Modified Glucose-Insulin-Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery

Background Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin-glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double-blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in-hospital major adverse cardiac events including all-cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate-1 and protein kinase B in the hearts of GIK-treated patients. Systemic blood lactate was also reduced in GIK-treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in-hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT01516138

Cardiology News/Literature Review/2021

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Effects of remote ischaemic preconditioning on peri-operative myocardial injury and clinical outcomes in patients undergoing elective cardiac bypass surgery

Ischaemic heart disease (IHD) is a major cause of morbidity and mortality in the world. Coronary artery bypass graft (CABG) surgery is the revascularisation strategy of choice in a significant number of patients, particularly those with diabetes mellitus and complex coronary disease. During cardiac surgery, the myocardium is subjected to peri-operative myocardial injury (PMI), which has been associated with worse short and long-term clinical outcomes. Higher-risks patients are currently being operated on with subsequent higher risk of PMI and worse prognosis: therefore new strategies are required to potentiate the innate mechanisms of cardioprotection. In this regard, remote ischaemic preconditioning (RIPC) is a promising non-invasive intervention able to reduce PMI in these patients: however, not all the studies have shown significant cardioprotection with RIPC for a number of factors, amongst which the intensity of the preconditioning stimulus may play a significant role. We therefore investigated whether an enhanced RIPC stimulus, given with transient simultaneous multi-limb ischaemia/reperfusion, was able to reduce PMI and improve short-term clinical outcomes in patients undergoing elective cardiac surgery: we demonstrated that our preconditioning stimulus can significantly reduce PMI, length of intensive care unit (ICU) stay and incidence of atrial fibrillation (AF) in these patients. In addition, further retrospective analyses showed improved myocardial protection in preconditioned diabetic patients undergoing CABG surgery and in control CABG subjects receiving combined antegrade and retrograde cardioplegia compared to control CABG patients having antegrade cardioplegia or intermittent cross-clamp-fibrillation. We also conducted a multi-centre, double-blinded randomised control clinical trial, in which we investigated the effects of RIPC on clinical outcomes at 1 year in high-risk patients undergoing elective CABG surgery with or without valve surgery (the ERICCA trial). The results of this study are due to be presented in March 2015 and have the potential to significantly impact on clinical practice in cardiac surgery

Anticoagulation control in patients with atrial fibrillation

To examine self-reported depression, anxiety, beliefs about medication, knowledge of AF, and quality of life in newly anticoagulated atrial fibrillation (AF) patients and to investigate anticoagulation control, measured by time in therapeutic range (TTR) in AF patients and operated valvular heart disease (VHD) patients, prescribed long-term VKA therapy. Study I: AF patients have low levels of depression and anxiety, and positive beliefs about medication. AF knowledge and quality of life was poor. Results were unchanged at 6 months but AF symptoms and awareness of AF consequences improved. Study 2: TTR was significantly lower in South-Asians (60.5%) and Afro-Caribbeans (61.3%) compared to Whites (67.9%; p<0.00 1] despite similar INR monitoring intensity. TTR was similar among elderly (≥80 vs. <80 years) patients and those with/without chronic kidney disease. Non-white ethnicity was the strongest independent predictor of poor TTR. Study 3: TTR was significantly poorer in operated VHD patients with AF (55.7%) compared to those without AF (60.1 %; p=0.002). Independent predictors of poor TTR: female sex. AF and anaemia/bleeding history. Conclusion: Newly anticoagulated AF patients had poor quality of life and limited AF knowledge. 1TR was sub-optimal (TTR<70%) among non-white AF patients and operated VHD patients with AF

Front Lines of Thoracic Surgery

Front Lines of Thoracic Surgery collects up-to-date contributions on some of the most debated topics in today's clinical practice of cardiac, aortic, and general thoracic surgery,and anesthesia as viewed by authors personally involved in their evolution. The strong and genuine enthusiasm of the authors was clearly perceptible in all their contributions and I'm sure that will further stimulate the reader to understand their messages. Moreover, the strict adhesion of the authors' original observations and findings to the evidence base proves that facts are the best guarantee of scientific value. This is not a standard textbook where the whole discipline is organically presented, but authors' contributions are simply listed in their pertaining subclasses of Thoracic Surgery. I'm sure that this original and very promising editorial format which has and free availability at its core further increases this book's value and it will be of interest to healthcare professionals and scientists dedicated to this field

Effects of inhaled therapies on pulmonary hypertension and right ventricular function in cardiac surgery

Au Canada, on estime que 30 000 chirurgies cardiaques sont effectuées chaque année (1). L'insuffisance ventriculaire droite demeure une complication courante chez les patients subissant une chirurgie cardiaque. L'incidence de l’insuffisance ventriculaire droite périopératoire aiguë sévère peut aller de 0,1 % après une cardiotomie à 20 à 30 % après l'implantation d'un dispositif d'assistance ventriculaire gauche (2). La survenue d'une défaillance ventriculaire droite est encore plus fréquente en présence d'hypertension pulmonaire. Les conséquences de l'insuffisance ventriculaire droite en chirurgie cardiaque comprennent une détérioration périopératoire et des effets indésirables tels qu'un sevrage difficile de la circulation extracorporelle, une utilisation accrue d'agents vasoactifs intraveineux, et un risque accru de mortalité. Par conséquent, le diagnostic et le traitement de l’hypertension pulmonaire et de la dysfonction ventriculaire droite sont essentiels dans la période périopératoire pour éviter les complications. La surveillance simultanée et en continue des courbes de pression de l’artère pulmonaire et du ventricule droit à l'aide du cathétérisme de l'artère pulmonaire est un outil de surveillance important chez les patients en chirurgie cardiaque pour la détection précoce d'un dysfonctionnement du ventricule droit et pour évaluer la réponse au traitement. Les stratégies thérapeutiques dans ce contexte devraient se concentrer sur la réduction de la postcharge du ventricule droit et l'amélioration de la fonction du ventricule droit tout en évitant l'hypotension systémique. Les hypothèses de cette thèse sont les suivantes : 1) les vasodilatateurs inhalés sont supérieurs aux agents administrés par voie intraveineuse pour le traitement et la gestion de l’hypertension pulmonaire en chirurgie cardiaque, 2) la combinaison d'époprosténol inhalé et de la milrinone inhalée (iE&iM) est une stratégie efficace pour faciliter le sevrage de la circulation extracorporelle et pour réduire les besoins en inotropes intraveineux, 3) tous les patients n'ont pas une réponse vasodilatatrice positive à la combinaison de l’iE&iM, 4) la réponse à l’iE&iM est associée à des changements des courbes de pression du ventricule droit et de l’artère pulmonaire, et 5) le gradient de la chambre de chasse du ventricule droit et la vitesse d’augmentation de la pression intraventriculaire droite (dP/dt) ont le potentiel d'être des marqueurs pharmacodynamiques de la réponse au traitement. Le travail compris dans cette thèse consiste en 3 études. La première est une revue systématique et méta-analyse d'essais contrôlés randomisés démontrant que l'administration de vasodilatateurs inhalés pour le traitement de l’hypertension pulmonaire pendant la chirurgie cardiaque est associée à une amélioration de la performance du ventricule droit comparé aux agents administrés par voie intraveineuse. La deuxième étude est une analyse de cohorte rétrospective de 128 patients recevant l’iE&iM avant la circulation extracorporelle. Cette étude a démontré une réponse vasodilatatrice au traitement par l’iE&iM chez 77% des patients. Une réponse favorable était associée à un sevrage facile de la circulation extracorporelle plus fréquent et à une utilisation plus faible d'inotropes intraveineux. De plus, cette étude a également démontré qu'une hypertension pulmonaire plus sévère est prédictive d'une réponse vasodilatatrice pulmonaire positive, tandis qu'un European System for Cardiac Operative Risk Evaluation score (EuroSCORE) II élevé est un prédicteur de non-réponse au traitement. La dernière étude de cette thèse est une étude de cohorte prospective incluant 26 patients recevant iE&iM avec surveillance continue de la courbe de pression du ventricule droit démontrant l'innocuité et l'efficacité de cette approche thérapeutique dans l'amélioration de la fonction ventriculaire droite.In Canada there is an estimated 30,000 cardiac surgeries that are performed each year (1). Right ventricular failure (RVF) remains a common complication in patients undergoing cardiac surgery. The incidence of severe acute perioperative RVF can range from 0.1% after cardiotomy to 20-30% after left ventricular assist device implantation (2). The occurrence of RVF is even more frequent in the presence of pulmonary hypertension (PH). Consequences of RVF in cardiac surgery include perioperative deterioration and adverse outcomes such as difficult separation from cardiopulmonary bypass (CPB), increased use of intravenous (IV) vasoactive agents and an increased risk of mortality. Therefore, the diagnosis and treatment of PH and right ventricular (RV) dysfunction is essential in the perioperative period to circumvent complications. Continuous and simultaneous monitoring of both pulmonary artery pressure (Ppa) and RV pressure (Prv) waveforms using pulmonary artery catheterization is an important monitoring tool in cardiac surgery patients for early detection of RV dysfunction and for evaluating response to treatment. Therapeutic strategies in this context should focus on reducing RV afterload and improving RV function while avoiding systemic hypotension. The hypotheses of this thesis are the following: 1) inhaled aerosolized vasodilators are superior to IV administered agents for the treatment and management of PH in cardiac surgery, 2) the combination of inhaled epoprostenol and inhaled milrinone (iE&iM) is an effective strategy to facilitate separation from CPB and reduce the requirements for IV inotropes, 3) not all patients have a positive vasodilator response to iE&iM, 4) response to iE&iM is associated with changes in RV and PA pressure waveforms, and 5) RV outflow tract (RVOT) gradient and RV maximal rate of pressure rise during early systole (dP/dt) have the potential to be pharmacodynamic markers of response to treatment. The work comprised in this thesis consist of 3 studies. The first is a systematic review and meta-analysis of randomized controlled trials showing that administration of inhaled vasodilators for the treatment of PH during cardiac surgery is associated with improved RV performance compared to IV administered agents. The second study is a retrospective cohort analysis of 128 patients receiving iE&iM before CPB. This study showed that 77% of patients have a vasodilator response to iE&iM treatment. A favorable vasodilator response was associated with more frequent easy separation from CPB and lower use of IV inotropes post-CPB. In addition, more severe PH at baseline is shown to be predictive of a positive pulmonary vasodilator response while high European System for Cardiac Operative Risk Evaluation score (EuroSCORE) II is a predictor of non-response to treatment. The last study of this thesis is a prospective cohort study including 26 patients receiving iE&iM with continuous monitoring of Prv waveform demonstrating the safety and efficacy of this treatment approach in improving RV function

Clinical Handbook of Antithrombotic : A Practical Guide

Antithrombotic agents are high-risk medications associated with significant rates of medication errors. The use of antithrombotic agents is extensively high in cardiology and medical specialties; thus, a good understanding of antithrombotic agents is essential. A group of pharmacists has worked collectively to come out with this handbook focusing on antithrombotic agents that are commonly established in Sarawak Heart Centre. The purpose of this handbook is to serve as reference material on antithrombotic agents for pharmacists, nurses, medical officers, medical interns, students and other healthcare providers in the medical field. Therefore, additional basic knowledge of pharmacogenetics and pharmacogenomics information of patients’ response to certain antithrombotic agents are also highlighted in this handbook. I hope the healthcare providers, trainees and students will find this handbook useful during their course of duties