Pediatric Donor Management: A Case Study

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Pediatric Donor ManagementA Case Study
Thomas A. Nakagawa, M.D, FAAP, FCCM Pediatric
Critical Care Medicine Brenner Childrens
Hospital, North Carolina Baptist Medical Center
Department of Anesthesiology and Pediatrics Wake
Forest University School of Medicine Winston-Salem
, North Carolina
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Questions To Run On

• What can we do to optimize donation for children
  and their families?
• What effective practices can we provide to our
  colleagues to increase organs available for
  transplantation in children?

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Case presentation

• A 2 year old presents to an outside hospital
  with a chief complaint of lethargy. On the day of
  admission the child was lethargic, had a low
  grade fever and emesis in the early morning.
  Examination revealed blood pressure of 100/66,
  heart rate of 96, respiratory rate of 16,
  temperature 99.6. This child is lethargic, but
  does arouse to noxious stimulation. Pupils are
  equal and reactive to light. Lungs are clear to
  auscultation. He is warm and well perfused. He
  is given a single dose of Ceftriaxone and a
  lumbar puncture is performed. CSF is cloudy with
  120,000 WBCs and gram positive cocci noted on
  the gram stain. Differential is 90 PMN cells.
  CSF chemistries reveal a protein of 1500, glucose
  lt 10. Arrangements are made for hospital
  admission.

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Case presentation (cont)

• Two hours following his lumbar puncture the
  child has an episode of emesis, becomes
  bradycardic, and develops apnea followed by
  asystole. Closed chest compressions are
  initiated, he is intubated with possible
  aspiration of gastric contents reported. He
  receives 2 doses of epinephrine and one dose of
  atropine with ROSC after 6 minutes. His blood
  pressure is 60/40. He receives a fluid bolus of
  normal saline and a dopamine infusion is started.
  Provisions are made for transport to the
  tertiary care childrens hospital.
• En route to the childrens hospital this child
  has another cardiac arrest. His dopamine had
  been escalated to 20 mcg/kg/min and he received
  an additional dose of epinephrine with ROSC.
  Upon arrival to the PICU, this child is comatose.
  Vital signs blood pressure is 80/36, heart
  rate is 110, no spontaneous respiratory effort is
  noted. Temperature is 93.6. Neurologic exam
  reveals fixed and dilated pupils. No cough,
  corneal or gag reflexes are noted. He has
  minimal movement of his left shoulder with
  noxious central stimulation. He continues on a
  dopamine infusion at 20 ug/kg/min an epinephrine
  infusion at 0.3 ug/kg/min. He has brisk clear
  urine output.

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Has this child achieved neurologic death?

• He has fixed and dilated pupils.
• He has no cough corneal or gag reflexes.
• His body temperature is 93.6
• His blood pressure is relatively low for a 4
  year old
• Systolic blood pressure 2(age in years) 80
• Lowest acceptable SBP 2(age in years) 70

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• There are no unique legal issues in determining
  brain death in children as compared with adults.
  The unique issues are all medical ones and
  related directly to the more difficult tasks of
  confirming brain death in young children

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• C. Older than one year of age when an
  irreversible cause exists, ancillary testing is
  not required and an observation period of 12
  hours is recommended. There are conditions,
  particularly hypoxic ischemic encephalopathy, in
  which is it difficult to assess the extent of
  reversible brain damage. This is particularly
  true if the first examination is performed soon
  after the acute event. In this situation, a more
  prolonged period of at least 24 hours of
  observation is recommended. The observation
  period may be decreased if the EEG demonstrates
  electrocerebral silence or the cerebral
  radionuclide or cerebral angiography study
  demonstrates no flow or visualization of the
  cerebral vessels.

American Academy of Pediatrics Task Force, 1987
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Understanding limitations of pediatric brain
death guidelines

• Guidelines that are almost 20 years old
• Guidelines that did not address the trauma
  population
• Guidelines based upon limited clinical experience
  at the time of publication
• Guidelines based upon age criteria
• No guidelines for neurologic death in neonates
• Waiting times have never been validated

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This child has not achieved neurologic death

• Although he has lost most of his brain stem
  reflexes, he has some movement with central
  stimulation
• He has received atropine
• Atropine dilates pupils but does not make them
  non-reactive
• Brain death criteria in children requires two
  examinations according to the Task Force
  Guidelines published in 1987

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So now what will you do?

• A. Do nothing
• B. Tell the parents the situation is hopeless
  and allow the child to die
• C. Continue supportive care to maintain blood
  pressure and organ system function

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• Supportive care was continued. Central venous
  access and arterial cannulation have occurred.
  Inotropic support was continued along with volume
  resuscitation. Mechanical ventilation continued
  with increased PEEP due to a PaO2 of 140 on an
  FiO2 of 1.0. Urine output was excessive. Urine
  output was replaced cc/cc with 1/2 NS.
  Antibiotic therapy was continued. It was unclear
  if this child received vancomycin at the
  referring facility. A vancomycin level on
  admission was 1.6.
• Discussions with the parents occurred throughout
  the day. The parents understood that their
  childs condition was critical and that he may
  not survive this event.

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• Over the next several hours hemodynamics
  remained unstable. Inotropic support was
  titrated to maintain systolic blood pressures
  gt 84 mmHg. Oxygenation and ventilation were
  easily controlled. PaO2 increased to 410 torr on
  an FiO2 of 1.0. Lactate was 1.9. Serum Na had
  increased from 139 to 156 mg/dl. Urine output
  replacement continued and a vasopressin infusion
  was started to help control urine output.

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Pharmacologic Management of Diabetes Insipidus

• Vasopressin (Pitressin)
• Correction of hypernatremia with hemodynamic
  instability
• Dose
• Continuous IV infusion 0.5 milliunits/kg/hour
  titrated to effect
• Desmopressin (DDAVP)
• Correction of hypernatremia without hemodynamic
  instability secondary to greater ADH effect
• Correction of hypernatremia with associated
  bleeding problems ( coagulopathy)
• Dose
• Continuous infusion rate 0.5 µg/hour titrated
  to effect
• These agents are ineffective when administered by
  the intranasal or subcutaneous route in this
  patient population

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So now what will you do?

• A. Continue current care to maintain blood
  pressure and organ system function
• B. Initiate a thyroid hormone infusion
• C. Administer IV solucortef
• D. Tell the parents the situation is hopeless
  and allow the child to die

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Hormonal replacement therapy

• Consider using HRT early in the course of donor
  management
• There is no contraindication to using HRT in a
  patient prior to neurologic death
• Steroids for sepsis
• Thyroid hormone in post-operative cardiac
  patients and patients with hypothyroidism
• Vasopressin and desmopressin are routinely used
  for the treatment of DI
• Hormonal replacement therapy decreases the need
  for inotropic support in children
• Zuppa AF, Nadkarni V, Davis L, et al. The effect
  of a thyroid hormone infusion on vasopressor
  support in critically ill children with cessation
  of neurologic function.
• Crit Care Med 2004322318-2322.
• As neurologic death occurs, alteration in the
  hypothalamic-pituitary-adrenal axis (HPA axis)
  occurs

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Impairment of the HPA axis
Impaired posterior pituitary function results in
loss of anti-diuretic hormone (ADH)
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Hormone Replacement Therapy

• Thyroid hormone replacement
• Levothyroxine (T4)
• Triidothyronine (T3)
• Steroid replacement
• Hydrocortisone
• Control of DI
• Vasopressin (Pitressin)
• Desmopressin (DDAVP)
• Control of hyperglycemia
• Insulin

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Thyroid hormone

• Effects of thyroid hormone
• Increases cardiac output
• Increases heart rate
• Increases ventilation rate
• Increases basal metabolic rate
• Affects cellular metabolism
• Administration of thyroid hormone
• Triiodothyronine (T3)
• Active form of thyroid hormone
• T3 is converted from T4 (thyroxine) in the
  peripheral circulation by deiodinase
• T3 is 4 times more active than T4
• Dose 0.05-0.15 mcg/kg/hour titrated to effect
• Thyroxine (T4)

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Thyroid hormone (cont)

• Levothyroxine (Synthroid, T4)
• Route of administration IV continuous infusion
• Dose 1 mcg/kg/hour titrated to effect

Zuppa AF, et al. Critical Care Medicine
2004322318-2322
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Additional considerations

• Dopamine for hemodynamic support
• Dopamine inhibits TSH production
• Decreased TSH production results in decreased
  release of thyroid hormone from therapy to
  maintain hemodynamic stability
• Decrease of TSH from CNS insult and alteration of
  the HPA axis
• Potential donor is in a relative hypothyroid state

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Steroids

• Steroid production will be inhibited or lost due
  to CNS insult and loss of the HPA axis
• The use of steroids should be considered early in
  the course of the child with hemodynamic
  instability that is minimally responsive to
  aggressive inotropic support
• Steroids up-regulate adrenergic receptors making
  them more sensitive to the effects of
  catecholamines
• Enhance response to inotropes
• May provide an important role in stabilization of
  pulmonary function for the potential donor

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Why start HRT early?

• HRT is inexpensive
• Adverse effects to the potential donor are
  minimal
• It may increase graft function post-operatively
• Continued therapy for the dying child reinforces
  to the parents that everything humanly possible
  is being done for their child

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• HRT using levothyroxine and solucortef was
  initiated. Vasopressin was continued with
  improved control of urine output. Over the next
  12 hours inotropic support had been reduced to 4
  ug/kg/min of dopamine. Serum Na had decreased
  to 140 mg/dl. This childs neurologic exam
  continued to deteriorate and he eventually lost
  all movement to noxious central stimulation. An
  apnea test was performed. There was no
  spontaneous respiratory effort with a PaCO2 of 87
  torr after 10 minutes.
• Supportive care was continued. The parents were
  present during the examination and understood the
  clinical implications of the neurologic
  examination and apnea test. A second brain death
  examination occurred 12 hours later.

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• The following morning this childs clinical
  examination remained unchanged. A second brain
  death exam including an apnea test was performed.
  The brain death examination remained consistent
  with neurologic death. The child was pronounced
  at 0745 hours.
• The parents consented to organ donation. 26
  hours after declaration of death, this child went
  to the operating suite for recovery of organs.

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The importance of declaring neurologic death in a
timely manner

• Allows families and society to begin the grieving
  process
• Prevents us from wasting valuable resources in
  critical care units
• 25 of potential donors are lost due to
  hemodynamic instability following neurologic
  death
• Early and aggressive use of hormonal replacement
  therapy can enhance organ recovery and result in
  improved graft function
• Rosendale JD, Kauffman HM, McBride MA, et al.
  Aggressive pharmacologic donor management results
  in more transplanted organs. Transplantation
  200375482-487.

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• Early HRT is only part of good donor management
• Donor management must be guided with input from
  the pediatric intensivist and critical care team
• Collaboration with the transplant coordinator,
  OPO, chaplain, social and other support services
  is vital for successful donation to occur
• Communication with the family is imperative for
  donation to be successful
• Hormonal replacement therapy can be initiated
  prior to declaration of death
• Hormonal replacement therapy appears to decrease
  the need for inotropic support
• Zuppa AF, Nadkarni V, Davis L, et al. The effect
  of a thyroid hormone infusion on vasopressor
  support in critically ill children with cessation
  of neurologic function.
• Crit Care Med 2004322318-2322.
• Does early HRT improve organs available for
  transplantation?

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Pediatric Donors Brenner Childrens Hospital,
Wake Forest University Baptist Medical Center.
2004-2006
2004-2005 10 donors Recovered 4.5 organs per
donor Transplanted 4.1 organs per
donor 2006 5 donors Recovered 4 organs per
donor Transplanted 4 organs per donor
2007 2 donors Recovered 3 organs per
donor Both donors were DCD donors ages
18 and 10 months
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Questions To Run On

• What information have you gained from this
  presentation that can help you optimize donation
  for children and their families?
• What effective practices can we provide to our
  colleagues to increase organs available for
  transplantation in children?

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Conclusions

• Good donor management equals good patient care
• Collaboration between the OPO and the Pediatric
  Intensivist and critical care team is essential
  for good outcomes
• Early hormonal replacement therapy can increase
  the number and quality of organs available for
  transplantation
• DCD has the potential to increase organs
  available for transplantation in children
• Timely declaration of neurologic death and
  meticulous care directed towards the preservation
  of organs for transplantation is essential for
  positive outcomes
• In cases where homicide has claimed the life of a
  child, early involvement and close collaboration
  with the medical examiner and investigative team
  can help alleviate any conflict between
  preservation of evidence and organ recovery

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Bold Request

• Meet with your transplant coordinators and your
  colleagues to discuss issues pertaining to
  pediatric donation.
• Make the commitment to make your center a center
  of excellence for end of life care
• Physician accountability and responsibility
• Choose one of the best practices and institute
  this practice in your unit to see if it improves
  your outcome with recovered organs for your next
  three potential organ donors.
• A strong relationship with the OPO
• Early involvement of the OPO
• Declaration of death in a timely manner
• Early hormonal replacement therapy to assist with
  hemodynamic instability

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Important area for growth

• Pediatric DCD
• DCD targets the two most needed organs for
  children
• DCD requires extensive collaboration with the
  physicians, nursing staff, OR staff, OPO, and the
  family to ensure the best outcomes
• Although DCD pediatric donors may be a small
  percentage of the entire pediatric donor pool,
  DCD should be considered for any child, and their
  family, who are facing end-of-life issues
• Ethical issues surrounding DCD
• Utilize colleagues who are comfortable with this
  type of donation to care for and work with
  families who request donation
• Work to improve understanding of all issues
  related to DCD
• Better understand issues of when a person is
  really dead

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Pediatric DCD donors
Scientific Registry of Transplant Recipients.
2006 Pediatrics patients lt 18 years of age
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Potential for DCD to increase organ donation in
children

• The potential for DCD to increase organ donation
  is children
• The routine use of NHBD has the potential to
  increase organ donation at our institution by 42
• Koogler T, Costarino AT Jr. The potential
  benefits of the pediatric nonheartbeating organ
  donor. Pediatrics. 19981011049-1052.
• 7 additional donors and 14 additional kidneys
  over a 3 year period (47 consent rate
  assumption)
• Durall AL, Laussen PC, Randolph AG. Potential
  for donation after cardiac death in a childrens
  hospital. Pediatrics 2007119e219-224.