Therapeutic Hypothermia After Cardiac Arrest in Non Shockable Rhythm (HYPERION)

Therapeutic Hypothermia After Cardiac Arrest in Non Shockable Rhythm at Rescue Arrival: The HYPERION Study

Cardiac arrest is at present a major cause of mortality as well as a cause of disability for the surviving victims.In Europe, every year counts as 300,000 cardiac arrests responsible for 250,000 deaths. Thus, less than 20 % of patients discharged home with impaired quality of life associated with symptoms of tiredness, stress, anxiety. The prognosis is related to the initial cardiac rhythm present during the initiation of resuscitation. Recent progress in the improvement of mortality and neurological outcome has been achieved over the last decade thanks to the systematic implementation of a period of targeted temperature control between 32 and 34 ° C in patients who benefited from the realization of at least one electrical external shock. There are theoretical and clinical arguments to think that achieving the same way a period of targeted temperature control between 32 and 34 ° C in patients treated for cardiac arrest with a non- shockable rhythm on arrival can also benefit from this procedure. However other arguments are against this hypothesis including an increase in the risk of infection , worsening of the patient's hemodynamic status with no benefit to him. To answer this question, we conduce a randomized multicenter study testing the potential improvement of neurological outcome through this procedure targeted temperature control between 32.5 and 33.5 ° C in these patients.

Therapeutic hypothermia, Targeted controlled temperature, Cardiac arrest, Non shockable rhythm, successful resuscitation

Patients will be placed in targeted temperature control between 32.5 and 33.5 ° C for 24 hours and then slowly rewarmed for targeted temperature control between 36.5 and 37.5 ° C for 24 hours.

Therapeutic hypothermia ie targeted controlled temperature between 32.5° and 33.5°C will be induced in the active group. Usual method of controlled temperature will be use in ICU: internal active method or external active method.

Temperature was maintain between 36.5° and 37.5°C in the control group. In case of temperature superior to 37.5°C or inferior to 36.5°C, a pharmaceutical treatment and/or active cooling or warming was introduce to maintain temperature between the range of 36.5 - 37.5°C.

Participants will be followed for the duration of Intensive Care Unit stay, an expected average of 7 days.

Quality of life at day 90 will be assessed by 36-Items Short Form for Health Survey telephonic interview

Life autonomy will be assessed by Index Activity of Daily Living, modified Barthel index, and by two normative question about life autonomy

Neurocognitive status will be assessed by telephonic validated version of Mini Mental State Examination

Participants will be followed for the duration of Intensive Care Unit stay, an expected average of 7 days

Participants will be followed for the duration of mechanical ventilation, an expected average of 4 days

Severe hemorrhage is define by transfusion of 1 or more blood product requirement and/or intracranial hemorrhage. Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.

Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.

Participants will be followed for the duration of mechanical ventilation, an expected average of 4 days

Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.

Total dose of different inotropic drugs (Epinephrine, Norepinephrine, Dobutamine) will be compare between 2 groups during targetted controlled temperature management period.

Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days

Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.

Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days

Severe arrythmia will be define by salvo of ventricular extrasystole, ventricular fibrillation, ventricular tachycardia, need an external shock, need anti-arrhythmic treatment. Participants will be followed for the duration of Intensive Care Unit stay, an expected average of 7 days.

Inclusion Criteria: Cardiac arrest in non shockable rhythm Glasgow score ≤ 8 Exclusion Criteria: No flow > 10 min Low flow > 60 min Major hemodynamic instability Delay between cardiac arrest and inclusion > 300 min Cirrhosis Child C Age < 18 years Pregnant women Patient with no liberty Lack of informed consent Prior inclusion in a research protocol involving cardiac arrest with draw, and whose primary endpoint focuses on the evaluation of a neurological score Day 90

Ziriat I, Le Thuaut A, Colin G, Merdji H, Grillet G, Girardie P, Souweine B, Dequin PF, Boulain T, Frat JP, Asfar P, Francois B, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Massart N, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Reignier J, Cariou A, Lascarrou JB. Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data. Ann Intensive Care. 2022 Oct 17;12(1):96. doi: 10.1186/s13613-022-01071-z.

Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J; CRICS-TRIGGERSEP Group. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Engl J Med. 2019 Dec 12;381(24):2327-2337. doi: 10.1056/NEJMoa1906661. Epub 2019 Oct 2.

Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, Asfar P, Frat JP, Dequin PF, Gouello JP, Delahaye A, Hssain AA, Chakarian JC, Pichon N, Desachy A, Bellec F, Thevenin D, Quenot JP, Sirodot M, Labadie F, Plantefeve G, Vivier D, Girardie P, Giraudeau B, Reignier J; Clinical Research in Intensive Care and Sepsis (CRICS) Group and HYPERION Study Group. Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial. Scand J Trauma Resusc Emerg Med. 2015 Mar 7;23:26. doi: 10.1186/s13049-015-0103-5.