Brain Death Guideline 2011

DOI: 10.1542/peds.2011-1511; originally published online August 28, 2011; 2011;128;e720Pediatrics

Neurology of the American Academy of Pediatrics, and the Child Neurology Societythe Society of Critical Care Medicine, Section on Critical Care and Section on

Update of the 1987 Task Force RecommendationsGuidelines for the Determination of Brain Death in Infants and Children: An

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Clinical Report—Guidelines for the Determination ofBrain Death in Infants and Children: An Update of the1987 Task Force Recommendations

abstractOBJECTIVE: To review and revise the 1987 pediatric brain death guidelines.METHODS: Relevant literature was reviewed. Recommendations weredeveloped using the GRADE system.CONCLUSIONS AND RECOMMENDATIONS: (1) Determination of braindeath in term newborns, infants and children is a clinical diagnosisbased on the absence of neurologic function with a known irreversiblecause of coma. Because of insufficient data in the literature, recommen-dations for preterm infants less than 37 weeks gestational age are notincluded in this guideline.

(2) Hypotension, hypothermia, and metabolic disturbances should betreated and corrected and medications that can interfere with the neu-rologic examination and apnea testing should be discontinued allowingfor adequate clearance before proceeding with these evaluations.

(3) Two examinations including apnea testing with each examinationseparated by an observation period are required. Examinations shouldbe performed by different attending physicians. Apnea testing may beperformed by the same physician. An observation period of 24 hours forterm newborns (37 weeks gestational age) to 30 days of age, and 12hours for infants and chi (� 30 days to 18 years) is recommended. Thefirst examination determines the child has met the accepted neurologicexamination criteria for brain death. The second examination confirmsbrain death based on an unchanged and irreversible condition. Assess-ment of neurologic function following cardiopulmonary resuscitation orother severe acute brain injuries should be deferred for 24 hours orlonger if there are concerns or inconsistencies in the examination.

(4) Apnea testing to support the diagnosis of brain death must be per-formed safely and requires documentation of an arterial PaCO2 20 mm Hgabove the baseline and� 60mm Hgwith no respiratory effort during thetesting period. If the apnea test cannot be safely completed, an ancillarystudy should be performed.

(5) Ancillary studies (electroencephalogram and radionuclide cerebralblood flow) are not required to establish brain death and are not asubstitute for the neurologic examination. Ancillary studies may be us dto assist the clinician in making the diagnosis of brain death (i) whencomponents of the examination or apnea testing cannot be completedsafely due to the underlying medical condition of the patient; (ii) if thereis uncertainty about the results of the neurologic examination; (iii) if amedication effect may be present; or (iv) to reduce the inter-examinationobservation period. When ancillary studies are used, a second clinicalexamination and apnea test should be performed and components thatcan be completed must remain consistent with brain death. In this in-stance the observation interval may be shortened and the second neu-rologic examination and apnea test (or all components that are able to becompleted safely) can be performed at any time thereafter.

(6) Death is declared when the above criteria are fulfilled. Pediatrics 2011;128:e720–e740

Thomas A. Nakagawa, MD, Stephen Ashwal, MD, MuditMathur, MD, Mohan Mysore, MD, and THE SOCIETY OFCRITICAL CARE MEDICINE, SECTION ON CRITICAL CARE ANDSECTION ON NEUROLOGY OF THE AMERICAN ACADEMY OFPEDIATRICS, AND THE CHILD NEUROLOGY SOCIETY

KEY WORDSapnea testing, brain death, cerebral blood flow, children,electroencephalography, infants, neonates, pediatrics

ABBREVIATIONSEEG—electroencephalogramCBF—cerebral blood flowCT—computed tomographyMRI—magnetic resonance imagingETT—endotracheal tubeCPAP—continuous positive airway pressureICP—intracranial pressureECS—electrocerebral silence

The guidance in this report does not indicate an exclusivecourse of treatment or serve as a standard of medical care.Variations, taking into account individual circumstances, may beappropriate.

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PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

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Guidance for the Clinician inRendering Pediatric Care

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INTRODUCTIONIn 1987, guidelines for the determina-tion of brain death in children werepublished by a multi-society taskforce.1,2 These consensus based guide-lines were developed because existingguidelines from the President’s Com-mission failed to adequately addresscriteria to determine brain death in pe-diatric patients. They emphasized theimportance of the history and clinicalexamination in determining the etiol-ogy of coma so that correctable or re-versible conditions were eliminated.Additionally, age-related observationperiods and the need for specific neu-rodiagnostic tests were recom-mended for children younger than 1year of age. In children older than 1year, it was recommended that the di-agnosis of brain death could be madesolely on a clinical basis and labora-tory studies were optional. Little guid-ance was provided to determine braindeath in neonates less than 7 days ofage because of limited clinical experi-ence and lack of sufficient data.

These guidelines generally have beenaccepted and used to guide clinicalpractice; however they have not beenreviewed nor revised since originallypublished. Several inherent weak-nesses have been recognized includ-ing: (1) limited clinical information atthe time of publication; (2) uncertaintyconcerning the sensitivity and specific-ity of ancillary testing; (3) biological ra-tionale for the use of age-based crite-ria; and (4) little direction as towhether, when and how the diagnosisof brain death could be made in neo-nates. Despite national and legal ac-ceptance of the concept of brain death,these limitations have resulted in thelack of a standardized approach to de-termining brain death in children.3–9

These issues are not unique to infantsand children10 nor limited to the UnitedStates. The American Academy of Neu-rology published guidelines to deter-

mine brain death in adults in 1995which have been revised in 2010.11,12

Additionally, guidelines to determinebrain death in adults and childrenhave been published in Canada.13

The Society of Critical Care Medicine(SCCM) and the Section on CriticalCare and Section on Neurology of theAmerican Academy of Pediatrics (AAP),in conjunctionwith the Child NeurologySociety (CNS), formed a multidisci-plinary committee of medical and sur-gical subspecialists under the aus-pices of the American College ofCritical Care Medicine (ACCM) to re-view and revise the 1987 guidelines. Itspurpose was to review the neonataland pediatric literature from 1987, in-cluding any prior relevant literature,and update recommendations regard-ing appropriate examination criteriaand use of ancillary testing to diag-nose brain death in neonates, infantsand children. The committee was alsocharged with developing a checklist toprovide guidance and standardizationto document brain death. Uniformity inthe determination of brain deathshould allow physicians to pronouncebrain death in pediatric patients in amore precise and orderly mannerand ensure that all components ofthe examination are performed andappropriately documented.

Tables 1–3 of this publication containthe committee’s updated recommen-dations, the GRADE classification sys-tem, and clinical and neurologic exam-ination criteria for brain death.Appendices 1–7 provide additional in-formation concerning the diagnosis ofbrain death in children. Appendix 1(check list) and Appendix 2 (pharma-cological data for the time interval totesting after medication discontinua-tion) provide additional resources toaid the clinician in diagnosing braindeath. Appendix 3 summarizes data re-garding apnea testing. Appendices4–6 provide data on the diagnostic

yieldofancillary testing, specifically elec-troencephalography (EEG), and radionu-clide cerebral blood flow (CBF) studies.Appendix 7 compares the 1987 guide-line’s criteria to the revised recommen-dations. Appendix 8 provides an algo-rithm for the determination of braindeath in infants and children.

This update affirms the definition ofdeath as stated in the 1987 pediatricguidelines. This definition had been es-tablished by multiple organizations in-cluding the American Medical Associa-tion, the American Bar Association, theNational Conference of Commissionerson Uniform State Laws, the President’sCommission for the Study of EthicalProblems in Medicine and Biomedicaland Behavioral Research and the Ameri-can Academy of Neurology as follows:“An individual who has sustained either(1) irreversible cessation of circulatoryand respiratory functions, or (2) irre-versible cessation of all functions of theentire brain, including the brainstem, isdead. A determination of death must bemade in accordancewith acceptedmed-ical standards.”1

METHODS

A multidisciplinary committee com-posed of physicians and nurses withexpertise in pediatrics, pediatric criti-cal care, neonatology, pediatric neu-rology and neurosurgery, nuclearmedicine, and neuroradiology wasformed by the SCCM and the AAP to up-date the guidelines for the diagnosis ofpediatric brain death. The committeewas divided into threeworking groups,each charged with reviewing the liter-ature on brain death in neonates, in-fants and children for the followingspecific areas: (1) examination criteriaand observation periods; (2) ancillarytesting; and (3) declaration of death bymedical personnel including legal andethical implications.

A Medline search of relevant literaturepublished from January 1987 to June

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TABLE 1 Summary Recommendations for the Diagnosis of Brain Death in Neonates, Infants, and ChildrenRecommendation Evidence

ScoreRecommendation

Score

1. Determination of brain death in neonates, infants and children relies on a clinical diagnosis that is based on the absence ofneurologic function with a known irreversible cause of coma. Coma and apnea must coexist to diagnose brain death. Thisdiagnosis should be made by physicians who have evaluated the history and completed the neurologic examinations.

High Strong

2. Prerequisites for initiating a brain death evaluationa. Hypotension, hypothermia, and metabolic disturbances that could affect the neurological examination must becorrected prior to examination for brain death.

High Strong

b. Sedatives, analgesics, neuromuscular blockers, and anticonvulsant agents should be discontinued for a reasonable timeperiod based on elimination half-life of the pharmacologic agent to ensure they do not affect the neurologic examination.Knowledge of the total amount of each agent (mg/kg) administered since hospital admission may provide usefulinformation concerning the risk of continued medication effects. Blood or plasma levels to confirm high orsupratherapeutic levels of anticonvulsants with sedative effects that are not present should be obtained (if available)and repeated as needed or until the levels are in the low to mid therapeutic range.

Moderate Strong

c. The diagnosis of brain death based on neurologic examination alone should not be made if supratherapeutic or hightherapeutic levels of sedative agents are present. When levels are in the low or in the mid-therapeutic range, medicationeffects sufficient to affect the results of the neurologic examination are unlikely. If uncertainty remains, an ancillarystudy should be performed.

Moderate Strong

d. Assessment of neurologic function may be unreliable immediately following cardiopulmonary resuscitation or othersevere acute brain injuries and evaluation for brain death should be deferred for 24 to 48 hours or longer if there areconcerns or inconsistencies in the examination.

Moderate Strong

3. Number of examinations, examiners and observation periodsa. Two examinations including apnea testing with each examination separated by an observation period are required. Moderate Strongb. The examinations should be performed by different attending physicians involved in the care of the child. The apnea test maybe performed by the same physician, preferably the attending physician who is managing ventilator care of the child.

Low Strong

c. Recommended observation periods:(1) 24 hours for neonates (37 weeks gestation to term infants 30 days of age) Moderate Strong(2) 12 hours for infants and children (� 30 days to 18 years).d. The first examination determines the child has met neurologic examination criteria for brain death. The secondexamination, performed by a different attending physician, confirms that the child has fulfilled criteria for brain death.

Moderate Strong

e. Assessment of neurologic function may be unreliable immediately following cardiopulmonary resuscitation or othersevere acute brain injuries and evaluation for brain death should be deferred for 24 to 48 hours or longer if there areconcerns or inconsistencies in the examination.

Moderate Strong

4. Apnea testinga. Apnea testing must be performed safely and requires documentation of an arterial PaCO2 20 mm Hg above the baselinePaCO2 and� 60 mm Hg with no respiratory effort during the testing period to support the diagnosis of brain death.Some infants and children with chronic respiratory disease or insufficiency may only be responsive to supranormalPaCO2 levels. In this instance, the PaCO2 level should increase to� 20 mm Hg above the baseline PaCO2 level.

Moderate Strong

b. If the apnea test cannot be performed due to a medical contraindication or cannot be completed because ofhemodynamic instability, desaturation to� 85%, or an inability to reach a PaCO2 of 60 mm Hg or greater, an ancillarystudy should be performed.

Moderate Strong

5. Ancillary studiesa. Ancillary studies (EEG and radionuclide CBF) are not required to establish brain death unless the clinical examination orapnea test cannot be completed

Moderate Strong

b. Ancillary studies are not a substitute for the neurologic examination. Moderate Strongc. For all age groups, ancillary studies can be used to assist the clinician in making the diagnosis of brain death to reducethe observation period or when (i) components of the examination or apnea testing cannot be completed safely due tothe underlying medical condition of the patient; (ii) if there is uncertainty about the results of the neurologicexamination; or (iii) if a medication effect may interfere with evaluation of the patient. If the ancillary study supports thediagnosis, the second examination and apnea testing can then be performed. When an ancillary study is used to reducethe observation period, all aspects of the examination and apnea testing should be completed and documented.

Moderate Strong

d. When an ancillary study is used because there are inherent examination limitations (ie, i to iii), then components of theexamination done initially should be completed and documented.

High Strong

e. If the ancillary study is equivocal or if there is concern about the validity of the ancillary study, the patient cannot bepronounced dead. The patient should continue to be observed until brain death can be declared on clinical examinationcriteria and apnea testing, or a follow-up ancillary study can be performed to assist with the determination of braindeath. A waiting period of 24 hours is recommended before further clinical reevaluation or repeat ancillary study isperformed. Supportive patient care should continue during this time period.

Moderate Strong

6. Declaration of deatha. Death is declared after confirmation and completion of the second clinical examination and apnea test. High Strongb. When ancillary studies are used, documentation of components from the second clinical examination that can becompleted must remain consistent with brain death. All aspects of the clinical examination, including the apnea test, orancillary studies must be appropriately documented.

High Strong

c. The clinical examination should be carried out by experienced clinicians who are familiar with infants and children, andhave specific training in neurocritical care.

High Strong

The “evaluation score” is based on the strength of the evidence available at the time of publication.The “recommendation score” is the strength of the recommendations based on available evidence at the time of publication. Scoring guidelines are listed in Table 2.



2008 was conducted. Key words includ-ed: brain death, neurologic death, neo-natal, pediatric, cerebral blood flow,electroencephalography, apnea test,and irreversible coma with the sub-heading, “children.” Additional articlescited in the post 1987 literature thatwere published prior to 1987were alsoreviewed if they contained data rele-vant to this guideline. Abstracts andarticles were independently reviewedand summarized by at least two indi-viduals on each committee. Data weresummarized into five categories: clini-cal examination, apnea testing, obser-vation periods, ancillary tests, andother considerations.

Methodological issues regarding anal-ysis of evidence warrant further dis-cussion as they directly affected thedecision of how information and rec-ommendations about brain death arepresented. No randomized control tri-als examining different strategies re-

garding the diagnosis of brain deathexist. Standard evidence-based ap-proaches for guidelines used by manyorganizations attempting to link the“strength of the evidence” to the“strength of the recommendations”therefore cannot be used in this in-stance. There is, however, consider-able experiential consensus within ob-servational studies in the pediatricpopulation. Grading of Recommenda-tions Assessment, Development andEvaluation (GRADE), a recently devel-oped standardized methodologicalconsensus-based approach, allowspanels to evaluate the evidence andopinions and make recommenda-tions.14–17 GRADE uses 5 domains tojudge the balance between the desir-able and undesirable effect of an inter-vention. Strong recommendations aremade when there is confidence thatthe desirable effects of adherence to arecommendation outweigh the unde-

sirable effects. Weak recommendationsindicate that the desirable effects of ad-herence to a recommendation probablyoutweigh the undesirable effects, butthe panel is less confident. No specificrecommendations are made when theadvantages and disadvantages of al-ternative courses of action are equiva-lent or where there is insufficient evi-dence on which to formulate arecommendation.15,18 Table 2 outlinesthe GRADE methodology used in formu-lating recommendations for thisguideline. Each committeemember as-signed a GRADE score for (i) thestrength of evidence linked to aspecific recommendation and (ii) indi-cated (a) “yes,” (b) “no” or (c) “uncer-tain” for each of the six recommenda-tions listed at the end of this report. Bya priori consensus, the committee de-cided that a “strong” recommendationcould only bemade if greater than 80%of the committee members voted “yes”

TABLE 2 Grading of Recommendations Assessment, Development and Evaluation (GRADE) System14-18

1. Classification of evidenceGradeA. High Further research is very unlikely to change our confidence in the estimate of effectB. Moderate Further research is likely to have an important impact on our confidence in the estimate of effect and

may change the estimateC. Low Further research is very likely to have an important impact on confidence in the estimate of effect and

is likely to change the estimateD. Very low Any estimate of effect is very uncertain

2. Recommendations: The strength of arecommendation reflects theextent to which we can beconfident that desirable effectsof an intervention outweighundesirable effects.

Strong When the desirable effects of an intervention clearly outweigh the undesirable effects, or clearly do not.(a) For patients—most people in your situation would want the recommended course of action andonly a small proportion would not

(b) For clinicians—most patients should receive the recommended course of action(c) For policy makers—the recommendation can be adopted as a policy in most situations

Weak Evidence suggests that desirable and undesirable effects are closely balanced or the quality ofevidence is low.(a) For patients—most people in your situation would want the recommended course of action, butmany would not

(b) For clinicians—you should recognize that different choices will be appropriate for differentpatients and you must help each patient to arrive at a management decision consistent with his orher values and preferences.

(c) For policy makers—policy making will require substantial debate and involvement of manystakeholders

No specific recommendations The advantages and disadvantages of the recommendations are equivalent or where there isinsufficient evidence on which to formulate a recommendation





for a recommendation and that a“weak” recommendation was made ifgreater than 60% but less than 80%voted “yes.” “No recommendation”wasmade if less than 60% of the committeevoted “yes” for a specific recommen-dation. Table 1 summarizes GRADE rec-ommendations and evidence scores.

The committee believes these reviseddiagnostic guidelines, summarized inTable 1 and a standardized checklist

form (Appendix 1), will assist physi-cians in determining and documentingbrain death in children. This should en-sure broader acceptance and utiliza-tion of such uniform criteria. Thecommittee recognizes that medicaljudgment of involved pediatric special-ists will direct the appropriate coursefor the medical evaluation and diagno-sis of brain death. The committee alsorecognizes that no national brain

death law exists. State statutes andpolicy may restrict determination ofbrain death in certain circumstances.Physicians should become familiarwith laws and policies in their respec-tive institution. The committee alsorecognizes that variability exists forthe age designation of pediatrictrauma patients. In some states, theage of the pediatric trauma patient isdefined as less than 14 years of age.

TABLE 3 Neurologic Examination Components to Assess for Brain Death in Neonates, Infants and Children* Including Apnea Testing

Reversible conditions or conditions that can interfere with the neurologic examination must be excluded prior to brain death testing.See text for discussion1. Coma. The patient must exhibit complete loss of consciousness, vocalization and volitional activity.

● Patients must lack all evidence of responsiveness. Eye opening or eye movement to noxious stimuli is absent.● Noxious stimuli should not produce a motor response other than spinally mediated reflexes. The clinical differentiation of spinal responses from retainedmotor responses associated with brain activity requires expertise.

2. Loss of all brain stem reflexes including:Midposition or fully dilated pupils which do not respond to light.Absence of pupillary response to a bright light is documented in both eyes. Usually the pupils are fixed in a midsize or dilated position (4–9 mm). Whenuncertainty exists, a magnifying glass should be used.Absence of movement of bulbar musculature including facial and oropharyngeal muscles.Deep pressure on the condyles at the level of the temporomandibular joints and deep pressure at the supraorbital ridge should produce no grimacing or facialmuscle movement.Absent gag, cough, sucking, and rooting reflexThe pharyngeal or gag reflex is tested after stimulation of the posterior pharynx with a tongue blade or suction device. The tracheal reflex is most reliably testedby examining the cough response to tracheal suctioning. The catheter should be inserted into the trachea and advanced to the level of the carina followed by 1or 2 suctioning passes.Absent corneal reflexesAbsent corneal reflex is demonstrated by touching the cornea with a piece of tissue paper, a cotton swab, or squirts of water. No eyelid movement should beseen. Care should be taken not to damage the cornea during testing.Absent oculovestibular reflexesThe oculovestibular reflex is tested by irrigating each ear with ice water (caloric testing) after the patency of the external auditory canal is confirmed. The headis elevated to 30 degrees. Each external auditory canal is irrigated (1 ear at a time) with�10 to 50 mL of ice water. Movement of the eyes should be absentduring 1 minute of observation. Both sides are tested, with an interval of several minutes.3. Apnea. The patient must have the complete absence of documented respiratory effort (if feasible) by formal apnea testing demonstrating a PaCO2

> 60 mm Hg and > 20 mm Hg increase above baseline.● Normalization of the pH and PaCO2, measured by arterial blood gas analysis, maintenance of core temperature� 35°C, normalization of blood pressureappropriate for the age of the child, and correcting for factors that could affect respiratory effort are a prerequisite to testing.

● The patient should be preoxygenated using 100% oxygen for 5–10 minutes prior to initiating this test.● Intermittent mandatory mechanical ventilation should be discontinued once the patient is well oxygenated and a normal PaCO2 has been achieved.● The patient’s heart rate, blood pressure, and oxygen saturation should be continuously monitored while observing for spontaneous respiratory effortthroughout the entire procedure.

● Follow up blood gases should be obtained to monitor the rise in PaCO2 while the patient remains disconnected from mechanical ventilation.● If no respiratory effort is observed from the initiation of the apnea test to the time the measured PaCO2� 60 mm Hg and� 20 mm Hg above the baselinelevel, the apnea test is consistent with brain death.

● The patient should be placed back on mechanical ventilator support and medical management should continue until the second neurologic examinationand apnea test confirming brain death is completed.

● If oxygen saturations fall below 85%, hemodynamic instability limits completion of apnea testing, or a PaCO2 level of� 60 mm Hg cannot be achieved, theinfant or child should be placed back on ventilator support with appropriate treatment to restore normal oxygen saturations, normocarbia, andhemodynamic parameters. Another attempt to test for apnea may be performed at a later time or an ancillary study may be pursued to assist withdetermination of brain death.

● Evidence of any respiratory effort is inconsistent with brain death and the apnea test should be terminated.4. Flaccid tone and absence of spontaneous or induced movements, excluding spinal cord events such as reflex withdrawal or spinal myoclonus.

● The patient’s extremities should be examined to evaluate tone by passive range of motion assuming that there are no limitations to performing such anexamination (eg, previous trauma, etc) and the patient observed for any spontaneous or induced movements.

● If abnormal movements are present, clinical assessment to determine whether or not these are spinal cord reflexes should be done.* Criteria adapted from 2010 American Academy of Neurology criteria for brain death determination in adults (Wijdicks et al, 2010).



Trauma and intensive care practitio-ners are encouraged to follow state/local regulations governing the speci-fied age of pediatric trauma patients.The committee believes these guide-lines to be an important step in pro-tecting the health and safety of all in-fants and children. These revisedguidelines and accompanying check-list are intended to provide a frame-work to promote standardization ofthe neurologic examination and use ofancillary studies based on the evi-dence available to the committee atthe time of publication.

TERM NEWBORNS (37 WEEKSGESTATIONAL AGE) TO CHILDREN18 YEARS OF AGE

Definition of Brain Death andComponents of the ClinicalExamination (Recommendation 1,Table 1 and Table 3)

Brain death is a clinical diagnosisbased on the absence of neurologicfunction with a known diagnosis thathas resulted in irreversible coma.Coma and apnea must coexist to diag-nose brain death. A complete neuro-logic examination that includes the el-ements outlined in Table 3 ismandatory to determine brain deathwith all components appropriatelydocumented.

Prerequisites for Initiating aClinical Brain Death Evaluation(Recommendations 2a–d, Table 1)

Determination of brain death by neuro-logic examination should be per-formed in the setting of normal age-appropriate physiologic parameters.Factors potentially influencing the neu-rologic examination that must be cor-rected before examination and apneatesting include: (1) shock or persistenthypotension based on normal systolicor mean arterial blood pressure val-ues for the patient’s age. Systolic bloodpressure or MAP should be in an ac-

ceptable range (systolic BP not lessthan 2 standard deviations below ageappropriate norm) based on age; (2)hypothermia; (3) severe metabolic dis-turbances capable of causing a poten-tially reversible coma including elec-trolyte/glucose abnormalities; (4)recent administration of neuromuscu-lar blocking agents; and (5) drug intox-ications including but not limited tobarbiturates, opioids, sedative and an-esthetic agents, antiepileptic agents,and alcohols. Placement of an indwell-ing arterial catheter is recommendedto ensure that blood pressure remainswithin a normal range during the pro-cess of diagnosing brain death and toaccurately measure PaCO2 levels dur-ing apnea testing.

Hypothermia is used with increasingfrequency as an adjunctive therapy forindividuals with acute brain injury.19–22

Hypothermia has also been used fol-lowing cardiac arrest to protect thebrain because it reduces cerebralmet-abolic activity.23–26 The clinician caringfor critically ill infants and childrenshould be aware of the potential im-pact of therapeutic modalities such ashypothermia on the diagnosis of braindeath. Hypothermia is known to de-press central nervous system func-tion27–29 andmay lead to a false diagno-sis of brain death. Hypothermia mayalter metabolism and clearance ofmedications that can interfere withbrain death testing. Efforts to ade-quately rewarm before performingany neurologic examination and main-tain temperature during the observa-tion period are essential. The 1987guidelines stated that the patient mustnot be significantly hypothermic how-ever no definition was provided.1 It isreasonable that the core body temper-ature at the time of brain death exam-ination be as close to normal to repro-duce normal physiologic conditions. Acore body temperature of �35°C(95°F) should be achieved and main-

tained during examination and testingto determine death. This temperatureis consistent with current adult guide-lines and is relatively easy to achieveand maintain in children.11,13

Severe metabolic disturbances cancause reversible coma and interferewith the clinical evaluation to deter-mine brain death. Reversible condi-tions such as severe electrolyte imbal-ances, hyper or hyponatremia, hyperor hypoglycemia, severe pH distur-bances, severe hepatic or renal dys-function or inborn errors of metabo-lism may cause coma in a neonate orchild.28,29 These conditions should beidentified and treated before evalua-tion for brain death, especially in situ-ations where the clinical history doesnot provide a reasonable explanationfor the neurologic status of the child.

Drug intoxications including barbitu-rates, opioids, sedatives, intravenousand inhalation anesthetics, antiepilep-tic agents, and alcohols can cause se-vere central nervous system depres-sion and may alter the clinicalexamination to the point where theycan mimic brain death.28,29 Testing forthese drugs should be performed ifthere is concern regarding recent in-gestion or administration. When avail-able, specific serum levels of medica-tions with sedative properties or sideeffects should be obtained and docu-mented to be in a low to mid therapeu-tic range before neurologic examina-tion for brain death testing. Longeracting or continuous infusion of seda-tive agents can also interfere with theneurologic evaluation. These medica-tions should be discontinued. Ade-quate clearance (based on the age ofthe child, presence of organ dysfunc-tion, total amount of medication ad-ministered, elimination half-life of thedrug and any active metabolites)should be allowed before the neuro-logic examination. In some instancesthis may require waiting several half-





lives and rechecking serum levels ofthe medication before conducting thebrain death examination. If neuromus-cular blocking agents have been used,they should be stopped and adequateclearance of these agents confirmedby use of a nerve stimulator with doc-umentation of neuromuscular junctionactivity and twitch response. Other un-usual causes of coma such as neuro-toxins, and chemical exposure (ie, or-ganophosphates, and carbamates)should be considered in rare caseswhere an etiology for coma has notbeen established. Recommendationsof time intervals before brain deathevaluation for many of the commonlyusedmedications administered to crit-ically ill neonates and children arelisted in Appendix 2.

Clinical criteria for determining braindeath may not be present on admis-sion and may evolve during hospital-ization. Assessment of neurologicfunction may be unreliable immedi-ately following resuscitation after car-diopulmonary arrest30–33 or otheracute brain injuries and serial neuro-logic examinations are necessary toestablish or refute the diagnosis ofbrain death. Additionally, initial stabili-zation may take several hours duringwhich time correcting metabolic dis-turbances and identifying and treatingreversible conditions that may imitatebrain death can be accomplished. It isreasonable to defer neurologic exami-nation to determine brain death for 24hours or longer if dictated by clinicaljudgment of the treating physician insuch circumstances. If there are con-cerns about the validity of the exami-nation (eg, flaccid tone or absentmovements in a patient with high spi-nal cord injury or severe neuromuscu-lar disease) or if specific examinationcomponents cannot be performed dueto medical contraindications (eg, ap-nea testing in patients with significantlung injury, hemodynamic instability,

or high spinal cord injury), or if exam-ination findings are inconsistent, con-tinued observation and postponingfurther neurologic examinations untilthese issues are resolved is warrantedto avoid improperly diagnosing braindeath. An ancillary study can be pur-sued to assist with the diagnosis ofbrain death in situations where cer-tain examination components cannotbe completed.

Neuroimaging with either computedtomography (CT) or magnetic reso-nance imaging (MRI) should demon-strate evidence of an acute centralnervous system injury consistent withthe profound loss of brain function. Itis recognized that early after acutebrain injury, imaging findings may notdemonstrate significant injury. In suchsituations, repeat studies are helpfulin documenting that an acute severebrain injury has occurred. CT and MRIare not considered ancillary studiesand should not be relied on to makethe determination of brain death.

Number of Examinations,Examiners and ObservationPeriods (Recommendations 3a–e,Table 1)

Number of Examinations andExaminers

The 1987 guidelines recommended ob-servation periods between brain deathexaminations based on age and the re-sults of neurodiagnostic testing.1 Twoexaminations and EEG’s separated byat least 48 hours were recommendedfor infants 7 days to 2 months. Two ex-aminations and EEG’s separated by atleast 24 hours were recommended forchildren 2 months to 1 year. A repeatEEG was not necessary if a cerebralradionuclide scan or cerebral angiog-raphy demonstrated no flow or visual-ization of the cerebral arteries. Forchildren older than 1 year, an observa-tion period of 12 hours was recom-mended and ancillary testing was not

required when an irreversible causeexisted. The observation period in thisage group could be decreased if therewas documentation of electrocerebralsilence (ECS) or absent cerebral bloodflow (CBF).1 The general consensuswas the younger the child, the longerthe waiting period unless ancillarystudies supported the clinical diagno-sis of brain death and if so, the obser-vation period could be shortened.

The current committee supports the1987 guideline recommending perfor-mance of two examinations separatedby an observation period. The commit-tee recommends that these examina-tions be performed by different attend-ing physicians involved in the care ofthe child. Children being evaluated forbrain death may be cared for and eval-uated bymultiple medical and surgicalspecialists. The committee recom-mends that the best interests of thechild and family are served if at leasttwo different attending physicians par-ticipate in diagnosing brain death toensure that (i) the diagnosis is basedon currently established criteria, (ii)there are no conflicts of interest in es-tablishing the diagnosis and (iii) thereis consensus by at least two physiciansinvolved in the care of the child thatbrain death criteria are met. The com-mittee also believes that because theapnea test is an objective test, it maybe performed by the same physician,preferably the attending physicianwho is managing ventilator care of thechild.

Duration of Observation Periods

A literature review of 171 children di-agnosed as brain dead found that 47%had ventilator support withdrawn anaverage of 1.7 days after the diagnosisof brain death was made.34 Seventy-nine children (46%) in whom supportwas continued after declaration ofbrain death suffered a cardiac arrestan average of 22.7 days later. The re-



maining children died by an unknownmechanism (5%), or made an incom-plete (1%) or complete recovery(0.5%). Review of the children who sur-vived indicates they did not fulfill braindeath criteria by accepted medicalstandards. The age range of the chil-dren in this study included pretermand term neonates and older infantsand children up to 18 years of age.These data and the reports of more re-cent studies35,36 suggest that there islikely no biological justification for us-ing different durations of observationto diagnose brain death in infantsgreater than one month of age. In fact,there are no reports of children recov-ering neurologic function after meet-ing adult brain death criteria based onneurologic examination findings.37 Al-though some authors have reportedapparent reversibility of brain death,further review of these cases revealsthese children would not have fulfilledbrain death criteria by currently ac-cepted US medical standards.38

Based on the above data, currentlyavailable literature and clinical experi-ence, the committee recommends theobservation period between examina-tions should be 24 hours for neonates(37 weeks up to 30 days), and 12 hoursfor infants and children (� 30 days to18 years). The first examination deter-mines the child has met neurologic ex-amination criteria for brain death. Thesecond examination confirms braindeath based on an unchanged and ir-reversible condition. Timing of the firstclinical brain death examination, re-duction of the observation period, anduse of ancillary studies are discussedin separate sections of this guideline.

Apnea Testing (Recommendations4a,b, Table 1)

Apnea testing should be performedwith each neurologic examination todetermine brain death in all patientsunless a medical contraindication ex-

ists. Contraindications may includeconditions that invalidate the apneatest (such as high cervical spine in-jury) or raise safety concerns for thepatient (high oxygen requirement orventilator settings). If apnea testingcannot be completed safely, an ancil-lary study should be performed to as-sist with the determination of braindeath.

The normal physiologic threshold forapnea (minimum carbon dioxide ten-sion at which respiration begins) inchildren has been assumed to be thesame as in adults with reports demon-strating that PaCO2 levels in the normalrange (24–38 mm Hg) may be ade-quate to stimulate ventilatory effort inchildren with residual brainstem func-tion.39 Although expert opinion hassuggested a range of PaCO2 levels from44 to 60 mm Hg for apnea testing inadults, the general consensus in in-fants and children has been to use 60mm Hg as a threshold.40–42 Appendix 3summarizes data from 4 studies (3 be-ing prospective) on 106 apnea tests in76 children 2 months old to 17 yearswith suspected brain death.39–42 73 of76 children had no spontaneous venti-latory effort. In 3 of these studiesmeanPaCO2 values were 59.5 � 10.2, 68.1 �17.7, and 63.9 � 21.5 mm Hg; in thefourth study, mean PaCO2 values werenot reported, only the range (ie, 60–116 mm Hg).39–42 Three children exhib-ited spontaneous respiratory effortwith measured PaCO2 levels � 40mm Hg.39,42 Serial measurements ofPaCO2 were done in most studies and15 minutes was the usual end point oftesting although patients may havehad apnea for longer periods. Themax-imum rate of PaCO2 increase usually oc-curred within 5 minutes. Sixty five chil-dren had no ventilatory effort duringthe apnea test. After completion of ap-nea testing, support was withdrawn inall of these patients. Patient outcomewas not reported for one study al-

though these 9 children all had absentbrainstem reflexes for a period of �72 hours.41 In one study 4/9 patientshad phenobarbital levels that were in-terpreted as not affecting the resultsof apnea testing.41

There are three case reports discuss-ing irregular breaths orminimal respi-ratory effort with a PCO2� 60mm Hg inchildren who otherwise met criteriafor brain death.43–45 Two children died,one after meeting all criteria for braindeath including a second apnea test.The remaining child survived and wassupported in a chronic care facilitywith a tracheostomy, chronic mechan-ical ventilation and a gastrostomytube. One other report describes a3-month-old who met all criteria forbrain death including 2 apnea testswith serial PCO2’s of 69.3 mm Hg and62.1 mm Hg respectively. This infantwas declared dead on hospital day 5.This infant developed irregular sponta-neous respirations at a rate of two tothree breaths per minute 38 days laterwhich continued while receiving me-chanical ventilator support until deathon day 71.46 Review of this case andothers remind us to be cautious in ap-plying brain death criteria in young in-fants. However, these cases should notbe considered to represent reversibledeficits or failure of current braindeath criteria.47

Technique for Apnea Testing

Apnea testing in term newborns, in-fants, and children is conducted simi-lar to adults. Normalization of the pHand PaCO2, measured by arterial bloodgas analysis, maintenance of core tem-perature � 35°C, normalization ofblood pressure appropriate for theage of the child, and correcting for fac-tors that could affect respiratory ef-fort are a prerequisite to testing. Thepatient must be preoxygenated using100% oxygen for 5–10 minutes beforeinitiating this test. Intermittent manda-





tory mechanical ventilation should bediscontinued once the patient is welloxygenated and a normal PaCO2 hasbeen achieved. The patient can then bechanged to a T piece attached to theendotracheal tube (ETT), or a self-inflating bag valve system such as aMapleson circuit connected to the ETT.Tracheal insufflation of oxygen using acatheter inserted through the ETT hasalso been used, however caution iswarranted to ensure adequate gas ex-cursion and to prevent barotrauma.High gas flow rateswith tracheal insuf-flation may also promote CO2 washoutpreventing adequate PaCO2 rise duringapnea testing. Continuous positive air-way pressure (CPAP) ventilation hasbeen used during apnea testing. Manycurrent ventilators automaticallychange from a CPAP mode to manda-tory ventilation and deliver a breathwhen apnea is detected. It is also im-portant to note that spontaneous ven-tilation has been falsely reported to oc-cur while patients were maintained onCPAP despite having the trigger sensi-tivity of the mechanical ventilator re-duced to minimum levels.48 Physi-cian(s) performing apnea testingshould continuously monitor the pa-tient’s heart rate, blood pressure, andoxygen saturation while observingfor spontaneous respiratory effortthroughout the entire procedure.PaCO2, measured by blood gas analysis,should be allowed to rise to � 20mm Hg above the baseline PaCO2 leveland � 60 mm Hg. If no respiratory ef-fort is observed from the initiation ofthe apnea test to the time the mea-sured PaCO2 � 60 mm Hg and � 20mm Hg above the baseline level, the ap-nea test is consistent with brain death.The patient should be placed back onmechanical ventilator support andmedical management should continueuntil the second neurologic examina-tion and apnea test confirming braindeath is completed. If oxygen satura-tions fall below 85%, hemodynamic in-

stability limits completion of apneatesting, or a PaCO2 level of� 60 mm Hgcannot be achieved, the infant or childshould be placed back on ventilatorsupport with appropriate treatment torestore normal oxygen saturations,normocarbia, and hemodynamic pa-rameters. In this instance, another at-tempt to test for apnea may be per-formed at a later time or an ancillarystudy may be pursued to assist withdetermination of brain death. Evidenceof any respiratory effort that is incon-sistent with brain death and the apneatest should be terminated and thepatient placed back on ventilatorysupport.

Ancillary Studies(Recommendations 5a–e, Table 1)

The committee recommends that an-cillary studies are not required to es-tablish brain death and should not beviewed as a substitute for the neuro-logic examination. Ancillary studiesmay be used to assist the clinician inmaking the diagnosis of brain death (i)when components of the examinationor apnea testing cannot be completedsafely due to the underlying medicalcondition of the patient; (ii) if there isuncertainty about the results of theneurologic examination; (iii) if a medi-cation effect may be present; or (iv) toreduce the inter-examination observa-tion period. The term “ancillary study”is preferred to “confirmatory study”since these tests assist the clinician inmaking the clinical diagnosis of braindeath. Ancillary studies may also behelpful for social reasons allowingfamily members to better comprehendthe diagnosis of brain death.

Four-vessel cerebral angiography isthe gold standard for determining ab-sence of CBF. This test can be difficultto perform in infants and small chil-dren, may not be readily available at allinstitutions, and requires moving thepatient to the angiography suite poten-

tially increasing risk of exacerbatinghemodynamic and respiratory insta-bility during transport of a critically illchild outside of the intensive care unit.Electroencephalographic documenta-tion of electrocerebral silence (ECS)and use of radionuclide CBF determi-nations to document the absence ofCBF remain the most widely usedmethods to support the clinical diag-nosis of brain death in infants and chil-dren. Radionuclide CBF testingmust beperformed in accordance with guide-lines established by the Society of Nu-clear Medicine and the American Col-lege of Radiology.49,50 EEG testing mustbe performed in accordance with stan-dards established by the AmericanElectroencephalographic Society.51 In-terpretation of ancillary studies re-quires the expertise of appropriatelytrained and qualified individuals whounderstand the limitations of thesestudies to avoid any potentialmisinterpretation.

Similar to the neurologic examination,hemodynamic and temperature pa-rameters should be normalized beforeobtaining EEG or CBF studies. Pharma-cologic agents that could affect the re-sults of testing should be discontinued(Appendix 2) and levels determined asclinically indicated. Low to mid thera-peutic levels of barbiturates shouldnot preclude the use of EEG testing.48

Evidence suggests that radionuclideCBF study can be used in patients withhigh dose barbiturate therapy to dem-onstrate absence of CBF.52,53

Diagnostic Yield of the EEG inSuspected Brain Dead Children

Appendix 4 summarizes EEG data from12 studies in 485 suspected brain deadchildren in all age groups.34,54–65 Thedata show that 76% of all children whowere evaluated with EEG for braindeath on the first EEG had ECS. MultipleEEGs increased the yield to 89%. Forthose children who had ECS on their



first EEG, 64/66 patients (97%) had ECSon a follow-up EEG. The first exceptionwas a neonate who had a phenobarbi-tal level of 30�g/mL when the first EEGwas performed.65 The second excep-tion was a 5 year old head trauma pa-tient who was receiving pentobarbitaland pancuronium at the time of the ini-tial EEG.62 This patient also had a CBFstudy performed demonstrating flow.In retrospect, these two patientswould not havemet currently acceptedstandards for brain death based onpharmacologic interference with EEGtesting. Additionally, of those patientswith EEG activity on the first EEG, 55%had a subsequent EEG that showedECS. The remaining 45% either hadpersistent EEG activity or additionalEEGs were not performed. All died(spontaneously or by withdrawal ofsupport). Only one patient survivedfrom this entire group of 485 patients,a neonate with an elevated phenobar-bital level whose first EEG showed pho-tic response and survived severelyneurologically impaired.

Diagnostic Yield of RadionuclideCBF Studies in Suspected BrainDead Children

Appendix 5 summarizes CBF data from 12studies in 681 suspected brain dead chil-dren in all age groups.36,54,55,57,59,60,63,64–68

Different but well standardized andconventional radionuclide cerebral an-giography methods were used. AbsentCBF was found in 86% of children whowere clinically brain dead and the yielddid not significantly change if morethan one CBF study was done (89%).Appendix 5 also summarizes follow-updata on children whose subsequentCBF study showed no flow. 24/26 pa-tients (92%) had no flow on follow-upCBF studies when the first studyshowed absent flow. The two excep-tions where flow developed later werenewborns. The first newborn had min-imal flow on the second study and ven-tilator support was discontinued. The

other newborn developed flow on thesecond study and had some spontane-ous respirations and activity. A pheno-barbital level two days after the sec-ond CBF study with minimal flow was 8�g/mL.65

In those patients with preserved CBFon the first CBF study, 26% (9/34) had asecond CBF study that showed no flow.The remaining 74% either had pre-served flow or no further CBF studieswere done and all but one patient died(either spontaneously or by with-drawal of support). Only one patientsurvived with severe neurologic im-pairment from this entire group ofpatients—the same neonate as notedpreviously with no CBF on the firststudy but presence of CBF on the sec-ond study.

Diagnostic Yield of the Initial EEGVersus Radionuclide CBF Studies inBrain Dead Children

Appendix 6 summarizes the compara-tive diagnostic yield of EEG versus CBFdeterminations in children who hadboth studies done as part of the initialbrain death evaluation. Data from the12 studies cited in Appendices 4 and 5were stratified by 3 age groups: (i) allchildren (n� 149); (ii) newborns (� 1month of age, n � 30); and (iii) chil-dren age � 1 month to 18 years (n �119).36,54–56,58–68

The data in Appendices 4 and 5 showthat the yield from the initial CBF stud-ies was higher (86%) than from the ini-tial EEG (76%) but no differences werepresent for any CBF study (89%) vs anyEEG study (89%). In contrast the data inAppendix 6 for all children show thatwhen both studies are initially per-formed, the diagnostic yield is thesame (70% had ECS; and 70% showedabsent CBF). The diagnostic yield forchildren greater than 1 month of agewas similar for both tests (EEG withECS, 78%; no CBF, 71%). For newborns,EEG with ECS was less sensitive (40%)

than absence of CBF (63%) when con-firming the diagnosis of brain deathbut even in the CBF group the yield waslow.

In summary, both of these ancillarystudies remain accepted tests to as-sist with determination of brain deathin infants and children. The data sug-gest that EEG and CBF studies are ofsimilar confirmatory value. Radionu-clide CBF techniques are increasinglybeing used inmany institutions replac-ing EEG as an ancillary study to assistwith the determination of brain deathin infants and children.5,69 Other ancil-lary studies such as the TranscranialDoppler study and newer tests such asCT angiography, CT perfusion using ar-terial spin labeling, nasopharyngealsomatosensory evoked potential stud-ies, MRI-MR angiography, and perfu-sion MRI imaging have not been stud-ied sufficiently nor validated in infantsand children and cannot be recom-mended as ancillary studies to assistwith the determination of brain deathin children at this time.

Repeating Ancillary Studies

If the EEG study shows electrical activ-ity or the CBF study shows evidence offlow or cellular uptake, the patientcannot be pronounced dead at thattime. The patient should continue to beobserved and medically treated untilbrain death can be declared solely onclinical examination criteria and ap-nea testing based on recommendedobservation periods, or a follow-up an-cillary study can be performed to as-sist and is consistent with the determi-nation of brain death, or withdrawal oflife-sustaining medical therapies ismade irrespective of meeting criteriafor brain death. A waiting period of 24hours is recommended before furtherancillary testing, using a radionuclideCBF study, is performed allowing ade-quate clearance of Tc-99m.49,50 While noevidence exists for a recommended





waiting period between EEG studies, awaiting period of 24 hours is reason-able and recommended before repeat-ing this ancillary study.

Shortening the Observation Period

If an ancillary study, used in conjunc-tion with the first neurologic examina-tion, supports the diagnosis of braindeath, the inter-examination observa-tion interval can be shortened and thesecond neurologic examination andapnea test (or all components that canbe completed safely) can be per-formed and documented at any timethereafter for children of all ages.

SPECIAL CONSIDERATIONS FORTERM NEWBORNS (37 WEEKSGESTATION) TO 30 DAYS OF AGE(RECOMMENDATIONS 1–5, TABLE 1)

Preterm and term neonates youngerthan 7 days of age were excluded fromthe 1987 Task Force guidelines. Theability to diagnose brain death in new-borns is still viewed with some uncer-tainty primarily due to the small num-ber of brain-dead neonates reported inthe literature54,65,70 and whether thereare intrinsic biological differences inneonatal brain metabolism, blood flowand response to injury. The newbornhas patent sutures and an open fonta-nelle resulting in less dramatic in-creases in intracranial pressure (ICP)after acute brain injury when com-pared with older patients. The cascadeof events associated with increasedICP and reduced cerebral perfusion ul-timately leading to herniation are lesslikely to occur in the neonate.

Clinical Examination

Limited data are available regardingthe clinical examination for braindeath in preterm and term infants.70 Ithas been recognized that examinationof the preterm infant less than 37weeks gestation to determine if theymeet brain death criteria may be diffi-cult because of the possibility that

some of the brainstem reflexes maynot be completely developed and that itis also difficult to assess the level ofconsciousness in a critically ill, se-dated and intubated neonate. Becauseof insufficient data in the literature,recommendations for preterm infantsless than 37 weeks gestational agewere not included in this guideline.However, as discussed in the followingsection on observation periods, theavailable data suggest that recovery ofneurologic function is unlikely when aterm newborn is diagnosed with braindeath. Based on review of the litera-ture, the task force supports that braindeath can be diagnosed in term new-borns (37 weeks gestation) and older,provided the physician is aware of thelimitations of the clinical examinationand ancillary studies in this age group.It is important to carefully and repeat-edly examine term newborns, with par-ticular attention to examination of brain-stem reflexes and apnea testing. As witholder children, assessment of neuro-logic function in the term newborn maybe unreliable immediately following anacute catastrophic neurologic injury orcardiopulmonary arrest. A period of 24hours or longer is recommended beforeevaluating the term newborn for braindeath.

Apnea Testing

Neonatal studies reviewing PaCO2thresholds for apnea are limited. How-ever, data from 35 neonates who wereultimately determined to be braindead revealed a mean PaCO2 of 65mm Hg suggesting that the thresholdof 60 mm Hg is also valid in the new-born.35 Apnea testing in the term new-bornmay be complicated by the follow-ing: (1) Treatment with 100% oxygenmay inhibit the potential recovery ofrespiratory effort.71,72 (2) Profoundbradycardia may precede hypercarbiaand limit this test in neonates. A thor-ough neurologic examination must beperformed in conjunction with the ap-

nea test to make the determination ofdeath in any patient. If the apnea testcannot be completed as previously de-scribed, the examination and apnea testcan be attempted at a later time, or anancillary study may be performed to as-sist with determination of death. Ancil-lary studies in newborns are less sensi-tive than in older children. There are noreported cases of any neonate who de-veloped respiratory effort after meetingbrain death criteria.

Observation Periods in TermNewborns

There is some experience concerningthe duration of observation periods inneonates being evaluated for braindeath. A review of 87 newborns re-vealed that the duration of coma frominsult to brain death was 37 hours andthe duration of time from the initialneurologic examination being indica-tive of brain death to final confirmationwas 75 hours. The overall average du-ration of brain death in these neonateswas about 95 hours or almost 4 days.37

53 neonates less than 7 days of agedonating organs for transplantationhad a total duration of brain death in-cluding time to transplantation that av-eraged 2.8 days; for neonates 1–3weeks of age, the duration of braindeath was approximately 5.2 days.37

None of these patients recovered anyneurologic function. These data sug-gest that once the diagnosis of braindeath ismade in newborns, recovery isunlikely. Based on data extracted fromavailable literature and clinical experi-ence the committee recommends theobservation period between examina-tions should be 24 hours for term new-borns (37 weeks) to 30 days of age.

Ancillary Studies

Ancillary studies performed in thenewborn � 30 days of age are lim-ited.70 As summarized in Appendix 6,ancillary studies in this age group areless sensitive in detecting the pres-



ence/absence of brain electrical activ-ity or cerebral blood flow than in olderchildren. Of the two studies, detectingabsence of CBF (63%) was more sensi-tive than demonstration of ECS (40%)in confirming the diagnosis of braindeath, however even in the CBF studygroup the sensitivity was low.70

EEG activity is of low voltage in new-borns raising concerns about agreater chance of having reversibleECS in this age group. In a retrospec-tive review of 40 newborns with ECS,9/10 with ECS on the initial EEG showedECS on repeated studies.70 The remain-ing patient had a phenobarbital level of30 �g/mL at the time of the initial EEG,probably accounting for the initial ECS.Several other cases have been re-ported with initial ECS but careful re-view found that the patients were notclinically brain dead. Based on avail-able data it is likely that if the initialEEG shows ECS (assuming an absenceof correctable conditions) in a new-born who meets all clinical criteria forbrain death, then it is an accurate andreliable predictor of brain death andrepeat EEG studies are not indicated.

CBF in viable newborns can be ex-tremely low because of the decreasedlevel of brain metabolic activity.50 How-ever earlier studies using stable xenoncomputed tomography measurementsof CBF have shown that the level of CBFin brain dead children is much lowerthan that seen in viable newborns.73,74

The available data suggest that ancil-lary studies in newborns are less sen-sitive than in older children. This canpose an important clinical dilemma inthis age group where clinicians mayhave a greater level of uncertaintyabout performing a valid neurologicexamination. There is a greater need tohave more reliable and accurate ancil-lary studies in this age group. Aware-ness of this limitation would suggestthat longer periods of observation andrepeated neurologic examinations are

needed beforemaking the diagnosis ofbrain death and also that as in olderinfants and children, the diagnosisshould bemade clinically and based onrepeated examinations rather than re-lying exclusively on ancillary studies.

DECLARATION OF DEATH (FOR ALLAGE GROUPS)(RECOMMENDATIONS 6a–c, TABLE1 AND APPENDIX 8 ALGORITHM)

Death is declared after the secondneurologic examination and apneatest confirms an unchanged and irre-versible condition. An algorithm (Ap-pendix 8) provides recommendationsfor the process of diagnosing braindeath in children. When ancillary stud-ies are used, documentation of compo-nents from the second clinical exami-nation that can be completed,including a second apnea test, mustremain consistent with brain death. Allaspects of the clinical examination, in-cluding the apnea test, or ancillarystudies must be appropriately docu-mented. A checklist outlining essentialexamination and testing componentsis provided in Appendix 1. This check-list also provides standardized docu-mentation to determine brain death.

ADDITIONAL CONSIDERATIONS(FOR ALL AGE GROUPS)

In today’s modern pediatric and neo-natal intensive care units, critical carepractitioners and other physicianswith expertise in neurologic injury areroutinely called on to declare death ininfants and children. Because the im-plications of diagnosing brain deathare of great consequence, examinationshould be conducted by experiencedclinicians who are familiar with neo-nates, infants and children and havespecific training in neurocritical care.These physicians must be competentto perform the clinical examinationand interpret results from ancillarystudies. Qualified clinicians include:pediatric intensivists and neonatolo-

gists, pediatric neurologists and neu-rosurgeons, pediatric trauma sur-geons, and pediatric anesthesiologistswith critical care training. Adult special-ists should have appropriate neurologicand critical care training to diagnosebrain death when caring for the pediat-ric patient from birth to 18 years of age.Residents and fellows should be encour-aged to learn how to properly performbrain death testing by observing andparticipating in the clinical examinationand testing process performed by expe-rienced attending physicians. It is rec-ommended that both neurologic exami-nations be performed and documentedby an attending physician who is quali-fied and competent to perform the braindeath examination.

These revisedpediatricbraindeathdiag-nostic guidelinesare intended toprovidean updated framework in an effort topromote standardization of the neuro-logic examination and use of ancillarystudies. A standardized checklist (Ap-pendix 1)will help to ensure that all com-ponents of the examination, and ancil-lary studies if needed, are completedand documented appropriately. Pediat-ric specialists shouldbe invited topartic-ipate in the development of institutionalguidelines to ensure that the brain deathexamination is conducted consistentlyeach time the diagnosis is being consid-ered. A comparison of the 1987 pediatricbrain death guidelines and 2011 updatefor neonatal and pediatric brain deathguidelines are listed in Appendix 7.

Diagnosing brain death must never berushed or take priority over the needsof the patient or the family. Physiciansare obligated to provide support andguidance for families as they face dif-ficult end-of-life decisions and attemptto understand what has happened totheir child. It is the responsibility of thephysician to guide and direct familiesduring the treatment of their child.Communication with families must beclear and concise using simple termi-





nology so that parents and familymembers understand that their childhas died. Permitting families to be pres-ent during the brain death examination,apnea testing and performance of ancil-lary studies can assist families in under-standing that their child has died. Thefamily must understand that once braindeath has been declared, their childmeets legal criteria for death. Familiesmay otherwise become confused or an-gry if discussions regarding withdrawalof support or medical therapies are en-tertained after declaration of death. Itshould be made clear that once deathhas occurred, continuation of medicaltherapies, including ventilator support,is no longer an option unless organ do-nation is planned. Appropriate emo-tional support for the family should beprovided including adequate time togrieve with their child after death hasoccurred. Consultation or referral to themedical examiner or coronermay be re-quired by state law in certain situationswhen death occurs.

FUTURE DIRECTIONS

Development of a national database totrack infants and children who are di-agnosed as brain dead should bestrongly considered. Information com-piled from this database would in-crease our knowledge about braindeath, especially in neonates.

1. Studies comparing traditional ancil-lary studies to newer methods to as-sess CBF and neurophysiologic func-tion should be pursued. Furtherinformation about ancillary studies,waiting periods, and research re-garding validity of newer ancillarystudies is needed for future recom-mendations to assist with determina-tion of brain death in children.

2. Cerebral protective therapies suchas hypothermia may alter the natu-ral progression of brain death andtheir impact should be reviewed asmore information becomes avail-

able. The clinician caring for criti-cally ill infants and children shouldbe aware of the potential impact ofnew therapeutic modalities on thediagnosis of brain death.

3. While each institution and state mayhave specific guidelines for the deter-mination of brain death in infants andchildren, we should work with na-tional medical societies to achieve auniform approach to declaring deaththat can be incorporated in all hospi-tal policies.75 This will help eliminateconfusion among medical personnelthereby fostering further trust fromthe community of patients and fami-lies that we serve.

4. Additional information or studiesare required to determine if a sin-gle neurologic examination is suffi-cient for neonates, infants, and chil-dren to determine brain death ascurrently recommended for adultsover 18 years of age.12,76

ENDORSEMENTS AND APPROVALS

This document has been reviewed andendorsed by the following societies:

American Academy of Pediatrics

Sub sections:

Section on Critical Care

Section on Neurology

American Association of Critical CareNurses

Child Neurology Society

National Association of Pediatric NursePractitioners

Society of Critical Care Medicine

Society for Pediatric Anesthesia

Society of Pediatric Neuroradiology

World Federation of Pediatric Intensiveand Critical Care Societies

American Academy of Neurologyaffirms the value of this manuscript.

The following societies have had theopportunity to review and comment onthis document

American Academy of Pediatrics

Sub sections:

Committee on Bioethics

Committee on Child Abuse and Neglect

Committee on Federal Government Affairs

Committee on Fetus and Newborn

Committee on Hospital Care

Committee on Medical Liability andRisk Management

Committee on Pediatric EmergencyMedicine

Committee on Practice and Ambula-tory Medicine

Committee on State Government Affairs

Council on Children With Disabilities

Section on Anesthesiology and PainMedicine

Section on Bioethics

Section on Child Abuse and Neglect

Section on Critical Care

Section on Emergency Medicine

Section on Hospital Medicine

Section on Neurology

Section on Perinatal Pediatrics

Section on Neurological Surgery

Section on Pediatric Surgery

The Pediatric Section of the AmericanAssociation of Neurosurgeons and theCongress of Neurologic Surgeons havebeen provided the opportunity to re-view this document

ACKNOWLEDGMENTSSCCM staff support:

Laura Kolinski. SCCM.Mount Prospect, Ill

Lynn Retford. SCCM.Mount Prospect, Ill

SCCM Board of Regents:

M. Michele Moss, MD, FCCM

Tim Yeh, MD, FCCM

SCCM Facilitator:

Lorry Frankel, MD, FCCM

Roman Jaeschke, MD, for his directionin the GRADE evaluation process.



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APPENDIX 1 Check List for Documentation of Brain Death





APPENDIX 2 Medications Administered to Critically Ill Pediatric Patients and Recommendations for Time Interval to Testing After Discontinuation

Medication Infants/ChildrenElimination 1⁄2 life

NeonatesElimination 1⁄2 life

Intravenous induction, anesthetic, andsedative agentsThiopental Adults: 3–11.5 hours (shorter 1⁄2 life in children)Ketamine 2.5 hoursEtomidate 2.6–3.5 hoursMidazolam 2.9–4.5 hours 4–12 hours77-80

Propofol 2–8 minutes, Terminal 1⁄2 life 200 minutes (range 300–700 minutes)Dexmedetomidine Terminal 1⁄2 life 83–159 minutes79-81 Infants have faster clearance81-83

Antiepileptic drugsPhenobarbital Infants: 20–133 hours* 45–500 hours*79,84,85

Children: 37–73 hours*Pentobarbital 25 hours*Phenytoin 11–55 hours* 63–88 hours*Diazepam 1 month–2 years: 40–50 hours 50–95 hours79,86,87

2 years–12 years: 15–21 hours12–16 years: 18–20 hours

Lorazepam Infants: 40.2 hours (range 18–73 hours) 40 hours86

Children: 10.5 hours (range 6–17 hours)Clonazepam 22–33 hoursValproic Acid Children� 2 months: 7–13 hours* 10–67 hours*

Children 2–14 years: Mean 9 hours; range 3.5–20 hoursLevetiracetam Children 4–12 years: 5 hoursIntravenous narcoticsMorphine sulfate Infants 1–3 months: 6.2 hours (5–10 hours) 7.6 hours (range 4.5–13.3 hours)79,89-91

6 months–2.5 years: 2.9 hours (1.4–7.8 hours)Children: 1–2 hours

Meperidine Infants� 3 months: 8.2–10.7 hours (range 4.9–31.7 hours) 23 hours (range 12–39 hours)Infants 3–18 months: 2.3 hoursChildren 5–8 years: 3 hours

Fentanyl 5 months–4.5 years: 2.4 hours (mean) 0.5–14 years: 21 hours(range 11–36 hours for long term infusions)

1–15 hours

Sufentanil Children 2–8 years: 97� 42 minutes 382–1162 minutesMuscle relaxantsSuccinylcholine 5–10 minutes

Prolonged duration of action in patients withpseudocholinesterase deficiency or mutation

Pancuronium 110 minutesVecuronium 41 minutes 65 minutesAtracurium 17 minutes 20 minutesRocuronium 3–12 months: 1.3� 0.5 hours

1 to� 3 years: 1.1� 0.7 hours3 to� 8 years: 0.8� 0.3 hoursAdults: 1.4–2.4 hours

Modified from Ashwal and Schneider.57

Metabolism of pharmacologic agents may be affected by organ dysfunction and hypothermia.Physicians should be aware of total amounts of administered medication that can affect drug metabolism and levels.* Elimination 1⁄2 life does not guarantee therapeutic drug levels for longer acting medications or medications with active metabolites. Drug levels should be obtained to ensure that levels arein a low to mid therapeutic range prior to neurologic examination to determine brain death. In some instances this may require waiting several half-lives and rechecking serum levels of themedication before conducting the brain death examination.



APPENDIX 3 Apnea Testing in Pediatric Brain Death

Author n Age Range PaCO2 Comments

Rowland (1984)41 9 children, 16 apneatests performed

4 months–13 years Range: 60–116 mm Hg after 15minutes of apnea

No spontaneous respiratory effort noted in anypatient during testing. Phenobarbital levels of10,11.6,18,25 mg/dL were measured in 4 patients,

Outwater & Rockoff(1984)40

10 children 10 months–13years

Mean 59.5� 10.2 mm Hg after 5minutes of apnea

No spontaneous respiratory effort noted in anypatient during testing or after support waswithdrawn

Riviello (1988)39 19 children 2 months–15 years Mean 63.9� 21.5 mm Hg 2 children with PCO2 levels of 24 mm Hg and 38mm Hg had spontaneous respirations duringthe apnea test. All other children had nospontaneous respiratory effort noted aftersupport was withdrawn.

Paret (1995)42 38 children, 61 apneatests performed

2 months–17 years Mean 68.07� 17.66 after 5 minutes 1 child had spontaneous respiratory effort with aPaCO2 of 49 mm Hg. This patient was retested24 hours later and had no respiratory effort.

Mean 81.8� 20.2 after 10 minutesMean 86.88� 25.6 after 15 minutes

APPENDIX 4 EEG in Pediatric Brain Death: Diagnostic Yield From First Versus Any Study

Study Total # Ptsin Study

% Patients With ECSon EEG#1

% Patients With ECSon Any EEG

% Pts With ECS on f/u EEGWhen First EEG Had ECS

% Pt With ECS on Later EEGsWhen First EEG Had Activity

Ruiz-Garcia et al, 2000 (60) 125 72% (88/122) 91% (111/122) NA 68% (23/34)Drake et al, 198655 61 70% (33/47) 91% (43/47) 100% (17/17) 71% (10/14)Parker et al, 199536 60 100% (9/9) 100% (9/9) NA NAAlvarez et al, 198856 52 100% (52/52) 100% (52/52) 100% (28/28) NAAshwal, 199354 52 85% (28/33) 85% (28/33) 100% (3/3) 0% (0/1)Ruiz-Lopez et al, 199961 51 48% (14/29) 72% (21/29) NA 47% (7/15)Ashwal & Schneider, 198965 18 50% (9/18) 78% (14/18) 88% (7/8) 56% (5/9)Holzman et al, 198362 18 61% (11/18) 67% (12/18) 67% (2/3) 14% (1/7)Ashwal et al, 197758 15 67% (10/15) 73% (11/15) 100% (2/2) 20% (1/5)Coker et al, 198659 14 100% (11/11) 100% (11/11) 100% (5/5) NAFurgiuele et al, 198463 11 100% (10/10) 100% (10/10) NA NAOkuyaz et al, 200464 8 100% (8/8) 100% (8/8) NA NATotal 485 76% (283/372) 89% (330/372) 97% (64/66) 55% (47/85)

EEG Electroencephalogram.ECS Electrocerebral silence.

APPENDIX 5 CBF in Pediatric Brain Death: Diagnostic Yield From First Versus Any Study

Study Total # ofPts inStudy

CBF#1: % PatientsWith Absent CBF*

% Patients With AbsentCBF on Any Study**

% Pts With No CBF on f/uStudy When First StudyHad Shown No CBF

% Pt With No CBF on LaterStudy When First StudyHad CBF Present

Shimizu et al, 200066 228 100% (27/27) 100% (27/27) NA NARuiz-Garcia et al, 200060 125 92% (83/90) 92% (83/90) NA NADrake et al, 198655 61 68% (32/47) 81% (38/47) 100% (17/17) 40% (6/15)Parker et al, 199536 60 87% (26/30) 87% (26/30) NA NACoker et al, 198659 55 100% (55/55) 100% (55/55) NA NAAshwal, 199354 52 86% (19/22) 86% (19/22) NA NAAhmann et al, 198767 32 83% (6/6) 83% (6/6) NA NAAshwal &Schneider, 198965 18 65% (11/17) 65% (11/17) 71% (5/7) 0% (0/3)Holzman et al, 198362 18 39% (7/18) 44% (8/18) 100% (2/2) 9% (1/11)Ashwal et al, 197758 15 100% (11/11) 100% (11/11) NA NASchwartz et al, 198468 9 100% (9/9) 100% (9/9) NA NAOkuyaz et al, 200464 8 75% (6/8) 100% (8/8) NA 100% (2/2)Total 681 86% (292/340) 89% (301/340) 92% (24/26) 26% (9/34)* # pts with no CBF on first study/# pts with first CBF study.** # pts with no CBF on any study/# pts with any CBF.CBF Cerebral blood flow.





APPENDIX 6 EEG and CBF Diagnostic Screening Yield by Age Groups

ECS EEG� Total Diagnostic Screening Yield

All children (n� 149)*No CBF 86 18 104 % pt with ECS� 70%CBF� 19 26 45 % pts with no CBF� 70%Total 105 44 149Just newborns (� 1 month of age; n� 30)**No CBF 8 11 19 % pt with ECS� 40%CBF� 4 7 11 % pts with no CBF� 63%Total 12 18 30Children (� 1 month of age; n� 119)***No CBF 78 7 85 % pt with ECS� 78%CBF� 15 19 34 % pts with no CBF� 71%Total 93 26 119

* Data extracted from references cited in Appendix 4,5.** Data extracted from references cited in Ashwal S.35*** Data represent the differences between “All children” and “just newborns” groups.ECS Electrocerebral silence.CBF Cerebral blood flow.EEG� Activity on EEG.CBF� Cerebral blood flow present.

APPENDIX 7 Comparison of 1987 Pediatric Brain Death Guidelines and the Updated Guideline for Determination of Brain Death in Infants and Children

1987 Updated Guidelines

Waiting period before initial braindeath examination

Not specified 24 hours following cardiopulmonary resuscitation or severeacute brain injury is suggested if there are concernsabout the neurologic examination or if dictated by clinicaljudgment

Clinical examination Required RequiredCore body temperature Not specified � 35°C (95°F)Number of examinations Two exams Two exams, irrespective of ancillary study results

2nd examination not necessary in 2 months–1year age group if initial examination, EEG andconcomitant CBF consistent with brain death

(if ancillary testing is being done in lieu of initialexamination elements that cannot be safely performed,the components of the second examination that can bedone must be completed)

Number of examiners Not specified Two (Different attending physicians must perform the firstand second exam)

Observation interval betweenneurologic examinations

Age dependent Age Dependent

● 7 days–2 months: 48 hours ● Term newborn (37 weeks gestation) to 30 days of age: 24hours

● 2 months–1 year: 24 hours ● 31 days–18 years: 12 hours● �1 year: 12 hours (24 hrs if HIE)

Reduction of observation periodbetween exams

Permitted only for� 1 year age group if EEG orCBF consistent with brain death

Permitted for both age groups if EEG or CBF consistent withbrain death

Apnea testing Required, number of tests ambiguous Two apnea tests required unless clinically contraindicatedFinal PCO2 threshold for apnea testing Not specified �60 mm Hg and�20 mm Hg above the baseline PaCO2Ancillary study recommended ● Age dependent 7 days–2 months: 2 EEGs

separated by 48 hrsNot required except in cases where the clinical examinationand apnea test cannot be completed

● 2 months–1 year: 2 EEG’s separated by 24hours. CBF can replace the need for 2nd EEG

● Term newborn (37 weeks gestation) to 30 days of age:EEG or CBF are less sensitive in this age group. CBF maybe preferred.

● �1 year: No testing required ● �30 days–18 years: EEG and CBF have equal sensitivityTime of death Not specified Time of the second examination and apnea test (or

completion of ancillary study and the components of thesecond examination that can be safely completed)

EEG Electroencephalogram.CBF Cerebral blood flow.HIE Hypoxic ischemic encephalopathy.



APPENDIX 8 Algorithm to Diagnose Brain Death in Infants and Children





APPENDIX 9 Taskforce Organization

Sub-Committee ChairsBrain death examination criteria and testing intervals: Mudit Mathur, MD, FAAP, Mohan Mysore, MD, FAAP, FCCM, Thomas A. Nakagawa, MD, FAAP, FCCMAncillary testing: Stephen Ashwal, MD, FAAPDeclaration of death, legal, and ethical implications: Jacqueline A. Williams-Phillips, MD, FCCMTaskforce Committee MembersStephen Ashwal, MD. Professor of Pediatrics. Department of Pediatrics, Chief, Division of Child Neurology. Loma Linda University School of Medicine. LomaLinda, CADerek Bruce, MD Professor of Neurosurgery and Pediatrics. Children’s National Medical Center, Washington, DCEdward E. Conway Jr MD, MS, FCCM. Professor of Pediatrics. Beth Israel Medical Center, Hartsdale, NYSusan E Duthie, MD Pediatric Critical Care. Rady Children’s Hospital-San Diego, San Diego, CAShannon Hamrick, MD Assistant Professor of Pediatrics. Emory University, Children’s Healthcare of Atlanta. Atlanta GARick Harrison, MD Professor of Pediatrics. David Geffen School of Medicine UCLA. Medical Director Mattel Children’s Hospital UCLA. Los Angeles, CAAndrea M. Kline, RN, MS, FCCM Nurse Practitioner. Riley Hospital for Children. Indianapolis, INDaniel J. Lebovitz, MD Associate Professor of Pediatrics. Cleveland Clinic Lerner College of Medicine. Cleveland Clinic Children’s Hospital, Cleveland, OHMaureen A. Madden, MSN, PCCNP, FCCM Assistant Professor of Pediatrics. Robert Wood Johnson Medical School. Pediatric Critical Care Nurse Practitioner.Bristol-Myers Squibb Children’s Hospital. New Brunswick, NJMudit Mathur, MD, FAAP Associate Professor of Pediatrics. Division of Pediatric Critical Care. Loma Linda University School of Medicine. Loma Linda, CAVicki L. Montgomery, MD, FCCM Professor of Pediatrics. University of Louisville. Chief, Division of Pediatric Critical Care Medicine. Medical Director. PatientSafety Officer. Norton Healthcare Kosair Children’s Hospital. Louisville, KYMohan R. Mysore, MD, FAAP, FCCM Professor of Pediatrics, University of Nebraska College of Medicine. Director Pediatric Critical Care. Children’s Hospital andMedical Center. Omaha, NEThomas A. Nakagawa, MD, FAAP, FCCM Professor Anesthesiology and Pediatrics. Wake Forest University School of Medicine. Director, Pediatric Critical Care.Brenner Children’s Hospital at Wake Forest University Baptist Medical Center. Winston-Salem, NCJeffrey M. Perlman, MBChB, FAAP, Professor of Pediatrics. Weill Cornell Medical College. New York, NYNancy Rollins, MD Professor of Pediatrics and Radiology. Children’s Medical Center. Southwestern University, Dallas, TexasSam D. Shemie, MD, FAAP, Professor of Pediatrics. Montreal Children’s Hospital. Montreal, CanadaAmit Vohra, MD FAAP Assistant Professor of Pediatrics, Wright State University, Pediatric Critical Care, Children’s Medical Center. Dayton, OH.Jacqueline A. Williams-Phillips, MD, FAAP, FCCM Associate Professor of Pediatrics. UMDNJ-Robert Wood Johnson Medical School. Director, Pediatric IntensiveCare Unit. Bristol-Myers Squibb Children’s Hospital. New Brunswick, NJ



DOI: 10.1542/peds.2011-1511; originally published online August 28, 2011; 2011;128;e720Pediatrics

Neurology of the American Academy of Pediatrics, and the Child Neurology Societythe Society of Critical Care Medicine, Section on Critical Care and Section on

Update of the 1987 Task Force RecommendationsGuidelines for the Determination of Brain Death in Infants and Children: An

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Brain Death Guideline 2011

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