Neuroprognostication following Cardiac Arrest

Cardiac Arrest (CA) following a non-traumatic cause is associated with a poor outcome. In United Kingdom, NHS ambulance services attend to approximately 30,000 patients a year for Out-of-Hospital Cardiac Arrest (OHCA) [Perkins, 2015].

and according to the latest National Cardiac Arrest Audit data there were 10,414 patients who suffered an In-hospital Cardiac Arrest (IHCA) [NCAA, 20-21].

Average survival to hospital discharge for Out of Hospital Cardiac Arrest (OHCA) patients was only 8.6% [Resus Council, 2015] and for inpatients was 21.8% [NHCAA, 20-21]. Equivalent results are also recorded in the American continent [Geocadin, 2017].

Despite advances in post-resuscitation care management, about 50% of resuscitated patients from 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 [Nolan, 2015].

The associated costs and length of stay is also significantly higher in patients with poor neurological outcome. [Petrie, 2014]. 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 [Eveson, 2017].

The ‘Chain of Survival’, an internationally recognised concept summarises the important components of successful resuscitation.

The first three link 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 decision like continuation of resuscitation, likelihood of survival with good neurological outcome and 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 are less well defined. This is highly influenced by the hospital to which 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.

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.

Pre-Cardiac Arrest factors associated with adverse outcome

Patient factors:

• Increasing Age
• Associated Co-morbidities

Event related factors:

• Unwitnessed Event

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

Post Cardiac Arrest factors associated with adverse outcome

• Lack of Targeted Temperature Management (TTM) Although most guidelines have not been updated since the publication of the TTM2 trial.
• 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)

Prognostication Strategy: (Farag, 2017)

At the recently concluded International Symposium on Intensive Care and Emergency Medicine, the experts in this field suggested a strategy for the treating physicians.

The key principles of this strategy are:

Early Communication with the next of kin
It is important to provide early on a meaningful information and make them aware of patient’s critical condition. This helps the physician to understand the expectations, but it is vital to convey that physicians will take decision in the best interest of the patient.

Delay the timing of prognostication
The current recommendations are to consider prognosis at 24 or 72 hours depending on patient not receiving or receiving temperature management. 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
It is highly recommended for the physicians to use clinical examination, electrophysiological tests, biochemical markers and radiological tests while considering neuro-prognostication. This is discussed subsequently in further detail.

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: (Sandroni, 2014)

The key recommendations are summarised below:

1. Clinical examination

• Using the bilateral pupillary and corneal reflexes at 72 h or more from ROSC
• Prolonging observation of clinical signs beyond 72 h when interference from residual sedation or paralysis is suspected, so that the possibility of obtaining false positive results is minimised;
• Not to use absent or extensor motor response to pain (M 2) alone to predict poor outcome as it has a high false-positive rate.

2. Myoclonus and status myoclonus

• Using the term status myoclonus to indicate a continuous and generalised myoclonus persisting > 30 mins in comatose survivors of CA;
• Using the presence of a status myoclonus within 48 h from ROSC in combination with other predictors.
• Evaluate patients with post-arrest status myoclonus off sedation whenever possible.

3. Bilateral absence of Somatosensory Evoked Potential (SSEP) 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)

• Absence of EEG reactivity to external stimuli, presence of burst suppression or status epilepticus at 72 h after ROSC to predict poor outcome in comatose survivors from CA.

5. Biomarkers

• Use high Neuron Specific Enolase at 48-72 h from ROSC.
• no threshold enabling prediction with zero false-positive results can be recommended.
• Utmost care and preferably multiple sampling should be employed to avoid false positive results due to haemolysis.

6. Imaging

• Use the presence of a marked reduction in grey matter/white matter ratio or sulcal effacement on brain CT within 24 hours after ROSC.
  presence of the extensive reduction in diffusion on brain MRI at 2-5 days after ROSC.

Point of Care Focussed Echocardiography:

In recently published systematic review, 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. There is currently not enough evidence and still very early on to consider focused echocardiography as a part of multimodal prognostication strategy [Tsou, 2017].

Brain Stem Death, also referred as Brain Death is an irreversible cessation of brain stem function whether induced by intra-cranial events or the result of extra-cranial phenomena, such as hypoxia, will produce this clinical state and therefore irreversible cessation of the integrative function of the brain stem equates with the death of the individual and allows the medical practitioner to diagnose death. Though, this is mainly assessed in intensive care settings, it is essential part of understanding for any acute physician.

Three things should be noted in this regard:

1. The irreversible loss of the capacity for consciousness does not by itself entail individual death. Patients in the vegetative state (VS) have also lost this capacity. The difference between them and patients who are declared dead by virtue of irreversible cessation of brain-stem function is that the latter cannot continue to breathe unaided without respiratory support, along with other life-sustaining biological interventions. This also means that even if the body of the deceased remains on respiratory support, the loss of integrated biological function will inevitably lead to deterioration and organ necrosis within a brief time.

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.

The following conditions must be fulfilled to allow the diagnosis of death following irreversible cessation of brainstem function to be undertaken.

1. Aetiology of irreversible brain damage should be known.
2. Exclusion of potentially reversible causes of coma.

The patient is deeply comatose, unresponsive and apnoeic, with his/her lungs being artificially ventilated.

• There should be no evidence that this state is due to depressants drugs.
• Primary hypothermia as the cause of unconsciousness must have been excluded.
• Potentially reversible circulatory, metabolic and endocrine disturbances must have been excluded as the cause of the continuation of unconsciousness.

3. Exclusion of potentially reversible causes of apnoea.

• 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.

Repetition of testing See Fig 3.

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 patients 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. Although death is not confirmed until the second test has been completed the legal time of death is when the first test indicates death due to the absence of brain-stem reflexes.

• Current Prevalence of Cardiac Arrest
• Concept of Chain of Survival
• Factors influencing survival to hospital discharge
• Principles of Prognostication Strategy
• Multimodal evaluation technique
• Diagnosing Brain Stem Death

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