Table 2 Inclusion/exclusion criteria

Inclusion criteria

1. Informed consent

 2. Age ≥ 18 years

 3. Confirmed septic shock:

  a. Confirmed or suspected infection

  b. Acute increase of ≥ 2 points on SOFA Score

  c. Need for continuous vasopressor therapy to maintain a mean arterial pressure (MAP) of > 65 mmHg despite adequate fluid resuscitation

  d. Blood lactate > 2 mmol/L (18 mg/dL)^a

 4. Tachycardia and/or tachyarrhythmia with heart rate ≥ 95 bpm

 5. Norepinephrine infusion rate ≥ 0.2 μg/kg/min at the time of study inclusion

 6. Patients must have undergone a hemodynamic optimization period of at least 24 h but a maximum of 36 h, during which period they received continuous vasopressor treatment and standard treatment for septic shock according to the SSCG 2016 guidelines

^aPresence of blood lactate > 2 mmol/L (18 mg/dL) and increase of ≥ 2 points on SOFA score are mandatory for the diagnosis of septic shock, but must not necessarily be present at the time of study inclusion

Exclusion criteria:

 1. Any form of compensatory tachycardia

 2. β-blocker treatment within 72 h before randomization

 3. Sick sinus syndrome, or second or third degree AV block

 4. Patients with any form of cardiac pacing

 5. A known serious cardiovascular condition such as ischemic stroke or transient ischemic attack within the last six months, or pre-existing heart failure NYHA class III or IV

 6. Cardiogenic shock

 7. MAP < 65 mmHg

 8. Known pulmonary hypertension

 9. Known terminal illness other than septic shock with expected patient’s survival < 28 days

 10. Known presence of an advanced condition to withhold life-sustaining treatment

 11. Patients for whom a “Do Not Resuscitate” (DNR) order exists

 12. Known sensitivity to any component of the study medication (e.g. landiolol, mannitol)

 13. Participation in a clinical drug trial within 30 days before randomization

 14. Any condition that, in the investigator’s opinion, makes the individual unsuitable for study participation (to be documented)

 15. Pregnant or breast-feeding patients

 16. Untreated pheochromocytoma