Determination of Brain Death

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Preface

1.1 The medical and legal communities have indicated that locally acceptable guidelines are to be used for the diagnosis of death. This document establishes the Massachusetts General Hospital criteria to be implemented when rendering a diagnosis of death based on failure of brain function. This has been referred to as brain death, but must be understood to be no different than a diagnosis of death made by other criteria. Death by brain criteria is defined under Massachusetts state law as the total and irreversible cessation of spontaneous brain functions, in which further attempts of resuscitation or continued supportive maintenance would not be successful in restoring such function. (See 10 C.M.R. 800.004; Commonwealth v. Golston, 373 Mass. 249, 355 N.E. 2nd 744, 1977.)

1.2 Brain death is defined as the irreversible loss of the clinical function of the whole brain, including the brain stem. Brain death from primary neurological disease usually is caused by severe head injury or cerebrovascular events. In patients in medical and surgical intensive care units, however, global ischemic brain insults or fulminant hepatic failure may result in irreversible loss of brain function.

1.3 These guidelines do not replace the physician's judgment in individual cases, since brain death is a clinical diagnosis. The guidelines are not intended to encourage use of resources to establish the diagnosis. Ancillary testing is required only in situations in which the clinical determination is unavoidably inadequate, e.g. in cases of severe facial trauma, drug intoxication or severe metabolic disturbances. The guidelines are felt to be reasonable, current and generally accepted criteria for use in the diagnosis death by brain criteria.

1.4 Please refer to the policy Death: Determination using Brain Criteria for Infants and Children located in the Clinical Policy and Procedure Manual.

Important First Steps and New Requirements

2.1 Please read this entire document before starting the process of declaration, as it contains important procedural information and identifies common pitfalls.

2.2 If the patient is under the care of a non-neurological physician, then an attending neurologist or neurosurgeon must be consulted to assist in the diagnosis of brain death.

2.3 Contacting the New England Organ Bank (1-800-446-6362) prior to any discussion about organ donation with the family is now mandatory for any patient who is likely to meet criteria for organ donation. The NEOB coordinator will review the case with the health care team and approach the family together with the health care team to offer the opportunity for donation.

2.4 Attempt to bring the PCO2 between 35-45 mm Hg and the pH between 7.35-7.45 at least 20 minutes prior to apnea testing, since this will reduce the chances of hemodynamic instability during the testing. Apnea testing can still be performed if the patient is acidotic or hypercapneic (see below I.B.3). A member of the Respiratory Therapy department must be present during apnea testing.

2.5 Avoid the use of psychoactive/sedating medications, especially those with a longer half-life. (If psychoactive medications have recently been given, please see section I.3. below.) 2.6 In cases in which the process of determining death by brain criteria may be in conflict with religious, cultural or personal beliefs of the patient or the patient's family, consultation of the Medical Ethics Committee (Optimum Care Committee) may be helpful.

Technical Criteria

3.1 Diagnostic Criteria for Clinical Diagnosis of Brain Death:

• Prerequisites:
  1. The proximate cause must be known, and must be known to be irreversible. There must be clinical or neuroimaging evidence of an acute central nervous system catastrophe that is compatible with the clinical diagnosis of death by brain criteria. (In particular cases, e.g. in the acute setting after a cardiac arrest, a period of observation and repeat examination may be warranted; a period of 6 hours has been recommended, but this amount of time is arbitrary.)
  2. Exclusion of complicating medical conditions that may confound the clinical assessment (acid-base or severe electrolyte disturbances, including hyperammonemia, or endocrine disturbances).
  3. Serum toxicology screening with a demonstrated absent barbiturate level and no evidence of other drug intoxication or poisoning. If a barbiturate level is present, it must be < 10 mcg/ml. If significant doses of CNS depressing medications (e.g. narcotics, sedatives, hypnotics, anticholinergics, etc.) have been administered recently, the reliability of the clinical examination should be called into question, and ancillary testing should be considered.
  4. Demonstrated absence of neuromuscular blockade (e.g. with train of four nerve stimulation) if the patient has received recent or prolonged use of neuromuscular blocking agents.
  5. Core temperature = 36.5 ° C (96.8 ° F)
  6. In the presence of confounding variables, brain death may still be determined with the aid of ancillary tests (see below).

3.2 The three cardinal findings in brain death: coma or unresponsiveness, absence of brain stem reflexes, and apnea.

1. Coma defined as the absence of any cerebrally mediated motor response to noxious stimuli, including pain in all extremities (nail-bed pressure) and supraorbital pressure.
2. Absence of brain stem reflexes
   • Pupils
     • No response to bright light (a magnifying glass may be useful if response is questionable)
     • Size: from midposition (4 mm) to dilated (9 mm) small or pinpoint pupils should alert the clinician to the possibility of narcotic intoxication (but may also be seen with pontine damage).
   • Ocular movement
     • No oculo-cephalic reflex (testing only when the integrity of the cervical spine is assured)
     • No vestibulo-ocular reflex: deviation of the eyes to irrigation in each ear with 30-50 ml of ice water. (Observe for 1 minute after irrigation, and at least 5 minutes between testing on each side) Testing may be confounded with blood or cerumen in the auditory canal, a disrupted tympanic membrane, or injury to the globes or orbits.
   • Facial motor response to stimulation
     • No corneal reflex to touch with a cotton swab
     • No jaw reflex
     • No facial grimacing to deep pressure on nail bed, supraorbital ridge, or temporomandibular joint
     • Facial myokymias, resulting from denervation of the facial nerve, are spontaneous and permissible.
   • Pharyngeal and tracheal reflexes
     • No response to stimulation of the posterior pharynx with tongue blade
     • No coughing or significant bradyarrhythmia to bronchial suctioning
3. Apnea: Apnea testing performed as follows:
   • The NeuroIntensive Care Unit (726-8071) staff are available for assistance with apnea testing (or any other aspect of the guidelines) if needed.
   1. Prerequisites
      • Core temperature 36.5 C (96.8 F)
      • Systolic blood pressure > 90 mm Hg. If the patient is requiring significant amounts of vasopressor agents to support the blood pressure to this range, or is having unstable cardiac dysrhythmias, then ancillary testing should be considered in lieu of apnea testing.
      • Correct the electrolyte disturbances of diabetes insipidus, with a positive fluid balance in the past 6 hours if severe hypernatremia present.
      • Adjust the ventilator to obtain an arterial pH to 7.35-7.45 and pCO2 to 35-45 mm Hg if possible at least 20 minutes prior to initiating the test.
      • Preoxygenation with 100% FiO2 for 5 minutes or to arterial PO2 > 200 mm Hg if possible
   2. Assure the proper functioning of a pulse oximeter. Attach a catheter to an oxygen source and deliver 100% O2 at 8-10 L per minute via the endotracheal tube or tracheostomy to the level of the carina immediately after disconnecting the ventilator. Because most ventilators do not supply a steady flow of oxygen unless the ventilator is cycling, and because the ventilator can register breaths inappropriately with stimuli, it is recommended to disconnect the ventilator during the test.
   3. Observe closely for respiratory movements (defined as abdominal or chest excursions). Chest wall excursions secondary to cardiac pulsations are not considered respiratory efforts. pH usually decreases by at least 0.02 units per minute of apnea.
   4. Measure PO2, PCO2, and pH after approximately 8 minutes and reconnect the ventilator. The apnea test must be terminated if the patient becomes hypoxic, cyanotic or hemodynamically unstable (see below).
   5. If respiratory movements are absent and the final arterial blood gas shows
      • pH < 7.30 (from a patient with pre-test pH of > 7.4) or
      • PCO2 increases from 40 up to 60 mm Hg or 20 mm Hg increase from the pre-test baseline then,
      • apnea has been demonstrated, supporting the diagnosis of death by brain criteria.
   6. If respiratory movements are observed or the blood gas criteria are not met, the apnea test result is negative: apnea has not been demonstrated and this does not support the clinical diagnosis of death by brain criteria.
   7. If during testing the patient becomes cyanotic, systolic blood pressure becomes < 90 mm Hg, the pulse oximeter indicates significant oxygen desaturation or cardiac arrhythmia develop, then immediately draw an arterial blood sample and reconnect the ventilator. If the patient has remained apneic during the test and blood gas values meet the criteria above (see item e.), then apnea has been demonstrated. If the blood gas values do not meet the criteria, the apnea test is indeterminate and additional confirmatory testing should be performed.

Pitfalls in the Diagnosis of Brain Death

The following conditions may interfere with the clinical diagnosis of brain death, so that the diagnosis cannot be made with certainty on clinical grounds alone. In such cases, confirmatory tests are recommended.

4.1 Severe facial trauma

4.2 Preexisting pupillary abnormalities

4.3 Toxic levels of any sedative drugs, aminoglycosides, tricyclic antidepressants, anticholinergics, antiepileptic drugs, chemotherapeutic agents, or neuromuscular blocking agents

4.4 Sleep apnea or severe pulmonary disease resulting in severe chronic retention of CO2

Clinical Observations Still Compatible with the Diagnosis of Brain Death

These manifestations are occasionally seen and should not be misinterpreted as evidence for brain stem function.

5.1 Spontaneous 'spinal' movements of limbs (not to be confused with pathologic flexion or extension response)

5.2 Respiratory-like movements (shoulder elevation and adduction, back arching, intercostal expansion without significant tidal volumes)

5.3 Sweating, blushing, tachycardia

5.4 Normal blood pressure in the absence of pharmacologic support

5.5 Absence of diabetes insipidus (i.e., normal osmolar control mechanism)

5.6 Deep tendon reflexes, triple flexion responses or Babinski's reflex, all of which may be spinally-mediated reflexes.

5.7 Facial myokymias.

Confirmatory Laboratory Tests Supporting the Diagnosis of Brain Death

Determination of death by brain criteria is a clinical diagnosis. A confirmatory test is not mandatory, but should be used as supportive data in those patients in whom specific components of clinical testing cannot be reliably performed or evaluated. Write the name of the attending physician interpreting the ancillary test, as well as the time of interpretation, as this is the official time of death, and should be documented as such in the Declaration of Death Note.

6.1 Conventional angiography: No intracerebral filling at the level of the carotid bifurcation or circle of Willis. The external carotid circulation is patent, and filling of the superior saggital sinus may be delayed. Should show no intracerebral filling, with contrast filling of the internal carotid artery abruptly stopping at the petrous portion, where the artery becomes intracranial. The external carotid circulation is patent, and delayed filling of the superior saggital sinus may be seen. A 4-vessel study should be performed, showing no intracranial filling of the anterior or posterior circulation.

6.2 SPECT using Technetium 99m hexamethylpropyleneamineoxime (HMPAO) brain scan: No uptake of isotope in the brain parenchyma as interpreted by an attending Nuclear Medicine physician. The extracranial circulation should still fill, allowing for uptake within the meninges and skull vessels.

6.3 Electroencephalography: Should show an absence of any electrocerebral activity during at least 30 minutes of recording that adheres to the minimal technical criteria for electroencephalographic recording in suspected brain death, as adopted by the American Electroencephalographic Society, including 16-channel electroencephalographic instruments. It should include the absence of non-artifactual activity and there should be no change with auditory, visual, or painful stimulation. Electrocardiographic artifact should be visible. There is no need for the patient to be normothermic but core body temperature should be above 36.5 C (96.8oF). If an EEG is obtained, the absence of EEG activity should be confirmed by a member of the neurology staff prior to the declaration of brain death. This should be noted in the patient's medical record.

6.4 Transcranial Doppler ultrasonography:

• 6.4.1 Criteria for TCD were set forth by the task force group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology in 1998. Small systolic peaks in early systole occurring without diastolic flow or with reverberating flow are indicative of very high vascular resistance associated with greatly increased intracranial pressure and lack of tissue blood flow. The test must be performed bilaterally, and confirmed on 2 examinations 30 minutes apart.
• 6.4.2 Diagnosis established by intracranial examination must be confirmed by the extracranial bilateral recording of the common carotid, internal carotid, and vertebral arteries.
• 6.4.3 It is also recommended that the posterior circulation also show reversal of intracranial flow (although this is not specified in the guidelines from the World Federation of Neurology).

6.5 Non-validated Confirmatory Tests, or Under Investigation:

• Somatosensory evoked potentials: SSEPs for the determination of brain death have been called into question, and are no longer commonly implemented as a confirmatory test. Bilateral absence of N20-P22 response with median nerve stimulation. The recordings should adhere to the minimal technical criteria for somatosensory evoked potentials recording in suspected brain death as adopted by the American Electroencephalographic Society.
• MRAngiography, CTAngiography: are both under investigation as confirmatory tests, but neither has been validated to date.

Medical Record Documentation

The declaration of death by brain criteria should be documented in the medical record in a manner similar to any other declaration of death and include the following:

7.1 The date and time of death

7.2 The name of the attending neurologist or neurosurgeon declaring death by brain criteria.

7.3 Etiology and irreversibility of condition.

7.4 Absence of brain stem reflexes.

7.5 Absence of motor response to pain.

7.6 Details of the apnea test, including time of apnea, pre and post test values of pH and CO2.

7.7 Justification for confirmatory testing if indicated, and results of confirmatory test(s) if performed with the name of the staff physician responsible for interpretation.

7.8 Results of repeat neurologic examinations if performed.

7.9 Indication that the Medical Examiner was contacted if appropriate (see guidelines in the Report of Death Form).

Selected References

1. Practice parameters for determining brain death in adults (Summary Statement).
2. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1995;45:1012-1014.
3. Wijdicks EFM. The diagnosis of brain death. N Engl J Med. 2001;344:1215-1221.
4. Ducrocq X, Hassler W, Moritake K et al. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography. Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. J Neurol Sci. 1998;145-150.
5. Goudreau JL, Wijdicks EFM, Emery SF. Complications during apnea testing in the determination of brain death: Predisposing factors. Neurology. 2000;55:1045-1048.
6. Canadian Neurocritical Care Group. Guidelines for the diagnosis of brain death. Can J Neurol Sci. 1999;26:64-66. Wieler H, March K, Kaisar KP et al. Tc-99 HMPAO cerebral scintigraphy: a reliable, noninvasive method for determination of brain death. Clin Nuc Med.1993;18:104-109.

Authoring Information

Reviewed/Approved by: Department of Neurology, Critical Care Committee, Clinical Policy and Records Committee, Medical Policy Committee, and David M. Greer, M.D.

Last updated: 7/25/2007

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