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Chronic “brain death”

Meta-analysis and conceptual consequences
D. Alan Shewmon, MD

Article abstract-Objective: One rationale for equating “brain death” (BD) with death is that it reduces the body to a
mere collection of organs, as evidenced by purported imminence of asystole despite maximal therapy. To test this
hypothesis, cases of prolonged survival were collected and examined for factors influencing survival capacity. Methods:
Formal diagnosis of BD with survival of 1 week or longer. More than 12,200 sources yielded approximately 175 cases
meeting selection criteria; 56 had sufficient information for meta-analysis. Diagnosis was judged reliable if standard
criteria were described or physicians made formal declarations. Data were analyzed by means of Kaplan-Meier curves,
with treatment withdrawals as “censored” data, compared by log-rank test. Results: Survival probability over time
decreased exponentially in two phases, with initial half-life of 2 to 3 months, followed a t 1 year by slow decline to more
than 14 years. Survival capacity correlated inversely with age. Independently, primary brain pathology was associated
with longer survival than were multisystem etiologies. Initial hemodynamic instability tended to resolve gradually; some
patients were successfully discharged on ventilators to nursing facilities or even t o their homes. Conclusions: The
tendency to asystole in BD can be transient and is attributable more to systemic factors than to absence of brain function
per se. If BD is to be equated with death, it must be on some basis more plausible than loss of somatic integrative unity.
NEUROLOGY 1998;51:1538-1545

The equivalence of “brain death” (BD) with death is inexorably and imminently deteriorate to cardiovas-
one of the few bioethical issues of this decade consid- cular collapse despite the most aggressive therapy
ered relatively settled.l(P115) (Together with Veatch? I and resuscitative efforts. The BD literature, right up
prefer to place “brain death” in quotation marks on to the present, is replete with statements to this
account of its semantic ambig~ity.~ For purposes of effect,16-21
such as the following (emphases added):
this paper, the term will be taken to mean “whatever Even with extraordinary medical care, these [somatic]
most people understand by the term ‘brain death’ functions cannot be sustained indefinitely-typically,
[with whatever ambiguity and inconsistency that en- no longer than several days (President’s Commission)
tails] ,” or equivalently, “a clinical neuropathologic (p. 351.13
state fulfilling official diagnostic algorithms and le- Despite all efforts to maintain the donor’s circulation,
gally equated with death in most jurisdictions [re- irreversible cardiac arrest usually occurs within 48 to 72
gardless of the rationale for, or validity of, that hours of brain death in adults, although it may take as
equation].”) What has been settled, however, is long as 10 days in children. Indeed, general acceptance
merely statutory definition and diagnostic proto- of the concept of brain death depended on this close
C O ~ S . ’ , ~Beneath
~~ this superficial consensus there is temporal association between brain death and cardiac
tremendous confusion about the fundamental ratio- arrest (p. 816).22
nale for equating the death of one particular organ What was clearly established in the early 1980s was
with death of the entire o r g a n i ~ m .In ~ the
~ ~ United
~~-~~ that no patient in apneic coma declared brain dead ac-
States and most other countries where a quasi- cording to the very stringent criteria of the United King-
official rationale has been articulated, the rationale dom code . . . had ever failed to develop asystole within a
is that the brain is the “central integrator” or “criti- relatively short time. That fundamental insight remains
cal organ” of the body, and its destruction or irre- as valid today as it was 20 years ago-and not only in
versible nonfunction entails a loss of somatic the United Kingdom but throughout the world (preface
integrative unity, a thermodynamic “point of no re- to second edition).23
turn,” a literal “dis-integration”of the organism as a It is important t o distinguish between this line of
~hole.lJ~-~~ reasoning and a conflation of prognosis of eventual
One line of evidence usually cited is that BD bod- death with diagnosis of present death. As David
ies cannot be maintained indefinitely; rather, they Lamb eloquently explained:

See also page 1530

From the Department of Pediatrics, Division of Neurology, UCLA Medical School, Los Angeles, CA.
Received September 3, 1997.Accepted in final form July 17, 1998.
Address correspondence and reprint requests to D. Alan Shewmon, MD, Department of Pediatrics, Division of Neurology, UCLA Medical Center, MDCC
22-474,Box 951752,Los Angeles, CA 90095-1752.
1538 Copyright 0 1998 by the American Academy of Neurology

That structural disintegra. Survival curves of age and etiology subgroups were ences. Terminal event (spontaneous asystole versus treatment ical support (emphasis in original. reason for prolonged sup. trans- aggressive support. though of considerable interest for survival standard was employed. mechan. There is no pretension that these Methods. analysis because. of information. the purported immi. they WA) spreadsheet for statistical analysis and graphical rep. the brain or also affected multiple organs. patient identification. Although itemized separately in the NAPS table. age at BD. Often the diagnosis was confirmed by multiple phy. each case and compiled into an Excel (Microsoft. and institu. contains the remaining 56 cases subjected to meta-analysis nence of asystole is cited as much by British proponents of (see Note at end of text). however. An attempt was made to compile all known cases constitute a random or representative sampling of cases of BD with survival of 1 week or longer through the entire BD population. strictly for exploratory purposes within the set of cases collection of articles. that organ the President’s Commission13and in whom some residual donation was proposed to the family). specialties. including at least one neurologist or neurosurgeon. vival potential. were unsuitable for meta-analysis because of in- “brainstem” standard were nevertheless included because sufficient individual data (most reported as grouped statis- the intrinsic survival capacity of a BD body should not be tics). 36-37).. ~ ~ ) . etiology. rather than brain destruction per se. might limit sur- only mimics integrated life. the adult heart stops within a week fer from hospital). numbers because of overlap among sources. experience (2 cases). court transcripts (2 declared by (presumably) competent physicians. city. terminal event (spontaneous asystole into the clinical course and revolved around the interpreta- versus treatment withdrawal).” onym) in a nursing article had so many features in com- As much information as possible was collected about mon that they were assumed to be the same patient. not cases). tem. Results. nursing literature (2 taken to include only cases in which BD had been formally cases). whereas the other text of a dead brainstem. One table on file with NAPS itemizes these affected by possible residual cortical function in the con.219 articles. merely journalistic hearsay in which the reporter might about which 79 articles were obtained). When evidence is cited to show that. An article was examined if either cases of BD with survival of at least 1 week (the approxi- title or abstract suggested a possible case of prolonged mation stemming from two articles that reported survival survival. diabetes insipidus. and source(s) of brainstem death and that of a child within two weeks. Articles approximately 175 is less than the sum of the foregoing typically stated physicians’ names.24 withdrawal or ongoing survival) distinguished “deaths” from “censored data” according to Kaplan-Meier methodol- Recent literature and collective personal experi- ogy. and systematic database searches. A few cases involving the British duration. In the medical articles and distribution of sources was as follows: author’s personal personal sources the basis for diagnosis was usually thor. resentation. three cases were ex- sicians. a US-style “whole-brain’’ able diagnoses.. known “brainstem death” as by US proponents of “whole-brain through the news media. it is depending on whether the primary insult was restricted to a necessary consequence of the death of the critical sys. and that of “Sheila” (a pseud- death. and newspapers or news wire services (17 cases. lications Service (NAPS) (see Note at end of text).g. nonpurpose.. confirmatory tests. If patient names were public knowledge. medical oughly documented. What is being said is that a point has been their original reference or by code. cases were identified as in of death. The death of the brain is the point beyond which Data were analyzed with Kaplan-Meier survival curves. the statistical techniques were personal experiences of the author and other professionals. pp. ences and 270 footnotes. the evidence ated clinical findings (e. collected. which constitute an integral part “pregnancy. are available in two tables. other professionals (6 cases). In most. or without. diagnostic criteria turned).” and “life support. along with refer- engines and Lexis-Nexis libraries. from the National Auxiliary Pub- Cases were selected if BD was formally diagnosed ac.” The data for these cases. From the news stories great care was literature (approximately 154 cases). miscellaneous details (e. bioethics literature (2 cases). These controversies arose many days ful movements). EEG activity of uncertain significance reportedly re- Despite the internationality of cases. reached where the various subsystems lack neurological To study the extent to which associated systemic inju- integration and their continued (artificial) functioning ries. The case of Tracy Bucher. one is not marshalling empirical support for a prediction they were included. c a s t serious doubt on this long- statistically compared using the Mantel-Haenszel (log- standing doctrine.” using a variety of search of this article. otherwise. tion of return of muscle tone or certain spontaneous or December 1998 NEUROLOGY 5 1 1539 . Seattle. Combined sources yielded approximately 175 yielding 12. News media were surveyed through the World durations grouped as mean and standard d e v i a t i ~ n ~ ~ . The following data categories were of particu. Wide Web and Lexis-Nexis on key words “brain death. approximately 119 segregated cases. The cording t o customary criteria. strongly favored BD. An additional approximately 115 cases with reli- were fairly uniform. clinical of occurrence but were nevertheless included for meta- signs essential to the diagnosis. described circumstances comprehensible only if the cases whose case occurred before diagnostic standardization by truly involved formal declarations of BD (e. cluded due t o extreme paucity of information and one due Many articles mentioned results of confirmatory tests or t o lack of certainty of diagnosis (Rosemarie Maniscalco. despite the most port. etiologies were divided into two categories tion follows brain death is not a contingent matter. pregnancy outcome. were analyzed as a single case. rank) test. in the author’s opinion. tions. Moreover. A few cases featured diagnostic controversy at the time lar interest: survival duration.g. Some partitionings of data were also evaluated by the chi-square test. Melvyl Medline (UCLA) was searched on the key word “brain death” over the entire history of BD (1966 to 19971. For purposes of meta-analysis. associ. The stated total of have confused BD with vegetative state or coma.g. other systems cannot survive with.

” “TK”). Both spontaneous trunk and limb uncertainty can be taken into account statistically by re- movement^^^-^^ and respiratory-like movement^^^. and 7 at least sets in. whereas spontaneous arrests were widely distrib. 0. The fulfilled early in the patients’ courses (when organs could resulting curve is a better indicator of intrinsic survival have been legally removed or life-support terminated and capacity than those of figure 1. including inef- fectual respiratory-like movements on rare occasions been shifted up and to the right by unknown extents. before the second. phase weeks. 79%)occurred after 220 4 weeks. approximately 20 at least 2 months. 8 Most treatment withdrawals (15/19. An age-partition until spontaneous cardiac arrest (36 cases plus 1 still sur- viving) and those from whom treatment was withdrawn 70 (19 cases). Scatter plot of age at brain death versus log- If support had hypothetically been continued in the with. Chi-square testing 1 0 revealed a window of statistical significance for placement Survival Duration of the survival-duration partition between 21. I I I years) that a logarithmic scale was required to fit every.5 days. 50 thing meaningfully on a single chart. with slightly more than 0 one-half (21/37.5 1 I . all 17 mately 15 a t least 2 months. Conversely. markedly to the right. (2. steps and the 20 censored cases (19 withdrawals and 1still especially because criteria for BD were incontrovertibly surviving) modify the probability level at each step.1 1 dY 1wk 1mO 1 yr lOyr 0 Survival Duration 1 dY 1w k 1mO 1 yr lOyr Survival Duration Figure 1.8 -. more gradual. two of mented survivals of a t least 1 week. most of which involved adult patients.^^ have garding the treatment withdrawals as “censored” data in been described as spinal cord-mediated phenomena in Kaplan-Meier methodology. with the first phase (still nearly Survival durations. approximately 67 at whom were newborns. The The 56 cases with sufficient individual information for inverse relationship between age and maximum survival meta-analysis are shown in figure 1 as actuarial survival duration was nearly linear on the semilog plot. approximately 80 sponding to a half-life of 2 to 3 months) extending as long survived at least 2 weeks. “TK”). 6 months. approximately 32 at least 4 weeks. surviving patient analyzed as “censored”data) represent- ing probability of survival as a function of duration of brain death. with an initially rapid exponen- tial decay followed by a very slow decline. curves for the whole group and for the two subgroups dis. 1540 NEUROLOGY 51 December 1998 .5 days ( p = 0. Figure 3 shows a scatter plot of age a t BD through news media or mentioned merely in passing in versus log(duration) for all 56 cases. months were younger than 18 years. patients over age 30 survived less than 2% months.7.5 and 38. approxi. there remained approximately 161 docu. Note that it has shifted the later controversies never have arisen). Rader.4 n. The longest survivals were so great (up to 14.* Therefore. the overall survival curve would have maximum survival and age.2 0. analogous to patients lost to well-documented cases of BD and are explicitly compatible follow-up or still alive at data collection in a typical sur- with the diagnosis according to the American Academy of vival study. Of the approximate total of 175 linear on the semilog plot. but with shallower slope corre- BD patients surviving a t least 1 week. Kaplan-Meier survival curve corresponding to event-spontaneous cardiac arrest or treatment figure 1 (with the 19 treatment withdrawals and 1 still withdrawal. The longest survivors medical articles. This (“Baby A. in by such movements were not considered in themselves suf. 5. and all nine survivors beyond 4 least 2 weeks. (survival duration) shows inverse relationship between drawal subgroup.1. reflex movements (Camp.5 years) were all young children. The drop-off of all 50 three curves was biphasic. Total Group 1 0. with maximum significance at 28. Even excluding the 14 cases known only Age efect. which the 36 spontaneous arrests constitute the vertical ficient grounds to reject a case from the current study. and 14. 57%) before 4 weeks.006). approximately 44 a t least 4 as 1 to 2 years. Accordingly. the diagnostic disputes engendered formed into the single Kaplan-Meier curve of figure 2. and 7 at least 6 months.7 06 ‘5 o’5 3 n ’ 0. Figure 3. the transition g 40 $33 occurring around 4 to 6 months. Survival curve for the 56 cases subjected to meta-analysis (“Total”) subdivided according to terminal Figure 2. 0.3 0. Age also influenced the proportion of treatment withdraw- tinguished by terminal event: those supported indefinitely als. 10 uted across survival durations.9 0. the three curves of figure 1 trans- Neurology.

with of log(age) versus log(duration) according to etiology cate- gory.4. The higher the partition. the more Figure 5.5 The greatest significance was for an age group between a days. divergent the survival curves (that of the older subgroup broken down according to etiology category. Figure 4 exemplifies this with a the interaction between age and etiology of brain death as partition a t 35 years. 47%of cases (16/34) ended by treatment withdrawal compared with only 14% (3/22) for age 14 or younger ( p = 0.2. Overall. '< Because the age effect was statistically overpowering a t 0. 61%) had multisystem insult and 45 years ( p = 0.. anywhere between 13 and 22 years yielded a statistically significant chi-square test. 1 L. ! 01 : ::::! : : ! : ::::::Id : :::::::! : ' 1 dY 1w k Im.7 spite etiologies of severe hypoxia-ischemia.3 L 0. but at the extremes of age. where statistical significance was co-determinants of survival capacity. above and below an age-partition placed anywhere be- Nevertheless. Age Effect I I I 1 ETIOLOGY 0. By contrast.00519 newborns (lower right corner) had very long survivals de- = 0. and uncertain (8).07) for survival-duration partitions placed between 40.- was best appreciated in the large age group between these 0. illustrating shifting more to the left).0000003). Etiology effect abstracted from age effect by ex- years and an upper age limit anywhere from 13 to 48 years cluding extremes of age. 67%)had primary brain Within the category of primary brain pathology. This etiology effect was not accounted for by age independent effect of age was even more powerful than it as a proxy variable because a separate plot of etiology was across combined etiologies. tween 22 and 49 years were statistically significant (maxi- nants of survival probability. . p = 0.5 and 48. sult (241. The distribution of etiology category was as multisystem insult with shorter.01).7 40 44% Multisystem x ? $ 0. Exploratory analysis was performed by sys- tematically varying its upper and lower bounds and com..5 CP x"*4 x oo g L1 0. lower bound of 5 to 9 months and a n upper bound of 43 to ogy category (17/28. follows: primary brain pathology (241.? 0. Figure 5 shows a scatter plot mally so between 34 and 45 years. the contribution of etiology Primaly Brain 0.00002).3- . the effect of etiology was overshadowed by that of age. Kaplan-Meier curves show the effect of age at brain death on survival capacity: patients at or below age 35 years survived significantly longer than did those over 35. Upon defining treatment withdrawals as censored data.I I II I two extremes. 1 0. Etiology= both ends of the age spectrum. 1 Yr 10yr Survival Duration categories within illustrated in figure 6. below which the majority of cases with known etiol. but the two extremes of age clearly consti- tute notable exceptions to this general trend.005). longer survival capacity than multisystem insult. 0.2 . Chi-square testing revealed a region of statistical near-significance ( p = 0. December 1998 NEUROLOGY 51 1641 . diffuse systemic in. The association of primary brain pathology with 6 mo < Age <= 44 yr longer survivals and diffuse pathology with shorter surviv- als is evident. age and etiology interacted as determi. brain pathology was associated with longer survivals and Etiology.-. primary greatest ( p = 0. There was a broad region approxi- mately defined by a lower age limit between 1 month and 2 Figure 6. the pathology.6 31 o x 8 8 6 0. above which the majority (12/18..4 10 yr 0 0 r X n 0. Kaplan-Meier curves show that within which primary brain pathology was significantly primary brain pathology is significantly associated with associated with longer survival than multisystem insult. with maximal significance at age 14. older than this. Comparisons of survivals versus age revealed no relationship between the two.8 -.- Age > 35 Years I L-I .$ 06 older adults had shorter survivals regardless of etiology. E . 04 : : : : : ! : : ! : : :::::d ! : ::::::! : I paring the Kaplan-Meier curves for the two known etiology 1 dY 1wk Im. The two p = 0. 1 dY lwk Irm 1 Yr 10 yr Kaplan-Meier curves for "young" and "old" subgroups dif- Survival Duration fered significantly for age-partitions placed anywhere be- tween 27 and 57 years.5 z .1 . 1 yr 10 yr Survival Duration Figure 4.9 100 yr Primary Brain 0. Scatter plot of log(age) versus log(duration).

changes occur prior to 48 and even 24 hours after brain vivals than the older subgroup. multiple clinical examinations. Parallel comparisons within the multisystem category could not be That observation carries little weight. therefore. the general conclusions are robust and ex.” yond the “few days” typically cited as maximum pos. intracranial Furthermore. substantially since those pioneering studies. and four (7%) more than third of cases support was withdrawn. patients with agnosed and that BD declarations are inherently un.38 mally until asystole-is unknowable but surely also vival data from a recent Taiwanese prospective small. Even excluding news stories. cases. inviting from similar but smaller studiesZ3(p 30) because pa- the criticism of possible misdiagnoses. it is difficult to interpret the dismal sur- apy. Unfortunately for BD research. If patients were “brain dead” scientific methodology. The most straightforward reason could be called No investigator contributing to this volume has pre. Although detailed inferences must be viewed cau. ble bodily death. and many day2fl.37.35. never becomes manifest.12 mained even after excluding extremes of age. death (p. Studies permitting organ do- enough to qualify as organ donors. But those who survive gradually stabilize: ho- and children). the record being 14% years (and still going). the apparent imminence of asys- more potential cases have never been manifest be. by contrast. Validity of cases. philosophical bias and sheer inertia of tradition may tremely relevant to whether BD represents loss of have contributed t o perpetuating the anachronism somatic integrative unity. Some Undoubtedly. ~ ~ ~ it is difficult to draw conclusions re- 1 9 7 0 Again.) diorespiratory ~ u p p o r t . The same disclaimer applies to the landmark review article that same year by one section of Discussion. neuro-intensive care has improved blood flow. given the lack of systematic attempt to maintain BD cessive inhomogeneity of data. very unstable hemodynamics or multisystem failure reliable. the amount and garding intrinsic survival capacity from this and quality of information vaned tremendously. tole is no evidence for limited intrinsic survival cause BD is nearly always a self-fulfilling prophecy capacity.25. meaningfully accomplished due to small numbers and ex. ” 3Perhaps ~ more inter- Enough information was available on 56 cases for institutional variation in “fullness of support” exists meta-analysis of factors affecting survival capacity. more cases of prolonged survival aspects then would be considered substandard to- have occurred than have been reported. they were surely nation are particularly unhelpful because the best “brain dead” enough to qualify for this study. and necropsy findings. Finally. and most often these final irreversible meostasis adjusts. however. the meaningful ratio is not nearly study of “brain-stem dead” patients given “full car- so tiny as it might initially seem. the small propor. This striking effect re.^^ (Thus.” The acute loss of all brain-based sented evidence that irreversible cardiac arrest may be somatic regulation predisposes to cardiovascular col- postponed more than a week (exclusiveof that in infants lapse. seven underestimate BD survival potential because in one- (13%)more than 6 months. Contrary t o popular belief. ethical physicians. An exhaustive search yielded approximately from three neurosurgical units during the 1960s and 175 cases surviving 1week or more. The data collected here actually nearly one-third (17/56) more than 2 months. Naturally. To donor candidates have the most intact organs and dismiss the cases as presumptive misdiagnoses therefore also the greatest survival potential. hemodynamic status improves. Terminal event. “somatic plasticity. thereby biasing out- examples remain of unequivocal BD confirmed by comes toward early asystole. 1542 NEUROLOGY 51 December 1998 .the younger subgroup manifesting considerably longer sur. EEGs. despite increasingly abundant published counterevi- Durations of suruiual. that time. than is generally recognized. patients aggressively to determine survival capacity. But even in tients who did not succumb quickly to asystole (near- cases with least information. which would imply that organ donors are also often misdi. one-half (28/56) survived more than 1 month. and 57% of spontaneous arrests in which: before.^^. Another oft-cited study involved 609 BD cases sible. of somatic demise through organ harvesting or dis. formal diagnoses were ly one-half of the 609) were typically disconnected unquestionably rendered by presumably competent from support. usually including at least one neurologist patient management is incompatible with optimal or neurosurgeon. mately 4 weeks into BD there was a statistically If many of these cases have been in the medical significant transition in the proportion of treatment literature for some years. how did the “few days at withdrawal versus spontaneous asystole. Given that BD pregnant women have been main- continuation of upp port. Approxi- 1year. Of the meta-analyzed dence. The 198436and virtually indefinitely with hormonal ther- relevant denominator-the number supported maxi. 27). one cannot help wondering to what extent tiously. there are which equated the very essence of BD with “inevita- many well-documented BD cases with survival be. of withdrawals after.26.therefore. with 79% most” dictum ever become so firmly entrenched? Fre- quently cited is a 1978 multidisciplinary conference. tained for months and that Japanese teams have tion of prolonged survivals among all BD cases in no supported BD patients extensively as far back as way diminishes their conceptual importance. many striking are typically rejected as donors.

By integrative unity t o at least the same degree as the contrast. physiologic environment for the developing fetus Of the two cases known personally to the author. tions. and if the concept of somatic stage (before versus after recovery from spinal plasticity is valid. it is directed toward maintaining an optimal longed survival. For such simple treatments to permit virtually tail a several week latency. trauma” is a commonly stated category. after several weeks in an intensive care cate lack of unity in BD bodies in general. The three most spectacular survi. children have more robust nations for the discrepancy are differences in clinical health than do the elderly. and no spontaneous respirations or brainstem re. Similarly. This age effect described with pregnant BD women. and many dinary for contemporary ICU standards. pro- Perhaps the circumstances of treatment with. remains incontrovertible: BD does not necessarily Even in the acute phase. will be considered in the following. for a pregnant woman is not merely the minimum to Complexity of care required. complexity of “BES” was an almost-14-year-old head-trauma vic. and basic nursing care. Several Japanese studies teach a similar lesson. tole despite aggressive therapy? The heterogeneity Hardly any laboratory tests were obtained. “head cranial peaks. Survival suggests a difference in somatic substrate. Multiple EEGs have been isoelectric.” “aggressive. just as they have more neuroplasticity. Listings of etiologies in the Multimodality evoked potentials revealed no intra. and head. and overall man. function). indefinite survival. management in the pregnancy cases does not indi- tim who.Similar ~ ~ . latter. Five other cases transferred to nursing facilities For current purposes. not merely rare anecdotal excep- a fetus brought to viability) merely happened to en. grative unity. parenteral fluids. Such relative simplicity of treatment contrasts vors-with durations of more than 2 years-were all markedly with the technologic tour de force typically young children. but motor closed no intracranial blood flow. That many others must have an unrealized potential to do so. shock. Plausible expla- is not surprising. Age and survival capacity were in. children must have more of it than shock) and therapeutic goal. the effort required to lead to imminent asystole. stable hemodynamics were maintainable in all and those relatively stable (implying some minimal patients seemingly indefinitely. quite alive argues strongly that the former possess cumbed to spontaneous arrest within 4 months. “heroic. He is fed by neural integration” a downward hemodynamic spiral gastrostomy.26Because these studies were prospective. Supporting evidence. BD literature often obscure this. etiologies were December 1998 NEUROLOGY 51 1643 . therefore. one possible somatic factor is di- flexes have been observed over the past 14% years. The other (‘‘TK”) is now an 18%-year-old boy who because the difference between two subgroups (im- contracted Haemophilus influenzae meningitis at age minence versus nonimminence of asystole) cannot 4. dicting the brain-as-somatic-integrator hypothesis. the underlying somatic substrate Regardless of the interpretation. dency to stabilization seems strong evidence for inte. Apart from age. unit (ICU). with return of spinally chronic survival in BD does not necessarily require mediated autonomic tone and reflexes. mean There also may be two subpopulations of BD pa. “Baby Z”) similarly exemplify how to recovery from spinal shock.” or “sophisticated technology. By merely adding vasopressin to epinephrine. (and with great enthusiasm). Cerebral edema was so extreme that the cranial derive from what is common to both (lack of brain sutures split. one should not attribute to “loss of ghost-like outlines of the former brain. and for the last 6 years has been thriv. and neuroimaging vehicle accidents or severe falls are much more likely showed the entire cranial cavity t o be filled with to damage internal viscera than are gunshots to the disorganized membranes. Adults treated indefinitely all suc. contra- was cut short at 65 days by untreated sepsis. If some BD patients can survive a skilled nursing facility. ~ ~results ferred from the relationship between etiology and have been obtained with cortisol and triiodothyro- survival duration. “Baby A ) or home (Hamilton. Seven very unusual sustain her own body. At least some bodies with sustain most BD patients is not particularly extraor- dead brains have survived chronically. and the epinephrine degree of integrative unity). with minimal enthusiasm of the health care team). actually need much less sophisticated management Age factor. rect multisystem injury. proteinaceous fluids.enteral nutrition can be resumed. ally indefinitely. survival times in BD increased to 23 days. two being newborns. For example. children seemed capable of surviving virtu. Such ten. the main point must be considerably integrated already. nine. The treatment regimen adults. This may be largely attributable case of Pinkus. the agement simplifies. requirement gradually d e c r e a ~ e d . in. longed survivability seems representative of BD drawal in many cases (especially cesarean delivery of patients in general. There he received nothing apparently indefinitely with relatively simple inter- more than mechanical ventilation. than many other ICU patients who are nevertheless versely related. desmopressin ventions. (Chamberlain. as in other BD cases (often cases prove that complex technology and extraordi. Thus. magnetic resonance angiography dis. was transferred at the parents’ request t o Etiology factor. actually caused by cardiac contusion or hypovolemic ing sui generis on a ventilator at home. nary clinical effort are not always necessary for pro. In general. rather.38With tients: those absolutely unstable (possibly although pressor rather than antidiuretic doses of vasopres- not necessarily because of lack of integrative unity) sin. why do others deteriorate quickly to asys- acetate.

disseminated intravascular coagulation add postage of $4. PhD. neurogenic pulmonary edema (mani.00 for each 10 pages of material thereafter. Rep 1997. system injury.17:265-270. 23(6):41. Bernat JL. alive. and tests.49:570-572. death: medical. on all orders filled before payment. 1992:23-51. 14. Outside the United States and Canada. and a r r e ~ t ) .1:261- 262.^^^^^ Gastrointestinal hem.classified as either “primary brain” or “multisystem. 702). eds. Brody B. orrhage from neurologically induced stress ulcers can also complicate management. 1544 NEUROLOGY 5 1 December 1998 . Carrasco de Paula I. (Scripta Varia 83). Working Group on the sider cardiovascular stability a relative requirement Determination of Brain Death and its Relationship to Human for heart d o n a t i ~ n . inexorable deterioration in a minority 1. American Academy of Neurology Quality Standards Subcom- hearts due to intrinsic cardiac pathology. 5. ~ O * ~ l and Mane1 Baucells for assistance in the advanced use of Excel. Conversely. In: White RJ. older adults had sonhood” from a biologically live body. 11. pracritical damage to multiple organs. MD.50 for the first 20 pages and $1. Arthur Allen. Thus. NY 11552. Neurology 1995~45:1003-1011. especially the 3. The impending collapse of the whole-brain defini- tive organ donor^^^. Affairs. Veatch RM. and Tsu-pei Hung. in a chapter on head injury these “mul. Truog RD. Shewmon DA. Vatican City: Pontifical Academy of Sciences. a book chapter entitled “Multisystem sequelae of se. transplant specialists ironically con. wurm H. MD. not under separate cover. not from a top- vivals with multisystem insults. 1994:113-143. Rosa Lynn Pinkus. Excluding age down imposition of one “critical organ” upon an oth- extremes. for sharing infor- mation about their cases. DC: US Government Printing Office. tone.42. Additionally.4:253-264.^^. renal water conservation. Request document no. Head-injured patients frequently sustain Semin Neurol 1997. 8. therefore. Whether other rationales. Wijdicks EF. in US funds only.^^) is therefore less attributable t o tion of death [published erratum in Hastings Cent Rep 1993. 10. crite- Head i n j u r y c a n n o t be considered an isolated. Medicine and Biomedical and Behavioral Research. If BD is to be additive determinants of survival capacity.00 for photocopies . This is not a multiarticle and subendocardial microinfarcts have been de.00 for each fiche thereafter. endorsement is beyond the scope of this physiologic thology secondarily induced by sympathetic storm inquiry. Reexamining the definition and criteria of death. Ann NY Acad Sci 1978.23(4):18-24.45:1012-1014. MD. The concept of death: derangements are cited as evidence that the patient summary.45 tory. hypertension. PhD. President’s Commission for the Study of Ethical Problems in Ironically.00 for microfiche. 9. There is a $25. unique effects of head trauma o n the hypothalamic. Taylor RM. PhD.00 invoicing charge to 65%of BD organ donor^. blurred by semantic ambiguity.Hastings Cent Rep 1993. it must be on tremes the age effect predominated. . 10-14 December. fested by difficulty maintaining oxygenation). Brain death: reconciling definitions. 05467. Boston: Butterworth- of BD patients (only approximately 10% of prospec. and glucose metabolism . etiology and age were independent and erwise mere bag of organs and tissues. and shorter sur.75 for the first microfiche and occurs commonly with severe head injury and in 25 $1. 2. Halevy A. E q u a l l y important are the multi. Tomlinson T. gastric acid secretion. ria. Youngner SJ. single.43human BD autop.27(1):29-37. He also thanks Charles Cannon. from the process of brain herniation before BD and not attributable to mere absence of brain function Acknowledgment afterward. Conference of Medical Royal Colleges and their Faculties in . o t h e r o r g a n trauma.) ceptually more viable or desirable for societal A second possible somatic factor is systemic pa. These are common with serious neurologic injuries in general. Defining death: a superficial and fragile consen- temic functions as blood coagulation. Bioeth- system effects of trauma t o a n y p a r t of the body and the ics 1990. Korein J. Ethical issues in neurology. quality functional survival the United Kingdom. whereas in a typical chapter on BD the same 1981. p u l m o n a r y venular sus. legal. for statistical ad- vice.^^ ~ i e s and or $5. such as loss of “per- perinatal asphyxia. Readers can obtain 25 pages of supplementary material culminating in BD. least hemodynamic stability have the least usable 4. document. 7. Indeed. absence of brain function per se than it is to su. Neurogenic pulmonary edema from the National Auxiliary Publications Service.315:19-38. Diagnosis of death. Practice parameters for determining brain death in These considerations are elegantly summarized in adults (summary statement). Lancet 1979. (At ex. The phenomenon of chronic BD im- Longer survivals (more than 6 weeks) were associ. cardiac arrhythmias. Defining tisystem derangements” are interpreted as therapeu. obviously d e p e n d s o n a t t e n t i o n to these multisystem de- 12. References The rapid. equated with human death. ~~. which influences s u c h diverse pansys. scribed in experimental BD. 1984. Ann Intern Med 1993. Misunderstanding death on a respirator. Angst- heart. Swedish Committee on Defining Death. mittee. and ethical issues in the determination tic challenges to keep a critically injured patient of death. mutual interaction among its parts. West Hempstead.119:519-525. Stockholm: Swedish Ministry of Health and Social had already died. babies “A” some basis more plausible than that the body is and “ Z had very long survivals despite an etiology of dead. plies that the body’s integrative unity derives from ated with primary brain pathology. Is it time to abandon brain death? Hastings Cent p i t u i t a r y axis. or $1. 13. and and Frank Lopez for assistance in the Lexis-Nexis retrieval of subendocardial infarctions (manifested by refractory news media references. 1989. ~ ~ICU management of organ donor^.Conversely. Remit with your order.~~ BD patients with Death. Arch Neurol 1992. Washington. Heinemann. Complications include transient severe The author thanks Ronald Cranford. Determining brain death in adults. Donald Guthrie. 248 Hempstead Turnpike. hypotension. ‘Brain death’: a valid theme with invalid varia- tions. The problem of brain death: development and his- rangements (p. might be con- shorter survivals regardless of etiology.” Conclusion. vere head injury” (significantly not about BD): 6. $15. Neurology 1995. so they are hardly surprising in cases Note.

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