As a demonstration of destruction of the medulla, it has become customary to perform an “apnea test” to demonstrate unresponsiveness of the medullary centers to a high carbon dioxide tension. This test is conducted by first employing preoxygenation of the lungs for several minutes with high inspired oxygen tension, the purpose of which is to displace nitrogen from the alveoli and create a reservoir of oxygen that will diffuse into the pulmonary circulation. The patient can then be disconnected from the respirator for several minutes, during which time 100 percent oxygen is being delivered by cannula or ventilator that has its pumping mechanism turned off; this allows the arterial PCO2 to rise to above 50 or 60 mm Hg (typically, CO2 rises approximately 2.5 mm Hg/min at normal body temperature—slower if the patient is hypothermic). The induced hypercarbia serves both as a stimulus to breathing and confirms that spontaneous ventilation mediated by medullary centers has failed. (Of course, peripheral causes of ventilatory failure such as paralytic drugs should not be present.) If no breathing is observed and blood gases show that an adequate level of PCO2 has been attained, this component of brain death is corroborated. Several sets of formal criteria have incorporated a CO2 concentration of 60 mm Hg (7.98 kPa [kilopascals]) as adequate to stimulate the medulla, even under circumstances in which it has been badly damaged. In our experience, patients who have severely brainstem damage but nonetheless breathe and therefore are not brain dead, have shown this activity at a PCO2 well below 50 mm Hg, but there are exceptions in which higher levels are required as a stimulus.
The risks of apnea testing are minimal, as discussed in the American Academy of Neurology’s 2010 document, but hypotension, hypoxemia, cardiac arrhythmias, and lung barotrauma may occasionally occur. In patients who cannot tolerate the test for more than a brief period because it produces hypotension, raising the arterial CO2 by insufflation of this gas has been suggested, but this approach has not been studied extensively. Delivering oxygen during the test with a low tidal volume and a ventilator rate of 1 to 2 breaths per minute or by continuous positive airway pressure may ameliorate hypoxia and resultant hypotension, but this technique has also not been adequately studied.
Most, but not all, brain-dead patients have diabetes insipidus. The absence of this syndrome in some cases reflects the imprecision of the clinical examination in detecting a total loss of brain function. Other ancillary bedside tests may be conducted to corroborate brain death. Among the ones used in special circumstances is the absence of tachycardia in response to the injection of atropine; this reflects the loss of cardiac innervation by damaged medullary vagal neurons.
The authors have observed a number of dramatic spontaneous movements when severe hypoxia is attained following terminal disconnection from the ventilator. These include opisthotonos with chest expansion that simulates a breath, elevation of the arms and crossing them in front of the chest or neck (given the name Lazarus sign by Ropper in 1984), head-turning, shoulder-shrugging, and variants of posturing-like movements. For this reason it may be advisable for the family not to be in attendance immediately after mechanical ventilation has been discontinued.
The EEG provides confirmation of cerebral death, and some institutions prefer to include corroboration by the demonstration of electrocerebral silence (“flat” or, more accurately, isoelectric EEG, shown first by Schwab). However, most U.S. institutions do not require an EEG for the confirmation of death. Electrocerebral silence is considered to be present if there is no electrical potential of more than 2 mV during a 30-min recording except for artifacts created by the ventilator, electrocardiograph, and surrounding electrical devices; as importantly, the absence of these artifacts suggests a technical problem with the recording.