Scintigraphy as a confirmatory test of brain death

doi:10.1016/S0001-2998(03)00034-5

Seminars in Nuclear Medicine

Volume 33, Issue 4, October 2003, Pages 312-323

https://doi.org/10.1016/S0001-2998(03)00034-5 Get rights and content

Abstract

The concept of “brain death” was introduced to medicine in the second half of the 20th century, when technological advancements began to allow sustaining cardiorespiratory functioning of the body in the absence of brain function. Although physicians generally agree that a patient can be declared brain dead when the loss of brain function is total and irreversible, different approaches have been taken to define what constitutes brain death. A thorough clinical examination is essential to the diagnosis. The role of confirmatory tests differ among countries in the world but generally are indicated when a specific part of the clinical examination cannot be performed or is deemed unreliable. Under certain circumstances, confirmatory tests can be used to shorten the clinical observation. Of the confirmatory tests recommended by the American Academy of Neurology and the American Academy of Pediatrics, cerebral scintigraphy is a safe, reliable, and widely available alternative. Once the radiopharmaceutical is properly compounded, cerebral scintigraphy can be performed rapidly and can be interpreted in a straightforward manner. It is tolerant of metabolic aberrations and pharmacologic intoxicants. It is not affected by electrical interference, and the presence of skull defects or scalp trauma do not preclude its performance. The radiopharmaceuticals used in scintigraphy have no deleterious effects on potential donor organs. Cerebral radionuclide angiography has been highly sensitive. Either cerebral planar scintigraphy or cerebral scintitomography with Tc-99m hexamethylpropyleneamineoxime also are highly sensitive, but, in addition, appear to be 100% specific.

Section snippets

Definition of brain death

The Uniform Determination of Death Act (UDDA) forms the basis of brain death statutes for many states within the United States.4 It declares “An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. A determination of death must be made in accordance with accepted medical standards.” The Act does not define these medical standards; rather, it

Clinical criteria

The American Academy of Neurology (AAN), in its summary statement, lists the following prerequisites for the diagnosis of brain death in adults (1) clinical or neuroimaging evidence of acute central nervous system catastrophe; (2) exclusion of complicating medical conditions, such as severe electrolytic, acid-base, or endocrine disturbance; (3) absence of drug intoxication; and (4) core body temperature of at least 32°C (90°F).19 These prerequisites are followed by a clinical examination to

Confirmatory tests

Although several countries mandate the use of confirmatory tests in specific circumstances, they remain optional in the United States.2, 3 For adults, the AAN summary suggests a confirmatory test be performed when specific components of the clinical examination cannot be performed or are unreliable. The AAN summary lists the following confirmatory tests in their specified order of decreasing sensitivity: conventional contrast angiography, electroencephalography, transcranial Doppler

Scintigraphy as a confirmatory test

A comparison of the guidelines published by the American College of Radiology (ACR)23 and the Society of Nuclear Medicine (SNM),24 with the summary statement published by the AAN,19 reveals a few interesting differences. The approach of the ACR is “to determine if there is cerebral blood flow,” and that of the SNM is “to assess brain blood flow.” Therefore, they list radiotracers excluded by the blood-brain barrier, such as Tc-99m pertechnetate, Tc-99m pentetic acid (DTPA) and Tc-99m

Summary

Cerebral scintigraphy is a safe, reliable, and widely available confirmatory examination to the clinical diagnosis of brain death. Once the radiopharmaceutical is properly compounded, cerebral scintigraphy can be performed rapidly, and its interpretation will be relatively straightforward. Metabolic aberrations, pharmacologic intoxicants, electrical interference, and the presence of skull defects or scalp trauma do not preclude its performance. Cerebral radionuclide angiography has been highly

Acknowledgements

The authors thank Susan Miller, CNMT, Martha Saylor, CNMT, Elizabeth Cheatham, CNMT, Stephen Richmond, CNMT, and Jennifer Thompson, CNMT for their technical assistance; and John Ritter, MD, for his assistance with the collection of the cases.

References (83)

S.B. Coker et al.
Radionuclide cerebral imaging for confirmation of brain death in childrenThe significance of dural sinus activity
Pediatr Neurol
(1986)
R.D. Tien et al.
The “hot nose” sign in the cerebral radionuclide angiogram
Semin Nucl Med
(1992)
S. Ashwal et al.
Radionuclide bolus angiographyA technique for verification of brain death in infants and children
J Pediatr
(1977)
P. Mollaret et al.
Le coma dépassé (mémoire préliminaire)
Rev Neurol (Paris)
(1959)
E.F. Wijdicks
Brain death worldwide. Accepted fact but no global consensus in diagnostic criteria
Neurology
(2002)
W.F. Haupt et al.
European brain death codesA comparison of national guidelines
J Neurol
(1999)
Virg Stat §...
Virg Stat §...
Alaska Stat §...

Geor Stat §...

Kent Stat KRS...

Fla Stat Ann title XXIX ch...

New Jersey Stat Ann, §...

New York Comp Codes Reg, Rules 7 REGS, title 10 §...

Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain DeathA definition of irreversible coma

JAMA

(1968)

R.E. Cranford

Minnesota Medical Association criteria. Brain death: Concept and criteria, I

Minn Med

(1978)

R.E. Cranford

Minnesota Medical Association criteria. Brain death: concept and criteria, II

Minn Med

(1978)

Conference of Medical Royal Colleges and their Faculties in the United KingdomDiagnosis of brain death

Br Med J

(1976)

An appraisal of the criteria of cerebral death. A summary statement. A collaborative study

JAMA

(1977)

Guidelines for the determination of death

JAMA

(1981)

Practice parameters for determining brain death in adults (summary statement)

Neurology

(1995)

H. Baumgartner et al.

Diagnosing brain death without a neurologist

BMJ

(2002)

M.Y. Wang et al.

Brain death documentationAnalysis and issues

Neurosurgery

(2002)

Report of special Task Force. Guidelines for the determination of brain death in children

Pediatrics

(1987)

K.J. Donohoe et al.

Procedure guideline for brain death scintigraphy

J Nucl Med

(2003)

H.M. Abdel-Dayem et al.

The hollow skullA sign of brain death in Tc-99m HM-PAO brain scintigraphy

Clin Nucl Med

(1989)

E.F. Wijdicks

Determining brain death in adults

Neurology

(1995)

J.M. Goodman et al.

Determination of brain death by isotope angiography

JAMA

(1969)

J. Korein et al.

Radioisotopic bolus technique as a test to detect circulatory deficit associated with cerebral death. 142 studies on 80 patients demonstrating the bedside use of an innocuous IV procedure as an adjunct in the diagnosis of cerebral death

Circulation

(1975)

I.I. Kricheff et al.

Isotopic and angiographic determination of cerebral blood flow. A correlation in patients with cerebral death

Acta Radiol

(1976)

J.M. Goodman et al.

Confirmation of brain death at bedside by isotope angiography

JAMA

(1977)

J.M. Goodman et al.

Confirmation of brain death with portable isotope angiographyA review of 204 consecutive cases

Neurosurgery

(1985)

D.R. Brill et al.

Variant flow patterns in radionuclide cerebral imaging performed for brain death

Clin Nucl Med

(1985)

W.M. Flowers et al.

Radionuclide angiography as a confirmatory test for brain deathA review of 229 studies in 219 patients

South Med J

(1997)

H. Weibull et al.

Does cerebral angiography of cadaveric kidney donors interfere with graft function?

Acta Radiol

(1987)

C.E. Nagle

Use of immediate static scans in combination with radionuclide angiography as a confirmatory test in the diagnosis of brain death

Clin Nucl Med

(1980)

B.H. Holzman et al.

Radionuclide cerebral perfusion scintigraphy in determination of brain death in children

Neurology

(1983)

C.C. Kuni et al.

Radionuclide brain perfusion studies in suspected brain death

Clin Nucl Med

(1986)

Y.P. Patel et al.

Brain deathConfirmation by radionuclide cerebral angiography

Clin Nucl Med

(1988)

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Scintigraphy as a confirmatory test of brain death

Abstract

Section snippets

Definition of brain death

Clinical criteria

Confirmatory tests

Scintigraphy as a confirmatory test

Summary

Acknowledgements

Pediatr Neurol

Semin Nucl Med

J Pediatr

Le coma dépassé (mémoire préliminaire)

Rev Neurol (Paris)

Brain death worldwide. Accepted fact but no global consensus in diagnostic criteria

Neurology

European brain death codesA comparison of national guidelines

J Neurol

Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain DeathA definition of irreversible coma

JAMA

Minnesota Medical Association criteria. Brain death: Concept and criteria, I

Minn Med

Minnesota Medical Association criteria. Brain death: concept and criteria, II

Minn Med

Conference of Medical Royal Colleges and their Faculties in the United KingdomDiagnosis of brain death

Br Med J

An appraisal of the criteria of cerebral death. A summary statement. A collaborative study

JAMA

Guidelines for the determination of death

JAMA

Practice parameters for determining brain death in adults (summary statement)

Neurology

Diagnosing brain death without a neurologist

BMJ

Brain death documentationAnalysis and issues

Neurosurgery

Report of special Task Force. Guidelines for the determination of brain death in children

Pediatrics

Procedure guideline for brain death scintigraphy

J Nucl Med

The hollow skullA sign of brain death in Tc-99m HM-PAO brain scintigraphy

Clin Nucl Med

Determining brain death in adults

Neurology

Determination of brain death by isotope angiography

JAMA

Radioisotopic bolus technique as a test to detect circulatory deficit associated with cerebral death. 142 studies on 80 patients demonstrating the bedside use of an innocuous IV procedure as an adjunct in the diagnosis of cerebral death

Circulation

Isotopic and angiographic determination of cerebral blood flow. A correlation in patients with cerebral death

Acta Radiol

Confirmation of brain death at bedside by isotope angiography

JAMA

Confirmation of brain death with portable isotope angiographyA review of 204 consecutive cases

Neurosurgery

Variant flow patterns in radionuclide cerebral imaging performed for brain death

Clin Nucl Med

Radionuclide angiography as a confirmatory test for brain deathA review of 229 studies in 219 patients

South Med J

Does cerebral angiography of cadaveric kidney donors interfere with graft function?

Acta Radiol

Use of immediate static scans in combination with radionuclide angiography as a confirmatory test in the diagnosis of brain death

Clin Nucl Med

Radionuclide cerebral perfusion scintigraphy in determination of brain death in children

Neurology

Radionuclide brain perfusion studies in suspected brain death

Clin Nucl Med

Brain deathConfirmation by radionuclide cerebral angiography

Clin Nucl Med