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Year : 2020  |  Volume : 16  |  Issue : 2  |  Page : 55-60

Determination of brain stem death

Department of Neuroanaesthesia and NeuroCritical Care, Glenegales Global Health City, Chennai, Tamilnadu, India

Date of Submission22-Jan-2020
Date of Acceptance24-May-2020
Date of Web Publication18-Aug-2020

Correspondence Address:
Dr. Rajagopal Ramanan
Department of Neuroanaesthesia and Neurocritical Care, Gleneagales Global Health City, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AMJM.AMJM_4_20

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This article will focus on a step by step description of the process of brain stem death testing as per Indian Society of Critical Care Medicine (ISCCM) guidelines. This will be followed by a narrative on how the testing criteria differ among the various international guidelines. The importance of identifying a potential brain stem dead patient and confirming the same, zeroes down to two reasons. First and foremost, confirmation of death is needed for both the treating team of doctors and relatives to make informed decisions regarding ongoing care, including futility. The second is that it opens the opportunity to discuss the possibility of organ donation with the relatives. The criteria to diagnose brain stem death follows a stringent protocol and is laid in a fool proof manner so that the chances of making an error is infinistically minimal.

Keywords: Apnea testing, brain stem death, brain death criteria

How to cite this article:
Ramanan R. Determination of brain stem death. Amrita J Med 2020;16:55-60

How to cite this URL:
Ramanan R. Determination of brain stem death. Amrita J Med [serial online] 2020 [cited 2023 Mar 30];16:55-60. Available from: https://ajmonline.org.in/text.asp?2020/16/2/55/292432

  Introduction Top

This article will focus on a step-by-step description of the process of brain stem death testing as per the Indian Society of Critical Care Medicine (ISCCM) guidelines.[1] This will be followed by a narrative on how the testing criteria differ among the various international guidelines.

As per the Transplantation of Human Organs (THO) Act, 1994, “Brain-stem death” means the stage at which all functions of the brain stem have permanently and irreversibly ceased.[2] However, the cause of irreversible coma has to be established, preconditions met, and confounding factors are to be ruled out.

Brain stem death, which has been equated to death as per the THO Act, happens only when the cerebral perfusion pressure has equaled the intracranial pressure. The importance of identifying a potential brain stem dead patient and confirming the same, zeroes down to two reasons. First and foremost, confirmation of death is needed for both the treating team of doctors and relatives to make informed decisions regarding ongoing care, including futility. The second is that it opens up the opportunity to discuss the possibility of organ donation with relatives.[3] The criteria to diagnose brain stem death follows a stringent protocol and is laid in a foolproof manner so that the chances of making an error are infinistically minimal.

  When to Suspect Brain Stem Death? Top

The suspicion of brain stem death arises when a patient with a Glasgow Coma Scale of 3/15 with nonreactive pupils and absent brain stem reflexes, in whom all reversible causes which could explain the patient's present condition have been ruled out.[1]

The table provides a guideline on the period of observation before commencing brain stem death testing.[1]

The process of brain stem death testing is divided into three sequential steps as per Kerala Network for Organ Sharing guidelines.[4]

  the Prerequisites (Step 1) Top

  • The presence of irreversible coma
  • Neuroimaging evidence of acute central nervous system pathology
  • Toxic and metabolic causes ruled out
  • Drugs are known to alter the neurologic, neuromuscular function, and electroencephalographic testing, such as anesthetic agents, neuroparalytic drugs, methaqualone, barbiturates, benzodiazepines, high-dose beryllium, amitriptyline, trichloroethylene, and alcohols
  • Review medication and intensive care unit observation chart for drugs given, need to wait for at least five half-lives with normal renal and liver function to exclude a drug effect. Use peripheral nerve stimulator for train-of-four response to rule out muscle relaxant effect. This is particularly important where patients are referred from periphery to tertiary care center
  • Core temperature more than 35°C – Although brain stem reflexes are generally considered resistant to hypothermia unless core temperature decreases below 27°C, hypothermia is a reversible cause of brain stem dysfunction, and it must be ruled out.[5]

  Testing the Cranial Nerves (Step 2) Top

The following brain stem reflexes should be tested and confirmed to be absent before subjecting the patient to the apnea test.

  1. Nonreactive pupils – Pupillary reflex is the reflex constriction of the pupils when light is shown on the eye. The afferent is the optic nerve and efferent runs through the oculomotor nerve. Direct pupillary reflex is the constriction of the ipsilateral pupil and indirect is the constriction of the contralateral pupil. When light is shown on the pupils both the direct and indirect pupillary reflexes should be absent. Usually, the pupils are fixed at a size of 4–6 mm. Larger pupils are compatible with brain stem death as the intact sympathetic cervical spine pathways connected to the radially arranged fibers of the dilator muscle may remain intact.[5] Constricted pupils suggest the possibility of drug intoxication
  2. After ensuring that the cervical spine is intact, the patient's eyes are held open by an assistant, and the examiner briskly turns the head from side to side with the head held briefly at the end of each turn. A positive response occurs when the eyes rotate to the opposite side to the direction of head rotation, thus indicating that the brain stem (cranial nerves 3, 6, 8) is intact. Some guidelines make no mention of the oculocephalic or doll's eye reflex. Wijdicks does not include the oculocephalic reflex in his guidelines, arguing that this reflex lacks sensitivity in adult brain-injured patients[6]
  3. Absence of corneal reflex – Corneal reflex is the involuntary blinking of the eyelids elicited by the stimulation of the cornea. The afferent for this is through the nasociliary branch of the trigeminal nerve and the efferent is through the facial nerve. The absent 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 be seen. Both eyes are tested separately. Facial myokymias may be due to muscle contraction from denervation and deafferentation of the facial nucleus and is compatible with brain stem death[5]
  4. Absent facial movement to a noxious stimulus is verified by applying the pressure over supraorbital nerve in the supraorbital ridge, deep pressure on both the condyles at the level of the temporomandibular joint and also over the nail beds
  5. The absence of the pharyngeal and tracheal reflexes - the pharyngeal or gag reflex is tested after stimulation of the posterior pharynx with a tongue blade or suction device. The afferent is through the glossopharyngeal nerve and the efferent is through the vagus nerve. The tracheal reflex is most reliably tested by 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 1 or 2 suctioning passes
  6. The absence of ocular movements during oculovestibular reflex testing
  7. The oculovestibular reflex (cold caloric test) is done after confirming that the tympanic membrane is intact and free of wax or other foreign particles. After the patency of the external auditory canal is confirmed, the head is elevated to 30°, which makes the horizontal canal in the middle ear vertically aligned. Each external auditory canal is irrigated (one ear at a time) with approximately 50 mL of ice-cold water. A cold stimulus results in sedimentation of the endolymph and stimulation of the hair cells. The normal response in a comatose patient is slow deviation of the eyes toward the cold stimulus. This is absent in brain stem death and should be observed for at least 1 min after the stimulus. Both sides are tested, with an interval of at least 5 min. Basal fracture of the petrous bone abolishes the caloric response only unilaterally and can be identified by the presence of Battle's sign.[5]

  Apnea Test (Step 3) Top

The apnea test is based on the fact that to initiate a breath, the brain stem respiratory center is more sensitive to a hypercarbic stimulus rather than a hypoxic stimulus. The key to conducting a successful apnea test is to maintain all other vital parameters such as temperature, oxygen saturation, and blood pressure (BP) in its normal level and allow only the CO2 to increase. The apnea test is deemed positive if a patient is unable to initiate a respiratory attempt despite the CO2 levels increasing to beyond 60 mm Hg or 20 mm Hg from the baseline. The usual rate of increase of the CO2 is about 4–6 mmHg in the first minute followed by 2–4 mm Hg for every minute thereafter.

  Who Can Perform? Top

As per the THO 1994, there should be a group of at least four doctors who are not part of the transplant team. They include the Registered Medical Practitioner (RMP) in charge of the hospital, the specialist doctor usually intensivist or anesthesiologist, a neurosurgeon or neurologist and the RMP taking care of the patient.[2] The ISCCM guidelines specify that at least a team of four doctors, as mentioned above, must be there in the certification of brain stem death. The Government of Kerala GO stipulates that of the four doctors, two must be from a different hospital and one should be from a government hospital.[1],[7]

  When to Do? Top

Fulfilling Step 1 and 2 are a prerequisite to perform apnea testing.

Suggested observation period (in hours) for brain stem death testing is given in [Table 1].[1]
Table 1: Examples of the observation period (in hours) for brain stem death testing

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  Procedure Top

  • Preoxygenate for at least 10 min with 100% oxygen to a PaO2 around 200 mm Hg.
  • Reduce ventilation frequency to 10 breaths per minute to achieve eucapnia.
  • Reduce positive end-expiratory pressure (PEEP) to 5 cm H2O (oxygen desaturation with decreasing PEEP may suggest difficulty with apnea testing).
  • If pulse oximetry oxygen saturation remains 95%, obtain a baseline blood gas (PaO2, PaCO2, pH, bicarbonate, and base excess).
  • Disconnect the patient from the ventilator.
  • Preserve oxygenation (e.g., place an insufflation catheter through the endotracheal tube and close to the level of the carina and deliver 100% O2 at 6 L/min).
  • Look closely for respiratory movements for 8–10 min. Respiratory movement is defined as abdominal or chest excursions and may include a brief gasp.
  • Abort if systolic BP decreases to 90 mm Hg or bradycardia ensues. Retry procedure once hemodynamically stable.
  • Abort if oxygen saturation measured by pulse oximetry is 85% for 30s. Retry procedure with T-piece, continuous positive airway pressure 10 cm H2O, and O2 12 L/min.
  • If no respiratory drive is observed, repeat blood gas (PaO2, PaCO2, pH, bicarbonate, and base excess) after approximately 8 min.
  • If respiratory movements are absent and arterial PCO2 is >60 mm Hg (or 20 mm Hg increase in arterial PCO2 over a baseline normal arterial PCO2), the apnea test result is positive (i.e., supports the clinical diagnosis of brain stem death).
  • If the test is inconclusive, i.e., arterial PCO2 has not risen to the required level, but the patient is hemodynamically stable during the procedure, apnea may be prolonged for a longer period (10–15 min) to achieve adequate arterial PCO2 levels.

  Can the Patient Move during the Apnea Test? Top

Troubleshooting during apnea testing:

Hypotension: Make sure that the patient has at least 500–600 ml positive fluid balance in the previous 6 h before conducting the apnea test to avoid hypotension. Hypotension should be managed with inotropes/vasopressors as needed. The apnea test is aborted if the systolic BP falls <90 mm Hg

CO2 not building up: Ensure temperature more than 35°C. Decrease the respiratory rate by 2–4 before commencing the apnea testing and if the patient is hemodynamically stable and maintaining oxygen saturation, we can continue the period of apnea to 10–15 min.

Movements and physiological changes compatible with apnea test:[8],[9]

  • Spinal reflexes: These can be either spontaneous or elicited by stimulation, including a painful stimulus applied to limbs or sternum, tactile stimulation applied to palmar or plantar areas, neck flexion, limb elevation, or hypoxia (such as during ventilation disconnection). Spinal reflexes are not to be confused with a pathological flexion or extension response. Spinal movements may include:
  • Extension-pronation movements of the upper limbs or nonspecific flexion of the lower limbs;
  • Undulating toe reflex (plantar flexion of great toe, followed by brief plantar flexion sequentially of second to fifth toes);
  • Lazarus sign or Lazarus reflex is a reflex movement in brain stem dead patients, which causes brief bilateral arm flexion, shoulder adduction, hand raising to above the chest, and may include flexion of trunk, hips, and knees. Sometimes, patients drop the hands crossed on their chests after raising (in a position similar to some Egyptian mummies)
  • Deep tendon reflexes;
  • Plantar responses, either flexor or extensor;
  • Respiratory-like movements (shoulder elevation and adduction, back arching or intercostal expansion) without significant tidal volume; and
  • Head turning;
  • Sweating, blushing, tachycardia

  • Observations incompatible with apnea test:

  • Decerebrate or decorticate posturing
  • Extensor or flexor motor responses to painful stimuli
  • Seizures.

  What Is the Role of Ancillary Tests in the Confirmation of Brain Stem Death? Top

No additional testing is required if the clinical examination and the apnea test is conclusive.[5] Ancillary tests have been used to supplement the diagnosis of brain stem death provided the complete range of clinical tests could not be performed. The many ancillary tests available can be broadly divided into tests of cerebral blood flow (four-vessel angiogram, transcranial Doppler, ultrasound scan, magnetic resonance angiogram, computerized Tomography angiogram, nuclear brain scan), tests of cerebral electrical activity (electroencephalogram, auditory somatosensory evoked potential, and bispectral index) and tests of cerebral oxygenation (venous oxygen saturation in the Jugular bulb, brain tissue oxygenation).

The following can be taken as indications for ancillary tests:

  • Patients with high cervical injuries or major hemodynamic instability
  • Severe facial trauma or otorrhagia that prevents conduct of all cranial nerve tests
  • To reassure family members
  • Doubt or disagreement of diagnosis within the panel of doctors.

It is important to note that Transplantation of Human Organs act 1994 (THOA) does not comment on the use or indications of ancillary tests and the Government of Kerala suggests to abandon declaration of brain stem death rather than opt for ancillary tests if clinical findings are unreliable. Therefore, currently, ancillary tests may not be used legally to aid the determination of brain stem death in India.[1],[7]

  Controversies in the Neurological Determination of Brain Stem Death Top

Despite claims to the contrary in the lay press and social media, recovery of neurological function after fulfilling brain death criteria according to AAN 1995 guidelines has not been reported in medical literature.[10],[11] The guidelines used in India are derived from the AAN1995 guidelines and are, in fact, more stringent, as shown in [Table 2].[9],[10],[11],[12],[13],[14]
Table 2: Comparison of various brain stem death testing guidelines

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  Brain Stem Death Determining Criteria Across the World Top

The criteria to determine brain stem death evolved over the years and have become fairly standardized worldwide. Having said that, the terminologies used and the finer details of the tests used do vary not only among different various counties, but also within a country.[15],[16] [Table 2] highlights the differences between some of the major guidelines. The readers are requested to refer to Wahlster's article for a more detailed country-wise analysis.[17]

  Confounding Factors Top

It is generally accepted that the physiology of the person should be brought as close to normal as possible before checking for brain stem death. However, the definition of what values to be achieved (including temperature) and what duration they need to be maintained for before embarking on testing, varies among societal guidelines. There is no clear cut instruction on the duration that one needs to wait for the clearance of potentially confounding drugs in cases of renal or/and liver impairment. Therapeutic drug monitoring may be used if facilities are available. While apnea testing is universally applied, the specific PaCO2 thresholds to be achieved before a positive test may be declared, varies. Some societies mention threshold of pH values as well. Although many guidelines mention about the Lazarus sign, most do not elaborate on the acceptable and nonacceptable involuntary movements during apnea testing.

  Legal Time of Death Top

Some countries take the time of the first apnea as the time of death. However, in India, the time when PCO2 reaches the target during the second apnoea test is taken as the legal time of death.[1]

Guidelines vary on the expertise required to perform brain stem death testing. Most guidelines exclude physicians involved in the transplant team for this purpose.[5],[18]

It is important to note that even though minor variations exist, the various brain stem death testing guidelines are all conceptually the same and differences exit only in the technicalities. As Dr. Wijdicks states, “it is a fundamental observation that the brainstem controls the brain function, and without it there is none. No brain stem-no brain. It is a black-and-white issue and makes it a rather unique situation in the practice of medicine where doubt is pervasive.”[5]

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  References Top

Pandit RA, Zirpe KG, Gurav SK, Kulkarni AP, Karnath S, Govil D, et al. Management of potential organ donor: Indian society of critical care medicine: Position statement. Indian J Crit Care Med 2017;21:303-16.  Back to cited text no. 1
[PUBMED]  [Full text]  
Available from: http://www.health.bih.nic.in/Rules/THOA-1994.pdf. [Last accessed on 2019 Oct 06].  Back to cited text no. 2
Drake M, Bernard A, Hessel E. Brain death. Surg Clin North Am 2017;97:1255-73.  Back to cited text no. 3
G.O (Ms.) No. 53/2018/H and FWD. Government of Kerala, India. Dated Thiruvananthapuram 03.04.2018. Available at: https://www.mohanfoundation.org/government-orders/53-2018-BRAIN-DEATH-SOP.pdf..  Back to cited text no. 4
Wijdicks EF. Brain Death. 3rd Ed. New York, NY: Oxford University Press; 2017.  Back to cited text no. 5
Wijdicks EF. Brain death worldwide: Accepted fact but no global consensus in diagnostic criteria. Neurology 2002;58:20-5.  Back to cited text no. 6
G.O (Ms.) No. 16/2017/H and FWD. Government of Kerala, India. Dated Thiruvananthapuram 01.02.2017. Available at http://knos.org.in/pdf/go_ms_40_2018.pd. [Last accessed 2020 Jun 18].  Back to cited text no. 7
Urasaki E, Fukumura A, Itho Y, Itoyama Y, Yamada M, Ushio Y, et al. Lazarus' sign and respiratory-like movement in a patient with brain death. No To Shinkei 1988;40:1111-6.  Back to cited text no. 8
Australian and New Zealand Intensive Care Society. The ANZICS Statement on Death and Organ Donation. 3.2 Ed. Melbourne: ANZICS; 2013.  Back to cited text no. 9
Wijdicks EF, Varelas PN, Gronseth GS, Greer DM, American Academy of Neurology. Evidence-based guideline update: Determining brain death in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74:1911-8.  Back to cited text no. 10
Wijdicks EF. Determining brain death in adults. Neurology 1995;45:1003-11.  Back to cited text no. 11
A Code of Practice for the Diagnosis and Confirmation of Death. London: Academy of the Medical Royal Colleges; 2008.  Back to cited text no. 12
Shemie SD, Doig C, Dickens B, Byrne P, Wheelock B, Rocker G, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ 2006;174:S1-13.  Back to cited text no. 13
Brain Injury Evaluation Quality Control Centre of National Health and Family Planning Commission. Criteria and practical guidance for determination of brain death in children (BQCC version). Chin Med J (Engl) 2014;127:4140-4.  Back to cited text no. 14
Greer DM, Wang HH, Robinson JD, Varelas PN, Henderson GV, Wijdicks EF. Variability of brain death policies in the United States. JAMA Neurol 2016;73:213-8.  Back to cited text no. 15
Shemie SD, Hornby L, Baker A, Teitelbaum J, Torrance S, Young K, et al. International guideline development for the determination of death. Intensive Care Med 2014;40:788-97.  Back to cited text no. 16
Wahlster S, Wijdicks EF, Patel PV, Greer DM, Hemphill JC 3rd, Carone M, et al. Brain death declaration: Practices and perceptions worldwide. Neurology 2015;84:1870-9.  Back to cited text no. 17
Baron L, Shemie SD, Teitelbaum J, Doig CJ. Brief review: History, concept and controversies in the neurological determination of death. Can J Anaesth 2006;53:602-8.  Back to cited text no. 18


  [Table 1], [Table 2]


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  In this article
When to Suspect ...
the Prerequisite...
Testing the Cran...
Apnea Test (Step 3)
Who Can Perform?
When to Do?
Can the Patient ...
What Is the Role...
Controversies in...
Brain Stem Death...
Confounding Factors
Legal Time of Death
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