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 d...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-06-01
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| Series: | Annals of Intensive Care |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13613-020-00693-5 |
| _version_ | 1818502734794457088 |
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| author | Sandrine Valade Eric Mariotte Elie Azoulay Michael Darmon |
| author_facet | Sandrine Valade Eric Mariotte Elie Azoulay Michael Darmon |
| author_sort | Sandrine Valade |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:14:24Z |
| format | Article |
| id | doaj.art-505bb0feee044250ab0cfa549b499f38 |
| institution | Directory Open Access Journal |
| issn | 2110-5820 |
| language | English |
| last_indexed | 2024-12-10T21:14:24Z |
| publishDate | 2020-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Annals of Intensive Care |
| spelling | doaj.art-505bb0feee044250ab0cfa549b499f382022-12-22T01:33:21ZengSpringerOpenAnnals of Intensive Care2110-58202020-06-011011510.1186/s13613-020-00693-5High-dose methotrexate in ICU patients: a retrospective studySandrine Valade0Eric Mariotte1Elie Azoulay2Michael Darmon3Medical ICU, APHP, Saint-Louis HospitalMedical ICU, APHP, Saint-Louis HospitalMedical ICU, APHP, Saint-Louis HospitalMedical ICU, APHP, Saint-Louis HospitalAbstract 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.http://link.springer.com/article/10.1186/s13613-020-00693-5MethotrexateAcute kidney injuryOutcomeHematological malignanciesDrug-related side effectsAntineoplastic agents |
| spellingShingle | Sandrine Valade Eric Mariotte Elie Azoulay Michael Darmon High-dose methotrexate in ICU patients: a retrospective study Annals of Intensive Care Methotrexate Acute kidney injury Outcome Hematological malignancies Drug-related side effects Antineoplastic agents |
| title | High-dose methotrexate in ICU patients: a retrospective study |
| title_full | High-dose methotrexate in ICU patients: a retrospective study |
| title_fullStr | High-dose methotrexate in ICU patients: a retrospective study |
| title_full_unstemmed | High-dose methotrexate in ICU patients: a retrospective study |
| title_short | High-dose methotrexate in ICU patients: a retrospective study |
| title_sort | high dose methotrexate in icu patients a retrospective study |
| topic | Methotrexate Acute kidney injury Outcome Hematological malignancies Drug-related side effects Antineoplastic agents |
| url | http://link.springer.com/article/10.1186/s13613-020-00693-5 |
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