Elsevier

Resuscitation

Volume 93, August 2015, Pages 164-170
Resuscitation

Clinical Paper
Neurological prognostication after cardiac arrest and targeted temperature management 33 °C versus 36 °C: Results from a randomised controlled clinical trial

https://doi.org/10.1016/j.resuscitation.2015.04.013Get rights and content

Abstract

Background

The reliability of some methods of neurological prognostication after out-of-hospital cardiac arrest has been questioned since the introduction of induced hypothermia. The aim of this study was to determine whether different treatment temperatures after resuscitation affected the prognostic accuracy of clinical neurological findings and somatosensory evoked potentials (SSEP) in comatose patients.

Methods

We calculated sensitivity and false positive rate for Glasgow Coma Scale motor score (GCS M), pupillary and corneal reflexes and SSEP to predict poor neurological outcome using prospective data from the Target Temperature Management after Out-of-Hospital Cardiac Arrest Trial which randomised 939 comatose survivors to treatment at either 33 °C or 36 °C. Poor outcome was defined as severe disability, vegetative state or death (Cerebral Performance Category scale 3–5) at six months.

Results

313 patients (33%) were prognostically assessed; 168 in the 33 °C, and 145 in the 36 °C group. A GCS M ≤2 had a false positive rate of 19.1% to predict poor outcome due to nine false predictions. Bilaterally absent pupillary reflexes had a false positive rate of 2.1% and absent corneal reflexes had a false positive rate of 2.2% due to one false prediction in each group. The false positive rate for bilaterally absent SSEP N20-peaks was 2.6%.

Conclusions

Bilaterally absent pupillary and corneal reflexes and absent SSEP N20-peaks were reliable markers of a poor prognosis after resuscitation from out-of-hospital cardiac arrest but low GCS M score was not. The reliability of the tests was not altered by the treatment temperature.

Introduction

Brain injury is the predominant cause of death after resuscitation from out-of-hospital cardiac arrest.1, 2 Induced hypothermia has been reported to improve mortality and long-term neurological function in these circumstances.3, 4 Thus, since 2005 this treatment has been recommended in international post-cardiac arrest guidelines.5 Several uncontrolled studies suggest existing methods of neurological prognostication for comatose patients after resuscitation from cardiac arrest are affected by hypothermia treatment.6, 7, 8, 9, 10, 11, 12 Consequently, current recommendations suggest that prognostic assessment should be multimodal and delayed beyond the previously recommended 72 h after cardiac arrest.13, 14 The field has become even more complex since the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial found no differences in mortality or neurological outcome in patients randomised to 33 °C or 36 °C.15, 16 The present study examines whether these treatment temperatures affected the prognostic reliability of clinical findings and somatosensory evoked potentials (SSEP) for comatose patients in the TTM trial.

Section snippets

Materials and methods

This study, approved by the TTM trial steering committee before data analysis, is a post hoc analysis of prospectively collected data from 939 adult comatose survivors of out-of-hospital cardiac arrest of primary cardiac origin between November 2010 and January 2013. The TTM trial design, statistical analysis plan, and primary, secondary and tertiary outcomes have previously been published.15, 16, 17, 18 The trial is registered at clinicaltrials.gov NCT01020916. Briefly, a target core

Patients

The baseline characteristics of the intervention groups (Table 1) were similar. Of the 939 included patients, 452 regained consciousness and 139 died before prognostic assessments were performed (Fig. 1). In these 139, presumed causes of death were cerebral injury in 44 (32%); 16 of whom were diagnosed brain dead and five had myoclonic status epilepticus. Sixty-three (45%) died of cardiac or haemodynamic causes and 32 (23%) died of multi-organ failure. Prognostic assessment was not performed in

Discussion

Induced hypothermia treatment has made the validity of previously acknowledged prognostic clinical and SSEP findings6, 7, 8, 9, 10, 11, 21, 22 for comatose patients after cardiac arrest questionable. In this study, using prospectively collected data from 939 patients with out-of-hospital cardiac arrest of primary cardiac origin, we found that different target treatment temperatures of 33 °C and 36 °C had no significant influence on the prognostic value of GCS M score, bilateral absent pupillary

Authors’ contribution

ID and TC designed the study and wrote the first draft of the manuscript. JH and MK contributed to the present study concept and design. MK and JC were principal investigators in the TTM trial. NN was the chief-investigator of the TTM trial and participated in the design and development of the present study. SU was study statistician.

All authors of the manuscript were involved in the analysis and interpretation of the data and reviewed and edited the manuscript.

Funding

The TTM-trial and the present study was funded by independent research grants from the non-profit or governmental agencies: Swedish Heart Lung Foundation (grant no. 20090275); Arbetsmarknadens försäkringsaktiebolag AFA-Insurance Foundation (grant no. 100001); The Swedish Research Council (grant no. 134281, 296161, 286321); Regional research support, Region Skåne; Governmental funding of clinical research within the Swedish NHS (National Health Services) (grant no. M2010/1837, M2010/1641, 353301

Conflict of interest statement

ID, JH, MK, SU, JW, JC, CH, TC have no conflicts of interests to report. HF reports personal fees from Natus Inc, and personal fees from Bard Medical. NN reports personal fees from Bard Medical.

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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.2015.04.013.

    1

    These authors contributed equally to the manuscript.

    2

    A complete list of investigators participating in TTM trial is available in the Supplemental Data file.

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