Management of Pediatric Transplant Patients in the Emergency Department (Pharmacology CME)

Table of Contents

 

About This Issue

Transplant patients are at risk for unique illnesses and complications after transplantation. Many complications of transplantation present similarly, and often with vague signs and symptoms. The emergency clinician must have a high clinical suspicion even for children who present with seemingly benign presentations. This issue discusses the general approach to the management of pediatric transplant patients in the emergency department (ED), with a focus on general and organ-specific complications after solid organ transplantation. Management of hematopoietic stem cell transplant patients is also discussed; the approach to these patients differs slightly from that of solid organ transplant patients. Key concepts include:

All transplant patients should be triaged as high acuity and seen promptly.

In general, complications occurring after solid organ transplantation are associated with rejection, infection, or adverse effects from medications.

Transplant patients frequently require further workup for unique and complex illnesses, given their history and immunosuppressed status.

A thorough history is important when assessing a transplant patient in the ED; determine the reason for the transplant, when the transplant occurred, and what medications the patient is taking including recent changes in medications.

For solid organ transplant patients, fever may be a sign of infection or rejection, so it is important to consider both.

Fever and leukocytosis may be blunted in immunosuppressed patients, so have a high suspicion for infection even in the absence of fever.

Diagnostic studies should focus on assessing not only the presenting symptoms but also the integrity of the transplanted organ. Even small deviations from a patient’s baseline may be indicative of a more serious process.

Immunosuppressive agents have interactions with numerous medications, so careful consideration is required when beginning antibiotics or other therapeutic agents.

For hematopoietic stem cell transplant patients, graft-versus-host disease is a major source of morbidity and mortality that must be considered.

Management of all transplant patients should include consultation with the patient’s transplant team to ensure appropriate testing, treatment, and disposition for these patients.

1. About This Issue
2. Abstract
3. Case Presentations
4. Introduction
5. Critical Appraisal of the Literature
6. Etiology and Pathophysiology
7. Differential Diagnosis
8. Prehospital Care
9. Emergency Department Evaluation
   1. History
   2. Physical Examination
10. Diagnostic Studies
    1. Laboratory Studies
    2. Imaging Studies
11. Treatment
12. Solid Organ Transplantation
    1. General Solid Organ Transplantation Complications
       1. Graft Rejection
       2. Infection
          • Early Infection: <1 Month Posttransplantation
          • Intermediate Infection: 1 to 6 Months Posttransplantation
          • Late Infection: >6 Months Posttransplantation
       3. Medication Effects
       4. Posttransplant Lymphoproliferative Disorder
    2. Organ-Specific Complications
       1. Kidney Transplant Complications
          • Kidney Transplant Rejection
       2. Liver Transplant Complications
          • Liver Transplant Rejection
       3. Heart Transplant Complications
          • Heart Transplant Rejection
       4. Lung Transplant Complications
          • Lung Transplant Rejection
13. Hematopoietic Stem Cell Transplantation
    1. Hematopoietic Stem Cell Transplantation Complications
       1. Infection
       2. Graft-Versus-Host Disease
          • Acute Graft-Versus-Host Disease
          • Chronic Graft-Versus-Host Disease
       3. Medication Effects
14. Special Considerations
    1. Vaccinations
    2. Transition of Care
15. Controversies and Cutting Edge
    1. Advancements in Pediatric Transplantation
    2. End-of-Life and Palliative Care
16. Disposition
17. Summary
18. Risk Management Pitfalls for Pediatric Transplantation Patients
19. Time- and Cost-Effective Strategies
20. Case Conclusions
21. Tables
    1. Table 1. Selected List of CYP3A Inhibitors and Inducers
    2. Table 2. Overview of Solid Organ Transplant Complications
    3. Table 3. Overview of Immunosuppressive Medications*
    4. Table 4. Clinical Manifestations of Acute and Chronic Graft-Versus-Host Disease
22. References

Abstract

Transplant patients are at risk for illnesses and complications days, months, or years after transplantation, and they can present complex challenges for emergency clinicians. This review discusses the general approach to the management of pediatric transplant patients in the emergency department, with a focus on general complications and organ-specific complications after solid organ transplantation. Hematopoietic stem cell transplantation and its common complications will also be discussed. A key step in the management of all transplant patients includes consultation with the patient’s transplant team to ensure appropriate testing, treatment, and disposition for these patients.

Case Presentations

An 11-year-old boy who received a heart transplant 8 months ago presents to the ED for evaluation of fever…

• He has had a mild cough and rhinorrhea for the past 2 days and developed a fever to 38°C this morning. He received his heart transplant for hypoplastic left heart syndrome and has been doing well on his maintenance immunosuppression medications. He sees his transplant physician every 2 months and has had no complications. There are no sick contacts at home, but the child does attend school.
• Given the boy’s history of transplantation, he was triaged as a high-acuity case. His vital signs are: temperature, 38.6°C; heart rate, 185 beats/min; respiratory rate, 25 breaths/min; blood pressure, 105/82 mm Hg; oxygen saturation, 95% on room air. On physical examination, you note crackles at the lung bases bilaterally.
• Knowing this patient is immunocompromised, you are worried about a lower respiratory tract infection, but you are also concerned this could be an episode of acute rejection manifesting as early congestive heart failure. As you consider the possible diagnoses, you think about your next steps. Which laboratory tests would be most helpful? Which antibiotics does he need? Should corticosteroids be started to treat possible rejection?

A 3-year-old girl with a history of acute lymphoblastic leukemia who underwent a hematopoietic stem cell transplant 3 months ago presents to the ED for evaluation of fever...

• The girl’s parents say she has had a runny nose and mild cough over the last 2 days. Today, she has been fussier than usual. They took her temperature at home, noted a fever of 39.7°C, and called their transplant physician, who advised them to go to the nearest ED.
• When the girl arrived to the ED, she was alert and fussy, but consolable. Given her history, despite her mild symptoms, she was triaged as a high-acuity patient. Her vital signs are: temperature, 39.4°C; heart rate, 190 beats/min; respiratory rate, 30 breaths/min; blood pressure, 85/66 mm Hg; oxygen saturation, 98% on room air. Her physical examination is notable for rhinorrhea and referred upper airway congestion. She has a subcutaneous port over her right chest, with no overlying erythema or warmth.
• While you are obtaining the history from the parents, they mention that the girl was diagnosed with acute graft-versus-host disease 1 week ago and was started on some new medications to treat it. You are not at the patient’s transplant center and do not have access to their records. You wonder whether the girl’s symptoms are from the acute graft-versus-host disease or a new infection? Which antibiotics are most appropriate in this situation? How will the history of new medications change your management of this patient?

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Tables and Figures

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Key References

Following are the most informative references cited in this paper, as determined by the authors.

1. U.S. Department of Health & Human Services. National Data: Organ Procurement and Transplantation Network. Accessed September 15, 2021. (National database)

7. * Zhong D, Liang SY. Approach to transplant infectious diseases in the emergency department. Emerg Med Clin North Am. 2018;36(4):811-822. (Review article) DOI: 10.1016/j.emc.2018.06.010

9. * Sanchez-Fueyo A, Strom TB. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology. 2011;140(1):51-64. (Review article) DOI: 10.1053/j.gastro.2010.10.059

17. * Weigel F, Lemke A, Tonshoff B, et al. Febrile urinary tract infection after pediatric kidney transplantation: a multicenter, prospective observational study. Pediatr Nephrol. 2016;31(6):1021-1028. (Prospective study; 137 patients) DOI: 10.1007/s00467-015-3292-2

25. * Joong A KA. Emergency department evaluation of the pediatric heart transplant recipient. Clin Pediatr Emerg Med. 2018;19(4):353-357. (Review article) DOI: 10.1016/j.cpem.2018.12.006

32. * Faro A, Mallory GB, Visner GA, et al. American Society of Transplantation executive summary on pediatric lung transplantation. Am J Transplant. 2007;7(2):285-292. (Review article) DOI: 10.1111/j.1600-6143.2006.01612.x

36. * Fraint E, Holuba MJ, Wray L. Pediatric hematopoietic stem cell transplant. Pediatr Rev. 2020;41(11):609-611. (Review article) DOI: 10.1542/pir.2020-0130

44. * Dulek DE, de St Maurice A, Halasa NB. Vaccines in pediatric transplant recipients-past, present, and future. Pediatr Transplant. 2018;22(7):e13282. (Review article) DOI: 10.1111/petr.13282

47. * Blondet NM, Healey PJ, Hsu E. Immunosuppression in the pediatric transplant recipient. Semin Pediatr Surg. 2017;26(4):193-198. (Review article) DOI: 10.1053/j.sempedsurg.2017.07.009

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Keywords: transplant patients, pediatric transplant patients, posttransplant patients, posttransplantation, complications after transplantation, complications after transplant, organ transplantation, solid organ transplantation, hematopoietic stem cell transplantation, HSCT, infection, rejection, hyperacute rejection, acute rejection, chronic rejection, medication adverse effects, graft-versus-host disease, GVHD, acute graft-versus-host disease, acute GVHD, chronic graft-versus-host disease, chronic GVHD, kidney transplant, heart transplant, liver transplant, lung transplant, immunosuppression, immunosuppressive medications, transplant infection, vaccines transplant patient, cytomegalovirus infection, CMV, Epstein-Barr virus infection, EBV, BK virus, posttransplant lymphoproliferative disorder, PTLD, hepatic artery thrombosis, HAT, portal vein thrombosis, PVT