrease in platelet reactivity and an increase on fibrinolysis tests.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00965406.

Myocardial protection with Glucose-Insulin-Potassium infusion during adult cardiac surgery.

Background & Objective:Recent meta-analysis reports have called for more randomized trials to evaluate the effectiveness of GIK solution in patients of cardiac surgery. So this study was conducted to evaluate the effectiveness of Glucose-insulin-potassium (GIK) solutions in non-diabetic patients undergoing coronary artery bypass grafting.Methods:A total number of one hundred and sixty (160) patients were randomized into two equal groups; GIK Group and non-GIK group. In GIK group, 5% dextrose containing 70 IU/L regular insulin and 70 meq/L of potassium was administered. The infusion was started at a rate of 30 ml/hour after induction of anesthesia and before the start of cardiopulmonary bypass. The infusion was started again after removal of aortic cross clamp and was continued for six hours after the operation.Results:In early post-operative period, peak CKMB levels were high in non-GIK group 48.50±19.79 IU/L versus 33.40±14.69 IU/L in GIK group (p-value <0.001). There was no statistically significant difference in requirements of inotropic support between the groups. The mean duration of inotropic support in GIK group was only 5.50±6.88 hours in GIK group and 8.64±7.74 hours in non-GIK group (p-value 0.008). Mean ventilation time in GIK group was 5.06±2.39 hours versus 6.55±3.58 hours in non-GIK group (p-value 0.002). Similarly, ICU stay period was also shorter in GIK group (p-value 0.01). We did not found any detrimental effect of GIK infusion on non-cardiac complications e.g. renal, pulmonary and neurologic complications.Conclusion:Glucose-insulin-potassium (GIK) infusion has a beneficial role in myocardial protection and is associated with better post-operative outcomes without increasing the risk of non-cardiac complications.

Glucose-Insulin-Potassium Alleviates Intestinal Mucosal Barrier Injuries Involving Decreased Expression of Uncoupling Protein 2 and NLR Family-Pyrin Domain-Containing 3 Inflammasome in Polymicrobial Sepsis.

Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which may play a key role in the development of sepsis, and insulin has been reported to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly allocated into five groups: control group, cecal ligation and puncture (CLP) group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h after surgery. Histological and cytokine analyses, intestinal permeability tests, and western blots of intestinal epithelial tight junction component proteins and UCP2 were performed. Compared with CLP group, the CLP + GIK group had milder histological damage, lower levels of cytokines in the serum and ileum tissue samples, and lower UCP2 expression, whereas the CLP + GK group had no such effects. Moreover, the CLP + GIK group exhibited decreased epithelial permeability of the ileum and increased expression of zonula occludens-1, occludin, and claudin-1 in the ileum. The findings demonstrated that the UCP2 and NLR family-pyrin domain-containing 3/caspase 1/interleukin 1β signaling pathway may be involved in intestinal barrier injury and that GIK treatment decreased intestinal barrier permeability. Thus, GIK may be a useful treatment for intestinal barrier injury during sepsis.

Very early administration of glucose-insulin-potassium by emergency medical service for acute coronary syndromes: Biological mechanisms for benefit in the IMMEDIATE Trial

In the IMMEDIATE Trial, intravenous glucose-insulin-potassium (GIK) was started as early as possible for patients with suspected acute coronary syndrome by ambulance paramedics in communities. In the IMMEDIATE Biological Mechanism Cohort substudy, reported here, we investigated potential modes of GIK action on specific circulating metabolic components. Specific attention was given to suppression of circulating oxygen-wasting free fatty acids (FFAs) that had been posed as part of the early GIK action related to averting cardiac arrest. We analyzed the changes in plasma levels of FFA, glucose, C-peptide, and the homeostasis model assessment (HOMA) index. With GIK, there was rapid suppression of FFA levels with estimated levels for GIK and placebo groups after 2 hours of treatment of 480 and 781 μmol/L (P<.0001), even while patterns of FFA saturation remained unchanged. There were no significant changes in the HOMA index in the GIK or placebo groups (HOMA index: placebo 10.93, GIK 12.99; P = .07), suggesting that GIK infusions were not countered by insulin resistance. Also, neither placebo nor GIK altered endogenous insulin secretion as reflected by unchanging C-peptide levels. These mechanistic observations support the potential role of FFA suppression in very early cardioprotection by GIK. They also suggest that the IMMEDIATE Trial GIK formula is balanced with respect to its insulin and glucose composition, as it induced no endogenous insulin secretion.

Effect of glucose-insulin-potassium on hyperlactataemia in patients undergoing valvular heart surgery: A randomised controlled study.

Hyperlactataemia represents oxygen imbalance in the tissues and its occurrence during cardiac surgery is associated with adverse outcomes. Glucose-insulin-potassium (GIK) infusion confers myocardial protection against ischaemia-reperfusion injury and has the potential to reduce lactate release while improving its clearance. The objective of this study is to compare the effect of GIK on the incidence of hyperlactataemia in patients undergoing valvular heart surgery. A randomised controlled study. Single university teaching hospital. One hundred and six patients scheduled for elective valvular heart surgery with at least two of the known risk factors for hyperlactataemia. Patients were randomly allocated to receive either GIK solution (insulin 0.1 IU kg(-1) h(-1) and an infusion of 30% dextrose and 80 mmol l(-1) potassium at 0.5 ml kg(-1) h(-1)) or 0.9% saline (control) throughout surgery. The primary outcome was the incidence of hyperlactataemia (lactate ≥ 4 mmol l(-1)) during the operation and until 24 h after the operation. Secondary outcomes included haemodynamic parameters, use of vasopressor or inotropic drugs, and fluid balance until 24 h postoperatively. Postoperative morbidity endpoints were also assessed. The incidences of hyperlactataemia were similar in the groups (32/53 patients in each of the control and GIK groups, P > 0.999). There were no intergroup differences in haemodynamic parameters, use of vasopressor and inotropic drugs, or fluid balance. The incidences of postoperative morbidity endpoints were similar in both groups. Despite its theoretical advantage, GIK did not provide beneficial effects in terms of the incidence of hyperlactataemia or outcome in patients undergoing valvular heart surgery. Clinicaltrials.gov identifier: NCT01825720.

Combination therapy with remote ischaemic conditioning and insulin or exenatide enhances infarct size limitation in pigs

Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in patients. Our objective was to investigate whether the combination of RIC with either exenatide or glucose-insulin-potassium (GIK) is more effective than RIC alone. Pigs were submitted to 40 min of coronary occlusion followed by reperfusion, and received (i) no treatment, (ii) one of the following treatments: RIC (5 min ischemia/5 min reperfusion × 4), GIK, or exenatide (at doses reducing infarct size in clinical trials), or (iii) a combination of two of these treatments (RIC + GIK or RIC + exenatide). After 5 min of reperfusion (n = 4/group), prominent phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) was observed, both in control and reperfused myocardium, in animals receiving GIK, and mitochondria from these hearts showed reduced ADP-stimulated respiration. (1)H NMR-based metabonomics disclosed a shift towards increased glycolysis in GIK and exenatide groups. In contrast, oxidative stress (myocardial nitrotyrosine levels) and eNOS uncoupling were significantly reduced only by RIC. In additional experiments (n = 7-10/group), ANOVA demonstrated a significant effect of the number of treatments after 2 h of reperfusion on infarct size (triphenyltetrazolium, % of the area at risk; 59.21 ± 3.34, 36.64 ± 3.03, and 21.04 ± 2.38% for none, one, and two treatments, respectively), and significant differences between one and two treatments (P = 0.004) but not among individual treatments or between RIC + GIK and RIC + exenatide. GIK and exenatide activate cardioprotective pathways different from those of RIC, and have additive effects with RIC on infarct size reduction in pigs.

Myocardial protection by glucose–insulin–potassium in acute coronary syndrome patients undergoing urgent multivessel off-pump coronary artery bypass surgery

The aim of this randomized and controlled trial was to investigate the effect of a glucose-insulin-potassium (GIK) solution on myocardial protection in acute coronary syndrome (ACS) patients undergoing urgent multivessel off-pump coronary artery bypass (OPCAB) surgery. Sixty-six patients were randomly allocated either to receive 0.3 ml kg(-1) h(-2) GIK solution (potassium 80 mEq and regular insulin 325 IU in 500 ml of 50% glucose) or equivalent volume of normal saline (control) upon anaesthetic induction until 6 h after reperfusion. The primary endpoints were to compare the concentrations of creatine kinase-MB (CK-MB) and troponin-T between the groups after reperfusion. The secondary endpoints were to compare the incidences of postoperative troponin-T >0.8 ng ml(-1) and myocardial infarction (MI) between the groups. Highest CK-MB [8.7 (4.4) vs 13.1 (7.9) ng ml(-1), P=0.006] and troponin-T [0.20 (0.13-0.49) vs 0.48 (0.18-0.91) ng ml(-1), P<0.0001] values after reperfusion were significantly lower in the GIK group compared with the control group. The area under the curve of serially measured troponin-T was also significantly smaller in the GIK group compared with the control group [0.83 (0.43-1.81) vs 0.46 (0.31-1.00), P=0.036]. Significantly fewer patients in the GIK group showed troponin-T >0.8 ng ml(-1) after reperfusion compared with the control group (3 vs 11, P=0.033). The incidence of postoperative MI was similar between the groups. GIK administration in ACS patients undergoing urgent multivessel OPCAB significantly attenuated the degree of ensuing myocardial injury without complications related to glycaemic control. Clinical Trial Registry. URL: http://clinicaltrials.gov/ct2/show/NCT01384656?term=GIK+AND+OPCAB&rank=1. Unique identification number NCT01384656.

Glucosa-Insulin-Potassium (GIK) Solution Used with Diabetic Patients Provides Better Recovery After Coronary Bypass Operations

Tight blood glucose control has become a therapeutical goal for anesthetic management for patients scheduled for cardiac surgery, especially if they are diabetic patients. This study was created to confirm the benefits of intraoperative GIK solution usage during coronary bypass operation of diabetic patients. Patients with type 1 and 2 diabetes mellitus (DM) referred for coronary artery bypass grafting (CABG) were randomized to receive GIK solution (GIK--study group) in the first 24 hours intraoperatively or to receive official Clinical protocol without GIK solution (non GIK - control group). The primary clinical outcome was the cardiac index (CI) since it represents the most sensitive measure of cardiac work in the immediate postoperative period, and the secondary clinical outcomes were the glycemic control, insulin consumption, duration of mechanical ventilation (MV), potassium level and atrial fibrillation (AF) appearance. One hundred diabetic patients, divided into two groups, were included in the study. The cardiac index did not show a significant difference, although the study group had CI with only minor variations than those of the controlled group, hence the reason we considered the study group as the more stable. The atrial fibrillation showed a difference between two groups, with 14 (28%) patients with postoperative AF in the control group compared with 3 (6%) patients with postoperative AF in the study group. As potassium values were stable in study group, we concluded that it can be one of the reasons for less postoperative AF in this group. The duration of MV showed a significant difference (0,003) between the two groups as well. In the study group the average MV time was 534,38 minutes, compared with the control group with 749,20 minutes. The average value of glucose was 11.1 mmol/l in the control group vs. 9.8 mmol/l in the study group. The study group had less insulin consumption in order to maintain target glycemia (p = 0.001). In the non GIK group average insulin consumption was 44 IJ per patient vs. 28.5 IJ in the GIK group. Intraoperative GIK solution given to diabetic patients with CABG operation provides more stable CI, shorter time of MV, more stable values of potassium which provides normal rhythm and less AF onset, less insulin to maintain target glycemia. All the above mentioned provides more stable intraoperative hemodynamic and better recovery of diabetic