Coma, Brain Death, End-of-life

Question 1

Clinical features of coma

Answer 1

• sleep-like, unarousable (not alert or awake even after painful stimuli), unresponsive state (unable to communicate or interact).
• only brain stem reflexes are clinically testable, since cortical function is absent.
• comatose pts may fully recover, partly improve or progress to brain death.
  
  • After days to wks, a pt with nonprogressive cortical damage (such as anoxic encephalopathy after cardiac arrest) may transition from coma to the persistent vegetative state.
    
    • CP of PVS:
      
      • eyes periodically open or move
      • sleep and wake cycles occur
      • pain responsiveness may return
      • BUT…meaningful interaction remains absent since severe cortical impairment persists.

Question 2

Pathogenesis of coma

Answer 2

• Severe metabolic or systemic conditions that diffusely depress cortical function may cause coma.
• What can directly impair neuronal function:
  
  • Hypoxia
  • inadequate cerebral blood flow
  • hypoglycemia
  • drug intoxication or overdose
• What can indirectly affect cerebral cortex?
  
  • systemic infection
  • metabolic disturbances
  • hepatic or renal failure .
• Timely correction of these conditions is critical
• Various disorders or diseases may produce coma from bilateral lesions in the cerebral hemispheres:
  
  • ischemic infarction
  • hemorrhage
  • head trauma
  • tumor
  • infection.
• a solitary, unilateral cerebral lesion does not produce coma unless it adversely affects the opposite hemisphere via brain edema or herniation.
• Coma may be produced by a brain stem lesion if it disrupts the reticular formation.
  
  • The tegmental brain stem reticular formation, projecting to thalamic and subcortical nuclei, is important for wakefulness and arousal.

Question 3

Examination of the unresponsive patient

Answer 3

• Serial, repeated observations of the patient may show a progressive loss of neurological function and brain stem reflexes, often indicative of a rostral to caudal deterioration due to edema or inflammation.
  
  • This limited examination includes:
    
    • evaluation of motor responses, breathing patterns, pupil size and reactivity, and reflexive ocular movements.
• asymmetrical neurological signs strongly suggest a structural lesion, such as an ischemic infarction, hemorrhage, or tumor
• symmetrical abnormalities usually are due to a more diffuse or toxi-metabolic process, such as anoxia.
• Strictly speaking, motor responses to command or withdrawal to painful stimuli do not occur in coma, since an appropriate, localizing response to a noxious stimulus requires some cortical function.
• Decorticate posturing is flexion of the upper limbs with extension of the lower limbs, associated with a lesion at the level of the cerebral cortex or hemisphere.
• Decerebrate posturing is extension of the upper and lower limbs, associated with a lesion at the level of the midbrain (red nucleus).
• Cheyne-Stokes respiration is a very distinctive pattern of alternating tachypnea and apnea (crescendo-decrescendo respiration).
  
  • In a comatose patient, this pattern is produced from bilateral cortical involvement due to metabolic encephalopathy, such as renal failure, a unilateral lesion with severe brain edema, or from bilateral structural lesions in cerebral cortex.
  • On occasion, C-S may be seen in noncomatose patients with CHF
  • Elderly, otherwise healthy subjects also may have C-S while they sleep.
• An increased respiratory rate, or hyperventilation, may be related to anxiety or fear, or may be a reflexive response to pulmonary congestion.
• Rarely, central neurogenic hyperventilation may result from a lesion or edema in the low midbrain to upper pons.
• An ataxic respiration pattern consists of variable breaths at an irregular rate from a lesion or edema in the medulla, involving the cardiorespiratory control centers there.
• The size of the pupils and the pupillary light reflex is important in the examination of the unconscious patient.
  
  • Often in coma from metabolic causes the pupillary light reflex is preserved despite loss of other brain stem or cranial nerve reflexes.
• A tectal (dorsal) midbrain lesion selectively involves the parasympathetic fibers, causing large, fixed pupils (unopposed sympathetic fibers).
• The presence of a larger, “blown,” fixed pupil which is unresponsive consensually or directly to light often is due to compression of the ipsilateral oculomotor nerve (CN III) from a swollen temporal lobe (uncal herniation).
  
  • This is a neurological emergency since progressive edema and herniation of the brain stem is fatal.
• A pontine lesion selectively involves the sympathetic fibers, causing small, pinpoint pupils (unopposed parasympathetic fibers).
• Reflexive eye movements are also important to check in every unresponsive patient.
• In trauma cases, a cervical fracture must first be excluded before the patient’s neck is moved during this part of the examination.
• reflexive eye movements may be suppressed by vestibulotoxic drugs, such as benzodiazepines, in the absence of a brain stem lesion.

Question 4

Types of reflexive ocular movement tests

Answer 4

• oculoCEPHALIC reflex “doll’s eyes reflex”
  
  • brain stem mediated reflex (1/2)
  • can be tested in comatose patients
  • The eyes should normally move in the direction opposite to the lateral turn of the head by the examiner.
  • In fully conscious or mildly drowsy patients, functional cerebral cortex can fixate or “command” the eyes into varied positions regardless of how the head is passively moved.
• oculoVESTIBULAR (cold caloric) reflex
  
  • brain stem mediated reflex (2/2)
  • can be tested in unconscious patients.
  • Before testing the pt, the examiner must use an otoscope to exclude blockage of the ear canal or a ruptured tympanic membrane.
  • Pt head is then elevated about 30 degrees above horizontal and one ear canal is irrigated with up to 100 cc of ice water.
  • induced convection movement of cooled endolymph creates reduced vestibular activity from that ipsilateral semicircular canal, causing the eyes to normally move slowly toward the cold (irrigated) ear.
  • A conscious patient would have the same response, plus cortically- mediated nystagmus, with the eyes beating toward the opposite, non-irrigated ear.
  • While examining the eyes of comatose patients, it is also helpful to check for the corneal and palpebral reflexes.

Question 5

Emergency treatment of the comatose patient

Answer 5

• “ABC’s” of Airway, Breathing, and Circulation.
• Immediately rule out hypoglycemia (fingerstick testing device) or empirically give 50% dextrose intravenously.
• A structural cause of coma, such as a hemorrhage, ischemic infarction, or mass lesion, is more likely in the presence of asymmetrical neurological signs.
  
  • A comatose trauma pt is suspected to have intracranial bleeding unless it is ruled out.
  • brain CT or MRI scan while basic resuscitative measures are carried out.
  • Tx of brain edema + surgical removal of the hematoma may be needed.
• General measures to reduce increased intracranial pressure (ICP) in comatose patients include mechanical hyperventilation and osmotic diuretics like mannitol.
  
  • With hyperventilation, intracranial blood volume is reduced since hypocarbia causes arterial vasoconstriction.
  • Cerebral water vol. is reduced by the effect of osmotic diuretics on the intact BBB in nml brain tissue.
  • IV corticosteroids (dexamethasone) can counteract the edema produced by a cerebral tumor, abscess or encephalitis
    
    • Brain edema from ischemic infarction or hemorrhage is unaffected by corticosteroids, but these pts may survive after decompressive craniectomy or hematoma removal.
• Toximetabolic (symmetrical neurological signs)
  
  • pts should be evaluated for electrolyte abnormalities, hypothermia, hepatic or renal failure, CO poisoning, or drug intoxication/OD.
  • While waiting for the results of urine or serum drug screens, narcotic or benzodiazepine antagonists could be given
• Coma can be also caused by SAH or meningoencephalitis
  
  • brain CT or MRI scan and lumbar puncture would be indicated

Question 6

Significance and pathology of brain death

Answer 6

• In brain death there is irreversible loss of function for both cerebrum and brain stem, leading to the inevitable failure of other vital organs (*heart)
• Brain death=death of the entire body, can be diagnosed while the heart is still beating.
• Brain death may be the consequence of hemorrhage from trauma, uncontrolled HTN, or a ruptured berry aneurysm.
  
  • Other causes: large or multiple ischemic infarctions, meningoencephalitis, and anoxia from cardiac arrest.
  • Extensive areas of the brain become ischemic with shifting or herniation of vital areas due to edema.
• In cerebral anoxia (after cardiac arrest) gross brain is fragile and easily disintegrates when removed at autopsy.
• Evidence of herniation caused by edema may be found at the temporal lobes and foramen magnum.
• Necrosis is most severe in the cerebral cortex and cerebellar folia.
• Characteristic ischemic “red neurons” in the cerebral cortex
  
  • appear eosinophilic and shrunken
• in the cerebellum Purkinje cells are ischemic or absent.
• Ischemic infarction or hemorrhage may be seen in other areas of the brain.

Question 7

Diagnosis of brain death

Answer 7

• In order to declare brain death, the apparent cause should be known and must be of sufficient severity to account for the irreversible coma.
• In brain death, there is no neurological improvement despite adequate treatment of any reversible causes of coma, such as drug intoxication, circulatory shock, or hypothermia (core temperature below 32C).
• Severe metabolic or endocrine abnormalities should be corrected and the effect of anesthetics and neuromuscular blocking drugs should be allowed to dissipate if coma occurs in the postoperative period.
• When the etiology of coma is known and no reversible causes require treatment, the generally accepted observation period is 6 hours; an “absolute” time period has not been established.
  
  • The brains of infants or children tend to withstand anoxia better than the adult brain, and occasionally undergo remarkable recovery.
    
    • 7 d-2 mo (48 hrs)
    • 2 mo-1 yr (24 hrs)
    • >1 yr old (12-24 hrs).
• The bedside neurological examination should not show any hint or suggestion of cerebral function in a comatose patient unresponsive to painful stimuli.
  
  • ​Thus, there should be no decorticate or decerebrate posturing, seizures, swallowing, yawning, or vocalizations.
  • some spinal cord mediated movements may still persist (muscle stretch reflexes or the Babinski sign).
• All CN or brain stem reflexes must be absent without any spontaneous respirations.
• Apnea can be verified by specific testing methods (if pt remains hemodynamically stable).
  
  • The ventilated pt is given 100% oxygen for 10 mins to create an oxygen reserve in the lungs
  • baseline arterial blood gas is tested.
  • ventilator discontinued while 100% oxygen is still supplied through the tubing.
  • If the ensuing hypercarbia induces respiratory movements, apnea is ruled out.
  • If no respiratory movements occur after 10 mins, another arterial blood gas is tested.
  • Apnea is confirmed if no breathing is observed despite reaching a pCO2 of 60 mm Hg or greater (or perhaps a pCO2 20 mm Hg above baseline value).
  • The mechanical ventilator is restarted at the end of the test
• Confirmatory tests of brain death are not required, but are used in setting of severe facial and ocular trauma or edema.
  
  • Confirmatory testing should also be done in comatose children <1 yr
  • A “flat line” or isoelectric EEG after 30 min of recording with a special protocol was the “classical” way of confirming the clinical diagnosis of brain death
  • Another “classical” confirmatory test of brain death: cerebral angiography
    
    • helpful in comatose patients with absent cerebral responsiveness and brain stem reflexes, but no clearly discernible cause of brain death.
  • A radioisotope brain scan is often the currently preferred confirmatory test also demonstrates absence of cerebral blood flow over a 10 min pd, (it can be performed at the bedside instead of the angiography suite)

Question 8

Coma prognosis

Answer 8

• Cortical function can return fully
  
  • if coma is from a reversible cause, treated in time
• Cortical function can return minimally
  
  • days to weeks after cerebral anoxia, the patient may periodically appear awake, with roving eyes and pain-responsiveness, but no meaningful interaction (persistent vegetative state)
• Coma may deteriorate to brain death
  
  • from progressive edema & neuronal death due to head trauma, tumor, hemorrhage, ischemia or infection

Question 9

Wakefulness and arousal

Answer 9

Depends on the ascending reticular activating system

(ARAS): tegmental pons -> midbrain -> thalamic intralaminar nuclei/basal forebrain -> cerebral cortex

(especially frontal & limbic system)