Treatment of intraoperative hypotension with cafedrine/theodrenaline versus ephedrine
Authors: Eberhart L. , Geldner G. , Kowark A. , Zucker T.-P. , Kreuer S. , Przemeck M. , Huljic S. , Koch T. , Keller T. , Weber S. , Kranke P. ,   the HYPOTENS study group, Rosendahl Adelheid , Nasralla Ahmed , Lay Alexander , Reich Alexander , Zarbock Alexander , Kratt Alexandra , Ghazi Ali , Lipka Alien , Opazo Saez Anabelle , Bergner Anca , Gottschalk Andre , Biedler Andreas , Buchbinder Andreas , Fröhlich Andreas , Hettel Andreas , Thierbach Andreas , Weyland Andreas , Diers Anja , Reifenstein Anja , Ribeaucourt Anke , Schag Annette , Schlemmer Annika , Schubert Ann-Kristin , Helf Antonia , Junger Axel , Heller Axel R. , Schneider Axel , Schwenn Babett , Hauer Bastian , Gebel Benjamin , Rehm Benjamin , Vojnar Benjamin , Bachmann-Mennenga Bernd , Dohmen Bernd , Wetzel Bert , Bein Berthold , Olberding Birgit , Gärten-Schneider Bodo , Larsen Brita , Wempe Carola , Asam Christian , Frenkel Christian , Gereke Christian , Höhn Christian , Koch Christian , Mey Christian , Schlegel Christian , Schütz Christian , Oschewski Christine , Radenbach Christoph , Graml Claudia , Trebes Claudia , Greim Clemens-Alexander , Ebert Cornelie , Galati Dafni , Schulte Dagmar , Chappell Daniel , Westerheide Diana , Henzler Dietrich , Meininger Dirk , Drop Edith , Strach Edith , Hüttemann Egbert , Schneck Emmanuel , Sickmüller Erdmann , Bucher Eva , Kranke Eva , Darstein Fabian , Geiselbrecht Fabian , Brinkmann Felix , Jakob Franziska , Fiedler Fritz , Fröba Gebhard , Rohe Georg , Kalmus Gerald , Gerbershagen Hans Jürgen , Nitzsche Hendrik , Weigt Henry , Schaedel Hermann , Wrigge Hermann , Wulf Hinnerk , Janssen Holger , Kummer Ilse , Lotze Ina , Guzman Ines , Bartlan Jan , Hirsch Jan , Wallenborn Jan , Bolten Jana , Baumert Jan-Hinrich , Bartl Jannis , Große Joachim , Kuhn Johannes , Engel Jörg , Kieckhäfer Jörg , van Waesberghe Julia , Schön Julika , Friedrich Jürgen , Becke Karin , Oppenrieder Karin , Brün Kathrin , Meiers Kathrin , Neubieser Katja , Baumann Katrin , Müller-Dang Kerstin , Rämisch Kirsten , Savadkouhi Kourosh , Korf Lena , Müller Lukas , Haupt Manuela , Ensink Marco , Piontek Margarethe , Kiesel Marina , Kluth Mario , Santamaria Mario , Coburn Mark , Barnscheidt Markus , Benz Markus , Bruckner Markus , Lange Markus , Müller Markus , Paxian Markus , Grapengeter Martin , Kelbel Martin , Lipp Martin , Pesch Martin , Bauer Martina , Schäfer Max , Markmann Melanie , Booke Michael , Cercasov Michael , Fritz Michael , Henrich Michael , Höra Michael , Pohl Michael , Sander Michael , Lange Mirko , Bleise Monika , Richter Monique , Obradovic Neda , Krug Nico , Lorenz Nico , Preußler Niels Peter , Ulsamer Nils , Schneider Norbert , Schnobrich Norbert , Simon Olaf , Kunitz Oliver , Kienbaum Peter , Scharmann Peter , Tepaß Petra , Weber Philipp , Hammels Phillip , Simon Phillip , Singer Rabea , Müllenbach Ralf , Babian Renate , Hennebach Ria , Hanß Robert , Horodko Robert , Liedel Robert , Rossaint Rolf , Körner Sabine , Jünger Sandra , Valle Sandro , Reinecke Sebastian , Ziemann Sebastian , Kutz Silke , Ruhrmann Sophie , Hecht Sören , Czarnecki Stefan , Hübner Stefan , Rußwurm Stefan , Seyboth Stefan , Schneider Stephanie , Engels-Mühlen Susanne , Albrecht Svenja , Pabel Svenja , Just Theresa , Hirschberg Thilo , Demme Thomas , Grote Thomas , Pelchen Thomas , Standl Thomas , Volk Thomas , Zinsmeister Thomas , Quellenberg Thorsten , Lohoff Tim , Kiel Tobias , Diederichs Tristan , Lienstedt Ulf , Fink Uwe , Hölternamm Walter , Osthaus Wilhelm Alexander , Geisser Wolfgang , Funk Wolgang , Jelting Yvonnne 
Published: November 2020

Abstract
Background
Sympathomimetic drugs are a therapeutic cornerstone for the management of hypotensive states like intraoperative hypotension (IOH). While cafedrine/theodrenaline (C/T) is widely used in Germany to restore blood pressure in patients with IOH, more research is required to compare its effectiveness with alternatives such as ephedrine (E) that are more commonly available internationally.

Methods
HYPOTENS (NCT02893241, DRKS00010740) was a prospective, national, multicenter, open-label, two-armed, non-interventional study that compared C/T with E for treatment of IOH. We describe a prospectively defined cohort of patients ≥50 years old with comorbidities undergoing general anesthesia induced with propofol and fentanyl. Primary objectives were to examine treatment precision, rapidity of onset and the ability to restore blood pressure without relevant increases in heart rate. Secondary endpoints were treatment satisfaction and the number of required additional boluses or other accompanying measures.

Results
A total of 1496 patients were included in the per protocol analysis. Overall, effective stabilization of blood pressure was achieved with both C/T and E. Post-hoc analysis showed that blood pressure increase from baseline was more pronounced with C/T. Fewer additional boluses or other accompanying measures were required in the C/T arm. The incidence of tachycardia was comparable between groups. Post-hoc analysis showed that E produced dose-dependent elevated heart rate values. By contrast, heart rate remained stable in patients treated with C/T. Physicians reported a higher level of treatment satisfaction with C/T, with a higher proportion of anesthetists rating treatment precision and rapidity of onset as good or very good when compared with E.

Conclusion
Neither drug was superior in restoring blood pressure levels; however, post-hoc analyses suggested that treatment is more goal-orientated and easier to control with C/T. Heart rate was shown to be more stable with C/T and fewer additional interventions were required to restore blood pressure, which could have contributed to the increased treatment satisfaction reported by anesthetists using C/T.