Week 6: Organ Transplant

Question 1

Brain death diagnostic and declaration

Answer 1

• apneaic testing
• testing with cranial nervees
• diagnostics with brain imaging and brain blood flow: If the first 2 are inconclusive, then this one is done or under the age of 1

Question 2

Uniform determination of death act

Answer 2

• irreversible cessation of circulatory and respiratory function
• irreversible cessation of all functions of the entire brain, including the brain stem, is dead.
• A determination of death must be made in accordance with accepted medical standards.

Question 3

Diagnosis of Brain Death

Answer 3

• Brain death is a clinical diagnosis. It can be made without confirmatory testing if you are able to establish the etiology, eliminate reversible causes of coma, complete fully the neurologic examination and apnea testing.
• The diagnosis requires demonstration of the absence of both cortical and brain stem activity, and demonstration of the irreversibility of this state.

Question 4

• Severe head trauma
• Aneurismal subarachnoid hemorrhage
• Cerebrovascular injury
• Hypoxic-ischemic encephalopathy
• Fulminant hepatic necrosis
• Prolonged cardiac resuscitation or asphyxia
• Tumors

Answer 4

Etiology of Brain Death

Question 5

Exclusion of reversible medical conditions that can confuse the clinical assessment:

Answer 5

• Severe electrolyte, acid base and endocrine disturbance
• Absence of drug intoxication and poisoning
• Absence of sedation and neuromuscular blockade
• Hypotension (suppresses EEG activity and CBF)
• Absence of severe hypothermia (core temp < 35 C)

Question 6

What are the cranial nerve responses we see in brain death?

Answer 6

• No pupillary response to light. Pupils midline and dilated 4-6mm.
• No oculocephalic reflex (Doll’s eyes) – contraindicated in C- spine injury.
• No oculovestibular reflex (tonic deviation of eyes toward cold stimulus) – contraindicated in ear trauma.
• Absence of corneal reflexes
• Absence of gag reflex and cough to tracheal suction.

Question 7

Apnea Testing

Answer 7

• Once coma and absence of brain stem reflexes have been confirmed –>Apnea testing.
• Verifies loss of most rostral brain stem function
• Confirmed by: PaCO2 > 60mmHg, or PaCO2 > 20mmHg over baseline value.
• Testing can cause hypotension, severe cardiac arrhythmias and elevated ICP.
• Therefore, apnea testing is performed last in the clinical assessment of brain death.

Question 8

Following conditions must be met before apnea test can be performed:

Answer 8

• Core temp > 35.0 C
• Systolic blood pressure > 90mmHg.
• Euvolemia
• Corrected diabetes insipitus
• Normal PaCO2 ( PaCO2 35 - 45 mmHg).
• Preoxygenation (PaO2 > 200mmHg).

Question 9

Criteria for Brain Death in Children

Answer 9

• Neonate less than 7 days —> Brain death testing is not valid.
• 7 days – 2 months: Two clinical exams and two EEG 48 hrs apart.
• 2 months – 1 year: Two clinical exams and two EEG 24 hrs apart, or two clinical exams, EEG and blood flow study.
• Age > 1 year to 18 years: Two clinical exams 12 hrs apart, confirmatory study (Optional)

Question 10

Confirmatory testing is?

Answer 10

• Purely optional when the clinical criteria are met unambiguously.
• A confirmatory test is needed for patients in whom specific components of clinical testing cannot be reliably evaluated
• Incomplete brain stem reflex testing
• Incomplete apnea testing
• Toxic drug levels
• Children younger than 1 year old.
• Required by institutional policy

Question 11

Confimatory tests for Brain Death

Answer 11

• Cerebral Blood Flow (CBF) Studies: Cerebral Angiography, Nuclear Flow Study
  - you will see lack of blood flow to the brain
• EEG (when brain scan is not utilized)

Question 12

What are the elements of brain death declaration after it is confirmed?

Answer 12

• Date
• Time
• Detailed documentation of Clinical Exam including specifics of Apnea Testing
• Physician signature

Question 13

Loss of brain stem function results in systemic physiologic instability including?

Answer 13

• Loss of vasomotor control leads to a hyperdynamic state.
• Cardiac arrhythmias
• Loss of respiratory function
• Loss of temperature regulation –> Hypothermia
• Hormonal imbalance –> DI, hypothyroidism

Question 14

Once brain death is declared therapy shift in emphasis from ___ to ____?

Answer 14

Therapy shifts in emphasis from cerebral resuscitation to optimizing organ fxn for subsequent transplantation.

Question 15

Without appropriate intervention brain death is followed by severe injury to most other organ systems within?

Answer 15

Circulatory collapse will usually occur within 48hrs.

Question 16

Brain death results in a massive release of?

Answer 16

Massive release of catecholamines, aka “autonomic storm”

Question 17

Phase 1 of autonomic storm

Answer 17

*Phase I: severe hypertension and increased systemic vascular resistance (Cushing response)

• Tachycardia
• Elevated C.O.
• Vasoconstriction
• Hypertension

Question 18

Phase 2 of autonomic storm

Answer 18

*Phase II: systemic vasodilation resulting in hypotension and loss of hypothalamic and pituitary function:

• Decreased levels of circulating Anti-diuretic Hormone
• Loss of thermoregulation

Question 19

Failure of the hypothalamus results in?

Answer 19

• Impaired temperature regulation - hypothermia or hyperthermia
• Leads to vasodilation without the ability to vasoconstrict or shiver (loss of vasomotor tone)
• Leads to problems with the pituitary …

Question 20

Pituitary failure results in?

Answer 20

• ADH ceases to be produced = Diabetes Insipidus
• Can lead to hypovolemia and electrolyte imbalances
• Leads to problems with the thyroid gland

Question 21

Thyroid failure leads to?

Answer 21

• Cardiac instability
• Labile blood pressure
• Potential coagulation problems

Question 22

Intensive care management of cardiovascular sytem rule of 100’s

Answer 22

• Maintain SBP > 100mmHG
• HR < 100 BPM
• UOP < 100ml/hr
• PaO2 > 100mmHg

Question 23

Aggressive fluid resuscitative therapy directed at restoring and maintaining intravascular volume.

Answer 23

Aggressive fluid resuscitative therapy directed at restoring and maintaining intravascular volume. SBP > 90mmHg (MAP > 60mmHg) or CVP ~ 10 mmHg.

Question 24

Respiratory effects of brain death

Answer 24

• Altered permeability of the pulmonary capillary bed
• High pulmonary artery pressures during autonomic storm
• Decreased osmotic gradient secondary to hypotonic fluid administration
• Adverse effects result in increased lung water
• Pre-existing risk factors for pneumonia and
• atelectasis

Question 25

What is DIC and what is it also affected by?

Answer 25

• Results from the passage of necrotic brain tissue into the circulation
• Leads to coagulopathy and sometimes progresses further to DIC
• DIC may persist despite factor replacement requiring early organ recovery
• _Also affected by: _Hypothermia, release of catecholamines, hemodilution as a result of fluid resuscitation)

Question 26

5 parts of organ donor management

Answer 26

• Hypertension —> Hypotension
• Excessive Urinary Output
• Impaired Gas Exchange
• Electrolyte Imbalances
• Hypothermia

Question 27

Hypotension management

Answer 27

• Fluid Bolus – NS or LR ((Followed by MIVF (maitenance IV fluids) NS or .45 NS))
• Consider colloids
• Dopamine: increase contractility of the heart and promote vasoconstriction
• Neosynephrine: increase contractility of the heart and promote vasoconstriction
• Vasopressin: helps with urine output
• Thyroxine (T4 protocol)

Question 28

Why use the T4 protocol

Answer 28

• Brain death leads to sudden reduction in circulating pituitary hormones
• May be responsible for impairment in myocardial cell metabolism and contractility which leads to myocardial dysfunction
• Severe dysfunction may lead to extreme hypotension and loss of organs for transplant
• T4 protocol reduces need for vasopressors and improves number of organs transplanted per donor and graft function

Question 29

T4 Protocol

Answer 29

Bolus:

• 15 mg/kg Methylpred
• 20 mcg T4 (Levothyroxine)
• 20 units of Regular Insulin
• 1 amp D50W

Infusion:

• 200 mcg T4 in 500 cc NS
• Run at 25 cc/hr (10 mcg/hr)
• Titrate to keep SBP >100
• Monitor Potassium levels closely!

Question 30

Vassopressin and Vassopressin protocol

Answer 30

• Low dose shown to reduce inotrope use
• Plays a critical role in restoring vasomotor tone

Vasopressin Protocol

• 4 unit bolus IVP
• 1- 4 u/hour – titrate to keep SBP >100 or MAP >60

Question 31

Diabetes Insipidus Management

Answer 31

• Treatment is aimed at correcting hypovolemia
• Desmopressin (DDAVP) 1 mcg IV, may repeat x 1 after 1 hour.
• Replace hourly U.O. on a volume per volume basis with MIVF to avoid volume depletion
• Leads to electrolyte depletion/instability monitor closely to avoid hypernatremia and hypokalemia

Question 32

• Goal is UOP 1-3 ml/kg/hr
• Rule of thumb – 500 ml UOP per hour x 2 hours is DI
• Severe cases – Notify OPC. Assess clinical situation.

Answer 32

Diabetes Indipidus

Question 33

Impaired Gas Exchange Management in Brain Death

Answer 33

• Maintain PaO2 of >100 and a saturation >95%
• Monitor ABG’s q2h or as requested by OPO
• PEEP 5 cm, HOB up 30o
• Increase ET cuff pressure immediately after BD declaration
• Aggressive pulmonary toilet (Keep suctioning & turning q2h)
• CXR (Radiologist to provide measurements & interpretation)
• OPO may request bronchoscopy
• CT of chest requested in some cases

Question 34

Impaired Gas Exchange Goals

Answer 34

• Goals are to maintain health of lungs for transplant while optimizing oxygen delivery to other transplantable organs
• Avoid over-hydration
• Ventilatory strategies aimed to protect the lung
• Avoid oxygen toxicity by limiting Fi02 to achieve a Pa02 100mmHg & PIP < 30mmHg.

Question 35

ELECTROLYTE IMBALANCE MANAGEMENT (3 things)

Answer 35

Hypokalemia
-If K+ < 3.4 – Add KCL to MIVF
(anticipate low K+ with DI & T4 administration)

Hypernatremia
-If NA+ >155 – Change MIVF to include more free H20, —-Free H20 boluses down NG tube (this is often the result of dehydration, NA+ administration, and free H20 loss 2o to diuretics or DI)

Calcium, Magnesium, and Phosphorus
-Deficiencies here common…often related to polyuria associated with osmotic diuresis, diuretics & DI.

Question 36

Hypothermia Management

Answer 36

• Monitor temperature continuously
• NO tympanic, axillary or oral temperatures. Central only.
• Place patient on hypothermia blanket to maintain normal body temperature
• In severe cases (<95 degrees F) consider:
  - warming lights
  - covering patient’s head with blankets
  - hot packs in the axilla
  - warmed IV fluids
  - warm inspired gas

Question 37

Anemia treatment

Answer 37

• Hematocrit < 30% must be treated
• Transfuse 2 units PRBC’s immediately
• Reassess 1o after completion of 2nd unit and repeat infusion of 2 units if HCT remains below 30%
• Assess for source of blood loss and treat accordingly

Question 38

Overall Management Goals in Patients with Brain Death

Answer 38

• SBP 90-110 mmHg
• U/O 1-3 cc/kg
• HR 60-140
• PAWP (pulmonary artery wedge pressure) 7-12 mmHg
• Serum electrolytes WNL
• CBC and coags WNL
• SPO2 >95%
• PaO2 90-110
• pH 7.35-7.5
• PCO2 25-45
• PF ratio >300

Question 39

Organ Preservation Time after being removed from the body

Answer 39

• Heart: 4-6 hours
• Lungs: 4-6 hours
• Liver: 12 hours
• Pancreas: 12-18 hours
• Kidneys: 72 hours
• Small Intestines: 4-6 hours

Question 40

Second Brain Death note is ?

Answer 40

Official time of death

Question 41

Indications for solid organ transplant (good candidates)

Answer 41

• Death within 12–24 months in the absence of an organ transplant
• Unacceptable quality of life without transplant: Intractable pruritis in progressive sclerosing cholangitis (PSC), Severe COPD
• Potentially lethal complications of the underlying illness: Intractable cardiac arrhythmia
• Prevention of the manifestation of a genetic illness: Familial Amyloid Polyneuropathy (FAP), Metabolic diseases of the liver
• All other forms of medical and surgical management have been tried and failed

Question 42

Absolute Contraindications for Receiving Organ Donation

Answer 42

• Systemic and/or uncontrolled infection
• Active untreated or untreatable malignancy
• Post-transplant Lymphoproliferative Disease (PTLD) unless no active disease demonstrated by negative PET scan and resolved adenopathy on CT/MRI
• Active alcohol and/or other substance abuse Requires six months of documented abstinence through participation in a structured alcohol/substance abuse program with regular meeting attendance and negative random drug testing
• AIDS
• Inability to give informed consent
• Significant uncorrectable life-limiting medical conditions
• Irreversible severe brain damage
• History of non-compliance that has not been successfully remediated

Question 43

Relative Contraidications for Receiving Organ Donations

Answer 43

• Recent graft loss
• Recent history of malignancy (treated) within five years
• Active psychiatric or behavioral disorder
• Remote history (more than six months in the past) of alcohol or substance abuse or occasional recreational use of marijuana
• Insufficient social (caregiver) support
• HIV infection without AIDS and with sustained CD4 counts > 200/mm3
• BMI ≥ 35 kg/m2
• Chronic peptic ulcer disease, GI bleeding, diverticulitis
• High dose systemic corticosteroid use (> 10mg prednisone/day or equivalent)

Question 44

Minimum patient evaluation requirements for Organ Recipients

Answer 44

• Psychosocial evaluation and clearance
• Echocardiogram or MUGA with LVEF > 40 percent OR cardiology clearance
• Colonoscopy (if indicated or > age 50) with removal of any polyps
• Liver function tests (LFT) with transaminases ≤ 3x upper limit of normal and total bilirubin < 2.5mg/dl
• HIV testing
• Hepatitis A, B and C serology
• Serum creatinine < 2.5 mg/dl (≤ 1.5 mg/dl in children) or GFR > 35 ml/min. If abnormal, may be eligible for a combined transplant
• Carotid Doppler ultrasound (with known coronary artery disease or > age 50) — abnormal findings evaluated further; intervention and/or clearance required for abnormal findings
• Ankle-Brachial Index (ABI) (if indicated or > age 50); ABI < 0.95 may indicate peripheral artery disease (PAD); intervention and/or clearance required
• Dental examination; required dental work completed prior to transplant
• Ophthalmology examination (for diabetics) — baseline
• Mammogram (if indicated or > age 40) — intervention and/or clearance required for abnormal findings
• GYN examination with Pap smear (if indicated or > age 18) — intervention and/or clearance required for abnormal findings
• Immunizations up to date when indicated: Hepatitis A, Hepatitis B, influenza and pneumonia

Question 45

Organ Allocation guidelines

Answer 45

• Children have priority over adults
• Body habitus
• Blood group
• Human leukocyte antigens (HLA) match
• High panel reactive antibody (PRA) score: highly sensitized recipients