Continuous electrodermal activity as a potential novel neurophysiological biomarker of prognosis after cardiac arrest – A pilot study

doi:10.1016/j.resuscitation.2015.06.006

Resuscitation

Volume 93, August 2015, Pages 128-135

https://doi.org/10.1016/j.resuscitation.2015.06.006 Get rights and content

Abstract

Aims

Neurological outcome prognosis remains challenging in patients undergoing therapeutic hypothermia (TH) after cardiac resuscitation. Technological advances allow for a novel wrist-worn device to continuously record electrodermal activity (EDA), a measure of pure sympathetic activity.

Methods

A prospective cohort study was performed to determine the yield of continuous EDA in patients treated with TH for coma after cardiac arrest during hypothermia and normothermia. Association between EDA parameters (event-related and nonspecific electrodermal responses (ER-EDR, NS-EDR)) and outcome measures (cerebral performance category [CPC]) (Full Outline in UnResponsivenss (FOUR) score) were assessed.

Results

Eighteen patients were enrolled. Total number of EDR (66.4 vs 12.0/24 h, p = 0.02), ER-EDR (39.5 vs 11.2/24 h, p = 0.009), median amplitude change of all EDR (0.08 vs 0.03 μSI, p = 0.03) and ER-EDR (0.14 vs 0.05 μSI, p = 0.025) were higher in patients with favorable (CPC 1–2) versus poor outcome (CPC 3–5) during hypothermia. Greater differences in EDA parameters were observed during hypothermia than normothermia. The FOUR score was correlated to the number of all EDR and median amplitudes.

Conclusions

Continuous EDA potentially opens a new avenue for autonomic function monitoring in neurocritically ill patients. It is feasible in the ICU setting, even during hypothermic states. As a measure of a complete neurophysiological circuit, it may be a novel neurophysiologic biomarker of outcome after cardiac resuscitation.

Introduction

Since the implementation of therapeutic hypothermia (TH) for comatose survivors after cardiac arrest (CA), approximately, half the patients still have poor outcome.¹ Although early identification of patients with poor prognosis is possible with good reliability by assessing electroencephalogram (EEG) background reactivity,² median nerve somatosensory evoked potentials,³ and neuron -specific enolase (NSE) levels,⁴ early identification of patients with favorable outcome remains difficult.⁵ Development of robust prognostic tools is critical, especially since it is likely that multimodal assessment will provide a more accurate prediction than any single predictor alone.⁶

Electrodermal activity (EDA), representing changes in skin potential related to an increase in sympathetic tone,⁷ is a measure of pure sympathetic activity, devoid of parasympathetic input. Because EDA involves several central nervous system structures, including the medullary reticularis nucleus, which is crucial for arousal, it may be an excellent candidate to improve outcome prognostication after CA. Older studies have shown that some EDA parameters reflect depth of coma.8, 9, 10

Until recently, EDA recordings allowed for only short-term recordings,⁷ moreover they were difficult to obtain in comatose patients.⁸ A small, wireless, battery-powered integrated sensor with conductive fabric electrodes rather than gel-based Ag/AgCl electrodes, has recently been developed.¹¹ These features allow for unobtrusive and non-invasive prolonged EDA recordings. We performed a single center prospective pilot study to evaluate the yield of prolonged EDA recordings in TH outcome.

Section snippets

Cohort description

All consecutive adult patients treated with TH for coma after CA at the Brigham and Women's Hospital were screened once TH was ordered. Patients with implanted pacemakers were excluded. The local institutional review board approved this study.

Hypothermia protocol

The institution's TH protocol has been described previously.¹² Briefly, TH is initiated within 6–12 h on comatose survivors of CA due to cardiac or pulmonary origins with successful restoration of a perfusion cardiac rhythm to a target temperature of 32–34

Cohort description

During the study period (Nov 1st 2013–May 31 2014), 26 patients were screened and 18 patients entered the study (Table 1, Fig. 1). None of them had any known prior autonomic disturbances. A total of 44% of the patients remained comatose during the entire hospital stay; - 2 patients in vegetative or minimal conscious states ultimately died because of nonneurologic issues (care withdrawn because of diffuse advanced adenocarcinoma, and known patient wishes respectively). Less than half of the

Discussion

We demonstrate that continuous EDA recording is feasible in patients undergoing therapeutic hypothermia, and that it may be a novel prognostic neurophysiological biomarker after cardiac arrest. Most of the EDA parameters during hypothermia and several parameters early after rewarming were strongly associated with favorable CPC scores (1–2). The patients who had poor outcome (CPC 3–5) throughout their post CA hospital admission exhibited fewer EDRs with lower median amplitudes than the patients

Conclusion

In conclusion, we demonstrated for the first time that EDA responses can be reliably recorded in patients undergoing therapeutic hypothermia, and prolonged EDA recording may be a novel neurophysiological biomarker of prognosis after cardiac arrest. This technology is practical to implement in the ICU setting without interference with clinical care, as opposed to the current neurophysiological methods (EEG and evoked potentials) that may be technically challenging and require extensive hardware

Conflicts of Interest and Disclosures Statement

Affectiva, Inc. donated the biosensors used in this study. The company was not involved in this study at any point. Dr. Alvarez was funded by the Swiss National Science Foundation. during the research period, grant: P2GEP3_148510 and the Gottfried und Julia Bangerter-Rhyner Foundation. Dr. Reinsberger has received research funding from the American Epilepsy Society. and is a consultant for SleepMed. Dr. Scirica reports grants from AstraZeneca, grants from Bristol-Myers Squibb, grants from

Acknowledgments

The authors would like to thank the Epilepsy Research Group at the Brigham and Women's Hospital for their valuable advice and insights during the manuscript preparation.

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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.2015.06.006.

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Clinical PaperContinuous electrodermal activity as a potential novel neurophysiological biomarker of prognosis after cardiac arrest – A pilot study☆

Abstract

Aims

Methods

Results

Conclusions

Introduction

Section snippets

Cohort description

Hypothermia protocol

Cohort description

Discussion

Conclusion

Conflicts of Interest and Disclosures Statement

Acknowledgments

Neuropsychologia

Neurosci Lett

Diabetes Metab

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

N Engl J Med

Early EEG correlates of neuronal injury after brain anoxia

Neurology

Prediction of poor outcome within the first 3 days of postanoxic coma

Neurology

Neuron-specific enolase correlates with other prognostic markers after cardiac arrest

Neurology

“Are you sure she will not recover?” Multimodal prognostication provides increased certainty about poor outcomes prediction

Crit Care Med

Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia

Crit Care Med

Sympathetic skin response

Differentiation of autonomic nervous activity in different stages of coma displayed by power spectrum analysis of heart rate variability

Eur Arch Psychiatry Clin Neurosci

Spontaneous activity of autonomic functions in coma due to drug overdose

Arch Toxicol

Clinical Paper
Continuous electrodermal activity as a potential novel neurophysiological biomarker of prognosis after cardiac arrest – A pilot study☆