Bispectral Index to Predict Neurological Outcome Early After Cardiac Arrest

doi:10.1016/j.resuscitation.2014.09.009

Resuscitation

Volume 85, Issue 12, December 2014, Pages 1674-1680

https://doi.org/10.1016/j.resuscitation.2014.09.009 Get rights and content

Abstract

Aim of the study

To address the value of continuous monitoring of bispectral index (BIS) to predict neurological outcome after cardiac arrest.

Methods

In this prospective observational study in adult comatose patients treated by therapeutic hypothermia after cardiac arrest we measured bispectral index (BIS) during the first 24 hours of intensive care unit stay. A blinded neurological outcome assessment by cerebral performance category (CPC) was done 6 months after cardiac arrest.

Results

Forty-six patients (48%) had a good neurological outcome at 6-month, as defined by a cerebral performance category (CPC) 1-2, and 50 patients (52%) had a poor neurological outcome (CPC 3-5). Over the 24 h of monitoring, mean BIS values over time were higher in the good outcome group (38 ± 9) compared to the poor outcome group (17 ± 12) (p < 0.001). Analysis of BIS recorded every 30 minutes provided an optimal prediction after 12.5 h, with an area under the receiver operating characteristic curve (AUC) of 0.89, a specificity of 89% and a sensitivity of 86% using a cut-off value of 23. With a specificity fixed at 100% (sensitivity 26%) the cut-off BIS value was 2.4 over the first 271 minutes. In multivariable analyses including clinical characteristics, mean BIS value over the first 12.5 h was a predictor of neurological outcome (p = 6E-6) and provided a continuous net reclassification index of 1.28% (p = 4E-10) and an integrated discrimination improvement of 0.31 (p = 1E-10).

Conclusions

Mean BIS value calculated over the first 12.5 h after ICU admission potentially predicts 6-months neurological outcome after cardiac arrest.

Introduction

Successfully resuscitated cardiac arrest remains a condition with a high mortality rate, even when applying the best medical care to the patients.1, 2, 3, 4 This high mortality of about fifty percent of the patients admitted to the hospital after successful pre-hospital resuscitation is mainly due to neurological impairment consecutive to the anoxic period during cardiac arrest and possibly during reperfusion.5, 6 The ability to predict outcome early after cardiac arrest would represent a major breakthrough towards personalized medicine by adapting the treatment strategy individually to the patient. This early prediction would allow avoiding futile healthcare to patients with irreversible neurological damage while maintaining resources in patients most likely to benefit. However, neurological prognostication of comatose patients after successful resuscitation and admission to the intensive care unit (ICU) remains a challenge.⁷

Several studies have focused on the prognostic value of biomarkers and electrophysiological parameters, but none could demonstrate an accurate prediction of outcome within the first 24 hours after cardiac arrest in hypothermia-treated patients.7, 8, 9, 10 Thus, there is an unmet need for early prediction tools. The actual lapse of time to reliably predict outcome, generally 24, 48 or even 72 hours after cardiac arrest, might be too lengthy if therapeutic decisions on highly invasive acute cardiac assistance have to be taken.11, 12 In previous reports, bispectral index (BIS), a processed electroencephalogram, initially designed to assess the depth of anesthesia, has potential to predict outcome early after cardiac arrest.13, 14, 15, 16, 17 In these studies, either BIS value monitored at a single time-point or the lowest recorded BIS value were considered in prediction analyses.

The aim of this study was to refine the value of BIS as an early predictor of outcome after cardiac arrest. Using serial measurements of BIS over the first 24 hours after admission to the ICU, we determined BIS cut-off values and time of recording providing optimal prediction of outcome.

Section snippets

Patients

We included all successfully resuscitated adult cardiac arrest patients enrolled in a prospective local registry admitted from February 2009 to June 2013 to our general ICU. Part of the patients have been involved in previous studies, although none of these addressed the prognostic value of continuous BIS monitoring.16, 18, 19, 20 All patients were older than 18 years, unconscious (Glasgow coma score below or equal to 8) and received induced hypothermia at 33 °C with sedation and neuromuscular

Patients

Over the four year enrollment period, 121 patients were admitted to our ICU after cardiac arrest. Twenty-five patients had to be excluded (Figure 1). Thus, 96 patients were enrolled in this study. Median time from ROSC to first BIS measurement was 197 [166–246] minutes and time to target temperature was 300 [237–391] minutes. Median doses of midazolam, fentanyl and cisatracurium were respectively: 0.16 [0.12-0.25] mg/kg/h, 1.69 [0.99-2.4] μg/kg/h and 0.11 [0.08-0.12] mg/kg/h. There was no

Discussion

This study supports the hypothesis that continuous monitoring and calculation of mean BIS during the first 24 hours after ICU admission allows an early and accurate prediction of outcome. We determined cut-off values for BIS and duration of monitoring that allow optimal prediction. BIS monitoring had an additive prognostic value to standard clinical parameters.

Patients with good and poor neurological outcome differed in terms of age, time to ROSC, illness severity score (SAPS II) and initial

Conclusions

Calculation of the mean BIS value over the first 12.5 hours after ICU admission might be another potential predictor of neurological outcome after cardiac arrest. Further studies are warranted to confirm and refine these findings.

The data of this paper do not overlap with previous publications and the manuscript, including related data, figures and tables, have not been published previously and the manuscript is not under consideration elsewhere.

Conflicts of interest: None.

Financial support:

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgements

We are grateful to Jacqueline Kieffer for her meticulous work for data extraction. We thank Loredana Jacobs, Mélanie Vausort, Christelle Nicolas and Bernadette Leners for technical assistance.

This work was supported by grants from the Ministry of Culture, Higher Education and Research of Luxembourg.

References (30)

O. Tomte et al.
Strong and weak aspects of an established post-resuscitation treatment protocol-A five-year observational study
Resuscitation
(2011)
J.P. Nolan et al.
Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke
Resuscitation
(2008)
T. Oksanen et al.
Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia
Resuscitation.
(2009)
M. Rundgren et al.
Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia
Resuscitation.
(2009)
T. Cronberg et al.
Neurological prognostication after cardiac arrest--recommendations from the Swedish Resuscitation Council
Resuscitation.
(2013)
P. Stammet et al.
Bispectral index (BIS) helps predicting bad neurological outcome in comatose survivors after cardiac arrest and induced therapeutic hypothermia
Resuscitation.
(2009)
M. Leary et al.
Neurologic prognostication and bispectral index monitoring after resuscitation from cardiac arrest
Resuscitation.
(2010)
P. Stammet et al.
Modeling serum level of s100beta and bispectral index to predict outcome after cardiac arrest
Journal of the American College of Cardiology.
(2013)
N. Nielsen et al.
Target Temperature Management after out-of-hospital cardiac arrest--a randomized, parallel-group, assessor-blinded clinical trial--rationale and design
American heart journal
(2012)
N. Nielsen et al.
Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
The New England journal of medicine.
(2013)

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

The New England journal of medicine

(2002)

S.A. Bernard et al.

Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia

The New England journal of medicine.

(2002)

V. Lemiale et al.

Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort

Intensive care medicine.

(2013)

M. Oddo et al.

Predicting neurological outcome after cardiac arrest

Current opinion in critical care.

(2011)

C. Adrie et al.

Predicting survival with good neurological recovery at hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA score

European heart journal.

(2006)

Cited by (33)

Bispectral index and suppression ratio after cardiac arrest: are they useful as bedside tools for rational treatment escalation plans?
2022, Revista Espanola de Cardiologia
La disfunción miocárdica contribuye a la mortalidad precoz (24-72 horas) de los supervivientes de parada cardiaca (PC). Actualmente, la decisión de implantar un dispositivo de soporte circulatorio en este contexto se toma con información limitada acerca del potencial de recuperación neurológica (PRN) del paciente, lo que en muchas ocasiones termina en infratratamiento. Por tanto, requerimos de herramientas accesibles y fiables que añadan información sobre el PRN y ayuden a establecer planes individualizados de escalada terapéutica.
Se recogieron valores de índice biespectral (BIS) y tasa de supresión (TS) en supervivientes de una PC sometidos a control de la temperatura corporal. La función neurológica se evaluó con la escala Cerebral Performance Category (CPC).
Se incluyeron 340 pacientes. En la primera evaluación neurológica completa, 211 (62,1%) alcanzaron buen pronóstico (CPC 1-2). Los valores de BIS fueron significativamente mayores y los de TS menores, en pacientes con CPC 1-2. Un BIS promedio > 26 en las primeras 12 horas predijo buena evolución neurológica (sensibilidad 89,5%; especificidad 75,8%; AUC = 0,869), mientras que una TS promedio > 24 en las primeras 12 horas predijo mala evolución o CPC 3-5 (sensibilidad 91,5%; especificidad 81,8%; AUC = 0,906). Los valores horarios de BIS/TS mostraron buena capacidad predictiva (AUC > 0,85) desde la 2.^a hora para TS y 4.^a para BIS.
El BIS/TS permiten estimar el PRN tras una PC. Este hallazgo puede contribuir a crear conciencia con respecto a evitar la limitación de escalada terapéutica en pacientes potencialmente recuperables.
Myocardial dysfunction contributes to early mortality (24-72 hours) among survivors of a cardiac arrest (CA). The benefits of mechanical support in refractory shock should be balanced against the patient's potential for neurological recovery. To date, these early treatment decisions have been taken based on limited information leading mainly to undertreatment. Therefore, there is a need for early, reliable, accessible, and simple tools that offer information on the possibilities of neurological improvement.
We collected data from bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale.
We included 340 patients. At the first full neurological evaluation, 211 patients (62.1%) achieved good outcome or CPC 1-2. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2. An average BIS > 26 during first 12 hours of TTM predicted good outcome with 89.5% sensitivity and 75.8% specificity (AUC of 0.869), while average SR values > 24 during the first 12 hours of TTM predicted poor outcome (CPC 3-5) with 91.5% sensitivity and 81.8% specificity (AUC, 0.906). Hourly BIS and SR values exhibited good predictive performance (AUC > 0.85), as soon as hour 2 for SR and hour 4 for BIS.
BIS/SR are associated with patients’ potential for neurological recovery after CA. This finding could help to create awareness of the possibility of a better outcome in patients who might otherwise be wrongly considered as nonviable and to establish personalized treatment escalation plans.
Full English text available from:www.revespcardiol.org/en
European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care
2021, Resuscitation
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation, and organ donation.
Post-cardiac arrest care and targeted temperature management: A consensus of scientific statement from the Taiwan Society of Emergency & Critical Care Medicine, Taiwan Society of Critical Care Medicine and Taiwan Society of Emergency Medicine
2021, Journal of the Formosan Medical Association
Post-cardiac arrest care is critically important in bringing cardiac arrest patients to functional recovery after the detrimental event. More high quality studies are published and evidence is accumulated for the post-cardiac arrest care in the recent years. It is still a challenge for the clinicians to integrate these scientific data into the real clinical practice for such a complicated intensive care involving many different disciplines.
With the cooperation of the experienced experts from all disciplines relevant to post-cardiac arrest care, the consensus of the scientific statement was generated and supported by three major scientific groups for emergency and critical care in post-cardiac arrest care.
High quality post-cardiac arrest care, including targeted temperature management, early evaluation of possible acute coronary event and intensive care for hemodynamic and respiratory care are inevitably needed to get full recovery for cardiac arrest. Management of these critical issues were reviewed and proposed in the consensus
The goal of the statement is to provide help for the clinical physician to achieve better quality and evidence-based care in post-cardiac arrest period.
The revised Cerebral Recovery Index improves predictions of neurological outcome after cardiac arrest
2018, Clinical Neurophysiology
Analysis of the electroencephalogram (EEG) background pattern helps predicting neurological outcome of comatose patients after cardiac arrest (CA). Visual analysis may not extract all discriminative information. We present predictive values of the revised Cerebral Recovery Index (rCRI), based on continuous extraction and combination of a large set of evolving quantitative EEG (qEEG) features and machine learning techniques.
We included 551 subsequent patients from a prospective cohort study on continuous EEG after CA in two hospitals. Outcome at six months was classified as good (Cerebral Performance Category (CPC) 1-2) or poor (CPC 3-5). Forty-four qEEG features (from time, frequency and entropy domain) were selected by the least absolute shrinkage and selection operator (LASSO) method and used in a Random Forests classification system. We trained and evaluated the system with 10-fold cross validation. For poor outcome prediction, the sensitivity at 100% specificity ( $S e_{100}$ ) and the area under the receiver operator curve (AUC) were used as performance of the prediction model. For good outcome, we used the sensitivity at 95% specificity ( $S e_{95}$ ).
Two hundred fifty-six (47%) patients had a good outcome. The rCRI predicted poor outcome with AUC = 0.94 (95% CI: 0.83–0.91), $S e_{100}$ = 0.66 (0.65–0.78), and AUC = 0.88 (0.78–0.93), $S e_{100}$ = 0.60 (0.51–0.75) at 12 and 24 h after CA, respectively. The rCRI predicted good outcome with $S e_{95}$  = 0.72 (0.61–0.85) and 0.40 (0.30–0.51) at 12 and 24 h after CA, respectively.
Results obtained in this study suggest that with machine learning algorithms and large set of qEEG features, it is possible to efficiently monitor patient outcome after CA. We also demonstrate the importance of selection of optimal performance metric to train a classifier model for outcome prediction.
The rCRI is a sensitive, reliable predictor of neurological outcome of comatose patients after CA.
Continuous surface EMG power reflects the metabolic cost of shivering during targeted temperature management after cardiac arrest
2018, Resuscitation
Shivering may interfere with targeted temperature management (TTM) after cardiac arrest, contributing to secondary brain injury. Early identification of shivering is challenging with existing tools. We hypothesized that shivering detected by continuous surface sEMG monitoring would be validated with calorimetry and detected earlier than by intermittent clinical observation.
This prospective observational study enrolled a convenience sample of comatose adult cardiac arrest patients treated with TTM at 33 °C. Clinical shivering was monitored hourly using the Bedside Shivering Assessment Scale (BSAS) by bedside nurses who administered intermittent neuromuscular blockade (NMB) when BSAS ≥ 1. The research team monitored independently for shivering with BSAS every 15 min during continuous blinded monitoring of oxygen consumption (VO₂) via indirect calorimetry and sEMG power during the maintenance phase of TTM. A sustained 20% increase in the 5-min rolling average of VO₂ above baseline identified the Gold Standard shivering threshold (VO₂-20).
Among 18 patients, clinical shivering was detected 23 times in 14 patients. Hierarchical models to predict a shiver event determined by the VO₂-20 for sEMG power and BSAS revealed an AUC for sEMG power of 0.92 (95%CI = 0.88–0.95), and 0.90 (CI = 0.87–0.94) for BSAS. The optimal threshold of sEMG to predict VO₂-20 was 32 decibels (dB), and this was exceeded 38 (29–56) min before nurse-detected shivering.
Shivering was detected by sEMG power earlier than by clinical assessment with BSAS, with similar accuracy compared to the indirect calorimetry gold standard. Continuous sEMG monitoring appears useful for clinical assessment and research for shivering during TTM.
The validation of simplified EEG derived from the bispectral index monitor in post-cardiac arrest patients
2018, Resuscitation
Citation Excerpt :
Unfortunately, our time point of validation was situated approximately three days after CA. As previous studies showed that the prognostic power of EEG lies within the first 24 h, we acknowledge that the prognostic value of simplified BIS EEG warrants further examination in a similar time window [14,15,35–37]. Aside from experienced neurophysiologists, treating physicians should also be capable of interpreting simplified EEG traces on the BIS monitor as they can play a prominent role in the early identification of epileptic activity.
We aimed to validate retrospectively the accuracy of simplified electroencephalography (EEG) monitoring derived from the bispectral index (BIS) monitor in post-cardiac arrest (CA) patients.
Successfully resuscitated CA patients were transferred to the Catherization Lab followed by percutaneous coronary intervention when indicated. On arrival at the coronary care unit, bilateral BIS monitoring was started and continued up to 72 h. Raw simplified EEG tracings were extracted from the BIS monitor at a time point coinciding with the registration of standard EEG monitoring. BIS EEG tracings were reviewed by two neurophysiologists, who were asked to indicate the presence of following patterns: diffuse slowing rhythm, burst suppression pattern, cerebral inactivity, periodic epileptiform discharges and status epilepticus (SE). Additionally, these simplified BIS EEG tracings were analysed by two inexperienced investigators, who were asked to indicate the presence of SE only.
Thirty-two simplified BIS EEG samples were analysed. Compared to standard EEG, neurophysiologists interpreted all simplified EEG samples with a sensitivity of 86%, a specificity of 100% and an interobserver variability of 0.843. Furthermore, SE was identified with a sensitivity of 80% and a specificity of 94% by two unexperienced physicians.
Using a simple classification system, raw simplified EEG derived from a BIS monitoring device is comparable to standard EEG monitoring. Moreover, investigators without EEG experience were capable to identify SE in post-CA patients. Future studies will be warranted to confirm our results and to determine the added value of using simplified BIS EEG in terms of prognostic and therapeutic implications.

View all citing articles on Scopus

^☆: 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.2014.09.009.

View full text

Clinical PaperBispectral Index to Predict Neurological Outcome Early After Cardiac Arrest☆

Abstract

Aim of the study

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Patients

Discussion

Conclusions

Conflict of interest

Acknowledgements

Resuscitation

Resuscitation

Resuscitation.

Resuscitation.

Resuscitation.

Resuscitation.

Resuscitation.

Journal of the American College of Cardiology.

American heart journal

Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest

The New England journal of medicine.

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

The New England journal of medicine

Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia

The New England journal of medicine.

Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort

Intensive care medicine.

Predicting neurological outcome after cardiac arrest

Current opinion in critical care.

Predicting survival with good neurological recovery at hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA score

European heart journal.

Clinical Paper
Bispectral Index to Predict Neurological Outcome Early After Cardiac Arrest☆