Background
Out-of-hospital cardiac arrest (OHCA) is associated with a high mortality. Average survival to hospital discharge for OHCA patients in England in 2013 was only 8.6% [
1]. Despite advances in post-resuscitation care management, about 50% of resuscitated patients from cardiac arrest (CA) die or have a poor neurological prognosis. One of the major causes of mortality following CA is severe neurological damage due to post-anoxic brain injury [
2]. The cost and length of stay is higher in patients with poor neurological outcome, which can be up to £50,000 per survivor [
3]. There are further considerations like community care and rehabilitation, quality of life and emotional impact on the family. It is therefore essential to predict neurological outcome in this group of patients as early as possible, in order to potentially enable early withdrawal of life-saving treatment (WLST) in those patients predicted to have a poor outcome.
Cardiac arrest causes a significant pathological and clinical impact, known as ‘post-cardiac arrest syndrome’ [
4].
The four key components of post-cardiac arrest syndrome were identified as:
I.
Post-cardiac arrest brain injury;
II.
Post-cardiac arrest myocardial dysfunction;
III.
Systemic ischaemic / reperfusion injury;
IV.
Persisting precipitating pathology
Post-resuscitation care aims to reduce this impact; it has developed and evolved significantly since 2003, following recommendations by the Advanced Life Support (ALS) task force of the International Liaison Committee on Resuscitation (ILCOR) to implement Therapeutic Hypothermia (TH) in unconscious survivors following OHCA [
5]. The 2015 European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) guidelines on post-resuscitation care made strong recommendations to avoid severe hyperoxia (large amounts of oxygen) for patients following CA [
6‐
8], emergency cardiac catheterisation ± immediate percutaneous coronary intervention (PCI) and targeted temperature management (TTM) between 32–36 °C [
9].
In 2015, ERC-ESICM recommended a multimodal prognostication approach for comatose survivors following CA [
10]. It was based on a robust analysis of evidence and provided a practical recommendation. Hence, it formed the basis of ERC guidelines on resuscitation published in 2015.
The key recommendations are summarised below with a great emphasis on the fact that they should be used in conjunction with each other:
2.
Myoclonus and status myoclonus
-
Using the term status myoclonus to indicate a continuous and generalised myoclonus persisting > 30 min in comatose survivors of CA;
-
Using the presence of a status myoclonus within 48 h from ROSC in combination with other predictors to predict poor outcome in comatose survivors of CA, either TH or non-TH treated.
3.
Bilateral absence of SSEP (somatosensory-evoked potentials) N20 wave
-
Using bilateral absence of SSEP N20 wave at ≥ 72 h from ROSC to predict outcome in comatose survivors following CA treated with controlled temperature;
-
There was suggestion to use SSEP at ≥ 24 h from ROSC to predict outcome in comatose survivors following CA not treated with controlled temperature.
4.
Electroencephalogram (EEG)
The quality of evidence on which the above strategy is developed and recommended is low to very low. Golan et al. in their meta-analysis showed that only three tests accurately predicted poor prognosis with low false positive rates (FPR): bilateral absences of pupillary reflex more than 24 h after CA (FPR 2%, confidence interval (CI) 1–6%), bilateral absence of corneal reflex more than 24 h post CA (FPR 4%, CI 1–9%) and bilateral absence of SSEP between day 1 and 7 (FPR 3%, CI 1–7%). FPR were higher for a Glasgow Coma Score-Motor response (GCS-M) less than 2, unfavourable EEG patterns, myoclonic status epilepticus and elevated NSE [
11].
Also, despite the recommended delayed prognostication strategy, a large single-centre study of 326 patients found that 30% of patients have delayed awakening (i.e. still in coma after TTM and sedation withdrawal) and up to 20% remained comatose at 1 week [
12].
There are other modalities like bispectral index (BIS) monitor and infrared pupillometry, which are currently being trialled to predict neurological outcome [
13‐
15]. These are non-invasive techniques and can be used in emergency or intensive care settings with a certain degree of training. We suggest, given the available low quality of evidence and recommended multimodal approach, that there is definitely a place for a new modality. This study aims to look at the available evidence to support early use of Bispectral Index and burst suppression (BR) monitoring especially in the emergency department (ED) to help predict neurological outcome.
BIS monitor
BIS monitor is the brain monitoring system for critical care developed by Covidien-Medtronic. A sensor is placed on the patient’s forehead and raw electroencephalogram (EEG) data is collected. The EEG information is processed by the system and calculates a number between 0 and 100. This provides a direct measure of a patient’s level of consciousness. See Table
1 for interpretation of BIS value and clinical state.
Table 1
BIS value and clinical states
100 | Awake: responds to normal voice |
80 | Light to moderate sedation: may respond to loud commands |
60 | General anaesthesia |
40 | Deep hypnotic state |
20 | Burst suppression |
0 | Flat-line EEG |
BSR
During the burst suppression phase, suppression wave (amplitude < 0.5 μV) follows burst wave (amplitude > 0.5 μV). The suppression ratio is expressed as a percentage and is the ratio of total duration of suppression wave to total duration of analysis [
16].
Primary hypothesis
In a patient who remains comatose following ROSC after cardiac arrest, low BIS value (< 20) and high burst suppression ratio is a predictor of poor neurological outcome. The aim of this study is to analyse the available evidence to support early use of BIS and BSR monitoring in the ED to help predict neurological outcome.
Discussion
OHCA is associated with significant mortality or may have a poor neurological outcome. Prognostication of OHCA survivors poses a significant challenge. The current delayed multimodal prognostication model is recommended on the basis of currently available low to very low quality of evidence. BIS monitoring is currently not widely used; however, it is relatively simple to use, easy to train operators, non-invasive, can be used in emergency and intensive care settings and multiple readings can be available at various timelines during post-resuscitation care management. This review will synthesize the evidence available on the use of BIS monitors at various timelines after achieving ROSC and may help contribute as an additional modality to the current multimodal prognostication model.
Acknowledgements
The authors would like to acknowledge the contribution of Mr. Philip Barlow, who assisted in developing the search strategy.
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