Brain Death

Article Author:
Ryan Starr
Article Author (Archived):
Prasanna Tadi
Article Editor:
Nicholas Pfleghaar
Updated:
3/24/2019 10:36:59 PM
PubMed Link:
Brain Death

Introduction

Brain death is both a legal and clinical term. The term has been present in medical literature and texts for many years but as part of the National Conference of Commissioners on Uniform State Laws in 1980, the Uniform Determination of Death Act (UDDA) was drafted' this was later adopted by the American Medical Association and the American Bar Association. The act was drafted in response to medical advances in life support in the late 1970s that allowed for complete respiratory and circulatory support despite complete cessation of brain function. This reads as follows “[Determination of Death]. An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. A determination of death must be made in accordance with accepted medical standards.”

Unfortunately, the UDDA did not go on to establish what “accepted medical standards’ were, only that they existed. The most current standards were initially published by the American Academy of Neurology (AAN) in 1995 and then updated in 2010.[1]

Based on the published standards there are three findings that must be present to establish brain death, the AAN defines them as “coma (with a known cause), the absence of brainstem reflexes, and apnea.” [2][3][4]

Etiology

Brain Death occurs after the destruction of enough neuronal cells in the brain that there is both an irreversible loss of consciousness (coma) and the absence of brainstem reflexes including the inability of the lungs to inhale and exhale without external positive pressure support (apnea). [3]

In adults and children, the precipitant of brain death is either from an intracranial or extracranial cause. First, we have to establish the acute and irreversible cause. Intracranial injuries leading to brain death in adults are most commonly traumatic brain injury or subarachnoid hemorrhage, in children the most common cause is non-accidental trauma. Extracranial cause of brain death is most commonly cardiopulmonary arrest with inadequate cardiopulmonary resuscitation. [5]

We have to exclude the presence of any drugs or poisoning in the system. This can be accomplished by history, drug screen, etc. A through lab testing to be done to exclude severe endocrine, acid-base and electrolyte disturbances.

Epidemiology

The processes that lead to brain death are in order of frequency: cardiopulmonary arrest, traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage.

For extracranial causes of brain death, patients that present with cardiopulmonary arrest, 8.9% of those initially resuscitated will progress to brain death, and patients presenting with traumatic brain injury 2.8-6.1% of those patients will die of brain death.

For intracranial etiologies of brain death, of patients presenting with a subarachnoid hemorrhage 8.5-10.7% of those patients will progress to brain death and those with intracerebral hemorrhage 6.1-9.6% of them will. [6][7]

By definition, brain death carries a 100% mortality. 

Pathophysiology

The physiology of brain death is similar regardless of the etiology. Inadequate tissue oxygenation leads to a progressive cascade of further edema, increasing intracranial pressure, further decrease in cerebral perfusion and eventual herniation or complete cessation of blood flow and aseptic necrosis of brain tissue.

In anoxic brain injuries, mainly inadequate CPR following a cardiopulmonary arrest, tissue hypoxia leads to the release of cytotoxic material that leads to progressive cerebral edema and eventually the cascade described above.

For traumatic brain injuries or other intracranial injuries, the presence of increasing intracranial pressure as a result of injury beyond the mean arterial pressure will prevent adequate oxygenation of neuronal tissues. This situation will result in further injury, edema and eventually the process initially described above. [8][7]

Histopathology

Microscopic evaluation of the post-mortem brain dead patients reveals varying degrees of neuronal ischemic changes. The hemispheric lobes and basal ganglia are the most common areas to experience severe ischemic change followed by the pons, medulla oblongata, midbrain, and thalamus respectively. Autolysis of the cerebellum can also be appreciated in many autopsies. [9]

History and Physical

Once the decision to proceed with the brain death determination has been made, three conditions must be present: coma, the absence of brainstem reflexes, and apnea.

Coma should be evaluated by ensuring a lack of responsiveness to noxious stimuli, no eye or motor reflex should be present in response to stimuli. Additionally, the cause of coma should be identified by neuroimaging, history and physical or laboratory testing. 

The following brainstem reflexes should be tested in the physical exam of a patient deemed for brain death evaluation, they all must be absent in order for a patient to be diagnosed as brain dead:

  • The pupillary reflex to light – must be fixed at a mid position, usually around 4mm and must not respond to light.
  • Oculocephalic reflex – performed by rapidly turning the head.
  • Oculovestibular reflex (cold caloric) – absence when the head is held at 30 degrees and cold water instilled in the ear canal.
  • Corneal reflex – stimulate with a swab.
  • Gag reflex – stimulate posterior pharynx.
  • Cough reflex – stimulate with endotracheal suctioning.
  • The facial movement to noxious stimuli – apply noxious pressure to the supraorbital ridge, there should be no facial muscle response.

Evaluation

Before deciding to proceed with the diagnosis of brain death, several conditions must be evaluated and met:

  • Ensure no recent neuromuscular blocking agents have been administered (must wait five times the drug half-life).
  • Drug screen to ensure no CNS depressents are present. 
  • Normal core temperature must be present >36 C
  • Normal systolic blood pressure >100mmHg, vasopressors may be administered if necessary. 
  • No severe electrolyte, acid-base or endocrine disturbance. 
  • Neurologic examination, in most US states 1 attending physician exam is sufficient; however, some states require 2. 

If the above conditions are present, and there is an identified cause of coma and complete lack of brainstem reflex you may proceed with apnea testing. 

Apnea testing is performed by the following procedure as recommended by the AAN:

  • Preoxygenate for at least 10 minutes with 100% FiO2 to a PaO2 >200mmHg
  • Reduce ventilator frequency to 10 breaths per minute. 
  • Reduce positive end-expiratory pressure to 5 cm H2O.
  • If SPO2 remains >95% obtain baseline blood gas. 
  • Disconnect patient from the ventilator, preserve oxygenation with oxygen delivered through insufflation tubing given at 100% FiO2 at 6L/min near the level of the carina through the endotracheal tube. 
  • Look for respiratory movements for 8-10 minutes.
  • If no respiratory drive is observed, repeat blood gas at approximately 8 minutes. 
  • If no respiratory movements are observed and PCO2 is >60mmHg, the apnea test result is positive. 

If the above list is completed, and coma, the absence of brainstem reflexes and a positive apnea test are present, the diagnosis of brain death can be made. This procedure is validated and supported by several professional organizations. 

Although not required for the diagnosis of brain death, hospitals frequently have additional ancillary tests that are available to confirm the diagnosis of brain death. These include EEG, cerebral angiography, nuclear scan, transcranial doppler, CTA, and MRI/MRI. These tests are used when apnea testing is inconclusive, or patients are too unstable to proceed with apnea testing. [2][8] 

In the case of cerebral angiography, there is no intracerebral filling is noticed in the carotid or vertebral arteries at the skull entry-level and maintained blood flow in the external carotid artery. In the case of EEG, there is no electrographic reactivity is noticed after intense stimuli either somatosensory or audiovisual. [10]  It is very important to understand that there is no need to establish the death of every neuron in the brain in order to demonstrate brain death. For example, even after brain stem and cerebral hemispheres death there is a neuroendocrine function is preserved. [11] MRI brain is not yet accepted as an ancillary test for brain death determination.

Treatment / Management

Once brain death has been diagnosed the patient is clinically and legally declared as deceased with the time of death after testing. At this time depending on family and patient preference cardiopulmonary support should be withdrawn, or arrangements for organ harvest should begin. It is imperative that adequate documentation of all criteria of the diagnosis of brain death is included in the patient's medical record. It is recommended that some form of checklist be used to ensure completeness of testing. [5]

Differential Diagnosis

Several conditions may mimic brain death these include:

  • Locked-in syndrome
  • Hypothermia
  • Drug intoxication
  • Guillan-Barre syndrome
  • Delayed paralytic clearance

Adequate clinical evaluation to ensure these conditions are not present and must be done before proceeding with the diagnosis of brain death. It is extremely important to differentiate the difference between coma and brain death. When the AAN guidelines are followed, there have been no misdiagnosis of brain death reported in the literature, of the reported misdiagnosis at least one violation of the AAN guidelines identified [5][12]

Prognosis

The prognosis of brain death by definition is 100% fatal. 

Complications

Questioning the diagnosis of brain death only arise when AAN guidelines or protocols for brain death determination are not followed. These complications are limited to the misdiagnosis of a different neurologic condition as brain death and the ultimate death of a patient that was not brain dead. 

Deterrence and Patient Education

The diagnosis of brain death is difficult for families to accept. However, there is research to support asking the family to witness the clinical evaluation of brain death will help them understand the diagnosis. Multiple meetings, with more than one provider, clergy, social workers or other ancillary staff may be necessary for the family acceptance of the diagnosis. [12]

Pearls and Other Issues

Requirements for the diagnosis of brain death: 

  • Coma with an identified cause
  • The absence of brainstem reflexes
  • Apnea

The diagnosis is best made by closely following the American Academy of Neurology guidelines.

Enhancing Healthcare Team Outcomes

The designation of brain death will often involve a multidisciplinary team. Nurses, physicians, social workers, and clergy will play a vital role in working with families during and once the diagnosis is made. Subspecialists, such as neurology, neurosurgery, and radiology may be required to aid in the interpretation of ancillary testing if clinical diagnosis is inadequate. While the diagnosis is considered, a multidisciplinary team specially trained in organ procurement should be involved, these specialty teams should handle all aspects of care only once the diagnosis of brain death has been made to ensure adequate protection for the team that cared for the patient up until death. 


References

[1] Russell JA,Epstein LG,Greer DM,Kirschen M,Rubin MA,Lewis A, Brain death, the determination of brain death, and member guidance for brain death accommodation requests: AAN position statement. Neurology. 2019 Jan 2;     [PubMed PMID: 30602465]
[2] Wijdicks EF,Varelas PN,Gronseth GS,Greer DM, Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010 Jun 8;     [PubMed PMID: 20530327]
[3] Wijdicks EF, Determining brain death in adults. Neurology. 1995 May;     [PubMed PMID: 7746373]
[4] Capron AM, Death and the law: a decade of change. Soundings. 1980 Fall;     [PubMed PMID: 11645435]
[5] Drake M,Bernard A,Hessel E, Brain Death. The Surgical clinics of North America. 2017 Dec;     [PubMed PMID: 29132508]
[6] Sandroni C,D'Arrigo S,Callaway CW,Cariou A,Dragancea I,Taccone FS,Antonelli M, The rate of brain death and organ donation in patients resuscitated from cardiac arrest: a systematic review and meta-analysis. Intensive care medicine. 2016 Nov;     [PubMed PMID: 27699457]
[7] Kramer AH,Zygun DA,Doig CJ,Zuege DJ, Incidence of neurologic death among patients with brain injury: a cohort study in a Canadian health region. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2013 Dec 10;     [PubMed PMID: 24167208]
[8] Spinello IM, Brain Death Determination. Journal of intensive care medicine. 2015 Sep;     [PubMed PMID: 24227449]
[9] Neuropathology of brain death in the modern transplant era., Machado C,Korein J,, Neurology, 2009 Mar 17     [PubMed PMID: 19289748]
[10] Machado C,Pérez-Nellar J,Estevez M,Gonzalez E, Evidence-based guideline update: Determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2011 Jan 18;     [PubMed PMID: 21242502]
[11] Lewis A,Adams N,Varelas P,Greer D,Caplan A, Organ support after death by neurologic criteria: Results of a survey of US neurologists. Neurology. 2016 Aug 23;     [PubMed PMID: 27449064]
[12] Youn TS,Greer DM, Brain death and management of a potential organ donor in the intensive care unit. Critical care clinics. 2014 Oct;     [PubMed PMID: 25257743]