Challenges in Brain Death Declaration

Challenges in Brain Death Declaration MJ Souter MB ChB FRCA Professor, Anesthesiology & Pain Medicine ; Neurological Surgery (adj) University of Washington.Medical Advisor, LifecenterNW

Aims • Investigate and discuss practice of declaration of death by neurologic criteria, examining • Presenting pathology • Confounding circumstances • Problems in clinical assessment • Ancillary tests

Core of declaration • Coma - supported by history of complaint and radiological findings • Absence of response to noxious stimulation • Absence of cranial nerve reflexes • Absence of respiratory drive on pCO2 (pH) challenge • All examination is performed in circumstances of normoxia, normotension, normal temperature, normal biochemistry and absence of toxins

UDDA STATE ADOPTIONS AlabamaAlaskaArizonaArkansasCaliforniaColoradoConnecticutDelawareDistrict of ColumbiaGeorgiaIdahoIndianaKansasMaineMaryland MichiganMinnesotaMississippiMissouriMontanaNebraskaNevadaNew HampshireNew Mexico New York *North Carolina *North DakotaOhioOklahomaOregon PennsylvaniaPuerto RicoRhode IslandSouth CarolinaSouth DakotaTennesseeU.S. Virgin IslandsUtahVermontWashingtonWest VirginiaWisconsinWyoming * Substantially Similar

Declaration of Sydney • 1968 World Medical Assembly • Death is a process • In a complex organism a number of cells may be alive, but this did not mean that the organism as a whole is alive • Death could be said to have occurred when there is certainty that this process is irreversible

Case 1 • 52 year old man with acute brainstem hemorrhage (24 hours ago) • Intubated in the field • EVD insertion for hydrocephalus, on admission • Has fixed pupils at 3 mm • No cough or gag • Unresponsive to peripheral nailbed pressure • No spontaneous facial or peripheral movement • No sedation since insertion of EVD • Hypertensive – controlled with nicardipine

Would you do a brain death exam? • 1. No – because its less than 72 hours since event • 2. Yes – after reversal of muscle relaxation • 3. No - because his clinical signs may change

Difficulties • The UDDA defines death as being an irreversible absence of function of the entire brain – including the brain stem • The brain stem is the CONDUIT of neural traffic both TO and FROM the neocortex • Primary brainstem dysfunction can occur independently of cortical dysfunction • If protracted over time, it can induce cortical dysfunction • The question is whether it is “irreversible”

Difficulties • The UDDA defines death as being an irreversible absence of function of the entire brain – including the brain stem • The brain stem is the CONDUIT of neural traffic both TO and FROM the neocortex • Primary brainstem dysfunction can occur independently of cortical dysfunction • If protracted overtime, it can induce cortical dysfunction • The question is whether it is “irreversible”

Locked-in Syndrome Ventral Pontine Lesion • Complete Paralysis • Preserved Consciousness • Preserved Eye Movement

Survival after brain stem hemorrhage • Retrospective review of 212 patients with primary brain stem hemorhage • 3 month poor outcome was associated with • GCS < 8, pupillary abnormality, hematoma extension (vertical / bilateral), hematoma volume • These were not absolute • Survivors (including good outcome) displayed the above characteristics Takeuchi et al. Clinical Neurology and Neurosurgery 2013; 115(6): 732-735

3 month outcome

Jang et al. Journal of Korean Medical Science, 26 (2011), pp. 100–107

Can We Resolve This?

Careful of the Logical Fallacy • Brain stem hemorrhages do not always progress to brain death, therefore brain stem hemorrhage is not equivalent to brain death • “Brain death is not equivalent to brain stem hemorrhage, therefore should not be diagnosed after brain stem hemorrhage”

Rational Deduction • Premise is that exam features may be transient – • but support is necessary for opportunity of recovery so maintain active resuscitation • Functional assessment is limited in accuracy • Ancillary testing may allow assessment of cortical viability • EEG – can reveal cortical activity • CBF – may demonstrate absence of flow • Persistent flow does not mean life – merely inability to declare at this time • TCD – bedside CBF • that can demonstrate changes over time • Rostrocaudal progression in 12 of 91 patients declared by TCD • Sharma, Souter et al. Neurocritical Care 2011;14(3):370-6

Ancillary testing • There should be no “false positives”, i.e., when the test confirms “brain death” there should be none who recover or who have the potential to recover. • The test should be sufficient on its own to establish that brain death is or is not present. • The test should not be susceptible to “confounders” such as drug effects or metabolic disturbances. • The test should be standardized in technology, technique and classification of results. • The test should be available, safe and readily applied.....ideally it could be applied within any intensive care unit (ICU) and the technique should be reliable and mastered with out difficulty. • Young et al.The role of ancillary tests in the neurological determination of death. Can J Anesth, 2006; 53(6 ): 620–627 Variability of brain death determination guidelines in leading US neurologic institutions. Greer DM; Varelas PN; Haque S; Wijdicks EF Neurology. 70(4):284-9, 2008 Jan 22.

Cerebral Angiography

Radio-isotope scan (scintigraphy) ‘HOT NOSE’ sign

Transcranial Doppler Ducrocq et al. Journal of the Neurological Sciences 1998; 159: 145–150

Hypothermia – Case 2 • 47 yr old woman – opiate induced overdose • Found in PEA, resuscitated at scene • Hypothermia – treated to 33 degrees Celsius for 24 hours. • Now rewarmed over 6 hours. At 36.6 degrees • Unresponsive – no cough, gag, cranial or peripheral reflexes, ‘riding’ the ventilator…

When could you test for brain death? • 1. After warming to 37 degrees Celsius • 2. Now • 3. After 24 hours of normothermia

Observation Periods • Apneic coma after • Major neurosurgery • Confirmed Aneurysm > 4 hours • Aneurysmal re-bleed • Head injury No secondary brain damage > 6 hoursfrom hematoma, shock, or brain hypoxia • Spontaneous intracranial hemorrhage (without secondary > 6 hours hypoxic brain damage) • Brain hypoxia > 24 hours(drowning, cardiac arrest etc) • Any of the above(with suspicion of drug intoxication 50-100 hoursbut no screening facilities)

A cautionary tale…

Whats safe • 24-48 hour post rewarming • Arbitrary • Mechanism dependent • Anoxia versus trauma? • Persistent drug effects • CyP450 – 72 hour effect • Ancillary testing • EEG not helpful – electrical activity = 60% of brain metabolism – affected by sedative drugs • Need assessments of CBF

Limitations of hypothermia • Globally reduces metabolism • Not enough to withstand complete ischemia • 15 °C for circulatory arrest • Remaining metabolism necessitates flow • No flow = cell death Lanier J NeurosurgAnesth 1995; 7(3): 216-221

Case No. 3 • 19 year old male in MVC, GCS 4 at scene and since admission (E1, M2, V1t) • Widespread cerebral contusions affecting both hemispheres, with intracranial hypertension (30-40 mmHg ICP), treated with bolused 23.4% hypertonic saline (HTS) and 3% HTS infusion for 72 hours • This morning, ICP increased to 70, unresponsive to all stimuli, fixed pupils at 5 mm, normotensive • Serum sodium is 168 mEq/L

When can you do a brain death exam? • 1. Now • 2. After sodium corrected to < 155 at 0.5 mEq/hour • 3. After sodium corrected to < 145 at 1 mEq/hour

Hypernatremia • Well accepted effect of electrolyte abnormalities on neurological function • Hypernatremia induces shrinkage of the brain • Consequent distortion of anatomy • Shrinkage can stretch bridging veins, and induce subdural hemorrhage • BUT THIS ASSUMES AN UNSWOLLEN BRAIN • Disease states inducing hypernatremia • are more likely causes of neurologic dysfunction themselves e.g. dehydration • Not relevant in the context of iatrogenic sodium load for an edematous swollen brain • Hypernatremia is associated with mortality • More so in patients receiving mannitol • Aiyagari et al. Journal of Critical Care 2006;21(2):163-172 • Association versus causality...

Increased sodium increases rate of sodium influx through activated channels • Hyperactivity of electrochemical effects rather than depression

Case No. 4 • A 44 year old man was declared dead earlier that day by clinical testing. You are now on call. The nurse in the room calls you urgently – she is concerned by the patient’s response to stimuli. You see the following examination

Video

Which cases represent brain death • 1. Video 1 • 2. Video 2 • 3. Video 3

Spinal reflexes • Neuronal interconnections present in the spinal cord are thought to be involved in the generation of spinal reflex movements – “central generators”. • The corticospinal and rubrospinal tracts in the spinal lateral funiculusare control pathways for distal motor control of the extremities. • The vestibulospinal and reticulospinal tracts located ventrally in the spinal white matter are the media of control over muscle tone, posture, and ‘synergistic’ whole limb movement. • These tracts (and the central generators) are inhibited by supraspinalglycinergic neurotransmission. • Disconnection from inhibition after spinal cord injury or brain death increases excitability at the spinal level – initiating spinal reflex movements to varying stimuli.

40-50% of patients exhibit reflex movements after declaration of brain death • Often complicates management, concerning staff and families Saposnik et al. Can J Neurol Sci. 2009 Mar;36(2):154-60.

Case no 5. • A 36 yr old man self-inflicts a gunshot wound to the head, with a bullet trajectory across the mid-brain. • He was emergently decompressed with a craniectomy, but has been subsequently unresponsive to all stimuli, for 72 hours. • He had a clinical examination earlier today (with apnea trial) which indicated brain death. • The on-call resident decided to get a CBF study (rather than do another exam), which documented persistent cerebral blood flow….

Now what? • 1. Ignore it – the patient is brain dead • 2. Repeat a further clinical exam • 3. Recommend withdrawal of care to the family with donation after cardiac death

Devil in the details • The central nervous system receives, analyses and responds to external stimuli • An image of the brain does not assess any part of that arc of function • Analogous to using a chest X-ray to measure pulmonary function – you may gain some assessment of pathology and its functional impact – but it does not offer accuracy.

BRAINFUNCTION MRI CT EP CBF EEG TCD

Summary • There are clear principles guiding the diagnosis of brain death • The details of care seek to trap the unwary • Exert care in excluding confounders • You can always repeat or add an assessment • More data points usually increase accuracy • Be prepared however to rank the data points in functional significance • Know the limitations of the data and the science

Questions ? • “I know that you believe you understand what you think I said, but I'm not sure you realize that what you heard is not what I meant.” • Robert McCloskey, White House Spokesman 1967 • “If I seem unduly clear to you, you must have misunderstood what I said.” • Alan Greenspan, Chairman of the US Federal Reserve, 1987.

Challenges in Brain Death Declaration