BRAIN DEATH IN CHILDREN - PowerPoint

							 BRAIN DEATH IN CHILDREN
AND CARE OF THE POTENTIAL
      ORGAN DONOR

            Andrew W. Kiragu, MD, FAAP
            Medical Director, PICU
            Hennepin County Medical Center
            Assistant Professor of Pediatrics
            University of Minnesota



                                                S
Think of your child; then, not as dead, but as living; not as a flower
  that has withered, but as one that is transplanted, and touched by a
  divine hand, is blooming in richer colors and sweeter shades …….

                         Richard Hooker
           OBJECTIVES OF THIS
             PRESENTATION


S To discuss a representative patient case report

S To briefly discuss brain death in pediatric patients.

S To discuss the pathophysiologic changes that occur as a
   result of brain death.
S To discuss the ICU management of these physiologic
   derangements.
S To discuss some of the other challenges faced in the
   management of the potential organ donor.
CASE REPORT
                     CASE REPORT


S EP is an 8 yo boy admitted to the PICU for management after he
  was struck by a van while riding his bicycle.

S Sustained a severe brain injury with an initial GCS at the scene of
  3.

S Patient noted to have agonal respirations and intubated at the
  scene.

S Brought to ED for initial evaluation and management. Local OPO
  contacted.
                   CASE REPORT



S The patient sustained significant thoracic trauma with initial
  radiographs showing multiple rib fractures and bilateral
  pulmonary contusions as well as fractures of his pelvis and right
  tibia
S On exam the patient is hypotensive and tachycardic with BP
  80/30 and HR 140. His exam is significant for a laceration and
  swelling over the right temporal region of his skull with no
  noted step-off.
S Pupils are fixed and dilated. ETT in place with notable bloody
  aspirate. Patient has no cough or gag reflexes with suctioning.
                CASE REPORT



S Chest exam shows significant bruising and coarse rhonchi
  bilaterally

S Cardiac exam significant for tachycardia and a flow murmur

S Abdominal exam shows significant ecchymosis over LUQ.
  Abdominal CT shows Grade 2 splenic laceration. RLE
  splint placed.

S Neurologic exam remarkable for no response to noxious
  stimulus. Absent reflexes. Head CT shows diffuse cerebral
  edema and evidence for severe diffuse axonal injury.
                  CASE REPORT



S The patient is sent up to the PICU for ongoing management

S Ventriculostomy placed and initial ICP is 40. No significant
   response to hypertonic saline and hyperventilation

S The patient receives significant fluid resuscitation but
   remains hypotensive and is therefore started on inotropic
   support

S Also started on insulin drip for glycemic control and
   triiodothyronine drip given significant inotrope requirement
                  CASE REPORT



S The patient is subsequently noted to put out significant
  amounts of dilute urine and lab evaluation consistent with
  DI. Vasopressin drip initiated.
S The patients clinical status/exam concerning for brain
  death.
S Brain death examination and cerebral blood flow study
  confirm the clinical suspicion.
S These findings discussed with the family who request
  information about organ donation.
                  INTRODUCTION



Patients on waiting list 9/18/08   99,654




Transplants January-June 2008      13,813




Organ Donors January-June 2008     6,986




                                            OPTN Data 9/18/08
                   INTRODUCTION



                       2007           2006
All Ethnicities        14,400(100%)   14,755(100%)
White                  9,872(68.6%)   10,190(69.1%)
African-American       1,991(13.8%)   2,061(14%)
Hispanic               1,972(13.7%)   1,968(13.3%)
American               75(0.5%)       67(0.5%)
Indian/Alaska Native
Asian                  397(2.8%)      363(2.5%)
Pacific Islander       25(0.2%)       26(0.2%)
Multiracial            68(0.5%)       80(0.5%)

                                             OPTN Data 8/28/08
               INTRODUCTION



S Medicine and society continue to struggle with the
  definition of death.
S The progression of life-sustaining ICU therapies challenge
  our concepts of death.
S Questions about when a disease process is irreversible, when
  additional treatment is ineffective or when death has
  occurred preoccupy us and are independent of and
  galvanized by the practice of organ donation.
               INTRODUCTION



S Historically, death identified with cessation of pulse and
  respiratory effort since these findings herald the
  “dissolution” of the individual.
S In 1950’s and 1960’s with advent of ICU’s, a group of
  patients began to emerge who had persistent pulse and
  circulation in the absence of detectable neurologic function
S The concept of death as the absence of clinical brain
  function began to develop
                  INTRODUCTION



S Advances in transplantation technology

S “Brain dead” patients a potential source of organs but during
  those earlier years fraught with legal and ethical difficulties
S Need for a medical and legal definition of brain death

S First certification of brain death by the Ad Hoc Committee of
  the Harvard Medical School in 1968
S In the 1990’s the Uniform Determination of Death Act legally
  recognized that death could be defined using neurological criteria
    DETERMINATION OF BRAIN
            DEATH


S Begins with formal neurological examination

S AAN has set forth practice parameters for diagnosis of
  brain death

S AAP guidelines developed to help in the diagnosis of brain
  death in pediatric patients. These guidelines for the most
  part similar to adult guidelines except for timelines

S Radiographic support for intracranial catastrophe
    DETERMINATION OF BRAIN
            DEATH


S Based upon the absence of brainstem and hemispheric
   function

S Patients in a persistent vegetative state are not brain dead

S It is not necessary to diagnose brain death in order to
   discontinue extraordinary measures of support or to tell the
   parents the child’s outlook is hopeless

S Once brain death criteria are met, the patient is legally dead
    DETERMINATION OF BRAIN
            DEATH


S Exclusion and correction of conditions that confound diagnosis
  of brain death (electrolyte abnormalities, intoxication,
  hypothermia, drugs)

S The child should not have received recent doses of sedative
  hypnotic or neuromuscular blocking agents

S The child must not be significantly hypotensive for age

S Neurologic exam then proceeds with aim of determining three
  principle findings in brain death: coma, absence of brainstem
  reflexes and apnea (coma and apnea must coexist)
      DETERMINATION OF BRAIN
              DEATH


S Absence of brainstem function as defined by:
  S Mid-position or fully dilated pupils that do not respond to light
  S Absence of spontaneous eye movements induced by occulocephalic
    or occulovestibular (cold calorics) testing
  S Absence of bulbar function including facial and oropharyngeal
    muscles (Corneal, cough, gag, and rooting reflexes are absent)
  S Respiratory movements are absent off ventilator support

S Flaccid tone and absence of spontaneous or induced movements
  (excluding spinal cord events such as reflex withdrawal or spinal
  myoclonus)
   DETERMINATION OF BRAIN
           DEATH


S The recommended observation period depends on the age
  of the patient and the ancillary testing utilized

S 7 days to 2 months : Two examinations and EEG’s
  separated by at least 48 hours

S 2 months to one year of age : Two examinations and EEG’s
  separated by at least 24 hours. A repeat EEG is not
  necessary if a cerebral radionuclide scan or cerebral
  angiography demonstrates no flow or visualization of the
  cerebral arteries
    DETERMINATION OF BRAIN
            DEATH


S 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.

S 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.
      CONFIRMATORY TESTING



S Not required in adults or children older than 1 year.
  However, often helpful in providing an additional objective
  finding
S In situations where neurological exam cannot be
  dependably done and in children younger than 1 year,
  recommended
S Classified in two groups; assessment of electrical activity
  and assessment of blood flow
     CONFIRMATORY TESTING



S EEG

S Radionuclide Scans

S Intracranial pressure monitoring

S Somatosensory evoked responses

S Transcranial Doppler

S Cerebral angiography
ELECTROENCEPHALOGRAPHY


S The absence of electrical activity during at least 30 minutes
  of EEG recording supports diagnosis of brain death.
S Validated for adults but not pediatric patients

S Concerns also about preservation of EEG activity despite a
  clinical exam consistent with brain death and absence of
  cerebral blood flow
       SOMATOSENSORY EVOKED
            POTENTIALS


S SEP are a measure of electrical potentials produced in response
  to stimulation of the sensory system
S Stimulus typically applied to a peripheral mixed sensory and
  motor nerve e.g. median nerve and potential measured at
  downstream site along neural pathway
S Bilateral absence of response to nerve stimulation consistent with
  brain death
S SEP found useful in confirming brain death in children and
  infants.
    CEREBRAL ANGIOGRAPHY



S Performed by injection of contrast into aortic arch and
  looking for blood flow to carotids and vertebral vessels

S When ICP exceeds MAP angiography demonstrates
  absence of blood flow beyond carotid bifurcation

S This study not routinely performed although in cases where
  brain dead patient is in a barbiturate coma it can be used
  without the necessary wait for the medication to leave the
  system
            NUCLEAR STUDIES



S Radionuclide studies performed by measuring a tracer
  intravenously and obtaining static images at between 30 and
  60 minutes and 2 hours

S Absence of uptake of isotope in brain parenchyma is
  supportive of a diagnosis of brain death

S Caution needed in the child age <2 months.
NUCLEAR STUDIES
        TRANSCRANIAL DOPPLER




S Blood flow through MCA can detected by applying a Doppler US
  probe over the temporal bone bilaterally.
S Small systolic peaks in early systole without diastolic flow or
  reverberating flow indicate very high vascular resistance and are
  supportive of the diagnosis of brain death
S However ~10% of patients do not have adequate windows for
  insonation and so results need to be interpreted cautiously.
     MANAGEMENT OF THE BRAIN-
        DEAD ORGAN DONOR


S Trauma patients represent a large percentage of those declared brain
  dead in the PICU and therefore a large pool of potential organ
  donors
S Significantly wide gap between organs available for transplantation
  and those awaiting transplantation
S Improvement in consent rates for transplantation from current 40-
  60% will help bridge this gap
 MANAGEMENT OF THE BRAIN-
    DEAD ORGAN DONOR


S ICU management of the potential organ donor plays a key
  role in maintaining and increasing current number of donor
  organs

S Early identification of potential donors e.g. patients with
  catastrophic TBI

S Early notification of OPO

S Preparation of the family
 DONOR ACCEPTANCE CRITERIA



S Exclusion criteria include infectious diseases such as HIV, viral
  hepatitis, encephalitis, active CMV infections, active HSV, active
  TB and untreated syphilis

S Disseminated malignancies also preclude organ donation

S Age > 65years generally precludes donation, although
  approximately 10% of organ donors >65
 PATHOPHYSIOLOGY OF BRAIN
          DEATH


S The potential organ donor at high risk for instability due to
  the loss of homeostatic mechanisms dependent on the CNS

S Hemodynamic instability and cardiac arrest after brain
  death accounts for the loss of as many as 25% of potential
  organ donors

S Loss of hormonal and metabolic equipoise also a significant
  contributor to the physiologic derangements seen in brain
  dead patients
    CARDIOVASCULAR CHANGES



S Hypertension and bradycardia preceding brain death characterize
  the Cushing’s response.

S Ischemia of the vagal nucleus in the medulla oblongata results in
  uncontrolled sympathetic stimulation-the catecholamine “storm”

S This results in systemic hypertension, tachycardia and possibly
  tissue ischemia including pituitary ischemia.

S Duration and severity of this “storm “ varies but within hours
  results in depletion of catecholamines with subsequent
  generalized vasodilation and hemodynamic collapse
  CARDIOVASCULAR CHANGES



S Total infarction of the vasomotor centers in the brain lead to
  an abrupt loss in sympathetic tone and hypotension

S Myocardial injury can result in right and/or left ventricular
  dysfunction

S This contributes to hemodynamic instability and organ
  dysfunction
        HORMONAL CHANGES



S Infarction of the HPA during the course of brain death
  impairs the release of ADH

S The consequent DI results in problems with hemodynamic
  stability and fluid and electrolyte balance

S Absence of DI after brain death likely due to preserved
  pituitary circulation
          HORMONAL CHANGES



S Notable reduction in thyroid hormone levels after brain
  death

S Study evidence that thyroid hormone supplementation may
  reverse metabolic abnormalities and stabilize hemodynamic
  parameters

S Hormonal resuscitation now a management strategy for
  UNOS
        HORMONAL CHANGES



S Studies regarding ACTH and cortisol levels inconclusive.

S Unclear whether steroids make any significant improvement
  in organ preservation

S Hyperglycemia with catastrophic TBI common likely due to
  increased catecholamines and relative insulin resistance
ELECTROLYTE AND ACID-BASE
      DISTURBANCES


S Hypernatremia

S Hypokalemia

S Hypophosphatemia

S Hypomagnesemia

S Hypocalcemia

S Metabolic acidosis
HEMATOLOGIC ABNORMALITIES



S Coagulation abnormalities may be present due to previous
  anticoagulant use, dilution, consumption of factors, DIC,
  etc.

S Coagulation and platelet function may also be affected by
  hypothermia

S Blood loss from trauma may lead to anemia, hemodynamic
  instability etc

S Questions regarding transfusion
            IMMUNE SYSTEM
           PATHOPHYSIOLOGY


S Following brain death, increased secretion of
  proinflammatory cytokines, chemokines and adhesion
  molecules resulting in a systemic inflammatory response

S Cytokine release may exacerbate tissue injury associated
  with the catecholamine surge

S Inflammatory upregulation may also impact organ function
  post transplant and increase likelihood of rejection

S Effect of steroids
ICU MANAGEMENT OVERVIEW



S Key to management is anticipation of complications,
  frequent reassessment and titration of therapies

S Maintenance of vital organ function and prevention and
  treatment of complications are goals of therapy

S Routine care of the ICU patient applies to the potential
  organ donor as well
ICU MANAGEMENT OVERVIEW



S Resuscitation

S Oxygen delivery to the tissues

S Hydration and perfusion

S Restoration of normal ventilation

S Thermal regulation

S Regulation of neuroendocrine function
                  MONITORING



S Arterial and central venous pressure monitoring

S If necessary, pulmonary artery catheter placement

S Core temperature monitoring and pulse oximetry

S Routine laboratory testing e.g. blood gases, electrolytes and
  hematologic indices monitoring
        HEMODYNAMIC AND
      CARDIOVASCULAR SUPPORT


S Hemodynamic Goals

S Blood Pressure is age related
       S Birth to 2 months – Systolic > 60 mm Hg and < 90 mm Hg
       S 2 months to 1 year – Systolic > 70 mm Hg and < 100 mm
         Hg
       S 1 year -10 years – Systolic > (2 x age + 70) and < 40 + (2 x
         age + 70)
       S > 10 years – Systolic > 100 mm Hg and < 140 mm Hg
     HEMODYNAMIC AND
   CARDIOVASCULAR SUPPORT


S CVP 5-10 mm Hg

S SvO2 saturation (mixed venous saturation) > 70%

S SaO2 saturation > 93%

S Normal serum lactate and base deficit

S Urine output > 1 ml/kg/hr and < 10 ml/kg/hr

S Good capillary refill and pulse quality
     HEMODYNAMIC AND
   CARDIOVASCULAR SUPPORT


S Initial period of severe HTN may be managed with short-
  acting B-blocker such as esmolol

S Hypotension, however, poses the greatest risk to organ
  viability

S Management of this involves use of crystalloid, colloid,
  blood products as needed.

S Also judicious use of vasopressor agents
     HEMODYNAMIC AND
   CARDIOVASCULAR SUPPORT


S Initial vasopressor choice unclear. Many centers start with
  dopamine. Epinephrine and norepinephrine are also choices
S Second-line therapy includes vasopressin

S A levothyroxine (4-10mcg/hour) and other hormonal
  replacement an integral part of UNOS management
  protocols
S Regimen may use a T3 ( 0.05-0.2mcg/kg/hour drip) instead
  of levothyroxine
          RESPIRATORY SUPPORT



S Ventilatory support should aim to provide adequate ventilation and
  oxygenation
S Goal FiO2 is 40%, PEEP 5, PIP< 30-35 mmHg, TV of 8-10 ml/kg
  (or 6-8 ml/kg if ARDS)
S Goals are normal pH and pCO2, PaO2>100, PaO2:FiO2 ratio>300

S Minimize potential for VILI and hemodynamic instability

S Aggressive pulmonary toilet including VEST therapy

S Bronchoscopy with BAL pre-transplant and as needed for refractory
  atelectasis etc.
        METABOLIC EQUIPOISE



S Fluid management to maintain euvolemia

S Significant challenge is management of fluid status in face
  of DI
S Use of vasopressin or DDAVP

S Treatment of electrolyte abnormalities particularly
  hypernatremia, hypophosphatemia and hypomagnesemia
S Aggressive glycemic control
HEMATOLOGIC INTERVENTIONS



S Correction of consumption coagulopathy which is
  secondary to release of tissue thromboplastin from the
  injured brain. Hypothermia can worsen this coagulopathy

S Therapy includes FFP, Cryoprecipitate, platelets, Vitamin K

S In some situations, transfusion with packed red blood cells
  may be required

S Prevention or correction of hypothermia which may
  exacerbate the coagulopathy
         HORMONAL THERAPY



S As neurologic death occurs, alteration in the hypothalamic-
  pituitary-adrenal axis (HPA axis) is inevitable.

S Thus, we should be using HRT early on in the course of
  donor management. No contraindications in using prior to
  neurologic death.

S HRT decreases the need for inotropic support in children
  and associated with increased number of organs donated
               HORMONAL THERAPY




From: Rosendale: Transplantation, Volume 75(4).February 27, 2003.482-487
         HORMONAL THERAPY



S Thyroid replacement, increases cardiac output, increases
  heart rate, increases ventilation rate and increases basal
  metabolic rate

S Thyroid hormone administration typically with T3
  (triiodothyronine) which is the active form of thyroid
  hormone.

S T3 is converted from T4 by deiodinase. T3 is 4 X more
  active than T4

S Dose of T3: 0.05-0.15 mcg/kg/hour titrate to effect
         HORMONAL THERAPY



S Steroid production will be inhibited or lost due to CNS
  insult and loss of the HPA axis.

S Steroids upregulate adrenergic receptors thus enhancing
  response to inotropes. May also help pulmonary function.

S Protocols may use hydrocortisone (Solucortef) 1.5 mg/kg IV
  Q 6 hours (max dose of 100 mg) or single dose of
  methylprednisolone 15 mg/kg in adults and 1 mg/kg in
  children (max dose of 2 gm)
S Vasopressin (0.5mU/kg/hour) for management of diabetes
  insipidus. Titrate up as needed to maintain UOP at less than
  4 ml/kg/hr

S Insulin 0.05-0.1U/kg/hour titrated to maintain glucose at
  80-120

S Hourly glucose checks so as to avoid hypoglycemia
           OTHER ASPECTS OF
            MANAGEMENT


S Temperature control

S Antibiotic therapy

S Nutrition

S Support of the family
CONSENT AND COORDINATION
      WITH THE OPO


S Optimum medical management key to successful donation

S However, significant impediment to organ donation is
  refusal of families to consent
S Donor consent rates approximately 50%

S A number of factors contribute to this and include both
  patient/family factors and health care professional/facility
  factors
  CONSENT AND COORDINATION
        WITH THE OPO


S Early involvement of OPO personnel

S Designated requestor (usually OPO coordinator)

S Preparation of family including previous discussion of brain
  death
S Multidisciplinary support for entire family

S Clarification of ongoing physiologic support despite brain death

S Sensitivity to family’s psychological, religious and cultural needs
                 CHALLENGES



S Supply of cadaveric organ donors is limited

S Societal concerns about the definition of brain death

S Cultural and familial concerns

S The challenges of medical management of the brain dead
  organ donor

S Legal and logistical concerns
                   CHALLENGES



S Medical and ethical questions remain despite current guidelines

S Is the brain truly “dead” when clinical diagnosis of brain death
  made.
S Some patients meeting brain death criteria still produce AVP

S Others may still have electrical activity on EEG

S No neurophysiologic testing exists that can accurately verify the
  permanent cessation of functioning of the entire brain
                  CHALLENGES



S In addition clinician differences in application of testing for
   determination of brain death

S State differences in criteria for brain death determination
   also confounds the issue.

S Difficulty in grasping concept of brain death given personal,
   ethnic and religious beliefs
                 CHALLENGES



S Education

S Sensitivity to cultural and family concerns

S Concerns about child abuse victims as donors

S Additional research and improvements in the medical
  management of the brain dead donor
                  CONCLUSIONS



S Medicine and society continue to struggle with the definition of
  death.
S Determination of brain death a clinical diagnosis although age-
  related issues can make confirmation of brain death more
  difficult.
S Most organ recipients rely on the gift of an organ from a brain
  dead donor.
S There continues to be a significant gap between those patients
  needing transplants and the number of available organs.
                 CONCLUSIONS



S Recognition and proper care of the brain dead potential
  organ donor key in increasing the number of organs
  available for transplantation.
S Significant physiologic derangements occur as a result of
  brain death and the importance of skilled management of
  these derangements cannot be overstated.
S Preparation of the potential donors family also key to this
  process
S There continue to be significant challenges in increasing
  consent rates for organ donation, particularly in minority
  populations.
QUESTIONS?