Neuroprognostication following Cardiac Arrest

In the United Kingdom, out-of-hospital cardiac arrests (OHCA) reported to ambulance services amount to over 110,000 per year, with resuscitation attempted in around 45,000 cases, and in-hospital cardiac arrests (IHCA) around 12,000 annually. [1] This is associated with high mortality, but a considerable proportion of those who survive the event have a poor neurological recovery.

Overall, 30-day survival for OHCA in England remains low at 9.5%. Results are slightly better for IHCA with 25.8% surviving to discharge, or up to 52.9% if the initial rhythm is ventricular fibrillation (VF) or ventricular tachycardia (VT). [2]

Despite advances in post-resuscitation care management, about 50% of resuscitated patients from cardiac arrests (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 associated costs and length of stay is also significantly higher in patients with poor neurological outcome. [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, to potentially enable early withdrawal of life-saving treatment (WLST) in those patients predicted to have a poor outcome. [4]

The ‘Chain of Survival’, an internationally recognised concept summarises the important components of successful resuscitation. This is achieved by development, implementation and standardisation of national guidelines and treatment protocols. The links in the chain need to be strengthened by research, community programmes and raising awareness. This will automatically improve the survival to discharge. [5,6]

There are several factors prior, during and post cardiac arrest which can influence the outcome of cardiac arrest. The prognostication strategy follows some key principles; Early communication, Delay timing of prognostication, Multimodal evaluation and Being patient.

The first three links in the chain are widely agreed and is well covered in national and international guidelines. The emergency physician is one of the initial points of contact, who is responsible for effective resuscitation and visits factors like co-morbidities, arrest events or do not resuscitate orders. This has direct influence on the decision such as continuation of resuscitation, likelihood of survival with good neurological outcome and it lays the platform for the equally vital post-resuscitation care. The final link of post-resuscitation care and its components, which offer the best probability of survival, is highly influenced by the hospital where a person is taken, cardiac interventional procedures, the indications and aims of various medical interventions in the intensive care unit, the indications for implantable defibrillators or cardiac resynchronisation devices, and optimal arrangements for cardiac and neurological rehabilitation. [5,6]

2025 resuscitation guidance positions the Chain of Survival within a broader, systems-based survival ecosystem. It is presented as part of a comprehensive public health strategy that emphasises system performance, community readiness, policy support and lifelong survivorship. [7]

Factors influencing survival to hospital discharge following Cardiac Arrest:

There are several stages in this chain of survival and multiple factors which influence these stages. It is therefore essential for an Emergency Physician to consider all these factors during the decision making process. [8]

1. Pre-Cardiac Arrest factors associated with adverse outcome

Patient factors:

• Increasing Age
• Associated Co-morbidities

Event related factors:

• Unwitnessed Event

2. During Cardiac Arrest factors associated with adverse outcome

• Delayed Initiation of Cardio-Pulmonary Resuscitation (CPR)
• Pulseless Electrical Activity (PEA) or Asystole as initial rhythm
• Delayed Defibrillation of patients in Ventricular Fibrillation (VF) or Pulseless Ventricular Tachycardia (VT)
• Longer Duration of CPR

3. Post Cardiac Arrest factors associated with adverse outcome

• temperature over 37.7
• Delayed Coronary Catheterisation in patients who had a shockable initial rhythm (VF or VT)
• Excessive oxygenation of patients
• Inadequate maintenance of Arterial Blood Pressure (BP)
• Early prognostication and withdrawal of life support treatment (WLST)

At the 2017 International Symposium on Intensive Care and Emergency Medicine, the experts in this field suggested a strategy for treating physicians. This has further developed through joint collaboration by European Resuscitation Council (ERC) and European Society for Intensive Care Medicine (ESICM) in 2021 and 2025. [2]

The key principles of this strategy are [9]:

Early Communication with the next of kin

It is important to provide early and meaningful information to the patient’s next of kin. This makes them aware of the patient’s critical condition and enables the physician to better understand the expectations of families/friends. It is however vital to convey that physicians will take decisions in the best interests of the patient.

Delay the timing of prognostication

The current recommendations are to consider prognosis in the unconscious patient at ≥72hrs from ROSC once confounders have been excluded. The phenomenon of ‘late awakening’ has been observed and an extremely small number of patients who do not respond for 5-7 days recover with intact neurology.

Use of Multimodal Evaluation tool for prognostication

ERC/ESICM also recommend that in patients who are comatose after resuscitation from cardiac arrest, neurological prognostication should be performed using clinical examination, electrophysiology, biomarkers, and imaging. This is discussed subsequently in further detail. [2]

Be patient

This a key attribute and the treating physician should approach individual cases differently but follow the suggested principles. There is no harm in involving your fellow colleagues in the decision-making process.

Multimodal Evaluation Strategy

The key recommendations are summarised below: 

1. Clinical examination

• Perform a daily neurological examination in patients who are unconscious after cardiac arrest
• It should be noted that clinical examination is prone to interference from sedatives, opioids or muscle relaxants, so potential confounding from residual sedation should always be considered and excluded.
• In unconscious patients at 72 h or later after ROSC, the following tests may predict a poor neurological outcome:
  • The bilateral absence of the pupillary light reflex.
  • The bilateral absence of corneal reflex
  • The presence of myoclonus within 96 h and, in particular, status myoclonus within 72 h.
• Guidelines also suggest to record an EEG in the presence of myoclonic jerks to detect any associated epileptiform activity or to identify EEG signs, such as background reactivity or continuity, that may suggest a potential for neurological recovery.

2. Neurophysiology

• EEG can be performed from day 1 after ROSC to predict outcome and detect seizure activity in comatose patients. Routine EEG or continuous EEG monitoring can also be considered though is not available in all units.
• Suppressed background with or without periodic discharges and burst suppression on EEG (i.e. ‘highly malignant’ patterns) are accurate indicators of a poor prognosis.
• The bilateral absence of somatosensory evoked cortical N20 potentials also indicates poor prognosis after cardiac arrest.
• EEG and somatosensory evoked potentials (SSEPs) results should always be assessed in the context of clinical examination findings and other tests. [2]

3. Biomarkers

• Biomarkers are released with different latency and speed following acute brain injury. The kinetics of neuron specific enolase (NSE) are not completely known however advice is to use serial measurements of NSE to predict outcome after cardiac arrest.
• Increasing values between 24 and 48 h or 72 h in combination with high values at 48 and 72 h indicate a poor prognosis.
• Conversely NSE levels tend to decrease over 72hrs in patients with favourable outcome.

4. Imaging

• Brain imaging studies should be used to help predict poor neurological outcome after cardiac arrest.
• The presence of a marked reduction in grey matter/white matter ratio on CT Brain within 72hrs after ROSC indicates generalised brain oedema and in the context of cardiac arrest usually suggests hypoxic ischaemic brain injury.
• The presence of extensive diffusion restriction on MRI Brain at 2-7 days after ROSC usually indicates the same, and correlates with poor outcome.
• A repeat CT Brain should be done if the patient remains unconscious at time of prognostication (72 h–96 h after ROSC) if the first CT Brain does not show signs of hypoxic ischaemic brain injury. [2] 

It is strongly recommended that the above prognostication markers should be used in combination and not independently.

Point of Care Focussed Echocardiography

Post-resuscitation myocardial dysfunction and low cardiac index may occur in up to 60 % of post-cardiac arrest patients and may be even more common in patients with an acute myocardial infarction (AMI) as the cause of the arrest. [2]

Early echocardiography can identify underlying cardiac pathology (as possible cause of cardiac arrest), quantify the degree of myocardial dysfunction and help guide haemodynamic management.

However, evidence for its use in prognostication is limited. A systematic review in 2017 by Tsou, et al. [10] showed patients with a low pre-test probability for ROSC and absence of spontaneous cardiac movement on echocardiography can predict a low likelihood of survival and can guide the decision of resuscitation termination.

Two other, more recent studies showed no clear association of low cardiac output (or index) and poor outcome – sub study of TTM2 showed if lactate clearance is maintained then low cardiac index may not be associated with poor outcome. A further sub study of the Blood Pressure and Oxygenation Targets After OHCA (BOX) trial, in a multivariable analysis, showed a low cardiac index at admission was not associated with increased mortality.

Definition

There is only one definition of death – the permanent loss of the capacity for consciousness, combined with permanent loss of the capacity to breathe – but there are three sets of diagnostic criteria.

Brain death (or death by neurological criteria) is the permanent cessation of brain function, whether as a consequence of cardiorespiratory arrest or devastating brain injury, that will produce the permanent loss of the capacities for consciousness and for breathing and thus induce the clinical state of death. Therefore, a diagnosis of permanent cessation of brainstem function means the person has died and allows a competent individual to confirm the person’s death. Though, this is mainly assessed in intensive care settings, it is essential for all acute physicians to have some understanding.

Three things should be noted in this regard:

1. The irreversible loss of capacity for consciousness does not by itself entail individual death. Patients in a vegetative state (VS) or unresponsive wakefulness syndrome have lost this capacity. However, patients with these syndromes are not dead as they have persisting brainstem function, notably some aspects of consciousness (e.g. arousal, wakefulness) and the capacity to breathe. In patients with brain death, they can no longer breath unaided without respiratory support or intrinsically perform other life-sustaining biological interventions. So, within a brief time, even if the patient remained on respiratory support there would be an inevitable deterioration and organ necrosis.
2. The diagnosis of death because of cessation of brainstem function does not entail the cessation of all neurological activity in the brain. What does follow from such a diagnosis is that none of these potential activities indicates any form of consciousness associated with human life, particularly the ability to feel, to be aware of, or to do, anything. Where such residual activity exists, it will not do so for long due to the rapid breakdown of other bodily functions.
3. There may also be some residual reflex movement of the limbs after such a diagnosis. However, as this movement is independent of the brain and is controlled through the spinal cord, it is neither indicative of the ability to feel, be aware of, or to respond to, any stimulus, nor to sustain respiration or allow other bodily functions to continue.

Brain-stem death is not part of the VS, which has been defined as a clinical condition of unawareness of self and environment in which the patient breathes spontaneously, has a stable circulation, and shows cycles of eye closure and opening which may simulate sleep and waking.

The current position in law is that there is no statutory definition of death in the United Kingdom. Subsequent to the proposal of the ‘brain death criteria’ by the Conference of Medical Royal Colleges in 1976, the courts in England and Northern Ireland have adopted these criteria as part of the law for the diagnosis of death. There is no reason to believe that courts in other parts of the United Kingdom would not follow this approach.

Conditions necessary for the diagnosis of death by Neurological criteria:

The Academy of Medical Royal Colleges (AoMRC) recently updated their guidelines on confirmation of death in 2025. [11]

The confirmation of death using neurological criteria is a clinical diagnosis that should be made by at least two doctors who have had full registration with the General Medical Council (GMC) – or equivalent international professional body recognised by the GMC – for more than 5 years and are competent to diagnose and confirm death using neurological criteria in the UK. At least one of the doctors must be a consultant.

The diagnosis should be undertaken by the two doctors working together but each independently ensuring that the diagnosis is carried out in an accurate, standardised and timely manner. The two doctors then must be satisfied that all the necessary preconditions for the application of neurological criteria are met or can be mitigated by the addition of an ancillary investigation

Specific preconditions must be fulfilled before the two doctors can commence their clinical testing:

• Aetiology severe enough to cause permanent cessation of brainstem function
  • This diagnosis must be evaluated with neuroimaging as a minimum but can also include electrophysiological or invasive intracranial pressure measurements
• Assessment period sufficient to exclude the potential for recovery.
  • In all cases neurological criteria should not be applied until at least 6hrs following the loss of the last observed brainstem reflex or spontaneous breath
  • In the context of post cardiac arrest, neurological criteria should not be applied until at least 24hrs following the loss of the last observed brainstem reflex or spontaneous breath
• Exclusion of potentially reversible factors materially contributing to the coma or apnoea. Examples include:
  • Hypothermia (specifically any temp <36^oC)
  • Depressant/sedative drugs
  • Profound neuromuscular weakness
  • Cervical spinal cord pathology
  • Electrolyte disturbances (specifically sodium, potassium, glucose and phosphate + magnesium)
  • Endocrine disturbances (such as myxoedema or addisonian crisis)
• Additional caution for diagnosing death using neurological criteria in uncommon circumstances.
  • Steroids
  • Primary posterior fossa/brainstem aetiology
  • Therapeutic decompressive craniectomy
  • Children <2yrs old

Absence of brain stem reflexes

1. The pupils are fixed and do not respond to sharp changes in the intensity of incident light.
2. There is no corneal reflex; care should be taken to avoid damage to the cornea.
3. The oculo-vestibular reflexes are absent.
4. No motor responses within the cranial nerve distribution can be elicited by adequate stimulation of any somatic area.
5. There is no cough reflex response to bronchial stimulation by a suction catheter placed down the trachea to the carina, or gag response to stimulation of the posterior pharynx with a spatula.
6. The process for testing the respiratory response to hypercarbia (apnoea test) should be the last brain-stem reflex to be tested and should not be performed if any of the preceding tests confirm the presence of brain-stem reflexes.
7. AoMRC updated their guidance and parameters for hypercarbia testing with 2025 guidelines to correlate with international guidelines. It is now as follows [11]:

Start: paCo2 ≥ 5.3 KPa

End: PaCO2 ≥ 8.0 kPa, pH < 7.3 + Rise PaCO2 ≥ 2.7 kPa

Time: Minimum 5 minutes

Repetition of testing

1. The diagnosis of death by brain-stem testing should be made by at least two medical practitioners who have been registered for more than five years and are competent in the conduct and interpretation of brain-stem testing. At least one of the doctors must be a consultant.
2. Those carrying out the tests must not have, or be perceived to have, any clinical conflict of interest and neither doctor should be a member of the transplant team.
3. Testing should be undertaken by the nominated doctors acting together and must always be performed on two occasions. A complete set of tests should be performed on each occasion, i.e., a total of two sets of tests will be performed.
4. Doctor A may perform the tests while Doctor B observes; this would constitute the first set. Roles may be reversed for the second set. The tests, in particular the apnoea test, are therefore performed only twice in total.
5. If the first set of tests shows no evidence of brain-stem function, there need not be a lengthy delay prior to performing the second set.
6. A brief period will be necessary after reconnection to the ventilator to allow return of the patient’s arterial blood gases and baseline parameters to the pre-test state, rechecking of the blood sugar concentration and for the reassurance of all those directly concerned.
7. Death is confirmed when the two doctors undertaking the process are satisfied that all the relevant neurological criteria to diagnose and confirm death are met. This would ordinarily be at the time of completion of second set of clinical tests. [11]

1. University of Warwick. Annual Epidemiology and Outcomes Reports (OHCAO). Out-of-Hospital Cardiac Arrest Outcomes Registry: 2025. University of Warwick, 2024.
2. Nolan JP, Sandroni C, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2025: post-resuscitation care. Resuscitation. 2025 Oct; Vol 215: sup 1.
3. Petrie J, Easton, S, et al. Hospital costs of out-of-hospital cardiac arrest patients treated in intensive care; a single centre evaluation using the national tariff-based system. BMJ Open 2015;5:e005797. doi:10.1136/bmjopen-2014-005797
4. Eveson L, Vizcaychipi M, Patil S. Role of Bispectral index monitoring and burst suppression in prognostication following out-of-hospital cardiac arrest: a systematic review protocol. Systematic Reviews 2017 (6):191
5. Resuscitation Council, UK. Resuscitation to Recovery: A national framework to improve care of people with out-of-hospital cardiac arrest in England. March 2017.
6. Resuscitation Council UK. Consensus Paper on out-of-hospital cardiac arrest in England.
7. Resuscitation Council UK. Systems Saving Lives Guidelines. 27 October 2025.
8. Intensive Care National Audit & Research Centre (ICNARC). National Cardiac Arrest Audit: Public Report 2022–23 – Summary Statistics. 2024.
9. Farag M, Patil S. Prognostication Following Out‑of‑Hospital Cardiac Arrest. ICU Management & Practice. 2017;17(2).
10. Tsou PY, Kurbedin J, Chen YS, et al. Accuracy of point-of-care focused echocardiography in predicting outcome of resuscitation in cardiac arrest patients: A systematic review and meta-analysis. Resuscitation. 2017 May;114:92-99.
11. Academy of Medical Royal Colleges (AoMRC). A Code of Practice for the diagnosis and confirmation of death. 2025.
12. Grand J, Kjaergaard J, Bro-Jeppesen J, et al. Cardiac output, heart rate and stroke volume during targeted temperature management after out-of-hospital cardiac arrest: association with mortality and cause of death. Resuscitation. 2019; 142:136-143
13. Grand J, Hassager C, Schmidt H, et al. Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest. Crit Care. 2023; 27:410.