The Cardiac Effects of Prolonged Hypothermia After Cardiac Arrest

This PhD study is a sub study in a randomized clinical controlled multicenter trial named "TTH48" (ClinicalTrials.gov Identifier: NCT01689077). The TTH48 trial examines prolonged mild therapeutic hypothermia ("MTH") at 32-34°C in 24 versus 48 hours with the primary outcome Cerebral Performance Category after 6 month in comatose out-of-hospital cardiac arrest patients. THE OVERALL AIM OF THIS PhD STUDY IS TO INVESTIGATE THE CARDIAC FUNCTION AND THE HEMODYNAMICS BY BIOCHEMICAL CARDIAC MARKERS, ECHOCARDIOGRAPHY, BY ANALYZING THE USAGE OF INOTROPES/VASOPRESSORS AND BY ANALYZING ECG DATA FOR ARRHYTHMIAS IN THE 24 VERSUS 48 HOURS MTH GROUPS.

The PhD-study contains 3 sub studies: Study 1 estimates the extend of myocardial damage resulting from the primary arrest and from the reperfusion injuries: Area under the curve of cTnT and CK-MB as 12 repeated measurements and NT-proBNP as 4 measurements post arrest -Hypothesis: There is a statistically significantly greater release of the cardiac biomarkers cTnT and NT-proBNP quantified by the area under the curve in the 24 versus the 48 hours group in the intervention period from 24 to 72 hours. Study 2 investigates MTH´s influence on systolic and diastolic function by standard and Tissue Doppler (TDI) echocardiography after 24, 48 and 72 hours. The primary endpoint is mitral annular systolic velocity ("S´ max") -Primary hypothesis: There is statistically significant improvement in S' max from the time T24 to T72 in the 48 versus the 24 hours group. -Secondary hypothesis: There is statistically significantly better systolic function at T48 measured in terms of individual S' max-change in the 48 hours group (still hypothermic) versus the 24 hours group (reached normothermia). Study 3 investigates MTH´s influence on the need for vasopressor or inotrope and the duration of arrhythmias during the first 72 hours post arrest. Primary hypothesis: There is a statistically significantly increased tendency of arrhythmias in the 48 versus the 24 hours group measured in the period from T0 to T72. Secondary hypothesis: There is a statistically significantly reduced need for inotropes in the 48 versus the 24 hours group measured by cumulative vasopressor index in the period from T0 to T72.

The patient will be treated with mild therapeutic hypothermia for 24 hours after reaching the target temperature between 32-34°C.

The patient will be treated with mild therapeutic hypothermia for 48 hours after reaching the target temperature between 32-34°C.

Inclusion Criteria: Resuscitated after cardiac arrest outside hospital with suspected cardiac triggering cause (and stabile circulation for at least 20 minutes after return of spontaneous circulation, Glasgow coma score < 8 and Age ≥ 18 years and < 80 years. Exclusion Criteria: Cardiac arrest of suspected non-cardiac triggering cause (e.g. trauma, aortic dissection, massive bleeding, hypoxia or accidental hypothermia), >60 minutes from cardiac arrest to ROSC, Time from cardiac arrest until start of cooling >4 hours, Terminal illness, Coagulopathy (medical anticoagulation treatment including thrombolysis is not a contraindication), Unwitnessed arrests with asystolia as presenting rhythm, Pregnancy, Persistent cardiogenic shock, Systolic blood pressure <80 mmHg despite vasoactive treatment and intra-aortic balloon pump CPC 3-4 before the cardiac arrest, Suspected/confirmed acute intra cerebral hemorrhage or stroke, Acute CABG or other operation in connection with performing CPR, Lack of consent from the relatives, Lack of consent from the GP and Lack of consent from the patient if he/she wakes up and is relevant.

Research Center of Emergency Medicine and Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Skejby, Denmark

Research Center of Emergency Medicine and Department of Anesthesiology and Intensive Care Medicine, Stavanger University Hospital

Jensen TH, Juhl-Olsen P, Nielsen BRR, Heiberg J, Duez CHV, Jeppesen AN, Frederiksen CA, Kirkegaard H, Grejs AM. Echocardiographic parameters during prolonged targeted temperature Management in out-of-hospital Cardiac Arrest Survivors to predict neurological outcome - a post-hoc analysis of the TTH48 trial. Scand J Trauma Resusc Emerg Med. 2021 Feb 19;29(1):37. doi: 10.1186/s13049-021-00849-7.

Grejs AM, Nielsen BRR, Juhl-Olsen P, Gjedsted J, Sloth E, Heiberg J, Frederiksen CA, Jeppesen AN, Duez CHV, Hamre PD, Soreide E, Kirkegaard H. Effect of prolonged targeted temperature management on left ventricular myocardial function after out-of-hospital cardiac arrest - A randomised, controlled trial. Resuscitation. 2017 Jun;115:23-31. doi: 10.1016/j.resuscitation.2017.03.021. Epub 2017 Apr 2.