Cardiac Arrest, Heart Arrest, Hypothermia
Conditions
Keywords
cardiac arrest, targeted temperature management, hypothermia induced, shockable rhythm
Brief summary
Comparing the production of interleukin 6 (inflammatory cytokine) in two heating speed (slow rewarming rate: 0.25 ° C / h or fast rewarming rate 0.50 ° C / h) at the completion of a period of targeted temperature at 33°C after cardiac arrest supported by shockable rhythm and successfully resuscitated.
Detailed description
Cardiac arrest (CA) is at present a major cause of mortality as well as a cause of disability for the surviving victims. In France, every year counts as 50,000 cardiac arrests responsible for 40 000 deaths. Thus, less than 20% of patients with heart failure discharged home. Then these patients had impaired quality of life associated with symptoms of fatigue, stress, anxiety hindering the resumption of business activity including. The prognosis is related in part to the initial cardiac rhythm present at the establishment of specialized resuscitation. Recent progress in improving mortality and neurological outcome has been achieved over the last decade with systematic implementation of a period of targeted temperature management between 32 and 34 ° C (TTM 32-34) in patients with cardiac arrest and who benefited from the completion of at least one external electrical shock when help arrived. The mechanisms underlying this improvement of neurological prognosis are many, but mainly related to an attenuation of post resuscitation syndrome that combines in one hand an inflammatory response (mediated by pro-inflammatory cytokines including interleukin 6) and secondly the formation of reperfusion injury related to the production of radical oxygen species (free radicals). While some studies have shown the feasibility of induction of this TTM 32-34 in prehospital conditions, no prospective study has evaluated the significant speed of warming in the end. An observational study in which the heating was carried passively, found that patients with an extended heating period (600 minutes) had a worse neurological outcome than patients with a duration of shorter warming (479 minutes) while a second retrospective study concluded the opposite in case of active warming . Besides the fact that these studies were observational, in the two originals randomized studies on TTM 32-34 in CA, the rate of warming was not like: * Objective 6 hours with active warming is 0.5 ° C / h in the Australian study with an OR of 5.25 (1.47 - 18.76) for the neurological prognosis * Objective 8 hours with passive warming of 0.37 ° C / h in the European study with an OR of 1.4 (1.08 - 1.81) for the neurological prognosis Although populations of two studies are obviously not comparable, it is possible that suboptimal speed of rewarming could mitigate some of the gain related to the implementation of TTM 32-34. In this context, investigators propose to conduct a randomized, single-center pilot study comparing a fast warming in a slow warming when performing a TTM 33 patients presented with a shockable cardiac arrest.
Interventions
PROCEDURELow Speed of Rewarming
Speed of rewarming will be at 0.25°C/h with specific temperature controlled external device
PROCEDUREHigh Speed of Rewarming
Speed of rewarming will be at 0.50°C/h with specific temperature controlled external device
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
University Hospital, Tours
Centre Hospitalier Departemental Vendee
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has been supported for a shockable cardiac arrest with successful resuscitation. * Coma persistent at ICU admission (Glasgow score less than or equal to 8) in the absence of sedation. If the patient is sedated in ICU admission, the glasgow score will be held the last evaluated by the doctor who provided the pre-hospital care of the patient score. * Body temperature\> 33 ° C * Specific device used to targeted temperature management at 33°C
Exclusion criteria
* Lack of witness of cardiac arrest. * Duration of no-flow\> 10 minutes (time between the onset of cardiac arrest and the start of external cardiac massage). * Duration of low-flow\> 60 minutes (the period between the start of external cardiac massage and recovery of an effective cardiac activity). * Major hemodynamic instability (dose norepinephrine and / or epinephrine \> 1 µg / kg / min to maintain MAP\> 65 mmHg). * Time between cardiac arrest and more than 480 minutes inclusion * Moribund. * Presence of histologically confirmed cirrhosis of Child class C. * Patient treatment in blocking the production of Il6 (Ro-tocilizumab or Actemra ®) * Patient under corticosteroid treatment (dose\> 5 mg of prednisolone equivalent) * Pregnant woman, parturient or lactating. * Inpatient without consent and / or deprived of liberty by a court decision. * Patient under guardianship * Inclusion in advance a research protocol with the draw, and whose primary endpoint is on interleukin-6. * Lack of social security. * Refusal of the trusted person or patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target | 48 hours | Median AUC for serum IL6 levels over time |
Countries
France
Participant flow
Recruitment details
All patients were admitted in medical-surgical ICU at local hospital of La Roche sur Yon, France. and assessed for eligibility between February 12, 2016, and May 15, 2020. Patients were included at ICU admission. Randomization occurred at the end of the hypothermia maintenance phase, i.e., 18-24 h after reaching 33 °C.
Pre-assignment details
Of 160 patients assessed for eligibility, 102 did not meet inclusion criteria, 58 were included and 50 were randomized
Participants by arm
| Arm | Count |
|---|---|
| Rewarming at 0.25°C/h Speed of rewarming will be at 0.25°C/h with specific temperature controlled external device | 25 |
| Rewarming at 0.50°C/h Speed of rewarming will be at 0.50°C/h with specific temperature controlled external device | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Rewarming at 0.25°C/h | Rewarming at 0.50°C/h | Total |
|---|---|---|---|
| Age, Continuous | 66.2 years | 53.8 years | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target
Median AUC for serum IL6 levels over time
Time frame: 48 hours
Population: One patient died between H32 and H40 and was not included in this analysis given the absence of data for the H40 and H48 time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rewarming at 0.25°C/h | Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target | 12389 pg/mL*h |
| Rewarming at 0.50°C/h | Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target | 8859 pg/mL*h |
p-value: 0.55Wilcoxon's rank test