14 June 2016William A Knight IV, MD, FACEP, FNCSUniversity of Cincinnati

Our role in organ donation and death by neurologic criteria

William.Knight@uc.edu@waknight4

whoever saves a life…it is considered as if he saved an entire world.

-- Mishnah Sanhedrin 4:5 Babylonian Talmud Tractate Sanhedrin 37a

Where is the soul/life force?

Heart vs. Brain (vs. Liver)

Stethoscope improvements▪ Notion of heart as a fuel pump took some getting used to

The majority of the patients that proceed to donation are neurologically injured

We are TERRIBLE at accurate prognosis

• Overall 50.8 % survived• 13.2% had good functional outcome• Bilaterally reactive pupils and GCS 3 = 75% survival

There are no instances in which physiologically sound resuscitation of the patient will harm organ donation Nor should that matter (in general)

Alignment of parallel intentions Resuscitation of patient

If that fails organ viability

Good critical care trumps all else

Care for them like any other patient

Do no more, do no less

Good for the brain is good for the body Don’t be confused by rumor and innuendo

Solid organs:

2 lungs

Heart

2 kidneys

Pancreas

Liver

Small bowel

Tissues:

Heart valves

Skin

Corneas

Bone

Inner ear

Cartilage / tendons

Organ donation is part of the thought process well before brain death occurs

Any patient in whom we are considering limitation of care should be thought of as a potential donor

Donor management begins and ends with autonomy

Donation

Brain Death Donation (BDD)

Donation after Circulatory

Death (DCD)

• Physician role to predict death within 60 – 90 minutes

• Challenging to do well– family is relying on you

Establish irreversible and proximate cause of coma

Known neurologic process▪ Guillain-Barre, brainstem encephalitis

▪ Hepatic failure, uremia, hyperosmolar coma, hypophosphatemia

No metabolic or electrolyte abnormalities

Absence of hypotension▪ pressors

Core body temperature > 92.5 F (vs 96.5F)

No central nervous system depressants ▪ Intoxication

▪ Medical therapy ▪ Barbiturates, paralytics, narcotics, benzodiazepines, amitriptyline, toxic alcohols

Are there patients who fulfill the clinical criteria of brain death who recover brain function?

No

What is an adequate observation period to ensure that cessation of neurologic function is permanent?

Insufficient evidence to determine

Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death?

Yes

Wijdicks, Evidence-based guideline update. Neurology 2010

What is the comparative safety of techniques for determining apnea? Apnea testing is safe but insufficient data to compare different techniques

Are there new ancillary tests that accurately identify patientswith brain death?

Because of a high risk of bias and inadequate statistical precision, there is insufficient evidence to determine if any new ancillary tests accurately identify brain death.

Wijdicks, Evidence-based guideline update. Neurology 2010

Consequence of raised ICP + herniation

Brainstem ischemia, rostral to caudal

MIDBRAIN▪ Apnea

▪ Bradycardia

▪ Hypotension

▪ Drop in cardiac output (vagal mediation from midbrain ischemia)

PONS: Sympathetic stimulation superimposed on vagal

▪ Leads to bradycardia with hypertension ▪ Cushing’s reflex

MEDULLA: Vagal cardiomotor nucleus becomes ischemic

▪ Prevents tonic vagal stimulus

Unopposed sympathetic stimulation

Rise of epinephrine ~ the rate of rise of the ICP

Post storm hypotensive phase secondary to reduced sympathetic flow

Diminished end organ blood flow Further exacerbates prior ischemia if present

Much effort targeted at re-establishing normal CO/CI

Cardiovascular response Autonomic storm Washout instability

Neuroendocrine Response Autonomic storm Posterior pituitary – vasopressin Anterior pituitary – glycemic control and adrenal function

▪ Usually preserved

Temporal considerations Deregulation will often resolve spontaneously

“Autonomic storm” of brain death Pulmonary edema End-organ ischemia Profound vasoconstriction

▪ End organ ischemia despite hypertension

Considerable myocardial ischemia▪ Leads to stunned myocardium

This is not unfamiliar physiology: SAH Severe sepsis (EGDT trial, 2001)

Neurogenic pulmonary edema

PATIENT A

Has severe sepsis Lactate 6.2 mM

MAP 59 mmHg

PATIENT B

Has severe sepsis Lactate 6.2 mM

MAP 105 mmHg

Mortality: 42% Mortality: 61%

Available evidence does not support the need for immediate procurement after brain death

Taking time to optimize perfusion and allow recovery of cardiac function is appropriate

78% of brain dead donors will develop diabetes insipidus Vasopressin

▪ V1 – vascular smooth musclemediates tone

▪ V2 – renal collecting duct antidiuretic

▪ V3 – anterior pituitarymediates ACTH release

DDAVP is selective V2 with no pressor activity▪ Desmopressin

▪ No effect on graft function or survival

Large debate

Literature is conflicting

UNOS data supports it

Data adjustment lacking in trial analysis

Systematic Review and Meta-Analysis of 3 primary donor questions:

• Desmopressin• T3• Ischemic Preconditioning

Don’t send mixed messages after brain death We are supporting organs, not life Do not examine or talk to the patient after declaration It is acceptable to be sad “Grief teaches the steadiest minds to waver”

Use all hospital supportive resources Chaplains / priests, ODA, Social work, OPO

Set time limits for continued organ support

Never introduce the topic

Organ Procurement Organization (OPO) should be involved early and available to speak with the family once declared

If family brings up topic

Support they good intentions and let them know the people that can help with that decision are available

Remember an open casket is possible after donation & autopsy

UCMC, UC Health Policy # II-312, Determination of Death; 2009 American Academy of Neurology, Quality Standards Subcommittee. Practice Parameters: Determining

Brain Death in Adults. Neurology 45:1012-1014; 1995. Wijdicks, EF. The Diagnosis of Brain Death. NEJM 344(16):1215-1221; 2001. Goudreau JL, Wijdicks EF, Eelco FM, Emery S. Complications during apnea testing in the determination

of brain death; Predisposing factors. Neurology 55(7): 1045-1048; 2000. Busl KM and Greer DM. Pitfalls in the Diagnosis of Brain Death. Neurocrit Care 11(2):276-287; 2009. Saposnik, Basile, Young. Movements in Brain Death: A systemic review. Can J Neurol Sci 36:154-160;

2009. Ducrocq, X et al. Consensus opinion on diagnosis of cerebral circulatory arrest using doppler-

sonography. J of Neuro Sci 159:145-150; 1998. Munari et al. Confirmatory tests in the diagnosis of brain death: comparison between SPECT and CTA.

Crit Care Med 33(9):2068-2073; 2005. Excudero et al. Diagnosing brain death by CT perfusion and multislice CTA. Neurocrit Care 11:261-271;

2009. Wijdicks, EF. Evidence-based guideline update: Determining brain death in adults: Report of the

Quality Standards Subcommittee of the American Academy of Neurology. Neurology 74: 1911-1918; 2010.

Triple flexion Babinski sign Preserved DTRs Abdominal and cremasteric

reflexes Sweating Blushing Respiratory-like movements

without significant TV Shoulder elevation and

adduction Back arching Intercostal expansion

Head turning

Spontaneous movements or with painful stimuli (if no full decerebrate or decorticate response considered to be at spinal level): Brief slow movements of upper

limbs

More complex movements (Lazarus signs) come from spinal cord Stretching of the arms,

followed by crossing or touching of the arms on the chest, and finally falling of the arms alongside the torso.

Report of the Quality Standards Subcommittee of the American

Academy of Neurology, 1995

Wijdicks, NEJM 2001

Apnea Test Vitals: Core temperature > 36.5º C or 97º F

SBP > 90mm Hg▪ Can use pressors

Draw a baseline ABG, PCO2 must be ~ 40▪ COPD

Pre-oxygenate with 100% FiO2

Disconnect ventilator, give O2 at 8-12 lpm by tracheal cannula Observe for any respiratory movements

AAN Practice Parameter 1994

Apnea Test Duration varies Usually 5-10 minutes

▪ General rule: ▪ after 2 minutes off ventilator PCO2 will

increase by 5, then for every additional minute the PCO2 will increase by 2.

Draw post-test ABG and reconnect the ventilator.

The patient has no CNS respiratory drive if PCO2 > 60mm Hg. ▪ Adjust criteria for known CO2

retention▪ 20mm Hg above baseline

During test if patient becomes hemodynamically unstable, stop testing, draw ABG and reconnect the ventilator. ▪ Test is indeterminate if PCO2 <

60mm Hg. ▪ Consider confirmatory studies.

AAN Practice Parameter 2010

Complications of apnea testing Hypotension Hypoxia Cardiac arrhythmias Death…

Factors associated with complications pH < 7.3 or > 7.5 Plasma Na <120 or >170 Serum potassium <3.0 or >6.0 Calcium <8.0 or >10.5 Pretest hypotension or administration of vasopressors High oxygen requirements

If apnea test is aborted and pCO2 is not ≥60mmHg an ancillary test must be performed

Goudreau et al, Neurology 2000

Brain death criteria are met if there is no response to any component of the examination.

Confirmatory tests are NOT necessary.

Recommended if unable to assess all cranial nerves.

Options include: ▪ Digital subtraction angiography

▪ EEG

▪ Transcranial Dopplers

▪ Nuclear medicine – brain scintigraphy

Barbiturate levels are required in setting of barbiturate coma▪ ½ life = 15-50 hours

Systole – brief forward flow

Diastole – abrupt flow reversal

Artifact Drug effects Sedation Hypothermia Toxic Metabolic