Clinical trial NCT04316611: Potassium Chloride in Out-of-hospital Cardiac Arrest Due to Refractory Ventricular Fibrillation
Official title: Evaluation of the Effectiveness of Potassium Chloride in the Management of Out-of-hospital Cardiac Arrest by Refractory Ventricular Fibrillation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Out-of-hospital Cardiac Arrest (OHCA)
Keywords: Out-of-hospital cardiac arrest (OHCA)
Potassium chloride
Refractory ventricular fibrillation
External electric shock
Defibrillation
Amiodarone
Lidocaine
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: URC-CIC Paris Descartes Necker Cochin
First posted: 2020-03-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate, in patients presenting with out-of-hospital cardiac arrest (OHCA) by ventricular fibrillation, refractory to 3 external electric shocks, the efficacy of a direct intravenous injection of 20 mmol KCl on their survival at hospital arrival.

Detailed description: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis, with an overall survival rate of about 5% at discharge. Shockable rhythm cardiac arrests (ventricular fibrillation (VF) and pulseless ventricular tachycardia) have a better prognosis.

In case of shockable rhythm, treatment is based on defibrillation, thereafter failure of 3 external electric shocks, on direct intravenous administration of 300 mg amiodarone, followed in case of ineffectiveness by an additional direct intravenous administration of 150 mg amiodarone. Lidocaine, which has long been used in this indication, is currently only recommended when amiodarone is unavailable or inefficient. Nevertheless, these 2 drugs, while they may be effective in converting refractory ventricular fibrillation to normal rhythm, have marked cardiodepressant effects (bradycardia, and/or negative inotropic effect) that persist after direct intravenous administration. This explains, at least partially, why a recent study did not show a significant difference in hospital discharge survival between amiodarone, lidocaine and placebo in patients presenting with OHCA by refractory ventricular fibrillation.

During surgical procedures under extracorporeal circulation, a cardioplegia solution is administered to interrupt cardiac activity and facilitate the surgical procedure. From a patho-physiological level, the mode of action of these solutions is based on a high concentration of potassium, which reduces the membrane resting potential of the myocytes. By extension, direct intravenous administration of 20 mmol potassium chloride (KCl) has been shown to convert ventricular fibrillation, resulting in a return to an hemodynamically efficient organized heart rate within a few minutes. The kalemia were at the upper limit of normal (5.5 mmol/l) 10 min after this injection, and normal at 20 min. A recent clinical case of a patient under extracorporeal circulation resuscitation, presenting with a refractory ventricular fibrillation, demonstrated the efficacy of direct intravenous injection of 3 g potassium chloride, resulting in a return to a sinus rhythm within a few minutes.

The immediate advantage of potassium chloride, compared to amiodarone (and also lidocaine), is the absence of cardiodepressant effect (bradycardia and/or hypotension) persisting after a while from the injection time. The mode of action of direct intravenous injection of potassium chloride to reduce ventricular fibrillation is indeed linked to the peak of hyperkalemia, whereas since the kalaemia are afterwards rapidly normalized in a few minutes, there is no persistent deleterious effect following this injection of potassium chloride. In addition, in the case of cardiac arrest, since the patient is already under continuous external cardiac chest compressions, no supplementary deleterious consequences related to this transient hyperkalemia are expected.

Direct intravenous injection of potassium chloride into a patient in out-of-hospital cardiac arrest with refractory ventricular fibrillation with 3 external electric shocks, instead of amiodarone, should interrupt this ventricular fibrillation and then allow a rapid return to an organized heart rhythm, and thus restore effective spontaneous cardiac activity.

Eligibility criteria: Inclusion Criteria:

* Adult patient (age 18 or over).
* Patient suffering from an outpatient cardiac arrest of presumed cardiac origin and presenting refractory ventricular fibrillation despite 3 external electric shocks.
* Patient with a health insurance plan.

Exclusion Criteria:

* Proven pregnancy.
* Major incompetent (patient under guardianship or curatorship).
* Patient who does not yet have a functional venous pathway after the 3 external electric shocks have been performed.

Primary outcomes:
measure: Survival at hospital admission
timeFrame: At hospital admission up to 1 day
Secondary outcomes:
measure: Number of pre-hospital return of spontaneous circulation (ROSC)
timeFrame: Pre-hospital setting, up to 1 day
measure: Time to pre-hospital return of spontaneous circulation (ROSC)
timeFrame: Pre-hospital setting, up to 1 day
measure: Total pre-hospital epinephrine dose
timeFrame: Pre-hospital setting, up to 1 day
measure: Total number of pre-hospital external electric shocks
timeFrame: Pre-hospital setting, up to 1 day
measure: Total number of persistent or recurrent shockable rhythm disorders
timeFrame: Pre-hospital setting, up to 1 day
measure: Heart rate at hospital admission
timeFrame: At hospital admission, up to 1 day
measure: Blood pressure at hospital admission
timeFrame: At hospital admission, up to 1 day
measure: Survival with good neurological outcome (Cerebral Performance Category (CPC) 1 or 2)at hospital discharge
timeFrame: At hospital discharge, up to maximum 3 months
measure: Survival with good neurological outcome (Cerebral Performance Category 1 or 2)at 3 months
timeFrame: At 3 months
Other outcomes:
Locations:
city: Paris
country: France
facility: AP-HP - SAMU de Paris
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Romain Jouffroy, MD
role: STUDY_DIRECTOR
References: