A definition of irreversible coma. Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death.
JAMA. 1968 Aug 5;205(6):337-40.
Abstract/Text
President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Defining death. Washington DC: Government Printing Office; 1981.
Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research.
JAMA. 1981 Nov 13;246(19):2184-6.
Abstract/Text
Practice parameters for determining brain death in adults (summary statement). The Quality Standards Subcommittee of the American Academy of Neurology.
Neurology. 1995 May;45(5):1012-4.
Abstract/Text
An appraisal of the criteria of cerebral death. A summary statement. A collaborative study.
JAMA. 1977 Mar 7;237(10):982-6.
Abstract/Text
Based on the findings in a collaborative study of 503 comatose and apneic patients, the establishment of cerebral death requires (1) that all appropriate examinations and therapeutic procedures have been performed, (2) that cerebral unresponsivity, apnea, dilated pupils, absent cephalic reflexes, and electrocerebral silence be present for 30 minutes at least six hours after the ictus, and (3) that if one of these standards is met imprecisely or cannot be tested, a confirmatory test be made to demonstrate the absence of cerebral blood flow. This would allow the diagnosis of a dead brain to be made in patients with small amounts of sedative drugs in the blood, In patients undergoing therapeutic procedures that make examination of one or more of the cranial nerves impossible, and in patients otherwise meeting the criteria whose pupils are small.
Diagnosis of brain death. Statement issued by the honorary secretary of the Conference of Medical Royal Colleges and their Faculties in the United Kingdom on 11 October 1976.
Br Med J. 1976 Nov 13;2(6045):1187-8.
Abstract/Text
C Pallis
ABC of brain stem death. Reappraising death.
Br Med J (Clin Res Ed). 1982 Nov 13;285(6352):1409-12.
Abstract/Text
Eelco F M Wijdicks, Panayiotis N Varelas, Gary S Gronseth, David M Greer, American Academy of Neurology
Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.
Neurology. 2010 Jun 8;74(23):1911-8. doi: 10.1212/WNL.0b013e3181e242a8.
Abstract/Text
OBJECTIVE: To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death?
METHODS: A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults.
RESULTS AND RECOMMENDATIONS: In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain.
時実利彦. 「脳死と脳波に関する委員会」中間報告. 日本医事新報 1969; 2358: 106.
厚生科学研究費特別研究事業 脳死に関する研究班 昭和60年度研究報告書. 脳死の判定指針および判定基準. 日医雑誌 1985; 94: 1949-72.
竹内. 厚生省厚生科学研究費特別研究事業「脳死に関する研究班」、昭和59年度報告書. 日本医事新報 1985; 3188: 112-4.
厚生省厚生科学研究費特別研究事業「脳死判定手順に関する研究班」平成11年度報告書: 法的脳死判定マニュアル. 1999.
Eelco F M Wijdicks, Alejandro A Rabinstein, Edward M Manno, John D Atkinson
Pronouncing brain death: Contemporary practice and safety of the apnea test.
Neurology. 2008 Oct 14;71(16):1240-4. doi: 10.1212/01.wnl.0000327612.69106.4c.
Abstract/Text
BACKGROUND: Little is known of hospital practice in brain death determination, specialty involvement, and followed procedures, including the apnea test.
METHODS: We reviewed 228 patients pronounced brain dead at Mayo Clinic from 1996 to 2007. We performed a detailed review of clinical determination of brain death, intensive care support, apnea test procedure, and complications.
RESULTS: There were 228 patients who were pronounced brain dead, mostly after traumatic brain injury, cerebral hematoma, or aneurysmal subarachnoid hemorrhage. Brain death was declared within 24 hours of ictus in 30% of the patients and within 3 days in 62%. All patients were using one or more vasopressors, and 61% of the patients received vasopressin for diabetes insipidus. An apnea test could not be performed in 7% of the patients because of hemodynamic instability or poor oxygenation at baseline. In 3% of the patients, the apnea test procedure was aborted because of hypoxemia or hypotension. No major complications (cardiac arrest or pneumothorax) occurred during the apnea test. Polytrauma resulting in brain death was significantly more common in patients with aborted or not attempted apnea tests than in patients with completed apnea tests (p = 0.0004). During the study epoch, we found a shift toward determination of the tests by neurointensivists, pediatric neurologists, and neurosurgeons.
CONCLUSIONS: Brain death declaration is frequent within the first 3 days of admission. It is usually performed in hemodynamically unstable patients requiring vasopressors and vasopressin. If preconditions are met, apnea testing using an oxygen-diffusion technique is safe. However, in 1 of 10 patients, an apnea test could not be completed and confirmatory tests were needed.
Simon Lévesque, Martin R Lessard, Pierre C Nicole, Stéphan Langevin, François LeBlanc, François Lauzier, Jacques G Brochu
Efficacy of a T-piece system and a continuous positive airway pressure system for apnea testing in the diagnosis of brain death.
Crit Care Med. 2006 Aug;34(8):2213-6. doi: 10.1097/01.CCM.0000215114.46127.DA.
Abstract/Text
OBJECTIVE: To prospectively compare three methods of apnea testing for the confirmation of brain death.
DESIGN: Prospective, randomized, crossover study.
SETTING: Intensive care unit of a tertiary care university hospital.
PATIENTS: Twenty adult patients requiring apnea testing for confirmation of brain death.
INTERVENTIONS: Ten minute apnea testing was repeated in random order for every patient with the three oxygenation systems: oxygen catheter inserted through the endotracheal tube (oxygen 6 L/min), T-piece system (oxygen 12 L/min), and continuous positive airway pressure (CPAP) system 10 cm H2O (oxygen 12 L/min).
MEASUREMENTS AND MAIN RESULTS: Arterial blood was drawn at 0, 2, 5, and 10 mins of each test. Compared with baseline, Paco2 increased by 30.6 +/- 7.4, 30.0 +/- 7.3 and 30.2 +/- 7.5 mm Hg during the apnea period (p = .96), reaching 73.3 +/- 8.3, 71.6 +/- 11.1, and 72.7 +/- 9.0 mm Hg at the end of the apnea test (p = .73) for the oxygen catheter, the T-piece, and the CPAP, respectively. Pao2 decreased less with the CPAP compared with the oxygen catheter or the T-piece (-22.4 +/- 76, -99.1 +/- 158, and -91.6 +/- 133 mm Hg, respectively, p < .01). In two patients, apnea testing could not be completed with the oxygen catheter and the T-piece because of desaturation, although it could be completed with the CPAP.
CONCLUSIONS: The T-piece and the CPAP systems are effective alternatives to the standard oxygen catheter technique for apnea testing. Oxygenation was best maintained with the CPAP system, which can be useful in some patients.
Benoît Vivien, Frédéric Marmion, Sabine Roche, Catherine Devilliers, Olivier Langeron, Pierre Coriat, Bruno Riou
An evaluation of transcutaneous carbon dioxide partial pressure monitoring during apnea testing in brain-dead patients.
Anesthesiology. 2006 Apr;104(4):701-7.
Abstract/Text
BACKGROUND: Diagnosis of brain death usually requires an arterial carbon dioxide partial pressure (Paco2) of 60 mmHg during the apnea test, but the increase in Paco2 is unpredictable. The authors evaluated whether transcutaneous carbon dioxide partial pressure (Ptcco2) monitoring during apnea test can predict that a Paco2 of 60 mmHg has been reached.
METHODS: The authors compared Ptcco2 measured with a transcutaneous ear sensor (V-Sign Sensor, Sentec Digital Monitoring System; SENTEC-AG, Therwil, Switzerland) and Paco2 obtained from arterial blood gas measurements in 32 clinically brain-dead patients.
RESULTS: In the first 20 patients, the mean Paco2-Ptcco2 gradient was 0.7 +/- 3.6 mmHg at baseline and 8.7 +/- 7.1 mmHg after 20 min of apnea. Using receiver operating characteristic curve analysis (area under the curve: 0.983 +/- 0.013), the best threshold value of Ptcco2 to predict that a Paco2 of 60 mmHg had been reached was 60 mmHg (positive predictive value: 1.00 [0.93-1.00]). In the following 12 patients investigated with use of this Ptcco2 target value of 60 mmHg, the mean duration of the apnea test (11 +/- 4 vs. 20 +/- 0 min; P < 0.001), hypercapnia (74.0 +/- 4.9 vs. 98.3 +/- 20.0 mmHg; P < 0.001), acidosis (pH: 7.18 +/- 0.06 vs. 7.11 +/- 0.08; P < 0.001), and decrease in arterial oxygen partial pressure (-47 +/- 44 vs. -95 +/- 89; P < 0.05) at the end of the test were reduced as compared with the 20-min apnea test group.
CONCLUSION: During the apnea test in brain-dead patients, a Ptcco2 of 60 mmHg accurately predicts that a Paco2 of 60 mmHg has been reached. This may allow a reduction in the duration of the apnea test and consecutively limit occurrence of complications.
C J G Lang, J G Heckmann, F Erbguth, A Druschky, M Haslbeck, F Reinhardt, M Winterholler
Transcutaneous and intra-arterial blood gas monitoring--a comparison during apnoea testing for the determination of brain death.
Eur J Emerg Med. 2002 Mar;9(1):51-6.
Abstract/Text
Intra-arterial (i.a.) and transcutaneous (t.c.) blood gas monitoring were compared with in vitro blood gas analysis (abg) during apnoea testing for the determination of brain death in a prospective observational study. All three methods were used simultaneously in 19 patients in whom brain death was suspected. Brain death was confirmed in each case adhering to the recommendations of the Scientific Advisory Board of the German Federal Chamber of Physicians which demand a PCO2 of at least 60 mmHg. In vitro parameters ranged from 23.2 to 80.4 mmHg (PCO2), 52.7 to 509.9 mmHg (PO2), and 7.072 to 7.591 (pH). The intra-individual correlations between both monitoring methods (rPCO2=0.958, rPO2=0.859) and between each of them and abg (r>0.960) were high. Absolute deviations from abg for the corrected as well as uncorrected measurements were similar for both methods, except with regard to group bias where an advantage for the i.a. values emerged. Since many of the i.a. measurements failed and the disposable i.a. probes cost much more than the t.c. electrodes, the i.a. technique at present holds no advantage over t.c. measurements in testing for apnoea in suspected brain death except where simultaneous monitoring of pH and temperature are desired.
Eelco F M Wijdicks, Edward M Manno, Steven R Holets
Ventilator self-cycling may falsely suggest patient effort during brain death determination.
Neurology. 2005 Sep 13;65(5):774. doi: 10.1212/01.wnl.0000174626.94197.62.
Abstract/Text
S M Willatts, G Drummond
Brainstem death and ventilator trigger settings.
Anaesthesia. 2000 Jul;55(7):676-7.
Abstract/Text
A patient with cerebral infarction was certified clinically brainstem dead. However, 4 h after the diagnosis of death, while the patient was being ventilated using the biphasic positive airway pressure mode, the 'assist' indicator light on the Drager Evita 2 ventilator illuminated intermittently. There was no evidence of spontaneous breathing. 'Triggering' was probably caused by a decrease in airway pressure in time with cardiac contraction. The trigger flow rate is crucial as factors other than the patient's inspiratory effort can initiate flow from the ventilator with very sensitive settings.
Gustavo Saposnik, Vincenzo S Basile, G Bryan Young
Movements in brain death: a systematic review.
Can J Neurol Sci. 2009 Mar;36(2):154-60.
Abstract/Text
Brain death is the irreversible lost of function of the brain including the brainstem. The presence of spontaneous or reflex movements constitutes a challenge for the neurological determination of death. We reviewed historical aspects and practical implications of the presence of spontaneous or reflex movements in individuals with brain death and postulated pathophysiological mechanisms. We identified and reviewed 131 articles on movements in individuals with confirmed diagnosis of brain death using Medline from January 1960 until December 2007, using 'brain death' or 'cerebral death' and 'movements' or 'spinal reflex' as search terms. There was no previous systematic review of the literature on this topic. Plantar withdrawal responses, muscle stretch reflexes, abdominal contractions, Lazarus's sign, respiratory-like movements, among others were described. For the most part, these movements have been considered to be spinal reflexes. These movements are present in as many as 40-50% of heart-beating cadavers. Although limited information is available on the determinants and pathophysiological mechanisms of spinal reflexes, clinicians and health care providers should be aware of them and that they do not preclude the diagnosis of brain death or organ transplantation.
W D Goldie, K H Chiappa, R R Young, E B Brooks
Brainstem auditory and short-latency somatosensory evoked responses in brain death.
Neurology. 1981 Mar;31(3):248-56.
Abstract/Text
Thirty-five patients who met all clinical criteria for brain death and 53 patients who did not were tested with brainstem auditory (BAER) and short-latency somatosensory (SER) evoked responses. Of the brain-dead patients, 77% had no waves present in the BAER, including wave I, whereas 69% had medullary components present in the SER. These data suggest that the SER has greater clinical utility in the brain-death setting, because it is important to have a wave present that established that the input signal has reached the central nervous system. No brain-dead patients had subsequent waves in either test. These results are correlated with neuropathologic findings and contrasted with data obtained in the comatose but not brain-dead patients.
A R Møller, P Jannetta, M Bennett, M B Møller
Intracranially recorded responses from the human auditory nerve: new insights into the origin of brain stem evoked potentials (BSEPs).
Electroencephalogr Clin Neurophysiol. 1981 Jul;52(1):18-27.
Abstract/Text
Auditory evoked potentials were recorded intracranially from the 8th nerve during neurosurgical procedures. The potentials had a large negative peak that occurred 3.0--3.7 msec after the onset of the stimulus (2 000 Hz tone bursts). When these potentials were compared with the scalp recorded brain stem evoked potentials (BSEPs) the intracranial response was found to match the latencies of the P2N3 complex of the BSEP. The results are interpreted as showing that the neural generator of the second peak of the BSEP is the intracranial portion of the auditory nerve and not, as was earlier assumed, the cochlear nucleus.
G Saposnik, J A Bueri, J Mauriño, R Saizar, N S Garretto
Spontaneous and reflex movements in brain death.
Neurology. 2000 Jan 11;54(1):221-3.
Abstract/Text
Spontaneous and reflex movements may be found in patients with brain death (BD). The authors prospectively evaluated their frequency using a standardized protocol. Among 38 patients who fulfilled criteria for BD, the authors found 15 (39%) with spontaneous or reflex movements. The most common movement was finger jerks. Undulating toe flexion sign, triple flexion response, Lazarus sign, pronation-extension reflex, and facial myokymia also were seen. These movements may be more common than reported and do not preclude the diagnosis of BD.
J F Spittler, D Wortmann, M von Düring, W Gehlen
Phenomenological diversity of spinal reflexes in brain death.
Eur J Neurol. 2000 May;7(3):315-21.
Abstract/Text
In brain death, spinal reflexes and automatisms are observed which may cause irritation and even doubt in the diagnosis. In the literature there are no dedicated descriptions of the diversity and of neuroanatomical considerations. In 278 examinations of 235 patients for the determination of brain death, on 42 occasions obvious spinal reflexes and/or spinal automatisms were observed in 27 brain dead bodies. Because they were not systematically searched for, minute forms have probably been missed. The reflexes (R) and automatisms (A) are described according to the time of observation in relation to the development of brain death, the presumable spinal localization and the possible phylogenetical interpretation. Especially disquieting examples are discussed in more detail, e.g. monophasic EndotrachealSuction-ThoracicContraction-R supposedly switched in segments C2-6 or TrapeziusPinch-ShoulderProtrusion-R conveyed by the accessory nerve (terminology according to the scheme: for the reflexes, Trigger-Response-R: for the automatisms, Movement-A). After these experiences a more thorough examination showed frequent observations of rather minute forms of spinal reflexes, as well as automatisms and even the Lazarus sign (in possibly more than two thirds of the examinations). An estimation of the factual frequency would necessitate special attention to those much more frequent but less obvious minute spinal reflexes and automatisms.
Gustavo Saposnik, Jorge Maurino, Roberto Saizar, José A Bueri
Spontaneous and reflex movements in 107 patients with brain death.
Am J Med. 2005 Mar;118(3):311-4. doi: 10.1016/j.amjmed.2004.09.013.
Abstract/Text
J Santamaria, N Orteu, A Iranzo, E Tolosa
Eye opening in brain death.
J Neurol. 1999 Aug;246(8):720-2.
Abstract/Text
Maria Leticia C Araullo, Jeffrey I Frank, Fernando D Goldenberg, Axel J Rosengart
Transient bilateral finger tremor after brain death.
Neurology. 2007 Apr 17;68(16):E22. doi: 10.1212/01.wnl.0000260227.36359.18.
Abstract/Text
K-Y Jung, S-G Han, K H Lee, C-S Chung
Repetitive leg movements mimicking periodic leg movement during sleep in a brain-dead patient.
Eur J Neurol. 2006 Jul;13(7):e3-4. doi: 10.1111/j.1468-1331.2006.01270.x.
Abstract/Text
Manoj K Mittal, Grace M Arteaga, Eelco F M Wijdicks
Thumbs up sign in brain death.
Neurocrit Care. 2012 Oct;17(2):265-7. doi: 10.1007/s12028-012-9729-6.
Abstract/Text
INTRODUCTION: Spinal reflexes can be seen in the setting of brain death. We present a new spinal reflex. We also review spinal movements in pediatric brain death and provide suggestions to distinguish them from movements generated by the brain.
CASE REPORT: We report a five-year old girl admitted after an asystolic cardiac arrest and was soon declared brain death as a result of bilateral cerebellar hematoma. She had spinal movements including a "Thumbs up sign". These findings delayed organ procurement.
CONCLUSION: "Thumbs up sign" should be added to the list of spinal reflexes seen with brain death. Spinal reflexes in brain death can be clinically recognized and should explained to all involved parties to avoid unnecessary testing, confusion for family members, and delay or refusal of organ donation.
Eelco F. M. Wijdicks. The Comatose Patient. Second Edition. Oxford University Press, USA, pp 138-139, 2014.
園生雅弘. モノグラフ「臨床脳波を基礎から学ぶ人のために」No.21 脳死. 臨床神経生理 2008; 36: 47-55.
D Silverman, M G Saunders, R S Schwab, R L Masland
Cerebral death and the electroencephalogram. Report of the ad hoc committee of the American Electroencephalographic Society on EEG Criteria for determination of cerebral death.
JAMA. 1969 Sep 8;209(10):1505-10.
Abstract/Text
American Electroencephalographic Society Guidelines in EEG, 1-7 (revised 1985).
J Clin Neurophysiol. 1986 Apr;3(2):131-68.
Abstract/Text
Guideline three: minimum technical standards for EEG recording in suspected cerebral death. American Electroencephalographic Society.
J Clin Neurophysiol. 1994 Jan;11(1):10-3.
Abstract/Text
唐澤秀治. 脳死判定ハンドブック：イラストでわかる法的・医学的基礎知識と実施の手順. 東京: 羊土社, 2001.
園生雅弘, 畑中裕己, 東原真奈, 他. 他の脳死判定基準を満たす患者の脳波上に見られる筋電図活動：その本態と扱いについて. 脳死・脳蘇生 2007; 19: 93-9.
Hirsch H, Kubicki St, Kugler J, et al. Empfehlungen der Deutschen EEG-Gesellschaft zur Bestimmung der Todeszeit. Z EEG EMG 1970; 1: 53-4.
A S Wee
Scalp EMG in brain death electroencephalogram.
Acta Neurol Scand. 1986 Aug;74(2):128-31.
Abstract/Text
Electromyograms (EMGs) are usually considered artifacts during electroencephalographic (EEG) recording for determination of electrocerebral silence (ECS). Appearance of scalp motor unit activity, however, may reflect residual brainstem function and can introduce difficulty in establishing a secure diagnosis of brain death. In this study, ECS patients with and without scalp EMG were compared in terms of relationship to brainstem survivability. There was no correlation between length of survivability and presence of scalp EMG activity. No patient recovered brainstem function clinically. This study provides firm support for the usual practice of ignoring the EMG in brain death EEG. Scalp has no prognostic value.
M Sonoo, Y Tsai-Shozawa, M Aoki, T Nakatani, Y Hatanaka, A Mochizuki, M Sawada, K Kobayashi, T Shimizu
N18 in median somatosensory evoked potentials: a new indicator of medullary function useful for the diagnosis of brain death.
J Neurol Neurosurg Psychiatry. 1999 Sep;67(3):374-8.
Abstract/Text
OBJECTIVES: To record N18 in median somatosensory evoked potentials (SEPs) for deeply comatose or brain dead patients and to demonstrate the usefulness of N18 for the diagnosis of brain death in comparison with auditory brain stem responses (ABRs) and P13/14 in median SEPs, which have been conventionally used as complementary tests for the diagnosis of brain death.
METHODS: Subjects were 19 deeply comatose or brain dead patients. Thirteen recordings were performed in deeply comatose but not brain dead conditions, and 12 recordings were performed in brain death. N18 was evaluated in the CPi-C2S lead (or other scalp-C2S leads) to obtain a flat baseline.
RESULTS: N18 was preserved in 12 of 13 non-brain dead comatose recordings whereas it was completely lost for all of the 12 brain death recordings. P13/14 in median SEPs was preserved for all the comatose recordings, whereas apparent P13/14-like potentials, usually of low amplitude, were seen in nine of 12 brain death recordings-that is, frequent false positives. The ABRs already showed features which were characteristic for brain death (loss of components other than wave 1 or small wave 2) for four comatose recordings, in three of which N18 was preserved. The last result not only corresponds with the fact that ABRs can evaluate pontine and midbrain functions and not medullary function, but further supports the medullary origin of N18. In the four patients followed up for the course of progression from coma to brain death, N18s preserved in normal size during the comatose state were completely lost after brain death was established.
CONCLUSIONS: The N18 potential is generated by the cuneate nucleus in the medulla oblongata in the preceding studies. N18 is suggested to be a promising tool for the diagnosis of brain death because there were no false positives and rare false negatives in the present series for detecting the remaining brain stem function.
Enrico Facco, M Munari, F Gallo, S M Volpin, A U Behr, F Baratto, G P Giron
Role of short latency evoked potentials in the diagnosis of brain death.
Clin Neurophysiol. 2002 Nov;113(11):1855-66.
Abstract/Text
OBJECTIVE: The aim of this study is to confirm the effectiveness of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) in the diagnosis of brain death (BD).
METHODS: ABRs and SEPs were recorded at the same session in 130 BD patients (age range 8-77 years, 81 male and 49 female). Twenty-four cases were submitted to serial recordings from preterminal conditions through BD.
RESULTS: ABRs were absent in 92 cases (70.8%), only waves I or I-II were present in 32 cases (24.6%), while in the remaining 6 patients (4.6%) waves V and/or III were still present, excluding the death of the brain-stem. In 4 cases (3.1%) SEPs showed the absence of all components following the cervical N9, preventing the diagnosis of BD. Among 126 cases (96.9%) with preserved cervical N9-N13 SEPs confirmed the absence of brain-stem activity in 122 cases (93.7%), in whom no waves following P11 or P13 were recordable. SEPs excluded the diagnosis of BD in the remaining 4 cases (3.2%) showing preserved P14 and/or N18. In all pre terminal patients the far-field P14-N18 were present, and their disappearance was closely related to the onset of BD.
CONCLUSIONS: The combined us of ABRs and SEPs was able to confirm BD in almost all patients, providing an objective confirmation of the diagnosis, and to exclude it in 7 cases, thus improving the reliability of diagnosis.
塩貝敏之, 斎藤勇. 脳死判定における補助検査法. 日本臨床増刊号：現代臨床機能検査（上巻） 1997; 55: 301-9.
Christophe Quesnel, Jean-Pierre Fulgencio, Christophe Adrie, Béatrice Marro, Laurent Payen, Nadège Lembert, Sonia El Metaoua, Francis Bonnet
Limitations of computed tomographic angiography in the diagnosis of brain death.
Intensive Care Med. 2007 Dec;33(12):2129-35. doi: 10.1007/s00134-007-0789-6. Epub 2007 Jul 21.
Abstract/Text
OBJECTIVE: To evaluate the accuracy of cerebral computed tomographic angiography (CT-a) for the diagnosis of brain death (BD).
DESIGN AND SETTING: Prospective observational study in intensive care units.
PATIENTS: Twenty-one clinically BD patients enrolled over 12 months.
MEASUREMENTS AND RESULTS: All clinically BD patients were evaluated by electroencephalography (EEG) and CT-a after exclusion of hypothermia and drug intoxication. Data collected included: demographic characteristics, cause of BD, delay between in-hospital admission and BD diagnosis and between EEG and CT-a, occurrence of cardiac arrest, administration of vasoactive agents, results of EEG and CT-a. We evaluated the sensitivity of EEG and CT-a and their agreement. Groups were compared according to BD diagnosis by EEG and CT-a (E+C+), or only by EEG (E+C(-)). Statistical analysis were performed by Mann-Whitney test and Fisher's exact test. BD was confirmed by EEG in all cases (sensitivity 100%) whereas only 11 patients of 21 had no cerebral perfusion during CT-a (sensitivity 52.4%). No agreement was documented between EEG and CT-a for the diagnosis of BD (kappa = 0). Patients' characteristics did not differ between E+C+ and E+C(-) groups. In the E+C(-) group arterial opacification was observed in 100% of patients, but opacification of the internal cerebral veins was achieved in only 30%.
CONCLUSIONS: In clinically BD patients with no electroencephalographic activity CT-a documents opacification of the intracerebral vessels in a significant percentage of the cases. Therefore CT-a cannot be recommended as a means of BD diagnosis.
J-C Combes, A Chomel, F Ricolfi, P d'Athis, M Freysz
Reliability of computed tomographic angiography in the diagnosis of brain death.
Transplant Proc. 2007 Jan-Feb;39(1):16-20. doi: 10.1016/j.transproceed.2006.10.204.
Abstract/Text
OBJECTIVE: This study examined the validity of cerebral computed tomographic (CT) angiography in the diagnosis of brain death (BD) compared with conventional cerebral angiography.
METHODS: This prospective, monocentric study was performed over a 24-month period and included 43 patients, at least 18 years of age, with clinical criteria of BD. All patients underwent cerebral CT angiography and then cerebral angiography. To confirm BD, the CT scan had to show the absence of perfusion of A2 anterior cerebral artery segments (A2-ACA), M4 middle cerebral artery segments (M4-MCA), P2 posterior cerebral artery segments (P2-PCA), basilar artery, internal cerebral veins, and finally the great cerebral vein. Cerebral angiography showed cerebral blood flow arrest at the level of the foramen magnum for posterior circulation and carotid siphon for anterior circulation.
RESULTS: For 30 patients, BD was confirmed by both examinations. For 13 patients, cerebral angiography confirmed BD, whereas CT angiography still showed cerebral perfusion; the divergence rate was 30.2%.
CONCLUSIONS: CT angiography seems to be a promising exam to confirm BD. However, the divergence with cerebral angiography is significant mainly concerning A2-ACA, which are proximal. It may be possible to only use the absence of opacification of M4-MCA, P2-PCA, basilar artery, and venous blood return to remain in conformity with the French law. In all cases, the international medical community should obtain a consensus for the interpretation of CT angiography to use it extensively as a complementary exam for BD.
Tim Taylor, Rob A Dineen, Dale C Gardiner, Charmaine H Buss, Allan Howatson, Nathan Leon Pace
Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death.
Cochrane Database Syst Rev. 2014 Mar 31;3:CD009694. doi: 10.1002/14651858.CD009694.pub2. Epub 2014 Mar 31.
Abstract/Text
BACKGROUND: The diagnosis of death using neurological criteria (brain death) has profound social, legal and ethical implications. The diagnosis can be made using standard clinical tests examining for brain function, but in some patient populations and in some countries additional tests may be required. Computed tomography (CT) angiography, which is currently in wide clinical use, has been identified as one such test.
OBJECTIVES: To assess from the current literature the sensitivity of CT cerebral angiography as an additional confirmatory test for diagnosing death using neurological criteria, following satisfaction of clinical neurological criteria for brain death.
SEARCH METHODS: We performed comprehensive literature searches to identify studies that would assess the diagnostic accuracy of CT angiography (the index test) in cohorts of adult patients, using the diagnosis of brain death according to neurological criteria as the target condition. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5) and the following databases from January 1992 to August 2012: MEDLINE; EMBASE; BNI; CINAHL; ISI Web of Science; BioMed Central. We also conducted searches in regional electronic bibliographic databases and subject-specific databases (MEDION; IndMed; African Index Medicus). A search was also conducted in Google Scholar where we reviewed the first 100 results only. We handsearched reference lists and conference proceedings to identify primary studies and review articles. Abstracts were identified by two authors. Methodological assessment of studies using the QUADAS-2 tool and further data extraction for re-analysis were performed by three authors.
SELECTION CRITERIA: We included in this review all large case series and cohort studies that compared the results of CT angiography with the diagnosis of brain death according to neurological criteria. Uniquely, the reference standard was the same as the target condition in this review.
DATA COLLECTION AND ANALYSIS: We reviewed all included studies for methodological quality according to the QUADAS-2 criteria. We encountered significant heterogeneity in methods used to interpret CT angiography studies and therefore, where possible, we re-analysed the published data to conform to a standard radiological interpretation model. The majority of studies (with one exception) were not designed to include patients who were not brain dead, and therefore overall specificity was not estimable as part of a meta-analysis. Sensitivity, confidence and prediction intervals were calculated for both as-published data and as re-analysed to a standardized interpretation model.
MAIN RESULTS: Ten studies were found including 366 patients in total. We included eight studies in the as-published data analysis, comprising 337 patients . The methodological quality of the studies was overall satisfactory, however there was potential for introduction of significant bias in several specific areas relating to performance of the index test and to the timing of index versus reference tests. Results demonstrated a sensitivity estimate of 0.84 (95% confidence interval (CI) 0.69 to 0.93). The 95% approximate prediction interval was very wide (0.34 to 0.98). Data in three studies were available as a four-vessel interpretation model and the data could be re-analysed to a four-vessel interpretation model in a further five studies, comprising 314 patient events. Results demonstrated a similar sensitivity estimate of 0.85 (95% CI 0.77 to 0.91) but with an improved 95% approximate prediction interval (0.56 to 0.96).
AUTHORS' CONCLUSIONS: The available evidence cannot support the use of CT angiography as a mandatory test, or as a complete replacement for neurological testing, in the management pathway of patients who are suspected to be clinically brain dead. CT angiography may be useful as a confirmatory or add-on test following a clinical diagnosis of death, assuming that clinicians are aware of the relatively low overall sensitivity. Consensus on a standard radiological interpretation protocol for future published studies would facilitate further meta-analysis.
Andreas H Kramer, Derek J Roberts
Computed tomography angiography in the diagnosis of brain death: a systematic review and meta-analysis.
Neurocrit Care. 2014 Dec;21(3):539-50. doi: 10.1007/s12028-014-9997-4.
Abstract/Text
BACKGROUND: Physiological instability and confounding factors may interfere with the clinical diagnosis of brain death. Computed tomography angiography (CTA) has been suggested as a potential ancillary test for confirmation of brain death, but its diagnostic accuracy remains unclear.
METHODS: We searched MEDLINE, EMBASE, and CENTRAL for studies comparing CTA with other accepted methods of diagnosing brain death (clinical or radiographic). Summary estimates of diagnostic accuracy were computed using random effects models. Subgroup analyses and meta-regression were performed to assess associations between CTA sensitivity and study or patient characteristics.
RESULTS: Twelve studies, involving 541 patients, were included. If the CTA criterion for brain death was complete lack of opacification of intracranial vessels, then the pooled sensitivity was 62 % (50-74 %) for venous phase and 84 % (75-94 %) for arterial phase imaging. The sensitivity of CTA was higher when the criterion for brain death involved absence of opacification of internal cerebral veins, either alone (99 %, 97-100 %) or in combination with lack of flow to the distal middle cerebral artery branches (85 %, 77-93 %). CTA sensitivity was not influenced by different reference standards (clinical vs. radiographic) or predominant diagnostic category (stroke vs. brain trauma). Specificity of CTA could not be adequately determined from the existing data.
CONCLUSION: Many patients who progress to brain death by accepted clinical or radiographic criteria have persistent opacification of proximal intracranial vessels when CTA is performed. The specificity of CTA in the diagnosis of brain death has not been adequately assessed. Routine use of CTA as an ancillary test in the diagnosis of brain death is therefore not recommended until diagnostic criteria have undergone further refinement and prospective validation. Absence of opacification of the internal cerebral veins appears to be the most promising angiographic criterion.
Louisa M Monteiro, Casper W Bollen, Alexander C van Huffelen, Rob G A Ackerstaff, Nicolaas J G Jansen, Adrianus J van Vught
Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis.
Intensive Care Med. 2006 Dec;32(12):1937-44. doi: 10.1007/s00134-006-0353-9. Epub 2006 Sep 21.
Abstract/Text
OBJECTIVE: Barbiturate therapy or hypothermia precludes proper diagnosis of brain death either clinically or by EEG. Specific intracranial flow patterns indicating cerebral circulatory arrest (CCA) can be visualized by transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the validity of TCD in confirming brain death.
DESIGN: Meta-analysis of studies assessing the validity of TCD in confirming brain death.
METHODS: A systematic review of articles in English on the diagnosis brain death by TCD, published between 1980 and 2004, was performed. An oscillating or reverberating flow and systolic spikes were considered to be compatible with CCA. The quality of each study was assessed using standardized methodological criteria. The literature was searched for any article reporting a false-positive result.
RESULTS: Two high-quality and eight low-quality studies were included. Meta-analysis of the two high-quality studies showed a sensitivity of 95% (95% CI 92-97%) and a specificity of 99% (95% CI 97-100%) to detect brain death. Meta-analysis of all ten studies showed a sensitivity of 89% and a specificity of 99%. In the literature we found two false-positive results; however, in both patients brain-stem function did show brain death shortly thereafter.
CONCLUSIONS: CCA by TCD in the anterior and posterior circulation predicted fatal brain damage in all patients; therefore, TCD can be used to determine the appropriate moment for angiography. Further research is needed to demonstrate that CCA by TCD on repeated examination can also predict brain death in all patients.
A H Karantanas, G M Hadjigeorgiou, K Paterakis, D Sfiras, A Komnos
Contribution of MRI and MR angiography in early diagnosis of brain death.
Eur Radiol. 2002 Nov;12(11):2710-6. doi: 10.1007/s00330-002-1336-z. Epub 2002 Apr 17.
Abstract/Text
The objective of this study was to investigate whether the findings of MR imaging and MR angiography could accurately and early diagnose brain death in comatose patients. Thirty comatose patients were studied with MRI and MR arteriography. In 20 patients (group A) presenting with a Glasgow coma scale (GCS) 3-6, the final clinical diagnosis was brain death. In ten comatose patients with a GCS 4-6 and no clinical signs of brain death (group B), the clinical follow-up did not reveal brain death in a period of 12 months. The MRI examination consisted of turbo fluid-attenuated inversion recovery and T2 turbo spin-echo pulse sequences. The MR arteriography was performed with a 3D inflow pulse sequence. In 12 patients with brain death and 5 patients with no signs of brain death, a 3D phase contrast MR venography was also applied. Magnetic resonance imaging in all patients showed variable edema with swelling of the cerebral gyri, small ventricular system, and basilar subarachnoid spaces. In group A, MRI in addition showed tonsillar herniation. In group A, MR arteriography revealed no arterial flow in the intracranial circulation, whereas MR venography showed in 9 patients no opacification of the sagittal and straight sinuses or visualization of intracranial veins. In contrast, MR angiography showed intact intracranial vessels in patients of group B. In conclusion, MR imaging and MR angiography may be reliable ancillary tests for use in early diagnosis of brain death and further work is required to validate its utility.
K Ishii, T Onuma, T Kinoshita, G Shiina, M Kameyama, Y Shimosegawa
Brain death: MR and MR angiography.
AJNR Am J Neuroradiol. 1996 Apr;17(4):731-5.
Abstract/Text
SUMMARY: Four patients in whom brain deaths was identified on the basis of neurologic and electroencephalographic findings were examined with MR imaging and MR angiography. MR images showed diffuse swelling of the cerebral gyri and cerebellar cortex, which prolongation of both the T1 and T2 signal (representing hypoxic ischemic brain injury), downward displacement of the diencephalon and the brain stem (central and tonsillar herniation), and loss of flow void in the intracranial portions of both internal carotid arteries. MR angiograms did not show the intracranial vessels above the level of the supraclinoid portion of the internal carotid arteries. MR angiography and MR imaging are noninvasive and reliable methods for use in determining brain death.
A Matsumura, K Meguro, H Tsurushima, Y Komatsu, Y Kikuchi, M Wada, Y Nakata, N Ohashi, T Nose
Magnetic resonance imaging of brain death.
Neurol Med Chir (Tokyo). 1996 Mar;36(3):166-71.
Abstract/Text
Fifteen patients with clinical diagnosis of brain death were examined by magnetic resonance (MR) imaging. Aortography with intraarterial digital subtraction angiography (IADSA) was also performed in nine patients. MR imaging indications of the flow void phenomenon were evaluated in the cavernous portion of internal carotid artery (ICA) and the middle or anterior cerebral artery, and compared with the IADSA findings. The relative intensities of gray and white matters were also measured. MR imaging showed that flow voids were absent in the ICA in all eight patients in whom non-filling was confirmed by IADSA. In one patient, IADSA demonstrated intracranial flow despite the diagnosis of brain death and the flow void pattern was normal. Serial MR imaging showed disappearance or abnormality of flow voids after brain death in six patients and absence before brain death in one. Spotty flow voids became visible in the unilateral ICA of one case after brain death. Partial residual flow voids may be caused by to-and-fro blood movement which was demonstrated by transcranial Doppler sonography. The normal flow void pattern was seen in none of these patients, therefore absence of flow voids indicates cessation of intracranial blood flow. Proton density and T2-weighted MR images showed dissociated intensity changes between white and gray matters, which were thought to be characteristic of brain death. In conclusion, MR imaging can achieve non-invasive diagnosis of the non-filling phenomenon in patients with brain death.
K O Lövblad, C Bassetti, C Basssetti
Diffusion-weighted magnetic resonance imaging in brain death.
Stroke. 2000 Feb;31(2):539-42.
Abstract/Text
UNLABELLED: BACKGROUND; Traditionally the diagnosis of brain death is established on the basis of a combination of clinical signs and paraclinical methods. Diffusion-weighted MRI is a new method sensitive to cerebral ischemia. Its value in brain death has not been demonstrated until now.
CASE DESCRIPTION: A patient was referred to MRI with suspicion of a brain stem stroke. Echo-planar whole-brain, multislice, diffusion-weighted MRI was performed in addition to conventional sequences and MR angiography sequences. In addition to the extensive bilateral hyperintensities observed on T2-weighted images, diffusion-weighted MRI showed diffuse hyperintensities involving both hemispheres as well as a severe drop in the apparent diffusion coefficient in both affected hemispheres. There was also transtentorial herniation with compression of the brain stem as well as absence of flow voids on the T2-weighted images and absence of intracranial vessels on MR angiography. On the basis of the clinical and imaging findings, it was concluded that the patient was in a state of brain death. The patient died the same day.
CONCLUSIONS: With the use of new fast techniques such as diffusion-weighted imaging, now MRI can not only display anatomic changes associated with severe brain suffering but can also demonstrate ultrastructural changes secondary to brain death and differentiate them from edematous changes seen on T2-weighted images.
Kevin J Donohoe, Garima Agrawal, Kirk A Frey, Victor H Gerbaudo, Giuliano Mariani, James S Nagel, Barry L Shulkin, Michael G Stabin, Margaret K Stokes
SNM practice guideline for brain death scintigraphy 2.0.
J Nucl Med Technol. 2012 Sep;40(3):198-203. doi: 10.2967/jnmt.112.105130. Epub 2012 Jun 28.
Abstract/Text
Marina Munari, Pietro Zucchetta, Carla Carollo, Franco Gallo, Marco De Nardin, Maria Cristina Marzola, Stefano Ferretti, Enrico Facco
Confirmatory tests in the diagnosis of brain death: comparison between SPECT and contrast angiography.
Crit Care Med. 2005 Sep;33(9):2068-73.
Abstract/Text
OBJECTIVE: Cerebral blood flow tests have increasingly been advocated for the confirmation of brain death (BD). Four-vessel angiography has been considered the most reliable investigation in the diagnosis of BD for >30 yrs, but it is invasive. (99m)Tc-HMPAO SPECT provides noninvasive, multiplanar imaging of brain tissue perfusion. The aim of this study was to check the reliability of SPECT compared with contrast angiography.
DESIGN: Prospective, blind study.
SETTING: Neurointensive care unit of a university hospital.
PATIENTS: Consecutive clinically brain dead patients with flat electroencephalogram.
INTERVENTIONS: BD was diagnosed according to Italian law. (99m)Tc-HMPAO SPECT and four-vessel angiography were performed in the same session; the rater of each investigation ignored the results of the other. Blood pressure, Sp(O2), and P(ECO2) were monitored throughout the study: any episode of hypoxia or hypotension caused exclusion of the patient from the study.
MEASUREMENTS AND MAIN RESULTS: Twenty brain dead patients were enrolled. The cause of BD was head injury in seven cases (35%), subarachnoid hemorrhage in seven (30%), spontaneous hemorrhage in one (10%), brain tumors in two (10%), stroke in two (10%), and thrombosis of the sagittal sinus in one (5%). Both angiography and SPECT confirmed BD in 19 of 20 patients: angiography showed the absence of filling of intracranial arteries, while SPECT showed a picture of "empty skull." For the remaining patient, angiography showed slight and late filling of left vertebral, basilar, and posterior cerebral arteries, while SPECT showed faint traces of uptake in the posterior fossa on the right side and on the midline. For this patient, the tests were repeated 48 hrs later, and both showed the arrest of intracranial circulation, thus confirming BD.
CONCLUSIONS: Our results confirm the reliability of SPECT in the diagnosis of BD; because SPECT is noninvasive, it is a good candidate for the "gold standard" of diagnosis.
W P Dillon, R V Lee, M J Tronolone, S Buckwald, R J Foote
Life support and maternal death during pregnancy.
JAMA. 1982 Sep 3;248(9):1089-91.
Abstract/Text
Christopher M Burkle, Jennifer Tessmer-Tuck, Eelco F Wijdicks
Medical, legal, and ethical challenges associated with pregnancy and catastrophic brain injury.
Int J Gynaecol Obstet. 2015 Jun;129(3):276-80. doi: 10.1016/j.ijgo.2014.12.011. Epub 2015 Mar 3.
Abstract/Text
In late 2013, two women from North America gained attention after sustaining catastrophic brain injuries while pregnant. After Marlise Muñoz--who was at 14 weeks of pregnancy when she developed a pulmonary embolism--was pronounced brain dead, hospital officials initially refused to withdraw support, citing a Texas state law requiring them to maintain life-sustaining treatment for a pregnant patient to help to save the fetus. By contrast, when Robyn Benson was pronounced brain dead after a brain hemorrhage at 22 weeks of pregnancy, both her husband and the physicians agreed to continue support until a viable child could be delivered. The Muñoz and Benson cases offer an opportunity to explore the medical, legal, and ethical issues surrounding catastrophic brain injury in pregnant women. It is hoped that the present article will enable clinicians to better appreciate the history and present state of issues involving advance directives for pregnant women, maternal versus fetal interests, and the impact of fetal viability on medical decision making, as well as offer a practical assessment of the various US state laws concerning the rare, yet catastrophic event of brain injury in a pregnant woman.
Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Majid Esmaeilzadeh, Christine Dictus, Elham Kayvanpour, Farbod Sedaghat-Hamedani, Michael Eichbaum, Stefan Hofer, Guido Engelmann, Hamidreza Fonouni, Mohammad Golriz, Jan Schmidt, Andreas Unterberg, Arianeb Mehrabi, Rezvan Ahmadi
One life ends, another begins: Management of a brain-dead pregnant mother-A systematic review-.
BMC Med. 2010 Nov 18;8:74. doi: 10.1186/1741-7015-8-74. Epub 2010 Nov 18.
Abstract/Text
BACKGROUND: An accident or a catastrophic disease may occasionally lead to brain death (BD) during pregnancy. Management of brain-dead pregnant patients needs to follow special strategies to support the mother in a way that she can deliver a viable and healthy child and, whenever possible, also be an organ donor. This review discusses the management of brain-dead mothers and gives an overview of recommendations concerning the organ supporting therapy.
METHODS: To obtain information on brain-dead pregnant women, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included the age of the mother, the cause of brain death, maternal medical complications, gestational age at BD, duration of extended life support, gestational age at delivery, indication of delivery, neonatal outcome, organ donation of the mothers and patient and graft outcome.
RESULTS: In our search of the literature, we found 30 cases reported between 1982 and 2010. A nontraumatic brain injury was the cause of BD in 26 of 30 mothers. The maternal mean age at the time of BD was 26.5 years. The mean gestational age at the time of BD and the mean gestational age at delivery were 22 and 29.5 weeks, respectively. Twelve viable infants were born and survived the neonatal period.
CONCLUSION: The management of a brain-dead pregnant woman requires a multidisciplinary team which should follow available standards, guidelines and recommendations both for a nontraumatic therapy of the fetus and for an organ-preserving treatment of the potential donor.
