Post Cardiac Arrest Syndrome (PCAS)
Systemic ischemia during cardiac arrest and the reperfusion response after return of spontaneous circulation (ROSC) cause the post-cardiac arrest syndrome (PCAS). The severity and duration of this syndrome is determined by the cause and duration of cardiac arrest, as well as the quality of resuscitation and interventions after ROSC.
Mechanism:
Postcardiac arrest syndrome was once thought to be generally related to production of free radicals, although the pathophysiology is more complex.
• Hypoperfusion and ischaemia cause a cascade of events
o Disruption of homeostasis
o Free radical formation
o Protease activation
o A SIRS response resembling severe sepsis
• The disruption may continue for hours or days
• Hypothermia may slow down this cascade
Major manifestations:
- Postcardiac Arrest Brain Injury – Disruption on both a micro- and macro- circulatory levels may result in either ischaemia or hyperaemia.
- Postcardiac arrest myocardial dysfunction – Although the heart initially becomes hyperkinetic, likely due to circulating catecholamines, global hypokinesis often follows. Usually resolves within 72 hours.
- Systemic Ischaemia/Reperfusion Response – The response of the body is similar to the septic shock with activation of the immune and complement systems, and release of inflammatory cytokines and a wide range of cellular responses.
- Persistent precipitating pathology – The cause of the arrest may continue to impact physiological parameters.
Contributing factors:
• Post cardiac arrest brain injury
o Impaired cerebrovascular autoregulation
o Cerebral oedema
o Neurodegeneration
• Post cardiac arrest myocardial dysfunction
o Myocardial stunning – global hypokinesis
o Poor cardiac output
o Acute coronary syndromes
• Systemic ischaemia / reperfusion response
o Systemic inflammatory response syndrome (SIRS)
o Poor vasoregulation
o Microcirculatory failure
o Activation of coagulation cascade
o Adrenal suppression
o Poor tissue oxygen deliver and utilization
o Susceptibility to infection
• Persistent precipitating pathology
o Cardiovascular disease (e.g. myocardial ischemia, cardiomyopathy)
o Pulmonary disease (e.g. pulmonary embolus, asthma)
o CNS disease (e.g. stroke, subarachnoid hemorrhage)
o Poisoning
o Infection / Sepsis
o Hypovolaemia
Other complications of resuscitation such as injuries (e.g. rib fractures, sternal fractures), medication adverse effects and complications of invasive lines and monitoring.
Assessment tools for diagnosing PCAS: Hypoxic–ischaemic brain injury (HIBI)
• Hypoxic–ischaemic brain injury (HIBI) is the main cause of death in patients who are comatose after resuscitation from cardiac arrest.
• A poor neurological outcome—defined as death from neurological cause, persistent vegetative state, or severe neurological disability—can be predicted in these patients by assessing the severity of HIBI.
• The most commonly used indicators of severe HIBI include bilateral absence of corneal and pupillary reflexes, bilateral absence of N2O waves of short-latency somatosensory evoked potentials, high blood concentrations of neuron specific enolase, unfavourable patterns on electroencephalogram, and signs of diffuse HIBI on computed tomography or magnetic resonance imaging of the brain.
• Current guidelines recommend performing prognostication no earlier than 72 h after return of spontaneous circulation in all comatose patients with an absent or extensor motor response to pain, after having excluded confounders such as residual sedation that may interfere with clinical examination. A multimodal approach combining multiple prognostication tests is recommended so that the risk of a falsely pessimistic prediction is minimised.
a. Electroencephalography:
• The use of EEG is advocated to detect seizures and post-anoxic status epilepticus, particularly when detected early during TH.
• Good neurological outcome has been reported following aggressive anti-epileptic therapy for seizures occurring in the rewarming phase, especially in selected patients (that is, those with preserved brainstem reflexes, present cortical response on SSEPs and a reactive EEG).
• In addition to seizure detection, EEG has been used to identify specific patterns associated with outcome during HIE.
o A dichotomized definition of EEG patterns, such as malignant or benign, has been developed.
o EEGs are considered to have a malignant pattern if post-anoxic status epilepticus, alpha coma or burst suppression or generalized suppression is present.
o Other EEG patterns, including a generalized slowing activity, generalized alpha–theta frequencies or the presence of epileptiform discharges, are considered benign or of unclear significance.
b. Somatosensory evoked potentials:
• The SSEP is a small (<10 to 50 μV) electrical signal that can be recorded non-invasively from the skull after administering a set of electrical stimuli to one of the peripheral nerves.
• In CA patients, the median nerve is most commonly stimulated bilaterally at the wrist. Electrodes are then placed at the elbow, Erb’s point, the cervical medulla (peripheral) and on the parietal and frontal cortex (cortical); specific responses are commonly identified as N9 for Erb’s point, N14 for the cervical medulla and N20 for cortex. The cortical responses can only be reliably interpreted when the peripheral and spinal responses are also present.
• If peripheral responses are not present, this may be due to peripheral nerve damage. For prognosis of a poor outcome after CA, only the short cortical latencies (N20, expected to appear 20 milliseconds after median nerve stimulation) are used.
• In order to have absent SSEPs, predictive of a poor outcome, cortical responses have to be absent bilaterally in a technically well-performed test.
• In patients who remain comatose after CA, SSEPs have been shown to reliably predict poor outcome.
c. Biomarkers:
• Biomarkers are quantifiable biological substances, usually peptides, which can be easily measured in peripheral blood. Biomarkers of brain injury in comatose survivors from CA include NSE and S-100β.
• Before widespread use of TH, serum NSE levels >33 μg/l at 72 hours after CA were strongly associated with poor prognosis. Hypothermia may significantly reduce serum NSE levels, probably by selective attenuation of neuronal injury.
• High concentrations of S-100β have also been found in patients remaining comatose after CA; however, different cutoff levels, ranging from 0.2 to 1.5 mg/l, have been proposed to predict poor neurological outcome in this setting.
d. Imaging:
• Computed tomography (CT) imaging in neuro-prognostication of comatose CA survivors:
o Early CT can be helpful to rule out a cerebral cause of coma and/or CA, especially in cases with preceding neurological symptoms, in cases with nonshockable rhythms or in young patients without cardiovascular risk factors.
o Moreover, as brain death may occur in up to 10% of patients in the days following CA, CT can provide evidence of an irreversible neurological catastrophe in patients being considered for brain death determination.
o A loss of distinction between gray and white matter, indicating cerebral edema, has been associated with a lower likelihood of good outcome.
• Magnetic resonance imaging (MRI):
o Magnetic resonance imaging (MRI) provides a more sensitive indication of brain injury after CA compared with CT, and the use of apparent diffusion coefficient values has recently helped to quantify the degree of injury.
Monitoring options:
• General intensive care monitoring:
o Arterial catheter
o Oxygen saturation by pulse oximetry
o Continuous ECG
o CVP
o ScvO2
o Temperature (bladder, esophagus)
o Urine output
o Arterial blood gases
o Serum lactate
o Blood glucose, electrolytes, CBC, and general blood sampling
o Chest radiograph
• More advanced haemodynamic monitoring:
o Echocardiography
o Cardiac output monitoring (either non-invasive or PA catheter)
• Cerebral monitoring:
o EEG (on indication/continuously): early seizure detection and treatment
o CT/MR
Management:
• All survivors of out-of-hospital cardiac arrest should be considered for urgent coronary angiography unless the cause of cardiac arrest is clearly non-cardiac, or continued treatment is considered futile.
• Hypoxic-ischaemic brain injury is the commonest cause of death among those admitted to ICU but who do not survive to leave hospital.
• Interventions that may improve the chance of a good neurological outcome include:
o Controlled reoxygenation
o Controlled ventilation to achieve normocapnia
o Maintenance of adequate cerebral perfusion pressure
o Targeted temperature management (mild hypothermia and avoidance of hyperthermia)
o Glucose and seizure control.
• In patients remaining comatose after resuscitation from cardiac arrest, prediction of the final outcome is unreliable in the first few days. If therapeutic hypothermia has been used, prognostication should normally be delayed for at least 72 hours after return to normothermia and should involve more than one mode, for example, clinical examination combined with electrophysiological investigations.