Brain-Stem Death

Article Author:
Sunil Munakomi
Article Editor:
Yasir Al Khalili
12/13/2019 7:46:33 AM
PubMed Link:
Brain-Stem Death


Mollart and Goulon first coined the term  'coma depasse,' meaning a state beyond coma, for the brain death).[1]  The Conference of Royal Medical Colleges in 1976  came to the consensus that the brain stem death constitutes brain death. The revised memorandum in 1979 correlated the brain stem death with death itself.[1]  The American Academy of Neurology (AAN) has postulated  brain death as a “coma, absence of brainstem reflexes, and apnea.”[2] Academy of Medical Royal Colleges Working Party has defined brain stem death as 'The irreversible loss of the capacity for gaining consciousness, and the capacity to spontaneously breathe.'

Persistent vegetative state- loss of only cortical functions with intact brain stem functions

Brain-stem death- absent brain stem reflexes but the presence of few cortical as well as hypothalamic integrity such as osmoregulation

Whole Brain death- biological death with absent cortical and brainstem functions

Death- Whole-brain death along with the cardiopulmonary arrest


The following brainstem reflexes should be carried out for evaluating the clinical integrity of brain stem, [2][3][4]:

  • The corneal (blinking of eyelids after touching the cornea with a cotton wisp or small jet of water) and the pupillary light reflex (brisk constriction of the pupils after exposure a bright light in a room with a dimmed light). However,  precautions are necessary to rule out any previous eye surgeries, concurrent cataract, and use of drugs such as atropine.
  • Oculocephalic reflex (turning of the eyes to the opposite side of the head movement following the sudden turning of the head from the mid position to both sides after ruling out cervical cord injuries) and oculovestibular reflex (no eye movements after 50 ml of ice-cold water is instilled into the external auditory meatus over one minute after assuring patency of the tympanic membrane)
  • Gag reflex (gag or pharyngeal contraction after stimulating the pharynx with a spatula or tongue depressor) or cough reflex (cough after stimulation of the carina by bronchial catheter)
  • Response to noxious stimuli along with the distribution of cranial nerves (facial grimaces after pain in the supraorbital ridge supplied by the trigeminal nerve).  

 However, following confounding factors that can impede upon correct evaluation of the brainstem function must first be ruled out[2]:

  • No concurrent use of CNS depressant drugs or neuromuscular blocking agents (must wait five times the drug half-life)
  • Normal core body temperature 
  • Normal systolic blood pressure 
  • No severe electrolyte, acid-base or endocrine disturbances

When fulfilling the above criteria and the brainstem reflexes are absent, the clinician should perform apnea testing per the AAN recommendation[5] :

  • Connect a pulse oximeter, pre-oxygenate with 100% O2, and disconnect the ventilator.
  • Deliver 100% O2 at 6 l/min through a cannula from the trachea placed at the level of the carina.
  • If respiratory movements are absent despite arterial PCO2 of greater than or equal to 60 mm Hg or 20 mm Hg increase in PCO2 over a normal baseline PCO2, the apnea test result is considered positive.

The test is terminated in instances wherein there is hypotension, hypoxemia, or cardiac arrhythmias.

The absence of brainstem reflexes and a positive apnea test validate the brain death of the patient.

Ancillary tests such as

  • Flat electrical activity in 30 minute EEG
  • Absence of cerebral flow beyond the circle of Willis during angiography
  • No uptake of isotope within the blood vessel or brain parenchyma during a nuclear scan
  • Small systolic peaks in early systole without diastolic flow or reverberating flow in transcranial doppler

are only justified when apnea testing is inconclusive, or patients are too unstable to proceed with apnea testing or when brain stem reflexes cannot be carried out (vestibulo-ocular reflex in cervical spine injuries). 

Issues of Concern

Brain stem death is a clinical diagnosis made by a single examiner, and therefore ancillary tests are not essential for confirming brain death.[[1]

 Brian stem death has to be certified by the board members constituting of 

  •  Medical superintendent (MS) - in-charge of the hospital
  •  The treating medical specialist
  •  A neurologist or a neurosurgeon (with no inclusion any members from the organ donation or the transplantation team). 

The clinical diagnosis of brain death should take place in three steps

  • Establishing the etiology
  • Excluding possibly reversible syndromes that may produce signs similar to brain death
  • Demonstration of clinical signs of brain death including coma, brain stem areflexia, and apnea

However, when planning for organ donation, separate complete examinations by two physicians is recommended[6].

Ethical morality - justifying the use of limited medical resources, adding up the financial burden, and maximizing emotional troll to relatives in a hopeless clinical scenario

The whole-brain death concept- It is more prudent for the application of brainstem death rather than the whole brain death concept. It requires emphasis that though the brain stem is dead, there may still be some cortical and the hypothalamic functions (osmoregulation) intact in the patient. It is also distinct from cortical death (persistent vegetative state) wherein the brainstem functions are intact.

Concerns with the apnoea test- There are inherent confounding clinical factors that can invalidate the apnea test, such as hypoxia, hypotension, cervical cord injuries. Moreover, hypercarbia by causing cerebral vasodilation can further impede upon the cascade of impending cerebral herniation, thereby further complication the clinical scenario.

Public belief in brain death and organ procurement- There can be a significant concern among the relatives and the public that organ donation occurs when the patient heart is still beating, and the person is not entirely dead. There can be looming fear that death will be declared prematurely for the sake of organ and tissue retrieval.[7]

Is the brain dead person really dead? - Issues in defining biological death - certain pitfalls merit consideration while evaluating for brainstem death confirmation[8][9]:

  • The inexperience of the performing physician
  • Potential confounders - such as hypothermia, drugs, alcohol
  • Inadequate consideration during apnea test- such as low pCO2, Ventilator trigger settings
  • False Positive Brain Death Determination in scenarios such as barbiturate coma, baclofen toxicity
  • False Negative Brain Death Determination- spinal reflexes and automatisms, ventilator auto-triggering during the apnea test
  • Brain Death Different in Children-in 37 weeks of gestational age to 30 days, two examinations 24 hours apart whereas in 30 days to 18 years child, two examinations 12 hours apart
  • Limitations of Ancillary Tests- artifacts in EEG
  • Concerns relating to families and potential Organ Donation
  • Failure to Maintain adequate environment for Organ donation -systolic blood pressure of 100 mm Hg, urine output of at least 0.5 ml/kg/h; normal serum electrolytes and a tidal volume, not more than 8 ml/kg

Clinical Significance

The diagnosis of brain death is primarily derived clinically.[6]

The first step in determining brainstem death is to notify the next of kin about the process.

The interval observation period of 6 hour period is usually considered sufficient in adults and children over one year age. A reliable interval period has not been established for children less than seven days old. For children between 7 days to two months, two examinations and electroencephalograms (EEGs) should be separated by at least 48 hours. In contrast, in children between two months to one year, two examinations and EEGs should be separated by at least 24 hours. 

Repeat the clinical assessment of brain stem reflexes.

The steps and all examinations require full documentation.

Confirmatory testing should only take place out when deemed necessary and include:

  • Angiography: the absence of intracerebral filling at the level of the carotid bifurcation or circle of Willis.
  • Electroencephalography:  absent electrical activity during at least 30 minutes of recording 

  • Nuclear brain scan: the absence of uptake of isotope (“hollow skull phenomenon”)

  • Somatosensory evoked potentials: Brain death confirmed by the bilateral absence of N20-P22 response with median nerve stimulation.

  • Transcranial doppler ultrasonography: small systolic peaks confirm brain death in early systole without diastolic flow or reverberating flow.

Medical Record Documentation should include:

  • Etiology and irreversibility of coma

  • Absent motor response to pain

  • Absent  brainstem reflexes during two separate examinations separated by at least 6 hours

  • Absent respiration with pCO greater than or equal to 60 mm Hg

  • Justification for, and result of, confirmatory tests if applicable

Other Issues

Clinical instances that can be observed but compatible with the diagnosis of brain death [6]:

  • Spontaneous movements  other than pathologic flexion or extension response
  • Respiratory-like movements
  • Autonomic features such as sweating, flushing, tachycardia
  • Normal or sudden increases in blood pressure
  • Absence of diabetes insipidus
  • Deep tendon reflexes; superficial abdominal reflexes; triple flexion response
  • Babinski reflex

Enhancing Healthcare Team Outcomes

The healthcare staff should treat the family with sensitivity and respect, and their final decision about continuing medical support or matters related to organ donation requires strong contemplation. 

Because of differences in the definition of death owing to different cultural and religious grounds, it is challenging to obtain equivocal consensus for declaring brain stem death.[10]


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[2] Starr R,Tadi P,Pfleghaar N, Brain Death 2019 Jan;     [PubMed PMID: 30844186]
[3] Wijdicks EF, Determining brain death in adults. Neurology. 1995 May     [PubMed PMID: 7746373]
[4] Wijdicks EF, The diagnosis of brain death. The New England journal of medicine. 2001 Apr 19     [PubMed PMID: 11309637]
[5] Machado C,Perez J,Scherle C,Areu A,Pando A, Brain death diagnosis and apnea test safety. Annals of Indian Academy of Neurology. 2009 Jul     [PubMed PMID: 20174506]
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