Alexandre Brasseur Lina Khattar Benjamin Bailly Jean-Louis Vincent Fabio Silvio Taccone An unusual cause of hyperammonemia in a critically ill patient Accepted: 2 October 2012 Published online: 25 October 2012 Ó Springer-Verlag Berlin Heidelberg and ESICM 2012 Dear Editor, We report an unusual cause of hyperammonemia in a critically ill patient undergoing chemotherapy. A 62-year-old woman was admitted to our Intensive Care Unit (ICU) for respiratory failure and septic shock. She was diagnosed as having a disseminated T cell lymphoma com- plicating a chronic infection with Epstein-Barr virus. On admission, she was treated with mechanical ventila- tion and norepinephrine; bronchoalveolar lavage yielded wild- type Klebsiella pneumoniae for which piperacillin/tazobactam was admin- istered intravenously. Her clinical condition improved rapidly, but the total body computed tomography (CT) scan showed disseminated lymphomatous lesions in the lungs and the liver. Chemotherapy, con- sisting of cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone, was started on day 7 after admission. Bilirubin levels at this time were greater than 8 mg/dl, and blood ammonia (NH 4 ) levels were 80 lg/dl (Fig. 1). Unfortu- nately, there was no response to the initial chemotherapy, so a second- line chemotherapy was initiated consisting of prednisolone, metho- trexate, ifosfamide, etoposide and L-asparaginase. After the first admin- istration of L-asparaginase, NH 4 levels increased to 399 lg/dl, with no other alteration in liver function tests and no neurological signs or symp- toms. Oral lactulose (30 g q8h) was started. NH 4 levels increased again with the two subsequent L-asparagi- nase injections (Fig. 1). On day 26 (at the time of the last drug injection), serial NH 4 levels were 233 lg/dl before drug injection, 262 lg/dl at 1 h, 249 lg/dl at 4 h and 521 lg/dl at 8 h after asparaginase; levels pro- gressively decreased to 381 lg/dl the day after the injection and to less than 100 lg/dl 48 h thereafter. No specific neurological deterioration was observed at any time. Hyperammonemia can occur in critically ill patients, especially in those suffering from decompensated liver cirrhosis, acute liver failure or receiving certain drugs, such as val- proic acid [1]. If untreated, elevated NH 4 levels may progressively cause brain edema and subsequent hernia- tion. L-Asparaginase hydrolyzes the amino acid, asparagine, thus depriv- ing cancer cells of an essential compound for growth but also pro- ducing ammonia [2]. This patient had hepatic involvement from T cell lymphoma and had a mild, asymptomatic increase in NH 4 levels during the first day after ICU admis- sion. Her underlying septic shock may have been a predisposing factor for the development of severe hyper- ammonemia during L-asparaginase therapy. Several case reports have described the development of hyper- ammonemia during L-asparaginase therapy, notably in children or young patients undergoing chemotherapy for hematological diseases [2–4]. Our patient had no neurological abnor- malities, whereas in previous reports, most of the patients had a poor out- come with clinical signs of brain edema. We observed that the peak in NH 4 concentrations was observed a few hours after drug injection, and levels returned to baseline within 48 h without further therapy. In one report, clinical signs of brain edema appeared less than 2 h after drug administration, and the condition progressively deteriorated over subsequent days, necessitating administration of sodium benzoate [4]. Although hyperammonemia is a rare complication of chemotherapy, it is likely to be seen more frequently as the numbers of patients suffering from cancer and receiving chemo- therapy who are admitted to the ICU Fig. 1 Evolution of ammonium levels over time from ICU admission. Arrows indicate L- asparaginase injections Intensive Care Med (2013) 39:336–337 DOI 10.1007/s00134-012-2736-4 CORRESPONDENCE