How to perform a BD exam and
improve donor management
Panayiotis N. Varelas, MD, PhD
Director Neuro-ICU
Senior Staff Neurology / Neurosurgery
Henry Ford Hospital
Associate Professor of Neurology
Wayne State University
Detroit, MI
Topics for discussion
•
•
•
•
Management before BD is declared
How BD exam is performed
How to approach the family
Management after BD is declared
I have received
speaker honoraria and hold stock options
Potential
conflicts:
from The Medicines Company, which has sponsored my
research. I also receive royalties from the publication of
the book Seizures in the ICU, I am an editorial board
member of Neurocritical Care and serving in the
advisory board of Gift of Life of Michigan.
I have received speaker honoraria and holds stock options from The Medicines Company. The same company has sponsored research for which he served as primary investigator. He also receives royalties from the publication of the
book Seizures in the ICU, is an editorial board member of Neurocritical Care and is serving in the advisory board of Gift of Life of Michigan.
HFH Management Recommendations
BEFORE BD Declaration
HFH Management Recommendations
BEFORE BD Declaration
• These recommendations are to be discussed, agreed upon
and ordered by the ICU Primary Team (Senior Staff) and
collaboratively implemented by the ICU Primary team,
Gift of Life representative, and ICU nursing.
• These recommendations are not orders and should not be
used as such. If a decision is made to utilize one or more
of these recommendations, an order must be written by the
physician.
• Methods for attaining goals are just recommendations –
they should not be used if they are contraindicated to the
patient’s condition or contrary to patient’s /family’s
advance directives
HFH Management Recommendations
BEFORE Brain Death Declaration
•
•
MAP maintained ≥ 60 mmHg – Prevent Hypotension
Keep CPP > 70, if an ICP monitor is in place
–
–
–
–
–
Maintenance IV Fluid: 0.9% NS with 20 mEq KCl @ 100-150ml/hr.
(Saline may need to be adjusted for Na+ greater than 160, see
below.)
For hypovolemia: Bolus with 500mL 0.9% NS until MAP sustains
≥60 mmHg.
Start Dopamine and titrate to maintain MAP ≥ 60 mmHg (max 20
mcg/kg/min). Always notify the physician when starting pressors or
inotropes or transfusing blood products.
If Dopamine is at 20 mcg/kg/min, CVP greater than 10, and
MAP/CPP remains less than 60 mmHg, consider norepinephrine
infusion. Titrate to clinical effect (max 20 mcg/min)
If Hct ≤ 25%, recommend 1 unit of PRBC’s over 1 hour, repeat as
necessary to maintain HCT ≥ 25% or hemoglobin > 7.0.
HFH Management Recommendations
BEFORE Brain Death Declaration
•
Hypertension
–
•
Use IV Hydralazine prn. Avoid beta-blockers.
Hypothermia
–
•
Warming blanket to maintain core body temp between 36.5° – 37.2° C,
except for pts with induced-hypothermia.
Diabetes Insipidus (DI)
–
For urinary output greater than 4 mL/kg/hr X 2 hrs AND Na+ > 155 and
rising, recommend Vasopressin drip or replace urine output mL/mL:
If Na+ > 160, use Half NS (0.45%) for replacement
If Na+ ≤ 160, use NS 0.9% for replacement
Always notify the physician if pt hypotensive (CPP < 70,
MAP < 60) or tachycardic (HR > 90)
HFH Management Recommendations
BEFORE Brain Death Declaration
•
Hypoxemia
–
–
–
–
–
–
–
Titrate FiO2 to maintain SaO2 greater than 98% or
PaO2 > 300 on FiO2 1.00
Tidal Volume at 6 mL/kg
Add PEEP of 5-8 cmH2o
Rate adjusted to maintain normal pH (7.35-7.45)
Suction and turn patient q 1-2 hrs
Initiate Chest Percussion and Vibration q 1-2 hrs
Albuterol Nebulizers: 2.5mg q 4 hrs.
How to perform a BD exam?
Current BD criteria in the US
• Responsibility left to individual institutions: Each
hospital has to develop its own criteria, based on
• State laws  criteria based on “accepted medical
standards”, based on
• President’s Commission (1981), Uniform
Determination of Death Act (UDDA, 1993), AAN
(2010) or other Societies recommendations, which are
“advisory” and carrying the weight of “guidelines”
rather than standards
HFH: determination of brain death
• Determination of “death by brain criteria”
in accordance with MI law
• Two different physicians, licensed in MI:
1) The primary senior staff physician
2) Senior staff from Neurology or NS
or designated physician under direct
supervision, i.e resident, fellow
Determination of brain death - Process
• GCS ≤ 5
GOL notified within 1 hour
• If All prerequisites are met
• Clinical evaluation:
 Cerebral unresponsiveness: deep, irreversible coma
 Absence of brainstem reflexes
 Absence of respiration (Apnea test)
• ± Confirmatory testing
Determination of brain death - Prerequisites
• Established & sufficient cause of irreversible coma
• Age  7 days
• Exclusion of any complicating condition confounding
clinical assessment:
 Absence of deep sedation or peripheral nerve or muscle
dysfunction, i.e., (+) TOF, if NM blockade
 ToxScreen: ETOH < 80mg%,  < 10g/ml, drugs?
 Temp-core  32.2oC (90oF)
 SBP  90 mmHg or MAP > 60 mm Hg or age-specific
normotensive range in children
 Severe electrolyte, acid-base or endocrine disturbances
Suspicion of drugs – toxins?
• Administer antidotes
•
•
•
•
Narcotics  naloxone
Benzodiazepines  flumazenil
Carbon monoxide  oxygen
Carbon disulfide, cyanide, hydrogen sulfide  amyl nitrite
• Declare brain death if traces of drug are found below
therapeutic level
• Unable to quantify drug/poison  observe for x 5 half lives
• Unknown, but high suspicion  48 hrs observation, if no 
 confirmatory study
Wijdicks Brain Death 2001
Pitfall: Effect of hypothermia on sedative metabolism
Figure A shows the time course changes in
concentration of Midazolam in brain-injured
patients undergoing hypothermic therapy As
shown in (A) concentration of the agent
increased linearly until Body Temp reached
35 °C, after which the levels decrease
profoundly when Body Temp rose to 36 °C,
even during continuous administration of
Midazolam.
(B) Depicts the time course changes in
concentration of Midazolam in brain-injured
patients with normothermic therapy. In the
figure, the concentration of the agent
increased at 24 h after administration, then
plateaued from 72 h, lasting until 216 h,
during continuous infusion.
Fukuoka et al, Resuscitation 2004
Clinical Examination - Coma
• Lack of responsiveness to supraorbital nerve,
nail-bed or TMJ pressure
• Pitfalls:
Uncoordinated, non-integrated into posturing
responses = i.e. 2o to spinal cord reflexes
Partial eye opening in response to ipsilateral
nipple twisting 5 sec later (sympathetic fibers
to Muller’s muscle?)
(Santamaria et al., 1999)
Clinical Examination - Reflexes
• Mid-position (4-6 mm) or dilated pupils
• Pitfalls: Drugs that influence pupils:

Topical application of mydriatics

Atropine in IV doses 0.03 mg/kg  slight mydriasis,
but (+) reaction to light
(Goetting et al., 1991)

Escalating doses of non-depolarizing paralytics
lead from reversible   to non-reversible
mydriasis
(Schmidt et al., 2000)
Clinical Examination - Reflexes
• Oculocephalic reflex (Cervico-occular, COR)
• Cold calorics (VOR)
• Pitfalls:  or absent if:
 Toxic levels of aminoglycosides,
tricyclics, anticholinergics, antiepileptics
 Orbital edema
 Battle’s sign (ipsilaterally)
Clinical Examination - Reflexes
• Corneal, blinking to threat
• Grimacing to pain, jaw reflex
 Pitfall: facial myokymia/fibrillation from muscle
denervation may mimic facial movements
• Nasal tickle (V2 - XI)
• Gag, cough
• Over-breathing
• Atropine test:  tachycardia (↑ HR > 3%) to 2-3mg
IV atropine
(Huttemann et al., ICM 2000)
Apnea test
•
•
•
•
•
Pre-admission or
“normal” level for
the pt
Always with the second BD exam
Pre-oxygenation 100% FiO2
PaCO2 target: 60 mmHg or [baseline + 20]
PaCO2  by 3-6 mm Hg/min
Hypothermia ( CO2 production, left shift
O2 dissociation curve)  normothermia
• Hypotension  SBP goal 90 mm Hg
Apnea test - Solutions
•
Unable to complete the test??

CO2 augmentation (1 L/min) – PaCO2 > 60 mmHg
within 2 min
(Lang, 1995)

Bulk diffusion (set rate = 0, CPAP = 0, 100% FiO2, 40-60
L/min continuous flow) - 22/24 pts completed the test
 repeat after correcting the problem
 clinical exam + confirmatory test
 use tricks:
(al Jumah et al., 1992)

T-piece (12 L/min) with CPAP valve (10 cm H2O) – less
desaturation with T-piece compared to cannula inside
ETT or T-piece alone
(Levesque et al., CCM 2006)

ADVICE: perform apnea test even if pt on high FiO2 and
draw ABGs as O2 Sat reaches 90%!
HFH: determination of brain death - Observation
period between 2 clinical exams
• Structural brain lesions: 2 Clinical exams  6
hours + apnea  optional ConfTest
• Catastrophic structural brain lesion: 1 exam
+ ConfTest (CBF test) + apnea
• Ischemic/anoxic injury: 2 Clinical exams  24
hours + apnea  optional ConfTest (for ex. if
neuroimaging inconclusive)
HFH: determination of brain death Observation period between 2 clinical exams
(continue)
• Children 1 year – 18 years: 2 Clinical exams  12
hours + apnea ( optional ConfTest)
• Children 2 months – 1 year: 2 Clinical exams  24
hours + apnea + ConfTest
• Neonates 7 days – 2 months: 2 Clinical exams 
48 hours + apnea + ConfTest (2 EEGs 48 hours
apart or CBF study, if equivocal)
• Pregnant women: no BD exam or test, until
confirmation of viability of fetus
Confirmatory tests may be required
• Confirmatory Tests “are recommended”:
1.
Normal or inconclusive CTOH/MRI
2.
COPD or sleep apnea- ? chronic  PaCO2
3.
Inconclusive or indeterminable apnea test
4.
Children
5.
Inability to perform full clinical exam
6.
Severe facial trauma (ex. Racoon eyes)
Relevant racoon eyes
And NOT…
Confirmatory tests may be required
(continue)
7.
8.
9.
10.
11.
12.
Preexistent abnormal/surgical pupil
Severe cranial neuropathies
Toxic/therapeutic level of CNS
depressants, neuromuscular blocking agents,
aminoglycosides, anticholinergics
(?) complex/integrated motor activity
Injury as a result of crime (not at HF!)
If only one brain death exam is required
(as @ Henry Ford!!)
Electroretinogram
99mTc scintigraphy
SPECT with 99mTc-HMPAO
Clinical Questions
1.
2.
3.
4.
5.
Are there patients who fulfill the clinical criteria of brain
death who recover brain function?
What is an adequate observation period to ensure that
cessation of neurologic function is permanent?
Are complex motor movements that falsely suggest retained
brain function sometimes observed in brain death?
What is the comparative safety of techniques for
determining apnea?
Are there new ancillary tests that accurately identify patients
with brain death?
BRAIN DEATH
Approaching the family
AND NOT DISCUSSING ABOUT DONATION!!!
Consent rates
• Average national consent rate 45-50%
• Early referral
when BD is imminent
• Suitability for donation relies on OPO
(Franz et al., 1997, DeJong et al., 1998)
Consent rates
• Factors improving donation rates:
1.
Discussion in a quite environment
2.
Trained requester (i.e., OPO)
3.
Decoupling = family understands & accepts BD
before any donation mentioned
(Gortmaker et al., 1998)
4.
Within 30 min after BD notification (because if
simultaneous  donation rate  by 20-40% !)
(Niles & Mattice, 1996)
NICU Brain Death and Organ Donation Request Policy
(Helms et al. Neurology 2004)
• Donation was not discussed prior to brain death
• Brain death declared according to hospital and
AAN policies
• Family informed and brain death process
explained by treating attending physician
• Physician does not bring up donation to family
and leaves the room
• Procurement coordinator (OPO) makes the request
Organ and tissue donation consent rates 21 months before
and 21 months after the institution of policy change
(Helms et al. Neurology 2004)
Before %
After %
Odds ratio, 95% CI
p value
Eye
17.1
30.8
1.5, 0.6-3.6
0.5
Bone & Tissue
10.4
37.3
5.1, 1.7-15.9
0.002*
Solid organs
45.6
52.6
1.3, 0.5-3.1
0.7
Total
23.1
36.5
1.9, 1.15-3.15
0.01*
Eye
16.5
14.2
0.8, 0.5-1.4
0.5
Bone & Tissue
27.1
29.3
1.1, 0.6-2.0
0.8
Solid organs
45.0
61.5
1.9, 0.6-6.4
0.4
Total
19.7
22.4
1.2, 0.9-1.7
0.3
NICU
Other units
Approaching the family
1. Let family know that the 1st BD is done and a 2nd
will be performed at X time.
2. No mention about donation !
3. If family asks about it, refer them to GOL
4. After the 2nd exam (or after the only BD exam),
discuss again with family and explain the results
and that the pt is irreversibly and legally dead.
5. Allow time for them to absorb the info, introduce
GOL to them and then leave the room
Approaching the family
6. If the family decides for donation and
consent is signed  GOL takes over
 Help GOL with tests, procedures
7. If the family decides against donation 
pt is disconnected from vent within 1
hour
Time from declaration to VF- asystole
Time (hours) to asystole
No of
patients
<24
Jorgensen 1973
63
62%
Mohandas and Chou 1971
25
56%
Hicks and Torda 1979
25
80%
20%
Narimazie 1980
10
60%
40%
Jennett et al 1981
476
36%
Ouaknine 1975
40
“Generally between 1 and 7 days”
Kaste et al 1979
12
“On average 24 hours”
Nishimura 1984
12
“On average six days”
Goulon 1984
23
“Up to 128 hours”
Study
Kenneth Wood, DO, University of Wisconsin,
24-48
48-72
>72
25%
20%
31%
13%
16%
11%
8%
23%
Pallis ABC of Brain Stem Death 1996
Medical management after BD
• Integrative, multi-disciplinary and
collaborative approach between OPO and
Critical Care Team
• Pre-BD management, aiming at brain
function preservation, may compromise other
organs and contradict the post-BD/donor
management
• Aggressive donor management may allow up
to 84% of initially unsuitable donors to yield
transplantable organs
(Wheeldon et al., J Heart Lung Transpl 1995)
Kenneth Wood, DO, University of Wisconsin
Kenneth Wood, DO, University of Wisconsin
Hemodynamic Effects of Sympathomimetics
MAP
PCWP
CO
SVR
HR
Dobutamine
Dopamine – moderate
5-10 mcg/kg/min
Dopamine – high
> 10 mcg/kg/min
Isoproterenol
Norepinephrine
Epinephrine
CO – cardiac output; HR – heart rate; MAP – mean arterial pressure; PCWP –
pulmonary capillary wedge pressure; SVR – systemic vascular resistance.
Organ Donor - Heart
Myocardial Dysfunction
Sympathetic
Surge
Hormone
Depletion
• Myocardial
necrosis
secondary to
catecholamines
• Low circulating
levels thyroid
and cortisol
impair function
Subendo
Ischemia
• Decreased coronary
perfusion pressure
precipitates ischemia
impairing myocardial
function
Kenneth Wood, DO, University of Wisconsin
Changes in Ejection Fraction with Serial
Echocardiograms (16)
100

90
Ejection Fraction
80
70
60
50
40
30
20
























10
0
0
5
15
10
Time (hours)
20
25
30
Zaroff J Heart Lung Txp 2003; 22:383-388
Donor Management Assessment
Brain dead patient (< 65 years old)
Assess ventricular function by echocardiogram
Ejection function  45%
Norm
al
Pulmonary artery catheter placement
Patient age
Repeat echocardiography within 12 hours
< 40 years
> 40 years
Normal
Cardiac catheterization
Normal
Proceed to transplant
Abnormal**
Persistently abnormal*
Consider dobutamine
echocardiography (viability study)
Reversible
dysfunction
No reversible
dysfunction
Not a donor
Palac Prog Transplant 2003; 13:42-46
h Wood, DO, University of Wisconsin
Hormonal Therapy (BD Animal Models)
Pre- Treatment
MYOCARDIAL
Function
ATP
Creatine
Phosphate
Glycogen
Lactate
SYSTEMIC UTILIZATION
Glucose
Pyruvate
Palmitate
Lactate
Free fatty acids
Post Treatment
Aerobic  Anaerobic
Anaerobic  Aerobic












Insulin





Cortisol
T3





Novitzky Cryobiology 1987; 24: 1-10
Novitzky Transplantation 1988; 45:32-36
Rescue Hormone Therapy
If  10g/kg/min Vasoactive Support
• 1 ampule 50% dextrose – 20 u insulin
• 2 grams methylprednisolone
• 20 g levothyroxine  infusion 10 g/h
PRE
POST
Vasopressor ug/kg/min
11.1
6.4
Heart rate beats/min
120
113
Oxygen consumption ml/min/m2
107
123
Oxygen extraction %
16
18
Salim Arch Surg 2001; 136:1377-80
Aggressive Pharmacologic – Hormonal Replacement
Rosendale Transplantation 2003;75:482-487
Pulmonary Edema
Ware & Matthay, NEJM 2005
Role of Brain Death in Donor Lung Injury
Alvonitis Trasnaplantation 2003; 75:1928-1933
Neurogenic Pulmonary Edema
• “Blast Injury Theory” → Hemodynamic mechanism
Left
• Sympathetic surge
↑ SVR ↓CO ↑LAP
Right ↑ Pvc ↑ VR ↑PAP ↑Pul Volume
• Transient massive ↑ of hydrostatic pressure with
structural damage to pulmonary capillary endothelium
• Sympathetic alteration of capillary permeability
Inflammatory Response
• Cytokines → TNF, IL-1 activate endothelial cells to express ICAM-1 and
neutrophil migration to interstitium/alveolar spaces → release ROS and
proteolytic enzymes
Infection – atelectasis - hemo/pneumothorax
• ALI/ARDS in 15-20% of severely brain-injured pts
Neurogenic Pulmonary Edema in 11 chacma baboons
 ICP  Autonomic Storm
Catecholamine Excess
Intense Vasoconstriction
Right Circuit
Left Circuit
• Redistribution blood to RA/RV
• SVR 537%
• Adjustment to  VR by  COR
• MAP  196%
• PA flow  25%
• Aortic flow  42% LV failure
• mPAP  (14 34mmHg)
Exceeds for 1 minute
•  LAP (8-52mmHg)
• Capillary blood flow arrest
• Blood pooling -72% of total circ. volume in lungs
• Blast injury-disruption of anatomic integrity of pulm capillaries
Kenneth Wood, DO, University of Wisconsin
Novitzky Ann Thorac Surg 1987; 43:288-294
Kenneth Wood, DO, University of Wisconsin
Management of Respiratory Function in the Organ Donor
Goals of mechanical ventilation
FiO2: 0.40
PaO2 > 100 mmHg; or PaO2 > 300 on 100% FiO2
PaCO2: 30-35 mmHg
Arterial pH, 7.35-7.45
Tidal volume: 10-12 ml/kg of predicted body weight
PEEP: 5 cm of water
Peak airway pressure: < 30 - 35 mm Hg
CVP 6-8 mm Hg or PAWP 8-12 mm Hg
Recruitment maneuver: prone or CPAP 40 cm H2O x 30 sec,
repeated q 20 min x3
Kirschbaum & Hudson, Prog Transpl 2010
Management of Respiratory Function in the
Organ Donor
Goals of bronchoscopy
Evaluate anatomy; Assess for foreign body and assist in removal
Define and locate aspirated material or apparent infection;
Clearance of secretions
Goals of pulmonary hygiene
Prevent atelectasis with the use of q 2-4 hr ETT & supraglottic
suction, percussion, postural drainage and lung-expansion
techniques; Bronchodilators; Paralytics
Use of anti-infective & anti-inflammatory therapy
Use of antibiotics based on results of Gram’s staining of aspirated
secretions
Methyl-prednisolone 15 mg/kg IV plus 15 mg/kg IV q 6 hrs
Naloxone 8 mg IV to minimize Neurogenic Pulmonary Edema (?)
Kirschbaum & Hudson, Prog Transpl 2010
• Retrospective, all potential donors within a 5-year period
• 20 pts on ACV & 25 pts on APRV
• ACV: RR 10-12 breaths/min, TV 5-10ml/kg, 40%, PEEP 5
• APRV: 6-10 breaths/min, inspir pressure 20-25 cm H2O and 40%
Donated lungs:
7/40 (18%) in ACV vs
42/50 (84%) in APRV
(p < 0.001)
Partial pressure of arterial oxygen (PaO2)/fraction of inspired
oxygen (FIO2) ratios on admission to the intensive care unit
and following 100% oxygen challenge
Hanna, K. et al. Arch Surg 2011;146:325-328.
Management of Liver donors
Increased recipient death or re-transplantation:
• ABO incompatibility
• High Na+ levels (> 155 mEq/L)
• Long cold ischemia time
• Large platelet transfusions
• Prolonged recipient PTT
Ploeg et al., Transplant 1993; Figueras et al., Transplant 1996; Kutsogiannis et al., Can J Anaesth 2006
Management of Kidney donors
• + Immunomodulatory effects of catecholamines
Low dose dopamine (< 10 g/kg/min) or
epinephrine or vasopressin (< 0.04 U/min)
• Colloids can be used (hydroxyethyl starch)
• Avoid SBP < 80-90 mm Hg
• Keep urine output > 1 ml/kg/hr
• Avoid nephrotoxic drugs
Deman at al., Nephrol Dial Transplant 1999; Dictus et al., Clin Transplant 2009
Intensivist-Led Management of Brain-Dead Donors
Is Associated with an Increase in Organ Recovery
for Transplantation
In the before period, 66 out of
210 (33%) potentially
available organs vs. 113 out of
258 (44%) potentially
available organs in the after
period, p = 0.008
Singbartl et al, Am J Transpl 2011
Island of KEA, Greece