Etude de l effet de la carbétocine sur l intervalle QT corrigé au cours des césariennes

Dans le cadre de la prévention des hémorragies du post-partum après accouchement par césarienne, il est préconisé l administration de drogues utérotoniques : l ocytocine de synthèse (Syntocinon®) ou la carbétocine (Pabal®).Le Syntocinon® possède des effets hémodynamiques potentiellement graves et induit un allongement significatif de l intervalle QT. La carbétocine est un analogue synthétique de l ocytocine humaine de longue demi-vie, présentant les mêmes effets secondaires que le Syntocinon et dont l effet sur l intervalle QT n a jamais été publié. Les patientes devant bénéficier de césariennes sous anesthésie locorégionale ont été inclues dans cette étude prospective où des électrocardiogrammes étaient enregistrés sur une période de 15 minutes suivant l injection de carbétocine. L intervalle QT était mesuré manuellement puis corrigé par la formule de Fridericia. L analyse statistique a consisté en une analyse de variance pour mesures répétées.Vingt patientes ont été inclues. L intervalle QTcf augmentait de façon significative à partir de la 5e minute après administration de carbétocine jusqu à la fin des enregistrements. Comparé à la valeur post anesthésie, le QTcf était maximum à la 7e minute après administration de carbétocine (+18 +- 4 msec, p<0.01). Aucun trouble du rythme n a été constaté.La carbétocine administrée au cours des césariennes sous anesthésie locorégionale induit un allongement de l intervalle QTc.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Postoperative serum levels of Endocan are associated with the duration of norepinephrine support after coronary artery bypass surgery

International audienceBACKGROUND : Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response and an endothelial dysfunction, whose qualitative assessment appears to be a major issue. Endocan (ESM-1, endothelial cell specific molecule-1) is a protein preferentially expressed by the endothelium and previously associated with prognosis of septic shock or acute respiratory distress syndrome. In this pilot study, we investigated the kinetic of Endocan in planned coronary artery bypass grafting (CABG) surgery with CPB.PATIENTS AND METHODS : We conducted an observational, prospective, mono centre study. All adult patients with left systolic ejection fraction>50%, undergoing planned on-pump CABG, were screened for inclusion. A written informed consent was obtained. Measurements and main results Serum Endocan concentrations were respectively 2.4 [2.1-3.0] ng. mL-1, 10.4 [7.4-13.9] ng.mL-1, 5.7 [4.4-8.2] ng.mL-1, and 5.4 [4.1-7.5] ng.mL-1 at day 0, day 1, day 3 and day 5. Endocan concentrations increased at day 1, day 3, and day 5 in comparison with preoperative concentration (P<0.001). In the multivariate analysis, age (P=0.002), history of acute coronary syndrome (P=0.024) and the catecholamine-free days at day 28 (P=0.007) were associated to the increase of perioperative Endocan concentrations.CONCLUSION : Serum Endocan concentration increases after CABG surgery with CPB until day 1. The norepinephrine support increases the risk of Endocan release, suggesting a relationship between the kinetic of Endocan and the vasoplegic syndrome. At day 3, Endocan concentration decreases slowly but is not normalised at day 5. Further studies should investigate the prognostic value of the magnitude of postoperative Endocan concentration after cardiac surgery

PHARMECMO: Therapeutic drug monitoring and adequacy of current dosing regimens of antibiotics in patients on Extracorporeal Life Support

International audienceINTRODUCTION:Optimisation of antibiotic therapy for extracorporeal membrane oxygenation (ECMO) patients remains a pharmacological challenge. The objective of this study was to observe the plasma concentrations of commonly used antibiotics in intensive care for patients treated with extracorporeal membrane oxygenation.PATIENTS AND METHODS:The PHARMECMO study was a pilot, prospective study, conducted in a cardiac surgery intensive care unit. Every adult patient under ECMO support, with known or suspected sepsis and receiving antibiotic therapy, was eligible for inclusion. Plasma concentrations of antibiotics were determined by a combination of liquid chromatography and mass spectrometry.RESULTS:Forty-four eligible patients were enrolled for 68 inclusions on a twelve-month period. For the association piperacillin-tazobactam (n=19), 68.7% of CT50 and 93.7% of Cmin reached the pharmacokinetic goals defined (64 mg.L-1 for CT50 and 16 mg.L-1 for Cmin). For cefotaxime (n=12), the pharmacokinetic goals (4 mg.L-1 for CT50 and 1 mg.L-1 for Cmin) were achieved in 100% of the cases for CT50 and in 81.8% of the cases for Cmin. Regarding imipenem (n=10), the pharmacokinetic goals were 16 mg.L-1 for CT50 and 4 mg.L-1 for Cmin. Only one CT50 was above 16 mg.L-1. For Cmin, 60% of the doses did not reach the target concentration. In our 10 patients, only one patient was considered as reaching the pharmacokinetic goals. Finally, for amikacin (n=6), four Cmax (66.7%) were infra-therapeutics for a target between 60 and 80 mg.L-1.CONCLUSION:These preliminary results suggest that therapeutic drug monitoring could optimise the achievement of pharmacokinetic objectives associated with an effective antibiotic therapy. For most patients, the recommended doses of imipenem and amikacin did not achieve the pK targets

Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery: A Prospective Cohort Study

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The effect of local anesthetic continuous wound infusion for the prevention of postoperative pneumonia after on-pump cardiac surgery with sternotomy: the STERNOCAT randomized clinical trial

International audiencePURPOSE:Postoperative pain after cardiac surgery, exacerbated by cough and sternal mobilization, limits clearance of bronchopulmonary secretions and may predispose to postoperative pneumonia. In this study, we tested the ability of local anesthetic continuous wound infusion to prevent pneumonia after cardiac surgery with sternotomy and cardiopulmonary bypass (CPB) owing to better analgesia and bronchopulmonary drainage.METHODS:In this randomized, double-blind, placebo-controlled trial conducted in five academic centers, patients undergoing cardiac surgery with sternotomy and CPB were enrolled from February 2012 until November 2014, and were followed over 30 days. Patients were assigned to a 48-h infusion (10 ml h-1) of L-bupivacaine (12.5 mg h-1) or placebo (saline) via a pre-sternal multiperforated catheter. Anesthesia and analgesia protocols were standardized. The primary end point was the incidence of pneumonia during the study period, i.e., until hospital discharge or 30 days. We hypothesized a 30% reduction in the incidence of pneumonia.RESULTS:Among 1493 randomized patients, 1439 completed the trial. Pneumonia occurred in 36/746 patients (4.9%) in the L-bupivacaine group and in 42/739 patients (5.7%) in the placebo group (absolute risk difference taking into account center and baseline risk of postoperative pneumonia, - 1.3% [95% CI - 3.4; 0.8] P = 0.22). In the predefined subgroup of patients at high risk, L-bupivacaine decreased the incidence of pneumonia (absolute risk difference, - 5.6% [95% CI - 10.0; - 1.1], P = 0.01).CONCLUSIONS:After cardiac surgery with sternotomy, continuous wound infusion of L-bupivacaine failed to decrease the incidence of pneumonia. These findings do not support the use of local anesthetic continuous wound infusion in this indication. Further study should investigate its effect in high-risk patients

In Reply

We appreciate the interest of Lagier et al. in our article.1 The authors highlighted in their letter the work of Montaigne et al.,2 who have recently published on the circadian rhythm in relation to ischemia reperfusion injury in a single-center retrospective propensity-matched cohort study addressing this subject on 596 (matched-pairs) patients undergoing aor-tic valve replacement with or without coronary artery bypass grafting, together with a single-center randomized study in 88 patients undergoing isolated aortic valve replacement, in which the perioperative myocardial injury has been assessed with the geometric mean of perioperative cardiac troponin T release

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

Abstract 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