Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

BACKGROUND: Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. METHODS: We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- standard deviation) between the groups by a variance analysis and post hoc test. RESULTS: Desflurane 6% (84 +/- 6% of baseline) enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 +/- 8% of baseline, P < 0.0001). N-mercaptopropionylglycine (54 +/- 3% of baseline), 8-(p-Sulfophenyl)theophylline (62 +/- 9% of baseline), HOE140 (58 +/- 6% of baseline) abolished desflurane-induced postconditioning. Adenosine (80 +/- 9% of baseline) and bradykinin (83 +/- 4% of baseline) induced postconditioning (P < 0.0001 vs control), N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 +/- 8 and 58 +/- 5% of baseline, respectively). CONCLUSIONS: In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin administered at the beginning of reoxygenation, was mediated, at least in part, through ROS production

Development of a practical prediction score for chronic kidney disease after cardiac surgery

Background: Chronic kidney disease (CKD) is a frequent and serious complication of cardiac surgery. This study was designed to establish a scoring system, calculated in the immediate postoperative period, to assess the risk of CKD at 1 yr in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: We conducted a cohort study including patients with preoperative estimated glomerular filtration rate above 60 ml min-1 (1.73 m)-2 who underwent cardiac surgery with cardiopulmonary bypass. We identified risk factors for de novo CKD at 1 yr using logistic regression. We derived a risk score for CKD, and externally validated this score in a second cohort. Results: The incidence of CKD was 18% and 23% in the derivation and validation cohorts, respectively. We developed a scoring system that included (i) the occurrence of postoperative acute kidney injury according to the Kidney Disease: Improving Global Outcomes criteria, (ii) age older than 65 yr, (iii) preoperative glomerular filtration rate <80 ml min-1 (1.73 m)-2, (iv) aortic cross-clamping time longer than 50 min, and (v) the type of surgery (aortic or cardiac transplantation). This score predicted CKD with good accuracy (area under the receiver operating characteristic curve: 0.81; 95% confidence interval: 0.77-0.86 in the derivation cohort), and with fair accuracy in the validation cohort (area under the receiver operating characteristic curve: 0.78; 95% confidence interval: 0.72-0.83). Conclusions: We provide an easy-to-calculate scoring system to identify patients at high risk of developing CKD after cardiac surgery with cardiopulmonary bypass. This system might help clinicians to target more accurately patients requiring monitoring of renal function after cardiac surgery, and to design appropriate interventional trials aimed at preventing CKD or mitigating its consequences

Influence of bacterial resistance on mortality in intensive care units: a registry study from 2000 to 2013 (IICU Study)

International audienceBackground: Bacterial resistance to antibiotics is a daily concern in intensive care units. However, few data are available concerning the clinical consequences of in-vitro-defined resistance. Aim: To compare the mortality of patients with nosocomial infections according to bacterial resistance profiles. Methods: The prospective surveillance registry in 29 French intensive care units (ICUs) participating during the years 2000-2013 was retrospectively analysed. All patients presenting with a nosocomial infection in ICU were included. Findings: The registry contained 88,000 eligible patients, including 10,001 patients with a nosocomial infection. Among them, 3092 (36.7%) were related to resistant microorganisms. Gram-negative bacilli exhibited the highest rate of resistance compared to Gram-positive cocci (52.8% vs 48.1%; P < 0.001). In-hospital mortality was higher in cases of patients with antibiotic-resistant infectious agents (51.9% vs 45.5%; P < 0.001), and critical care length of stay was longer (33 +/- 26 vs 29 +/- 22 days; P < 0.001). These results remained significant after SAPS II matching (P < 0.001) and in the Gram-negative bacilli and Gram-positive cocci subgroups. No difference in mortality was found with respect to origin prior to admission. Conclusion: Patients with bacterial resistance had higher ICU mortality and increased length of stay, regardless of the bacterial species or origin of the patient. (C) 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved

Individualized Fluid Management Using the Pleth Variability Index: A Randomized Clinical Trial

BACKGROUND: The present trial was designed to assess whether individualized strategies of fluid administration using a noninvasive plethysmographic variability index could reduce the postoperative hospital length of stay and morbidity after intermediate-risk surgery. METHODS: This was a multicenter, randomized, nonblinded parallel-group clinical trial conducted in five hospitals. Adult patients in sinus rhythm having elective orthopedic surgery (knee or hip arthroplasty) under general anesthesia were enrolled. Individualized hemodynamic management aimed to achieve a plethysmographic variability index under 13%, and the standard management strategy aimed to maintain a mean arterial pressure above 65 mmHg during general anesthesia. The primary outcome was the postoperative hospital length of stay decided by surgeons blinded to the group allocation of the patient. RESULTS: In total, 447 patients were randomized, and 438 were included in the analysis. The mean hospital length of stay ± SD was 6 ± 3 days for the plethysmographic variability index group and 6 ± 3 days for the control group (adjusted difference, 0.0 days; 95% CI, -0.6 to 0.5; P = 0.860); the theoretical postoperative hospital length of stay was 4 ± 2 days for the plethysmographic variability index group and 4 ± 1 days for the control group (P = 0.238). In the plethysmographic variability index and control groups, serious postoperative cardiac complications occurred in 3 of 217 (1%) and 2 of 224 (1%) patients (P = 0.681), acute postoperative renal failure occurred in 9 (4%) and 8 (4%) patients (P = 0.808), the troponin Ic concentration was more than 0.06 μg/l within 5 days postoperatively for 6 (3%) and 5 (2%) patients (P = 0.768), and the postoperative arterial lactate measurements were 1.44 ± 1.01 and 1.43 ± 0.95 mmol/l (P = 0.974), respectively. CONCLUSIONS: Among intermediate-risk patients having orthopedic surgery with general anesthesia, fluid administration guided by the plethysmographic variability index did not shorten the duration of hospitalization or reduce complications

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

Remifentanil does not impair left ventricular systolic and diastolic function in young healthy patients

Experimental studies and investigations in patients with cardiac diseases suggest that opioids at clinical concentrations have no important direct effect on myocardial relaxation and contractility. In vivo data on the effect of remifentanil on myocardial function in humans are scarce. This study aimed to investigate the effects of remifentanil on left ventricular (LV) function in young healthy humans by transthoracic echocardiography (TTE). We hypothesized that remifentanil does not impair systolic, diastolic LV function, or both