Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis

Overview

This narrative review by Sandroni, Cronberg and Sekhon, published open access in Intensive Care Medicine in 2021, covers post-cardiac arrest brain injury (PCABI): its mechanisms, treatment, outcomes and prognostication. PCABI is the main cause of death in patients resuscitated from cardiac arrest and the main cause of long-term disability in those who survive the acute phase.

Pathophysiology

Injury occurs in two stages: primary ischaemic injury during the arrest and secondary reperfusion injury after return of spontaneous circulation. The brain is 2% of body weight but receives 15 to 20% of cardiac output, consciousness is lost within 4 to 10 seconds of absent blood flow, and CPR provides only about 25% of normal flow when 40 to 50% is needed. Calcium overload, glutamate excitotoxicity, mitochondrial failure, reactive oxygen species and inflammation drive the damage, and no-reflow, delayed hypoperfusion and impaired autoregulation (narrowed or right-shifted in about 30 to 50% of patients) may add to it. Raised intracranial pressure from oedema is associated with poor outcome.

Treatment

There is no direct treatment, so the aim is to prevent secondary injury by avoiding derangements in temperature, blood pressure, oxygenation and ventilation. The 2021 ERC-ESICM guideline advises avoiding a mean arterial pressure below 65 mmHg, keeping oxygen saturation at 94 to 98% and keeping PaCO2 normal (35 to 45 mmHg). A randomised trial of higher blood pressure targets showed no benefit. After the TTM2 trial found no advantage of cooling to 33 °C over normothermia, ILCOR now suggests actively preventing fever (at or below 37.5 °C) for at least 72 hours in patients who stay comatose. Clinical seizures occur in about a third of patients; status epilepticus is treated with sodium valproate and levetiracetam, but prophylactic antiepileptic treatment is not recommended.

Outcomes

After the first 48 to 72 hours PCABI accounts for about two thirds of deaths, most of them following withdrawal of life-sustaining therapy, and brain death occurs in about 5% of patients resuscitated with conventional CPR. Neurological outcome is measured with the Cerebral Performance Category or, as now recommended, the modified Rankin Scale. Most patients with a good outcome wake within days of stopping sedation, whereas late awakening (after 4 to 5 days) predicts worse recovery. Survivors can have subtle cognitive impairment, fatigue and reduced quality of life, and up to 55% report a lower quality of life than before the arrest.

Neuroprognostication

About 80% of patients are comatose after resuscitation. Prognostic tests risk a self-fulfilling prophecy, and sedation and extracerebral causes of death can confound them. Clinical examination at 72 hours or more after arrest is central, especially bilaterally absent pupillary or corneal reflexes (false-positive rate under 5%), with quantitative pupillometry preferred over the visual pupillary reflex. Early, generalised and prolonged (status) myoclonus is associated with worse outcome. Neuron-specific enolase above 60 µg/L at 48 to 72 hours is the recommended biomarker cut-off, with haemolysis excluded, and neurofilament light chain is promising. Bilaterally absent N20 waves on somatosensory evoked potentials also point strongly to severe injury.