Treatment of hyperammoniemia after orthotopic bilateral lung transplantation

Background. Hyperammonemia is a rare but potentially life-threatening condition that can occur in patients following lung transplantation. Elevated blood ammonia levels are associated with impaired nitrogen metabolism leading to severe neurological symptoms, including confusion, seizures, and coma. Given the growing number of lung transplants, the problem of hyperammonemia is particularly important, as timely diagnosis and treatment can significantly reduce the risk of mortality.

Objective. To present a case of acute hyperammonemia in a patient after bilateral lung transplantation, describing the treatment and successful outcome.

Material and methods. A 58-year-old lung transplant recipient with chronic obstructive pulmonary disease (GOLD IV, extremely severe course, with pronounced clinical symptoms (mMRС>3, CAT test more than 10 points), emphysematous phenotype, high risk of exacerbations, class E, severe exacerbation). The clinical case description was based on the results of general clinical and instrumental studies from the recipient's medical history and observation card.

Results. This article describes a clinical presentation of hyperazotemia and hyperammonemia, its successful treatment in a recipient following bilateral lung transplantation. By selecting an optimal treatment strategy, an adverse outcome was avoided and graft function was preserved.

Conclusion. Although the pathophysiological mechanism for elevated blood urea levels and hyperammonemia could not be determined, a multimodal treatment approach enabled the clinicians to select the best management strategy for this patient and achieve a favorable outcome.

1. Kotton CN, Huprikar S, Kumar D. Transplant infectious diseases: a review of the Scientific Registry of transplant recipients published data. Am J Transplant. 2017;17(6):1439–1446. PMID: 28066999 https://doi.org/10.1111/ajt.14195

2. Leger RF, Silverman MS, Hauck ES, Guvakova KD. Hyperammonemia post lung transplantation: a review. Clin Med Insights Circ Respir Pulm Med. 2020;14:1179548420966234. PMID:33192115 ht t p s ://doi.org/10.1177/1179548420966234

3. Buzo BF, Preiksaitis JK, Halloran K, Nagendran J, Townsend DR, Zelyas N, et al. Hyperammonemia syndrome postlung transplantation: case series and systematic review of literature. Transpl Infect Dis. 2022;24(6):e13940. PMID: 36039822 https://doi.org/10.1111/tid.13940

4. Kumar A, Advani S, Asim K, Mohamed MA, Wani F, Singh J, et al. Hyperammonemia in lung transplant patients and its management: a review. Indian J Thorac Cardiovasc Surg. 2022;38(Suppl 2):335–346. PMID: 35756952 https://doi.org/10.1007/s12055-021-01319-6

5. Roberts SC, Bharat A, Kurihara C, Tomic R, Ison MG. Impact of screening and treatment of Ureaplasma species on hyperammonemia syndrome in lung transplant recipients: a Single Center Experience. Clin Infect Dis. 2021;73(9):e2531–e2537. PMID: 33068392 https://doi.org/10.1093/cid/ciaa1570

6. Judde De Larivière M, Bürgisser N, Serratrice J, Leidi A. Hyperammoniemic encephalopathy: beyond the hepatic cause. Rev Med Suisse. 2024;20(891):1887-1891. (In French.). PMID: 39429177 https://doi.org/10.53738/REVMED.2024.20.891.1887

7. Roberts SC, Malik W, Ison MG. Hyperammonemia syndrome in immunosuppressed individuals. Current opinion in infectious diseases. 2022;35(3):262-2 6 8 . https://doi.org/10.1097/QCO.0000000000000828

8. Zhao L, Walline JH, Gao Y, Lu X, Yu S, Ge Z, et al. Prognostic role of ammonia in critical care patients without known hepatic disease. Front Med (Lausanne). 2020:7:589825. https://doi.org/10.3389/fmed.2020.589825

9. Yun S, Scalia C, Farghaly S. Treatment of hyperammonemia syndrome in lung transplant recipients. J Clin Med. 2023;12(22):6975. PMID: 38002590 https://doi.org/10.3390/jcm12226975

10. Lazebnik LB, Golovanova EV, Alekseenko SA, Bueverov AO, Plotnikova EYu, Dolgushina AI, et al. Russian Consensus “Hyperammonemia in Adults” (Version 2021). Experimental and Clinical Gastroenterology. 2021;(3):97–118. (In Russ.). https://doi.org/10.31146/1682-8658-ecg-187-3-97-118

11. Lichtenstein GR., Yang YX, Nunes FA, Lewis JD, Tuchman M, Tino G, et al. Fatal hyperammonemia after orthotopic lung transplantation. Ann Intern Med. 2000;132(4):283–287. PMID: 10681283 https://doi.org/10.7326/0003-4819-132-4-200002150-00006

12. Chen C, Bain KB, Iuppa JA, Yusen RD, Byers DE, Patterson GA, et al. Hyperammonemia syndrome after lung transplantation: a single center experience. Transplantation. 2016;100(3):678–684. PMID: 26335916 https://doi.org/10.1097/TP.0000000000000868

13. Bharat A, Cunningham SA, Scott Budinger GR, Kreisel D, DeWet CJ, Gelman AE, et al. Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans. Sci Transl Med. 2015;7(284):284re3. PMID: 25904745 https://doi.org/10.1126/scitranslmed. aaa8419

14. De Santo LS, Romano G, Amarelli C, Maiello C, Baldascino F, Bancone C, et al. Implications of acute kidney injury after heart transplantation: what a surgeon should know. Eur J Cardiothorac Surg. 2011;40(6):1355–1361. PMID: 21514175 https://doi.org/10.1016/j.ejcts.2011.02.068

15. Fidalgo P, Ahmed M, Meyer SR, Lien D, Weinkauf J, Cardoso FS, et al. Incidence and outcomes of acute kidney injury following orthotopic lung transplantation: a population-based cohort study. Nephrol Dial Transplant. 2014;29(9):1702–1709. https://doi.org/10.1093/ndt/gfu226

16. Krishnappa V, Gupta M, Manu G, Kwatra S, Owusu OT, Raina R. Acute kidney injury in hematopoietic stem cell transplantation: a review. Int J Nephrol. 2016;5:5163789. PMID: 27885340 https://doi.org/10.1155/2016/5163789

17. Anwar S, Gupta D, Ashraf MA, Khalid SA, Rizvi SM, Miller BW, et al. Symptomatic hyperammonemia after lung transplantation: lessons learnt. Hemodial Int. 2014;18(1):185–191. PMID: 23998793 https://doi.org/10.1111/hdi.12088

18. Bélanger-Quintana A, Arrieta Blanco F, Barrio-Carreras D, Bergua Martínez A, Cañedo Villarroya E, García-Silva MT, et al. Recommendations for the diagnosis and therapeutic management of hyperammonaemia in paediatric and adult patients. Nutrients. 2022;14(13):2755. PMID: 35807935 https://doi.org/10.3390/nu14132755

19. Kamel AY, Emtiazjoo AM, Adkins L, Shahmohammadi A, Alnuaimat H, Pelaez A, et al. Hyperammonemia after lung transplantation: systematic review and a mini case series. Transpl Int. 2022;35:10433. PMID: 35620675 https://doi.org/10.3389/ti.2022.10433

20. Córdoba J, López-Hellín J, Planas M, Sabín P, Sanpedro F, Castro F, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38–43. PMID: 15246205 https://doi.org/10.1016/j.jhep.2004.03.023

21. Gheorghe L, Iacob R, Vădan R, Iacob S, Gheorghe C. Improvement of hepatic encephalopathy using a modified high-calorie high-protein diet. Rom J Gastroenterol. 2005;14(3):231–238. PMID: 16200232

22. Leger RF, Silverman MS, Hauck ES, Guvakova KD. Hyperammonemia post lung transplantation: a review. Clin Med Insights Circ Respir Pulm Med. 2020;14:1179548420966234. PMID: 33192115 https://doi.org/10.1177/1179548420966234

23. Prado FA, Delfino VD, Grion CM, de Oliveira JA. Hyperammonemia in ICU patients: a frequent finding associated with high mortality. J Hepatol. 2015;62(5):1216–1218. PMID: 25617506 https://doi.org/10.1016/j.jhep.2015.01.009

24. Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ. 2004;328(7447):1046. PMID: 15054035 https://doi.org/10.1136/bmj.38048.506134.EE

25. Chiu CG, Zaghiyan KN, Silberman AW. Hyperammonemic encephalopathy associated with GI stromal tumor. J Clin Oncol. 2016;34(7):e51–53. PMID: 24982462 https://doi.org/10.1200/JCO.2013.48.9302

26. Machado MC, Pinheiro da Silva F. Hyperammonemia due to urea cycle disorders: a potentially fatal condition in the intensive care setting. J Intensive care. 2014;2(1):22. PMID: 25908985 https://doi.org/10.1186/2052-0492-2-22

27. Trivedi M, Zafar S, Spalding MJ, Jonnalagadda S. Ornithine transcarbamylase deficiency unmasked because of gastrointestinal bleeding. J Clin Gastroenterol. 2001;32(4):340–343. PMID: 11276280 https://doi.org/10.1097/00004836-200104000-00013

28. Cunningham SA, Mandrekar JN, Rosenblatt JE, Patel R. Rapid PCR detection of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. Int J Bacteriol. 2013;168742. PMID: 26904723 https://doi.org/10.1155/2013/168742