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BRAIN DEATH,[object Object],DR.SRIRAMA ANJANEYULU,[object Object]
 Brain death is defined as the irreversible loss of function of the brain, including the brainstem.,[object Object],Primary neurologic diseases; severe head injury , aneurysmal subarachnoid hemorrhage.,[object Object],Medical and surgical intensive care units, hypoxic-ischemic brain insults and fulminant hepatic failure.,[object Object], In children, abuse is a more common cause than motor vehicle accidents or asphyxia in USA.,[object Object], In large referral hospitals, neurologists make the diagnosis of brain death 25 to 30 times a year. ,[object Object],Overview ,[object Object]
Physicians, health care workers, members of the clergy, and laypeople throughout the world have accepted fully that a person is dead when his or her brain is dead. ,[object Object],In the United States, the principle that death can be diagnosed by neurologic criteria (designated as brain death) is the basis of the Uniform Determination of Death Act.,[object Object], There is a clear difference between severe brain damage and brain death. ,[object Object],The physician must understand this difference, because brain death means that life support is useless, and brain death is the principal requisite for the donation of organs for transplantation.,[object Object],OVERVIEW,[object Object]
Prior to the advent of mechanical respiration, death was defined as the cessation of circulation and breathing.,[object Object],1968 Irreversible Coma/Brain Death Harvard Medical School Ad Hoc Committee.,[object Object],1981 Uniform Determination of Death Act - President’s Commission for the Study of Ethical Problems in Medicine.,[object Object],1994 American Academy of Neurology Guidelines for the determination of Brain Death. ,[object Object],2005 NYS Guidelines for Determining Brain Death.,[object Object],Historical Perspective,[object Object]
Normal Brain Anatomy,[object Object],Cerebral Cortex,[object Object],Reticular Activating System,[object Object],Brain Stem,[object Object]
Cerebral Cortex,[object Object],Cognition,[object Object],Voluntary Movement,[object Object],Sensation,[object Object]
Brain Stem,[object Object]
Brain Stem,[object Object],Midbrain,[object Object],Cranial Nerve III,[object Object],[object Object]
 eye movement,[object Object]
 corneal reflex,[object Object]
 Tracheal (Cough) Reflex   Respiration,[object Object]
Mechanism of Cerebral Death,[object Object],ICP>MAP is incompatible with life,[object Object],Increased Intracranial ,[object Object], Pressure,[object Object]
Persistent Vegetative State,[object Object],Locked-in Syndrome,[object Object],Minimally Responsive State,[object Object],Conditions Distinct From Brain Death,[object Object]
Persistent Vegetative State,[object Object],Normal Sleep-Wake Cycles. ,[object Object],No Response to Environmental Stimuli.,[object Object],Diffuse Brain Injury with Preservation of Brain Stem Function.,[object Object]
Locked-in Syndrome,[object Object],Ventral Pontine Infarct,[object Object],[object Object]
 Preserved Consciousness
 Preserved Eye Movement,[object Object]
Asystole,[object Object],	AND,[object Object],Apnea,[object Object],Death: traditional cardiopulmonary definition,[object Object]
“An organ, brain or other, that no longer functions and has no possibility of functioning again is for all practical purposes dead.”,[object Object],A. determine presence of “a permanently nonfunctioning brain.”,[object Object],B. confirmatory data,[object Object],Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. A definition of irreversible coma. JAMA 1968;205:337-340,[object Object],Harvard Criteria,[object Object]
1. Unreceptivity and Unresponsitivity: “total unawareness to externally applied stimuli…even the most intensely painful stimuli evoke no vocal or other response, not even a groan, withdrawal of a limb, or quickening of respiration.”,[object Object],2. No Movements or Breathing: no spontaneous movements or spontaneous respiration (turn off respirator for 3 minutes; prior to trial breathing room air for ≥10 minutes and pCO2 normal) or response to pain, touch, sound or light for an hour.,[object Object],3. No reflexes: pupils fixed, dilated and absence of:,[object Object],Pupillary response to bright light,[object Object],ocular movement to head turning and ice water irrigation of ears,[object Object],blinking,[object Object],postural activity (decerebrate ),[object Object],Swallowing, yawning, vocalization,[object Object],Corneal reflexes,[object Object],Pharyngeal reflexes,[object Object],Deep tendon reflexes,[object Object],Respnse to plantar or noxious stimuli,[object Object],A. determine presence of “a permanentlynonfunctioning brain.”,[object Object]
4. isoelectric EEG (specifies technique;  “At least 10 full minutes of recording are desirable, but twice that would be better.” [!]),[object Object],EEG: “when available it should be utilized”,[object Object],If EEG unavailable, “the absence of cerebral function has to be determined by purely clinical signs…or by absence of circulation as judged by standstill of blood in the retinal vessels, or by absence of cardiac activity.”,[object Object],A and B all need to be repeated 24 hours later  in the absence of hypothermia (<90˚F [32.2˚C]) or CNS depressants, such as barbiturates, and determined only by a physician.,[object Object],B. confirmatory data,[object Object]
Diagnostic criteria for clinical diagnosis of brain death ,[object Object],A. Prerequisites. Brain death is the absence of clinical brain function when the proximate cause is known and demonstrably irreversible. ,[object Object],B. The three cardinal findings in brain death are coma or unresponsiveness,[object Object],    absence of brainstem reflexes,[object Object],    apnea.,[object Object], Practice parameters for determining brain death in adults: (summary statement) NEUROLOGY 1995;45:1012-1014: ,[object Object]
 Brain death is the absence of clinical brain function when the proximate cause is known and demonstrably irreversible. ,[object Object],1.Clinical or neuroimaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis of brain death.,[object Object],2. Exclusion of complicating medical conditions that may confound clinical assessment (no severe electrolyte, acid-base, or endocrine disturbance).,[object Object],3. No drug intoxication or poisoning. ,[object Object],4. Core temperature ≥ 32° C (90°F).,[object Object],Prerequisites,[object Object]
Coma or unresponsiveness--no cerebral motor response to pain in all extremities (nail-bed pressure and supraorbital pressure).,[object Object],    In step 1, the physician determines that there is no motor response and the eyes do not open when a painful stimulus is applied to the supraorbital nerve or nail bed.,[object Object]
2. Absence of brainstem reflexes ,[object Object],a) Pupils ,[object Object],(a) No response to bright light ,[object Object],(b) Size: midposition (4 mm) to dilated (9 mm) ,[object Object],b) Ocular movement ,[object Object],(a) No oculocephalic reflex (testing only when no fracture or instability of the cervical spine is apparent) ,[object Object],(b) No deviation of the eyes to irrigation in each ear with 50 ml of cold water (allow 1 minute after injection and at least 5 minutes between testing on each side) ,[object Object],c) Facial sensation and facial motor response ,[object Object],(a) No corneal reflex to touch with a throat swab ,[object Object],(b) No jaw reflex ,[object Object],(c) No grimacing to deep pressure on nail bed, supraorbital ridge, or temporomandibular joint ,[object Object],d) Pharyngeal and tracheal reflexes ,[object Object],(a) No response after stimulation of the posterior pharynx with tongue blade ,[object Object],(b) No cough response to bronchial suctioning ,[object Object]
In step 2, a clinical assessment of brain-stem reflexes is undertaken. The tested cranial nerves are indicated by Roman numerals; the solid arrows represent afferent limbs, and the broken arrows efferent limbs. Depicted are the absence of grimacing or eye opening with deep pressure on both condyles at the level of the temporomandibular joint (afferent nerve V and efferent nerve VII), the absent corneal reflex elicited by touching the edge of the cornea (V and VII), the absent light reflex (II and III), the absent oculovestibular response toward the side of the cold stimulus provided by ice water (pen marks at the level of the pupils can be used as reference) (VIII and III and VI), and the absent cough reflex elicited through the introduction of a suction catheter deep in the trachea (IX and X).,[object Object]
3. Apnea--test,[object Object],a) Prerequisites ,[object Object],(a) Core temperature ≥ 36.5°C or 97°F ,[object Object],(b) Systolic blood pressure ≥ 90 mm Hg ,[object Object],(c) Euvolemia. Option: positive fluid balance in the previous 6 hours ,[object Object],(d) Normal PCO2. Option: arterial PCO2 ≥ 40 mm Hg ,[object Object],(e) Normal PO2 Option: preoxygenation to obtain arterial PO2 ≥ 200 mm Hg ,[object Object],b) Connect a pulse oximeter and disconnect the ventilator. ,[object Object],c) Deliver 100% O2, 6 l/min, into the trachea. Option: place a cannula at the level of the carina. ,[object Object],d) Look closely for respiratory movements (abdominal or chest excursions that produce adequate tidal volumes). ,[object Object],e) Measure arterial PO2, PCO2, and pH after approximately 8 minutes and reconnect the ventilator. ,[object Object],f) If respiratory movements are absent and arterial PCO2 is ≥ 60 mm Hg (option: 20 mm Hg increase in PCO2 over a baseline normal PCO2), the apnea test result is positive (ie, it supports the diagnosis of brain death). ,[object Object],g) If respiratory movements are observed, the apnea test result is negative (ie, it does not support the clinical diagnosis of brain death), and the test should be repeated. ,[object Object],h) Connect the ventilator if, during testing, the systolic blood pressure becomes ≤ 90 mm Hg or the pulse oximeter indicates significant oxygen desaturation and cardiac arrhythmias are present; immediately draw an arterial blood sample and analyze arterial blood gas. ,[object Object],        If PCO2 is ≥ 60 mm Hg or PCO2 increase is ≥ 20 mm Hg over baseline normal PCO2, the apnea test result is positive (it supports the clinical diagnosis of brain death); ,[object Object],        If PCO2 is < 60 mm Hg or PCO2 increase is < 20 mm Hg over baseline normal PCO2, the result is indeterminate, and an additional confirmatory test can be considered. ,[object Object]
In step 3, the apnea test is performed; the disconnection of the ventilator and the use of apneic diffusion oxygenation require precautionary measures. The core temperature should be 36.5°C or higher, the systolic blood pressure should be 90 mm Hg or higher, and the fluid balance should be positive for six hours. After preoxygenation (the fraction of inspired oxygen should be 1.0 for 10 minutes), the ventilation rate should be decreased. The ventilator should be disconnected if the partial pressure of arterial oxygen reaches 200 mm Hg or higher and if the partial pressure of arterial carbon dioxide reaches 40 mm Hg or higher. The oxygen catheter should be at the carina (delivering oxygen at a rate of 6 liters per minute). The physician should observe the chest and the abdominal wall for respiration for 8 to 10 minutes and should monitor the patient for changes in vital functions. If there is a partial pressure of arterial carbon dioxide of 60 mm Hg or higher or an increase of more than 20 mm Hg from the normal base-line value, apnea is confirmed. ABP denotes arterial blood pressure, HR heart rate, RESP respirations, and SpO 2oxygen saturation measured by pulse oximetry.,[object Object]
The diagnosis of brain death -EELCO FM WIJDICKS N Engl J Med, Vol. 344, No. 16 April 19, 2001,[object Object]
Pitfalls in the diagnosis of brain death ,[object Object],Some conditions may interfere with the clinical diagnosis of brain death, so that the diagnosis cannot be made with certainty on clinical grounds alone. ,[object Object],Confirmatory tests are recommended. ,[object Object],A. Severe facial trauma ,[object Object],B. Preexisting pupillary abnormalities ,[object Object],C. Toxic levels of any sedative drugs, aminoglycosides, tricyclic antidepressants, anticholinergics,antiepileptic drugs, chemotherapeutic agents, or neuromuscular blocking agents ,[object Object],D. Sleep apnea or severe pulmonary disease resulting in chronic retention of CO2 ,[object Object]
These manifestations are occasionally seen and should not be misinterpreted as evidence for brainstem function. ,[object Object],A. Spontaneous movements of limbs other than pathologic flexion or extension response.,[object Object],B. Respiratory-like movements (shoulder elevation and adduction, back arching, intercostal expansion without significant tidal volumes). ,[object Object],C. Sweating, blushing, tachycardia. ,[object Object],D. Normal blood pressure without pharmacologic support or sudden increases in blood pressure.,[object Object],E. Absence of diabetes insipidus. ,[object Object],F. Deep tendon reflexes; superficial abdominal reflexes; triple flexion response.,[object Object],G. Babinski reflex. ,[object Object], Clinical observations compatible with the diagnosis of brain death ,[object Object]
Brain death is a clinical diagnosis.,[object Object], A repeat clinical evaluation 6 hours later is recommended, but this interval is arbitrary.,[object Object], A confirmatory test is not mandatory but is desirable in patients in whom specific components of clinical testing cannot be reliably performed or evaluated.,[object Object], It should be emphasized that any of the suggested confirmatory tests may produce similar results in patients with catastrophic brain damage who do not (yet) fulfill the clinical criteria of brain death. ,[object Object], Confirmatory laboratory tests (Options) ,[object Object]
The diagnosis of brain death EELCO FM WIJDICKS N Engl J Med, Vol. 344, No. 16 April 19, 2001,[object Object]
Confirmatory Testing,[object Object],Cerebral Angiography,[object Object],Normal,[object Object],No Intracranial Flow,[object Object]
Confirmatory Testing,[object Object],MR- Angiography ,[object Object]
Confirmatory Testing,[object Object],EEG,[object Object],Normal,[object Object],Electrocerebral Silence,[object Object]
Confirmatory Testing,[object Object],Transcranial Ultrasonography ,[object Object]
Confirmatory Testing,[object Object],Technetium-99 Isotope Brain Scan,[object Object]
A. Conventional angiography. No intracerebral filling at the level of the carotid bifurcation or circle of Willis. The external carotid circulation is patent, and filling of the superior longitudinal sinus may be delayed. ,[object Object],B. Electroencephalography. No electrical activity during at least 30 minutes of recording that adheres to the minimal technical criteria for EEG recording in suspected brain death as adopted by the American Electroencephalographic Society, including 16-channel EEG instruments. ,[object Object],C. Transcranial Doppler ultrasonography,[object Object],   1. Ten percent of patients may not have temporal insonation windows. Therefore,    the initial absence of Doppler signals cannot be interpreted as consistent with brain death. ,[object Object],   2. Small systolic peaks in early systole without diastolic flow or reverberating flow, indicating very high vascular resistance associated with greatly increased intracranial pressure. ,[object Object],D. Technetium-99m hexamethylpropyleneamineoxime brain scan. No uptake of isotope in brain parenchyma ("hollow skull phenomenon"). ,[object Object],E. Somatosensory evoked potentials. Bilateral absence of N20-P22 response with median nerve stimulation. The recordings should adhere to the minimal technical criteria for somatosensory evoked potential recording in suspected brain death as adopted by the American Electroencephalographic Society. ,[object Object],The following confirmatory test findings are listed in the order of the most sensitive test first. ,[object Object]
A. Etiology and irreversibility of condition ,[object Object],B. Absence of brainstem reflexes ,[object Object],C. Absence of motor response to pain ,[object Object],D. Absence of respiration with PCO2 ≥ 60 mm Hg ,[object Object],E. Justification for confirmatory test and result of confirmatory test ,[object Object],F. Repeat neurologic examination. Option: the interval is arbitrary, but a 6-hour period is reasonable. ,[object Object], Medical record documentation (Standard) ,[object Object]
Guidelines of 80 countries reviewed,[object Object],Legal standards on organ transplantation present in 69% (55 of 80 countries),[object Object],Practice guidelines for brain death for adults in 88%,[object Object],50% guidelines require >1 physician to declare,[object Object],All guidelines specified exclusion of confounders, presence of irreversible coma, absent motor response, and absent brainstem reflexes,[object Object],Apnea testing required in 59%,[object Object],differences in time of observation and required expertise of examining physicians,[object Object],Confirmatory laboratory testing mandatory in 28 of 70 (40%) guidelines,[object Object],Conclusion: “uniform agreement on the neurologic exam with exception of the apnea test; but other major differences found in the procedures for diagnosing brain death in adults, and standardization should be considered.”,[object Object],Brain Death around the worldWijdicks EFM. Brain death worldwide: Accepted fact but no global consensus in diagnostic criteria NEUROLOGY 2002;58.,[object Object]

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Brain death

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