Using steroids and cyclophosphamide together as a treatment for paraquat poisoning

Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.

Standard care for removing paraquat from the body involves vomiting, consuming activated charcoal or Fuller's Earth (which absorbs paraquat), and blood filtering. This review aims to assess the effects of giving patients steroids and cyclophosphamide in addition to standard care to prevent death after paraquat poisoning.

We found three small randomised controlled trials in which patients with moderate or severe poisoning were given either standard care only or standard care and steroids and cyclophosphamide. When the results of the three studies were combined, we found that patients who were given standard care and steroids and cyclophosphamide had a reduced risk of death of about 28% (statistically estimated likely range of reduced deaths from 41% to 11%) compared with patients given standard care alone. However, the studies were small and one was of low methodological quality so the benefit of this treatment should be interpreted with caution. To understand the effects of this treatment for poisoned patients better, we recommend it be given in the context of a randomised controlled trial so that future results can be analysed with similar studies.

Authors' conclusions: 

Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.

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Background: 

Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.

Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited.

The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied.

Objectives: 

To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis.

Search strategy: 

The most recent search was run on the 15th April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), trials registries, Chinese databases (数据库, 万方数据库, 维普数据库) and reference lists.

Selection criteria: 

RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care.

Data collection and analysis: 

The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model.

Main results: 

This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72; 95% CI 0.59 to 0.89).

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