PURPOSE: Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared. METHODS: In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence. RESULTS: Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3-6.8) and 7.3 h (95% CI 5-11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05). CONCLUSION: Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.

• Keywords
• Amiodarone, Atrial fibrillation, Atrial flutter, Cardioversion, Propafenone, Septic shock, Supraventricular arrhythmia,
• MeSH
• Amiodarone * therapeutic use   MeSH
• Anti-Arrhythmia Agents therapeutic use   MeSH
• Atrial Fibrillation * therapy   MeSH
• Ventricular Function, Left MeSH
• Humans MeSH
• Propafenone therapeutic use   MeSH
• Prospective Studies MeSH
• Shock, Septic * complications   drug therapy   MeSH
• Stroke Volume MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Amiodarone * MeSH
• Anti-Arrhythmia Agents MeSH
• Propafenone MeSH

INTRODUCTION: Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy. METHODS AND ANALYSIS: The trial includes septic shock patients with new-onset arrhythmia, but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient is randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the percentages of patients that needed rescue treatments (DC cardioversion or unblinding and crossover of the antiarrhythmics), the recurrence of arrhythmias, intensive care unit mortality, 28-day and 1-year mortality. In the posthoc analysis, we separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction. In the exploratory part of the study, we assess whether the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical SR and whether the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Considering that the restoration of SR within 24 hours occurred in 74% of the amiodarone-treated patients and in 89% of the patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05. ETHICS AND DISSEMINATION: The trial is recruiting patients according to its second protocol version approved by the University Hospital Ethical Board on the 6 October 2017 (No. 1691/16S-IV). The results will be disseminated through peer reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03029169.

• Keywords
• amiodarone, intensive care, propafenone, septic shock, supraventricular arrhythmia,
• MeSH
• Amiodarone therapeutic use   MeSH
• Anti-Arrhythmia Agents therapeutic use   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Ventricular Function, Left drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Propafenone therapeutic use   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Shock, Septic complications   drug therapy   physiopathology   MeSH
• Tachycardia, Supraventricular complications   drug therapy   physiopathology   MeSH
• Stroke Volume drug effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Amiodarone MeSH
• Anti-Arrhythmia Agents MeSH
• Propafenone MeSH

Beta-blockers are a potential option to manage peri-operative atrial fibrillation. Landiolol is a new ultra-short beta-blocker with a half-life of only 4 minutes and very high beta-1 selectivity which has been used for treatment and prevention of atrial fibrillation in pulmonary surgery and gastro-intestinal surgery. Due to its limited negative inotropic effect and high beta-1 selectivity landiolol allows for control of heart rate with minimal impact on blood pressure. Landiolol is well tolerated by the respiratory system. Additional benefits are related to the regulation of the inflammatory response and blunting of the adrenergic pathway. There is a limited number of trials with total of 61 patients undergoing lung resection or oesophagectomy who developed post-operative atrial fibrillation and were treated with landiolol. The experience with landiolol for prevention is more documented than landiolol application for treatment of post-operative atrial fibrillation. There are 9 comparative studies with a total of 450 patients administered landiolol for prevention of post-operative atrial fibrillation. The use of low dosage (5-10mcg/kg/min) is usually sufficient to rapidly control heart rate which is associated with earlier and higher rate of conversion to sinus rhythm as compared to the controls. The excellent tolerance of landiolol at lower dosage (3-5mcg/kg/min) allows to initiate prophylactic use during surgery and postoperatively. Landiolol prophylaxis is associated with reduced incidence of post-operative atrial fibrillation without triggering adverse events related to a beta-blockade.

• Keywords
• Antiarrhythmic therapy, Atrial fibrillation, Cardioversion, Diastolic dysfunction, Landiolol, Supraventricular arrhythmia,
• Publication type
• Journal Article MeSH