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The problematic symmetry between brain birth and brain death.

The possible symmetry between the concepts of brain death and brain birth (life) is explored. Since the symmetry argument has tended to overlook the most appropriate definition of brain death, the fundamental concepts of whole brain death and higher brain death are assessed. In this way, a context is provided for a discussion of brain birth. Different writers have placed brain birth at numerous points: 25-40 days, eight weeks, 22-24 weeks, and 32-36 weeks gestation. For others, the concept itself is open to question. Apart from this, it needs to be asked whether a unitary concept is an oversimplification. The merits of defining two stages of brain birth, to parallel the two definitions of brain death, are discussed. An attempt is then made to map these various stages of brain birth and brain death onto a developmental continuum. Although the results hold biological interest, their ethical significance is less evident. Development and degeneration are not interchangeable, and definitions of death apply specifically to those who are dying, not those who are developing. I conclude that while a dual concept of brain death has proved helpful, a dual concept of brain birth still has problems, and the underlying concept of brain birth itself continues to be elusive.

Beginning of Human Life↗

Brain death: physiologic definitions.

Brain death describes the clinical state of totally absent central nervous system function in a hemodynamically stable, normothermic, nonintoxicated patient, which is followed inevitably by cardiovascular collapse. This article outlines the evolution of the concept of brain death and its current definition and legal status.

Brain↗

Brain tissue oxygenation in brain death.

INTRODUCTION: The value of brain tissue oxygenation (PbtO2) measurements in determining brain death is unknown. METHODS: Eleven of 72 patients who had brain tissue oxygen monitors placed experienced brain death. Admission diagnoses included six severe traumatic brain injuries, one multiple trauma with cardiac arrest, one brain tumor, one subarachnoid hemorrhage, one intracerebral hemorrhage, and one cerebral stroke. Eleven males and zero females were studied, with an average age of 26 years (range: 20-70 years). Nine patients had Glasgow Coma Scores (GCS) of 3 on admission, one patient had a GCS of 5, and one patient had a GCS of 15. RESULTS: Time from admission to declaration of brain death varied from 5 hours to 7 days; the most common interval was 1 or 2 days. Cerebral perfusion pressure (CPP) fell to 0 in eight patients, which indicated primary failure of cerebral perfusion. CPP stayed above 60 mmHg in three patients, indicating primary tissue failure, possibly of the cerebral microvasculature. PbtO2 fell to 0 in all patients who experienced brain death, and all patients with PbtO2 of 0 experienced brain death. None of the 61 patients who did not experience brain death had confirmed PbtO2 readings of 0. CONCLUSION: PbtO2 can be successfully and accurately used as a bedside adjunctive test for brain death. The use of PbtO2 as a sole confirmatory test for brain death in the setting of an appropriate clinical examination will require the evaluation of a larger number of patients to assess its sensitivity and specificity.

Adult↗

Estimation of myocardial interstitial norepinephrine release after brain death using cardiac microdialysis.

Brain death is a pathophysiological condition associated with major hemodynamic changes, temporary myocardial ischemia, and histological damage of the heart. These modifications could be related to a major local release of norepinephrine from myocardial sympathetic nerve endings leading to norepinephrine cardiotoxicity. This study was designed to evaluate the utility of cardiac microdialysis to measure interstitial myocardial norepinephrine release resulting from brain death. The dialysis probe consisted in a 10 x 0.20-mm dialysis fiber with a 18,000 mol wt cutoff. Dialysis probes were implanted into the right and left ventricular walls of the beating heart in anesthetized pigs and perfused with Ringer solution at 2 microliters/min. Dialysate norepinephrine concentration was measured using HPLC with electrochemical detection. The relative recovery rate of norepinephrine in vivo was 34 +/- 4%. Interstitial fluid concentrations were obtained using the following formula: [C]interstitium = [C]dialysate/Recovery in vivo. After brain death, a transient increase in interstitial norepinephrine concentration was observed (from 0.74 +/- 0.20 to 4.50 +/- 0.60 ng/ml and 0.76 +/- 0.20 to 6.2 +/- 0.9 ng/ml in left and right ventricle, respectively, P < 0.01) which far exceeded plasma level increase (from 0.50 +/- 0.10 ng/ml to 0.91 +/- 0.20 ng/ml, P < 0.05). This increase in myocardial norepinephrine was, moreover, biphasic, with a second peak occurring 40 min after brain death. The present study confirms the onset of a dramatic increase in cardiac norepinephrine release from myocardial nerve endings following brain death, and demonstrate the utility of the new cardiac microdialysis technique to assess changes in interstitial fluid content.

Animals↗

[Clinical aspects of brain death].

The cause of brain death must be known irreversible primary or secondary structural damage of brain and brain stem. The clinical signs and symptoms of the irreversible cessation of brain functions enable to diagnose brain death. An EEG at maximal gain reflects absence of cerebral electrical activity. The presence of an isoelectric EEG is a mandatory requirement for the diagnosis of brain death. Angiographic, sonographic or other methods to assure cessation of cerebral blood flow but also other methods as the apnea test etc. are helpful but seem to be not necessary. Nearly in every case typical signs and symptoms of an acute midbrain- and bulbar brain syndrome can be diagnosed in the pre-stage of brain death. In about 60% medullary-initiated movements and spinal reflexes can appear and persist for prolonged periods in brain dead patients.

Brain Death↗

The problems with the validity of the diagnosis of brain death.

The diagnosis of brain death as 'death' and organ transplantation have been closely historically linked since the mid twentieth century. It will be argued in this article that the development of a neurological definition of death was introduced to justify the removal of fresh viable organs for transplantation. Brain death cannot be diagnosed reliably using 'established practices'. Improved understanding of the pathophysiology of raised intracranial pressure has challenged our understanding of brain death. We need to move forward in our conceptualization of phenomenon of profound coma associated with massive brain damage. If examination for 'brain death' is to be carried out at all, there needs to be an examination and re-evaluation of practices and protocols.

Brain Death↗

[Quantitative analysis of plasma concentration of barbiturate for diagnosis of brain death].

Organ transplantation from brain death patients started in Japan in 1997. However it is difficult to diagnose brain death in patients treated with barbiturate therapy. In this study, the influence of long continuous administration of barbiturate on diagnosis of brain death was investigated by measuring plasma concentration of barbiturate. In 15 patients treated with barbiturate therapy, plasma concentrations of thiamylal were measured by liquid chromatographic apparatus every day until it's level decreased below 0.1 microgram/ml after cessation of continuous administration. At the same time, plasma thiamylal levels were checked on the day when burst-suppression (b-s) pattern had disappeared in 9 cases, light reflex of pupil appeared in 7 cases and spontaneous respiration had been detected by trigger lamp in 11 cases. The plasma concentrations of thiamylal on the day when b-s pattern had disappeared differed clearly among the cases in the range of 8.8 to 37.9 micrograms/ml. Those cases in which light reflex of the pupil had been recognized were also different in the range of 17.8 to 57.8 micrograms/ml. The cases in which spontaneous respiration had been detected were in the range of 4.4 to 23.0 micrograms/ml. These concentrations varied about 4, 3 and 5 times among the cases examined. The intervals between cessation of continuous administration of thiamylal and the decrease of plasma concentration to below 0.1 microgram/ml also varied from 2 to 14 days from case to case. The minimum concentration of thiamylal on the day when b-s pattern had disappeared, light reflex of the pupil had been recognized and spontaneous respiration had been detected was 8.8, 17.8 and 4.4 micrograms/ml respectively. These results suggest that diagnosis of brain death in patients treated with barbiturate therapy is able to be made when the plasma thiamylal level is below 4.4 micrograms/ml.

Adolescent↗

Auditory brain-stem response in determination of brain death.

A diagnosis of brain death requires evidence of irreversible destruction (or dysfunction) of neurons in the brain stem and cerebrum. The physical examination is not a valid index of brain integrity in patients who are drug-intoxicated or receiving therapeutic paralyzing agents or high-dose barbiturates. We evaluated the use of the auditory brain-stem response (ABR) as an ancillary test in the determination of brain death. A total of 100 combined ABR and nuclear cerebral blood flow studies were completed at bedside with 81 acute, severely brain-injured adults. The ABR and cerebral blood flow outcomes were significantly correlated. We conclude that the ABR is a clinically feasible and useful procedure in the determination of brain death, especially in patients whose medical therapy compromises the neurologic examination.

Adolescent↗

Improved tolerance of the pediatric myocardium to brain death.

The occurrence of brain death has been shown to significantly diminish left ventricular function in the adult porcine model. This study examined whether the pediatric myocardium is as sensitive as the adult myocardium to the detrimental effects of brain death in the porcine model. Left ventricular intracavitary pressure and major and minor axis epicardial dimensions were measured in eleven 1-month old pigs (7.5 to 10 kg) during a vena caval occlusion. Brain death was induced in six pigs by acutely ligating the brachiocephalic and left subclavian arteries. The remaining five pigs served as controls. Data were then collected every hour for 6 hours. The plot of the stroke work versus the end diastolic volume, called the preload recruitable stroke work relationship, was determined from the measured pressure and calculated intracavitary volume data. The slope of this linear relationship is an index of contractility, and the x intercept (Vo) is an index of diastolic mechanics. At each hour after instrumentation two vena caval occlusions were performed, and the mean slope of the preload recruitable stroke work line was calculated as a percentage of the baseline slope in both the brain-dead and control group. The mean values from the brain-dead pigs were 118%, 138%, 126%, 154%, 123%, and 87% of the baseline value for the 6 hours after brain death. The mean control values were 128%, 117%, 133%, 123%, 114%, and 111% of baseline for the 6 hours after instrumentation alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Can pediatricians define and apply the concept of brain death?

OBJECTIVE: We sought to determine pediatric residents' and attending physicians' ability to define brain death, their ability to apply this standard of death to a clinical scenario, and their knowledge regarding the legal necessity of confirmatory testing when determining death by brain criteria. We compared resident and attending self-confidence at discussing brain death with their ability to define brain death and apply this concept to a clinical scenario. METHODOLOGY: A questionnaire was sent to 136 residents, postgraduate years 1 through 3, at four accredited pediatric training programs in the United States. Participation was tracked by return address. One follow-up request for participation was made. A similar procedure was followed for 140 faculty pediatricians at two of the institutions. Demographic information including level of training, subspecialty training, training program, and formal ethics training was collected. Respondents defined brain death, interpreted a clinical scenario, and stated whether confirmatory testing is legally required to determine death by brain criteria. Respondents rated their confidence at explaining brain death to a patient's family on a scale from 1 to 5. RESULTS: Eighty-seven percent (118/136) of resident surveys were returned. Thirty-six percent (42/118) of the residents correctly defined brain death. Forty-three percent (51/118) of residents correctly interpreted the clinical scenario. Fifty-five percent (65/118) of the residents correctly recognized that brain death could be determined without a confirmatory test. Residents who correctly defined brain death were as confident as those who did not (2.8 +/- 1 vs 1.5 +/- 1). Residents who correctly interpreted the clinical scenario were as confident as those who did not (2.6 +/- 1 vs 1.9 +/- 0.9). Eighty percent (112/140) of attending physician surveys were returned. Thirty-nine percent (44/112) of attending physicians correctly defined brain death. Fifty-three percent (59/112) correctly interpreted the clinical scenario. Fifty-eight percent (65/112) recognized that brain death can be diagnosed without confirmatory testing. All pediatric intensivists (n = 12) correctly answered all three questions. Their performance was significantly better than other pediatricians. Attendings who correctly defined brain death were more confident than those who did not (4.2 +/- 1 vs 1.1 +/- 0. 9). Attendings who correctly interpreted the clinical scenario were more confident than those who did not (3.8 +/- 1.2 vs 2.2 +/- 1.2). CONCLUSIONS: Pediatric residents and attendings have difficulty defining and applying the concept of brain death. This concept is difficult to grasp and internalize for many pediatricians. To ensure that critical decisions are made by knowledgeable physicians and well-informed families, more effective educational strategies need to be identified.

Brain Death↗

Families' understanding of brain death.

CONTEXT: Families' understanding of brain death may be a factor that contributes to decisions regarding organ donation. OBJECTIVE: To examine factors related to families' understanding of brain death and how those factors affect families' decisions about organ donation. DESIGN: Chart reviews were conducted on all deceased patients at 9 trauma hospitals. Interviews were then conducted with healthcare providers who spoke with families about organ donation and family decision makers. SETTING: Southwest Pennsylvania and Northeast Ohio. PARTICIPANTS: The sample consisted of 403 families of organ donor-eligible patients who reported that someone at the hospital told them the patient was brain dead. MAIN OUTCOME MEASURES: Families' awareness of brain-death testing procedures, understanding of brain death, and donation decision. RESULTS: Most families (96%) were told their family member was brain dead, but only 28.3% were able to provide a completely correct definition of brain death. No association between the definition of brain death and willingness to donate was found. Those who donated were less likely to agree with the statement that someone is dead only when the heart stops than those who did not donate. Respondents who accepted that their loved one was dead when informed the patient was brain dead were more likely to donate than those who did not consider the patient dead until mechanical support was turned off and the heart stopped.

Adolescent↗

A critique of ancillary tests for brain death.

The acceptance of brain death by society has allowed for the discontinuation of "life support" and the transplantation of organs. The standard clinical criteria for brain death, when rigorously applied, ensure that the brainstem is destroyed. Because more rostral structures are more vulnerable than the brainstem, these are almost invariably devastated when brainstem function is irreversibly lost as a result of whole brain insults. Then, clinical criteria for "brainstem death" ensure that "whole-brain death" is present. However, if the brainstem is selectively damaged or if brainstem function cannot be adequately assessed clinically, ancillary tests are needed to confirm whole-brain death with certainty. Ancillary tests are also required in very young children. In addition, some societies require their use as a matter of principle. Only tests of whole-brain perfusion adequately serve these purposes.

Brain Death↗

[Some practical problems of clinical diagnosis of brain death].

The authors experienced thirty brain deaths including eighteen head injuries and seven cerebrovascular accidents during the period from Nov. 1980 to Dec. 1982 and encountered with some practical problems on clinical diagnosis of brain death. In sixteen patients subjected to barbiturate (pentobarbital) therapy, the attempt to meet the criteria of brain death made it necessary to confirm the total cerebrocirculatory arrest as well as to measure the serum concentration of pentobarbital and assure its level low enough. But as a result of the angiograms performed in twenty-four cases the cerebral angiography sometimes failed to give sufficient evidence to confirm it not merely because of the angiographical intracranial delayed opacification but also because of the dissociation of filling between supra- and infratentorial spaces or between right and left hemispheres. And besides the contrast enhancement of cerebral vessels was verified in computed tomograms of two cases among ten cases who had already met the criteria and demonstrated angiographical nonfilling phenomenon. The angiographical narrowing of C 1-2, A 1, M 1 portions or basilar artery observed on serial angiograms preceding the angiographical nonfilling phenomenon was regarded as direct vascular compression by cerebral swelling or vasospasm and considered to suggest that brain death might be impending. At present the continuous monitoring of intracranial pressure performed in twenty-six cases proved to be a convincing guide to suspicion of brain death or impending brain death according to decrease in cerebral perfusion pressure and appearance of so-called plateau waves recorded in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Current concepts in diagnosing brain death in Germany].

Diagnosis of brain death requires definite evidence of an acute CNS catastrophe and exclusion of complicating medical conditions that may confound clinical assessment. Acute CNS catastrophe may be due to direct ("primary") brain damage (e.g., intracerebral hemorrhage, severe concussion, brain tumors), or indirect ("secondary") brain damage (e.g., cerebral hypoxia following cardio-pulmonary resuscitation). The cardinal findings in brain death are coma, absence of brainstem reflexes, and apnea. Persistence of these clinical signs determines brain death. In Germany, the intervals of a repeat clinical evaluation are at least 12 hours in patients with primary, and at least 72 hours in those with secondary brain damage. Electroencephalographically documented absence of electrical activity for at least 30 minutes or by means of transcranial Doppler ultrasonography or isotope angiography documented intracranial circulatory arrest also confirm brain death. Under such conditions, a repeat clinical evaluation is unnecessary in patients with clinical brain death signs. First of all, brain death is a clinical diagnosis. Confirmatory tests are not mandatory in most situations. In Germany, confirmatory tests are required in newborns, infants below the age of 2 years, and patients with infratentorial brain damage.

Brain Death↗

[99mTc-HMPAO SPECT in the brain death--a case report].

Brain single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethyl-propyleneamine oxime (HMPAO) was performed twice in a 78-year-old man clinically diagnosed as brain death according to the standard criteria of the Japanese Ministry of Welfare. The first brain SPECT demonstrated the tracer accumulation in the brain, indicating preserved cerebral blood flow. The second brain SPECT performed 3 days later revealed cessation of the blood flow. In patients with preserved cerebral blood flow, the diagnosis of brain death cannot be made, even if they meet the existing criteria, because previous report noted the recovery in some of those patients. Brain perfusion SPECT plays an important role as a confirmatory test for the diagnosis of the brain death.

Aged↗