Clinical paperThe influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest☆
Introduction
Cardiac arrest (CA) is a common cause of death with an annual incidence of 38 out-of-hospital cardiac arrests (OHCA) per 100,000 population in Europe.1 An increased survival from all-rhythm OHCA has been reported in several studies.2, 3 Contributing factors to this improvement include an increase in bystander cardiopulmonary resuscitation, improved chest compressions,4 increased cardiac interventions5, 6 and improved post cardiac arrest care, including induced hypothermia.7, 8 Despite these measures, mortality following hospital admission remains high, between 50 and 86% in Scandinavia9, 10 and 71% in the UK.11
The brain is particularly vulnerable to circulatory arrest due to its high metabolic ratio and limited energy reserves. In the large BRCT studies,12, 13 cardiac cause of death dominated, but in more recent studies brain-related causes account for two-thirds of all mortality after admission to ICU following OHCA.14, 15 Moreover, the majority of survivors suffer some degree of cognitive impairment.16 Mild hypothermia to 33 °C was neuroprotective in animal models17 and is a recommended therapy after CA,18 based on two randomized controlled trials.7, 8
The neurological assessment of prognosis following CA is critical for mortality since a “poor-prognosis-statement” often leads to withdrawal of life-sustaining treatments (WLST) and subsequent death of the patient. Neurological prognostication is based on a clinical neurological examination and electrophysiological investigations (electroencephalography, EEG, and somatosensory-evoked potentials, SSEP) and supported by neuroradiological examinations and biomarkers.18, 19, 20 The specificity of these instruments increase with time after CA and a well-founded judgment of prognosis can be made at 72 h after CA in the majority of patients not treated with hypothermia.20 Hypothermic treatment has been found to make a clinical neurological examination less reliable, possibly related to an increased use21 and decreased clearance22 of sedative medication. Therefore, delayed prognostication has been recommended in patients treated with hypothermia.19 Moreover, the reliability of a clinical brain death diagnosis has lately been questioned after CA and induced hypothermia.23
We introduced hypothermia treatment as part of a prospective observational study in 2003 and included delayed prognostic evaluation 72 h after return to normothermia (4.5–5 days after CA) in the protocol.16, 24, 25 In the present study, we investigate the influence of hypothermia and delayed prognostication on the mode of death after CA. Specifically, we characterize a small group of patients who were declared brain dead and became organ donors.
Section snippets
Methods
In a prospective observational study, the background material consisted of all patients who were treated with hypothermia after CA at the intensive care unit (ICU) and thoracic ICU at Lund University Hospital from January 2003 to December 2008. Comatose CA-survivors, with return of spontaneous circulation and without contraindications for hypothermia, were included and cooled to 33 °C for 24 h and rewarmed during 8 h as previously described.16, 25 Ethical permission was obtained from the Regional
Results
A total of 162 consecutive CA-patients with OHCA or in-hospital CA (IHCA) were included in the study. For patients characteristics, see Table 1. The mortality was 53% at hospital discharge and 54% at 6 months (Table 3), similar for OHCA and IHCA. The majority of the survivors (86%) had a good neurological function (CPC 1–2) at hospital discharge with further improvement at 6 months (Table 3). Eleven patients (14%) had major neurological disability (CPC 3) at hospital discharge, but only four
Discussion
We found that the majority of CA-patients treated with hypothermia died after WLST based on a prediction of poor neurological prognosis due to presumed severe hypoxic-ischemic brain injury.
It cannot be excluded that false predictions of poor prognosis may have affected our results as may occur in a minority of hypothermia-treated patients if prognostication is based solely on the clinical examination at 72 h after CA.21, 29 However, we liberally used multiple prognostic tools24 and delayed
Conclusions
We found that WLST due to presumed severe hypoxic-ischemic brain injury is the major cause of death in hypothermia-treated CA-victims. Multimodal prognostication according to current guidelines may prolong the time to death but without survival to a vegetative state. Young patients with a long time to ROSC may become brain dead and subsequent organ donors.
Conflict of interest statement
None.
Acknowledgments
The authors thank Dr Roger Siemund, Department of Radiology, Skåne University Hospital, Lund for help with review of neuroimaging.
Financial support. Regional Research Support, Region Skåne, Skåne University Hospital, Lund, to Tobias Cronberg, Malin Rundgren and Hans Friberg. ALF (Academic Learning and Research grants), Lund University Medical Faculty to Tobias Cronberg and Hans Friberg.
References (35)
- et al.
Incidence of EMS-treated out-of-hospital cardiac arrest in Europe
Resuscitation
(2005) - et al.
Improving outcome after out-of-hospital cardiac arrest by strengthening weak links of the local Chain of Survival; quality of advanced life support and post-resuscitation care
Resuscitation
(2010) - et al.
Effect of bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients in Sweden
Resuscitation
(2000) - et al.
Systematic review of percutaneous cardiopulmonary bypass for cardiac arrest or cardiogenic shock states
Resuscitation
(2006) - et al.
Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest
Resuscitation
(2007) - et al.
Major differences in 1-month survival between hospitals in Sweden among initial survivors of out-of-hospital cardiac arrest
Resuscitation
(2006) - et al.
In-hospital factors associated with improved outcome after out-of-hospital cardiac arrest. A comparison between four regions in Norway
Resuscitation
(2003) - et al.
Long-term neurological outcome after cardiac arrest and therapeutic hypothermia
Resuscitation
(2009) - et al.
European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support
Resuscitation
(2010) - et al.
Assessment of outcome after severe brain damage
Lancet
(1975)
The natural course of neurological recovery following cardiopulmonary resuscitation
Resuscitation
Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective
Heart
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest
N Engl J Med
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia
N Engl J Med
Outcome following admission to UK intensive care units after cardiac arrest: a secondary analysis of the ICNARC Case Mix Programme Database
Anaesthesia
Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest
N Engl J Med
A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest
N Engl J Med
Cited by (285)
Association between prehospital airway type and oxygenation and ventilation in out-of-hospital cardiac arrest
2023, American Journal of Emergency Medicine
- ☆
A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.09.015.