Clinical trial NCT02033720: Study of Survivors of Different Types of Cardiac Arrest and Their Neurological Recovery
Official title: Neurological Outcomes After Cardiac Arrest in Pulseless Electrical Activity in Comparison to Asystole. Are All Non-shockable Rhythms the Same?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Postcardiac Arrest
Pulseless Electrical Activity
Asystole
Keywords: postcardiac arrest
post cardiac arrest syndrome
post cardiac arrest hypothermia
pulseless electrical activity
asystole
therapeutic hypothermia
therapeutic hypothermia after cardiac arrest
therapeutic hypothermia neurologic outcome
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2014-01-13
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients admitted to the intensive care unit (ICU) with a diagnosis of postcardiac arrest between Jan 2008 and Dec 2012 will be examined.

Brief summary: After successful resuscitation from certain types of cardiac arrest, total body cooling is now a well established treatment that improves the chances of the brain recovering. This however, has only been definitively proven after a certain type of cardiac arrest that is "ventricular fibrillation / ventricular tachycardia". The purpose of this study is to explore if total body cooling is beneficial for patients recovering from another type of cardiac arrest that is "pulseless electrical activity".

HYPOTHESIS:

Patients undergoing post-cardiac arrest therapeutic hypothermia have better neurological outcomes if their initial arrest rhythm is pulseless electrical activity (PEA) in comparison to asystole.

Detailed description: STUDY RATIONALE AND BACKGROUND INFORMATION:

After successful resuscitation from cardiac arrest the body experiences a period of global reperfusion. During this period, patients may show signs of myocardial stunning, lactic acidosis, neurological injury and reperfusion syndrome. This constellation of findings constitutes what is known as post-cardiac arrest syndrome. The brain appears to be one of the most vulnerable organs to injury during this reperfusion phase and varying degrees of cognitive impairment may be the end result. Inducing mild therapeutic hypothermia has been shown to be protective for the brain in this setting and has been demonstrated to improve neurological recovery. The evidence for this however, is only conclusive in cases where the arrest is in a shockable rhythm i.e. pulseless ventricular tachycardia and ventricular fibrillation.

In 2002, two randomized controlled trials were published showing an improvement in neurological outcomes in patients treated with mild therapeutic hypothermia post resuscitation from shockable cardiac arrest. Therapeutic hypothermia has since been widely adopted by most authorities as part of the comprehensive treatment bundle for post cardiac arrest syndrome. Whether there is any benefit for patients arrested in non-shockable rhythms however, is a matter of controversy. Some have reported improved mortality and better neurological outcomes with therapeutic hypothermia in this patient population. Others have reported no benefit or even a trend towards harm. And although the matter remains controversial, the recommendation still stands for therapeutic hypothermia to be offered for all comatose survivors of cardiac arrest whatever the arrest rhythm.

Most previous reports have examined the differences between shockable and non-shockable rhythms in terms of neurological outcome and mortality rates after therapeutic hypothermia. To our knowledge, no study has examined the differences in outcome between the two types of non-shockable rhythms, that is pulseless electrical activity (PEA) and asystole. We hypothesize that during PEA arrests, patients may retain some degree of cerebral perfusion and hence have better neurological outcomes post-resuscitation. That is in contrast to asystole where patients are likely to have no cerebral perfusion. In this study we attempt to detect any possible differences in neurological recovery (as indicated by the Cerebral Performance Category scale on hospital discharge) after therapeutic hypothermia, between patients arrested in PEA arrest and those arrested in asystole.

Eligibility criteria: Inclusion Criteria:

* Admission to adult ICU (age ≥18 years) at London Health Sciences Centre
* Primary reason for ICU admission: postcardiac arrest
* Both in-hospital and out-of-hospital cardiac arrest will be included
* ICU admission between Jan 2008 and Dec 2012.

Exclusion Criteria:

- ICU admissions primarily for reasons other than cardiac arrest.

Primary outcomes:
measure: Cerebral performance category score on hospital discharge
timeFrame: Upon discharge from hospital, assessed up to 36 months postcardiac arrest
Secondary outcomes:
measure: Hospital length of stay postcardiac arrest
timeFrame: Days spent in hospital after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest
measure: Intensive care unit length of stay postcardiac arrest
timeFrame: Days spent in the intensive care unit after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest
measure: Neurological status after hospital discharge
timeFrame: Assessed up to 12 months from hospital discharge
Other outcomes:
measure: Time to obeying commands
timeFrame: Assessed up to 21 days postcardiac arrest
measure: Documented negative neurological prognosticators
timeFrame: Upon withdrawal of life support, assessed up to 3 months postcardiac arrest
measure: Post arrest neurological investigations (including imaging studies)
timeFrame: Performed within 21 days from cardiac arrest
Locations:
city: London
country: Canada
facility: University Hospital, London Health Sciences Centre, University of Western Ontario
state: Ontario
city: London
country: Canada
facility: Victoria Hospital, London Health Sciences Centre, University of Western Ontario
state: Ontario
Study officials:
affiliation: Western University, Canada
name: Eyad Althenayan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Western University, Canada
name: Philip Jones, MD, FRCPC
role: STUDY_DIRECTOR
affiliation: Western University, Canada
name: Bryan Young, MD, FRCPC
role: STUDY_CHAIR
affiliation: Western University, Canada
name: Ahmed F Hegazy, MD, FRCPC
role: STUDY_DIRECTOR
affiliation: Western University, Canada
name: Ana Igric, MD, FRCSC
role: STUDY_DIRECTOR
affiliation: Western University, Canada
name: Carolyn Benson, MD
role: STUDY_DIRECTOR
References:
citation: Holzer M. Targeted temperature management for comatose survivors of cardiac arrest. N Engl J Med. 2010 Sep 23;363(13):1256-64. doi: 10.1056/NEJMct1002402. No abstract available.
citation: Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002 Feb 21;346(8):557-63. doi: 10.1056/NEJMoa003289.
citation: Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. doi: 10.1056/NEJMoa012689.
citation: Hazinski MF, Nolan JP, Billi JE, Bottiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW, Jacobs I, Kleinman ME, Kloeck W, Koster RW, Lim SH, Mancini ME, Montgomery WH, Morley PT, Morrison LJ, Nadkarni VM, O'Connor RE, Okada K, Perlman JM, Sayre MR, Shuster M, Soar J, Sunde K, Travers AH, Wyllie J, Zideman D. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010 Oct 19;122(16 Suppl 2):S250-75. doi: 10.1161/CIRCULATIONAHA.110.970897. No abstract available.
citation: Arrich J; European Resuscitation Council Hypothermia After Cardiac Arrest Registry Study Group. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007 Apr;35(4):1041-7. doi: 10.1097/01.CCM.0000259383.48324.35.
citation: Testori C, Sterz F, Behringer W, Haugk M, Uray T, Zeiner A, Janata A, Arrich J, Holzer M, Losert H. Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation. 2011 Sep;82(9):1162-7. doi: 10.1016/j.resuscitation.2011.05.022. Epub 2011 Jun 12.
citation: Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pene F, Vivien B, Varenne O, Carli P, Jouven X, Empana JP, Cariou A. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation. 2011 Mar 1;123(8):877-86. doi: 10.1161/CIRCULATIONAHA.110.987347. Epub 2011 Feb 14.