Neurology -- Correspondence for Greer et al., 70 (4) 284-289

Correspondence published:

Variability of brain death determination guidelines in leading US neurologic institutions: Tia Powell, James Zisfein, John Halperin (12 March 2008)

Reply from the authors: David M. Greer, Panayiotis N. Varelas, Shamael Haque, Eelco F.M. Wijdicks (12 March 2008)

Variability of brain death determination guidelines in leading US neurologic institutions: Calixto Machado (14 February 2008)

Variability of brain death determination guidelines in leading US neurologic institutions: Kao-Chang Lin, Jinn-Rung Kuo, Neurosurgery, Chi Mei Medical Center (14 February 2008)

Reply from the authors: David M. Greer, MD, MA, Panayiotis Varelas MD, PhD, Shamael Haque DO, Eelco F.M. Wijdicks MD, PhD (14 February 2008)

Variability of brain death determination guidelines in leading US neurologic institutions 12 March 2008

Tia Powell,
New York State Task Force on Life & the Law
90 Church Street, 15th Floor, New York, NY 10007,
James Zisfein, John Halperin
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Re: Variability of brain death determination guidelines in leading US neurologic institutions

tpp03{at}health.state.ny.us Tia Powell, et al.

We appreciate the article by Greer et al. [1] Similar concerns led to a major review of brain death determinations in New York State and the release of updated guidelines for such determinations.
Brain death policies from facilities across New York were collected by the New York Organ Donor Network and revealed numerous significant differences across institutions and deviations from accepted guidelines. Variations included: the number of different professionals required, interval between determinations, role of ancillary testing, and timing of apnea tests. Some institutional policies had requirements that could delay or even prevent the diagnosis of brain death, such as waiting periods of 24 hours or more. The New York State Department of Health (NYSDOH) was concerned by this degree and type of variability.
In November 2004, NYSDOH convened a Brain Death Guideline Panel composed of external experts in conjunction with the New York State Task Force on Life & the Law, the state-level bioethics committee. This panel reviewed existing standards (including the 1995 AAN report [2]) and applicable state law and derived guidelines for the determination of brain death disseminated throughout New York State in December, 2005. [3]
Some key points are: (1) two clinical exams that document the absence of brain functions during a six-hour observation period, with a single apnea test at the end of that period, is adequate for diagnosis of brain death in most cases; (2) levels of intoxicants need not be zero but simply in a range not expected to �interfere significantly� with consciousness; (3) a confirmatory test (e.g., cerebral blood flow determination) is not routinely required but can be used when the diagnosis of brain death is uncertain on clinical grounds; and (4) physicians who diagnose brain death must be privileged for that task but there is no specific requirement for a neurologist or neurosurgeon; only one privileged physician is needed to make the diagnosis.
We do not believe that all hospital policies on brain death must be identical. However, variability should be based on local issues such as availability of ancillary tests and procedures for conflict resolution. On the basic principles of how brain death is diagnosed, we agree with Bernat that uniformity is a desirable goal. [4]
References
1. Greer DM, Varelas PN, Haque S, Wijdicks E. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology 2008;70:284-289.
2. Practice parameters for determining brain death in adults (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1995;45:1012�1014.
3. New York State Guidelines for Determining Brain Death, December 2005. http://www.health.state.ny.us/professionals/hospital_administrator/determination_of_brain_death/
4. Bernat JL. How can we achieve uniformity in brain death determinations? Neurology 2008; 70: 252-253.
Disclosure: The authors report no conflicts of interest.

Reply from the authors 12 March 2008

David M. Greer,
Massachusetts General Hospital
ACC 739A, 55 Fruit Street, Boston, MA, 02114,
Panayiotis N. Varelas, Shamael Haque, Eelco F.M. Wijdicks
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Re: Reply from the authors

dgreer{at}partners.org David M. Greer, et al.

We appreciate the comments of Drs. Powell, Zisfein and Halperin regarding the work done in the state of New York to assess and correct the problem of variability of brain death determination in that state. Their findings appear quite similar to what we found on a nationwide level, and we are pleased to hear that the New York State Department of Health took the problem so seriously, making efforts to provide guidelines that allow more specificity in terms of who can do the determination and what exactly is to be tested.
There are several important aspects of the �key points� mentioned that bear discussion. First, two clinical examinations are not something that is universally required, and it is feasible that one examination by a physician who is competent in the testing would be sufficient. On the other hand, erring on the side of certainty by having more examiners potentially may be helpful, but may not always be possible, depending on the staffing issues of the individual hospital.
Second, we agree that the level of intoxicants should not be at a level that might influence the clinical examination, but that defining exactly what this level is for each medication becomes quite murky.
Third, we would advocate that an ancillary test must be performed in certain clinical situations, and not be optional. These would include a patient too unstable for an apnea test, or one with significant facial trauma precluding the performance of an adequate examination.
Finally, we agree that in this age of limited resources, including the human resources of neurologists and neurosurgeons, having other physicians (e.g. intensivists) who are capable of accurately diagnosis brain death would be helpful in many hospitals.
We agree that there does not need to be absolute uniformity of guidelines for all hospitals, but certain key elements such as the prerequisites for testing, the details of the clinical examination, and the details of the apnea testing should be uniformly agreed upon on a national level, and deviations from these principles not be taken lightly.
Disclosure: Dr. Greer reports receiving speaker honoraria from Boehringer-Ingelheim Pharmaceuticals, Inc. Drs. Varelas reports being a speaker for UCB-Pharma and a consultant for Codman, and an advisor for the Medicines Company. Drs. Haque and Wijdicks report no conflicts of interest.

Variability of brain death determination guidelines in leading US neurologic institutions 14 February 2008

Calixto Machado,
AAN Corresponding Fellow
Institute of Neurology and Neurosurgery, 29 y D, Vedado, La Habana 10400, Cuba
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Re: Variability of brain death determination guidelines in leading US neurologic institutions

braind{at}infomed.sld.cu Calixto Machado

Greer et al. reported major differences in brain death (BD) guidelines in US hospitals. [1] Wijdicks published relevant worldwide differences on BD determination. [2] Although I expected those results from the Wijdicks� article, this paper surprised me considering the AAN practice parameters for determining BD established in 1995.
Most countries and states do not present an ordered formulation of three distinct elements: the definition of death, the anatomic-physiologic substratum (criterion), and the tests (clinical and ancillary) to confirm that the criterion has been satisfied. For example, the Commonwealth countries defend a brainstem standard of BD; meanwhile the Uniform Determination of Death Act in the United States demands proof of irreversible cessation of function of the whole brain. [3]
It is surprising that most institutions do not require a specific area of expertise in physicians involved in BD diagnosis which requires training. In Cuba, neurologists and neurosurgeons are mainly involved, although intensivists with previous training also participate.
Individual prerequisites vary: ensuring the absence of sedatives/paralytics, acid-base disorders, endocrine disorders, hypothermia or shock. These circumstances can mimic BD without being irreversible. Moreover, BD etiology has not always excluded possible causes of reversible coma. Apnea testing showed several variations.
Wijdicks also demonstrated differences among countries. [2] The use of transcranial Doppler (TCD) was only recommended in 42% of centers despite the AAN Therapeutics and Technology Assessment Subcommittee report, affirming that the TCD sensitivity and specificity for detecting circulatory arrest were 91-100 and 97-100%, respectively. [4]
In Cuba, we have proposed using confirmatory tests to prove absent cerebral blood flow (CBF) and to demonstrate loss of bioelectric activity. These tests should be used when clinical examination is not reliable, to shorten period of observation, and in primary brainstem lesions. Among those tests to detect absent CBF, we defended the use of TCD, and a neurophysiologic test battery (multimodality evoked potentials and electroretinography) to show loss of bioelectric activity. [5]
Considering the variability of BD guidelines in the US [1] and the rest of the world, [2] I agree with the authors that the AAN Guidelines should be reviewed, including this diagnosis in children. Furthermore, the World Federation of Neurology should also organize a Committee for reviewing and standardizing guidelines for worldwide consensus in BD diagnostic criteria.
References
1.Greer DM, Varelas PN, Haque S, Wijdicks EFM. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology 2008;70:1�1.
2.Wijdicks EFM. Brain death worldwide: Accepted fact but no global consensus in diagnostic criteria. Neurology 2002;58:20-25.
3.Machado C, ed. Brain Death: A Reappraisal. New York: Springer 2007:1-223.
4.Sloan MA, Alexandrov AV, Tegeler CH, et al. Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2004; 62:1468-1481.
5.Machado C, Abeledo M, �lvarez C, et al. Cuba has passed a law for the determination and certification of death. Adv Exp Med Biol. 2004; 550:139-142.
Disclosure: The author reports no conflicts of interest.

Variability of brain death determination guidelines in leading US neurologic institutions 14 February 2008

Kao-Chang Lin,
Neurology, Chi Mei Medical Center
901, Jong Hwa Rd, Yung Kung City, Tainan Hsien, Taiwan,
Jinn-Rung Kuo, Neurosurgery, Chi Mei Medical Center
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Re: Variability of brain death determination guidelines in leading US neurologic institutions

gaujang{at}mail2000.com.tw Kao-Chang Lin, et al.

Since the diagnosis of brain death (BD) can be made based on neurological examination, CO2 apnea tests, ancillary studies as electroencephalography (EEG), arteriography, or radionuclide scan [6], the use of TCD to determine BD seemed uncommon in the US. [1] The timing of confirmed �true� circulatory death is an ethical issue for all countries and cultures.
From the 2004 AAN reports, transcranial Doppler (TCD) used to confirm BD was 91-100% in sensitivity and 97-100% in specificity. [4] This simple technique is useful as a supplementary apparatus to verify physiological death once clinically diagnosed BD was made. However, the criticism was partly made because of the timing in performance, the flow spectrum, and the controversy in interpretation. If a standard protocol is set, neurologists and neurosurgeons could perform neurological assessments, TCD and apnea tests and additional procedures could be avoided. In some countries, TCD is allowed to confirm BD by law. [5]
We performed a four-year survey of 101 clinically-diagnosed BD by TCD monitoring. [7] The sensitivity and specificity was high (77% vs 100%) in middle cerebral artery and basilar artery. The positive predictive value was 100% on both. Specific flow patterns (both reverberating and small systolic flow) were characteristic of cerebral circulatory arrest. Although the lag period of these flow patterns were time-dependent (6~36 hrs), TCD should remain a first-line tool in the diagnosis of BD. [7]
References
6. Paolin A, Manuali A, Di Paola F, et al. Reliability in diagnosis of brain death. Intensive Care Med 1995; 21: 657-662.
7. Kuo JR, Chen CF, Chio CC, et al. Time-Dependent Validity in the Diagnosis of Brain Death Using Transcranial Doppler Sonography. JNNP 2006; 77: 646-649.
Disclosure: The authors report no conflicts of interest.

Reply from the authors 14 February 2008

David M. Greer, MD, MA,
Massachusetts General Hospital
ACC 739A, 55 Fruit Street, Boston, MA 02114,
Panayiotis Varelas MD, PhD, Shamael Haque DO, Eelco F.M. Wijdicks MD, PhD
Send Correspondence to journal:
Re: Reply from the authors

dgreer{at}partners.org David M. Greer, MD, MA, et al.

We agree with Dr. Machado that experienced physicians should determine death by neurological criteria, but also realize that neurologists, neurosurgeons, or both may not be readily available 24 hours a day in all institutions. For this reason, a method should be provided for intensivists to become trained and proficient in this determination.
The AAN has not endorsed any specialty to clinically determine death by brain criteria. We hope that the examination is done by experienced intensivists, neurologists, critical care neurologists, neurosurgeons and pediatricians, and hope that most hospitals involved with organ donation have a neurologist or neurosurgeon on staff.
Hospital practice protocols may or may not follow the AAN guidelines, and it is fair to say that they are in no way obligated to follow them. It is somewhat unsurprising to find differences. What is new is the introduction of criteria more complicated than the AAN guidelines, very similar to the results of the world survey. [2] Why would more be better? There should be a more uniform method of determination of death by brain criteria, at least in the US if not worldwide.
Again the issue of confirmatory tests in brain death determination seems to dominate the discussion in both letters by Dr. Machado and Dr. Lin, but we believe many of these tests are poorly validated. Even a time-honored EEG or cerebral angiogram is not without difficulty in interpretation. The basis for the use of transcranial Doppler (TCD) is primarily from the consensus statement from the task force of the World Federation of Neurology. [8]
The task force establishes TCD criteria for findings consistent with cerebral circulatory arrest, not brain death (although this may be implicit). The consensus opinion states a prerequisite that the patient first fulfill the clinical criteria for brain death, including permanent coma, exclusion of confounding circumstances, and two experienced examinations showing no evidence of cerebral and brainstem function.
Second, it is unclear, although perhaps implicit, as to whether systolic spikes or oscillating flow should be documented intracranially in both the anterior and posterior circulations. Finally, a lack of signal where one was previously seen is acceptable as proof of circulatory arrest, but this raises the question of technique or transmission problems. These features of the consensus statement may make many clinicians hesitant to incorporate TCD routinely in the diagnosis or confirmation of brain death.
The determination of death by brain criteria should remain a systematic, step-by-step, careful and comprehensive clinical evaluation done by a clinician experienced in the assessment. Leapfrogging to an ancillary test may lead to more confusion, more testing, and perhaps even a delay or deferral of organ donation.
Our article dealt with the problem of brain death guidelines in the US as it pertains to adults; the criteria in children may also need to be revisited. [9] Perhaps now is the time to modernize and systematize our approach to brain death determination in both the adult and pediatric populations.
References
8. Ducrocq X, Hassler W, Moritake K et al. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography. Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. J Neurol Sci 1998;159:145-150.
9. Report of special task force. Guidelines for the determination of brain death in children. American Academy of Pediatrics Task Force on Brain Death in Children. Pediatrics 1987;80:298-300.
Disclosure: The authors report no conflicts of interest.