Brain Death

Key points

Brain death in context

Critical care physicians are frequently called on to diagnose and manage brain death. Although the medical and legal concepts of brain death are generally accepted, establishing the diagnosis is not simple and must be performed accurately. The details of how to diagnose brain death have been codified in guidelines by panels of experts1, 2, 3, 4; however, precision in the brain death examination varies, and skepticism has been expressed in the lay literature about the accuracy of brain death

History

Mollaret and Goulon¹⁰ from the Hospital Claude Bernard in Paris first described irreversible coma (“le coma depasse”) in 1959. In 1968, Harvard Medical School convened an ad hoc committee to examine the concept of brain death from a clinical and ethical perspective. Led by renowned ethicist Henry Beecher, the committee published what it felt to be its unbiased and relatively simple assessment in JAMA that same year.¹¹ Three years later, Mohandas and Chou¹² expanded on this work by emphasizing

Brain death policies

Every hospital caring for patients with severe neurologic injury should have a policy for determining brain death. This policy should specify what specialties and professional roles (eg, attending, resident) might determine brain death, how they will be trained, whether credentialing for brain death determination will be required, and the precise criteria and parameters for the process. These should all be in accordance with or at least in consideration of the AAN guidelines.

A recent survey

Neuroimaging in brain death

Determination of brain death begins with identifying a cause. Cause is determined by history, clinical examination, and neuroimaging studies. Clinicians should take pause when the circumstances are unclear or when imaging appears normal. Computerized tomography (CT) findings after neurologic injury include hemorrhage, edema, mass lesions, or ischemia, but imaging may be normal in the first 24 to 48 hours or longer in situations of hypoxic injury and central nervous system (CNS) infection. In

Clinical criteria

After establishment of cause, review of neuroimaging and assurance that other prerequisites have been met, brain death determination may proceed. The process involves neurologic tests, consideration of confounders, resolution of any misleading or conflicting evidence, and if necessary, performance of confirmatory tests. Normothermia, hemodynamic stability, correction of extreme electrolyte disturbances, and confirmation of absence of neuromuscular blockade are essential before examination (Box 1

Apnea testing

After establishing coma and absence of the 7 brainstem reflexes, confirmation of apnea is the third and final step in determining brain death. Various methods exist but all of them rely on a period of observing the patient during cessation of mechanical ventilation.¹⁸ Essential steps are shown in Box 3. Before apnea testing, the patient must be preoxygenated for at least 10 minutes with 5 or more cm H₂O of positive end-expiratory pressure (PEEP) to wash out respiratory nitrogen and facilitate

Misleading motor movements

Muscle movements in brain dead patients can confuse and cause uncertainty among clinicians, staff, and families. The exact physiologic basis for such movements is not known.¹⁸ These movements arise from the spinal cord and include spontaneous twitches, movements of the limbs, including arm raises, head turning, toe twitching, positive Babinski, triple flexion response (hip and leg flexion and foot dorsiflexion), respiratorylike movements that can trigger the ventilator and confuse apnea

Conditions that mimic brain death

Three conditions may mimic brain death: locked-in syndrome, hypothermia, and drug intoxication. Locked-in syndrome results from an injury at the level of the pons with preservation of portions of the midbrain. The patient cannot move his or her limbs, grimace, or swallow but consciousness is preserved, as are blinking and vertical gaze. Locked-in syndrome most commonly results from basilar artery embolic stroke.²⁶ A similar clinical picture can occur with Guillan-Barre in which cranial and

Ancillary testing

Brain death is primarily a clinical diagnosis. After clinical confirmation of brain death as described previously, including confirmation of apnea, death may be declared. In adults, ancillary tests are not required except when the examination is not reliable or when mandated by institutional guidelines. Some advocate routine use of ancillary tests in conjunction with the clinical examination for the determination of brain death,³² whereas others argue that confirmatory tests are unnecessary and

Mechanistic basis for ancillary testing

Ancillary tests are based on either absence of cerebral blood flow or lack of electrical activity (see Box 5). To understand the mechanism by which confirmatory tests determine brain death, one must consider brain death physiology. Palmer and Bader³⁴ suggest hypothetical mechanisms for brain death. First, intracranial pressure exceeds mean arterial pressure (ICP > MAP) resulting in brain and brainstem death due to lack of blood flow. This first hypothesis is the one on which most ancillary

Types of ancillary testing

The 3 most commonly performed ancillary tests are cerebral scintigraphy (hexamethylpropyleneamine oxime [HMPAO]), cerebral angiography, and electroencephalogram (EEG). Other potential confirmatory tests include transcranial Doppler study (TCD), CT angiography, and magnetic resonance angiography (MRA). Conventional MRI and CT lack the sensitivity and specificity required to act as an ancillary test for brain death. The Canadian Guidelines³⁸ and the Australian-New Zealand Intensive Care Society

Cerebral angiography

Cerebral angiography is the test by which most other ancillary tests are referenced. However, angiography is invasive, requires prolonged travel to the angiography suite, is not readily available and interpretable at many centers, and is relatively expensive. Proper technique for cerebral angiography is specified in the AANPP guideline and includes high-pressure injection into the aortic arch, contrast medium should reach both anterior and posterior circulations, no intracerebral filling at the

Cerebral scintigraphy

Scintigraphy, often called nuclear flow testing or SPECT (single-photon emission CT), uses a gamma-emitting radioactive tracer instilled into the venous system and detected by a radio counter in nuclear medicine. Reliability is comparable to cerebral angiography.⁴¹ The tracer is technetium 99m-HMPAO (Tc99-HMPAO). Nuclear scintigraphy requires instrumentation, a radiologist with expertise to interpret the test, and the relatively expensive radioisotope that must be reconstituted by a specialty

Electroencephalography

EEG in brain dead patients seeks to establish a lack of reactivity to intense somatosensory or audiovisual stimuli. Techniques for reliable testing are demanding and specific and include a minimum of 8 scalp electrodes, a check of the entire recording system, a distance between electrodes of least 10 cm, and sensitivity increased to at least 2 μV for 30 minutes.² EEG is the most technically cumbersome to perform and interpret, time-consuming, and least often used ancillary test.

Transcranial Doppler ultrasonography

Transcranial doppler ultrasonography (TCD) is noninvasive, bedside, and relatively quick to perform and interpret, but there is little consensus on the usefulness of TCD as an ancillary test, as it does not necessarily quantify cerebral blood flow. TCD is very technician and interpreter-dependent. It requires visualization of each hemisphere (both internal carotid arteries and the basilar artery) and demonstration of an abnormal flow pattern. TCD is useful only if a reliable signal is found. Up

Computed tomography angiography

Computed tomography angiography (CTA) was first reported as an ancillary test in the diagnosis of brain death in 1998 as having 100% specificity.⁴⁶ It is used widely in Europe as an ancillary test to determine cessation of cerebral blood flow but has not yet been adopted in the United States.⁴⁷ CTA is readily available, relatively inexpensive, easy to acquire, minimally invasive, and fast, but requires precision performance. Diagnostic criteria are lack of intracranial arterial contrast

Magnetic resonance angiography

Determination of brain death by MRA should be based on the same criteria as CTA. Although likely a reliable test for cerebral blood flow, MRA has not yet been proven as an ancillary test in brain death. Like any MRI, the patient must be transported to the radiology suite, examination time is longer than CT or HMAO-SPECT, and the patient and monitors must be MRI-compatible.²

Regardless of the test used, radiologists and others who interpret the tests hold a precarious position in brain death

Documentation of brain death

The authors endorse the use of the checklists provided in both adult and pediatric published guidelines.2, 3 We include these in the documentation of brain death examination in the electronic health record at our institution and believe it serves to remind the examiner to perform a complete examination and documents the examination accurately in the medical record. If all requirements are not met, the electronic record should not accept the note.

Critical care of the brain dead patient

Cerebral ischemia progresses from rostral to caudal as brain death ensues and physiologic changes occur simultaneously. First, cerebral ischemia results in vagal activation with bradycardia and possibly hypotension. Next, the pons becomes ischemic, stimulating the Cushing response of sympathetic stimulation with parasympathetic modulation resulting in moderate hypertension and bradycardia. With uncal herniation, the upper medulla becomes ischemic. A “sympathetic storm” is caused by sympathetic

Variability in brain death determination among nations

In the United States, the UDDA makes the regulatory definition of death clear; however, in other countries such regulatory consistency is not always present. Although most European nations rely primarily on clinical examination and view brain death similar to the United States, in several European countries, ancillary testing is mandatory.⁷³ Cultural and religious differences between nations coincide with differences in the concept of the meaning of death. For this reason, an international

Brain death and the law

In 1978, as definitions regarding determinations of death were being increasingly scrutinized in criminal and civil litigation, the Uniform Law Commissioners created the Uniform Brain Death Act. This Act was modified to become the UDDA in 1980. The UDDA sought to clarify terminology and added “irreversible cessation of circulatory and respiratory functions” as an alternative to the standards. The act is designed to address minimum reasonable standards and is intentionally vague. By recognizing

Brain death and religion

Early scholars of brain death asserted that its concept and practice were compatible with the beliefs of the world’s principal religions.⁷⁷ Most Christians accept brain death without serious exception.⁷⁸ Before an International Transplant Society meeting in 2000, Pope John Paul II affirmed brain death to be compatible with Catholic beliefs.⁷⁹ A rabbinic debate persists in Judaism. Reform and Conservative rabbis accept brain death almost without exception but this is not the case within more

Ethical challenges

Ethical controversy exists among medical practitioners of the same specialty regarding the real meaning and definition of brain death. Even neurologists lack a consistent teleologic definition of brain death and argue about the optimal diagnostic tests for brain death. Almost half of neurologists accept brain death fundamentally as a state of permanent unconsciousness, but many do not consider brain death as equivalent to circulatory death.85, 86, 87 Wijdicks writes “confirmatory tests do not

Summary

Brain death determination is a fundamental part of surgical critical care. It has an interesting history and continuing ethical implications. Statutory guidance is minimal. Practice guidelines exist but are not widely implemented. Significant policy and practice variation exists, putting the ill-informed or inexperienced intensivist at risk. The gravity of brain death determination is arguably the greatest of any clinical assessment we perform. We should feel confident in following our own