just basics for post graduate

1. BRAIN DEATH DR.SRIRAMA ANJANEYULU

2. Brain death is defined as the irreversible loss of function of the brain, including the brainstem. Primary neurologic diseases; severe head injury , aneurysmal subarachnoid hemorrhage. Medical and surgical intensive care units, hypoxic-ischemic brain insults and fulminant hepatic failure. In children, abuse is a more common cause than motor vehicle accidents or asphyxia in USA. In large referral hospitals, neurologists make the diagnosis of brain death 25 to 30 times a year. Overview

3. 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. 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. There is a clear difference between severe brain damage and brain death. 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. OVERVIEW

4. Prior to the advent of mechanical respiration, death was defined as the cessation of circulation and breathing. 1968 Irreversible Coma/Brain Death Harvard Medical School Ad Hoc Committee. 1981 Uniform Determination of Death Act - President’s Commission for the Study of Ethical Problems in Medicine. 1994 American Academy of Neurology Guidelines for the determination of Brain Death. 2005 NYS Guidelines for Determining Brain Death. Historical Perspective

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

6. Cerebral Cortex Cognition Voluntary Movement Sensation

7. Brain Stem

11. Tracheal (Cough) Reflex Respiration

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

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

14. Persistent Vegetative State Normal Sleep-Wake Cycles. No Response to Environmental Stimuli. Diffuse Brain Injury with Preservation of Brain Stem Function.

16. Preserved Consciousness

18. Asystole AND Apnea Death: traditional cardiopulmonary definition

19. “An organ, brain or other, that no longer functions and has no possibility of functioning again is for all practical purposes dead.” A. determine presence of “a permanently nonfunctioning brain.” B. confirmatory data 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 Harvard Criteria

20. 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.” 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. 3. No reflexes: pupils fixed, dilated and absence of: Pupillary response to bright light ocular movement to head turning and ice water irrigation of ears blinking postural activity (decerebrate ) Swallowing, yawning, vocalization Corneal reflexes Pharyngeal reflexes Deep tendon reflexes Respnse to plantar or noxious stimuli A. determine presence of “a permanentlynonfunctioning brain.”

21. 4. isoelectric EEG (specifies technique; “At least 10 full minutes of recording are desirable, but twice that would be better.” [!]) EEG: “when available it should be utilized” 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.” 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. B. confirmatory data

22. Diagnostic criteria for clinical diagnosis of brain death A. Prerequisites. Brain death is the absence of clinical brain function when the proximate cause is known and demonstrably irreversible. B. The three cardinal findings in brain death are coma or unresponsiveness absence of brainstem reflexes apnea. Practice parameters for determining brain death in adults: (summary statement) NEUROLOGY 1995;45:1012-1014:

23. Brain death is the absence of clinical brain function when the proximate cause is known and demonstrably irreversible. 1.Clinical or neuroimaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis of brain death. 2. Exclusion of complicating medical conditions that may confound clinical assessment (no severe electrolyte, acid-base, or endocrine disturbance). 3. No drug intoxication or poisoning. 4. Core temperature ≥ 32° C (90°F). Prerequisites

24. Coma or unresponsiveness--no cerebral motor response to pain in all extremities (nail-bed pressure and supraorbital pressure). 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.

25. 2. Absence of brainstem reflexes a) Pupils (a) No response to bright light (b) Size: midposition (4 mm) to dilated (9 mm) b) Ocular movement (a) No oculocephalic reflex (testing only when no fracture or instability of the cervical spine is apparent) (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) c) Facial sensation and facial motor response (a) No corneal reflex to touch with a throat swab (b) No jaw reflex (c) No grimacing to deep pressure on nail bed, supraorbital ridge, or temporomandibular joint d) Pharyngeal and tracheal reflexes (a) No response after stimulation of the posterior pharynx with tongue blade (b) No cough response to bronchial suctioning

26. 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).

27. 3. Apnea--test a) Prerequisites (a) Core temperature ≥ 36.5°C or 97°F (b) Systolic blood pressure ≥ 90 mm Hg (c) Euvolemia. Option: positive fluid balance in the previous 6 hours (d) Normal PCO2. Option: arterial PCO2 ≥ 40 mm Hg (e) Normal PO2 Option: preoxygenation to obtain arterial PO2 ≥ 200 mm Hg b) Connect a pulse oximeter and disconnect the ventilator. c) Deliver 100% O2, 6 l/min, into the trachea. Option: place a cannula at the level of the carina. d) Look closely for respiratory movements (abdominal or chest excursions that produce adequate tidal volumes). e) Measure arterial PO2, PCO2, and pH after approximately 8 minutes and reconnect the ventilator. 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). 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. 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. 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); 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.

28. 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.

29. The diagnosis of brain death -EELCO FM WIJDICKS N Engl J Med, Vol. 344, No. 16 April 19, 2001

30. Pitfalls in the diagnosis of brain death Some conditions may interfere with the clinical diagnosis of brain death, so that the diagnosis cannot be made with certainty on clinical grounds alone. Confirmatory tests are recommended. A. Severe facial trauma B. Preexisting pupillary abnormalities C. Toxic levels of any sedative drugs, aminoglycosides, tricyclic antidepressants, anticholinergics,antiepileptic drugs, chemotherapeutic agents, or neuromuscular blocking agents D. Sleep apnea or severe pulmonary disease resulting in chronic retention of CO2

31. These manifestations are occasionally seen and should not be misinterpreted as evidence for brainstem function. A. Spontaneous movements of limbs other than pathologic flexion or extension response. B. Respiratory-like movements (shoulder elevation and adduction, back arching, intercostal expansion without significant tidal volumes). C. Sweating, blushing, tachycardia. D. Normal blood pressure without pharmacologic support or sudden increases in blood pressure. E. Absence of diabetes insipidus. F. Deep tendon reflexes; superficial abdominal reflexes; triple flexion response. G. Babinski reflex. Clinical observations compatible with the diagnosis of brain death

32. Brain death is a clinical diagnosis. A repeat clinical evaluation 6 hours later is recommended, but this interval is arbitrary. A confirmatory test is not mandatory but is desirable in patients in whom specific components of clinical testing cannot be reliably performed or evaluated. 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. Confirmatory laboratory tests (Options)

33. The diagnosis of brain death EELCO FM WIJDICKS N Engl J Med, Vol. 344, No. 16 April 19, 2001

34. Confirmatory Testing Cerebral Angiography Normal No Intracranial Flow

35. Confirmatory Testing MR- Angiography

36. Confirmatory Testing EEG Normal Electrocerebral Silence

37. Confirmatory Testing Transcranial Ultrasonography

38. Confirmatory Testing Technetium-99 Isotope Brain Scan

39. 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. 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. C. Transcranial Doppler ultrasonography 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. 2. Small systolic peaks in early systole without diastolic flow or reverberating flow, indicating very high vascular resistance associated with greatly increased intracranial pressure. D. Technetium-99m hexamethylpropyleneamineoxime brain scan. No uptake of isotope in brain parenchyma ("hollow skull phenomenon"). 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. The following confirmatory test findings are listed in the order of the most sensitive test first.

40. A. Etiology and irreversibility of condition B. Absence of brainstem reflexes C. Absence of motor response to pain D. Absence of respiration with PCO2 ≥ 60 mm Hg E. Justification for confirmatory test and result of confirmatory test F. Repeat neurologic examination. Option: the interval is arbitrary, but a 6-hour period is reasonable. Medical record documentation (Standard)

41. Guidelines of 80 countries reviewed Legal standards on organ transplantation present in 69% (55 of 80 countries) Practice guidelines for brain death for adults in 88% 50% guidelines require >1 physician to declare All guidelines specified exclusion of confounders, presence of irreversible coma, absent motor response, and absent brainstem reflexes Apnea testing required in 59% differences in time of observation and required expertise of examining physicians Confirmatory laboratory testing mandatory in 28 of 70 (40%) guidelines 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.” Brain Death around the worldWijdicks EFM. Brain death worldwide: Accepted fact but no global consensus in diagnostic criteria NEUROLOGY 2002;58.

42. CHECK LIST FOR BRAIN DEATH

43. 1. Evaluate the irreversibility and potential causes of coma; 2. Initiate the hospital policy for notifying the next of kin; 3. Conduct and document the first clinical assessment of brain stem reflexes; 4. Observe the individual during a defined waiting period for any clinical inconsistencies with the diagnosis of brain death; 5. Conduct and document the second clinical assessment of brain stem reflexes; 6. Perform and document the apnea test; 7. Perform confirmatory testing, if indicated; 8. If the individual’s religious or moral objection to the brain death standard is known,implement hospital policies for reasonable accommodation; 9. Certify brain death; and 10. Withdraw cardio-respiratory support in accordance with hospital policies, including those for organ donation. NEW YORK STATE DEPARTMENT OF HEALTHGUIDELINES FOR DETERMINING BRAIN DEATHDECEMBER 2005