S1 File -

PurposeOut-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 (VT)) have a better prognosis. In case of shockable rhythm, treatment is based on defibrillation, and thereafter, in case of failure of 3 external electric shocks (EES), on direct intravenous administration of 300 mg amiodarone, or lidocaine when amiodarone is unavailable or inefficient.During surgical procedures under extracorporeal circulation, a high potassium cardioplegia solution is administered to interrupt cardiac activity and facilitate surgical procedure. By extension, direct intravenous administration of potassium chloride (KCl) has been shown to convert VF, resulting in return to a hemodynamically efficient organized heart rate within a few minutes.The aim of this study is to provide clinical evidence that direct intravenous injection of KCl, into a patient presenting with OHCA due to refractory VF although 3 EES, should interrupt this VF and then allow rapid restauration of an organized heart rhythm, and thus return of spontaneous circulation (ROSC).MethodsA multicenter, prospective, single group, phase 2 study will be conducted on 81 patients presenting with refractory VF. After failure of 3 EES, each patient will receive direct intravenous injection of 20 mmol KCl instead of amiodarone. The primary outcome will be survival rate at hospital admission. Major secondary outcomes will include ROSC and time to ROSC in the prehospital setting, number of VF recidivism after KCl injection, survival rate at hospital discharge with a good neurologic prognostic, and survival rate 3 months after hospital discharge with a good neurologic prognostic.ResultsNo patient is currently included in the study.DiscussionConventional guideline strategy based on antiarrhythmic drug administration, i.e. amiodarone or lidocaine, for OHCA due to shockable rhythm, has not yet demonstrated an increase in survival at hospital admission or at hospital discharge. This may be related to the major cardiodepressant effect of those drugs.Trial registrationClinicalTrials.gov Identifier: NCT04316611. Registered on March 2020. AP-HP180577 / N° EUDRACT: 2019-002544-24. Funded by the French Health Ministry. https://clinicaltrials.gov/ct2/show/NCT04316611.</div

Distribution of the patients according to distance walked during the 6-minute walking test, expressed as % of the expected value.

<p>Distribution of the patients according to distance walked during the 6-minute walking test, expressed as % of the expected value.</p

Fig 1 -

Management algorithm for a patient with out of hospital cardiac arrest (OHCA) by VF according to international recommendations (Fig 1A) and in the context of this research (Fig 1B). Epinephrine injections are not shown in the figure for simplicity.</p

Clinical and laboratory characteristics according to the SpO₂ decline induced by the 6-minute walking test.

<p>BMI, body mass index; VOC, vasoocclusive crisis; ACS, acute chest syndrome; 6 MWT, 6-minute walking test.</p

Distribution of the patients according to distance walked during the 6-minute walking test, expressed as % of the expected value.

<p>Distribution of the patients according to distance walked during the 6-minute walking test, expressed as % of the expected value.</p

Clinical and laboratory characteristics of patients according to lowest nocturnal SpO_2.

<p>BMI, body mass index; VOC, vasoocclusive crisis; ACS, acute chest syndrome; 6 MWT, 6-minute walking test.</p

S2 File -

PurposeOut-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 (VT)) have a better prognosis. In case of shockable rhythm, treatment is based on defibrillation, and thereafter, in case of failure of 3 external electric shocks (EES), on direct intravenous administration of 300 mg amiodarone, or lidocaine when amiodarone is unavailable or inefficient.During surgical procedures under extracorporeal circulation, a high potassium cardioplegia solution is administered to interrupt cardiac activity and facilitate surgical procedure. By extension, direct intravenous administration of potassium chloride (KCl) has been shown to convert VF, resulting in return to a hemodynamically efficient organized heart rate within a few minutes.The aim of this study is to provide clinical evidence that direct intravenous injection of KCl, into a patient presenting with OHCA due to refractory VF although 3 EES, should interrupt this VF and then allow rapid restauration of an organized heart rhythm, and thus return of spontaneous circulation (ROSC).MethodsA multicenter, prospective, single group, phase 2 study will be conducted on 81 patients presenting with refractory VF. After failure of 3 EES, each patient will receive direct intravenous injection of 20 mmol KCl instead of amiodarone. The primary outcome will be survival rate at hospital admission. Major secondary outcomes will include ROSC and time to ROSC in the prehospital setting, number of VF recidivism after KCl injection, survival rate at hospital discharge with a good neurologic prognostic, and survival rate 3 months after hospital discharge with a good neurologic prognostic.ResultsNo patient is currently included in the study.DiscussionConventional guideline strategy based on antiarrhythmic drug administration, i.e. amiodarone or lidocaine, for OHCA due to shockable rhythm, has not yet demonstrated an increase in survival at hospital admission or at hospital discharge. This may be related to the major cardiodepressant effect of those drugs.Trial registrationClinicalTrials.gov Identifier: NCT04316611. Registered on March 2020. AP-HP180577 / N° EUDRACT: 2019-002544-24. Funded by the French Health Ministry. https://clinicaltrials.gov/ct2/show/NCT04316611.</div

SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents*.

SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents*.</p

Main characteristics of the 39 children and adolescents with sickle cell disease (part 1).

<p>Main characteristics of the 39 children and adolescents with sickle cell disease (part 1).</p

Risk factors for at least one type of hypoxemia (day, night, and postexercise).

<p>BMI, body mass index; VOC, vasoocclusive crisis; ACS, acute chest syndrome; 6 MWT, 6-minute walking test.</p