Clinical paperNSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest☆
Introduction
Sudden cardiac arrest is still a major cause of death.1 Since therapeutic hypothermia (TH) has been introduced as a standardized therapy for resuscitation survivors, prognosis has improved significantly.2, 3, 4 However, prognostication has become more challenging, and there is only limited evidence to predict the outcome of hypothermic cardiac arrest survivors treated with TH.5
Patients treated with TH are usually pharmacologically sedated and paralyzed in order to prevent shivering,6 rendering established prognostic methods such as a basic neurological examination with pupillary reflexes, corneal reflexes and motor response in the first 72 h difficult.7 Serum biochemical markers such as neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) have been proposed as early prognostic markers.8, 9, 10, 11, 12 These markers have been evaluated in patients treated with hypothermia and are available earlier than 72 h after the return of spontaneous circulation (ROSC).13, 14, 15
The aim of our study was to evaluate these biochemical markers in a clinical routine compared to a simple neurological examination.
Section snippets
Methods
Our study was performed in the intensive care unit (ICU) of Medizinische Klinik Innenstadt (Ludwig-Maximilians-Universität), Munich, Germany. It was a retrospective data analysis of all patients in the years 2007–2012.
The main inclusion criterion was coma after cardiac arrest with ROSC. Patients needed to be 18 years or older. Furthermore the decision to apply TH needed to be made by the attending physician. The patients also needed to survive the first night in the ICU.
Exclusion criteria were
Results
In the years 2007–2012, 123 patients (79.7% male, mean age 63 ± 14 years) were treated with TH (Table 1); one third (30.1%) had a known severe chronic illness according to APACHE II.17 Nearly all patients (89.4%) were out-of-hospital resuscitation survivors, and 74.8% had a witnessed cardiac arrest. Bystanders initiated CPR in 55.7% of all cases. During CPR, two thirds of all patients had a shockable initial rhythm (66.4%). The cumulative adrenaline dose administered during CPR was 3.0 mg (0.0–45.0
Discussion
Some authors suggest a predictive value for serum S-100B for patients without TH treatment and for patients treated with TH.13, 15, 20, 21 Two studies showed that TH has no influence on S-100B levels15, 20 with one study contradicting the results.13 The advantages of measuring S-100B are its short half-life of 30 min22 and earlier appearance in the serum compared to NSE. Due to the early appearance, it has been suggested that S-100B is a significant predictor already on admission. In our study,
Conclusion
Prognostication of comatose resuscitation survivors who receive treatment with TH is still very challenging. NSE and S-100B levels are associated with the outcome, as well as NSE progression and an absent motor response on day 3. However, all tests had false-positive results predicting a poor outcome. The use of previously described cut-off values was insufficiently predictive of neurologic outcome. Caution should be exercised in the use of these tests to provide neuroprognostication.
Conflict of interest
There is no conflict of interest.
Authors’ contributions
All of the authors have made substantial contributions to the following: (1) the concept and design of the study, acquisition of data, and analysis and interpretation of data; (2) drafting the article or revising it critically in regards to important intellectual content; (3) final approval of the version to be submitted. R. Gärtner, J. Schopohl and M. Angstwurm were responsible for patient treatment as attending physicians, and M. Angstwurm and T. Zellner were responsible for the concept and
Acknowledgements
We would like to thank Mrs. Rottenkolber for her statistical advice and Mrs. Maslov for her help collecting the data. No additional funding was received.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.03.021.