High-dose methotrexate in ICU patients: a retrospective study

Background

High-dose methotrexate (HD-MTX) is commonly used in the treatment of solid tumors and hematological malignancies. Severe toxicities are frequent, leading to organ dysfunction and death. Risk–benefit ratio of using HD-MTX in critically ill patients is unknown. This study aims to describe MTX-induced toxicities and to assess outcome in ICU patients. We conducted a retrospective single-center study conducted in a university hospital ICU between January 2002 and December 2018. Consecutive patients treated by HD-MTX were included

Results

33 patients (24 men and 9 women) aged 48 years [34–63], were included. B cell lymphoma had been diagnosed in 31 patients (Burkitt, n  = 14; diffuse large B-cell lymphoma with CNS (central nervous system) involvement, n  = 9; primary CNS lymphoma, n  = 5) and T-cell lymphoma in two patients. Patients were mainly admitted for coma ( n  = 14; 42%) or acute kidney injury ( n  = 8; 24%). MTX was administered at a median dose of 6.1 g [5–14]. Fourteen patients had concomitant medication interacting with MTX. Median MTX clearance was 4 days [4–5]. Frequent MTX-related complication were mucositis ( n  = 21, 64%), diarrhea ( n  = 14, 44%) or hepatic failure ( n  = 15, 45%). During ICU stay, 11 patients experienced acute kidney injury (KDIGO stage 3 [2–3]). Two patients received carboxypeptidase and three underwent dialysis. Overall, 19 patients (57%) required mechanical ventilation, 10 (30%) vasopressors. Hospital mortality was 30% ( n  = 10). Cox model identified MTX concentration 24 h after administration higher than 4.6 µmol/L as associated with hospital mortality (HR 6.7; 95% CI 1.6–27.3)

Conclusions

To our knowledge, this is the first study assessing characteristics and outcome of critically ill patients receiving HD-MTX. MTX concentration at H24 was associated with hospital mortality. Despite underlying malignancy, ICU support of these patients was associated with a meaningful survival.