Why is Diagnosing Brain Death So Confusng

8/18/2019 Why is Diagnosing Brain Death So Confusng

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CURRENTOPINION Why is diagnosing brain death so confusing?

Shivani Ghoshal and David M. Greer

Purpose of review

Although detailed practice parameters have been developed to help guide physicians in brain deathdetermination, guidelines based on these parameters widely vary. The recent case of Jahi McMath not onlyhighlights social misconceptions but also serves as a call to action to decrease medical variability andconfusion regarding brain death determination. This review discusses common sources of variations inbrain death determination – we divide these sources into before, during, and after brain death declaration.

Recent findings

We use four key studies to elucidate variable practice in brain death determination. Poor training of examiners and patient qualifications for brain death examination prior to testing, incomplete apnea testing,repeat examinations during testing, and the sometimes unjustified use of ancillary testing are highlighted asmain areas for improvement. Improved physician training and certification, as well as better

standardization of hospital protocols, may be answers to more universal practice.Summary

Diagnosing brain death is confusing because of numerous variations in practice, but this variation can beimproved. Improved and standardized physician training can help create a formal certification process forexaminers and help create uniformity in brain death determination. National standards will also helpdecrease variability of practice.

Keywords

brain death, guidelines, variability

INTRODUCTIONOn 9 December 2013, 13-year-old Jahi McMathunderwent elective tonsillectomy at the Children’sHospital Oakland, Oakland, California, USA. Herpostoperative course was complicated by massiveblood loss, leading to cardiac arrest and severehypoxic-ischemic brain injury. Three days later,the child was declared brain dead by the hospital’sphysicians.

Because of the concern of the hospital’s ‘conflictof interest’, the McMath family requested a tempor-ary restraining order until Jahi was determined dead

by an independent physician. On 23 December,independent assessment of brain death, includingan apnea test and an electroencephalography(EEG) with electrocerebral silence, was affirmed.The family appealed for continued ‘life support’measures, arguing that the Uniform Determinationof Death Act was a violation of her constitutionalreligious and privacy rights. Although the appeal wasdenied, the Children’s Hospital Oakland releasedMcMath’s body per her family’s request. Her bodywas transferred to St Peter’s Hospital in New Jersey,where it currently remains [1

&&

,2&&

].

OVERVIEWMs McMath’s case highlights continuing difficultiesin understanding and establishing brain death. In a2003 survey of families of brain dead patients, only28% were able to give a correct definition of braindeath and almost 60% of the families believed thattheir dead loved one was still alive. Although thedefinition of brain death depends on both social andmedical consensus, society acceptance dependsheavily on clear and consistent medical care [3].

Although detailed criteria for brain death havebeen established for several decades, practices for

brain death determination are far from universal,sometimes with variation even within the same city.These variations contribute markedly to ongoing

Department of Neurology, Yale University School of Medicine, New

Haven, Connecticut, USA

Correspondence to David M. Greer, MD, MA, FCCM, FAHA, FNCS,

FAAN, Department of Neurology, Yale University School of Medicine, 15

York Street, New Haven, CT06530, USA. Tel: +1 203785 5012; fax: +1

203 785 2238; e-mail: [email protected]

Curr Opin Crit Care 2015, 21:107–112

DOI:10.1097/MCC.0000000000000180

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REVIEW

mailto:[email protected]:[email protected]



confusion about brain death determination [4&&

].Brain death’s definition itself may vary internation-ally. Failures in practice consistency can be organ-ized by a preexamination, examination, andpostexamination timeline. This discussion outlinescommon pitfalls and notable reviews for eachcategory. We close with areas for improvement,training, and formal certification for physicians.

BRAIN DEATH AND ITS DEFINITIONS

Brain death was first conceptualized with the adventof ICU care and mechanical ventilation in the1950s; its definition has developed from that time.In 1981, the Uniform Determination of Death Actdeclared brain death as having equivalent legiti-macy to the more standard cardiopulmonary death,

‘in accordance with accepted medical standards’ [5].Unfortunately, although brain death has been inter-nationally accepted, what constitutes ‘acceptedmedical standards’ varies.

In the United States, brain death is considered a‘whole brain death’ concept, requiring irreversibleloss of function of the entire brain, includingthe brainstem. From the 2010 American Academyof Neurology (AAN) guidelines, brain death maybe declared when ‘brainstem reflexes, motorresponses, and respiratory drive are absent in anormothermic, nonintoxicated comatose patient

with no contributing metabolic derangements’[6]. In contrast, in the United Kingdom, ‘brainstemdeath’ equals brain death – irreversible loss of function in the brainstem constituting coma, totalbrainstem arreflexia, and apnea, regardless of cort-ical activity [5]. A third view is ‘neuroessentialism’,a concept in which loss of all higher brain functions(but with an intact or partially intact brainstem)questions the patient’s life from a more philosoph-ical point of view [6]. Although neuroessentialismhas some proponents in neuroethics, it is far frombeing widely accepted.

With whole brain, brainstem-only, and ‘higherbrain’ death all possible forms of brain death, estab-lishing a unifying definition for brain death hasbeen difficult [7]. In 2008 and 2011, the President’sCouncil agreed that total brain death constitutesdeath of the human organism [8

&&

]. In 2014, theInternational Guideline Development for the Deter-

mination of Death further defined death as ‘thepermanent loss of capacity for consciousness andall brainstem functions . . . that cannot resume spon-taneously and will not be restored through inter-vention’ [9

&&

]. The symposium called for the end of anatomically based terms such as ‘brain death’ or‘cardiac death’, as different terms could erroneouslyimply differences between types of death.

BRAIN DEATH VARIATIONS: BEFORE,DURING, AND AFTER THE EXAMINATION

Currently, declaration of brain death in the United

States is based on the 2010 American Academy of Neurology practice parameters, a four-step protocoland 26-point checklist outlining clinical prerequi-sites for candidacy for brain death determination, adetailed neurologic examination including anapnea test, ancillary testing if needed, and appro-priate documentation [6].

There is still uncomfortable variation, however,with gaps between intention and practice. For thepurposes of this discussion, we review these topicsfrom the lens of four key articles investigating differ-ences in the brain death declaration (Table 1).

(1) Wijdicks (2002): A survey of adult brain deathguidelines in 80 countries. Information wasobtained through a combination of literaturereview and personal letters [10].

(2) Greer et al. (2008): Review of hospital guidelinesfor AAN guideline performance, preclinical test-ing, clinical examination, apnea testing, andancillary tests in the top 50 US News and WorldReport neurology/neurosurgery institutions.Information was obtained by 38 participatinghospital guidelines [11].

(3) Lustbader et al. (2011): Review of intervals

between first and second clinical examinationsfor brain death in 1229 adult and 82 pediatricpatients. Information was obtained by review of the New York Organ Donor Network recordsfrom 2007 to 2009 [12].

(4) Shappell et al. (2013): Review of guideline per-formance, preclinical testing, clinical examin-ation, apnea testing, and ancillary test use in226 brain-dead organ donors from 68 hospitalsand medical centers in two states. Informationwas obtained through a hospital chart review in2011 [13

&&

].

KEY POINTS

Brain death determination is confusing because of poorpractice consistency in hospital guidelines and variationin care, both nationally and internationally.

Failures in practice consistency can be organized by apreexamination, examination, and postexamination

timeline.

Future directions for improving brain death diagnosisinclude standardization of hospital protocols inaccordance with national guidelines, as well as bettertraining and certification for physicians.

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Pitfalls before brain death examination

Appropriate examiners and patient candidacy prac-tice parameters exist, although with wide range of interpretation in hospital guidelines.

APPROPRIATE EXAMINERS: GREER ET AL., SHAPPELL ET AL., AND WIJDICKS

REVIEWSWho is responsible for brain death determination?Although the AAN practice parameters state that ‘itseems reasonable to require that all physicians mak-ing a determination of brain death be intimatelyfamiliar with brain death criteria and have demon-strated competence in this complex examination’,there is no formal certification process to be quali-fied for brain death determination [4

&&

].From the review of Greer et al. in 2008, a neurol-

ogist or neurosurgeon was required in only 42% of the guidelines; of these, only 35% required an

attending physician from neurology or neurosur-gery be involved [11]. From Shappell et al. in2013, although 95% of patients had a neurologistor neurosurgeon involved in their care, only 43% of patients had brain death declared by these special-ists. Of these brain death declarations, only 45% metstrict criteria, 37% met loose criteria, and 18% werewith incomplete criteria/data [13

&&

]. Wijdicks in2002 found similar variations. In Alaska andGeorgia, a registered nurse was delegated authorityto declare death according to the AAN criteria,with certification by a physician within 24 h. One

physician was sufficient for declaration in moststates, but California, Alabama, Iowa, Louisiana,Florida, Virginia, and Kentucky required independ-ent confirmation by another physician [10].

BRAIN DEATH CANDIDACY: GREER ET AL.AND SHAPPELL ET AL. REVIEWS

Determining candidacy for brain death examin-ation by ruling out potential confounders is crucial.Normothermia, electrolyte optimization, absence of hypotension, and drug clearance are all essential; adiagnosis of brain death is certainly not one to bemade under suspicion or possible confounding.Medications may undergo delayed clearance inpatients who have received therapeutic hypother-mia [14]. For patients with possible brain death,examination should be delayed if there is any sus-pected lingering effect of drugs or reversal agentsgiven, if possible [13

&&

].

In the review of Greer et al. [11], although 97% of hospital guidelines specified prerequisite body tem-peratures, serum electrolyte values, and provisionsfor drug clearance, the specific numbers widelyvaried. Despite the AAN guidelines, a staggering11 different minimum core temperatures were stipu-lated, with similarly varying minimum systolicblood pressures. The review of Shappell et al.[13

&&

] found that many of the brain death candidateshad hypothermia and severe electrolyte abnormal-ities: 15% had core body temperatures below 368Cand 13% had a serum sodium greater than 165.

Table 1. Four key articles investigating differences in brain death declaration

First author

Years for

data review

Number of

subjects Method Major findings

Wijdicks 2002 80 countries Literature review and personal survey Formal practice guidelines for 88%of countries; wide variations inapnea testing, required examiners,and approach to ancillary testing

Greer 2008 38 hospitals Procured hospital guidelines Major discrepancies in guidelineperformance, preclinical testing,apnea testing, and approachto ancillary testing

Lustbader 2007–2009 1229 adults,82 pediatric patients

Chart review of New York OrganBank donor records

Mean time to brain death declarationbetween two examinations was19.2h – three times longer thanproposed by guidelines, andassociated with increased costs anddecreased organ donation

Shappell 2011 226 patients Chart reviews from 68 hospitalsin two states

Major discrepancies in preclinicaltesting, apnea testing, and approachto ancillary testing. Only 44.7%met strict AAN practice parameters

AAN, American Academy of Neurology.

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Pitfalls during brain death examinationThe apnea test and repeat examinations are main-stays of the brain death examination, although theymay have marked error in their implementationand interpretation.

THE APNEA TEST: GREER ET AL. AND WIJDICKS REVIEWS

Apnea testing is a key element in brain death deter-mination; the AAN practice parameters detailminimum core temperature and systolic bloodpressure, preoxygenation, supplementary oxygen,and thresholds for arterial blood gas values for apneatesting. Despite these practice parameters, thereviews of Greer et al. and Wijdicks found markedinconsistency in hospital apnea testing guidelines.The review of Greer et al. [11] revealed that of the 38protocols reviewed, only 66% required an arterialblood gas prior to testing, 76% stipulated preoxyge-nation, and only 7% specified a mode for preoxyge-nation. Even reasons to abort the test varied, withdiffering apnea interpretations or acceptable finalvalues of carbon dioxide partial pressure (pCO2)[11]. From the study of Wijdicks [10], few centersworldwide consistently performed apnea testingwith pCO2 monitoring [10]. This is concerning,given that apnea testing depends on acute hyper-carbia and acidosis to stimulate respiratory centers.It is difficult to say that of this percentage of apneatests being performed, which were performed orinterpreted correctly [14].

REPEAT EXAMINATIONS: GREER ET AL.AND LUSTBADER ET AL. REVIEWS

Although repeat examinations are commonplace, itis unclear whether they are well tolerated or evennecessary. From the study of Greer et al. [11], 71% of guidelines required multiple examinations, and of these, 41% stipulated that the examinations beperformed by at least two separate physicians. Stipu-lated times between these examinations varied.Although an arbitrary 6 h was the most common

waiting period, the interval could be shortened perthe practitioner’s discretion if there was supportiveancillary testing, or lengthened for pediatricpatients [8

&&

]. In the review by Lustbader et al.[12], although the 2005 New York state criteriarequired an apnea test and two clinical brain deathexaminations separated by 6 h, for some institu-tions, one examination was sufficient, whereasone particular center required four. Of note, fromthese repeat examinations, no adult or pediatricpatient who satisfied criteria for brain death onthe first examination and apnea test had a differing

assessment on repeat examination. The averagetime between the two brain death examinationsfor the 1311 patients was 19.2 h, over three timesthe stipulated 6 h. Delay in declaration of braindeath had markedly negative consequences fororgan donation and organ procurement: of thepatients in the review by Lustbader et al. [12],

10% of patients suffered a cardiac arrest while await-ing a second brain death examination, and another4% experienced cardiac arrest after the secondexamination.

Pitfalls after brain death examination: therole of ancillary testing

Ancillary tests, intended for use only in situations of confounded interpretation of brainstem and apneatesting, have the danger to be misused to supplantthe bedside clinical examination. In cases such ascardiac arrest or hypothermia, in which the braindeath examination may be confounded by lingeringeffects of medications, ancillary tests can be helpfulin establishing irreversible loss of brain function.EEG, conventional angiography, and radionuclidescintigraphy are the most commonly used and bestvalidated ancillary tests. However, even in the bestof circumstances, any ancillary test can be subject toartifact and misinterpretation if care is not taken.For tests intended as a method of determination,this variation needs to be recognized in each clinicalsituation [14].

Variation between EEG and perfusion tests is not

uncommon, as noted in the review by Busl andGreer in 2009 [15]. EEG can be notoriously suscept-ible to artifact in the ICU. Cerebral perfusion studiescan be misinterpreted in cases of minimal flow inclinically dead patients. Transcranial Doppler ishighly dependent on available bone windows aswell as the technical skill of the sonographer.Evoked potentials have not been validated and arenot commonly used. Adding more types of ancillarytests for brain death determination may not lead tomore declaration but rather further ambiguity, con-troversy, and confusion [16–18].

PEDIATRIC BRAIN DEATH PRACTICEPARAMETERS

Although its scope requires a separate review of itsown, pediatric brain death merits a brief note. In1987, the American Academy of Pediatrics first cre-ated guidelines for brain death determination inchildren, which can be complicated, especially innewborns, due to maturational lag [19].

The current version of these guidelines by theAmerican College of Critical Care Medicine calls for

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two examinations separated by 24 h, and patientsmust be older than 37 weeks of gestational age.However, in the United Kingdom, Australia, andNew Zealand, children can only be declared braindead after 2 months of age. The American College of Critical Care Medicine criteria were created from aconsensus-based approach. There is little evidence

to further shape the criteria and little guidance tointerpret brainstem examinations for newborns orinfants [20]. Although the document is clear regard-ing the variable interpretation of ancillary testing, itstill offers their use for ‘social reasons’ or when ‘thereis uncertainty about the results of the neurologicexamination’. The notion of an ancillary test withvariable interpretation trumping a neurologic exam-ination is concerning.

BRAIN DEATH DETERMINATION WORLDWIDE: VARIATIONS AND PUBLIC

OPINIONThe study of Wijdicks [10] showed similar variationsin brain death determination internationally. Therewas marked variation in examiner number andqualifications. In Turkey, for example, brain deathdeclaration required a cardiologist, neurosurgeon,neurologist, and anesthesiologist to examine thepatient, followed by confirmatory testing [10].Regarding bedside examination, apnea testing wassimilarly variable internationally. Although allcriteria required a strict absence of brainstemreflexes, apnea testing with a pCO2 target was

recommended in only 59% of the guidelines andpreoxygenation in only 20 of the 71 guidelines.Ancillary testing was required in Europe for 11 of 25 guidelines; in the remaining 14, ancillary testswere thought to ‘facilitate’ brain death diagnosis.The stipulations and ancillary testing in Japan werenumerous, including intact tympanic membranes, aknown cause of cardiac arrest, and an isoelectric EEGalong with apnea testing and loss of brainstemreflexes. Children under the age of six were excludedfrom brain death determination in Japan [21]. Atthe time of the study by Wijdicks [10], the incidence

of brain death was 48–64 per million people in theUnited States compared with 0.25 per million in Japan.

A 2010 international survey sampled generalpublic opinions in Japan, the United Kingdom,Germany, France, and the United States. From therespondents, 29% of those in Japan and 57% of those in China had either not heard of brain deathor were uncertain of its meaning [20]. Only 60–70%of respondents in the United States and a smaller43% in Japan felt that brain death was an appro-priate standard for human death. Six Eastern

countries, including China, had neither a braindeath law nor a guideline [10,22].

CONCLUSION

It is clear that despite strong guidelines for braindeath determination, brain death is still sometimes

difficult to diagnose and/or accept [22]. In a 2004study survey of the general public, less than half of respondents identified a brain dead patient as‘unequivocally dead’; 43% felt that the patientwas ‘as good as dead’ and 16% felt that the patientwas still alive. Notably, only one-third of respond-ents felt that a brain dead patient was legally dead[23,24].

Social acceptance of brain death depends heav-ily on clear and consistent brain death determi-nation. Perhaps, the shortcomings of brain deathguidelines are not in the criteria themselves, butinstead inadequate physician training/expertiseand fear of error. Future directions for improvingbrain death diagnosis may not lie in additionalcriteria, but instead in additional training and sup-port for physicians [25

&&

]. Formal didactic coursesand simulation sessions can not only assess baselineknowledge for brain death determination but alsoprovide an effective model for brain death trainingand certification, as trialed by the simulation-basedtraining by MacDougall et al. in 2014 [25

&&

]. Uni-versalizing the training process and certification of the provider may help decrease variation in practiceand improve current pitfalls in brain death deter-

mination. Furthermore, national (and perhapsinternational) standardization of protocols for thedetermination of brain death will help to decreasevariability of practice, helping to build the trust of society in the process.

Acknowledgements

None.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.

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Authors created a simulation-based training course for brain death determinationbased on AAN practice parameters to better assess knowledge gaps and formallytrain physicians at an academic institution.

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Why is Diagnosing Brain Death So Confusng