• Sebastian Rehberg, Sandra Frank, Vladimír Černý, Radek Cihlář, Rainer Borgstedt, Gianni Biancofiore, Fabio Guarracino, Andreas Schober, Helmut Trimmel, Thomas Pernerstorfer, Christian Siebers, Pavel Dostál, Andrea Morelli, Michael Joannidis, Ingrid Pretsch, Christian Fuchs, Tim Rahmel, Matej Podbregar, Éva Duliczki, Kadri Tamme, Martin Unger, Jan Sus, Christoph Klade, Kurt Krejcy, Nairi Kirchbaumer-Baroian, Günther Krumpl, František Duška, and LANDI-SEP Study Group.
• Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, University Hospital of Bielefeld, Bielefeld, Germany. Sebastian.Rehberg@uni-bielefeld.de.
• Intensive Care Med. 2024 Oct 1; 50 (10): 162216341622-1634.

PurposeExcessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol.MethodsThis randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events.ResultsOut of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events.ConclusionThe ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.© 2024. The Author(s).

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