Brain Death Clinical evaluation & Ancillary tests P. Sariaslani Brain Death Clinical evaluation & Ancillary tests P.Sariaslani. MD Assistant Professor of Neurology Medical College of Kermanshah

The state of consciousness (arousal) The ascending RAS, from the lower border of the pons to the ventromedial thalamus The cells of origin of this system occupy a paramedian area in the brainstem

To cause coma, as defined as a state of unconsciousness in which the eyes are closed and sleep–wake cycles absent Lesion of the cerebral hemispheres extensive and bilateral Lesions of the brainstem: above the lower 1/3 of the pons and destroy both sides of the paramedian reticulum

Reticular Activating System Normal Brain Anatomy Cerebral Cortex Reticular Activating System Brain Stem

Brain Stem

Brain Stem Midbrain Cranial Nerve III pupillary function eye movement

Brain Stem Pons Cranial Nerves IV, V, VI conjugate eye movement corneal reflex

Brain Stem Medulla Cranial Nerves IX, X Pharyngeal (Gag) Reflex Tracheal (Cough) Reflex Respiration

In most adult series, trauma and subarachnoid hemorrhage are the most common event leading to brain death. Others include intracerebral hemorrhage, hypoxic ischemic encephalopathy, and ischemic stroke. Any condition causing permanent widespread brain injury can lead to brain death.

Causes of Brain Death Normal Cerebral Hemorrhage

Causes of Brain Death Cerebral Anoxia Normal

Subarachnoid Hemorrhage Causes of Brain Death Subarachnoid Hemorrhage Normal

Causes of Brain Death Normal Trauma

Causes of Brain Death Meningitis Normal

Mechanism of Cerebral Death ICP>MAP is incompatible with life Increased Intracranial Pressure

Conditions Distinct From Brain Death Persistent Vegetative State Locked-in Syndrome Minimally Responsive State

Vegetative state (coma vigil, apallic syndrome) Patients who survive coma do not remain in this state for > 2–3 weeks, but develop a persistent unresponsive state in which sleep–wake cycles return. After severe brain injury, the brainstem function returns with sleep–wake cycles, eye opening in response to verbal stimuli, and normal respiratory control.

Locked in syndrome Patient is awake and alert, but unable to move or speak. Pontine lesions affect lateral eye movement and motor control Lesions often spare vertical eye movements and blinking.

Vegetative Locked-in

Minimally Responsive State Static Encephalopathy Diffuse or Multi-Focal Brain Injury Preserved Brain Stem Function Variable Interaction with Environmental Stimuli

Brain Death Neurological Examination Clinical Prerequisites: Known Irreversible Cause Exclusion of Potentially Reversible Conditions Drug Intoxication or Poisoning Electrolyte or Acid-Base Imbalance Endocrine Disturbances Core Body temperature > 32° C

To ensure that the cessation of brain function is “irreversible,” physicians must: determine the cause of coma exclude mimicking medical conditions - observe the patient for a period of time to exclude the possibility of recovery

●Clinical or neuroimaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis of brain death, ie, the cause of brain death should be known. ●Core temperature >36ºC (97ºF). Hypothermia may also confound the diagnostic assessment of brain death and can also delay the increase in PaCO2 necessary to complete the apnea test. ● There is little evidence base for a choice of threshold temperature. Canadian forum recommendations published in 2006 use 34ºC as a standard . ●Normal systolic blood pressure >100 mm Hg. Vasopressors may be required.

Brain Death Current Consensus Absent Cerebral Function Absent Brainstem Function Apnea

Coma No Response to Noxious Stimuli Nail Bed Pressure Sternal Rub Supra-Orbital Ridge Pressure

Flexion of the upper limb with extension of the lower limb (decorticate response) and extension of the upper and lower limb (decerebrate response) indicate a more severe disturbance and prognosis.

Absence of Brain Stem Reflexes Pupillary Reflex Eye Movements Facial Sensation and Motor Response Pharyngeal (Gag) Reflex Tracheal (Cough) Reflex

Pupillary Reflex Pupils dilated with no constriction to bright light

Eye Movements Occulo-Cephalic Response “Doll’s Eyes Maneuver”

Oculo-Vestibular Response “Cold Caloric Testing”

Facial Sensation and Motor Response Corneal Reflex Jaw Reflex Grimace to Supraorbital or Temporo-Mandibular Pressure

Confounding Clinical Conditions Facial Trauma Pupillary Abnormalities CNS Sedatives or Neuromuscular Blockers Hepatic Failure Pulmonary Disease

Observations Compatible with Brain Death Sweating, Blushing Deep Tendon Reflexes Spontaneous Spinal Reflexes- Triple Flexion Babinski Sign

Dramatic spontaneous movements when severe hypoxia is attained upon terminal disconnection from the ventilator for Several minutes: These include opisthotonos with chest expansion that simulates a breath, elevation of the arms and crossing them in front of the chest or neck ( Lazarus sign ), head-turning, shoulder-shrugging, and variants of these posturing-like movements. For this reason the advice that the family not be in attendance immediately after mechanical ventilation has been discontinued.

:Confirmatory Testing - Recommended when the proximate cause of coma is not known or - when confounding clinical conditions limit the clinical examination

Confirmatory Testing Cerebral Angiography Normal No Intracranial Flow

Electrocerebral Silence Confirmatory Testing EEG Normal Electrocerebral Silence

Confirmatory Testing MR- Angiography

interpreted as consistent with brain death. Brain death confirmed by small systolic peaks in early systole without diastolic flow, or reverberating flow, indicating very high vascular resistance associated with greatly increased intracranial pressure Since as many as 10% of patients may not have temporal insonation windows because of skull thickness, the initial absence of Doppler signals cannot be interpreted as consistent with brain death. CT, transcranial Doppler (TCD), and SPECT findings(A) Noncontrast head CT. (B) Multi-depth TCD power-motion mode (upper panel) and single-depth spectral analysis (lower panel) show reverberating flow in the right vertebral artery characterized by brief forward flow in systole (long arrow) followed by abrupt flow reversal in diastole (short arrow). (C) Brain scintigraphy reveals absent intracranial flow.

Somatosensory Evoked Potentials Confirmatory Testing Somatosensory Evoked Potentials

Clinical Questions 1. Are there patients who fulfill the clinical criteria of brain death who recover brain function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death?

Methods MEDLINE and EMBASE January 1996 to May 2009 A secondary bibliography search of all full-text articles Relevant, fully published, peer-reviewed articles Search terms included the MeSH term brain death and the text words brain death, irreversible coma, and apnea test.

Literature Review 367 abstracts 38 articles Exclusion criteria: Articles that studied patients younger than 18 years Articles that confirmed prior observations Review articles, bioethical reviews, articles without description of a brain death examination Articles with questionable practices or describing rarely used ancillary technology

AAN Level of Recommendations A = Established as effective, ineffective or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population. B = Probably effective, ineffective or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population. C = Possibly effective, ineffective or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven. Note that recommendations can be positive or negative.

Analysis of Evidence Question 1: Are there patients who fulfill the clinical criteria of brain death who recover brain function?

Conclusion/Recommendation In adults, recovery of neurologic function has not been reported after the clinical diagnosis of brain death has been established using the criteria given in the 1995 AAN practice parameter. Recommendation: The criteria for the determination of brain death given in the 1995 AAN practice parameter have not been invalidated by published reports of neurological recovery in patients who fulfill these criteria (Level U).

Analysis of Evidence Question 2: What is an adequate observation period to ensure that cessation of neurologic function is permanent?

Conclusion/Recommendation There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Recommendation: There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly (Level U).

Analysis of Evidence Question 3: Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death?

Conclusion/Recommendation For some patients diagnosed as brain dead, complex, non-brain-mediated spontaneous movements can falsely suggest retained brain function. Additionally, ventilator autocycling may falsely suggest patient-initiated breathing. Recommendation: Complex–spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead (Level C).

Analysis of Evidence Question 4: What is the comparative safety of techniques for determining apnea?

Conclusion/Recommendation Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing.   Recommendation: There is insufficient evidence to determine the comparative safety of techniques used for apnea testing (Level U).

Analysis of Evidence Question 5: Are there new ancillary tests that accurately identify patients with brain death?

Conclusion/Recommendation Because of a high risk of bias and inadequate statistical precision, there is insufficient evidence to determine if any new ancillary tests accurately identify brain death. Recommendation: There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain (Level U).

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