Brain Death and Ethical Issues in Neuroanesthesia Practice

Introduction

Death has been traditionally defined as “irreversible cessation of circulatory and respiratory functions.” With rapid improvements in medical technology, it is possible to artificially support breathing and circulation by means of techniques like mechanical ventilation and extracorporeal membrane oxygenation in spite of no possibility of the patient to sustain life on his or her own. As cardiorespiratory function cannot be used in these situations to define death, there was a need to have another definition for death to prove the irreversible loss of brain function. Catastrophic brain injury (e.g., subarachnoid hemorrhage, intracranial hematoma, traumatic brain injury) causes acute swelling of the brain. As brain is enclosed inside a rigid skull, pressure inside the skull increases and stops the blood flow to the brain. This results in neuronal cell death. As neurons do not regenerate the damage is permanent and irreversible. In this context, brain death is defined in simple terms as complete and irreversible loss of brain function (including involuntary activity necessary to sustain life). However stated, it is difficult for the relatives to understand and accept brain death as the heart beat is still present at the time of diagnosis of brain death. In 2012, the World Health Organization in collaboration with Canadian blood services formulated the international guidelines for the determination of death phase I (accessed from http://www.who.int/patientsafety/montreal-forum-report.pdf ). They defined death as “Death occurs when there is permanent loss of capacity for consciousness and loss of all brainstem functions. This may result from permanent cessation of circulation and/or after catastrophic brain injury. In the context of death determination, ‘permanent’ refers to loss of function that cannot resume spontaneously and will not be restored through intervention.” The definition is based on cessation of function rather than on activities of cells.

Prerequisites

The following are required before proceeding to diagnose brain stem death.

• Hemodynamic stability (systolic blood pressure of at least 100 mm Hg)

• Rule out reversible causes of coma: e.g., depressant drugs (barbiturates, benzodiazepines), alcohol intoxication, endocrine disorders

• Rule out confounders: relaxants (neuromuscular blocking agents), hypothermia (<36°C), metabolic disturbances (glucose, electrolytes, calcium, magnesium, phosphates), brain stem encephalitis, Guillain–Barré syndrome (GBS), metabolic encephalopathy

Clinical Examination

• Patient should be deeply comatose

  • due to irreversible brain damage of known cause with either clinical or neuroimaging evidence. Examples include severe head injury, hypoxemic anoxic encephalopathy, cerebrovascular accidents like subarachnoid hemorrhage, intracerebral hemorrhage, and brain edema following hepatic necrosis

  • brain damage being supratentorial with infratentorial consequences of loss of brain stem function

  • isolated brain stem damage needs additional testing for confirming brain death

  • exclude reversible causes of coma

• Absent spontaneous movements and motor responses in cranial nerve distribution (exclude spinal reflexes—plantarflexion, triple flexion, muscle stretch reflex, Lazarus sign)

• All brain stem reflexes should be absent:

  • Pupillary light reflex: Pupils are dilated, fixed (4–9 mm), and do not react to light

  • Doll head eye movements (oculocephalic reflex): absence of conjugate deviation of eyes when head is fully rotated to one side (performed only when there is no fracture or instability of the cervical spine)

  • Corneal reflex is absent

  • No motor response to stimulation within any cranial nerve distribution (e.g., no response to the supraorbital pressure)

  • No gag (pharyngeal) reflex (to stimulation of pharynx)

  • No cough reflex (to suction catheter in the trachea)

  • Vestibulo-ocular reflex (oculovestibular reflex/caloric testing) is absent

    • Confirm patency of external auditory meatus and intact tympanic membrane. Ruptured membrane augments caloric responses

    • Keep head elevated to 30 degrees

    • Eye movements must be absent after installation of 50 mL of ice cold water into each external acoustic meatus for 1 min. Wait for at least 5 min before performing the test in the opposite ear

    • A few medications can attenuate this reflex. These include tricyclic anti-depressants (TCA), aminoglycosides, anti-cholinergics

    • Presence of eye trauma, eyelid swelling, and conjunctival chemosis limit eye movement and make interpretation difficult

    • Basal fracture of petrous bone abolishes this response

  • Atropine test

    • Administer 2 mg atropine intravenously and observe for heart beats. If heart rate does not increase beyond 3% compared to baseline the test is negative.

    • In primary infratentorial lesion, this test can be negative

    • Not applicable in patients with autonomic neuropathy, and cardiac denervation following cardiac surgery like transplantation.

• Apnea test (absence of respiratory movements after disconnection from the ventilator for sufficient duration to have pCO ₂ rise above threshold (>60 mm Hg) for stimulating respiration)

  • Prerequisites

    • Not under the influence of neuromuscular blocking drugs

    • Systolic blood pressure at least 100 mm Hg

    • Euvolemic

    • Eucapnic (PaCO ₂ 35–45 mm Hg; exception—patients with chronic obstructive pulmonary disease where rise of PaCO ₂ by 20 mm Hg above baseline is considered sufficient for diagnosing apnea)

    • pH >7.2

    • Minimum core body temperature of 36°C

    • No hypoxia

  • Procedure

    • Preoxygenate with 100% O ₂ for at least 10 min (PaO ₂ at least 200 mm Hg)

    • Obtain baseline arterial blood gas values (PaO ₂ , PaCO ₂ , pH, base excess, bicarbonate)

    • Disconnect from ventilator

    • Place a catheter through endotracheal tube at the level of carina and provide oxygen at 6 L/min

    • Observe for at least 8–10 min for respiratory movements (chest/abdominal excursions) and repeat blood gas analysis

    • Apnea test is positive if no respiratory movements are observed even at PaCO ₂ 60 mm Hg or rise by more than 20 mm Hg above baseline)

    • Procedure to be stopped if there is hemodynamic instability, arterial saturation falls below 85%, or respiratory movements are present.

    • Procedure time can be shortened by insufflating CO ₂ .

  • Complications

    • Hypoxemia, acidosis, hypotension, arrhythmias, worsen intracranial hypertension

Ancillary Tests

For details on performing ancillary tests, the readers are referred to Refs. These tests are preferable when clinical tests are not elicitable, to shorten the period between two observations, when there is conflict between medical experts’ opinion, and in primary brainstem lesions. The tests can be broadly classified into two categories—one demonstrating absent electrical activity and the other demonstrating absent brain circulation. Combination of ancillary tests is much better with higher sensitivity and specificity.