In the United States, each year 1% to 2% of deaths are brain deaths. Considerable variation in the practice of determining brain death still remains, despite the publication of practice parameters in 1995 and an evidence-based guideline update in 2010. This review is intended to give bedside clinicians an overview of definition, the causes and pitfalls of misdiagnosing brain death, and a focus on the specifics of the brain death determination process.
SchwabRPottsFBonazziA. EEG as an aid in determining death in the presence of cardiac activity (ethical, legal, and medical aspects). Electroencephalogr Clin Neurophysiol. 1963;15:147–148.
2.
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;205(6):337–340.
3.
MohandasAChouSN. Brain death: a clinical and pathological study. J Neurosurg. 1971;35(2):211–218.
4.
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. BMJ. 1976;2(6045):1187–1188.
5.
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 biochemical and behavioral research. JAMA. 1981;246(19):2184–2186.
6.
The Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults (summary statement). Neurology. 1995;45(5):1012–1014.
7.
WijdicksEFVarelasPNGronsethGSGreerDM, 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;74(23):1911–1918.
8.
PownerDJHernandezMRivesTE. Variability among hospital policies for determining brain death in adults. Crit Care Med. 2004;32(6):1284–1288.
9.
GreerDMVarelasPNHaqueSWijdicksEF. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology. 2008;70(4):284–289.
10.
MachadoC. Diagnosis of brain death. Neuro Int. 2010;2(1):e2.
11.
WijdicksEF. Determining brain death in adults. Neurology. 1995;45(5):1003–1011.
12.
AshwalSSchneiderS. Brain death in children. Pediatr Neurol. 1987;3(1):5–11.
13.
Conference of Medical Royal Colleges and their Faculties in the UK. Diagnosis of brain death. Br Med J. 1979;1(6159):322.
14.
PlumFPosnerJB. The Diagnosis of Stupor and Coma. Philadelphia: Davis; 1966.
15.
PattersonJRGraboisM. Locked-in syndrome: a review of 139 cases. Stroke. 1986;17(4):758–764.
16.
HaigAJKatzRTSahgalV. Mortality and complications of the locked-in syndrome. Arch Phys Med Rehabil. 1987;68(1):24–27.
17.
KatzRTHaigAJClarkBBDi PaoloRJ. Long-term survival, prognosis and life-care planning for 29 patients with chronic locked-in syndrome. Arch Phys Med Rehabil. 1992;73(5):403–408.
18.
BauerGGerstenbrandFRumplE. Variables of the locked-in syndrome. J Neurol. 1979;221(2):77–91.
HassanTMumfordC. Guillain-Barre syndrome mistaken for brain stem death. Postgrad Med J. 1991;67(785):280–281.
25.
MilanovicRHusedzinovicSBradicN. Induced hypothermia after cardiopulmonary resuscitation: possible adverse effects. Signa Vitae. 2007;2(1):15–17.
26.
DanzlDFPozosRS. Accidental hypothermia. N Engl J Med. 1994;331(26):1756–1760.
27.
GilbertMBusundRSkagsethANilsenPASolboJP. Resuscitation from accidental hypothermia of 13.7 degrees C with circulatory arrest. Lancet. 2000;355(9201):375–376.
28.
GinsbergMDBustoR. Combating hyperthermia in acute stroke: a significant clinical concern. Stroke. 1998;29(2):529–534.
29.
NakashimaKToddMM. Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke. 1996;27(5):913–918.
30.
MitaniAKataokaK. Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study. Neuroscience. 1991;42(3):661–670.
31.
CastilloJDavalosANoyaM. Aggravation of acute ischemic stroke by hyperthermia is related to an excitotoxic mechanism. Cerebrovasc Dis. 1999;9(1):22–27.
32.
Grattan-SmithPJButtW. Suppression of brain stem reflexes in barbiturate coma. Arch Dis Child. 1993;69(1):151–152.
33.
YangKLDantzkerDR. Reversible brain death: a manifestation of amitriptyline overdose. Chest. 1991;99(4):1037–1038.
FritzHGHolzmayrMWalterBMoeritzKLuppABauerR. The effect of mild hypothermia on plasma Fentanyl concentration and biotransformation in juvenile pigs. Anesth Analg. 2005;100(4):996–1002.
36.
ZanelliSBuckMFairchildK. Physiologic and pharmacologic considerations for hypothermia therapy in neonates. J Perinatol. 2011;31(6):377–386.
AndersonKBPoloyacSM. Therapeutic Hypothermia: Implications on drug therapy. INTECH, accessed June 17, 2013, http://dx.doi.org/10.5772/52667
39.
WijdicksEF. The diagnosis of brain death. N Engl J Med. 2001;344(16):1215–1221.
40.
WijdicksEF. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. Neurology. 2002;58(1):20–25.
41.
Virginia statute, section 54–1–2972; 1997.
42.
Florida statute annotated, section 382.009; 1997.
43.
New Jersey statute annotated, 26–6A-5, suppl. 1994; 1987.
44.
New York Compilation Codes Regulations, Rules 7 REGS, title 10, section 400.16 (d), (e)(3); 1992.
45.
Virginia statute, section 32.1–162.7 and section 32.1–162.1.
46.
JorgensenEO. Spinal man after brain death. the unilateral extension-pronation reflex of the upper limb as an indication of brain death. Acta Neurochir (Wien). 1973;28(4):259–273.
47.
DosemeciLCengizMYilmazMRamazanogluA. Frequency of spinal reflex movements in brain-dead patients. Transplant Proc. 2004:36(1):17–19.
48.
MuralidharanRMateenFJShinoharaRTShearsGJWijdicksEF. The challenges with brain death determination in adult patients on extracorporeal membrane oxygenation. Neurocrit Care. 2011;14(3):423–426.
49.
SmilevitchPLonjaretLFourcadeOGreeraertsT. Apnea test for brain death determination in a patient on extracorporeal membrane oxygenation. Neurocrit Care. 2013;19(2):215–217.
50.
WijdicksEF. The case against confirmatory tests for determining brain death in adults. Neurology. 2010;75(1):77–83.
51.
American Clinical Neurophysiology Society – 2006 - Guideline 3: Minimum Technical Standards for EEG Recording in Suspected Cerebral Death. www.acns.org/pdfs/Guideline%203.pdfAccessed August 15, 2012.
52.
DonohoeKJFreyKAGerbaudoVHMarianiGNagelJSShulkinB. Society of Nuclear Medicine Procedure Guideline for Brain Death Scintigraphy version 1.0, approved February 25, 2003. www.interactive.snm.org/docs/pg_ch20_0403.pdf. Accessed August 15, 2012.
53.
FrampasEVidecoqMde KervilerE. CT angiography for brain death diagnosis. AJNR. 2009;30(8):1566–1570.
54.
DupasBGayet-DelacroixMVillersDAntonioliDVeccheriniMFSoulillouJP. Diagnosis of brain death using two-phase spiral CT. Am J Neuroradiol. 1998;19(4):641–647.
55.
KassabMYMajidAFarooqMU. Transcranial Doppler: an introduction for primary care physicians. J Am Board Fam Med. 2007;20(1):65–71.
56.
DucrocqXBraunMDebouverieMJungesCHummerMVespignaniH. Brain death and transcranial Doppler: experience in 130 cases of brain dead patients. J Neurol Sci. 1998;160(1):41–46.
57.
NakagawaTAAshwalSMathurMMysoreM. Guidelines for the determination of brain death in infants and children: an update of the 1987 task force recommendations. Pediatrics. 2011;128(3):e720–e740.
58.
WijdicksEFSmithWS. Brain death in children: why does it have to be so complicated?Ann Neurol. 2012;71(4):442.
59.
ShemieSDDoigCDickensB. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ. 2006;174(6):S1.