166 SECTION II I Pediatric Critical Care Psychosocial and Societal Apnea testing requires preoxygenation with 100% oxygen to prevent hypoxia and enhance the chances of successful comple tion of the ap[.]
Trang 1166 SECTION III Pediatric Critical Care: Psychosocial and Societal
Apnea testing requires preoxygenation with 100% oxygen to
prevent hypoxia and enhance the chances of successful
comple-tion of the apnea test Mechanical ventilatory support should be
adjusted to normalize Paco2 initially Mechanical ventilation is
removed, permitting Paco2 to rise while observing the patient for
spontaneous respiratory effort During apnea testing, oxygenation
can be maintained by using a T-piece circuit connected to the
endotracheal tube (ETT) or attaching a self-inflating bag valve
system with titration of positive end-expiratory pressure (PEEP)
Tracheal insufflation of oxygen using a catheter inserted through
the ETT has also been used to provide supplemental oxygen This
technique is not recommended in children, as high gas flow rates
may promote CO2 washout preventing adequate Paco2 rise, and
catheter insertion too distally can potentiate barotrauma if gas
outflow is not optimal or catheter size is too big relative to the
ETT.6 , 7 False reports of spontaneous ventilation have been
re-ported with patients maintained on continuous positive airway
pressure for apnea testing despite having the sensitivity of the
mechanical ventilator reduced to minimum levels.6 , 7
Apnea testing is consistent with neurologic death if no
respira-tory effort is observed during the testing period The patient is
placed back on mechanical ventilator support following apnea
testing until death is confirmed with a second clinical
examina-tion and apnea test Apnea testing should be aborted if
hemody-namic instability occurs or oxygen saturation decreases to 85% or
less An ancillary study should be pursued to assist with the
deter-mination of neurologic death if targeted thresholds for apnea
testing cannot be achieved or there is any concern regarding the
validity of the apnea test If an ancillary study is used, a second
clinical examination and—if possible—a second apnea test must
be performed Any respiratory effort is inconsistent with
neuro-logic death
Ancillary Studies
Ancillary studies are not necessary or mandatory if a
determina-tion of neurologic death can be made based on clinical
examina-tion criteria and apnea testing.6 , 7 Ancillary studies can provide
additional supportive information to assist in neurologic death
Importantly, ancillary studies are not a substitute for a complete
physical examination If the clinical examination and apnea test
cannot be safely completed, an ancillary study should be used to
assist in the determination of death The need for an ancillary
study will be determined by the physician caring for the child
based on history, the ability to complete the clinical examination
and apnea testing, and state and local requirements.6 , 7 , 34 A
sec-ond neurologic examination and apnea test is required even if an
ancillary study is performed to determine neurologic death.6 , 7
Neurologic examination results must remain consistent with
neurologic death throughout the observation and testing period
In circumstances in which an ancillary study is equivocal, the
observation period can actually be increased until another study
or clinical examination and apnea test are performed to
deter-mine neurologic death A waiting period of 24 hours is
recom-mended before performing another neurologic examination or
follow-up ancillary study in situations in which the study is
equivocal.6 , 7eBox 20.4 lists clinical situations in which ancillary
studies may be useful
The most widely available and commonly performed ancillary
studies validated in children to assist with the determination of
neurologic death are radionuclide CBF study and
electroencepha-lography (EEG).6 , 7 Evaluation of anterior and posterior cerebral
circulation with four-vessel cerebral angiography is now rarely, if ever, used to evaluate blood flow in the determination of neuro-logic death in children This test is difficult to perform in small infants and children, requires transporting a potentially unstable patient to the angiography suite, and necessitates technical exper-tise that may not be available in every facility EEG and radionu-clide CBF studies are more easily accomplished without the need for extraordinary technical expertise EEG and radionuclide CBF studies evaluate different aspects of central nervous system (CNS) activity EEG testing evaluates cortical and cellular function while radionuclide CBF testing evaluates blood flow and uptake into cerebral tissue Each of these tests requires the expertise of appro-priately trained and qualified individuals who understand the limitations of these studies to avoid misinterpretation Specific criteria for these studies must be met to determine neurologic de ath.6 , 7 , 35 , 36 EEG may be more specific, although less sensitive, than the radionuclide CBF study.6 , 7 Radionuclide CBF studies have been used extensively with good results The use of a portable gamma camera for radionuclide angiography has made CBF stud-ies more accessible, allowing for the study to be undertaken at the bedside This study has become a standard in many institutions, replacing EEG as an ancillary study to assist with the determina-tion of neurologic death in infants and children.6 , 7 , 37 Transcranial Doppler sonography and brainstem audio-evoked potentials have not been studied extensively or validated in children.6 , 7 , 38 , 39 As a result, these studies—along with CT angiography, perfusion MRI, magnetic resonance angiography-MRI, (MRA-MRI), and Doppler ultrasonography of the central retinal vessels40 are not currently acceptable ancillary studies to assist with the determina-tion of neurologic death in infants and children.6 , 7
The sensitivity of EEG and CBF studies are weaker in the neonatal age group.6 , 7 , 41 , 42 Limited experience with ancillary stud-ies performed in newborns younger than 30 days of age indicates that EEG is less sensitive than CBF in confirming the diagnosis
of brain death The younger the child, particularly neonates less than 30 days of age, the more cautious one should be in determin-ing neurologic death If there is any uncertainty about the exami-nation, apnea testing, or the ancillary study, continued observa-tion is warranted Addiobserva-tional clinical evaluaobserva-tions and apnea testing or a repeat ancillary study followed by a second clinical examination and apnea test should be performed to make the determination of neurologic death
Technologic advances continue to impact our ability to deter-mine circulatory and neurologic death In certain circumstances, determination of neurologic death may be complicated by open cerebral trauma or decompressive craniectomy, mechanical sup-port with extracorporeal membrane oxygenation (ECMO), or use
of advanced ventilation modalities.43–45 Performing apnea testing for a patient supported with ECMO has been safely accom-plished.46 , 47 The patient is transitioned to a flow-inflating bag valve system with titration of PEEP and hypercapnia induced by reducing the sweep gas or adding exogenous CO2 to the circuit, thus permitting CO2 to rise to an appropriate level to stimulate respiration The rate of CO2 rise will be variable depending on how much the sweep gas is reduced.48 Adding exogenous CO2
may reduce the duration of the apnea test Patients supported on advanced mechanical ventilation modes (e.g., airway pressure re-lease ventilation, high-frequency oscillation ventilation) may not tolerate apnea testing due to impairment of oxygenation, ventila-tion, or hemodynamics Additionally, apnea testing may be al-tered by sedation and use of neuromuscular blockade commonly employed with advanced modes of ventilation Apnea testing
Trang 2• eBOX 20.4 Clinical Situations for Which Ancillary
Studies May Be Useful
• When the clinical examination or apnea testing cannot be safely completed
due to the underlying medical condition of the patient
• When there is uncertainty about the findings of the neurologic examination
• If a confounding medication effect may be present
• To expedite the determination of neurologic death by reducing the clinical
observation period
• Social, medical, and legal reasons
Trang 3CHAPTER 20 Organ Donation Process and Management of the Organ Donor
should be aborted if the patient becomes hemodynamically
un-stable or oxygen saturations fall to less than 85 mm Hg.6 , 7 The
updated guidelines make no provisions for determining an oxygen
saturation threshold for aborting apnea testing in patients with
cyanotic heart disease Patients with open craniocerebral trauma
or decompressive craniectomy may not exhibit the increased
in-tracranial pressure that commonly occurs in a closed skull or may
retain limited regional circulation In any situation in which the
clinical examination and apnea test cannot be completed, an
an-cillary study is recommended to assist with the determination of
neurologic death The clinician should be aware that neurologic
death cannot be determined if the required clinical examination
or ancillary study cannot be completed
Determining neurologic death has great implications with
profound consequences The clinical diagnosis of neurologic
death is highly reliable when made by experienced examiners
us-ing established criteria.6 , 7 Appropriate documentation of clinical
examination, apnea testing, and any ancillary studies should be
recorded when death has been determined The updated
guide-lines for the determination of neurologic death in infants and
children encourage the use of the incorporated guidelines
check-list to assist with standardizing the process and documentation of
neurologic death in children.6 , 7 For detailed information about
determining neurologic death, the reader is encouraged to
be-come familiar with the current pediatric guidelines6 , 7 and
supple-mental institutional or regional requirements
Brain Death Physiology
Progression to neurologic death results in neuroendocrine
dys-function requiring specific interventions to preserve organ
func-tion Efforts to control cerebral perfusion pressure, hemodynamic
manifestations of herniation, and loss of CNS function
contrib-ute to the instability that commonly occurs during and after
progression to neurologic death These physiologic changes clearly
affect end-organ viability in the prospective organ donor
Under-standing the physiologic changes and anticipating associated
complications with neurologic death is therefore critical for organ
function and recovery
Loss of CNS function causes diffuse vascular regulatory and
cellular metabolic injury.48 Neurologic death resulting from
cere-bral ischemia increases circulating cytokines,49 reduces cortisol
production,50 and precipitates massive catecholamine release The
combination of these factors may result in physiologic
deteriora-tion and, ultimately, end-organ failure if left untreated
Cerebral blood flow is approximately 50 mL/100 g per minute
and accounts for 15% of the cardiac output.51 Without substrate
consumption by the brain, glucose needs are reduced and the
patient is prone to hyperglycemia As neurologic death occurs,
cerebral metabolism is further decreased and CO2 production
falls, resulting in a reduction in Paco2 Hypothermia should be
anticipated as a result of hypothalamic failure and loss of
thermo-regulation Additionally, impaired adrenergic stimulation results
in loss of vascular tone with systemic vasodilation and amplified
heat losses Ischemia of the anterior and posterior pituitary results
in neuroendocrine dysfunction and pituitary hormone depletion
If left untreated, this leads to inhibition or loss of hormonal
stimulation from the hypothalamus with subsequent fluid and
electrolyte disturbances and, eventually, cardiovascular collapse
Hemodynamic deterioration associated with neurologic death
is initiated by a massive release of catecholamines, commonly
re-ferred to as sympathetic, catecholamine, or autonomic storm
This phenomenon is associated with cerebral ischemia and intra-cranial hypertension Clinical manifestations include systemic hypertension and tachycardia.48 , 52 Autonomic storm exposes or-gans to extreme sympathetic stimulation from increases in endog-enous catecholamines The local effects of elevated sympathetic stimulation include increased vascular tone, effectively reducing blood flow and potentially causing ischemia to donor organs Autonomic storm also has direct effects on the myocardium as the surge of catecholamines increases systemic vascular resistance (SVR), myocardial work, and oxygen consumption.53 Ischemic changes occur as a result of an imbalance between myocardial oxygen supply and demand, resulting in subendocardial is-chemia.48 , 54 Myocardial ischemia impairs cardiac output, leading
to dysfunction of donor organs Myocardial dysfunction leads to elevated left ventricular end diastolic pressure and consequent pulmonary edema This condition may be exacerbated by the displacement of systemic arterial blood into venous and pulmo-nary circulations due to catecholamine-mediated systemic vaso-constriction Increased pulmonary vascular resistance and right heart volume overload may displace the ventricular septum into the left ventricle, further impairing cardiac output by impeding left ventricular filling.55 Progression to neurologic death results in
a cascade of inflammatory mediator release, causing vasodilation
as loss of sympathetic tone and catecholamine depletion oc-curs.55–57 Additionally, a shift from aerobic to anaerobic metabo-lism transpires as a result of ischemia and depletion of pituitary hormones, affecting cardiac performance and end-organ function
Pediatric Donor Management
Perimortem management of the donor is a continuum of care extending from admission of a critically ill child to the recovery of organs for transplantation Treatment of the DBD donor and the DCD donor differ and are discussed separately
Following the determination of neurologic death and the deci-sion to proceed with organ donation, efforts to reduce intracranial pressure are abandoned and care shifts toward providing adequate circulation and oxygen delivery to preserve vital organ function for transplantation Subsequent care will differ from management prior to death Families and staff must be prepared for the paradigm shift in the goals of therapy from lifesaving to organ-preserving The critical care team should actively manage the po-tential donor and correct existing physiologic derangements that follow neurologic death to preserve the option of organ donation for the family.18 For example, decreased intravascular volume secondary to efforts aimed at reducing CBF and controlling intra-cranial hypertension (e.g., volume restriction and diuretic agents) must be repleted Metabolic derangements should be corrected, such as iatrogenic hypernatremia from hyperosmolar therapy and hyperglycemia associated with catecholamine release and reduced cerebral metabolism Volume loss from osmotic diuresis associ-ated with hyperglycemia and diabetes insipidus (DI) following neurologic death must be anticipated and addressed to prevent cardiovascular collapse Hemodynamic management goals are di-rected at maintaining normal peripheral perfusion and blood pressure for age Additional donor management goals include preserving lung function, normalization of Paco2, temperature regulation, and metabolic disturbances Infections present prior
to authorization must continue to be treated until organ procure-ment occurs Even if no infectious disease concerns exist, prophy-lactic antibiotics are routinely administered by many OPOs prior
to organ recovery.14 Progression from neurologic death to somatic
Trang 4168 SECTION III Pediatric Critical Care: Psychosocial and Societal
death and loss of transplantable organs can result if prompt
goal-directed care is not implemented.14 , 55 , 58 Donor management goals
are listed in Table 20.1
In addition to targeting restoration of normal organ
physiol-ogy, ideal donor management includes ongoing evaluation for
organ suitability, serial assessment of organ function,
immuno-logic testing, infectious disease screening, donor organ size
matching, organ allocation, and coordination of surgical teams
for organ retrieval.18 The goal of donor management therapy is
to restore and maintain adequate oxygenation, ventilation, and
perfusion to vital organs, thus preserving their function for
successful transplantation This can ultimately result in a higher
yield of transplantable organs and improved graft function that
may translate to a reduction in hospital length of stay and
decreasing acquired morbidity and mortality in the transplant
recipient.14 , 59–64
Treatment of Hemodynamic Instability
Cardiac instability is the greatest limiting factor to successful
or-gan recovery Of all physiologic abnormalities encountered in the
prospective organ donor, the cardiovascular system is fraught with
the most complexity and variation Hemodynamic instability and
organ dysfunction account for a loss of up to 25% of potential
donors when donor management is not optimized.58 Further-more, initiation of hormonal replacement therapy (HRT) early
in the donation process may assist with stabilization of the donor, improve the quality of organs recovered, and enhance posttransplant graft function.59 , 64–67 The tremendous physiologic derangements associated with neuroendocrine dysfunction re-quire specific interventions to restore normal physiology These derangements are detailed later in this chapter and in Chapters 28, 31, and 34
TABLE
20.1 Pediatric Donor Management Goals
Hemodynamic Support
• Normalization of blood pressure
• Systolic blood pressure appropriate for age (lower systolic blood pressures may be acceptable if biomarkers such as lactate and SVO 2 are normal)
• CVP ,12 mm Hg (if measured)
• Dopamine ,10 µg/kg/min or use of a single inotropic agent
Normal serum lactate
Oxygenation and Ventilation
• Maintain Pa o2 100 mm Hg
• F io2 0.40
• Normalize Pa co2 35–45 mm Hg
• Arterial pH 7.30–7.45
• Tidal volumes 8–10 mL/kg and PEEP of 5 cm H 2O or tidal volumes 6–8 mL/kg and PEEP of 8–10 cm H2 O
Fluids and Electrolytes Measurement Range
Serum Na 1 130–150 (mEq/L) Serum K 1 3.0–5.0 (mEq/L) Serum glucose 60–200 (mg/dL) Ionized Ca 11 0.8–1.2 (mmol/L)
Thermal Regulation
Core body temperature 36–38°C
Modified from Nakagawa TA North American Transplant Coordinators (NATCO) Updated Donor Management and Dosing Guidelines Lenexa, KS: 2008.
Hormonal Replacement Therapy
Significant volume resuscitation and inotropic support are rou-tinely required to correct severe cardiovascular derangements following neurologic death Anterior pituitary hormone deficits result in thyroid and cortisol depletion and may contribute to hemodynamic instability.50 HRT restores aerobic metabolism, replaces hormones derived from the hypothalamus and pituitary, augments blood volume, and minimizes the use of inotropic sup-port while optimizing cardiac output
HRT in adult donors is controversial, with correlations of hormone use, cardiac function, and variable clinical outcomes reported.64–67 , 77–80 One adult study demonstrated a reduced need for vasoactive infusions in 100% of unstable donors and abolished
Trang 5The sympathetic storm associated with cerebral ischemia and
intracranial hypertension results in intense but transient
hyper-tension If hypertension is severe and sustained, a cautious
approach to treatment can be considered using a single IV dose or
continuous infusion of a short-acting antihypertensive agent,
such as hydralazine, sodium nitroprusside, esmolol, labetalol, or
nicardipine titrated to effect Profound vasodilation and
hypoten-sion following neurologic death occur due to cessation of
sympa-thetic outflow This should be anticipated and treated to restore
normal circulation and perfusion
Profound and abrupt hypotension with release of
proinflam-matory mediators initiates a cascade of molecular and cellular
events with resultant ischemia and reperfusion injury in vital
organs.56 Management during this phase should target aggressive
restoration of circulating volume, optimizing cardiac output and
oxygen delivery to the tissues, and maintaining normal blood
pressure for age (see Table 20.1) using catecholamine infusions as
necessary.57 , 68 Isotonic crystalloid solutions—such as normal
sa-line, colloid solutions (e.g., 5% albumin), or blood products
(packed red blood cells for the anemic patient or plasma for the
patient with a coagulopathy)—can be used for volume
replace-ment The use of artificial plasma expanders, such as hespan or
dextran for volume resuscitation, should be avoided since large
volumes of these agents can promote coagulation disturbances
and impair renal function.14 , 68 , 69–71 Commonly used inotropic
agents—such as dopamine, dobutamine, and epinephrine—can
be titrated to effect Catecholamines and dopamine appear to
have immunomodulating effects that may help blunt the
inflam-matory response associated with brain death and improve kidney
graft function.72 , 73 Vasopressors such as norepinephrine,
vaso-pressin, and phenylephrine can be used in situations in which
there is profound vasodilation and low SVR, though high doses
can reduce perfusion to donor organs, potentially jeopardizing
their viability prior to recovery and transplantation Many OPOs
routinely use a combination of inotropic support, volume
resuscitation, and hormonal replacement therapy (HRT) to
re-duce vasoactive infusions that may impair perfusion to potential
donor organs Agents such as thyroid hormone, corticosteroids,
vasopressin, and insulin are commonly employed during donor
management.14 , 68 , 71 HRT can reduce circulatory instability
as-sociated with thyroid and cortisol depletion, especially in
situa-tions in which significant inotropic support is required.18 , 64–68
Acidosis, hypoxia, hypercarbia, and electrolyte disturbances can
alter myocardial performance and must be corrected Blood
pressure, central venous pressure (CVP), mixed venous oxygen
saturation, and serum lactate levels can guide adequate cardiac
performance and tissue oxygen delivery Echocardiography can
provide useful information about filling pressures, wall motion
abnormalities, and ventricular shortening or ejection fractions
Serial echocardiograms are routinely employed in donor man-agement and performed to assess cardiac function as treatment
of the donor progresses In many instances, cardiac perfor-mance improves with aggressive resuscitation and institution of HRT following neurologic death An initial echocardiogram showing poor myocardial function should not be used to pre-clude donation.14 , 18
Many commonly used clinical indicators of end-organ perfu-sion become less reliable once brain death has occurred For ex-ample, urine output is traditionally used as a gauge of adequate intravascular volume and renal perfusion but becomes unreliable
in the setting of brain death and DI Similarly, heart rate may not
be a reliable sign of intravascular volume status After death of the brainstem, there is loss of beat-to-beat variation, lack of vagal tone, and, thus, a fixed heart rate is commonly observed.74 Perfu-sion may be affected by temperature instability and hypothermia, resulting in delayed capillary refill time Biomarkers such as mixed venous oxygen saturation and serum lactate levels may be more useful to guide cardiovascular management to ensure optimal oxygen delivery to tissues Elevations in serum lactate and the development of metabolic acidosis provide evidence of tissue ischemia and should prompt immediate attention Importantly, elevated serum lactate may be present following CNS or multisys-tem trauma and may persist following neurologic death or in those with profound hepatic dysfunction
Arrhythmias can occur during progression and following neu-rologic death The catecholamine storm triggered by adrenergic stimulation results in myocardial ischemia and can cause necrosis
of the conduction system, promoting tachydysrhythmias Follow-ing neurologic death, bradyarrhythmias may not be responsive to atropine because of denervation of the heart; epinephrine then becomes the pharmacologic treatment of choice Other factors contributing to arrhythmias include hypoxemia, hypothermia, cardiac trauma, and the proarrhythmic properties of inotropes Hypotension from hypovolemia and vasodilation causes poor cardiac output and metabolic acidosis Metabolic acidosis from inadequate cardiac output and electrolyte disturbances (specifi-cally hypomagnesemia, hypocalcemia, and hypokalemia) that occur with DI may also promote rhythm disturbances Identifica-tion and correcIdentifica-tion of the underlying cause of the arrhythmia are essential to address and treat rhythm disturbances
Cardiac arrest may be treated as part of active donor manage-ment in a decedent following neurologic death.74a , 75 Extracorpo-real support for the hemodynamically unstable donor has been considered in extreme cases, including hemodialysis for correction
of fluid overload and electrolyte disturbances The use of extracor-poreal support to limit warm ischemic time for DCD donors should be avoided because anterograde circulation may be rees-tablished and negate determination of death.76