Hypoxic-Ischaemic Brain Injury After Cardiac Arrest

Hypoxic ischaemic brain injury after cardiac arrest is diffuse neuronal injury from global cerebral hypoperfusion during arrest, and further injury on reperfusion. It is the commonest cause of death and disability in patients resuscitated from out-of-hospital arrest.

Epidemiology. About 80% of patients resuscitated from cardiac arrest are comatose on admission. About 40 to 50% of them regain consciousness, and many die after withdrawal of life support. Neuronal injury evolves over the first 72 hours.

Pathophysiology. Loss of oxygen and glucose causes energy failure, glutamate release, calcium entry and cell death within minutes. Reperfusion causes free radical injury, inflammation, microvascular no reflow, disturbed autoregulation, seizures, cerebral oedema (late) and secondary injury from hypotension, hypoxia, hyperoxia, hypercapnia or hypocapnia, fever and hypoglycaemia.

Patterns. Selective vulnerability of the hippocampus, cortex (layers 3, 5 and 6), cerebellum, basal ganglia and thalamus. Brain death results when swelling raises intracranial pressure over arterial pressure.

Presentation is persistent coma with absent or reduced responsiveness, abnormal brainstem reflexes in severe injury, myoclonus (including status myoclonus within 72 hours), seizures, and later cognitive deficits, spasticity and Lance-Adams syndrome (action myoclonus after awakening). Survivors may have memory, attention and executive deficits.

Red flags.

• Early status myoclonus within 72 hours.
• Absent pupillary and corneal reflexes at 72 hours or more.
• Clinical seizures or EEG seizure activity.

Neurological examination off sedation (Glasgow motor score, pupillary light reflex, corneal reflex, myoclonus). Continuous or repeated EEG, somatosensory evoked potentials, serum neuron specific enolase at 24, 48 and 72 hours, CT head at 24 hours and later (loss of grey to white matter differentiation, sulcal effacement) and MRI with diffusion at 2 to 7 days. Exclude other causes (intracranial haemorrhage, drug effect, metabolic).

Differential diagnosis. Sedative and neuromuscular blocker accumulation, hypothermia, metabolic encephalopathy, nonconvulsive status epilepticus, stroke and intracranial haemorrhage.

Prevent secondary injury. Oxygen saturation 94 to 98%, PaCO2 4.7 to 6.0 kPa, mean arterial pressure at least 65 mmHg (some aim 70 to 80 mmHg), glucose 7.8 to 10 mmol/L, sodium 135 to 145 mmol/L, head elevation 30 degrees, and temperature control. Prevent fever over 37.7 °C for 72 hours and use a target of 32 to 37.5 °C for at least 24 hours.

Seizures and myoclonus.

• Levetiracetam 60 mg/kg IV (maximum 4500 mg), then 500 to 1000 mg every 12 hours, adjusted to eGFR.
• Valproate 40 mg/kg IV (maximum 3000 mg), or phenytoin. Propofol or midazolam infusion for refractory status.
• Clonazepam 0.5 to 1 mg orally or IV for myoclonus.
• Do not give prophylactic anti-seizure medicines.

Sedation. Short acting agents (propofol, remifentanil) allow earlier examination. Stop and allow clearance before prognostic examination. Allow at least 5 half lives, longer in hypothermia, liver or renal impairment.

Prognostication (at least 72 hours after return of circulation, and after normothermia).

• Exclude confounders (sedation, neuromuscular blockade, hypothermia, hypotension, metabolic disturbance).
• A poor outcome is likely when two or more of the following are present: no pupillary light reflex and corneal reflex at 72 hours or more; bilateral absent N20 waves on somatosensory evoked potentials; highly malignant EEG (suppressed background with or without periodic discharges, or burst suppression) beyond 24 hours; serum neuron specific enolase over 60 microgram/L at 48 hours or 72 hours; status myoclonus within 72 hours; diffuse anoxic injury on CT or MRI.
• If findings are uncertain, observe longer and repeat.

Withdrawal and decisions. Hold family meetings with a multidisciplinary team, address uncertainty openly, and consider organ donation. Brain death testing when criteria are met.

Rehabilitation. Early rehabilitation, cognitive and neuropsychological assessment, screening for depression, anxiety and post-traumatic stress, and support for carers.

Monitoring. Neurological examination every 4 hours, EEG, intracranial signs, electrolytes and temperature.

Referral and escalation. Neurology, neurophysiology, intensive care and rehabilitation services.

Special groups. In children, the same principles with age appropriate norms. In pregnancy, the same principles with obstetric input.