Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery.

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach.

OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. DESIGN AND SETTING: A systematic review of literature followed by web-based voting on findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from 61 countries. INTERVENTIONS: The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.

Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts.

As we previously demonstrated the role of different K(+) channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K(+) channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K(+) (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K(+) (KV) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca(2+)-activated K(+) (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.

Enhancing predictive accuracy of the cardiac risk score in open abdominal aortic surgery: the role of left ventricular wall motion abnormalities.

Background: Open abdominal aortic surgery carries many potential complications, with cardiac adverse events being the most significant concern. The Vascular Study Group Cardiac Risk Index (VSG-CRI) is a commonly used tool for predicting severe cardiac complications and guiding clinical decision-making. However, despite the potential prognostic significance of left ventricular wall motion abnormalities (LVWMAs) and reduced LV ejection fraction (LVEF) for adverse outcomes, the VSG-CRI model has not accounted for them. Hence, the main objective of this study was to analyze the added value of LV wall motion on the discriminatory power of the modified VSG-CRI in predicting major postoperative cardiac complications. Methods: A prospective study was conducted involving 271 patients who underwent elective abdominal aortic surgery between 2019 and 2021. VSG-CRI scores were calculated, and preoperative transthoracic echocardiography was conducted for all patients. Subsequently, a modified version of the VSG-CRI, accounting for reduced LVEF and LVWMAs, was developed and incorporated into the dataset. The postoperative incidence of the composite endpoint of major adverse cardiac events (MACEs), including myocardial infarction, clinically relevant arrhythmias treated with medicaments or by cardioversion, or congestive heart failure, was assessed at discharge from the index hospitalization, with adjudicators blinded to events. The predictive accuracy of both the original and modified VSG-CRI was assessed using C-Statistics. Results: In total, 61 patients (22.5%) experienced MACEs. Among these patients, a significantly higher proportion had preoperative LVWMAs compared to those without (62.3% vs. 32.9%, p < 0.001). Multivariable regression analysis revealed the VSG-CRI [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.21-1.77; p < 0.001] and LVWMA (OR 2.76; 95% CI 1.46-5.23; p = 0.002) as independent predictors of MACEs. Additionally, the modified VSG-CRI model demonstrated superior predictability compared to the baseline VSG-CRI model, suggesting an improved predictive performance for anticipating MACEs following abdominal aortic surgery [area under the curve (AUC) 0.74; 95% CI 0.68-0.81 vs. AUC 0.70; 95% CI 0.63-0.77; respectively]. Conclusion: The findings of this study suggest that incorporating preoperative echocardiography can enhance the predictive accuracy of the VSG-CRI for predicting MACEs after open abdominal aortic surgery. Before its implementation in clinical settings, external validation is necessary to confirm the generalizability of this newly developed predictive model across different populations.

Mitochondrial molecular basis of sevoflurane and propofol cardioprotection in patients undergoing aortic valve replacement with cardiopulmonary bypass.

BACKGROUND/AIMS: Study elucidates and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis. METHODS: Twenty-two patients were prospectively randomized in two groups regarding the anesthetic regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac injury and brain natriuretic peptide (BNP) were measured preoperatively and postoperatively. In tissue samples, taken from the interventricular septum, key mitochondrial molecules were determined by Western blot, real time PCR, as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis. RESULTS: The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content was higher in propofol than sevoflurane receiving patients. Propofol group also showed higher protein level of connexin 43 (Cx43) than sevoflurane group. Besides, immunogold analysis showed its mitochondrial localization. The mRNA level of mtDNA and uncoupling protein (UCP2) were higher in propofol than sevoflurane patients, as well. On the other hand, there were no significant differences between groups in hemodynamic assessment, intensive care unit length of stay, troponin I and BNP level. CONCLUSIONS: Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms. It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase, while the effects of propofol occur through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2.

Benefits, risks and complications of perioperative use of epidural anesthesia.

Use of thoracic epidurals is widespread for intraoperative and postoperative analgesia. Thoracic epidural anaesthesia (TEA) reduces sympathetic activity and thereby influences perioperative function of vital organ systems. A results of recent studies suggest that TEA decreases postoperative morbidity and mortality. There is better pain control with TEA in a wide range of surgical procedures. Use of TEA is associated with the risk of harm, but also the other methods used to control perioperative pain and stress response carry specific risks. Timely diagnosis and treatment of spinal compression or infection are crucial to ensure patient safety with TEA. The benefits of TEA outweigh the risks with respect to the perioperative outcome and organ protection, if basic guidelines are followed.

Steroids and statins: an old and a new anti-inflammatory strategy compared.

OBJECTIVES: This study compared the anti-inflammatory effects of methylprednisolone (MP) and atorvastatin and analysed their influences on clinical variables in patients undergoing coronary revascularization. METHODS: Ninety patients with compromised left ventricular ejection fraction (≤30%) undergoing elective coronary surgery were equally randomized to one of three groups: statin group, treatment with atorvastatin (20 mg/day) 3 weeks before surgery; methylprednisolone group, a single shot of methylpredniosolone (10mg/kg); and control group. RESULTS: Postoperative IL-6 was higher in the control group when compared to the methylprednisolone and statin groups (p<0.01). IL-6 was higher in the statin-treated patients (p<0.05 versus methylprednisolone). Administration of methylprednisolone as well as statin treatment increased postoperative cardiac index, left ventricular stroke work index, decreased postoperative atrial fibrilation rate and reduced ICU stay (p<0.05 versus control). The number of patients requiring inotropic support was lower in the methylprednisolone group when compared with the other two groups (p<0.01). Tracheal intubation time was reduced in patients who received methylprednisolone (p<0.01 versus control). CONCLUSIONS: Preoperative administration of either methylprednisolone or atorvastatin reduced pro-inflammatory cytokine release, improved haemodynamics, decreased postoperative atrial fibrilation rate and reduced ICU stay in patients with significantly impaired cardiac function undergoing coronary revascularization. Treatment with methylprednisolone was associated with less inotropic support requirements and reduced mechanical ventilation time.

Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.

Remote ischaemic preconditioning (RIPC) is a medical procedure that consists of repeated brief periods of transient ischaemia and reperfusion of distant organs (limbs) with the ability to provide internal organ protection from ischaemia. Even though RIPC has been successfully applied in patients with myocardial infarction during coronary revascularization (surgery/percutaneous angioplasty), the underlying molecular mechanisms are yet to be clarified. Thus, our study aimed to determine the role of nitric oxide synthase (NOS) isoforms in RIPC-induced protection (3 × 5 min of forearm ischaemia with 5 min of reperfusion) of arterial graft in patients undergoing urgent coronary artery bypass grafting (CABG). We examined RIPC effects on specific expression and immunolocalization of three NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) in patients' internal thoracic artery (ITA) used as a graft. We found that the application of RIPC protocol leads to an increased protein expression of eNOS, which was further confirmed with strong eNOS immunopositivity, especially in the endothelium and smooth muscle cells of ITA. The same analysis of two other NOS isoforms, iNOS and nNOS, showed no significant differences between patients undergoing CABG with or without RIPC. Our results demonstrate RIPC-induced upregulation of eNOS in human ITA, pointing to its significance in achieving protective phenotype on a systemic level with important implications for graft patency.

Preconditioning with glucose-insulin-potassium solution and restoration of myocardial function during coronary surgery.

The administration of glucose-insulin-potassium (GIK) solution has beeen shown to exert cardioprotective and immunomodulatory properties in coronary disease. 49 patients (pts.) for coronary surgery were randomly assigned to receive high-dose GIK treatment (30% glucose, insulin 2 IU.kg(-1).l(-1) and K(+) 80 mmo/l solution; 1 ml/kg/h); low-dose GIK treatment (10% glucose, insulin 32 IU l(-1) and K(+) 80 mmol/l solution; 1 ml/kg/h) or control treatment (Ringer solution 1 ml/kg/h). Haemodynamic measurements were done for four time points: T1 - after induction of anaesthesia; T2 - after the operation; T3 - 6 h after the operation and T4 - 24 h after the operation. Significant recovery of cardiac function was evident in high-dose GIK (H-GIK) and low-dose GIK (L-GIK) groups after 24 h (cardiac index improved considerably (p = 0.0002)), with a statistically significant difference between the groups (p = 0.005). LVSWI covariated with PCWP, improved over time in group H-GIK (p = 0.0008) and between the groups (p = 0.046). Oxygen supply-consumption ratio evidently improved in the GIK groups, while inotropic drug support was used in 5.5% pts. in group H-GIK vs. 13% in group L-GIK and 31% pts. in control (C) group. Glucose-insulin treatment has a potential cardioprotective effect in coronary surgery. The effect is independent of the glucose-insulin concentration and amount.

The fate of the radial artery conduit in coronary artery bypass grafting surgery.

Coronary artery bypass grafting (CABG) is the standard surgical procedure for the treatment of advanced coronary artery disease. CABG surgery has been demonstrated to improve symptoms and, in specific subgroups of patients, to prolong life. Despite its success, the long-term outcome of coronary bypass surgery is strongly influenced by the fate of the vascular conduits used. Impressive long-term disease-free patency rate of the left internal thoracic artery-left anterior descending coronary artery (LITA-LAD) graft, coupled with proven long-term survival benefits, has led to its becoming a 'golden standard' of CABG. Previous long-term studies have also shown unsatisfactory patency of saphenous vein grafts used for myocardial revascularization, compared with internal thoracic artery grafts. Thus, the use of arterial conduits has expanded beyond the internal thoracic arteries (ITAs) to include the right gastroepiploic artery, the inferior epigastric artery, and the radial artery. The assumption is that although the performance of one or two arterial ITA graft is superb, more arterial grafts should perform better in the long-term follow-up. Several studies concerning the use of the radial artery bypass grafts have documented excellent clinical results and satisfactory short-term as well as mid-term patency rates at restudy angiography, supporting its continued use as a bypass conduit. However, a note of caution concerning radial artery conduit patency rate have appeared in few recent reports. Thus, in this paper, we summarize the current evidence about the radial artery as a conduit in CABG surgery, with special emphasis on the clinical results.

Tandem pedicled internal thoracic artery conduit for sequential grafting of multiple left anterior descending coronary artery lesions.

A patient presented with severe triple-vessel coronary artery disease, including multiple lesions on the left anterior descending coronary artery (LAD), which supplied a well-contracting myocardium. In approaching our patient, we judged that a pedicled left internal thoracic artery (LITA) would not provide enough length for sequential grafting of the multisegment-diseased LAD. We also considered that a pedicled right internal thoracic artery (RITA) conduit would not be long enough to provide a free segment that would form a tandem graft with a LITA and then arrive at the marginal branch, unless it was detached at its origin. Consequently, we decided to form a composite graft that would connect a free, short segment (6-7 cm) of pedicled LITA to the in situ pedicled RITA, in an end-to-end fashion. This new composite conduit enabled us to perform sequential grafting (3 sequential anastomoses, 2 with the LITA segment) of the multisegment-diseased LAD, following the route anterior to the aorta. The in situ remnant of the LITA was grafted to the marginal branch. Although many large series have reported resourceful solutions, to the best of our knowledge, tandem arterial sequential grafting (an in situ pedicled RITA plus a free, short segment of a pedicled LITA) has not heretofore been reported in application to the multisegmented-diseased LAD artery. We strongly believe that this technique is an attractive variation on bilateral pedicled ITA left-sided revascularization in cases of multivessel coronary artery disease, including LADs with multiple lesions.

Copeptin Levels Do Not Correlate With Cross-Clamping Time in Patients Undergoing Carotid Endarterectomy Under General Anesthesia.

Copeptin is a sensitive and more stable surrogate marker for arginine vasopressin. In this study, we evaluated copeptin levels in carotid endarterectomy (CEA) patients, perioperatively, to determine whether copeptin levels can be related to carotid artery cross clamping (CC) time and to postoperative neurological outcomes. Copeptin, interleukin 6, C-reactive protein, cortisol, and brain natriuretic peptide were measured preoperatively (T1) and 3 hours postoperatively (T3) as well as intraoperatively (T2). We recruited 77 patients. Values of copeptin rose gradually over the observed times: T1 = 7.9 (6.4-9.6), T2 = 12.6 (9.3-16.8), and T3 = 72.3 (49.1-111.2) pmol/L. There was a significant difference for repeated measurement ( P = .000, P = .000, and P = .000). Duration of carotid artery CC during CEA does not affect postoperative copeptin level (CC ≤ 13 minutes: 106.8 ± 93.6 pmol/L, CC > 13 minutes: 96.7 ± 89.1 pmol/L; P = .634). Preoperative copeptin level was significantly higher in patients with ulcerated plaque morphology. Activation of the stress axis in patients undergoing CEA results in copeptin elevation. Duration of CC during CEA does not affect postoperative copeptin levels.

Hybrid Procedure for a Descending Thoracic and Subclavian Artery Aneurysm in a Patient with Previous Abdominal Aortic Surgery: Case Report.

INTRODUCTION: Hybrid procedures represent staged or simultaneous endovascular and open surgical techniques in the treatment of complex pathologies of the thoracic and abdominal aorta. We are presenting a patient with previous abdominal aortic surgery in whom hybrid vascular procedure for descending aorta and left subclavian artery aneurysm was performed. CASE OUTLINE: A 63-year-old female patient was admitted for computed tomography angiography. Descending aorta aneurysm (7.6 cm) as well as aneurysm of the left subclavian artery (LSA) was noted. Eight years ago she underwent abdominal aortic aneurysm resection and aortoiliac bypass. Standard TEVAR (thoracic endovascular aortic repair) procedure couldn't be done due to small dimensions of previous "Y" graft (12x6 mm), so first we did LSA transposition and after three days hybrid procedure. After "Y" graft exposure, anastomosis between the corps of "Y" graft and tubular graft 10 mm was created and through this conduit thoracic stent-graft was placed followed by complete "Y"graft replacement. After 6 months angiography showed regular postoperative findings. CONCLUSION: Combined surgical and endovascular procedures in thoracic aorta pathology treatment could be useful solutions with favorable outcome.

Heart surgery in patients on chronic dialysis.

INTRODUCTION: Patients on dialysis for end-stage renal failure are subjected to cardiac surgery with increasing frequency. End-stage renal failure is known to be an important risk factor for complications of cardiac operations performed with cardiopulmonary bypass. The aim of this study was to determine the impact of preoperative clinical status and operative variables on perioperative morbidity and mortality in hemodialysis-dependent patients subjected to a cardiac surgery. MATERIAL AND METHODS: The following operative variables were examined: urgency, type and duration of surgery and duration of extracorporeal circulation. The study is a retrospective analysis of consecutive patients with end-stage renal failure dependent on maintenance hemodialysis who underwent cardiac surgery during four years. RESULTS: The study included 46 patients. Operations performed included isolated coronary artery bypass grafting (CABG, n = 24), valve surgery alone (n = 6), and combined valve surgery or coronary artery bypass grafting and valve surgery (n = 16). The perioperative mortality rate was 13% with four fatal outcomes in patients who had undergone combined cardiac surgery. We found age > 70 years, preoperative New York Heart Association class IV, preoperative anemia, combined surgery and emergent surgery to be associated with a higher relative risk for perioperative death. CONCLUSION: Patients on dialysis have an increased morbidity and mortality following cardiac surgery; however, we believe that end-stage renal failure should not be regarded as a contraindication to cardiac surgery or cardiopulmonary bypass.

Mitral valve replacement with posterior transposition of the anterior mitral leaflet which covers and buttresses partially decalcified posterior mitral annular bed.

Mitral valve replacement (MVR) in the presence of the extensive calcification of the mitral annulus is a technical challenge. The heavily calcified annulus can cause great difficulty in the insertion of a prosthetic valve and periprosthetic leakage later on. Vigorous annular decalcification may cause circumflex coronary artery injury, atrioventricular rupture and thromboembolic events. We herein describe a surgical technique for MVR in such cases while focusing on partial decalcification of the posterior mitral annulus and its reinforcement and buttressing with the transferred anterior mitral leaflet (AML). At the same time, the transferred AML supports the posterior annular region and maintains ventricular-annular continuity, thus preserving the left ventricular function.

Different potassium channels are involved in relaxation of rat renal artery induced by P1075.

The ATP-sensitive K(+) channels opener (K(ATP)CO), P1075 [N-cyano-N'-(1,1-dimethylpropyl)-N″-3-pyridylguanidine], has been shown to cause relaxation of various isolated animal and human blood vessels by opening of vascular smooth muscle ATP-sensitive K(+) (K(ATP)) channels. In addition to the well-known effect on the opening of K(ATP) channels, it has been reported that vasorelaxation induced by some of the K(ATP)COs includes some other K(+) channel subtypes. Given that there is still no information on other types of K(+) channels possibly involved in the mechanism of relaxation induced by P1075, this study was designed to examine the effects of P1075 on the rat renal artery with endothelium and with denuded endothelium and to define the contribution of different K(+) channel subtypes in the P1075 action on this blood vessel. Our results show that P1075 induced a concentration-dependent relaxation of rat renal artery rings pre-contracted by phenylephrine. Glibenclamide, a selective K(ATP) channels inhibitor, partly antagonized the relaxation of rat renal artery induced by P1075. Tetraethylammonium (TEA), a non-selective inhibitor of Ca(2+)-activated K(+) channels, as well as iberiotoxin, a most selective blocker of large-conductance Ca(2+) -activated K(+) (BK(Ca)) channels, did not abolish the effect of P1075 on rat renal artery. In contrast, a non-selective blocker of voltage-gated K(+) (K(V)) channels, 4-aminopyridine (4-AP), as well as margatoxin, a potent inhibitor of K(V)1.3 channels, caused partial inhibition of the P1075-induced relaxation of rat renal artery. In addition, in this study, P1075 relaxed contractions induced by 20 mM K(+) , but had no effect on contractions induced by 80 mM K(+). Our results showed that P1075 induced strong endothelium-independent relaxation of rat renal artery. It seems that K(ATP), 4-AP- and margatoxin-sensitive K(+) channels located in vascular smooth muscle mediated the relaxation of rat renal artery induced by P1075.