Dataset Information

High-dose methotrexate in ICU patients: a retrospective study.

ABSTRACT:

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.

SUBMITTER: Valade S

PROVIDER: S-EPMC7293713 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

High-dose methotrexate in ICU patients: a retrospective study.

Valade Sandrine S Mariotte Eric E Azoulay Elie E Darmon Michael M

Annals of intensive care 20200613 1

<h4>Background</h4>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. Con ...[more]

PMID: 32535662

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Project description:Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction, but the guidelines for when to use it are unclear. An expert panel was convened to provide specific, expert consensus guidelines for the use of glucarpidase in patients who develop HDMTX-induced nephrotoxicity and delayed methotrexate excretion. The guideline provides recommendations to identify the population of patients who would benefit from glucarpidase rescue by more precisely defining the absolute methotrexate concentrations associated with risk for severe or life-threatening toxicity at several time points after the start of an HDMTX infusion. For an HDMTX infusion ≤24 hours, if the 36-hour concentration is above 30 µM, 42-hour concentration is above 10 µM, or 48-hour concentration is above 5 µM and the serum creatinine is significantly elevated relative to the baseline measurement (indicative of HDMTX-induced acute kidney injury), glucarpidase may be indicated. After a 36- to 42-hour HDMTX infusion, glucarpidase may be indicated when the 48-hour methotrexate concentration is above 5 µM. Administration of glucarpidase should optimally occur within 48-60 hours from the start of the HDMTX infusion, because life-threatening toxicities may not be preventable beyond this time point.Implications for practiceGlucarpidase is a rarely used medication that is less effective when given after more than 60 hours of exposure to high-dose methotrexate, so predicting early which patients will need it is imperative. There are no currently available consensus guidelines for the use of this medication. The indication on the label does not give specific methotrexate concentrations above which it should be used. An international group of experts was convened to develop a consensus guideline that was specific and evidence-based to identify the population of patients who would benefit from glucarpidase.

Dataset Information

High-dose methotrexate in ICU patients: a retrospective study.

Background

Results

Conclusions

Publications

High-dose methotrexate in ICU patients: a retrospective study.

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