Brain Death


Cerebrocirculatory Arrest

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Irreversible Brainstem Dysfunction

1. Description of the problem

What every clinician should know

Brain death is a state of irreversible cessation of brain activity. It is used to define the occurrence of death in a person who still has cardiorespiratory function. Brain death is a legally valid proclamation of death if decreed by a qualified physician and has been recognized as such for decades. Laws regarding the determination of brain death have been adopted by most countries over the past half-century.

In the United States, the President’s Commission produced the Uniform Determination of Death Act in 1980 that was subsequently adopted by most states. The act states that: “An individual who has sustained either: 1) irreversible cessation of circulatory and respiratory functions, or 2) irreversible cessation of all functions of the entire brain, including the brainstem, is dead. A determination of death must be made with accepted medical standards” (

The American Academy of Neurology published a practice parameter defining these medical standards for determining brain death and updated the practice parameter in 2010. The diagnosis focuses on coma, absence of brainstem reflexes, and apnea. Most hospitals have developed guidelines for determining brain death based on these practice parameters, with some variations from institution to institution.

Clinical features

The diagnosis of brain death must be undertaken with great caution given the obvious implications for the patient. Even in a patient with a clinical exam showing no evidence of brainstem reflexes or brain activity, the physician needs to be extremely careful. There should be a well-defined cause for the brain injury resulting in coma and a clinical history consistent with an irrecoverable brain injury. Confounding factors such as hypothermia, sedative medications, and toxic-metabolic coma must be eliminated. If any degree of uncertainty exists, confirmatory studies should be obtained. These confirmatory studies usually assess cerebral blood flow.

To state it differently, if the head CT shows minimal brain injury (of whatever etiology) or the clinical history does not describe a scenario likely to produce fatal brain injury (hypoxic, ischemic, traumatic, etc), you should consider a confirmatory test before contemplating a diagnosis of brain death. To make matters more complicated, keep in mind that while a rapid incomplete determination of brain death is inappropriate care for the patient and poor medical practice, lengthy brain death evaluations may result in loss of organ viability and potential for donation.

2. Emergency Management


3. Diagnosis

The 2010 update to the AAN Practice Parameter on Brain Death indicates that there are no reports of recovery after a diagnosis of brain death made using the 1995 guidelines. There is no defined minimum length of observation necessary prior to determining brain death assuming that confounding factors (see below) do not exist.

General approach
  • Confirm the cause of coma based on history and physical examination, laboratory testing and neuroimaging. Diabetes insipidus is often present but not universally so and is not a criterion for brain death.

  • Confirm the absence of sedative medications or drugs by history, toxicology screens and review of medical records (drugs given in the ambulance, emergency room, etc.). Allow an appropriate amount of time for drug metabolism, considering dose, age of the patient, renal or hepatic dysfunction.

  • No neuromuscular blockers, confirmed by bedside testing (for example, train-of-four testing).

  • Normothermia.The core temperature should be near normal (for example, above 35 degrees Celsius).

  • No significant hypotension, which could alter brain function.

  • Clinical neurologic examination demonstrating no evidence of brain activity. Spontaneous or reflexive motor movements such as tremors or plantar response/reflex can be present in a patient meeting the diagnosis of brain death. The neurologic exam should demonstrate an unresponsive coma, absence of brainstem reflexes (pupils, corneas, vestibulo-ocular, gag, cough), and no purposeful movement to painful stimulus (only reflexive responses or no movement). Some states require two serial examinations prior to the declaration of brain death and others only one. Also note that some state or hospital guidelines require specific qualifications beyond being a physician, -such as being a neurologist or neurosurgeon.

  • Apnea testing: The patient must exhibit an absence of respiration despite a rise in PCO2 (hypercapnea; typically greater than 60 mmHg or a 20-mmHg increase over baseline confirmed by blood gas analysis). No particular method of doing this is recommended over any other and a few different methods are described in the literature. Apnea testing should be aborted if the patient becomes hypoxic or hemodynamically unstable. In this case a confirmatory test is used (see below).

  • Exclude the following before making diagnosis: drug- or toxin-induced coma (such as opioid overdose), ictal or post-ictal state, brainstem infarction, locked-in syndrome, severe hypothermia, organophosphate poisoning, critical illness neuropathy/myopathy, others.

Confirmatory tests

Confirmatory tests are optional in the United States except for children under 1 year of age. However, many other countries require such testing in every case. They should be used in cases where uncertainty exists regarding the presence of irreversible catastrophic brain injury. These tests include electroencephalography, transcranial Doppler sonography, conventional cerebral angiography, CT or MR angiography, or a nuclear medicine cerebral perfusion study.

EEG is fraught with false positives when used to confirm electrocerebral silence in the critical care environment and is being supplanted by cerebral blood flow studies (any of the other tests listed above) in many centers. Choice of study will depend on availability and the experience/comfort level of the physician ordering the study. The examining physician must keep in mind that the confirmatory test may complicate the patient’s management by showing cerebral perfusion despite a clinical exam consistent with brain death. Finally, note that the guidelines indicate that a barbiturate level greater than10 mcg/ml precludes a diagnosis of brain death.

4. Specific Treatment

Once a diagnosis of brain death has been made by a qualified physician, the patient is declared dead (legally deceased). The patient can then be taken off life support (respiratory or circulatory support); alternately, proceed with organ donation.

5. Disease monitoring, follow-up and disposition


Incorrect diagnosis

A wrong diagnosis can be suspected when the head CT, identifiable brain injury, clinical history, or clinical exam is not consistent with a state of irreversible, complete cessation of brain function (i.e., not consistent with brain death).






Once a declaration of brain death has been made, the patient is considered legally dead and organ harvest can proceed or the patient can be removed from ventilatory support (or other organ support).

Special considerations for nursing and allied health professionals.

An apnea test will need to be performed by respiratory therapy in order to confirm an absence of respiration even in the presence of hypercapnia. Nurses, respiratory therapists and other allied health professionals need to remember that the patient must not be injured in the process of determining brain death, in case the patient is not in fact brain dead, as well as to allow successful organ preservation and procurement, if so desired by the patient/family. This injury can easily occur with untreated diabetes insipidus, hypoxia or hemodynamic instability during apnea testing, etc.

What's the evidence?

Wijdicks, EF, Varelas, PN, Gronseth, GS, Greer, DM. “Evidence-based guideline update”. Neurology. vol. 74. 2010 Jun 8. pp. 1911-8.

Wijdicks, EF. “The case against confirmatory tests for determining brain death in adults”. Neurology. vol. 75. 2010 Jul 6. pp. 77-83.