Elsevier

Resuscitation

Volume 84, Issue 3, March 2013, Pages 337-342
Resuscitation

Clinical paper
The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest

https://doi.org/10.1016/j.resuscitation.2012.09.015Get rights and content

Abstract

Background

Brain injury is considered the main cause of death in patients who are hospitalized after cardiac arrest (CA). Induced hypothermia is recommended as neuroprotective treatment after (CA) but may affect prognostic parameters. We evaluated the effect of delayed neurological prognostication on the mode of death in hypothermia-treated CA-survivors.

Study design

Retrospective study at a Swedish university hospital, analyzing all in-hospital and out-of-hospital CA-patients treated with hypothermia during a 5-year period. Cause of death was categorized as brain injury, cardiac disorder or other. Multimodal neurological prognostication and decision on level of care was performed in comatose patients 72 h after rewarming. Neurological function was evaluated by Cerebral Performance Categories scale (CPC).

Results

Among 162 patients, 76 survived to hospital discharge, 65 of whom had a good neurological outcome (CPC 1–2), and 11 were severely disabled (CPC 3). No patient was in vegetative state. The cause of death was classified as brain injury in 61 patients, cardiac disorder in 14 and other in 11. Four patients were declared brain dead and became organ donors. They were significantly younger (median 40 years) and with long time to ROSC. Active intensive care was withdrawn in 50 patients based on a statement of poor neurological prognosis at least 72 h after rewarming. These patients died, mainly from respiratory complications, at a median 7 days after CA.

Conclusion

Following induced hypothermia and delayed neurological prognostication, brain injury remains the main cause of death after CA. Most patients with a poor prognosis statement died within 2 weeks.

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.

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    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.

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