Introduction

 

The diagnosis of Brain Death in children is generally regarded as being more difficult than in adults and there is considerable variation in the exact protocol followed in different countries, and even between different states in the same country. Nevertheless, the diagnostic procedure is essentially by clinical examination.

 

The following guidelines are based on multiple sources, including the American Academy of Pediatrics Guidelines for the determination of brain death in children ^{1, 4}, the American Academy of Neurology evidence based guideline update 2010 ² and the Australian and New Zealand Intensive Care Society statement on death and organ donation, 2008 ³.

 

Definition

 

Brain death is defined as irreversible cessation of all functions of the entire brain, including the brain stem

 

Pre-requisites

 

The following conditions must be met before brain death can be determined:

 

1. There must be a recognized cause of coma sufficient to explain the irreversible cessation of all brain function. Both coma and apnea must coexist to declare brain death.
2. Potentially reversible causes of coma must be excluded
   1. Hypothermia – core body temperature must be > 35^o C, since severely hypothermic patients may appear brain dead
   2. Uncontrolled hypotension – the blood pressure must be normal for age (systolic BP not < 2 SD below norm for age)
   3. Sedatives and other CNS depressant drugs / toxins – sufficient time must be allowed for any CNS depressant agents to be metabolized. If this cannot be assured, a drug level may be obtained, if possible, to show that the drug in question does not exceed the normal therapeutic levels.
   4. If neuromuscular blocking agents have been administered, a peripheral nerve stimulator should be used to show that there is no residual neuromuscular blockade
   5. Severe metabolic derangements must be excluded, including markedly abnormal plasma concentrations of glucose, sodium, potassium, phosphate, magnesium, calcium
   6. Any other sign that suggests a potentially reversible cause of coma
3. Neurological assessment may be unreliable immediately following cardiopulmonary resuscitation or acute brain injury – brain death evaluation should be deferred by 24 hours in these circumstances.

 

Clinical Examination

 

The diagnosis of brain death is essentially clinical.

There must be absence of higher brain function – lack of consciousness

There must be absence of brain stem functions

 

 

Clinical testing	Test procedure and response	Comments
Coma	Apply noxious stimuli in the cranial nerve distribution and all four limbs and trunk. There should be no motor response	See note below
Pupillary light reflex-cranial nerves II & III	Shine a bright light into each eye and look for pupillary constriction. There should be no pupillary constriction	Pupils must be ≥ 4 mm in diameter. A magnifying glass may be used, if required. Use of anti-cholinergic drugs, such as Atropine, can cause pupillary dilatation
Corneal reflex – cranial nerves V & VII	Touch the corneas with soft cotton wool. There should be no blinking or withdrawal reflex	Touch only the lateral aspect of the cornea to avoid damage
Absence of movement of the bulbar musculature – cranial nerves V & VII	Apply deep pressure over the condyles at the temporo-mandibular joints and over the supra-orbital ridges. There should be no grimacing or facial muscle movement
Oculo-vestibular reflex – cranial nerves III, IV, VI & VIII	Inspect the external auditory meatus with an otoscope to make sure that the ear drum is visible and intact – if required, clean any cerumen before proceeding. Elevate head to 30o and place in the neutral position. Instill 20 – 50 ml of iced water into the ear canal with a syringe. Hold both eyes open and observe for at least 1 minute. There should be no response – both eyes should remain in the mid-position. Wait 5 minutes and repeat test in the other ear	Fracture of the skull base or petrous temporal may obliterate the response on the side of the fracture.
Gag reflex – cranial nerves IX & X	Stimulate the posterior pharyngeal wall on both sides with a tongue depressor. There should be no gag response	May be difficult to examine in orally intubated patients
Cough reflex – cranial nerve X	Stimulate the trachea with a suction catheter. There should be no cough
Flaccidity	Evaluate all extremities by passive range of motion (unless contra-indicated). There should be flaccid tone and no spontaneous or induced movements	See note below

 

NOTE

Observations that are compatible with brain death

 

The following observations can be present in brain death

 

• Spinal reflexes in response to stimulation
  • These may include movements of the upper limbs, deep tendon reflexes, plantar reflexes, respiratory like movements and head turning
• Sweating, blushing or tachycardia
• Normal blood pressure without pharmacological support
• Absence of diabetes insipidus

 

Observations that are incompatible with brain death

 

The following observations are incompatible with brain death:

 

• Decerebrate or decorticate posturing
• True extensor or flexor responses to painful stimuli
• Seizures

 

Number of tests and who should perform them

 

Two examinations (including two apnea tests) should be performed, separated by an interval.  A different Consultant Physician who is taking care of the child should perform each clinical examination. These physicians should have specific expertise and experience in performing such assessment and can include Pediatric Intensivists, Neurologists, Anesthetists, Neurosurgeons or Pediatricians. The same individual may perform the apnea tests. In case the testing is being performed for the purposes of organ harvesting, additional requirements from the individual State Governments may apply (such as pre-registration and authorization of the physician performing the tests).

 

Demonstration of apnea

 

The role of the apnea test has been questioned recently⁵. Nevertheless, it continues to be a part of the Brain Death testing protocol in most countries at this time. The apnea test must be performed twice (as part of each clinical exam), but may be performed by the same individual – preferably the physician who is managing the patient’s ventilator. The following section describes how to perform the apnea test.

 

The same pre-requisites apply as for performing the clinical tests – i.e. the patient should not be hypothermic, hypotensive or have a serious metabolic or endocrine disturbance. Additional contraindications include a high cervical spinal cord injury or very high oxygen / ventilatory requirements that will result in the inability to disconnect safely from the ventilator. If the apnea tests cannot be performed safely, then an ancillary test must be performed to determine brain death.

 

1. Pre-oxygenate the patient for 5 minutes with 100% oxygen.
2. The physician involved in certifying brain death should be physically present at the bedside during the test to attest to the presence of apnea.
3. Manipulate the ventilator to allow the PaCO₂ to rise to > 40 mm Hg – this baseline arterial CO₂ should be confirmed by blood gas analysis or end tidal CO₂
4. Monitor the patient during the test (ECG, blood pressure and SpO₂) and stop the test if there is significant hypotension, desaturation or cardiac arrhythmia
5. Disconnect the patient from the mechanical ventilator and insert an appropriately sized oxygen catheter into the endotracheal tube. Adjust the oxygen flow to deliver 100% oxygen at a flow rate between 2 – 6 L/min. Use only the minimum flow required to maintain adequate oxygen saturation. A T-piece or CPAP circuit can also be used to supply oxygen to the patient when disconnected from the ventilator.
6. After a period of apnea of between 5 – 10 minutes (depending on the PaCO₂ at the beginning of the test), perform an arterial blood gas. The PaCO₂ on the ABG should be ≥ 60 mm Hg and ≥ 20 mm Hg more than the baseline level. If the PaCO₂ does not meet these parameters, the test may be continued and the ABG repeated after 5 minutes, provided the patient continues to be stable.
7. Observe the patient continuously for the presence of any respiratory efforts. If any respiratory efforts are noted, abandon the test immediately. If there is complete apnea, note the duration of apnea and the PaCO₂ at the end of the test.
8. Reconnect the patient to the mechanical ventilator.

 

Response: In a brain dead patient, no respiratory efforts should be seen during the period of apnea.

 

ANCILLARY TESTS

Ancillary tests are not routinely required to determine brain death and are not a substitute for the clinical examination. However, they may be used in specific situations:

 

1. When the apnea test cannot be performed safely
2. If there is uncertainty regarding the results of the neurological examination
3. If a medication may be present that would preclude declaration of brain death
4. In order to reduce the waiting period between the two sets of tests

 

A number of ancillary tests are available.

 

EEG

A digital EEG should be performed by a technician who has experience in performing EEG’s for the purposes of determining brain death. In general, the sensitivity should be increased to 2 μV, the high frequency filter should be set above 30 Hz and the low frequency filter set not above 1 Hz. A minimum of eight scalp electrodes should be used. The EEG should demonstrate a lack of reactivity to intense somatosensory and audiovisual stimulation.

 

TESTS TO ASSESS INTRACRANIAL BLOOD FLOW

 

The purpose of these tests is to show that there is no flow in the intracerebral vessels, due to occlusion of the vasculature by cerebral edema. The various techniques by which intracranial blood flow can be assessed include four vessel cerebral angiography, Radionuclide imaging, CT angiography, Magnetic Resonance angiography and Trans Cranial Doppler ultrasonography. Of these techniques, four-vessel cerebral angiography is regarded as the gold standard and involves direct injection of contrast medium into both Carotid arteries and both Vertebral arteries.

 

Of all the confirmatory tests mentioned above, EEG is the most easily available test. Radionuclide cerebral blood flow assessment is also acceptable – the remainder are time consuming, not easily available, not always standardized, may require shifting an unstable patient and, in some cases, expensive. 

 

Any one of the following tests may be used (depending on availability) when an ancillary test is required:

1. EEG
2. Radionuclide cerebral blood flow assessment
3. Four vessel cerebral angiography.

 

TIME COURSE OF TESTS FOR BRAIN DEATH

 

• The clinical tests are performed twice, each time by a different physician
• The apnea test is performed twice – may be performed by the same physician
• Death is declared when the second neurological examination and apnea test confirm that the results of the first tests are unchanged and the changes are irreversible
• If an ancillary test performed after the first clinical examination/apnea test is consistent with brain death, then the second clinical examination / apnea test can be performed at any time

 

Table 1 below gives the time gap between the clinical tests.

 

Age	Clinical tests	Interval between tests	Ancillary tests
Term new born (> 37 weeks gestational age to 30 days	As adult	24 hrs	If required
31 days – 18 years	As adult	12 hrs	If required

Transplantation of Human Organs & Tissues Rules  2014  on Pediatric Brain Death and Apnea Test

The Indian law has the following in the Form no 10 for Brain Death  Certificate –

The minimum time interval between first and second testing will be six hours in adults. In case of children 6 to 12 years of age, 1 to 5 years of age and infants, the time interval shall INCREASE depending on the opinion of the above Brain Stem Death experts.  

Authors:

Dr. Bala  Ramachandran, Consultant and Head of the Department of Intensive Care & Emergency Medicine, Kanchi Kamakoti CHILDS Trust Hospital, Chennai [email protected]

 

Dr. Krishan Chugh, Head of the Department of Paediatrics, Sir Gangaram Hospital, Delhi [email protected]

 

Dr. Sunit Singhi, Head of the Department of Paediatrics, Post Graduate Institute for Medical Education and Research, Chandigarh [email protected]

 

Dr. Praveen Khilnani, Consultant Pediatric Intensivist, BL Kapur Hospital, New Delhi [email protected]

 

Dr. V. Viswanathan, Consultant Pediatric Neurologist, Kanchi Kamakoti CHILDS Trust Hospital, Chennai [email protected]

 

Dr. Joseph Mathew, Consultant Neurosurgeon, Christian Medical College, Vellore, TN [email protected]

 

Dr. Soonu Udani, Consultant Pediatric Intensivist, Hinduja Hospital, Mumbai [email protected]

 

Project Coordinated by

Dr.Sunil Shroff, MOHAN Foundation

www.mohanfoundation.org

[email protected]

 

Correspondence to:

 

Dr. Bala Ramachandran

PICU

Kanchi Kamakoti CHILDS Trust Hospital

12A Nageswara Road

Nungambakkam

Chennai – 600 034

REFERENCES

1. American Academy of Pediatrics, Task Force on Brain Death in Children. Report of Special Task Force: guidelines for determination of brain death in children. Pediatrics. 1987;80(2):298–300
2. Eelco F.M. Wijdicks, Panayiotis N. Varelas, Gary S. Gronseth, et al. Evidence-based guideline update: Determining brain death in adults : Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74;1911
3. Australian and New Zealand Intensive Care Society. The ANZICS Statement on Death and Organ Donation (3rd Edition). Melbourne: ANZICS, 2008
4. Nakagawa TA et al. Guidelines for the determination of brain death in infants and children: An update of the 1987 Task Force recommendations. Crit Care Med 2011; 39:2139-2155
5. Tibballs J. A critique of the apneic oxygenation test for the diagnosis of “brain death”. Ped Crit Care Med. 2010 Jul;11(4):475-8