BACKGROUND: Hyperammonemia syndrome (HS) is a rare but potentially fatal complication of Lung Transplantation (LT). Optimal screening methods are unknown: Here we investigated serum ammonia screening (SAS) for HS and compared it with PCR for Mollicutes (ureaplasma-producing bacteria). METHODS: All LT recipients from 07/2019-02/2020 and 10/2021-11/2022 with available donor bronchial wash samples from the LT biobank were included. Mollicute-PCR was performed using two commercially available kits. Daily ammonia serum levels were measured for the first 14 days. Recipients were prospectively followed for HS for 30 days post-LT. HS was defined by new neurological symptoms and the presence of elevated serum ammonium (>
1x >
70 µmol/l). RESULTS: Of 241 LT recipients, 5 (2%) developed HS within the first month post-LT. Median time to HS was 8 days (IQR 5-10). All HS were diagnosed within the first 14 days post-LT, while daily SAS was in place.Ammonia was confirmed elevated (>
1x >
70µmol/l) in 4% (9/241) during follow-up however, outside of HS, 4 were found to be liver disease-related. Donor Mollicute-PCR was positive in 8% (19/241), recipient M-PCR in 1% (1/72) at transplant. Donor Mollicute-PCR, in contrast to recipient Mollicute-PCR, was associated with HS but only in 2 of the 5 HS cases. No HS patient died within 90 days post-LT. CONCLUSION: HS was a rare complication in our LT cohort. Daily post-LT SAS might add to early HS diagnosis and treatment and is potentially associated with improved outcome. Donor screening with Mollicute-PCR has limited predictive value for HS post-LT.