Abstract
With scientific advancements and fast growth in medical technology, functions of many organs including heart, lungs, kidneys, and pancreas can be supported artificially. This required the definition of death to be revisited to avoid unnecessary futile treatments and to give way for organ donation. Although brain death is discussed with relation to organ donation, this was not the sole purpose of defining brain death. Both entities developed in parallel—brain death to prevent wastage of scarce intensive care unit resources and organ donation developed with improved surgical techniques and immunosuppressants. When both these issues were discussed together with patient relatives, a third issue arose—medical ethics. Medical ethics is a set of guidelines created to maintain self-discipline among medical fraternity and to protect patients’ health. Neuroanesthesia practice is unique in that we commonly encounter patients who are not in a position to give informed consent, and patient autonomy, an important principle in medical ethics, is at times difficult to practice. It is difficult to follow a single set of ethics guidelines due to regional variation in culture, ethnicity, socioeconomic status, literacy, and beliefs. Controversies also exist in end-of-life issues. In this chapter, brain death and medical ethics are discussed individually in two parts. In the first part, brain death definition, clinical criteria, ancillary tests, and controversies in using the tests are described. In the second part, some of the ethical issues related to neuroanesthesia practice, research, and end-of-life issues are discussed.
Keywords
Autonomy, Brain death, Consent, Ethics, Organ donation, Research
Outline
Part A: Brain Death 856
Introduction 856
Criteria for Diagnosing Death 856
Need for Brain Death Diagnosis 856
Rules Regulating Diagnosis of Brain Death 856
Criteria for Certifying Brain Stem Death 857
Prerequisites 857
Clinical Examination 857
Ancillary Tests 858
Electroencephalogram 858
Evoked Potentials 859
Four-Vessel Cerebral Angiography 859
Radionucleotide Studies 859
Transcranial Doppler 859
Heart Rate Variability 859
Pitfalls/Controversies 859
Conclusion 861
Appendix I 861
Part B: Ethical Issues in Neuroanesthesia Practice 863
Introduction 863
Ethical Issues in Clinical Care 863
Informed Consent 863
Decision Making for Incompetent Patients 864
Persistent Vegetative State and Minimally Conscious State 865
Defensive Medicine 865
End-of-Life Issues 865
Do Not Resuscitate Orders 865
Withdrawal of Life Support Facility 865
Organ Donation and Related Issues 866
Ethical Issues Related to Research 867
Ethical Issues Related to Team Work 868
Ethical Issues Related to Training 868
Ethical Issues Related to Innovative Neurosurgery 869
Conclusion 869
References 869
Part A: Brain Death
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.easyaccess1.lib.cuhk.edu.hk/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.
Criteria for Diagnosing Death
The criteria adopted for diagnosing death depend on who is certifying and the situation in which such a diagnosis is made.
- A.
Outside hospital (e.g., in home): Cessation of spontaneous respiration and absent pulse (at least for 5 min, excluding hypothermia).
- B.
Forensic medicine: Cadaveric signs—algor mortis, livor mortis, rigor mortis, cadaveric spasm, loss of muscle contractions, putrefactions.
- C.
In hospital [e.g., intensive care unit (ICU)]: irreversible loss of brain functions.
Need for Brain Death Diagnosis
As life-supporting measures are widely available, many patients who have irreversible brain damage continue to be on artificial ventilator causing wastage of resources and increasing financial burden to the families. With improvement in transplant surgeries, patients with irreversible organ ailments of kidney, liver, pancreas, and so on can have the opportunity to lead a healthy life if they undergo organ transplantation. This increases the demand for organs. Hence, diagnosing brain death is required to discontinue patients from artificial ventilation and to promote organ donation. Brain death certification facilitates organ retrieval from patients who still have circulation as this results in less ischemic injury to organs and more chances for successful transplantation.
Rules Regulating Diagnosis of Brain Death
In 1968, for the first time, “irreversible coma” was defined by Ad Hoc Committee of Harvard Medical School. The criteria were apneic coma with absent brain stem reflex for a period of 24 h confirmed by electroencephalogram (EEG). These criteria were laid to prevent prolonged futile life support.
Documenting irreversible loss of brain stem function as criteria for brain death was established by the Minnesota criteria in 1971 and by the Medical Royal Colleges in the United Kingdom in 1976. This criterion was laid down by keeping the following points in mind—midbrain death abolishes cognitive processing, pontomedullary death results in loss of ability to breathe spontaneously, and asystole inevitably follows brain stem death as cardiorespiratory centers are situated in pontomedullary areas of the brain.
In 1981, the US President’s commission defined brain death as “permanent and irreversible loss of all functions of the entire brain including brain stem.”
In 1994, the government of India enacted “Transplantation of Human Organs (THO)” law, and it was modified in 2011 and in 2014 ( http://notto.nic.in/act-end-rules-of-thoa.htm ). This law defines the legality of brain stem death to facilitate organ retrieval and transplantation. The criteria to be followed for certifying brain stem dead are given in Form 10 of THO Act, 2014 (see Appendix 1 ). This law requires certification by four medical experts independently by means of two clinical examinations performed at least 6 h apart. Imaging studies, EEG, and neurophysiological tests are not required by the Indian law to certify brain stem death, but these investigations could be performed if there are conflicts in opinion among the medical experts.
Criteria for Certifying Brain Stem Death
Prerequisites
The following are required before proceeding to diagnose brain stem death.
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Hemodynamic stability (systolic blood pressure of at least 100 mm Hg)
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Rule out reversible causes of coma: e.g., depressant drugs (barbiturates, benzodiazepines), alcohol intoxication, endocrine disorders
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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
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Patient should be deeply comatose
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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
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brain damage being supratentorial with infratentorial consequences of loss of brain stem function
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isolated brain stem damage needs additional testing for confirming brain death
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exclude reversible causes of coma
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Absent spontaneous movements and motor responses in cranial nerve distribution (exclude spinal reflexes—plantarflexion, triple flexion, muscle stretch reflex, Lazarus sign)
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All brain stem reflexes should be absent:
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Pupillary light reflex: Pupils are dilated, fixed (4–9 mm), and do not react to light
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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)
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Corneal reflex is absent
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No motor response to stimulation within any cranial nerve distribution (e.g., no response to the supraorbital pressure)
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No gag (pharyngeal) reflex (to stimulation of pharynx)
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No cough reflex (to suction catheter in the trachea)
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Vestibulo-ocular reflex (oculovestibular reflex/caloric testing) is absent
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Confirm patency of external auditory meatus and intact tympanic membrane. Ruptured membrane augments caloric responses
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Keep head elevated to 30 degrees
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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
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A few medications can attenuate this reflex. These include tricyclic anti-depressants (TCA), aminoglycosides, anti-cholinergics
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Presence of eye trauma, eyelid swelling, and conjunctival chemosis limit eye movement and make interpretation difficult
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Basal fracture of petrous bone abolishes this response
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Atropine test
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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.
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In primary infratentorial lesion, this test can be negative
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Not applicable in patients with autonomic neuropathy, and cardiac denervation following cardiac surgery like transplantation.
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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)
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Prerequisites
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Not under the influence of neuromuscular blocking drugs
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Systolic blood pressure at least 100 mm Hg
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Euvolemic
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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)
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pH >7.2
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Minimum core body temperature of 36°C
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No hypoxia
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Procedure
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Preoxygenate with 100% O 2 for at least 10 min (PaO 2 at least 200 mm Hg)
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Obtain baseline arterial blood gas values (PaO 2 , PaCO 2 , pH, base excess, bicarbonate)
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Disconnect from ventilator
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Place a catheter through endotracheal tube at the level of carina and provide oxygen at 6 L/min
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Observe for at least 8–10 min for respiratory movements (chest/abdominal excursions) and repeat blood gas analysis
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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)
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Procedure to be stopped if there is hemodynamic instability, arterial saturation falls below 85%, or respiratory movements are present.
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Procedure time can be shortened by insufflating CO 2 .
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Complications
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Hypoxemia, acidosis, hypotension, arrhythmias, worsen intracranial hypertension
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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.
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Electroencephalogram
A minimum of 30-min recording is required to document electrocerebral silence (ECS) (without confounding factors) as an indication of brain death with high specificity. A minimum of eight scalp electrodes and ear reference electrodes are used for documentation. Interelectrode resistances should be between 100 and 10,000 Ω, and the distances must be at least 10 cm. Gain should be set at 2.0 μV/mm. EEG during pain stimulation, loud noises, and light must be recorded. Performing EEG and documenting ECS shortens the time interval of confirmation as compared to two clinical examinations. False-positive rate is around 3.5%. Telephone transmitted EEGs are not appropriate for determination of ECS. The waveforms are significantly altered by hypothermia, metabolic changes, and drugs. EEG does not provide information about brainstem function, and waveforms could be flat in the presence of intact brainstem function [e.g., persistent vegetative state (PVS)].
Evoked Potentials
The advantages of evoked potentials are that these tests can be performed at the bedside and can be done in situations in which confounders are present (e.g., hypothermia, drug intoxication). Multimodal evoked potentials, a combination of somatosensory evoked potential (SSEP), visual evoked potential (VEP), and brainstem auditory evoked potential (BAEP) can differentiate brain death from other similar conditions like GBS (absent BAEP and SSEP but positive VEP). Even when EEG is flat, evoked potentials can still be recorded. Combined monitoring of evoked potentials tests the functions of the entire brain: SSEP tests integrity from parietal cortex to cervical spinal cord, including medulla oblongata; VEP tests fronto-occipital hemisphere components; and BAEP tests brainstem. It also helps in differentiating brain death from vegetative states (persistent BAEP and median SSEP).
Median Nerve Somatosensory Evoked Potential
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Bilaterally absent median nerve N20-P22 response.
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Persistence of N13/P13 cervical components.
Brain Stem Auditory Evoked Potential
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BAEP: no waves or isolate wave I. No waves from II–V.
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False-negatives are seen in temporal bone fractures, deafness, and ototoxic drugs
Four-Vessel Cerebral Angiography
Contrast agents must be injected at the level of aortic arch. Absent flow at both internal carotids and both vertebral arteries are required to confirm brain death. Block occurs at cranial base/siphon near clinoid process. No venous drainage even after 26 s. External carotid must fill and acts as control. Sometimes, contrast agents can be injected as a 60- to 80-mL bolus at the rate of 12–15 mL/s into brachial vein and digital subtraction angiography (DSA) performed (cerebral venous DSA).
Radionucleotide Studies
Technetium 99 isotope scan demonstrates no intracranial blood flow (hollow skull appearance). Tc-99m pertechnetate is injected into antecubital vein as bolus. Isotopic emission is recorded every 3 s for 24 s. No activity is noted when cerebral blood flow falls below 24% of baseline. For single-photon emission computed tomography (CT) study, Tc-99m hexamethylpropyleneamine oxime is given 15 min before scanning. This study is useful in children and in situations in which presence of confounding factors make clinical examinations difficult to interpret. However, this is not suitable for studying posterior fossa circulation.
Transcranial Doppler ( Figs. 52.1 and 52.2 )
As pressure within the skull (intracranial pressure) increases and goes beyond blood pressure, initially diastolic flow stops . Later, the systolic flow reduces, then becomes reverberating, and later, the flow totally stops. Bilateral insonation is a must, and at least one vessel on each side must be insonated. Two examinations must be performed at 30-min intervals. Oscillating flow or systolic spikes (<50 cm/s flow velocity for duration less than 200 ms in early systole without diastolic flow) are considered suggestive of brain death. Also, one must document flow in extracranial vessels. Absent flow is not a reliable criterion as the result could be due to poor acoustic window. However, absent flow in a patient who has prior documented flow is useful in conforming brain death. Presence of cranial defect and external ventricular drainage makes interpretation of values unreliable.
