The brain stem in brain death: a critical review.

• Author: Byrne, Paul A.

There is no sure foundation set on blood,

No certain life achieved by others' death.(1)

We would take the issue of brain death from the "misty court of `philosophy'"(2) and examine it in the cool light of medical science and clinical neurology, which will not cut corners and will be as exacting as is humanly possible. We are, after all, physicians and not metaphysicians. We also cannot be prophets of an ethical "slippery slope," although we are well qualified to observe and interpret what has already occurred in these matters.

At the very least, cessation of all functions of the entire brain (the language of the Uniform Determination of Death Act [UDDA]) should be present before declaring brain death. That such cessation is "imminent" is not sufficient or satisfactory as a criterion for organ donation.(3) Dying must never be confused with death.(4)

This article focuses on the practical difficulties encountered by a neurosurgeon or a pediatrician, as potential donors' doctors, in a metropolitan or suburban community hospital. There is a nearby university hospital with a transplantation protocol. Such protocols put emphasis on the "rapid acquisition of physiologically sound organs."(5) This puts the potential donor at risk. The declaration of brain death must be made as soon as possible, usually in less than twenty-four hours. According to the protocol, fresh vital organs should be obtained untainted by any measures the donor's doctor may have taken to preserve his patient's life: e.g., dopamine to maintain blood pressure or fluid intake at a reasonable level to prevent cerebral edema (rather than allowing a fluid overload so as to better preserve the kidneys for recipients).

The statement is too easily made that if the donor's doctor has conscientious reservations regarding brain death, he should withdraw from the case. In a community hospital of two or three hundred beds, there are often only two neurosurgeons. The other neurosurgeon may have the same reservations, so that moral compunctions cannot be easily avoided as in a larger hospital with eight or nine neurosurgeons having a spectrum of opinions on the subject.

Physicians in attendance on dying patients have to understand themselves and their positions regarding reverence for life. Sometimes they find themselves making the best compromise they can between their consciences and hospital and transplant team policy. Such a compromise, like all compromises, is too often unsatisfactory for a conscientious physician as well as the patient, who, if he is not already dead, will certainly be dead after lethal action has been carried out.

Furthermore, a community hospital may not have the facilities to test all the functions of the entire brain, even of the brain stem, as the UDDA specifies.(6)

Structure and Function of the Brain Stem

Two and a half inches in length (6-1/2 cm), the brain stem extends at the base of the brain from the spinal cord at the foramen magnum to the upper border of the mesencephalon. It is a compact tube of neural tissue containing the nuclei of cranial nerves III-XII and ascending sensory and descending motor tracts, both giving collaterals to the reflex-integrating reticular formation. The reticular formation extends throughout the medullary, pontine, and mesencephalic portions of the brain stem and rostrally into the diencephalon so that functionally the brain stem extends higher than its anatomic upper border.

The brain stem subserves cranial nerve functions (III-XII). Through afferent impulses from neck muscles, cervical vertebrae, and vestibules, its motor centers control body position in space.(7) By reflex adjustments in the reticular formation of the medulla oblongata and in the vagal nuclei, the blood pressure and heart rate can vary. (The heart, however, is driven by its own intrinsic pacemaker at a steady rate when central influences are lost.) The respiratory center in the reticular formation of the lower medulla sustains spontaneous respirations. The mesencephalic reticular formation, stimulated by collaterals from the ascending sensory tracts and projecting generally to the cerebral cortex, maintains alertness.(8) When the upper brain stem fails (as in transtentorial herniation), consciousness is lost; when the respiratory centers in the lower medulla don't function, breathing stops.

The isolated brain stems of decerebrate animals can manifest conditioned reflexes of reward and aversion; simple learning and memory; and the complex coordinated behaviors of eating, grooming, and attack.(9) Behavioral and motivational processes are organized at the brain stem level and modulated by higher centers.

With proper care including nutrition and hydration, the isolated brain stem in an anencephalic human infant can sustain respirations and reflexes essential to life for several weeks or longer.(10) Such infants often act like normal infants at this age. They can express hunger, fear, and contentment.

But is not the whole greater than any of its parts? If we equate brain stem death with death of the organism as a whole,(11) are we not making a serious philosophical and practical error? In certain cases of primary brain stem injury or infarct, the neocortex will be functioning, and the patient will be conscious but unable to breathe. Brain stem death cannot be equated with the UDDA "cessation of all functions of the entire brain," or with the death of the person.

Preconditions for Brain Death

There must be a history of a condition with the potential for causing "irreversible cessation of all functions of the brain," such as massive head injury, irremediable surgically and medically. All diagnostic measures, including computerized tomography (CT) scan, should have been carried out. Therapy should have been tried and found to be not effective. Time must be allowed for these efforts. In cases of hypoxia, or total anoxia (i.e., no circulation, thus ischemia), in adults for three to five minutes, a waiting period of at least twenty-four hours is advisable. On the other hand, it has been reported that patients with even five to twenty-two minutes of no circulation have made complete neurologic recovery.(12)

Drug intoxication is a reversible cause of nonfunction of the brain stem with electrocortical silence. Barbiturates, benzodiazepines, meprobamate, methaqualone, and other drugs may be taken with suicidal intent or as an accidental overdose by an addict. Full toxicological screening must be done, but drug blood levels lag behind brain levels and are notoriously unreliable.(13) The combination of head trauma and drug intoxication does occur and requires thorough drug screening. The neurologic effects of alcohol last usually no more than six to eight hours.(14) For other drugs, as much reliance should be placed on historical or circumstantial evidence of drug intoxication as on blood levels (keeping in mind that historical evidence is no more reliable than blood levels for the pronouncement of death). In cases of suspected intoxication no declaration of death should be made at least until the drug is known to have been metabolized.(15) The waiting period should be at least three days to cover phenobarbital, a drug with a long half-life (fifty or more hours).(16) New drugs, especially illicit drugs, do not have a known half-life. This may put a potential recipient patient at risk should the organs not be obtained rapidly enough and as a result not be "physiologically sound."(17) A physician should not be required to make a value judgment between a failed suicide, or an addict, and a socially more worthwhile person who may need a vital organ.

Hypothermia, especially when combined with head trauma, may be particularly deceptive. Hypothermia can actually protect the injured brain. Hypothermia alone can cause an isoelectric EEG. If the core temperature is below 33[degrees] C, the criteria for brain death cannot be applied. Body temperature should be restored to normal before considering brain-related criteria for death.(18)

Hypotension can mimic brain death; therefore, the blood pressure should be brought to normal.(19) There should be no evidence of autoregulation of these parameters when considering a diagnosis of brain death.

There are a few less common, but still potentially very confusing, conditions that can imitate findings consistent with brain death. One is polyradiculoneuropathy with peripheral and cranial nerve involvement.(20) Cranial nerve dysfunction and respiratory paralysis are present, but ophthalmoplegia is rare. The severe loss of motor and sensory function leads to clinical unresponsiveness and areflexia, but sleep pattern EEG activity is present. Absence of the usual causes of brain death, onset with fever, and elevation of spinal fluid protein should be helpful diagnostically. But if no EEG is taken (as in some brain death protocols), such conditions could be missed and the patient pronounced brain dead.

Another is prolonged neuromuscular blockade by drugs given to aid intubation, particularly in those patients unable to reverse the reaction to succinylcholine (due to enzyme deficiency of pseudocholinesterase).(21) The medication sheet should always be examined. The signs of nonfunction of the brain stem commonly evaluated are present: fixed pupils; no response to caloric testing or head turning (see below); and no gag, cough, or ciliospinal reflexes. The patient is unresponsive, but the EEG is normal. If patellar and Achilles reflexes are present, as they may be in brain death since the spinal cord is usually not affected, there is no neuromuscular blockade. In confusing cases a nerve stimulator can demonstrate retention of peripheral nerve function in brain death and absence of muscular reaction in enzyme-deficient neuromuscular blockade.

Brain stem encephalitis is another of the potentially reversible causes of apparent brain death.(22) There are external ophthalmoplegia, facial diplegia, and bulbar palsy...