Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

BACKGROUND: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. METHODS: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. RESULTS: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. CONCLUSIONS: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial.

Importance: Low cardiac output syndrome after cardiac surgery is associated with high morbidity and mortality in patients with impaired left ventricular function. Objective: To assess the ability of preoperative levosimendan to prevent postoperative low cardiac output syndrome. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted in 13 French cardiac surgical centers. Patients with a left ventricular ejection fraction less than or equal to 40% and scheduled for isolated or combined coronary artery bypass grafting with cardiopulmonary bypass were enrolled from June 2013 until May 2015 and followed during 6 months (last follow-up, November 30, 2015). Interventions: Patients were assigned to a 24-hour infusion of levosimendan 0.1 µg/kg/min (n = 167) or placebo (n = 168) initiated after anesthetic induction. Main Outcomes and Measures: Composite end point reflecting low cardiac output syndrome with need for a catecholamine infusion 48 hours after study drug initiation, need for a left ventricular mechanical assist device or failure to wean from it at 96 hours after study drug initiation when the device was inserted preoperatively, or need for renal replacement therapy at any time postoperatively. It was hypothesized that levosimendan would reduce the incidence of this composite end point by 15% in comparison with placebo. Results: Among 336 randomized patients (mean age, 68 years; 16% women), 333 completed the trial. The primary end point occurred in 87 patients (52%) in the levosimendan group and 101 patients (61%) in the placebo group (absolute risk difference taking into account center effect, -7% [95% CI, -17% to 3%]; P = .15). Predefined subgroup analyses found no interaction with ejection fraction less than 30%, type of surgery, and preoperative use of ß-blockers, intra-aortic balloon pump, or catecholamines. The prevalence of hypotension (57% vs 48%), atrial fibrillation (50% vs 40%), and other adverse events did not significantly differ between levosimendan and placebo. Conclusions and Relevance: Among patients with low ejection fraction who were undergoing coronary artery bypass grafting with cardiopulmonary bypass, levosimendan compared with placebo did not result in a significant difference in the composite end point of prolonged catecholamine infusion, use of left ventricular mechanical assist device, or renal replacement therapy. These findings do not support the use of levosimendan for this indication. Trial Registration: EudraCT Number: 2012-000232-25; clinicaltrials.gov Identifier: NCT02184819.

MNX (Medium Duration Nutrition and Resistance-Vibration Exercise) Bed-Rest: Effect of Resistance Vibration Exercise Alone or Combined With Whey Protein Supplementation on Cardiovascular System in 21-Day Head-Down Bed Rest.

Current inflight countermeasures do not completely prevent bone and cardiovascular changes induced by microgravity. High load Resistance Exercise combined with whole body Vibration (RVE) demonstrated benefits on bone and cardiovascular system during previous Head-Down Bed Rest (HDBR) studies. We examined the effectiveness of RVE alone or combined with a nutritional supplementation of Whey protein (NeX) on cardiovascular deconditioning. Eight male subjects (age 34 ± 8 years) in a crossover design completed three 21-day HDBR campaigns (Control-CON, RVE, and NeX). Pre and post HDBR Orthostatic Tolerance (OT) was evaluated by a 15-min head-up tilt test followed by increasing levels of Lower Body Negative Pressure (LBNP). Heart rate (HR), blood pressure (BP), and Sympathetic Index (ΣI) through spectral analysis were measured during OT test. Plasma Volume (PV), and Maximal Oxygen Uptake (VO2max) were measured before and after each campaign. Left ventricular mass, left ventricular end diastolic (LVEDV), end systolic (LVESV), stroke (SV) volumes, and circumferential deformation at rest and during an orthostatic stress simulated by a 30 mmHg LBNP were measured by cardiac MRI. RVE failed to prevent any change in these variables and NeX did not have any additional effect over exercise alone. In the 3 groups, (1) OT time dropped similarly (bed rest p < 0.001), (2) HR and ΣI were increased at rest at the end of HDBR and HR increased markedly during LBNP-tilt test, with inability to increase further the ΣI, (3) PV dropped (bed rest p < 0.001), along with LVEDV, LVESV and SV (p = 0.08, p < 0.001, and p = 0.045, respectively), (4) Left ventricle mass did not change significantly, (5) Deformation of the heart assessed by global circumferential strain was preserved and early diastolic circumferential strain rate was increased during orthostatic stress at the end of HDBR, illustrating preserved systolic and diastolic function respectively, without any difference between groups. Despite the drop in PV and LV volumes, RVE and NeX tended to alleviate the decrease in VO2max. In conclusion, RVE and NeX failed to prevent the cardiovascular deconditioning induced by a 21 day-HDBR.

WISE-2005: effect of aerobic and resistive exercises on orthostatic tolerance during 60 days bed rest in women.

Cardiovascular deconditioning after long duration spaceflight is especially challenging in women who have a lower orthostatic tolerance (OT) compared with men. We hypothesized that an exercise prescription, combining supine aerobic treadmill exercise in a lower body negative pressure (LBNP) chamber followed by 10 min of resting LBNP, three to four times a week, and flywheel resistive training every third day would maintain orthostatic tolerance (OT) in women during a 60-day head-down-tilt bed rest (HDBR). Sixteen women were assigned to two groups (exercise, control). Pre and post HDBR OT was assessed with a tilt/LBNP test until presyncope. OT time (mean +/- SE) decreased from 17.5 +/- 1.0 min to 9.1 +/- 1.5 min (-50 +/- 6%) in control group (P < 0.001) and from 19.3 +/- 1.3 min to 13.0 +/- 1.9 min (-35 +/- 7%) in exercise group (P < 0.001), with no significant difference in OT time between the two groups after HDBR (P = 0.13). Nevertheless, compared with controls post HDBR, exercisers had a lower heart rate during supine rest (mean +/- SE, 71 +/- 3 vs. 85 +/- 4, P < 0.01), a slower increase in heart rate and a slower decrease in stroke volume over the course of tilt/LBNP test (P < 0.05). Blood volume (mean +/- SE) decreased in controls (-9 +/- 2%, P < 0.01) but was maintained in exercisers (-4 +/- 3%, P = 0.17).Our results suggest that the combined exercise countermeasure did not significantly improve OT but protected blood volume and cardiovascular response to sub tolerance levels of orthostatic stress.

Effects of Resistance Exercise and Nutritional Supplementation on Dynamic Cerebral Autoregulation in Head-Down Bed Rest.

Head-down bed rest (HDBR) is commonly considered as ground-based analog to spaceflight and simulates the headward fluid shift and cardiovascular deconditioning associated with spaceflight. We investigated in healthy volunteers whether HDBR, with or without countermeasures, affect cerebral autoregulation (CA). Twelve men (at selection: 34 ± 7 years; 176 ± 7 cm; 70 ± 7 kg) underwent three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel, and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Cerebral blood flow velocity was assessed using transcranial Doppler ultrasonography. CA was evaluated by transfer function analysis and by the autoregulatory index (Mxa) in order to determine the relationship between mean cerebral blood flow velocity and mean arterial blood pressure. In RVE condition, coherence was increased after HDBR. In CON condition, Mxa index was significantly reduced after HDBR. In contrast, in RVE and NeX conditions, Mxa were increased after HBDR. Our results indicate that HDBR without countermeasures may improve dynamic CA, but this adaptation may be dampened with RVE. Furthermore, nutritional supplementation did not enhance or worsen the negative effects of RVE. These findings should be carefully considered and could not be applied in spaceflight. Indeed, the subjects spent their time in supine position during bed rest, unlike the astronauts who perform normal daily activities.

Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212].

INTRODUCTION: Microcirculatory blood flow, and notably gut perfusion, is important in the development of multiple organ failure in septic shock. We compared the effects of dopexamine and norepinephrine (noradrenaline) with those of epinephrine (adrenaline) on gastric mucosal blood flow (GMBF) in patients with septic shock. The effects of these drugs on oxidative stress were also assessed. METHODS: This was a prospective randomized study performed in a surgical intensive care unit among adults fulfilling usual criteria for septic shock. Systemic and pulmonary hemodynamics, GMBF (laser-Doppler) and malondialdehyde were assessed just before catecholamine infusion (T0), as soon as mean arterial pressure (MAP) reached 70 to 80 mmHg (T1), and 2 hours (T2) and 6 hours (T3) after T1. Drugs were titrated from 0.2 microg kg(-1) min(-1) with 0.2 microg kg(-1) min(-1) increments every 3 minutes for epinephrine and norepinephrine, and from 0.5 microg kg(-1) min(-1) with 0.5 microg kg(-1) min(-1) increments every 3 minutes for dopexamine. RESULTS: Twenty-two patients were included (10 receiving epinephrine, 12 receiving dopexamine-norepinephrine). There was no significant difference between groups on MAP at T0, T1, T2, and T3. Heart rate and cardiac output increased significantly more with epinephrine than with dopexamine-norepinephrine, whereas. GMBF increased significantly more with dopexamine-norepinephrine than with epinephrine between T1 and T3 (median values 106, 137, 133, and 165 versus 76, 91, 90, and 125 units of relative flux at T0, T1, T2 and T3, respectively). Malondialdehyde similarly increased in both groups between T1 and T3. CONCLUSION: In septic shock, at doses that induced the same effect on MAP, dopexamine-norepinephrine enhanced GMBF more than epinephrine did. No difference was observed on oxidative stress.

Safety of recombinant factor VIIa in patients under extracorporeal membrane oxygenation.

OBJECTIVES: To address the safety (rate of thromboembolic events and circuit complications) and efficacy (rate of bleeding control) of recombinant activated coagulation factor VII (rFVIIa) to treat severe bleeding refractory to all surgical and medical treatments in patients under veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support. METHODS: In a tertiary referral University Cardiothoracic Surgery Centre including three intensive care units, 30 patients received the rFVIIa during ongoing VA or VV ECMO support (8.6% of ECMO activity from 2005 to 2014; N = 347). Early and late clinical results were analysed (retrospective analysis of prospectively collected data). In a substudy, a case-matching procedure was performed among ECMO patients who received (Group A) or did not receive (Group B) rFVIIa treatment. RESULTS: The mediastinum was the most common site of refractory bleeding (after heart transplantation or other cardiac surgery; 90%); 90% (n = 27) of patients were on VA ECMO and the remainder on VV ECMO. The survival rate at ECMO explantation and at the 30th post-implantation day was 67 and 50%, respectively. The final efficacy rate of rFVIIa in stopping bleeding was 93.3%. The rate of thromboembolic events was 3.3% (1 case) and the rate of circuit change was 16.7% (without instances of overt circuit clotting). After case-matching, Group A comprised 23 patients and Group B included 43 patients. No statistically significant differences were observed among groups in terms of thromboembolic events (P = 0.99), circuit change, ventilation time (P = 0.71), infectious complications (P = 06) and survival at both ECMO explantation and the 30th post-implantation day. Late survival was comparable (Kaplan-Meier analysis; P = 0.42). CONCLUSIONS: In case of life-threatening bleeding refractory to all conventional therapies, rFVIIa presents an acceptable safety profile in patients under ECMO support. No circuit dysfunctions and limited rates of thromboembolism are observed.

Electrocardiographic and hemodynamic effects of intravenous infusion of bupivacaine, ropivacaine, levobupivacaine, and lidocaine in anesthetized ewes.

BACKGROUND AND OBJECTIVES: Neural blockade techniques are associated with a risk of acute cardiac toxicity after accidental intravenous (IV) injection of local anesthetics. The aim of this study was to compare electrocardiographic (ECG) and hemodynamic (HEM) effects induced by IV infusion of local anesthetics in an anesthetized ewe model. METHODS: Thirty-two anesthetized ewes received IV bupivacaine (BUPI), ropivacaine (ROPI), or levobupivacaine (S-BUPI) at an equimolar dose, or lidocaine (LIDO) at a 3-fold higher rate (n = 8 in each group). RR, PR, QRS, and QT intervals (QTc), changes (Delta) in systolic and diastolic arterial pressure (SAP and DAP), and in myocardial contractility (dP/dt), were assessed every 30 seconds for 7 minutes. From main ECG variables (RR, PR, QRS, QT), we proposed to use multiple correspondence analysis and hierarchical ascending classification to explore the structure of statistical dependencies among those measurements, and to determine the different patterns of ECG and HEM changes induced by infusion of BUPI, ROPI, S-BUPI, and LIDO. RESULTS: Graphic representation of multiple correspondence analysis associated BUPI with the most pronounced modifications in ECG and HEM variables, followed by in decreasing order ROPI, S-BUPI, and LIDO. Comparisons of clusters identified by hierarchical ascending classification confirmed this classification for ECG variables. Ventricular tachycardia occurred only in the BUPI group. CONCLUSIONS: In our anesthetized ewe model, high dose IV infusion of BUPI induced the most marked changes in RR, PR, QRS, QT, QTc intervals, DeltaSAP, and DeltadP/dt. ROPI altered ECG variables less than BUPI but more than S-BUPI. LIDO was associated with the smallest changes.