169CHAPTER 20 Organ Donation Process and Management of the Organ Donor the need in 53% of such donors 81 Decreased inotropic require ments have also been noted in children who received levothyrox ine[.]
CHAPTER 20 Organ Donation Process and Management of the Organ Donor the need in 53% of such donors.81 Decreased inotropic requirements have also been noted in children who received levothyroxine and vasopressin as part of donor management following neurologic death.82 Although studies are limited, HRT is a reasonable consideration when hemodynamic status does not improve with fluid and inotropic support Based on a retrospective analysis of 40,124 organ donors over a 10-year period, the optimal HRT combination associated with multiple organ recovery appears to be thyroid hormone, a corticosteroid, vasopressin, and insulin.83 Existing literature supports improved outcomes with HRT and greater procurement rates may be seen with earlier administration of HRT.84 No published studies are available in children; however, one unpublished abstract retrospectively reviewed 1903 pediatric donors and showed that HRT was associated with increased odds of having the liver and at least one kidney and lung transplanted The greatest benefit of HRT in donor management may, in fact, be improved graft function following transplantation.65,85,86 Given these observations, many OPOs have adopted the use of HRT as a routine part of donor management.14 Commonly used agents and doses for HRT in pediatric donors are listed in Table 20.2 Reduced free triiodothyronine (T3) levels following neurologic death may impair mitochondrial function and deplete energy stores Animal studies have shown that diminished circulating T3 and thyroxine levels impair oxygen utilization.48 The effects of thyroid hormone on myocardial contractility are complex and can be immediate or delayed The acute inotropic properties of T3 may occur as a result of beta-adrenoreceptor sensitization or may be completely independent of beta-adrenergic receptors.87–91 Furthermore, T3 administration may play an important role in maintaining aerobic metabolism at the tissue level after neurologic death has occurred.92,93 Beneficial hemodynamic effects in brain-dead patients receiving T3 administration have been variable.88,89 Levothyroxine (Synthroid) and T3 are the two IV thyroid agents available for administration T3 is used in some centers for HRT; however, the cost of this medication may be prohibitive No superiority of hemodynamic improvement or cardiac benefits of T3 has been demonstrated when compared with levothyroxine in hemodynamically unstable donors.89 Dosing of thyroid hormone for the pediatric organ donor (see Table 20.2) is weight-based and not well established One retrospective study showed that younger children received larger bolus and infusion doses than older children and demonstrated enhanced weaning of inotropic support in children who progressed to brain death.82 Corticosteroids such as hydrocortisone are another pharmacologic agent routinely used by many centers for HRT to assist with hemodynamic support There are little data demonstrating that hydrocortisone provides hemodynamic benefit in the potential pediatric organ donor.56 However, treatment of the donor with high doses of corticosteroids to reduce inflammation associated with neurologic death and modulate immune function may improve donor organ quality and posttransplant graft function.14 Additionally, the potential benefit of hydrocortisone and other steroids may lie in their ability to alter adrenergic receptors and regulate vascular tone by increasing sensitivity to catecholamines.93,94 Steroids have also been shown to stabilize pulmonary function, reduce lung water accumulation, and increase lung recovery from donors.95–98 The combination of thyroid hormone and steroids may be used to reduce vasoactive agent dose requirements in children Additionally, vasopressin for control of DI can reduce the need for 169 inotropic support Taken in sum, HRT may provide the greatest benefit to the recipient of transplanted organs by improving donor organ quality Management of Pulmonary Issues for the Potential Pediatric Organ Donor Increasing success with lung transplantation for the treatment of patients with end-stage lung and pulmonary vascular disease has placed a premium on the acquisition of lungs from the donor pool Children waiting for a lung transplant comprise less than 5% of the national pediatric waitlist.1 However, the demand for lungs far exceeds availability because lungs are the organs most likely to be found unsuitable for transplantation Recovery of lungs for transplantation accounts for 7% to 22% of the multiorgan donor pool.100,101 Low lung transplant recovery rates reflect stringent donor selection criteria and lack of suitable organs for transplantation A commonly used donor selection criterion is a ratio of Pao2 to fraction of inspired oxygen (Fio2) ratio greater than 300 mm Hg (Pao2 300 mm Hg with Fio2 1.0 using a PEEP of cm H2O) Every effort should be made to preserve lung function using lung-protective strategies, as many marginal lungs may become unsuitable for transplantation.101 Many factors contribute to the low rates of acquisition of lungs for transplantation in children Blunt trauma resulting in pulmonary contusion/hemorrhage and inhalational or thermal injuries may directly damage the lungs and airway structures Infection can compound the effects of existing lung disease or injury.97 Neurogenic pulmonary edema may develop during the progression or upon completion of neurologic death, resulting in high ventilator settings.55 Sympathetic storm associated with neurologic death causes systemic and pulmonary vasoconstriction Neurogenic pulmonary edema occurs as pulmonary venous pressure rises, causing pulmonary capillary wall disruption.102 This predictable deterioration of pulmonary function compounds secondary lung injury following neurologic death.101,103 Furthermore, lungs are particularly vulnerable in the face of critical illness, leaving them susceptible to complications such as fat emboli, pulmonary emboli, aspiration pneumonia, ventilator-associated pneumonia, and atelectasis.97 Each of these factors contributes to secondary lung injury, impairs ventilation and oxygenation, and reduces lung suitability for transplantation Management strategies to protect donor lungs have resulted in improved recovery and successful transplantation of these organs.104,105 These measures include diligent pulmonary secretion clearance with frequent suctioning, patient turning, and airway evaluation with flexible bronchoscopy.97,105 Ventilator management with attention to recruitment maneuvers such as sustained inflations and PEEP have been advocated to avoid the development of atelectasis and treat pulmonary edema associated with the catecholamine storm that occurs with neurologic death.104,106 The benefit associated with these maneuvers must be balanced against the risk of barotrauma and effects on preload that can potentially embarrass cardiac output in the donor with myocardial dysfunction Cardiovascular effects can be minimized if adequate preload is provided prior to escalation of PEEP Colloid solutions have been recommended to minimize accumulation of pulmonary edema.106 Albuterol has been shown to enhance clearance of pulmonary edema in an animal model77 and to improve mucociliary clearance.97 However, a randomized controlled trial using highdose albuterol nebulization did not show improvement in donor 170 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal oxygenation or lung utilization.107 Corticosteroids are frequently used in the donor and have been shown to reduce lung water accumulation and stabilize pulmonary function.95–98 Another novel therapy involves the use of naloxone to improve gas exchange in donor lungs,108 although a recent study showed no improvement in oxygenation compared with placebo in hypoxemic organ donors.109 The exact mechanism of action of naloxone to enhance pulmonary function is unknown, but free radical scavenging has been suggested Ventilatory requirements may become minimal in the donor as neurologic death progresses Respiratory alkalosis is common as the metabolic production of CO2 from the brain ceases and compliance of the chest wall changes Restoring normocarbia with a Paco2 goal of 35 to 40 mm Hg in the child who has progressed to neurologic death is ideal given the effects of pH on unloading characteristics of oxygen from hemoglobin Avoiding overdistension of the lungs during mechanical and manual ventilation is crucial to reducing the risk of barotrauma or further pulmonary injury.97,105 Donor management goals include achieving a Pao2 greater than 100 mm Hg and oxygen saturation greater than 95% using the least amount of Fio2 necessary Adequate alveolar recruitment may be obtained with a tidal volume of to 10 mL/kg, and PEEP of cm H2O or lower tidal volumes of to mL/kg and higher PEEP of to 10 cm H2O A randomized trial in adult donors demonstrated benefits of using lung-protective ventilation strategy with tidal volumes of to mL/kg, to 10 cm H2O PEEP, a closed circuit for suctioning, continuous positive airway pressure equal to previous PEEP for apnea tests, and recruitment maneuvers after any disconnection from the ventilator Lung re- covery rates doubled (54% vs 27%) compared with a conventional ventilator protocol.110 Elevation of the head of the bed and use of a cuffed endotracheal tube with high cuff pressures to reduce aspiration risk are also advocated.97 Additionally, oral care using chlorhexidine may reduce the chances of a ventilatorassociated infection Frequent turning and chest physiotherapy when appropriate are essential to prevent atelectasis Prone positioning may be beneficial to optimize ventilation perfusion matching Serial chest radiographs are commonly obtained to identify correctable issues or evaluate pulmonary pathology Donor management guidelines for oxygenation and ventilation are summarized in Table 20.1 Diagnostic and therapeutic flexible bronchoscopy can assist with the clearance of mucous plugs or blood clots that may contribute to impaired oxygenation Many OPOs advocate early bronchoscopic evaluation of the lungs to assess anatomy, address correctable issues, and maximize ventilation strategies to improve lung function Fluid and Electrolyte Disturbances Fluid and electrolyte disturbances in the pediatric donor are the result of physiologic abnormalities following neurologic death and the consequences of premortem medical management Commonly encountered derangements include dehydration; hyperglycemia; and sodium, potassium, and calcium disturbances If left untreated, these abnormalities can adversely affect donor organ viability Evaluation and treatment of such disorders in the pediatric organ donor are discussed here and in Chapter 71 TABLE 20.2 Pharmacologic Agents Used for Hormonal Replacement in Children Drug Dose Route Comments Desmopressin (DDAVP) 0.5 mg/h IV Terminal half-life of 75 (range, 0.4–4.0 h) Titrate to control urine output (2–4 mL/kg/h) May be beneficial in patients with an ongoing coagulopathy Vasopressin (Pitressin) 0.5 milliunits/kg/h IV Half-life of 10–35 Titrate to control urine output (2–4 mL/kg/h) Hypertension can occur Levothyroxine (Synthroid) 0.8–1.4 mg/kg/h Maximum 20 mg/h IV Titrate to effect Bolus dose 1–5 mg/kg can be administered (maximum dose 20 mg) Smaller infants and children require a higher bolus and infusion dose Triiodothyronine 0.05–0.2 mg/kg/h IV Titrate to effect Methylprednisolone 20–30 mg/kg Maximum dose g or use hydrocortisone infusion below IV Dose may be repeated in 8–12 hours Fluid retention and glucose intolerance can occur Hydrocortisone infusion ,25 kg, mg/kg/h 26–35 kg, 50 mg/h 36–45 kg, 75 mg/h 45 kg, 100 mg/h IV Maximum dose should not exceed 100 mg/h Insulin 0.05–0.1 U/kg/h IV Titrate to effect to control blood glucose levels Monitor for hypoglycemia Modified from Nakagawa TA North American Transplant Coordinators (NATCO) Updated Donor Management and Dosing Guidelines Lenexa, KS: 2008 170.e1 Intravascular volume depletion is frequently encountered in the child with traumatic brain injury who has progressed to neurologic death Fluid restriction is commonly employed in the management of cerebral edema, along with hypertonic solutions and osmotic diuretics Another contributor to intravascular volume depletion is osmotic diuresis from hyperglycemia secondary to steroid and catecholamine use and increased availability of glucose from loss of cerebral metabolism Furthermore, DI exacerbates sodium and water imbalance if not aggressively treated Intravascular volume and tissue perfusion must be restored and maintained guided by CVP, perfusion, serum electrolyte concentrations, and serial lactate measurements CHAPTER 20 Organ Donation Process and Management of the Organ Donor Diabetes Insipidus Ischemia and ultimate necrosis of the posterior pituitary following neurologic death leads to loss of central antidiuretic hormone secretion and central DI Uncontrolled urine output with free water losses results in severe hypernatremia, severe dehydration, hypovolemic shock, and eventual cardiovascular collapse Treatment of DI is detailed here and in Chapter 84 Oliguria Oliguria can be seen with volume depletion, acute renal insufficiency or failure, and overly aggressive pharmacologic management of DI If urine output falls to less than mL/kg/h and does not improve after decreasing or discontinuing vasopressin or desmopressin, intravascular volume status must be evaluated and appropriately treated using volume expanders If urine output does not recover, it may be improved by initiation of inotropic or vasopressor support Furosemide or mannitol can be used to stimulate urine output in the patient with adequate intravascular volume status A selective dopamine agonist, such as fenoldopam, can be used to enhance urine output and may provide renal protection in the normotensive or hypertensive patient.118 Treatment of glucose and electrolyte abnormalities that may be encountered in the potential organ donor patient is detailed next Coagulation Abnormalities Coagulation abnormalities can arise secondary to the release of tissue thromboplastin and cerebral gangliosides from the injured brain.55 Additionally, the catecholamine surge associated with traumatic brain injury may contribute to coagulation disturbances.119 Treatment of coagulation disturbances seen with brain injury/death is further detailed in Chapters 89 and 90 Thermoregulatory Instability Hypothermia is common after neurologic death due to loss of hypothalamic-pituitary function that maintains thermoregulation Vasodilation with an inability to compensate for heat loss by shivering or vasoconstriction is a common cause of thermoregulatory instability in this patient population Infusion of large volumes of room temperature IV fluids to treat DI and volume depletion contributes to hypothermia Hypothermia can promote cardiac dysfunction, arrhythmias, coagulopathy, a cold-induced diuresis secondary to decreased renal tubular concentration gradient, and a leftward shift of the oxyhemoglobin dissociation curve, resulting in decreased oxygen delivery to the tissues.122 Radiant warmers, warm blankets, thermal mattresses, warm IV fluids or a blood warmer for infusion of blood products, and environmental warming will help maintain body temperature Additionally, heating-inspired gases can assist in controlling body temperature Avoiding hypothermia is essential to prevent deterioration of the potential organ donor Medical Examiner and Coroner Issues and Organ Donation for Children Many children who die from head injuries are victims of nonaccidental trauma The medical examiner or coroner has a legal and social responsibility to determine the manner and cause of death 171 in these cases When a child’s death is ruled a homicide, great sensitivity is required to balance preserving the integrity of the ongoing criminal investigation while respecting the family’s desire for organ donation to occur Successful recovery of organs and the prosecution of the perpetrator may still occur in most cases with close cooperation between forensic investigators, treating physicians, transplant team, and OPO.4,14,123–126 Mechanisms have been described, including modification of surgical techniques, to preserve potential evidence and permit the mutual goals of the family and OPO.127 There is no reported case law in which organ donation has resulted in loss of evidence and inability to prosecute a perpetrator involved with the death of a child Early involvement of the medical examiner or coroner and protocols to facilitate organ recovery in homicide cases may reduce denials for organ donation.124–126,128 Data from the Collaborative Pediatric Critical Care Research Network would suggest that donation is still possible even when cases proceeded with autopsy initiated by the medical examiner or family.129 Involvement of the district attorney during protocol development may also be a consideration, especially in high-profile cases Efforts to reduce the number of medical examiner denials for donation are supported in the position statement by the National Association of Medical Examiners, which states, “Medical examiners and coroners should permit the recovery of organs and/or tissues from decedents falling under their jurisdiction in virtually all cases, to include cases of suspected child abuse, other homicides, and sudden unexpected deaths in infants.”130 Despite ongoing national efforts, many transplantable organs from potential pediatric donors go unrecovered and represent missed opportunities because of medical examiner/coroner denials.13 Donation after Circulatory Death While the vast majority of recovered organs from donors represent DBD, DCD has become an additional source of valuable organs for transplantation Formerly known as “non-heart-beating organ donor” or “donation after cardiac death,” DCD is not new Prior to the development of guidelines to determine neurologic death, cadaveric organs were routinely recovered after death was declared following loss of circulation DCD allows organ recovery of kidneys, liver, lungs, pancreas, and—in some instances—heart from patients with catastrophic brain injury who not progress to neurologic death The discussions and decision to donate organs must be clearly separated from, and can only occur after, the decision to withdraw life-sustaining medical therapy This avoids a perceived ethical conflict that the patient is being allowed to die primarily to recover organs Routine humanistic end-of-life care—specifically, comfort measures, including administration of analgesic and sedatives— must be provided as they would for any patient undergoing withdrawal of life-sustaining medical therapies.18 Management of the DCD donor differs from the brain-dead donor because a determination of death is prospective with the planned withdrawal of therapy Withdrawal of life-sustaining medical therapies can occur in the ICU or operating theater Logistics regarding patient transport to limit warm ischemic time and to allow family presence until a determination of circulatory death is confirmed are important considerations Additionally, the medical team should have provisions and prepare the family for ongoing care if donation is not possible Specific criteria must be met to ensure the viability of recovered DCD organs Circulatory arrest must usually occur within 171.e1 Hypernatremia (serum sodium 155 mEq/L) can affect organ suitability for transplantation and has been associated with worse graft outcomes following liver transplantation.14,111,112 In addition to hourly maintenance IV fluids, one-quarter or onehalf normal saline can be used to replace urine output in excess of to mL/kg until pharmacologic replacement therapy with vasopressin or desmopressin acetate (DDAVP) is implemented Glucose should be avoided in renal replacement fluids to prevent further exacerbation of hyperglycemia and osmotic diuresis Enteral free water supplementation administered through a nasogastric tube can be used for correction of severe hypernatremia However, enteral free water supplementation may be limited by gastrointestinal ischemia and impaired absorption Rapid osmotic shifts during correction of hypernatremia are inconsequential since neurologic death has already occurred Pharmacologic agents such as vasopressin or desmopressin are routinely used in HRT protocols to control excessive urine output and free water loss associated with DI Pharmacologic treatment is intended to reduce and not completely abolish urine output Donor management goals while treating DI include maintaining a normal serum sodium level and reducing excessive urine output Vasopressin is a polypeptide hormone secreted by the hypothalamus and stored in the posterior pituitary Vasopressin acts on V1 and V2 receptors stimulating contraction of vascular smooth muscle with resultant vasoconstriction It has a short half-life of 10 to 35 minutes and, unlike desmopressin, has no effect on platelets.14,71,113 Vasopressin can be administered by bolus or continuous IV infusion The most desirable features of this agent derive from its ease of titration to control urine output When discontinued, its effects are short-lived Vasopressin is administered at doses of 0.5 mU/kg per hour and can be titrated to control urine output to to mL/kg per hour.8,71,113 By titrating in this way, one preserves renal function and avoids volume overload and metabolic abnormalities such as hyponatremia and hyperkalemia Vasopressin acts synergistically and has a catecholaminesparing effect, making it ideal for the donor with DI and hemodynamic instability, requiring vasopressor support.66,68,71 The infusion may need to be reduced after several hours to avoid complete loss of urine output.14 Excessive dosing of vasopressin should be avoided to preserve end-organ function as high doses, especially when combined with other vasopressors, may potentially reduce splanchnic perfusion, affecting hepatic and pancreatic blood flow Additionally, vasoconstriction and increased smoothmuscle contractility may affect coronary and pulmonary blood flow.54 Excessive dosing of vasopressin should be avoided to preserve end-organ function DDAVP is a more potent synthetic polypeptide structurally related to vasopressin This agent lacks smooth-muscle contractile properties and is more specific for the V2 receptor Desmopressin enhances platelet aggregation and has a longer half-life of to 20 hours when administered as a single IV dose.115,116 Desmopressin may be a preferred agent for the correction of hypernatremia in hemodynamically stable donors who require no inotropic or vasopressor support or for the donor with ongoing bleeding issues because it enhances platelet aggregation Desmopressin can be administered by continuous infusion at 0.5 mg/h titrated to control urine output or as a single IV dose.68,71,117 Intramuscular and intranasal administration can result in erratic absorption and should be avoided The terminal half-life of desmopressin administered by continuous IV infusion is 75 minutes with a range of 0.4 to hours.117 The longer half-life of desmopressin may be less desirable compared with the shorter halflife of vasopressin in potential kidney donors However, desmopressin therapy may be discontinued to hours prior to organ recovery.68 ... and can only occur after, the decision to withdraw life-sustaining medical therapy This avoids a perceived ethical conflict that the patient is being allowed to die primarily to recover organs... heat loss by shivering or vasoconstriction is a common cause of thermoregulatory instability in this patient population Infusion of large volumes of room temperature IV fluids to treat DI and... be met to ensure the viability of recovered DCD organs Circulatory arrest must usually occur within 171.e1 Hypernatremia (serum sodium 155 mEq/L) can affect organ suitability for transplantation