Severe brain injury to neurological determination of death: Canadian forum recommendations

Overarching recommendations

In discussions related to Recommendations A.4: Apnea testing, A.5: Examination interval and A.7: Concept and definition of neurological death, FRG members identified the following overarching recommendations, which apply to all of the individual recommendations:

• We recommend that after NDD, the patient be declared dead.

• Existing provincial and territorial laws indicate that for the purposes of a post-mortem transplant, the fact of death shall be determined by at least 2 physicians in accordance with accepted medical practice. There is no clear medical basis for the law requiring a second physician to determine death before post-mortem transplantation.

• The first and second physicians' determinations, required by law, may be performed concurrently. However, if the determinations are performed at different times, a full clinical examination, including apnea testing, must be performed at each determination. No fixed interval of time is recommended for the second determination, except where age-related criteria apply.

Recommendation A.1: Minimum clinical criteria for NDD

We recommend use of the following minimum clinical criteria as a Canadian medical standard for NDD:

• Established etiology capable of causing neurological death in the absence of reversible conditions capable of mimicking neurological death

• Deep unresponsive coma with bilateral absence of motor responses, excluding spinal reflexes

• Absent brain stem reflexes as defined by absent gag and cough reflexes and the bilateral absence of

• • corneal responses

• • pupillary responses to light, with pupils at mid-size or greater

• • vestibulo-ocular responses

• Absent respiratory effort based on the apnea test

• Absent confounding factors

Key considerations

• A prerequisite for NDD is the absence of clinical neurological function with a known, proximate cause that is irreversible. There must be definite clinical or neuro-imaging evidence of an acute central nervous system (CNS) event consistent with the irreversible loss of neurological function.

• Deep unresponsive coma implies a lack of spontaneous movements as well as an absence of movement originating in the CNS, such as cranial nerve function, CNS-mediated motor response to pain in any distribution, seizures, decorticate and decerebrate responses. Spinal reflexes or motor responses confined to spinal distribution may persist.

• Minimum should not necessarily be understood as minimal. „Minimal” refers to the least possible that can be done and is an absolute value. „Minimum” refers to the lowest acceptable standard, which is a relative standard, often pitched above the minimal. The standard recommended by the forum sets minimum clinical criteria for NDD.

Recommendation A.2: Confounding factors

We recommend that, at the time of assessment for NDD, the following confounding factors preclude the clinical diagnosis:

• Unresuscitated shock

• Hypothermia (core temperature < 34°C)

• Severe metabolic disorders capable of causing a potentially reversible coma

• Severe metabolic abnormalities, including glucose, electrolytes (including phosphate, calcium and magnesium), inborn errors of metabolism, and liver and renal dysfunction may play a role in clinical presentation. If the primary etiology does not fully explain the clinical picture, and if in the treating physician's judgement the metabolic abnormality may play a role, it should be corrected.

• Peripheral nerve or muscle dysfunction or neuromuscular blockade potentially accounting for unresponsiveness

• Clinically significant drug intoxications (e.g., alcohol, barbiturates, sedatives, hypnotics); however, therapeutic levels or therapeutic dosing of anticonvulsants, sedatives and analgesics do not preclude the diagnosis.

Key considerations

• Neurological assessments may be unreliable in the acute post-resuscitation phase after cardiorespiratory arrest.13 In cases of acute hypoxic-ischemic brain injury, clinical evaluation for NDD should be delayed for 24 h subsequent to the cardiorespiratory arrest or an ancillary test could be performed (see Recommendation A.6).

• It is recognized that there are variations in confounding factors that may be associated with NDD; examiners are cautioned to review these confounding factors in the context of the primary etiology and examination. If physicians are confounded by data, either absolutely or by differing perspectives, they should not proceed with NDD. Clinical judgment is the deciding factor.

Recommendation A.3: Minimum temperature

The core body temperature required to apply the minimum clinical criteria (Recommendation A.1) should be ≥ 34°C.

Key considerations

• Core temperature should be obtained through central blood, rectal or esophageal–gastric measurement.

• The existing Canadian standard of 32.2°C was based on precedent.7 The relevance of the scientific evidence and the application of this standard in the context of severe brain injury is uncertain.

• Given that there is no evidence base, a decision was made to adopt 34°C as a rational, safe and attainable standard. This decision was based on the following rationale:

• ideally, temperature should be as close to normal as possible and this is the minimum temperature at which the test is valid

• raising a patient's temperature from 32.2°C to 34°C does not pose significant difficulty to the patient or treating physician.

Recommendation A.4: Apnea testing

We recommend that the thresholds at the completion of the apnea test be PaCO₂ ≥ 60 mm Hg (and ≥ 20 mm Hg above the pre-apnea test level) and pH ≤ 7.28. These thresholds must be documented by arterial blood gas measurement.

To interpret an apnea test correctly, the certifying physician must continuously observe the patient for respiratory effort throughout the administration of the test.

Key considerations

• Optimum administration of the apnea test requires a period of preoxygenation followed by 100% oxygen delivered via the trachea upon disconnection from mechanical ventilation.

• The following codicil is required to address severe lung disease: Caution must be exercised in considering the validity of the apnea test if, in the physician's judgment, there is a history suggestive of chronic respiratory insufficiency and responsiveness to only supranormal levels of carbon dioxide, or if the patient is dependent on hypoxic drive. If the physician cannot be sure of the validity of the apnea test, an ancillary test should be administered.

Recommendation A.5: Examination interval

We recommend that when a second determination is performed, there should be no fixed examination interval, regardless of the primary mechanism of the brain injury.

Recommendation A.6: Ancillary tests

We recommend that an ancillary test be performed when it is impossible to complete the minimum clinical criteria as defined in Recommendation A.1. At a minimum, 2 particular clinical criteria must be met before ancillary tests are performed:

• An established etiology capable of causing neurological death in the absence of reversible conditions capable of mimicking neurological death

• Deep unresponsive coma

We recommend that demonstration of the global absence of intracerebral blood flow be considered as the standard for NDD by ancillary testing.

Key considerations

• Before performing an ancillary test, unresuscitated shock and hypothermia must be corrected (see Recommendation A.2).

• The term „ancillary” should be understood to mean an alternative test to one that otherwise, for any reason, cannot be conducted. It replaces previous terminology such as „supplemental” (in addition to an already conducted test) or „confirmatory” (confirms a previously conducted test).

• Existing evidence, although not firmly established, suggests that for patients who fulfill minimum clinical criteria (see Recommendation A.1) under the circumstances of high-dose barbiturate therapy used for refractory intracranial hypertension to achieve deep coma or electrocerebral silence, NDD can be confirmed by the demonstration of absence of intracerebral blood flow.14

• A description of ancillary testing is provided in Appendix 3 .

Recommendation A.7: Concept and definition of neurological death

We recommend that neurologically determined death be defined as the irreversible loss of the capacity for consciousness combined with the irreversible loss of all brain stem functions (as defined in Recommendation A.1), including the capacity to breathe.

Key consideration

Death determined by neurological criteria may occur as a consequence of intracranial hypertension or primary direct brain stem injury or both. In instances of intracranial hypertension, ancillary testing demonstrating absence of intracerebral blood flow confirms death when application of minimum clinical criteria (as defined in Recommendation A.1) cannot be completed, or if the interpretation of clinical criteria is confounded. There are currently no satisfactory ancillary tests for confirmation of neurologically determined death in instances of isolated primary brain stem injury.

Recommendation A.8: Physicians declaring neurological death

We recommend that the minimum level of physician qualification required to perform NDD be

• Full and current licensure for independent medical practice in the relevant Canadian jurisdiction

• Skill and knowledge in the management of patients with severe brain injury and in NDD.

In cases of NDD for the purposes of postmortem donation, we recommend that any physician who has had any association with the proposed recipient that might influence the physician's judgment shall not take any part in the declaration of death.

Key considerations

• For the purposes of this recommendation, a physician with „full and current licensure for independent practice in the relevant Canadian jurisdiction”

• • is any physician licensed by the college of physicians and surgeons or licensing authority in that jurisdiction.

• • excludes physicians who are only on an educational register.

• • does not require a particular level of specialty certification; nonspecialists can declare NDD if they have the requisite skill and knowledge.

• The authority to perform NDD cannot be delegated.

Recommendation A.9: Age-related criteria

We recommend that recommendations A.1 to A.8 for NDD be applied to infants, children and adolescents, with the following qualifications.

NDD recommendations specific to children and adolescents

• For all children ≥ 1 year (corrected for gestational age), NDD standards established at the forum should apply. A second physician performing the NDD is required by law for the purposes of postmortem transplantation, with no fixed interval of time required, regardless of the primary mechanism of the brain injury (see Recommendation A.5).

• The minimum level of physician qualifications should be understood as specialists with skill and knowledge in the management of children and/or adolescents with severe brain injury and NDD (see Recommendation A.8).

NDD recommendations specific to infants aged 30 days to 1 year (corrected for gestational age)

• The minimum clinical criteria include the oculocephalic reflex, as this test may be more reliable than the vestibulo-ocular reflex in infants due to the unique anatomy of the external auditory canal (see Recommendation A.1).

• A repeat examination at a different time is recommended to ensure independent confirmation by another qualified physician, regardless of the primary mechanism of the brain injury. It is prudent to have an independent examination because of the lack of collective experience and research on brain death in this age group. There is no recommended minimum time interval between determinations. Should uncertainty or confounding issues arise that cannot be resolved, the time interval may be extended according to physician judgment, or an ancillary test demonstrating absence of intracerebral blood flow may be used.

• The minimum level of physician qualifications should be understood as specialists with skill and knowledge in the management of infants with severe brain injury and NDD (see Recommendation A.8).

Key considerations

• Studies should be undertaken to evaluate the necessity of this second examination relative to the risks (e.g., of repeating the apnea test, time delays with an impact on family stress and donor stability).

• Recommendations on NDD in newborns <30 days were addressed in a separate forum.

Neonatal recommendations

The Neonatal Reference Group recommends that all NDD standards established at the forum be adopted with the following adjustments and emphases:

NDD recommendations for term newborns aged < 30 days

• Standards apply to newborns aged > 36 weeks' gestation at the time of death.

• NDD is a clinical diagnosis, i.e., clinical criteria have primacy.

• Minimum clinical criteria include absence of oculocephalic reflex and suck reflex.

• Minimum temperature must be a core temperature ≥ 36°C.

• Minimum time from birth to first determination is 48 h.

• Two determinations are required, with a minimum interval of 24 h between examinations.

• Ancillary testing, as defined by demonstration of the absence of intracerebral blood flow, should be performed when any of the minimum clinical criteria cannot be established or confounding factors remain unresolved.

• „Minimum level of physician qualifications” should be understood as specialists with skill and knowledge in the management of newborns with brain injury and the determination of death based on neurological criteria.

Key considerations

• Accuracy of gestational age should be supported by clinical history (e.g., dates and prenatal ultrasound) and physical examination. Inability to confirm a gestational age > 36 weeks should preclude NDD.

• The higher recommended temperature thresholds reflect uncertainty about hypothermic effects on neurological function in the newborn and the fact that normothermia is an easily attainable standard.

• The 48-h recommendation from injury to first determination reflects a reduced certainty of neurological prognostication before the first 48 h of life.

• Prospective research should be done to confirm the necessity of the recommended 24-h interval between determinations.

Recommendation B.1: Legal timing of death

We recommend that the legal time of death be marked by the first determination of death.

Recommendation B.2: Reporting

We recommend that NDD be reported when determined.

Key consideration

Currently, there are no mechanisms to report the incidence of NDD in Canada. Given that NDD is a prerequisite for cadaveric organ donation, there is a need to record this information for use in the analysis of statistics on organ donation.

Recommendation B.3: Reporting mechanisms

We recommend that the mechanism for reporting NDD be through the medical certificate of death and that hospitals be responsible for directing completed information to the appropriate agencies, such as the Canadian Institute for Health Information.

Key considerations

• Physicians should be required to report NDD through a single mechanism.

• Specific provisions for reporting NDD should be included on the medical certificate of death. If the NDD portion of the certificate is not completed, it should be returned to the physician for completion.

Recommendation B.4: Legal issues

We recommend that Canadian medical requirements for NDD (determined at this forum) be embodied in medical standards and clinical practice guidelines.

Key consideration

Hospital practices related to NDD vary across the country. There is a need to align them (e.g., accreditation) with medical standards and clinical practice guidelines related to NDD.

Recommendation C.1: Recognition of NDD

We recommend that all patients who are suspected of being brain dead be assessed for NDD unless this has no implications for prognostication or management, including end-of-life care (see Recommendation C.3).

Recommendation C.2: Emergency department to ICU triage — evolving neuroprotective therapies

We recommend that all patients with severe brain injury who may benefit from treatment, prognostication or optimal end-of-life care within an ICU have access to these services.

Key considerations

• Patient and family wishes must be considered, e.g., wishes made known during clinician consultations, in advance directives, on organ donor cards and to an organ donor registry.

• ICU is defined as care provided in an ICU, not critical care offered in an emergency department.

• Access to ICU services for patients with severe brain injury should be in addition to preserving access to ICU for other critically ill patients.

• Resource and societal issues require consideration.

• Clinicians need to have some flexibility in decision-making.

Recommendation C.3: End-of-life care

We recommend that for patients who die as a result of severe brain injury, standard postmortem care should include the option of organ and tissue donation for eligible patients.

See also Appendix 5 and Appendix 6.