Brain Death Nawal Salahuddin MD, FCCP Associate Professor Section of Pulmonary & Critical Care Medicine AKUH
ICUs sometimes create an amalgam of Life-in-Death,
A state of being unable to participate in human life but also unable to die
Historical perspective (1)
The traditional concept of death emphasized cessation of respiration
In 1978, Sweet stated in the New England Journal of Medicine;
“ It is clear that a person is not dead unless his brain is dead. The time honored criteria of the stoppage of the heart beat and circulation are indicative of death only when they cause the brain to die”
Historical perspective (2)
Death is a loss of Cellular Function that leads to putrefaction
Death is an Irreversible cessation of the integrated functioning of the organization as a whole
Historical perspective (3)
With organ transplantation, resuscitative techniques (artificial cardiopulmonary support, cryopreservation) the diagnosis of Brain Death has become especially important
In 1981, the Uniform Determination of Death Act asserted the definition of Death as;
“ 1. Irreversible cessation of circulatory and respiratory functions
2. Irreversible cessation of all functions of the entire brain, including the Brain Stem”
Pathophysiology: Relevent brainstem anatomy
The primary Ventilatory Centre is located in the reticular core of the medulla oblongata.
The circulatory system is controlled by central neurons diffused throughout the reticular core of the pons and medulla
Pathophysiology: Relevent brainstem anatomy
The pupillary reflexes are mediated through the nuclei of cranial nerves II, III in the midbrain
The Doll’s eye (oculocephalic) reflex & cold calorics (vestibulo-ocular) reflexes are mediated by cranial nerves VIII, II ,VI and the pontine reticular formation
Pathophysiology: Relevant brainstem anatomy
Why are these reflex arcs important?
These cranial nerve nuclei lie next to the RAS, which spans the midbrain & pons.
The RAS is essential for consciousness and is not directly testable. If the adjacent nerve nuclei are not functioning there is no significant possibility that the RAS is intact
Causes of Brain Death
Global injury of the entire CNS
Circulatory failure (cardiac arrest)
Respiratory failure (anoxia from, CO poisoning)
Focal injury to the CNS
Primary Injury trauma, ischemia, IC heamorrhage
Secondary injury (herniation of brain stem)
Brain Death is defined as “ the complete & irreversible absence of all brain function”
Coma : Impaired consciousness either due to impairment of the RAS or cortex. Reversible
Persistent Vegetative state : Cortices failed, brainstem functions
Profound Hypothermia : can have clinical manifestations similar to brain death. So brain death cannot be diagnosed unless the core temperature is ≥ 32 º C
Brain Death implies failure of the Brain stem.
There may also be associated failure of cortical functioning that leads to loss of integrative activity and brainstem reflexes
Patients who fulfill criteria for brain death have;
NO PROSPECT OF SURVIVAL independent of artificial respiratory & circulatory support,
NO PROSPECT OF RECOVERY of brain function
NO PROSPECT OF IMPROVEMENT even to a persistent vegetative state or coma
Diagnosis of brain death
Measurement of blood flow
Transcranial doppler ultrasound
Diagnosis of brain death: Clinical Criteria (1)
Two preconditions must be met ;
The cause of injury is known: there must be clear evidence of an acute, catastrophic, irreversible brain injury.
Reversible conditions that may obfuscate the clinical diagnosis of brain death must be excluded.
Body temperature must be greater than 32C, to rule out hypothermia.
There is no chance of drug intoxication or neuromuscular blockade.
The patient is not in shock.
Diagnosis of brain death: Clinical Criteria (2)
The patient does not respond to verbal or visual command.
The patient makes no movements, no spontaneous movements, or any movement induced by painful reflex.
The pupils are fixed and nonreactive.
The patient has no oculocephalic reflex. When the patient’s eyes are opened and the head is turned from side to side, the eyes remain fixed in their position. Alternatively, the oculovestibular reflex may be tested. The patient’s ear canal is inspected to ensure an intact tympanic membrane. While the eyes are held open, ice water is injected into the ear canal.
The eyes of a brain-dead patient remain fixed in their position .
Diagnosis of brain death: Clinical Criteria (3)
The patient has no corneal reflexes when a cotton swab is dragged across the cornea while the eye is held open.
The patient has no gag reflex. The movement of the breathing tube (in and out) or insertion of a smaller tube down the breathing tube does not elicit a reflex.
The patient has no spontaneous ventilation. The patient is temporarily removed from life support (the ventilator). With the cessation of breathing by the machine, the body immediately starts to build up metabolic waste of CO2 in the blood. When the CO2 level reaches 55 mm Hg, an active brain causes the patient to breathe spontaneously. A dead brain gives no response.
Diagnosis of brain death: Clinical Criteria (4)
If, after this extensive clinical examination, the patient shows no sign of neurologic function and the cause of the injury is known, the patient can be pronounced brain-dead.
more than one physician is required to make this pronouncement for brain death to become legal death.
Although the patient has a dead brain and dead brainstem, spinal cord reflexes (eg, a knee jerk) can sometimes be elicited. In some brain-dead patients, a short reflex movement may occur when the hand or foot is touched
Diagnosis of brain death: Confirmatory testing (1)
All these tests measure cortical activity in some way.
Confirmatory tests are not generally required in the United States, but in several European, Central American, South American, and Asian countries, confirmatory testing is mandatory
Loss of bioelectrical brain activity as shown on the EEG (ie, isoelectric EEG) is a reliable confirmation of whole-brain death. Total electrical silence is not required for brain death.
It is important to note that an isoelectric EEG can be obtained after drug intoxication, such as intoxication with barbiturates and residual electrical activity may persist after BSD
Electrocerebral inactivity or electrocerebral silence is defined as no EEG activity above 2 mV/mm.
Confirmatory testing (3): Evoked responses
Brainstem auditory evoked potentials are signals generated at the level of the auditory nerves and brainstem in response to an acoustic stimulus.
Brainstem auditory evoked potentials consist of five identifiable waves. Wave I represents the vestibular nerve action potential; wave II, the vestibular and cochlear nerves; wave III, the lower pons; and waves IV and V, the upper pons and the midbrain The loss of waves III to V or II to V, or no reproducible brainstem auditory evoked potentials on both sides, is usually regarded as indicating BSD
Somatosensory evoked potentials are waves of neural activity generated from the neural structures along the afferent somatosensory pathways, which are generated after electrical stimulation of a peripheral nerve. The pathway starts at a peripheral nerve, then ascends by the brachial plexus, upper cervical cord, dorsal column nuclei, ventroposterior thalamus, and sensory cortex. Bilateral absence of specific waves following median nerve stimulation is consistent with brain death confirmatory laboratory finding
Confirmatory testing (4): Measurement of blood flow
Absence of blood flow to the brain leads to destruction of brain tissue. The greatest advantage of angiography for the determination of brain death is that it is influenced neither by central nervous system– depressant drugs nor by hypothermia.
Various CT techniques may be used, including CT angiography, CT perfusion, and xenon-CT perfusion, to demonstrate absent or nonviable cortical blood flow
MRI and magnetic resonance angiography should be used with caution in confirming brain death.
Tran cranial Doppler sonography.
Transcranial Doppler sonography uses a 2-MHz ultrasonic probe affixed to the temporal area, and the flow velocity of each of the major intracranial arteries may be measured.
In brain death, cerebral perfusion pressure approaches zero, and transcranial Doppler demonstrates systolic spikes; undetectable flow (i.e., no signal); or reversal of blood flow in diastole (i.e., to-and-fro or oscillating waveform) .These patterns were highly specific for brain death
Sedation & Analgesia in the ICU Nawal Salahuddin MD, FCCP Associate Professor Section of Pulmonary & Critical Care Medicine AKUH
A sedated patient is not necessarily a pain-free patient
Sources of pain;
Surgical incisions, trauma
Intravenous lines, bed sores, endotracheal suctioning
Vertebral body fractures, arthritis, prolonged immobility
Pain is misinterpreted as agitation
Adverse physiological effects of PAIN
Increased endogenous catecholamines
Hyper metabolic states
Sleep deprivation, agitation, anxiety, delirium
Opiate receptors are found in the CNS & PNS.
Clinically important receptors are designated µ & ĸ
These respiratory depressive effects are used in the ICU to treat ventilator-patient dyssynchrony, dyspnea , coughing
Opiates have minimal heamodynamic effects in euvolemic patients
Hypotension is seen in patients whose BP is maintained by sympathetic compensation
Morphine-induced histamine release is rarely clinically important in the ICU
Dependence & Withdrawal can be seen with prolonged infusions
Drugs most commonly used;
Recommendations for analgesic use in the ICU (1)
All critically ill patients should have the right to adequate analgesia and management of their pain.
Pain assessment and response to therapy should be performed regularly by using a scale appropriate to the patient population and systematically documented.
Patients who cannot communicate should be assessed through subjective observation of pain-related behaviors (movement, facial expression, and posturing) and physiological indicators (heart rate, blood pressure, and respiratory rate) and the change in these parameters following analgesic therapy.
Recommendations for analgesic use in the ICU (2)
A therapeutic plan and goal of analgesia should be established for each patient and communicated to all caregivers to ensure consistent analgesic therapy.
If intravenous doses of an opioid analgesic are required, fentanyl, hydromorphone, and morphine are the recommended agents.
Recommendations for analgesic use in the ICU (3)
Scheduled opioid doses or a continuous infusion is preferred over an “as needed” regimen to ensure consistent analgesia.
Fentanyl is preferred for a rapid onset of analgesia in acutely distressed patients.
Fentanyl or hydromorphone are preferred for patients with hemodynamic instability or renal insufficiency.
Morphine and hydromorphone are preferred for intermittent therapy because of their longer duration of effect.
Recommendations for analgesic use in the ICU (4)
NSAIDs or acetaminophen may be used as adjuncts to opioids in selected patients.
Ketorolac therapy should be limited to a maximum of five days, with close monitoring for the development of renal insufficiency or gastrointestinal bleeding. Other NSAIDs may be used via the enteral route in appropriate patients.
facilitate nursing care
reduce Oxygen consumption & CO2 production
When neuromuscular blockade is used
Should be individualized
Sedation – Agitation scale
Adaptation to ICU environment scale
Sedation: Drugs (1)
Benzodiazepines act by potentiating the GABA receptor mediated inhibition of the CNS
GABA receptors act by regulating a chloride channel on the cell membrane
By increasing the intracellular flow of Cl - neurons become hyperpolarized with a higher threshold for excitability
Sedation: Drugs (2)
All benzos are lipid soluble with a large volume of distribution
Duration of action after a bolus is determined by the rate of redistribution to the adipose tissues
Propofol acts on the GABA receptor, although the site of action on the receptor is different from benzos
Hydrophobic with high lipid solubility that allows for rapid crossing of the BBB and redistribution to peripheral tissues…. Rapid onset and short duration of action
It causes depressed responsiveness, anxiolysis and amnesia
Ventilatory depression & apnea. NOT an analgesic
Profound hypotension due to dilation of venous capacitance vessels & mild myocardial depression