Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study

Abstract

IntroductionSupraventricular 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 analysisThe 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 disseminationThe 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 numberNCT03029169.

Cardiac index and heart rate as prognostic indicators for mortality in septic shock: A retrospective cohort study from the MIMIC-IV database

“…The control of rapid heart rate plays a crucial role in stabilizing hemodynamics and improving cardiac diastolic function, especially in patients with septic shock. Increasing evidence suggests that in critically ill patients, controlling heart rate alone, such as with beta-blockers, amiodarone, propafenone, alpha-2 receptor agonists, etc., can improve hemodynamics without necessarily restoring the heart rate to sinus rhythm [ 43 ]. The decrease in heart rate is often accompanied by an increase in cardiac index and a decrease in central venous pressure, reflecting an improvement in myocardial work efficiency [ 44 ].…”

Echocardiography predictors of sustained sinus rhythm after cardioversion of supraventricular arrhythmia in patients with septic shock

“…The authors performed an a priori planned exploratory analysis of a registered prospective controlled randomized trial (24), carried out in the ICUs of two university hospitals in Prague. The primary aim of the study was to de ne suitable echocardiography parameters which may be predictive of arrhythmia recurrence in septic shock.…”

Echocardiography predictors of sustained sinus rhythm after cardioversion of supraventricular arrhythmia in patients with septic shock

“…Furthermore, there is a noticeable absence of studies on predictors of cardioversion in critically ill patients with septic shock and SVA, despite its high incidence and signi cant relationship to survival. The authors performed an a priori planned exploratory analysis of a registered prospective controlled randomized trial (24,25), carried out in the ICUs of two university hospitals in Prague. The primary aim of the study was to investigate echocardiography parameters which may be predictive of arrhythmia recurrence during infusion of antiarrhythmics administered for a newly occurring SVA in septic shock.…”

“…This study was an a priori planned exploratory sub-study within randomized controlled trial Propafenone Versus Amiodarone for SVA in Septic Shock (PRASE, NCT03029169). The full protocol of the PRASE trial has been published (24)and the main results have been accepted and are currently in press (25).…”