PURPOSE: Excessive 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. METHODS: This 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. RESULTS: Out 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. CONCLUSION: The 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.

Anaesthesiology and Intensive Care Unit Szabolcs Szatmár Bereg County Hospitals and University Teaching Hospital Jósa András Teaching Hospital Nyíregyháza Hungary

AOP Health International Management AG Ruggell Liechtenstein

AOP Orphan Pharmaceuticals GmbH Vienna Austria

Clinic of Anaesthesiology and Intensive Care 1St Intensive Care Unit Tartu University Hospital Tartu Estonia

Department of Anaesthesia and Critical Care Medicine Cardiothoracic and Vascular Anaesthesiology and Intensive Care Azienda Ospedaliero Universitaria Pisana Pisa Italy

Department of Anaesthesia and Intensive Care Charles University 3rd Medical Faculty and University Hospital Královské Vinohrady Prague Czech Republic

Department of Anaesthesiology and Intensive Care Hospital of Garmisch Partenkirchen Garmisch Partenkirchen Germany

Department of Anaesthesiology and Intensive Care Medicine Charles University Faculty of Medicine in Hradec Kralove Hradec Králové Czech Republic

Department of Anaesthesiology and Intensive Care Medicine University Hospital Hradec Králové Hradec Králové Czech Republic

Department of Anaesthesiology and Intensive Care Ordensklinikum Linz GmbH Barmherzige Schwestern Linz Austria

Department of Anaesthesiology and Transplant Intensive Care Unit University School of Medicine Pisa Pisa Italy

Department of Anaesthesiology Intensive Care Emergency and Pain Medicine University Hospital Greifswald Greifswald Germany

Department of Anaesthesiology Intensive Care Emergency Medicine Transfusion Medicine and Pain Therapy University Hospital of Bielefeld Bielefeld Germany

Department of Anaesthesiology Intensive Care Medicine and Pain Therapy University Hospital Knappschaftskrankenhaus Bochum Bochum Germany

Department of Anaesthesiology LMU University Hospital LMU Munich Munich Germany

Department of Anaesthesiology Perioperative Medicine and Intensive Care Masaryk Hospital Ústí Nad Labem Czech Republic

Department of Anesthesia Pain Management and Perioperative Medicine Dalhousie University Halifax Canada

Department of Anesthesiology and Intensive Care Hospital České Budějovice České Budějovice Czech Republic

Department of Anesthesiology Emergency Medicine and General Intensive Care State Hospital Wiener Neustadt Wiener Neustadt Austria

Department of Cardiology Klinik Floridsdorf and Karl Landsteiner Institute for Cardiovascular and Critical Care Research C O Klinik Floridsdorf Vienna Austria

Department of Clinical Internal Anesthesiological and Cardiovascular Sciences University of Rome La Sapienza Policlinico Umberto Primo Rome Italy

Department of Internal Medicine 2 Division of Cardiology and Intensive Care Paracelsus Medical University of Salzburg Salzburg Austria

Division of Emergency Medicine and Intensive Care Department Internal Medicine Medical University Innsbruck Innsbruck Austria

Internal Intensive Care Department General Hospital Celje Celje Slovenia

Medical Faculty University of Ljubljana Ljubljana Slovenia

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