Potassium Chloride in Out-of-hospital Cardiac Arrest Due to Refractory Ventricular Fibrillation (POTACREH)

Evaluation of the Effectiveness of Potassium Chloride in the Management of Out-of-hospital Cardiac Arrest by Refractory Ventricular Fibrillation

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.

Study Overview

• Status: Withdrawn
• Conditions: Out-of-hospital Cardiac Arrest (OHCA)
• Intervention / Treatment: Drug: Potassium chloride

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Benoît Vivien, MD, PhD; Phone Number: +33 1 44 49 23 67; Email: benoit.vivien@aphp.fr
• Study Contact Backup: Name: Nelly BRIAND, PhD; Phone Number: +33 1 44 38 18 62; Email: nelly.briand@aphp.fr

Study Locations

• France
  • Paris, France, 75015
    • AP-HP - SAMU de Paris
    • Contact: Benoît Vivien, MD, PhD; Phone Number: +33 1 44 49 23 67; Email: benoit.vivien@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Potassium chloride	Drug: Potassium chloride; Direct intravenous injection (IVD) 20 mmol potassium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at hospital admission	Survival (return of spontaneous circulation) at hospital admission	At hospital admission up to 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of pre-hospital return of spontaneous circulation (ROSC)	Return of spontaneous circulation in pre-hospital setting	Pre-hospital setting, up to 1 day
Time to pre-hospital return of spontaneous circulation (ROSC)	Time, in minutes, from cardiac arrest to return of spontaneous circulation in pre-hospital setting	Pre-hospital setting, up to 1 day
Total pre-hospital epinephrine dose	Total epinephrine dose in mg administered in the pre-hospital setting	Pre-hospital setting, up to 1 day
Total number of pre-hospital external electric shocks	Total number of external electric shocks delivered in the pre-hospital setting	Pre-hospital setting, up to 1 day
Total number of persistent or recurrent shockable rhythm disorders	Total number of persistent or recurrent rhythm disorders requiring an external electric shock in pre-hospital setting Total number of persistent or recurrent rhythm disorders requiring an external electric shock in pre-hospital setting Total number of persistent or recurrent rhythm disorders requiring an external electric shock in pre-hospital setting	Pre-hospital setting, up to 1 day
Heart rate at hospital admission	Measurement of heart rate when the patient arrives on the hospital ward	At hospital admission, up to 1 day
Blood pressure at hospital admission	Measurement of systolic and diastolic blood pressure when the patient arrives on the hospital ward	At hospital admission, up to 1 day
Survival with good neurological outcome (Cerebral Performance Category (CPC) 1 or 2)at hospital discharge	Survival with a good neurological prognosis (CPC scores 1 and 2) at hospital discharge	At hospital discharge, up to maximum 3 months
Survival with good neurological outcome (Cerebral Performance Category 1 or 2)at 3 months	Survival with a good neurological prognosis (CPC scores 1 and 2) at 3 months	At 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Director: Romain Jouffroy, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: March 18, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Lidocaine; Defibrillation; Amiodarone; Out-of-hospital cardiac arrest (OHCA); Potassium chloride; Refractory ventricular fibrillation; External electric shock
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Arrest; Ventricular Fibrillation; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: APHP180577; 2019-002544-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No