Indika Gawarammana1,2, Nicholas A Buckley2,3,4, Fahim Mohamed2,3, Kamal Naser5, K Jeganathan6,7, P L Ariyananada8, Klintean Wunnapuk9,10, Timothy A Dobbins3,11, John A Tomenson12, Martin F Wilks13, Michael Eddleston2,14, Andrew H Dawson2,3,4. 1. a Department of Medicine, Faculty of Medicine , University of Peradeniya , Peradeniya , Sri Lanka. 2. b South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine , University of Peradeniya , Peradeniya , Sri Lanka. 3. c Department of Pharmacology , University of Sydney , Sydney , Australia. 4. d Royal Prince Alfred Hospital , Sydney , Australia. 5. e Peradeniya Hospitals , Peradeniya , Sri Lanka. 6. f Anuradhapura Hospitals , Anuradhapura , Sri Lanka. 7. g Rathnapura Hospitals , Rathnapura , Sri Lanka. 8. h Faculty of Medicine , University of Ruhuna , Galle , Sri Lanka. 9. i Therapeutics Research Centre, School of Medicine , University of Queensland , Brisbane , Australia. 10. j Department of Forensic Medicine, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand. 11. k National Drug and Alcohol Research Centre , Sydney , Australia. 12. l Causation Limited , Macclesfield , UK. 13. m Swiss Centre for Applied Human Toxicology , University of Basel , Basel , Switzerland. 14. n Department of Pharmacology, Toxicology and Therapeutics , University/BHF Centre for Cardiovascular Science, University of Edinburgh and National Poisons Information Service - Edinburgh Unit, Royal Infirmary of Edinburgh , Edinburgh , UK.
Abstract
CONTEXT: Intentional self-poisoning with the herbicide paraquat has a very high case-fatality and is a major problem in rural Asia and Pacific. OBJECTIVES: We aimed to determine whether the addition of immunosuppression to supportive care offers benefit in resource poor Asian district hospitals. MATERIALS AND METHODS: We performed a randomised placebo-controlled trial comparing immunosuppression (intravenous cyclophosphamide up to 1 g/day for two days and methylprednisolone 1 g/day for three days, and then oral dexamethasone 8 mg three-times-a-day for 14 days) with saline and placebo tablets, in addition to standard care, in patients with acute paraquat self-poisoning admitted to six Sri Lankan hospitals between 1st March 2007 and 15th November 2010. The primary outcome was in-hospital mortality. RESULTS:299 patients were randomised to receive immunosuppression (147) or saline/placebo (152). There was no significant difference in in-hospital mortality rates between the groups (immunosuppression 78 [53%] vs. placebo 94 [62%] (Chi squared test 2.4, p = .12). There was no difference in mortality at three months between the immunosuppression (101/147 [69%]) and placebo groups (108/152 [71%]); (mortality reduction 2%, 95% CI: -8 to +12%). A Cox model did not support benefit from high-dose immunosuppression but suggested potential benefit from the subsequent two weeks of dexamethasone. CONCLUSIONS: We found no evidence that high dose immunosuppression improves survival in paraquat-poisoned patients. The continuing high mortality means further research on the use of dexamethasone and other potential treatments is urgently needed.
RCT Entities:
CONTEXT: Intentional self-poisoning with the herbicide paraquat has a very high case-fatality and is a major problem in rural Asia and Pacific. OBJECTIVES: We aimed to determine whether the addition of immunosuppression to supportive care offers benefit in resource poor Asian district hospitals. MATERIALS AND METHODS: We performed a randomised placebo-controlled trial comparing immunosuppression (intravenous cyclophosphamide up to 1 g/day for two days and methylprednisolone 1 g/day for three days, and then oral dexamethasone 8 mg three-times-a-day for 14 days) with saline and placebo tablets, in addition to standard care, in patients with acute paraquat self-poisoning admitted to six Sri Lankan hospitals between 1st March 2007 and 15th November 2010. The primary outcome was in-hospital mortality. RESULTS: 299 patients were randomised to receive immunosuppression (147) or saline/placebo (152). There was no significant difference in in-hospital mortality rates between the groups (immunosuppression 78 [53%] vs. placebo 94 [62%] (Chi squared test 2.4, p = .12). There was no difference in mortality at three months between the immunosuppression (101/147 [69%]) and placebo groups (108/152 [71%]); (mortality reduction 2%, 95% CI: -8 to +12%). A Cox model did not support benefit from high-dose immunosuppression but suggested potential benefit from the subsequent two weeks of dexamethasone. CONCLUSIONS: We found no evidence that high dose immunosuppression improves survival in paraquat-poisoned patients. The continuing high mortality means further research on the use of dexamethasone and other potential treatments is urgently needed.