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Determination of brain death
Determination of brain death From the Ad Hoc C o m m i t t e e on Brain Death,* The Children's Hospital, Boston
The paper by Fackler and Rogers in this issue of The Journal raises a very difficult and increasingly common dilemma in the pediatric intensive care settiTig: How is brain death to be defined under a variety of circumstances, including differing developmental ages, causes, therapies, and reasons for making such a determination. On the one hand, organ donation programs have mandated requirements for a strict definition of brain death, whereas humane treatment of patients, families, and staff dictates that procedures be minimized that will unnecessarily delay confirmation of that clinical determination, especially for minimal technicalities. To address these issues, The Children's Hospital in Boston organized an ad hoc committee of clinicians with legal counsel to make recommendations regarding the determination of brain death in children. The Committee report emphasized that the clinical examination is the most important component of the criteria for determination of brain death and that laboratory studies are to be used only as adjuncts to the clinical examination or as a means of confirming the irreversibility of the clinical state. What follows are excerpts from that Committee report, including a form to be completed by the patient's attending physician, which becomes part of the medical record. This procedure has helped to standardize the approach to the determination of brain death in children in a teaching hospital environment. DETERMINATION
OF B R A I N D E A T H
Brain death has occurred when cerebral and brainstem functions are irreversibly absent. Absent cerebral function is recognized clinically as the lack of receptivity and responsivity, that is, no autonomic or somatic response to Submitted for publication Sept._ 30, 1986; accepted Oct. 1, 1986. Reprint requests: Robert K. Crone, M.D., Director, Multidisciplinary ICU, Department of Anesthesia, The Children's Hospital, 300 Longwood Ave., Boston, MA 02115. *Ad Hoc Committee on Brain Death, The Children's Hospital, Boston: Robert K. Crone, M.D., Chairman; Michael J. Bresnanl M.D., Guiseppe Erba, M.D., E. Gary Fischer, M.D., S. Ted Treves, M.D., Ellen Covner Weiss, Esq.
any sort of external stimulation, mediated through the brainstem. Absent brainstem function is recognized clinically when pupillary light, corneal, oculocephalic, oculovestibular, oropharyngeal, and respiratory reflexes are irreversibly absent. Procedures for testing these reflexes are outlined below. Particularly in children, peripheral nervous activity, including spinal cord reflexes, may persist after brain death; however, decorticate or decerebrate posturing is incons~ten t with brain death. lrreversibility is recognized when the cause of coma is established and is sufficient to account for the loss of brain function, and when the possibility of recovery is excluded by observation for an appropriate period of time. It is important that the cause of coma be established when possible. Absence of brain function resulting from head trauma has different implications than that caused by a metabolic abnormality or intoxication. Important reversible causes that may mimic irreversibility are sedation, hypothermia, neuromuscular blockade, and shock. If the See related article, p. 84.
cause of coma cannot be established, these reversible conditions must be ruled out by appropriate laboratory studies, including analysis of blood and urine for clinically significant levels of toxic substances that might produce coma, such as sedative, hypnotic, and anesthetic agents; measurement of core body temperature, which must be higher than 32 ~ C; and measurement of peripheral neuromuscular function. T h e period of observation will also vary, depending on the circumstances and possible causes. In most cases in which the cause is established and seems appropriate, such as in severe inoperable head trauma, a period of 6 hours seems reasonable and is commonly recommended, whereas with hypoxic-ischemic encephalopathy, observation for 24 l~ours may be more appropriate. Confirmatory laboratory findings may be appropriate in determining primarily the irreversibility of brain death, and possibly accelerating the determination of irreversibility. However, i f cause and irreversibility are established and the clinical examination yields unequivocal findings, Text continued on page 18.
15
16
A d H o c C o m m i t t e e on Brain Death
The Journal o f Pediatrics January 1987
USE PLATE OR PRINT
PT. NAME
FIRST
LAST DIV.
DATE MEDICAL REC. NO.
BRAIN DEATH EXAMINATION FORM
Date, time of examination Probable cause of coma Diagnosis _ _ 1. Vital signs, chemistry values a. BP (systolic/diastolic) / _ b. Temperature ( r e c t a l ) _ Potassium mEq/L Osm/L c. Serum sodium mEq/L d. Urine sodium m E q / L Potassium mEq/L Osm/L e. Urine volume for past 4 h r ml/hr 2, Drugs a. Barbiturate level b. Other drugs c. Mydriatic drugs d. Neuromuscular blocking agents: Peripheral nerve stimulation test normal Metabolic abnormalities 3.
4.
5.
Yes Yes
No No
Cerebral responsivity a. Responsive to verbal commands Yes No b. Responsive to painful stimulation delivered to each extremity and to both sides of face Yes No Brainstem responsivity a. Fundi R b. Pupillary reaction R c. pupil size R mm L mm d. Ciliospinal reflex R e. Doll's eyes reflex R f. Corneal reflex R g. Response to noxious nasal mucosa s t i m u l a t i o n h. Iee water calories (25-50 ml, check tympanic membranes) R L i. Gag, cough Yes No j. Respirations Yes No k. Apnea test (100% 0 2 for 5 min on ventilator with rate adjusted to give Paco2 >35. Turn off ventilator rate, leaving continual flow of 100% 02 for 5 min. Determine arterial blood gases at end of 5 min, or sooner if respirations or cyanosis occur, or if heart rate or BP change >10%.) Arterial blood gases at end of test: Pao2 Paco2 pH
Volume 110 Number 1
6.
7.
Determination o f brain death
Additional supplemental clinical examination a- Deep tendon reflexes (0-4+) Biceps Triceps Knee Ankle b. Clonus c. Toes (t ~ 0) Supplemental laboratory tests a. Electroencephalogram #1: Date/time Staff interpretation ~:2: Date/time
Temperature _
_
Barbiturate level
Temperature _
_
Barbiturate level
Temperature _
_
Barbiturate level
Staff interpretation b. Evoked potentials Date/time Staff interpretation c. CT scan results Date/time Results d. Tc-99m cerebral radionuclide angiogram Date/time Results 8. 9. 10.
Family members notified, relationship Medical examiner's case Organ donation
Date/time
Signed Attending physician
Date/time
Signed Concurring physician
R R R R
L L L L
R
L
R
L
17
18
A d Hoe Committee on Brain Death
The Journal of Pediatrics January 1987
confirmatory tests are unnecessary. When they are appropriate, confirmatory laboratory examinations that may prove helpful include electroencephalography, radionuelide brain scan, and brainstem evoked potentials. Tc-99m cerebral radionuelide angiogram. To determine intracranial vascular perfusion, the cerebral radionuclide angiogram is used as a confirmatory test in the diagnosis of brain death, particularly when the EEG is equivocal or barbiturates are present in the blood. A bolus of Tc-99m as sodium pertechnetate (200 #Ci/ kg, minimum 5 mCi) is given intravenously in <3 seconds. The patient is imaged in the anterior projection, using a gamma, camera/computer system. Recording is begun at the time of injection at one frame per second for 60 seconds. Evaluation of the studY is visual on the series of images and on time-activity curves obtained from the regions of interest over the cerebral hemispheres. In cerebral death, the radionuelide cerebral angiogram shows (1) bilateral absence of the arterial phase (anterior and middle cerebral artery territories), (2) lack of visualization of the sagittal sinus during the venous phase, (3) lack of arterial peak of cerebral time-activity curves, and (4) perfusion of the extracranial tissues only. Electroencephalogram. The EEG is used to demonstrate absence of any spontaneous activity in scalp records whenever the clinical examination suggests that brain functions are totally and persistently abolished. Available data indicate that an isoelectric ("fiat") EEG, obtained and interpreted according to stringent criteria,* provides reliable evidence of cerebral death. Absence of electrical response to rousing stimuli adds further evidence. The EEG is particularly useful for assessing brain viability when the clinical examination is limited by the use of sedatives and muscle relaxants. A repeating EEG after 24 hours is indicated: 1. When the first isoelectric EEG was obtained in conditions of drug toxicity, especially CNS depressants; hypothermia, especially temperature _+32~ C; or both drug toxicity and hypothermia, even if body temperature is >32 ~ C. At the time of the second EEG, drug blood levels should be known to be below toxic levels, and body temperature should be brought to 36 ~ C. 2. When, despite clinical evidence of persistent and probably irreversible cerebral failure, the first EEG was
The indications for brainstem evoked potentials are the same as for the EEG: to demonstrate that reactivity to incoming stimuli (auditory, somatosensory) is absent in brainstem nuclei, except the first (cochlear) wave. A "flat" auditory brainstem response in the presence of viable peripheral conduction (cochlear wave) is considered unequivocal evidence of cerebral death because of the proximity of auditory nuclei to vital centers. If acoustic conduction is not demonstrable even at maximal stimulus intensity, auditory brainstem evoked potentials should be complemented by somatosensory brainstem evoked potentialsto rule out the possibility that a flat response is caused by peripheral deafness. Brainstem sensory evoked potentials are not a substitute for the EEG, but do effectively complement the information derived from spontaneous electrical cortical activity when cerebral death is suspected o n clinical grounds. Brainstem evoked potentials have the advantage of being free of artifact contamination and are less sensitive than the EEG to the effect of CNS depressants. The disappearance of activity from the EEG may precede the loss of brainstem responses because the cortical structures are
*EEG in the case of cerebral death is subject to much technicaland interpretivebias.In complyingwiththe minimumstandardsoutlinedby the AmericanEEG Societyrequiringmaximalamplificationof the signal,the record oftenbecomescontaminatedby a varietyof environmentalartifacts. To minimizesuch artifacts, equipmentmay have to be turnedoff temporarily, and personnelshouldbe expectedto withholdactivityin the vicinity of the patientwhennecessary.
*EEG in the case of cerebral death is subject to much technicaland interpretivebias. In complyingwiththe minimumstandardsoutlinedby the AmericanEEG Societyrequiringmaximalamplificationof the signal,the record oftenbecomescontaminatedby a varietyof environmentalartifacts. To minimizesuch artifacts, equipmentmay have to be turnedoff temporarily, and personnelshouldbe expectedto withholdactivityin the vicinity of the patientwhennecessary.
not isoelectric but showed some activity, such as lowvoltage background or burst-suppression pattern, which may represent agonal changes. 3. When the first EEG was isoelectric, but at the time the clinical examination showed persistence of some brainstem or spinal reflexes. 4. When the interpretation of the first EEG as isoelectric is controversial because of the presence of artifacts, which may closely resemble cerebral activity.* NOTE: When there is no doubt that an earlier EEG was isoelectric, a repeat EEG after 24 hours is not mandatory nor recommended (1) when clinical evidence points to persistent loss of cerebral functions, including the autonomic system; (2) when other factors that may temporarily depress CNS activity can be excluded; and (3) when the cause of death is known and well documented. However, the decision is made entirely on the clinician's judgment. For example, it is acceptable to repeat an isoelectric EEG mainly for humanitarian reasons, because it is common practice to prolong life-supporting measures beyond the point of reasonable hope for recovery.
Brainstem (far field) evoked potentials Indications.
Volume 110 Number 1
Determination o f brain death
more sensitive to the effects of severe insults than brainstem structures are. Thus, a t the time of an isoelectric EEG, brainstem responses may be abnormal though not completely absent. In this case, serial evoked potentials are indicated to provide evidence of deterioration in brainstem function. Brainstem evoked potentials are recommended when (1) the interpretation of the isoelectric EEG is controversial; (2) the EEG is not completely isoelectric (agonal stage); or
19
(3) the EEG is isoelectric but the effects of CNS depressants or hypothermia is present. DOCUMENTATION
OF BRAIN DEATH
Pertinent clinical examination and laboratory data are summarized on the Brain Death Examination Form (see example on pp. 16-17) dated and signed by the attending physician of record and a concurring attending physician.
FELLOWSHIPS Available fellowships in pediatric subspecialties and those for general academic pediatric training are listed once a year, in May, in The Journal of Pediatrics. Each October, forms for listing such fellowships are sent to the Chairman of the Department of Pediatrics at most major hospitals in the United States and Canada. Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to The C. V. Mosby Company by February 15 of the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, The C. V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, M O 63146/314-872-8370.
The paper by Fackler and Rogers in this issue of The Journal raises a very difficult and increasingly common dilemma in the pediatric intensive care settiTig: How is brain death to be defined under a variety of circumstances, including differing developmental ages, causes, therapies, and reasons for making such a determination. On the one hand, organ donation programs have mandated requirements for a strict definition of brain death, whereas humane treatment of patients, families, and staff dictates that procedures be minimized that will unnecessarily delay confirmation of that clinical determination, especially for minimal technicalities. To address these issues, The Children's Hospital in Boston organized an ad hoc committee of clinicians with legal counsel to make recommendations regarding the determination of brain death in children. The Committee report emphasized that the clinical examination is the most important component of the criteria for determination of brain death and that laboratory studies are to be used only as adjuncts to the clinical examination or as a means of confirming the irreversibility of the clinical state. What follows are excerpts from that Committee report, including a form to be completed by the patient's attending physician, which becomes part of the medical record. This procedure has helped to standardize the approach to the determination of brain death in children in a teaching hospital environment. DETERMINATION
OF B R A I N D E A T H
Brain death has occurred when cerebral and brainstem functions are irreversibly absent. Absent cerebral function is recognized clinically as the lack of receptivity and responsivity, that is, no autonomic or somatic response to Submitted for publication Sept._ 30, 1986; accepted Oct. 1, 1986. Reprint requests: Robert K. Crone, M.D., Director, Multidisciplinary ICU, Department of Anesthesia, The Children's Hospital, 300 Longwood Ave., Boston, MA 02115. *Ad Hoc Committee on Brain Death, The Children's Hospital, Boston: Robert K. Crone, M.D., Chairman; Michael J. Bresnanl M.D., Guiseppe Erba, M.D., E. Gary Fischer, M.D., S. Ted Treves, M.D., Ellen Covner Weiss, Esq.
any sort of external stimulation, mediated through the brainstem. Absent brainstem function is recognized clinically when pupillary light, corneal, oculocephalic, oculovestibular, oropharyngeal, and respiratory reflexes are irreversibly absent. Procedures for testing these reflexes are outlined below. Particularly in children, peripheral nervous activity, including spinal cord reflexes, may persist after brain death; however, decorticate or decerebrate posturing is incons~ten t with brain death. lrreversibility is recognized when the cause of coma is established and is sufficient to account for the loss of brain function, and when the possibility of recovery is excluded by observation for an appropriate period of time. It is important that the cause of coma be established when possible. Absence of brain function resulting from head trauma has different implications than that caused by a metabolic abnormality or intoxication. Important reversible causes that may mimic irreversibility are sedation, hypothermia, neuromuscular blockade, and shock. If the See related article, p. 84.
cause of coma cannot be established, these reversible conditions must be ruled out by appropriate laboratory studies, including analysis of blood and urine for clinically significant levels of toxic substances that might produce coma, such as sedative, hypnotic, and anesthetic agents; measurement of core body temperature, which must be higher than 32 ~ C; and measurement of peripheral neuromuscular function. T h e period of observation will also vary, depending on the circumstances and possible causes. In most cases in which the cause is established and seems appropriate, such as in severe inoperable head trauma, a period of 6 hours seems reasonable and is commonly recommended, whereas with hypoxic-ischemic encephalopathy, observation for 24 l~ours may be more appropriate. Confirmatory laboratory findings may be appropriate in determining primarily the irreversibility of brain death, and possibly accelerating the determination of irreversibility. However, i f cause and irreversibility are established and the clinical examination yields unequivocal findings, Text continued on page 18.
15
16
A d H o c C o m m i t t e e on Brain Death
The Journal o f Pediatrics January 1987
USE PLATE OR PRINT
PT. NAME
FIRST
LAST DIV.
DATE MEDICAL REC. NO.
BRAIN DEATH EXAMINATION FORM
Date, time of examination Probable cause of coma Diagnosis _ _ 1. Vital signs, chemistry values a. BP (systolic/diastolic) / _ b. Temperature ( r e c t a l ) _ Potassium mEq/L Osm/L c. Serum sodium mEq/L d. Urine sodium m E q / L Potassium mEq/L Osm/L e. Urine volume for past 4 h r ml/hr 2, Drugs a. Barbiturate level b. Other drugs c. Mydriatic drugs d. Neuromuscular blocking agents: Peripheral nerve stimulation test normal Metabolic abnormalities 3.
4.
5.
Yes Yes
No No
Cerebral responsivity a. Responsive to verbal commands Yes No b. Responsive to painful stimulation delivered to each extremity and to both sides of face Yes No Brainstem responsivity a. Fundi R b. Pupillary reaction R c. pupil size R mm L mm d. Ciliospinal reflex R e. Doll's eyes reflex R f. Corneal reflex R g. Response to noxious nasal mucosa s t i m u l a t i o n h. Iee water calories (25-50 ml, check tympanic membranes) R L i. Gag, cough Yes No j. Respirations Yes No k. Apnea test (100% 0 2 for 5 min on ventilator with rate adjusted to give Paco2 >35. Turn off ventilator rate, leaving continual flow of 100% 02 for 5 min. Determine arterial blood gases at end of 5 min, or sooner if respirations or cyanosis occur, or if heart rate or BP change >10%.) Arterial blood gases at end of test: Pao2 Paco2 pH
Volume 110 Number 1
6.
7.
Determination o f brain death
Additional supplemental clinical examination a- Deep tendon reflexes (0-4+) Biceps Triceps Knee Ankle b. Clonus c. Toes (t ~ 0) Supplemental laboratory tests a. Electroencephalogram #1: Date/time Staff interpretation ~:2: Date/time
Temperature _
_
Barbiturate level
Temperature _
_
Barbiturate level
Temperature _
_
Barbiturate level
Staff interpretation b. Evoked potentials Date/time Staff interpretation c. CT scan results Date/time Results d. Tc-99m cerebral radionuclide angiogram Date/time Results 8. 9. 10.
Family members notified, relationship Medical examiner's case Organ donation
Date/time
Signed Attending physician
Date/time
Signed Concurring physician
R R R R
L L L L
R
L
R
L
17
18
A d Hoe Committee on Brain Death
The Journal of Pediatrics January 1987
confirmatory tests are unnecessary. When they are appropriate, confirmatory laboratory examinations that may prove helpful include electroencephalography, radionuelide brain scan, and brainstem evoked potentials. Tc-99m cerebral radionuelide angiogram. To determine intracranial vascular perfusion, the cerebral radionuclide angiogram is used as a confirmatory test in the diagnosis of brain death, particularly when the EEG is equivocal or barbiturates are present in the blood. A bolus of Tc-99m as sodium pertechnetate (200 #Ci/ kg, minimum 5 mCi) is given intravenously in <3 seconds. The patient is imaged in the anterior projection, using a gamma, camera/computer system. Recording is begun at the time of injection at one frame per second for 60 seconds. Evaluation of the studY is visual on the series of images and on time-activity curves obtained from the regions of interest over the cerebral hemispheres. In cerebral death, the radionuelide cerebral angiogram shows (1) bilateral absence of the arterial phase (anterior and middle cerebral artery territories), (2) lack of visualization of the sagittal sinus during the venous phase, (3) lack of arterial peak of cerebral time-activity curves, and (4) perfusion of the extracranial tissues only. Electroencephalogram. The EEG is used to demonstrate absence of any spontaneous activity in scalp records whenever the clinical examination suggests that brain functions are totally and persistently abolished. Available data indicate that an isoelectric ("fiat") EEG, obtained and interpreted according to stringent criteria,* provides reliable evidence of cerebral death. Absence of electrical response to rousing stimuli adds further evidence. The EEG is particularly useful for assessing brain viability when the clinical examination is limited by the use of sedatives and muscle relaxants. A repeating EEG after 24 hours is indicated: 1. When the first isoelectric EEG was obtained in conditions of drug toxicity, especially CNS depressants; hypothermia, especially temperature _+32~ C; or both drug toxicity and hypothermia, even if body temperature is >32 ~ C. At the time of the second EEG, drug blood levels should be known to be below toxic levels, and body temperature should be brought to 36 ~ C. 2. When, despite clinical evidence of persistent and probably irreversible cerebral failure, the first EEG was
The indications for brainstem evoked potentials are the same as for the EEG: to demonstrate that reactivity to incoming stimuli (auditory, somatosensory) is absent in brainstem nuclei, except the first (cochlear) wave. A "flat" auditory brainstem response in the presence of viable peripheral conduction (cochlear wave) is considered unequivocal evidence of cerebral death because of the proximity of auditory nuclei to vital centers. If acoustic conduction is not demonstrable even at maximal stimulus intensity, auditory brainstem evoked potentials should be complemented by somatosensory brainstem evoked potentialsto rule out the possibility that a flat response is caused by peripheral deafness. Brainstem sensory evoked potentials are not a substitute for the EEG, but do effectively complement the information derived from spontaneous electrical cortical activity when cerebral death is suspected o n clinical grounds. Brainstem evoked potentials have the advantage of being free of artifact contamination and are less sensitive than the EEG to the effect of CNS depressants. The disappearance of activity from the EEG may precede the loss of brainstem responses because the cortical structures are
*EEG in the case of cerebral death is subject to much technicaland interpretivebias.In complyingwiththe minimumstandardsoutlinedby the AmericanEEG Societyrequiringmaximalamplificationof the signal,the record oftenbecomescontaminatedby a varietyof environmentalartifacts. To minimizesuch artifacts, equipmentmay have to be turnedoff temporarily, and personnelshouldbe expectedto withholdactivityin the vicinity of the patientwhennecessary.
*EEG in the case of cerebral death is subject to much technicaland interpretivebias. In complyingwiththe minimumstandardsoutlinedby the AmericanEEG Societyrequiringmaximalamplificationof the signal,the record oftenbecomescontaminatedby a varietyof environmentalartifacts. To minimizesuch artifacts, equipmentmay have to be turnedoff temporarily, and personnelshouldbe expectedto withholdactivityin the vicinity of the patientwhennecessary.
not isoelectric but showed some activity, such as lowvoltage background or burst-suppression pattern, which may represent agonal changes. 3. When the first EEG was isoelectric, but at the time the clinical examination showed persistence of some brainstem or spinal reflexes. 4. When the interpretation of the first EEG as isoelectric is controversial because of the presence of artifacts, which may closely resemble cerebral activity.* NOTE: When there is no doubt that an earlier EEG was isoelectric, a repeat EEG after 24 hours is not mandatory nor recommended (1) when clinical evidence points to persistent loss of cerebral functions, including the autonomic system; (2) when other factors that may temporarily depress CNS activity can be excluded; and (3) when the cause of death is known and well documented. However, the decision is made entirely on the clinician's judgment. For example, it is acceptable to repeat an isoelectric EEG mainly for humanitarian reasons, because it is common practice to prolong life-supporting measures beyond the point of reasonable hope for recovery.
Brainstem (far field) evoked potentials Indications.
Volume 110 Number 1
Determination o f brain death
more sensitive to the effects of severe insults than brainstem structures are. Thus, a t the time of an isoelectric EEG, brainstem responses may be abnormal though not completely absent. In this case, serial evoked potentials are indicated to provide evidence of deterioration in brainstem function. Brainstem evoked potentials are recommended when (1) the interpretation of the isoelectric EEG is controversial; (2) the EEG is not completely isoelectric (agonal stage); or
19
(3) the EEG is isoelectric but the effects of CNS depressants or hypothermia is present. DOCUMENTATION
OF BRAIN DEATH
Pertinent clinical examination and laboratory data are summarized on the Brain Death Examination Form (see example on pp. 16-17) dated and signed by the attending physician of record and a concurring attending physician.
FELLOWSHIPS Available fellowships in pediatric subspecialties and those for general academic pediatric training are listed once a year, in May, in The Journal of Pediatrics. Each October, forms for listing such fellowships are sent to the Chairman of the Department of Pediatrics at most major hospitals in the United States and Canada. Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to The C. V. Mosby Company by February 15 of the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, The C. V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, M O 63146/314-872-8370.