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Abstract
Introduction Nowadays, managing out-of-hospital cardiac arrest (OHCA) prioritises measures that achieve a good neurological outcome. Monitoring neurological function early is an essential step in identifying patients who could benefit from invasive techniques, such as extracorporeal membrane oxygenation, compared with patients suffering from irreversible hypoxic–ischaemic brain injury. Electroencephalography (EEG) has been used in the hospital; thus, its prehospital data are lacking. This study aimed to evaluate the feasibility of non-invasive EEG in the prehospital environment as a potential tool for neurological assessment.
Methods and analysis This feasibility trial will recruit 45 OHCA patients aged 18 and over in the catchment area of the physician response unit at the University Hospital Graz, Austria. Two different measurement conditions will be assessed: (1) during the phase of cardiopulmonary resuscitation (CPR) and (2) after the return of spontaneous circulation for those who achieve this condition. EEG not only has the potential to provide an early neurological prognosis for immediate treatments or outcome-related decisions but can also aid in better managing CPR-induced consciousness.
Ethics and dissemination The ethics committee of the Medical University of Graz (IRB00002556), decision number 35-352 ex 22/23, reviewed and approved this study protocol, registered at ClinicalTrials.gov (Identifier NCT06072092). The data generated from this research will be published openly alongside the study results.
Trial registration number NCT06072092.
- Out-of-Hospital Cardiac Arrest
- Electroencephalography
- Feasibility Studies
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This study evaluates the feasibility of employing frontal electroencephalography (EEG) monitoring during out-of-hospital cardiac arrest resuscitation in a prehospital setting using a physician-based emergency medical service (EMS) model.
The study employs a structured observational design, ensuring systematic data collection on EEG signal quality and practical applicability.
The sample size is restricted to 45 participants, which may influence the generalisability of the findings.
The study prioritises feasibility over clinical outcomes, indicating that patient benefit cannot be evaluated.
The reliance on a single EMS system may restrict the applicability of findings to other prehospital care models.
Introduction
The primary goal of cardiac arrest (CA) management is to achieve a return of spontaneous circulation (ROSC) and concomitant survival with good neurological function. However, the survival discharge rate remains low after out-of-hospital CA (OHCA), with reports indicating just 8% in Europe.1 Monitoring neurological function during CA, evaluating neurological rehabilitation potential and ultimately prognosticating are cornerstones in identifying patients who might benefit from invasive techniques, such as extracorporeal membrane oxygenation, compared with those suffering from irreversible hypoxic–ischaemic brain injury (HIBI). Frontal electroencephalograms (EEGs) have been thoroughly studied over the last decade, mainly using derived parameters from processed EEG—bispectral index brain monitoring (BIS), initially developed by Aspect Medical Systems, and subsequently distributed and enhanced by Medtronic (Dublin, Ireland). These studies aimed to assess its efficacy as a non-invasive predictive tool for neurological outcomes. The use of EEG following CA is well established and recommended as a means of detecting seizure activity indicative of HIBI.2 A recent systematic review and meta-analysis found that processed EEG can predict poor neurological outcomes in patients who have suffered from CA and demonstrated good diagnostic performance.3 The potential for neurological recovery in patients post-CA has also been investigated using BIS and the hospital’s derived suppression ratio, which indicated that recovery could be predicted with notable specificity and sensitivity.4 5
However, most studies have assessed BIS values while implementing therapeutic hypothermia (TH) or, more recently, targeted temperature management, and none of the studies have initiated measurements out of the hospital or during CA.6 7 An experimental study examined BIS during CA in a pig model and found a positive correlation among BIS, mean arterial pressure values and end-tidal CO2 (etCO2).8 Another study investigated BIS during CA in the emergency department and found that its reliability was compromised, mainly due to artefacts from cardiac compression.9
Cardiopulmonary resuscitation (CPR)-induced consciousness (CPRIC) has also been investigated recently. This phenomenon refers to patients regaining some level of consciousness during CPR despite the absence of spontaneous circulation. This rare occurrence, happening in less than 1% of patients with OHCA, presents significant challenges for prehospital teams, potentially hindering resuscitative efforts due to patient combativeness and agitation.10 11 The implications of CPRIC include improved survival rates, with higher incidences of ROSC and discharge survival observed in these patients than in those without CPRIC.10 12 Management often involves the use of sedative and paralytic agents, though the optimal protocol remains undetermined.11 12 Frontal EEG may enhance the detection and improve the study of CPRIC, which is another important focus.
Another potential application of prehospital frontal EEG is detecting seizures and status epilepticus (SE), which occur in nearly one-third of comatose CA survivors.13 While the literature extensively addresses SE with motor symptoms in these patients, there is less information regarding non-convulsive SE (NCSE). Among various studies, SE was identified in 29–96% of patients, with NCSE reported in 1–20%.13 The high prevalence of SE emphasises the necessity of continuous EEG monitoring to effectively detect and manage seizures in post-resuscitation care.13
This study aims to assess whether the early prehospital use of frontal EEG is feasible. A truly ‘feasible’ procedure should yield reliable and accurate results while being efficient and practically implementable in the target setting. Furthermore, we will evaluate whether it can serve as a prognostic indicator of neurological function following ROSC.
Methods and analysis
We will conduct a prospective observational feasibility study on patients with OHCA treated by the physician response unit (PRU) of the University Hospital Graz, Austria, in accordance with their standards. This unit, staffed by a prehospital emergency physician and a paramedic, serves the eastern part of Graz and its suburban areas, which have a population of approximately 200 000. The measurement will distinguish between the CPR and ROSC phases for all patients who reach this state. Adult patients (aged≥18 years) who are already in a state of CA on the arrival of the PRU team or develop it subsequently will be included. Patients who are unable to undergo EEG monitoring (for instance, following head injuries), those who do not receive advanced life support, patients who are already in a state of sustained ROSC on PRU arrival and those with clear signs of death will be excluded. The protocol was composed according to the requirements of the Strengthening the Reporting of Observational Studies in Epidemiology protocol.14 For the planned study, we will ensure compliance with the Declaration of Helsinki. The study is also registered at ClinicalTrials.gov (Identifier NCT06072092). The study commenced in 2024 and is ongoing, with the first half of 2025 designated as the planned end date for inclusions.
Informed consent
Due to the minimal interventional risk associated with this observational study and the inability to obtain patient consent at the scene, informed consent will not be secured before the study’s initiation. However, if patients achieve an ROSC, are reachable in the intensive care unit following the event and possess full capacity, they will be asked for their consent and approval retrospectively. If patients survive the event without regaining the full capacity necessary for consent, they will still be included without informed consent.
Sample size considerations
The incidence of resuscitation at the PRU is 55–65 per 100 000 per annum, resulting in 110–140 cases annually. Furthermore, 30–45% of those in whom CPR is initiated have at least one ROSC, leading to 35–60 cases with ROSC at the PRU each year. Approximately 10% of patients who receive CPR survive for 30 days, resulting in 10–15 survivors at the PRU. Due to the hectic environment in the prehospital setting, we anticipate that not all planned inclusions will adhere to the protocol and may need to be excluded due to insufficient data quality. However, given the novelty of this measurement in the prehospital setting, we cannot assume a drop-out rate.
Definitions
For this study, we will retrospectively define the ROSC time by monitoring data stored continuously during the mission. Sustained ROSC will be defined as no monitored CPR activity for more than 5 min following CPR without a declaration of death. The ROSC time will then be calculated by subtracting 5 min from this duration. This approach will exclude documentation bias and recurrent CA. Patients who experience further CA after our criterion for sustained ROSC has been met will need to satisfy our initial criteria once more. The last episode of sustained ROSC will be analysed in re-arrest patients.
Outcomes
Primary aim
The principal objective is to ascertain the feasibility of employing frontal EEG measurements and derived parameters (eg, BIS) during CPR and at ROSC in the prehospital environment. The feasibility assessment will occur in two distinct phases: CPR and ROSC for patients who achieve this state. Frontal EEG measurements rely heavily on the correct application of electrodes, and processed EEG measures (BIS) are derived from these signals. For the processed EEG, the measurement will be considered ‘feasible’ for each phase if quality parameters are met during at least 75% of the measurement period. These parameters include a reliable Signal Quality Index>50 and electromyogram<40 dB.15 High EMG artefacts are anticipated, particularly during transport, and will be assessed separately. We propose a minimum evaluation time of 5 min to assess the feasibility of each phase per patient. There will be no maximum time, as the sustained ROSC phase should ideally persist until hospital handover, which is highly variable.
Lastly, to improve the validity of this feasibility study, the time taken for measurement and the ease of use of equipment will be evaluated after each application using a simple questionnaire about EEG monitoring.
Secondary aim 1
The first secondary aim will be assessing neurological outcomes. All patients suffering from OHCA with ROSC will be followed up to determine their cerebral performance category (CPC) 1 month after the event in a structured follow-up assessment, including the Clinician-Administered PTSD Scale for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (CAPS-5) questionnaire.16
The neurological outcome will be assessed via the CPC 1 month after resuscitation.17 CPCs 1 and 2 reflect good neurological function, whereas 3–5 indicate poor outcomes. Examiners will evaluate the patients without knowledge of BIS values. Furthermore, the baseline CPC score before the event will be assessed and documented either prehospital by the attending team or in-hospital at the intensive care unit (ICU) through the relatives.
To fully understand potential changes in the quality of life (QoL), we will also ask close relatives of the patient to complete a brief questionnaire. This questionnaire, known as the Essener Trauma Inventory—External Assessment, is validated for obtaining an external perspective on patients following traumatic events such as CPR.18 Although it has not been specifically employed for patients after OHCA, this questionnaire will provide valuable insights into possible QoL changes following OHCA, which remains the primary goal of administering high-quality CPR.
Secondary aim 2
The second secondary aim is to investigate the potential correlation between BIS and etCO2 values in OHCA patients undergoing CPR. EtCO2 should be used for every OHCA case and serve as a quality indicator for CPR. Despite our independent assessment of CPR quality, we will also evaluate etCO2 due to its widespread application. We anticipate that the BIS readings will fluctuate with the quality of CPR: we expect a decrease with deteriorating CPR quality, using etCO2 as a surrogate marker, and an enhancement with improved CPR quality, reflected in rising etCO2 levels or ROSC. Brain perfusion during CPR relies on the quality of chest compressions, which acts as a confounding factor for EEG measurements. Consequently, we will implement an additional CPR metre for all patients receiving CPR to assess its quality. Furthermore, etCO2 is significantly influenced by manual or mandatory ventilation through a respirator. A sensitive flow metre will be employed to account for this confounder.
Given the significant differences in circulatory flows, we will assess this connection separately for patients in various states, specifically intra-arrest versus ROSC (figures 1 and 2).
Overview of the study steps and milestones. EEG, electroencephalography; ICU, intensive care unit; OHCA, out-of-hospital cardiac arrest; PRU, physician response unit; ROSC, return of spontaneous circulation.
Additional non-standard equipment used for the evaluation of the study aims. BIS, bispectral index brain monitoring; EEG, electroencephalography.
Secondary aim 3
The third secondary aim is to compare the time point of the first sedation after achieving ROSC between patients with lower BIS values and those with higher BIS values. We hypothesise that patients with higher mean BIS values (>25) at ROSC (as defined) will require faster and more sedation than those with lower readings (≤25) if no sedative agents were administered prior to ROSC. Accordingly, sedative agents used pre-arrest (medical history, hypothesised reason for the arrest and medical treatments before deterioration into CA), intra-arrest and post-arrest will be evaluated.
Secondary aim 4
The fourth secondary aim is to evaluate the timing of sedation cessation for ROSC patients in the ICU, as well as the timing of extubation, withdrawal of therapy, do not extubate/do not resuscitate orders, timing of HIBI diagnostics (needle EEG, cranial CT scan, somatosensory evoked potentials and timing of neurologist consultation) and potentially available neuromarkers for HIBI (S100B and serum neurofilament light chain/neuron-specific enolase), including the consequences of these measures. We anticipate that patients with lower mean BIS values (≤25) following ROSC will receive decisions regarding the withdrawal of therapy more swiftly than those with values >25.
Study process
When assigned to a potential CA case or managing a patient who subsequently experiences one, the PRU team will execute standard care procedures as routine. An auxiliary kit containing the specific equipment for this study will be carried to the patient’s location. This ensures that the CPRmeter (Laerdal, Stavanger, Norway) can be immediately used without invoking any treatment delays. After the initial interventions align with the current European Resuscitation Council guidelines (monitoring, intravascular access and airway management), the eligibility criteria for the patient’s inclusion in the study will be reviewed. On confirmation of eligibility, a team member will fix the EEG electrodes to the patient’s forehead and connect them to the monitor (Covidien, Mansfield, Massachusetts, USA), ensuring they do not interfere with any other ongoing medical interventions. The functionality of the BIS monitor will be verified.
Consequently, the flow sensor (Archeon Medical, Besançon, France, Europe) can be installed. The BIS sensor’s position and consistent performance should be verified periodically throughout the team’s presence. Patients in such circumstances are commonly conveyed to one of the ICUs at the Medical University of Graz. During handover, the team also informs the receiving unit of the patient’s inclusion in the study, enabling them to continue with the Case Report Form documentation throughout the patient’s stay. Post-handover, the PRU team completes a quick questionnaire to evaluate the BIS device.
Data analysis
Summary statistics of relevant patient characteristics, procedural variables, questionnaire items and outcomes will be presented as mean, SD, median and quartiles for continuous variables and as count and proportion for discrete variables. Diagnostic plots will be used to assess the normality of continuous variables. Where appropriate, correlations will be assessed using Spearman’s rho.
The sample will be analysed exploratively. Patient groups will be compared using Student’s t-test and Mann-Whitney U test for continuous variables and Fisher’s exact test for discrete variables. The time-to-event data will be analysed using Kaplan-Meier curves and log-rank tests.
The signal quality measures will also be evaluated using the mean, minimum and maximum values over time.
For secondary aim 1, the predictive performance of various variables, including the mean and minimum BIS recorded over different time intervals, will be assessed in an exploratory manner by calculating the area under the receiver operating characteristic. Given our expectation of high mortality and the limited number of patients with favourable neurological outcomes, the feasibility of conducting a more complex analysis of this endpoint will depend entirely on the data available.
For secondary aim 2, Spearman’s rho will be calculated to evaluate the correlations between BIS and etCO2 at various time points.
For secondary aim 3, the sedative agents will be analysed descriptively. Continuous variables will be compared using a t-test if they are normally distributed or the Mann-Whitney U test if they are not. The time to the first application of sedative medication will be assessed using Kaplan-Meier curves and log-rank tests.
For secondary aim 4, we will employ descriptive statistics.
No imputation for missing data is planned. All analyses will be conducted using the current version of R (R Core Team, 2024; R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
Patients and the public Statement
Patients and the public did not participate in developing this technical study protocol. Given the specific characteristics of the study population, the researchers solely crafted the protocol.
Ethics and dissemination
The Ethics Committee of the Medical University of Graz (IRB00002556), decision number 35–352 ex 22/23, reviewed and approved this study. In compliance with data protection protocols, data will be stored in a password-protected online database provided by the university. Access to the files is restricted to the researchers, who will manage pseudonymised data. After the data have been cleaned and the results published, they will be made available as open access in a repository.
Discussion
The primary aim of this observational study is to ascertain whether it is feasible to measure frontal EEG activity in a prehospital setting. This non-invasive and straightforward measurement has demonstrated various advantages in a hospital context. Currently, it remains unclear which processed EEG/BIS values can be derived during CPR or following ROSC and how these values fluctuate over time. Although some studies have gauged frontal EEG on arrival at the hospital, this has yet to be explored in the prehospital environment. At present, there is a deficiency of prognostic indicators in this area. Non-invasive frontal EEG monitoring could offer a practical method for bridging this gap. Furthermore, if feasible, this study may uncover non-convulsive seizures, particularly in patients who have received muscle relaxants, potentially leading to timely treatment. Additionally, a more thorough investigation could be pursued regarding the incidence and management of CPR-induced consciousness. The BIS advanced brain monitoring system was selected due to its wide availability, extensive research in hospital settings and applicability.
The study design aims to collect data on CPR, the patient and their overall outcomes. While the ultimate goal is for their lives to remain unchanged since before the event, most OHCA studies focus solely on the CPC score and do not delve deeper into evaluation. Currently, there is no standardised approach or questionnaire for assessing how a survivor of OHCA might have changed or how their quality of life may have been impacted.19 Consequently, we plan to use standardised questionnaires for post-traumatic events such as CPR to gather both internal and external perspectives on changes in QoL. This methodology may also be considered in future OHCA studies.
CAPS-5 will be used to assess the presence and severity of post-traumatic stress disorder (PTSD) symptoms in individuals 6 months after CPR. This tool is known for its diagnostic accuracy and sensitivity to change. It is an ideal choice for evaluating the psychological impact of traumatic events such as CPR and CPRIC. Administering CAPS-5 at the 6-month post-event interval allows for the assessment of early PTSD symptoms, providing critical insights into the psychological outcomes for patients following a life-threatening event and the need for early intervention strategies.16
Ethics statements
Patient consent for publication
Footnotes
X @traumameic, @PhZoidl, @SimonOrlob
Contributors MEichinger (principal investigator): conceptualisation, methodology, formal analysis, investigation, data curation, writing—original draft, project administration and funding acquisition. MEichinger is responsible for the overall content as guarantor. ACR (co-investigator): methodology, investigation, writing—review and editing. PZajic: methodology, visualisation, investigation, writing—review and editing. SH: methodology, investigation and writing—review and editing. TK: methodology, formal analysis and data curation. SO: conceptualisation, methodology, writing—review and editing and data curation. MEichlseder: methodology, writing—review and editing and funding acquisition. PZoidl: methodology, investigation, writing—review and editing. MR: methodology, investigation, writing—review and editing. AP: methodology, writing—review and editing. GH: methodology, investigation, writing—review and editing. LH: methodology, investigation, writing—review and editing. AE: methodology, investigation, writing—review and editing. HB-C: methodology, investigation, writing—review and editing and supervision. We used AI models to check for grammar and spelling. However, the authors checked and approved the manuscript’s content, which was not altered by the AI model.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Addendum The Doctoral School of Lifestyle-Related Diseases at the Medical University of Graz, Austria, mainly provided the publication fee for this open-access publication.