Newly Published
Perioperative Medicine  |   September 2017
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
Author Notes
  • From the Sector Cardiothoracic Anesthesiology, Thorax Centre, Rotterdam, The Netherlands (J. Hofland, I.d.L.); Service d’Anesthésie-Réanimation II, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (A.O.); Louis Pradel University Hospital, Lyon, France and Department of Anesthesiology and Intensive Care Medicine and Inserm U1060, Faculty of Medicine, Claude Bernard Lyon 1 University, Lyon, France (J.-L.F.); Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany (M.G., B.B.); Air Liquide Santé International, Paris-Saclay Research Center, Jouy-en-Josas, France (J. Hazebroucq); Department of Anesthesia, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France (C.E.); Department of Anesthesia and Intensive Care, Hôpital Cardiovasculaire et Pneumologique Louis Pradel, Bron, France (P.J.); Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany (M.H.); Service d’Anesthésie Réanimation Chirurgicale, Nouvel Hôpital Civil, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France (A.S.); Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany (M.C.); Department of Anesthesia and Intensive Care, Institut de Cardiologie - Chirurgie Cardiaque, Hôpital Pitié Salpetrière, Paris, France (J.A.); Service d’Anesthésie et Réanimation Chirurgicale, Hôpital G&R Laënnec, Centre Hospitalier Universitaire de Nantes, Nantes, France (B.R.); Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany (P.M.); Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (B.P.); Service d’Anesthésie et Réanimation Chirurgicale, Centre Hospitalier Universitaire de Caen, Caen, France (J.-L.H.); Department of Anesthesia and Intensive Care, Policlinico “Umberto I,” “La Sapienza,” University of Rome, Rome, Italy (L.T.); Department of Anesthesiology and Intensive Care, Klinikum Links der Weser gGmbH, Bremen, Germany (P.T.); Chirurgie Cardiovasculaire - Service de Réanimation, Centre Hospitalier Universitaire de Toulouse, Hospitalier de Rangueil, Toulouse, France (H.B.); and Clinic for Anesthesia and Critical Care Medicine, University Hospital Rostock, Rostock, Germany (J.P.R).
  • Service d’Anesthésie et Réanimation Chirurgicale, Centre Hospitalier Universitaire de Caen, Caen, France
  • Departments of Anesthesiology and Cardiothoracic Surgery, Thorax Centre, Rotterdam, The Netherlands
  • Departments of Anesthesiology and Cardiothoracic Surgery, Thorax Centre, Rotterdam, The Netherlands
  • Departments of Anesthesiology and Cardiothoracic Surgery, Thorax Centre, Rotterdam, The Netherlands
  • Service d’Anesthésie-Réanimation II, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
  • Universitäts Klinikum Schleswig-Holstein, Klinik für Anästhesiologie und Operative Intensivmedizin, Campus Kiel, Kiel, Germany
  • Universitäts Klinikum Schleswig-Holstein, Klinik für Anästhesiologie und Operative Intensivmedizin, Campus Kiel, Kiel, Germany
  • Universitäts Klinikum Schleswig-Holstein, Klinik für Anästhesiologie und Operative Intensivmedizin, Campus Kiel, Kiel, Germany
  • Universitäts Klinikum Schleswig-Holstein, Klinik für Anästhesiologie und Operative Intensivmedizin, Campus Kiel, Kiel, Germany
  • Universitäts Klinikum Schleswig-Holstein, Klinik für Anästhesiologie und Operative Intensivmedizin, Campus Kiel, Kiel, Germany
  • Air Liquide Santé International, Jouy-en-Josas, France
  • Department of Anesthesia, Hôpital Pontchaillou, Rennes, France
  • Department of Anesthesia, Hôpital Pontchaillou, Rennes, France
  • Department of Anesthesia, Hôpital Pontchaillou, Rennes, France
  • Department of Anesthesia, Hôpital Pontchaillou, Rennes, France
  • Department of Anesthesia and Intensive Care, Hôpital Cardiovasculaire et Pneumologique Louis Pradel, Bron, France
  • Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
  • Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
  • Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
  • Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
  • Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
  • Department of Cardiac and Thoracic Vascular Surgery, University of Lübeck, Lübeck, Germany
  • Service d’Anesthésie Réanimation Chirurgicale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
  • Service d’Anesthésie Réanimation Chirurgicale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
  • Service d’Anesthésie Réanimation Chirurgicale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
  • Service d’Anesthésie Réanimation Chirurgicale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
  • Service d’Anesthésie Réanimation Chirurgicale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
  • Service d’Anesthésie Réanimation Chirurgicale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
  • Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany
  • Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany
  • Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany
  • Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany
  • Department of Anesthesia and Intensive Care, Institut de Cardiologie - Chirurgie Cardiaque, Hôpital Pitié Salpetrière, Paris, France
  • Department of Anesthesia and Intensive Care, Institut de Cardiologie - Chirurgie Cardiaque, Hôpital Pitié Salpetrière, Paris, France
  • Department of Anesthesia and Intensive Care, Institut de Cardiologie - Chirurgie Cardiaque, Hôpital Pitié Salpetrière, Paris, France
  • Department of Anesthesia and Intensive Care, Institut de Cardiologie - Chirurgie Cardiaque, Hôpital Pitié Salpetrière, Paris, France
  • Service d’Anesthésie et Réanimation Chirurgicale, Hôpital G&R Laënnec, Centre Hospitalier Universitaire de Nantes, Nantes, France
  • Service d’Anesthésie et Réanimation Chirurgicale, Hôpital G&R Laënnec, Centre Hospitalier Universitaire de Nantes, Nantes, France
  • Service d’Anesthésie et Réanimation Chirurgicale, Hôpital G&R Laënnec, Centre Hospitalier Universitaire de Nantes, Nantes, France
  • Service d’Anesthésie et Réanimation Chirurgicale, Hôpital G&R Laënnec, Centre Hospitalier Universitaire de Nantes, Nantes, France
  • Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany
  • Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany
  • Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany
  • Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • Department of Anesthesia and Intensive Care, Policlinico “Umberto I,” “La Sapienza,” University of Rome, Rome, Italy
  • Department of Anesthesia and Intensive Care, Policlinico “Umberto I,” “La Sapienza,” University of Rome, Rome, Italy
  • Department of Anesthesia and Intensive Care, Policlinico “Umberto I,” “La Sapienza,” University of Rome, Rome, Italy
  • Chirurgie Cardiovasculaire - Service de Réanimation, Centre Hospitalier Regional Universitaire, Hospitalier de Rangueil, Toulouse, France
  • Clinic for Anesthesia and Critical Care Medicine, University Hospital of Rostock, Rostock, Germany
  • Clinic for Anesthesia and Critical Care Medicine, University Hospital of Rostock, Rostock, Germany
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication November 7, 2016. Accepted for publication July 25, 2017.
    Submitted for publication November 7, 2016. Accepted for publication July 25, 2017.×
  • *Members of the Xenon-CABG Study Group are listed in the appendix.
    Members of the Xenon-CABG Study Group are listed in the appendix.×
  • Acknowledgments: Medical writing services were provided by Kurt Liittschwager, Ph.D., (4Clinics, Paris, France).
    Acknowledgments: Medical writing services were provided by Kurt Liittschwager, Ph.D., (4Clinics, Paris, France).×
  • Research Support: This study was funded by grants, personal fees, or nonfinancial support from Air Liquide Santé International (Paris, France; to Drs. Hofland, Ouattara, Fellahi, Joseph, Lehot, de Liefde, Amour, Ait Hamou, Benhaoua, Coburn, Tritapepe, Steib, Hanouz, Bein, Gruenewald, Roesner, Heringlake, and Preckel).
    Research Support: This study was funded by grants, personal fees, or nonfinancial support from Air Liquide Santé International (Paris, France; to Drs. Hofland, Ouattara, Fellahi, Joseph, Lehot, de Liefde, Amour, Ait Hamou, Benhaoua, Coburn, Tritapepe, Steib, Hanouz, Bein, Gruenewald, Roesner, Heringlake, and Preckel).×
  • Competing Interests: Supported by personal fees (e.g. lecture fees), or nonfinancial support from ALSI for activities other than the submitted work (to Dr. Hofland, Ouattara, Joseph, Lehot, Coburn, Tritapepe, and Steib); a grant and personal fees from Baxter Healthcare (Unterschleißheim, Germany) and a grant from Deutsche Forschungsgesellschaft (Neuss, Germany) for activities outside the submitted work (to Dr. Coburn); personal fees from Abbvie (Wiesbaden, Germany), CSL Behring (Marburg, Germany), GE Healthcare (München, Germany), Pulsion Medical Systems (Feldkirchen, Germany), MSD, CNSystems (Graz, Austria), Edwards Life Sciences (Unterschleißheim, Germany), 3M (Neuss, Germany), Orion Pharma (Hamburg, Germany), The Medicines Company (München, Germany), TEVA Ratiopharm (Ulm, Germany), and MASIMO (Puchheim, Germany) for activities outside the submitted work (to Dr. Bein); personal fees from GE Healthcare, Fresenius Medical (Bad Homburg vor der Höhe, Germany), and Werfen Group (Kirchheim bei München, Germany) for activities outside the submitted work (to Dr. Gruenewald); and a Linde BOC Inspire Award (Eindhoven, The Netherlands) for conduct of a study and grants from the Society of Cardiovascular Anesthesiologists (Richmond, Virginia), the European Foundation for the Study of Diabetes (Düsseldorf, Germany), Nederlands Vereniging voor Anesthesiologie (Utrecht, The Netherlands), and Nederlandse Organisatie voor Gezondheidsonderzoek en Zorginnovatie ZonMW (The Hague, The Netherlands) for activities outside the reported work and speaker fees from Abbvie (Hoofddorp, The Netherlands), Orion Pharma (Mechelen, Belgium), and Philips Health Care (Eindhoven, The Netherlands) for activities outside the reported work (to Dr. Preckel). Dr. Hazebroucq was an employee of ALSI during the study. The other authors declare no competing interests.
    Competing Interests: Supported by personal fees (e.g. lecture fees), or nonfinancial support from ALSI for activities other than the submitted work (to Dr. Hofland, Ouattara, Joseph, Lehot, Coburn, Tritapepe, and Steib); a grant and personal fees from Baxter Healthcare (Unterschleißheim, Germany) and a grant from Deutsche Forschungsgesellschaft (Neuss, Germany) for activities outside the submitted work (to Dr. Coburn); personal fees from Abbvie (Wiesbaden, Germany), CSL Behring (Marburg, Germany), GE Healthcare (München, Germany), Pulsion Medical Systems (Feldkirchen, Germany), MSD, CNSystems (Graz, Austria), Edwards Life Sciences (Unterschleißheim, Germany), 3M (Neuss, Germany), Orion Pharma (Hamburg, Germany), The Medicines Company (München, Germany), TEVA Ratiopharm (Ulm, Germany), and MASIMO (Puchheim, Germany) for activities outside the submitted work (to Dr. Bein); personal fees from GE Healthcare, Fresenius Medical (Bad Homburg vor der Höhe, Germany), and Werfen Group (Kirchheim bei München, Germany) for activities outside the submitted work (to Dr. Gruenewald); and a Linde BOC Inspire Award (Eindhoven, The Netherlands) for conduct of a study and grants from the Society of Cardiovascular Anesthesiologists (Richmond, Virginia), the European Foundation for the Study of Diabetes (Düsseldorf, Germany), Nederlands Vereniging voor Anesthesiologie (Utrecht, The Netherlands), and Nederlandse Organisatie voor Gezondheidsonderzoek en Zorginnovatie ZonMW (The Hague, The Netherlands) for activities outside the reported work and speaker fees from Abbvie (Hoofddorp, The Netherlands), Orion Pharma (Mechelen, Belgium), and Philips Health Care (Eindhoven, The Netherlands) for activities outside the reported work (to Dr. Preckel). Dr. Hazebroucq was an employee of ALSI during the study. The other authors declare no competing interests.×
  • Reproducible Science: Full protocol available at: jan.hofland@radboudumc.nl. Raw data available at: jan.hofland@radboudumc.nl.
    Reproducible Science: Full protocol available at: jan.hofland@radboudumc.nl. Raw data available at: jan.hofland@radboudumc.nl.×
  • Correspondence: Address correspondence to Dr. Hofland: Radboud University Medical Center, P.O. Box 9109, 6500 HB Nijmegen, The Netherlands. jan.hofland@radboudumc.nl. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Cardiovascular Anesthesia / Pharmacology
Perioperative Medicine   |   September 2017
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
Anesthesiology Newly Published on September 7, 2017. doi:10.1097/ALN.0000000000001873
Anesthesiology Newly Published on September 7, 2017. doi:10.1097/ALN.0000000000001873
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.