*Department of Anesthesiology and Intensive Care Medicine, Technical University of Munich, School of Medicine, Munich, Germany

†Department of Anesthesiology and Intensive Care Medicine (CVK, CCM), Charité - Universitätsmedizin Berlin, Berlin, Germany

‡Department of Anesthesiology and Intensive Care Medicine, University of Ulm, Faculty of Medicine, Ulm, Germany

§Department of Vascular Surgery, Technical University of Munich, School of Medicine, Munich, Germany

∥Department of Orthopaedics, Technical University of Munich, School of Medicine, Munich, Germany

¶Department of Surgery, Technical University of Munich, School of Medicine, Munich, Germany

#Department of Traumatology, Technical University of Munich, School of Medicine, Munich, Germany

**Technical University of Munich, School of Medicine, Institute of Clinical Chemistry and Pathobiochemistry, Munich, Germany

The trial was approved by the Ethics Committee of the School of Medicine of the Technical University of Munich (359/16 on 14.09.2016). Patients gave their written informed consent during the preoperative anesthesia evaluation. The study was conducted according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP), and Declaration of Helsinki.

S.J.S., K.F., S.S., C.A.B.B., H.E., R.v.E.-R., H.F., C.K., and B.J. recruited and managed patients in the study. S.J.S., B.J., and M.B. were responsible for the conception and design of the study. S.J.S., K.F., S.S., M.B., and B.J. participated in protocol development. S.J.S., K.F., S.S., C.A.B.B., H.E., R.v.E.-R., H.F., C.K., and B.J. were responsible for the acquisition of data. S.J.S., B.U., S.S., M.B., and B.J. did the statistical analysis. All authors analyzed and interpreted the data. SJS prepared the first draft of the manuscript with the input of M.B. S.J.S., M.B., and B.J. were responsible for the final draft of the manuscript. All authors revised the manuscript, approved the final manuscript and its submission, and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.

M.B. received research support from MSD (Haar, Germany) not related to this manuscript, received honoraria for giving lectures from GE Healthcare (Helsinki, Finland) and Grünenthal (Aachen, Germany). M.B. is a consultant to HW Pharmaconsulting (Moosach, Germany), Cosinuss° (Munich, Germany), MIPM (Mammendorf, Germany), SENZIME (Uppsala, Sweden), and Aspen Germany (Munich, Germany). S.J.S. received grants and nonfinancial support from Reactive Robotics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany), STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants, personal fees, and nonfinancial support from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany), grants from the Innovationsfond of The Federal Joint Committee (G-BA), personal fees from Springer Verlag GmbH (Vienna, Austria) for educational purposes and Advanz Pharma GmbH (Bielefeld, Germany), nonfinancial support from national and international societies (and their congress organizers) in the field of anesthesiology and intensive care medicine, outside the submitted work. S.J.S. holds stocks in small amounts from Alphabeth Inc., Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. The remaining authors report no conflicts of interest.

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