What are the evidence-based guidelines for determining brain death in adults on Extracorporeal Membrane Oxygenation (ECMO)?

From the Guidelines

The determination of brain death in adults on Extracorporeal Membrane Oxygenation (ECMO) requires a modified approach that accounts for the altered physiology while maintaining the core principles of brain death determination, as outlined in the Extracorporeal Life Support Organization consensus guidelines 1.

Key Considerations

• The clinical examination remains the foundation, requiring documentation of coma, absence of brainstem reflexes, and apnea testing.
• Apnea testing requires temporary adjustment of ECMO settings: the sweep gas flow should be reduced to achieve a PaCO2 >60 mmHg or 20 mmHg above baseline while maintaining oxygenation through the ECMO circuit.
• Temperature must be maintained above 36°C, and confounding factors must be excluded, including sedatives, neuromuscular blockers, metabolic derangements, and hypotension.
• If clinical examination cannot be completed or is equivocal, ancillary testing becomes necessary, such as cerebral angiography, electroencephalography (EEG), transcranial Doppler, or nuclear medicine perfusion studies.
• For patients on venoarterial ECMO, cerebral blood flow assessment is particularly important as the retrograde arterial flow may complicate brain death determination.
• The observation period between examinations should be at least 6 hours, with longer periods for cases involving hypoxic-ischemic injury.

Ancillary Testing

• Ancillary studies are not required to establish brain death but can be used to assist the clinician in making the diagnosis of brain death when components of the examination or apnea testing cannot be completed safely.
• Ancillary studies can also be used to reduce the inter-examination observation period or when there is uncertainty about the results of the neurologic examination.

Important Recommendations

• A systematic review reported that an apnea test could be included in brain-death criteria in ECMO patients by reducing sweep gas flow or adding exogenous carbon dioxide 1.
• The Extracorporeal Life Support Organization consensus guidelines provide recommendations on apnea tests in ECMO patients, including the use of cerebral angiogram or nuclear scan when apnea testing is challenging due to hemodynamic/cardiopulmonary instability 1.

From the Research

Determining Brain Death in Adults on ECMO

The determination of brain death in adults on Extracorporeal Membrane Oxygenation (ECMO) is a complex process that requires careful consideration of various factors.

• The clinical evaluation starts with determination of futility of any medical or surgical intervention and an unmistakable certainty that the underlying diagnosis is correct 2.
• The actual neurologic evaluation in a patient suspected of being brain dead requires a series of tests and verifications, including examination of brainstem reflexes and apnea testing 2.
• Apnea testing is essential in the determination of brain death, but it can be challenging in patients on ECMO due to the provision of extracirculatory support and gas exchange 3, 4.
• Several methods have been proposed to perform apnea testing in patients on ECMO, including the use of an oxygenated apnea test on ECMO using continuous positive airway pressure (CPAP) through the ventilator or anesthesia bag, with an inline manometer and an end tidal CO(2) device 3.
• Ancillary tests, such as cerebral flow studies, CT angiography, and perfusion scintigraphy, may be useful in situations where clinical testing cannot be performed or when uncertainty exists about the reliability of its parts due to confounding conditions 5, 6.

Apnea Testing in ECMO Patients

• The apnea test can be performed in patients on ECMO by maximizing the reduction of the sweep gas flow to the oxygenator, maintaining an acceptable haemoglobin oxygenation level, and reducing elimination of carbon dioxide 4.
• Hypercapnia can be achieved via this method, allowing an apnea test to be conducted in the typical manner 4.
• In cases of profound desaturation and inadequate increase in arterial CO₂ concentration, the sweep gas flow rate may be increased to obtain the desired oxygenation level, and exogenous carbon dioxide may be added to achieve a target carbon dioxide level 4.

Guidelines and Recommendations

• The American Academy of Neurology guidelines have eliminated unnecessary tests and observation delays, and maintain a principle of simplicity 2.
• The Polish guidelines on the determination of brain death plan to incorporate an apnea test for ECMO patients in the next edition 4.
• Cerebral angiography and cerebral blood flow measurements are considered the most reliable investigations for confirming brain death, while the role of EEG and transcranial Doppler remains to be determined due to the presence of false negatives and positives 6.