171 e2 Glucose, Potassium, and Calcium Derangements Neurologic death causes major hormonal alterations resulting in insulin resistance and gluconeogenesis Hyperglycemia as a result of corticosteroid a[.]
171.e2 Glucose, Potassium, and Calcium Derangements Neurologic death causes major hormonal alterations resulting in insulin resistance and gluconeogenesis Hyperglycemia as a result of corticosteroid and catecholamine use and increased availability of glucose due to the loss of cerebral metabolism can lead to an osmotic diuresis, exacerbating an already depleted volume status in the donor Hyperglycemia can be avoided by frequently monitoring serum glucose concentration and making appropriate adjustments in the dextrose concentration in IV fluids If these simple maneuvers are unsuccessful in controlling blood glucose levels, an insulin infusion should be administered to maintain glucose levels within a reasonable range (60–200 mg/dL) Although target glucose levels for insulin therapy in the deceased donor continue to be debated, uncontrolled hyperglycemia should be treated.14 Serum glucose levels should be closely followed to avoid hypoglycemia Potassium derangements can result from diuresis, acute kidney injury, corticosteroid administration, and acid-base disturbances Potassium can be supplemented if hypokalemia is significant or if arrhythmias occur The adverse effects of hyperkalemia are clearly more hazardous than those of hypokalemia Hypocalcemia occurs commonly secondary to large volume replacement with colloids such as albumin, massive blood transfusions that result in large amounts of citrate reducing free calcium concentrations, and sepsis Calcium is necessary for myocardial contraction, and hypocalcemia can depress cardiac output, affect SVR, and affect organ perfusion.68 The use of calcium supplementation should be guided by ionized calcium levels 171.e3 Synthetic plasma expanders such as hespan are not recommended for volume replacement as they can promote or worsen coagulopathy.14,70,71,120 Thrombocytopenia and platelet dysfunction can be induced by commonly used drugs such as heparin, antibiotics, bblockers, calcium channel blockers, histamine H2 receptor antagonists, tromethamine, and hespan.70,121 Patients with hepatic disease or dysfunction have reduced synthesis of vitamin K-dependent clotting factors A dilutional coagulopathy can occur from massive red cell transfusions if coagulation factors are not replenished Coagulation abnormalities can also be exacerbated by hypothermia Coagulopathy can be treated by using fresh-frozen plasma, platelets, and cryoprecipitate, depending on the underlying abnormality, and by restoring and maintaining normothermia Coagulation abnormalities should be addressed prior to transport of the donor to the operating suite for organ recovery A minimum platelet count of 75,000/uL should be obtained prior to recovery of organs in the operating suite The use of aminocaproic acid (Amicar), an antifibrinolytic agent, and other similar hemostatic agents are not recommended for the treatment of bleeding since microvascular thrombosis may be induced in donor organs.55 172 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal 60 minutes after withdrawing life support The time constraint is important since longer periods of hypotension and/or hypoxia prior to circulatory arrest will result in organ ischemia, precluding viable organs for transplantation Following loss of pulse pressure (mechanical asystole ideally noted on arterial tracings), the patient is observed for to minutes before the recovery of organs can begin This 2- to 5-minute observation, or “hands-off” period, is crucial to ensure that autoresuscitation (anterograde flow of blood ejected from the heart) with restoration of spontaneous circulation does not occur.75 Prior to and during this observation period, CBF falls below a normal cerebral perfusion pressure threshold Cerebral activity in DCD patients, measured by EEG, ceases within 15 to 30 seconds after circulatory arrest.131–133 Importantly, it is the loss of circulatory function and not electrical activity (electrical asystole) that is required to determine death.76 Determining when a patient will develop circulatory arrest can be difficult Scoring tools have been developed in an effort to predict whether death will occur within the specified time period to permit DCD.134–136 These tools should be used in conjunction with the physical examination and in discussion with the critical care team and OPO to determine donor suitability and the likelihood of progressing to death in the allotted time If circulatory cessation does not occur within 60 minutes, organ recovery is aborted and comfort measures continue in the ICU or another predetermined location DCD requires close collaboration between the critical care team, operating room staff, and OPO to ensure the successful recovery of organs The reevaluation of this method of donation was prompted by an increasing need to meet the demands of a growing national transplant waitlist.137,139 There have been significant increases in the number of DCD donors over the past 15 years.1 This sustained practice of organ recovery in children accounts for more than 10% of all DCD donors.1 This method of donation has increased organ recovery from children and enhanced overall organ availability for transplantation.1,137,140–142 Individual numbers of DCD donors may be small at any one pediatric center but the collective impact from all pediatric centers supporting DCD has significantly increased organ availability.1,137,140–143 DCD focuses on recovery of the two most commonly needed organs for children: liver and kidney Success with transplantation of DCD organs, primarily kidney and liver, is occurring in many centers Rates of graft survival for DCD kidney and liver appear to be similar to organs recovered from donors following neurologic death.144–149 Results from pediatric DCD renal and liver transplants have been acceptable.2,150,151 Some centers have experienced an increased risk of biliary stenosis, hepatic infections, postoperative complications, and higher repeat transplantation rates with the use of DCD livers.14,152,153 A recent single-center comparison is more encouraging, with 100% 10-year patient and graft survival rates of livers procured from both DCD and neurologic death donors No ischemic biliary complications with DCD were noted.154 There is increasing experience with lung transplants from DCD donors in adults and children.1,155–158 Neonatal donor opportunities continue to be explored as another source of valuable organs for transplantation.159–163 Although neurologic death is rare in neonates, recovery of DCD organs is becoming more common Recovery of DCD neonatal kidneys has the potential to increase the number of kidneys available for transplantation.14,150,162,163 En bloc renal transplant from neonatal and pediatric DCD donors is occurring with good success, even in donors as small as 1.9 kg.150,163–165 Additionally, successful transplantation of three hearts recovered from neonatal DCD donors under an established research protocol10 and the use of ABO-incompatible hearts has occurred.166 Some controversy continues to exist over this method of donation Ethical concerns focus on the timing of death, whether the potential donor meets criteria for death at the time of organ recovery, and whether antemortem medical therapies result in nonbeneficence or potential maleficence.75,167–171 Although an ethical discussion on DCD donation is beyond the scope of this chapter, many national organizations in the United States and Canada have reviewed and concluded that DCD is ethically acceptable when performed within specific guidelines The Society of Critical Care Medicine, Institute of Medicine, American Medical Association, AAP, and Canadian and other medical societies support DCD as an acceptable means to recover organs for transplantation.4,172–177 The AAP recognizes ethical concerns and supports institutions in efforts to provide access to DCD while encouraging but not mandating physician participation with this type of donation.178 Ultimately, limiting family members’ desire to have their loved one become a donor is a restriction of autonomy.21 Education regarding this mode of donation is crucial for all healthcare personnel to identify and recover organs from this population of children successfully.3,179,180 Contraindications to Organ Donation There are relatively few medical contraindications to organ donation The ultimate decision on whether an organ is acceptable for transplantation is determined by the transplant surgeon and medical director of the OPO This decision is based on the patient’s history, laboratory studies, and inspection of organs at the time of recovery Overwhelming sepsis is usually a contraindication to donation In many of these cases, most organs will suffer from inadequate perfusion, rendering organs unacceptable for transplantation However, patients with meningitis or bacteremia can donate organs if they have been appropriately treated with antibiotics for 24 hours prior to organ recovery.14,18 Other CNS infections, such as encephalitis or disseminated viral infections, may pose too great a risk to the recipient, limiting donation potential in these patients The advent of direct-acting antiviral therapy for hepatitis has allowed hepatitis C donor organs to be transplanted into recipients with the same virus or hepatitis-negative recipients with reasonable outcomes.181–184 Patients with HIV were once considered ineligible to become donors However, the HIV Organ Policy Equity (HOPE) Act bill allows transplantation of HIV-positive organs from a donor with the same serotype With antiretroviral therapy, HIV is no longer considered a fatal disease In the United States, liver and kidney recovery from a deceased HIV-positive donor were transplanted into an HIV-positive recipient A living donor with HIV was able to donate a kidney to another HIV-positive recipient.185 Internationally, a unique transplant occurred in which an HIV-positive mother donated a portion of her liver to her HIV-negative child suffering from hepatic failure.186 Active malignancy is a contraindication to donation However, patients with cancer in remission may be candidates for donation depending on the duration of remission Patients with CNS tumors that have not metastasized may be eligible to donate organs However, surgical intervention or medical treatment of these tumors, including shunt placement or craniotomy, may limit eligibility for donation Concerns regarding donation potential should be discussed with the OPO medical director before a decision regarding donation eligibility can be established CHAPTER 20 Organ Donation Process and Management of the Organ Donor Evolving Areas of Transplantation Improved donor management, operative techniques, postoperative care, organ perfusion technology, and immunosuppressive therapy have advanced transplantation with recovery of more organs and better graft function These innovations assist in meeting the growing number of potential recipients waiting for a lifesaving transplant Organs once considered suboptimal are now considered for transplantation as medical care and technologies have enhanced donor organ function and engraftment Ex vivo and in situ perfusion technologies represent an evolving area of growth and development in the field of transplantation Regional techniques and organ-specific support systems are designed to improve quality and procurement rates prior to transplantation.187–194 These organ preservation systems specifically designed for kidney, heart, liver, and lungs overcome limitations from cold ischemic preservation that can affect graft performance following transplantation Ex vivo perfusion can potentially condition and maintain organs in a near-physiologic state (healthy and functioning), allowing for longer preservation time for procured organs prior to transplantation Ethical concerns exist regarding the use of regional extracorporeal support in the donor to minimize warm ischemic times for DCD abdominal organs At a minimum, impeding recirculation to the brain or thorax is essential to prevent potential reanimation and restoration of circulation that would negate the determination of circulatory death.76 Infants waiting for a transplant continue to have the highest death rate on the waiting list.1,2 Neonatal donation opportunities are rare but can increase organ availability for transplantation Novel donor populations, such as anencephalic infants, have the potential to increase organ availability for transplantation.195 Many infants waiting for a heart transplant may die because an organ never becomes available ABO-incompatible heart transplantation for children less than years and recovery of hearts from neonatal DCD donors may provide needed organs to decrease infant deaths on the national waitlist.160,166,196,197 As mechanical support devices become increasingly available as a bridge to heart transplantation, neonatal donation will require continued advocacy by neonatologists, OPOs, and institutions to limit missed opportunities for donation in the neonatal intensive care unit population Abdominal organs from neonates are being recovered and used for transplantation Special processing of liver cells from neonatal donors for liver cell transfusion is now entering into phase II clinical trials.198,199 Donor hepatocytes are infused into infants with urea cycle defects and Crigler-Najjar syndrome as a bridge to transplantation In addition, en bloc kidney recovery from neonatal donors is occurring and organs are being transplanted with good success.164,165 Intestinal transplantation may be indicated for children with anatomic or surgical short gut (e.g., intestinal atresia, gastroschisis, and volvulus) and those with severe functional or motility disorders (e.g., Hirschsprung disease, microvillus inclusion disease, visceral myopathy, and severe gastrointestinal neuropathy) Allograft types are classified by the inclusion of the liver or stomach, with a majority of recipients receiving the isolated small bowel or the small bowel with the liver In addition to complications associated with immediate postoperative care and immunosuppression, 5-year graft rejection rates requiring retransplantation occur in 35% to 79% of recipients despite improvement in 5-year survival rates from 47% to 56% to 80% to 93%.200–202 173 Experience with vascularized composite allograft (VCA) transplantation continues to advance These allografts include the face, hand, lower extremities, abdominal wall, penis, and uterus.203–207 A child who received VCA bilateral upper extremity grafts and a baby born to a uterus transplant recipient are recent advancements in this field.207,208 Vascularized composite allografts are included under the definition of an organ in the Organ Procurement Transplantation Network Final Rule.209 Summary Organ donation is a process that begins when a critically ill or injured child is identified as a potential donor with timely referral to the OPO Identifying and caring for the pediatric organ donor requires a skilled team of specialists who must not only deal with the deceased child but also the family Early involvement of the OPO allows coordination with the critical care team and family support services, enhancing the chance for the family to understand and accept the death of their child and authorize organ donation Timely and accurate determination of neurologic death allows the focus of medical management to transition toward care and preservation of organs for transplantation once authorization is obtained Management of the pediatric organ donor is a natural extension of care for a critically ill or injured child Meticulous care of the potential donor results in more transplantable organs with improved graft function Although adults continue to receive the majority of organs recovered from pediatric donors, more organs are being transplanted into pediatric recipients The option for organ donation should be made available to every family to preserve their autonomy regarding end-of-life decisions Families should be emotionally supported and approached about donation opportunities in a professional, compassionate manner that allows for open discussion during the most difficult, agonizing time in their lives The positive benefits of donation extend beyond the transplant recipient Donation helps families heal as they deal with the loss of their child Collaboration between pediatric critical care specialists, the critical care team, and other dedicated professionals providing specialized donor management can affect the lives not only of the donor family but also the many potential recipients and their families through the effects of a lifesaving and life-changing transplant For more information and additional resources about pediatric organ donation, visit the Organ Donation Toolbox at https:// organdonationalliance.org/organ-donation-toolbox/ Key References Korte C, Garber JL, Descourouez JL et al Pharmacist guide to management of the organ donors after brain death Am J Health-Syst Pharm 2016;73:1829-1839 Kotloff RM, Blosser S, Fulda GJ, et al Management of the potential organ donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement Crit Care Med 2015;43(6):1291-1325 Mallory GB Jr, Schecter MG, Elidemir O Management of the pediatric organ donor to optimize lung donation Pediatr Pulmonol 2009; 44(6):536-546 Martin DE, Nakagawa TA, Siebelink MJ, et al Pediatric deceased donation: a report of the Transplantation Society Meeting in Geneva Transplantation 2015;99:1403-1409 Nakagawa TA, Ashwal S, Mathur M, et al Guidelines for the determination of brain death in infants and children: an update of the 174 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal 1987 Task Force recommendations Crit Care Med 2011;39(9): 2139-2155 Nakagawa TA, Mou SS Management of the pediatric organ donor In: LaPointe D, Ohler L, Rudow T, et al., eds The Clinician’s Guide to Donation and Transplantation Lenexa, KS: North American Transplant Coordinators Organization (NATCO); 2006:839-845 Nakagawa TA, Shemie SD, Dreyden-Palmer K, et al Organ donation following neurologic and circulatory determination of death Pediatr Crit Care Med 2018:19:S26-S32 Sochet AA, Glazier AK, Nakagawa TA Diagnosis of brain death and organ donation after circulatory death In Mastropietro CW, Valentine KM Pediatric Critical Care Current Controversies Switzerland: Springer Nature; 2019:309-321 The President’s Council on Bioethics Controversies in the Determination of Death: A White Paper by the President’s Council on Bioethics Washington, DC: 2008 https://bioethicsarchive.georgetown.edu/ pcbe/reports/death/ Wood KE, Becker BN, McCartney JG, et al Care of the potential organ donor N Engl J Med 2004;351(26):2730-2739 The full reference list for this chapter is available at ExpertConsult.com ... Although an ethical discussion on DCD donation is beyond the scope of this chapter, many national organizations in the United States and Canada have reviewed and concluded that DCD is ethically acceptable... President’s Council on Bioethics Controversies in the Determination of Death: A White Paper by the President’s Council on Bioethics Washington, DC: 2008 https://bioethicsarchive.georgetown.edu/... of ABO-incompatible hearts has occurred.166 Some controversy continues to exist over this method of donation Ethical concerns focus on the timing of death, whether the potential donor meets criteria