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[.]
166 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal Apnea testing requires preoxygenation with 100% oxygen to prevent hypoxia and enhance the chances of successful completion 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 reported 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 respiratory 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 examination and apnea test Apnea testing should be aborted if hemodynamic instability occurs or oxygen saturation decreases to 85% or less An ancillary study should be pursued to assist with the determination 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 neurologic death Ancillary Studies Ancillary studies are not necessary or mandatory if a determination of neurologic death can be made based on clinical examination 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 second 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 determine neurologic death A waiting period of 24 hours is recommended before performing another neurologic examination or follow-up ancillary study in situations in which the study is equivocal.6,7 eBox 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 electroencephalography (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 neurologic 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 expertise that may not be available in every facility EEG and radionuclide 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 appropriately 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 studies 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 determination 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 determination 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 studies 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 determining neurologic death If there is any uncertainty about the examination, apnea testing, or the ancillary study, continued observation is warranted Additional clinical evaluations 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 determine circulatory and neurologic death In certain circumstances, determination of neurologic death may be complicated by open cerebral trauma or decompressive craniectomy, mechanical support 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 accomplished.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 release ventilation, high-frequency oscillation ventilation) may not tolerate apnea testing due to impairment of oxygenation, ventilation, or hemodynamics Additionally, apnea testing may be altered by sedation and use of neuromuscular blockade commonly employed with advanced modes of ventilation Apnea testing 166.e1 • 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 CHAPTER 20 Organ Donation Process and Management of the Organ Donor should be aborted if the patient becomes hemodynamically unstable 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 intracranial 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 ancillary 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 using 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 guidelines for the determination of neurologic death in infants and children encourage the use of the incorporated guidelines checklist 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 become familiar with the current pediatric guidelines6,7 and supplemental institutional or regional requirements Brain Death Physiology Progression to neurologic death results in neuroendocrine dysfunction requiring specific interventions to preserve organ function Efforts to control cerebral perfusion pressure, hemodynamic manifestations of herniation, and loss of CNS function contribute 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 Understanding 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 cerebral ischemia increases circulating cytokines,49 reduces cortisol production,50 and precipitates massive catecholamine release The combination of these factors may result in physiologic deterioration 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 thermoregulation 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 referred to as sympathetic, catecholamine, or autonomic storm 167 This phenomenon is associated with cerebral ischemia and intracranial hypertension Clinical manifestations include systemic hypertension and tachycardia.48,52 Autonomic storm exposes organs to extreme sympathetic stimulation from increases in endogenous 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 pulmonary circulations due to catecholamine-mediated systemic vasoconstriction 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 occurs.55–57 Additionally, a shift from aerobic to anaerobic metabolism 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 decision 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 organpreserving The critical care team should actively manage the potential 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 intracranial 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 associated with hyperglycemia and diabetes insipidus (DI) following neurologic death must be anticipated and addressed to prevent cardiovascular collapse Hemodynamic management goals are directed 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 procurement occurs Even if no infectious disease concerns exist, prophylactic antibiotics are routinely administered by many OPOs prior to organ recovery.14 Progression from neurologic death to somatic 168 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal death and loss of transplantable organs can result if prompt goaldirected care is not implemented.14,55,58 Donor management goals are listed in Table 20.1 In addition to targeting restoration of normal organ physiology, ideal donor management includes ongoing evaluation for organ suitability, serial assessment of organ function, immunologic 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 organ 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 Furthermore, 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 require specific interventions to restore normal physiology These derangements are detailed later in this chapter and in Chapters 28, 31, and 34 Hormonal Replacement Therapy Significant volume resuscitation and inotropic support are routinely 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 support 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 TABLE Pediatric Donor Management Goals 20.1 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 SVO2 are normal) CVP ,12 mm Hg (if measured) Dopamine ,10 µg/kg/min or use of a single inotropic agent Normal serum lactate Blood Pressure Age Systolic (mm Hg) Diastolic (mm Hg) Neonate 60–90 35–60 Infant (6 mo) 80–95 50–65 Toddler (2 y) 85–100 50–65 School Age (7 y) 90–115 60–70 Adolescent (15 y) 110–130 65–80 Oxygenation and Ventilation • • • • • Maintain Pao2 100 mm Hg Fio2 0.40 Normalize Paco2 35–45 mm Hg Arterial pH 7.30–7.45 Tidal volumes 8–10 mL/kg and PEEP of cm H2O or tidal volumes 6–8 mL/kg and PEEP of 8–10 cm H2O Fluids and Electrolytes Measurement Range Serum Na 130–150 (mEq/L) Serum K 3.0–5.0 (mEq/L) Serum glucose 60–200 (mg/dL) Ionized Ca11 0.8–1.2 (mmol/L) 1 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 168.e1 The sympathetic storm associated with cerebral ischemia and intracranial hypertension results in intense but transient hypertension 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 hypotension following neurologic death occur due to cessation of sympathetic outflow This should be anticipated and treated to restore normal circulation and perfusion Profound and abrupt hypotension with release of proinflammatory 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 saline, 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 replacement 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 inflammatory response associated with brain death and improve kidney graft function.72,73 Vasopressors such as norepinephrine, vasopressin, 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 reduce 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 associated with thyroid and cortisol depletion, especially in situations 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 management and performed to assess cardiac function as treatment of the donor progresses In many instances, cardiac performance improves with aggressive resuscitation and institution of HRT following neurologic death An initial echocardiogram showing poor myocardial function should not be used to preclude donation.14,18 Many commonly used clinical indicators of end-organ perfusion become less reliable once brain death has occurred For example, 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 Perfusion 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 multisystem trauma and may persist following neurologic death or in those with profound hepatic dysfunction Arrhythmias can occur during progression and following neurologic death The catecholamine storm triggered by adrenergic stimulation results in myocardial ischemia and can cause necrosis of the conduction system, promoting tachydysrhythmias Following 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 (specifically hypomagnesemia, hypocalcemia, and hypokalemia) that occur with DI may also promote rhythm disturbances Identification and correction 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 management in a decedent following neurologic death.74a,75 Extracorporeal 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 extracorporeal support to limit warm ischemic time for DCD donors should be avoided because anterograde circulation may be reestablished and negate determination of death.76 ... 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... release of catecholamines, commonly referred to as sympathetic, catecholamine, or autonomic storm 167 This phenomenon is associated with cerebral ischemia and intracranial hypertension Clinical manifestations... 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