High-dose methotrexate in ICU patients: a retrospective study

Area of Science:

• Oncology
• Critical Care Medicine
• Pharmacology

Background:

• High-dose methotrexate (HD-MTX) is a critical treatment for various cancers.
• Severe toxicities associated with HD-MTX can lead to organ dysfunction and mortality.
• The risk-benefit profile of HD-MTX in critically ill patients remains unclear.

Purpose of the Study:

• To characterize MTX-induced toxicities in intensive care unit (ICU) patients.
• To evaluate the outcomes of critically ill patients receiving HD-MTX.
• To identify factors associated with mortality in this patient cohort.

Main Methods:

• Retrospective single-center study of ICU patients treated with HD-MTX from 2002-2018.
• Inclusion of consecutive patients receiving HD-MTX.
• Analysis of patient demographics, diagnoses, MTX dosage, clearance, toxicities, ICU interventions, and mortality.

Main Results:

• 33 patients with lymphoma received HD-MTX at a median dose of 6.1g.
• Common toxicities included mucositis (64%), hepatic failure (45%), and acute kidney injury (33%).
• Hospital mortality was 30%, with MTX concentration >4.6 µmol/L at 24h post-administration significantly associated with mortality (HR 6.7).

Conclusions:

• This is the first study to assess the characteristics and outcomes of critically ill patients receiving HD-MTX.
• MTX concentration at 24 hours is a significant predictor of hospital mortality.
• Despite severe toxicities, ICU support can lead to meaningful survival in these patients.