Hyperammonemia syndrome in immunosuppressed individuals

Abstract

Purpose of reviewHyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients. Growing evidence suggests hyperammonemia syndrome is associated with systemic infections caused by urease-producing organisms, namely Ureaplasma spp., an organism unable to grow with routine culturing techniques. This review will summarize the epidemiology and clinical manifestations of hyperammonemia syndrome, as well as diagnostic and management strategies once hyperammonemia syndrome is suspected.Recent findingsHyperammonemia syndrome is being described in increasing frequency in the solid organ transplant population. Morbidity and mortality, even with treatment, is high once hyperammonemia syndrome occurs. Surveillance studies indicate the prevalence of lung donor colonization with Ureaplasma spp. is high, suggesting screening and treatment may be of benefit. Antibiotic resistance is common, and rapid diagnostics can facilitate appropriate antimicrobial therapy in the peri-transplant period.SummaryHyperammonemia syndrome is most commonly seen in lung transplant recipients and has a high mortality rate once it occurs. Screening for Ureaplasma spp. should be considered in all lung transplant donors.

Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report

“…The urease in Ureaplasma parvum can convert urea into ammonia and carbon dioxide. Clinical studies have shown the relationship between Ureaplasma infection and hyperammonemia [6,7]. Most cases of Ureplasma-linked hyperammonemia and Ureaplasma septic arthritis were reported in patients with immunocompromised status, such as iatrogenic immunosuppression after organ transplantation or hypogammaglobulinemia from B-cell deficiency [8,9].…”

Routine Donor and Recipient Screening for Mycoplasma hominis and Ureaplasma Species in Lung Transplant Recipients

“…It is possible that some of these patients developed AMS from an alternative etiology; however, the 3 cases associated with Mollicute infection had peak ammonia levels of 114, 275, and 1242 μmoL/L, suggesting true HS. Some authors have used a cutoff of 200 μmoL/L; however, cases with peak ammonia levels in the 50s have been attributed to HS in the literature [ 4 , 9 ]. There was also no association between HS and Mollicute infection, but this did not prevent inappropriate antibiotic therapy for patients with HS.…”

“…Post-transplant infections with M. hominis more typically present as mediastinitis, surgical site infection, or pleuritis [ 6 , 7 ]. As not all empiric post-transplant antibiotics cover Mollicutes, the reported mortality of HS in lung transplant recipients has been as high as 67% [ 8 , 9 ]. Both U. parvum and U. urealyticum alongside M. hominis have been shown to be donor-transmitted and can be part of normal genitourinary microbiota [ 10 ].…”

Hyperammonemia in lung transplantation: recognizing the gaps of our knowledge

“…A recent review proposed a definition of new neurologic symptoms within 45 days of transplantation and a serum ammonia level of greater than 200 µmol/L on at least one occasion, a metric supported by several groups as this is the level of ammonemia where cerebral edema is thought to occur. 6,7 However, ammonia levels can fluctuate widely depending upon clinical factors and adjunctive treatments, such as renal replacement therapy, laxative use, and diet. Cases consistent with HS have also been suspected with lower ammonia levels, including two cases in the current case series where ammonia levels remained below 100 µmol/L, although early identification and treatment may have mitigated progressive hyperammonemia, and reducing this cut-off will further limit specificity.…”

“…Defining HS is an additional challenge. A recent review proposed a definition of new neurologic symptoms within 45 days of transplantation and a serum ammonia level of greater than 200 μmol/L on at least one occasion, a metric supported by several groups as this is the level of ammonemia where cerebral edema is thought to occur 6,7 . However, ammonia levels can fluctuate widely depending upon clinical factors and adjunctive treatments, such as renal replacement therapy, laxative use, and diet.…”