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Gilles Lebuffe
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Helene Beloeil, M.D., Ph.D., Matthias Garot, M.D., Gilles Lebuffe, M.D., Ph.D., Alexandre Gerbaud, M.D., Julien Bila, M.D., Philippe Cuvillon, M.D., Ph.D., Elisabeth Dubout, M.D., Sebastien Oger, M.D., Julien Nadaud, M.D., Antoine Becret, M.D., Nicolas Coullier, M.D., Sylvain Lecoeur, M.D., Julie Fayon, M.D., Thomas Godet, M.D., Michel Mazerolles, M.D., Fouad Atallah, M.D., Stephanie Sigaut, M.D., Pierre-Marie Choinier, M.D., Karim Asehnoune, M.D., Ph.D., Antoine Roquilly, M.D., Ph.D., Gerald Chanques, M.D., Ph.D., Maxime Esvan, Ms.C., Emmanuel Futier, M.D., Ph.D., Bruno Laviolle, M.D., Ph.D., POFA Study Group , SFAR Research Network
Journal:
Anesthesiology
Anesthesiology. April 2021; 134(4):541–551
Published: April 2021
Abstract
Background It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil. Methods Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting. Results The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay. Conclusions This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia. Editor’s Perspective What We Already Know about This Topic It is hoped but not proven that opioid-free anesthesia provides adequate postoperative analgesia and reduced opioid-related side effects Dexmedetomidine is sometimes used to replace opioids in balanced opioid-free anesthetics What This Article Tells Us That Is New In a randomized, blinded, multicenter trial, study patients undergoing noncardiac surgery received a standard anesthetic featuring lidocaine and ketamine, plus either remifentanil or an alternative anesthetic where dexmedetomidine was substituted for remifentanil The primary outcome, composed of postoperative hypoxemia, ileus, and cognitive dysfunction, was more common among patients receiving opioid-free anesthesia Importantly, opioid-free anesthesia with dexmedetomidine was associated with severe bradycardia, and the study was terminated early for that reason
Articles
Tau Phosphorylation and Sevoflurane Anesthesia: An Association to Postoperative Cognitive Impairment
Hélène Le Freche, M.D., M.Sc., Jonathan Brouillette, Ph.D., Francisco-José Fernandez-Gomez, Ph.D., Pauline Patin, M.Sc., Raphaëlle Caillierez, M.Sc., Nadège Zommer, B.Sc., Nicolas Sergeant, Ph.D., Valérie Buée-Scherrer, Ph.D., Gilles Lebuffe, M.D., Ph.D., David Blum, Ph.D., Luc Buée, Ph.D.
Journal:
Anesthesiology
Anesthesiology. April 2012; 116(4):779–787
Published: April 2012
Abstract
Background There is a growing interest in the involvement of anesthetic agents in the etiology of postoperative cognitive dysfunction. Recent animal studies suggest that acute anesthesia induces transient hyperphosphorylation of tau, an effect essentially ascribed to hypothermia. The main aim of the present study was to investigate effects, in normothermic conditions, of acute or repeated exposure to sevoflurane, a halogenated anesthetic agent, on hippocampal tau phosphorylation and spatial memory in adult mice. Methods 5 to 6-month-old C57Bl6/J mice were submitted to acute (1 h) or repeated (five exposures of 1h every month) anesthesia using 1.5 or 2.5% sevoflurane, in normothermic conditions. In the acute protocol, animals were sacrificed 1 and 24 h after exposure. In the chronic protocol, spatial memory was evaluated using the Morris water maze following the fourth exposure, and tau phosphorylation evaluated 1 month following the last exposure using bi- and mono-dimensional electrophoresis. Results Acute sevoflurane anesthesia in normothermic conditions led to a significant dose-dependent and reversible hippocampal tau phosphorylation, 1 h following the end of exposure (P < 0.001). Conversely, repeated anesthesia led to persistent tau hyperphosphorylation and significant memory impairments, as seen in the retention phase of the Morris water maze in sevoflurane-anesthesized animals. These pathologic features may be related to the activation of both Akt and Erk pathways. Conclusions The present study demonstrates, in mice, that sevoflurane exposure is associated with increased tau phosphorylation through specific kinases activation and spatial memory deficits. These data support a correlation between exposures to this anesthetic agent and cognitive decline.
Articles
Benoit Tavernier, MD, Olivier Makhotine, MD, Gilles Lebuffe, MD, Jacques Dupont, MD, Philippe Scherpereel, MD
Journal:
Anesthesiology
Anesthesiology. December 1998; 89(6):1313–1321
Published: December 1998
Abstract
Background Monitoring left ventricular preload is critical to achieve adequate fluid resuscitation in patients with hypotension and sepsis. This prospective study tested the correlation of the pulmonary artery occlusion pressure, the left ventricular end-diastolic area index measured by transesophageal echocardiography, the arterial systolic pressure variation (the difference between maximal and minimal systolic blood pressure values during one mechanical breath), and its delta down (dDown) component (= apneic - minimum systolic blood pressure) with the response of cardiac output to volume expansion during sepsis. Methods Preload parameters were measured at baseline and during graded volume expansion (increments of 500 ml) in 15 patients with sepsis-induced hypotension who required mechanical ventilation. Each volume-loading step (VLS) was classified as a responder (increase in stroke volume index > or = 15%) or a nonresponder. Successive VLSs were performed until a nonresponder VLS was obtained. Results Thirty-five VLSs (21 responders) were performed. Fluid loading caused an overall significant increase in pulmonary artery occlusion pressure and end-diastolic area index, and a significant decrease in systolic pressure variation and delta down (P < 0.01). There was a significant difference between responder and nonresponder VLSs in end-diastolic area index, systolic pressure variation, and dDown, but not in pulmonary artery occlusion pressure. Receiver-operator curve analysis showed that dDown was a more accurate indicator of the response of stroke volume index to volume loading than end-diastolic area index and pulmonary artery occlusion pressure. A dDown component of more than 5 mmHg indicated that the stroke volume index would increase in response to a subsequent fluid challenge (positive and negative predictive values: 95% and 93%, respectively). Conclusion The dDown component of the systolic pressure variation is a sensitive indicator of the response of cardiac output to volume infusion in patient with sepsis-induced hypotension who require mechanical ventilation.
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