Research Article: Improvement in Survival after Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka

Date Published: February 26, 2008

Publisher: Public Library of Science

Author(s): Martin F Wilks, Ravindra Fernando, P. L Ariyananda, Michael Eddleston, David J Berry, John A Tomenson, Nicholas A Buckley, Shaluka Jayamanne, David Gunnell, Andrew Dawson, Mervyn Singer

Abstract: BackgroundPesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following its introduction into Sri Lanka.Methods and FindingsClinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standard formulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%–17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the original formulation to 55% with INTEON, p < 0.001). Median survival time increased from 2.3 d (95% CI 1.2–3.4 d) with the standard formulation to 6.9 d (95% CI 3.3–10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5–3.4) to 1.5 d (IQR 0.5–5.5); p = 0.02.ConclusionsThe survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption.

Partial Text: Self-poisoning with pesticides is a major public health problem in many developing countries, accounting for up to one-third of all suicides worldwide according to recent estimates [1]. While organophosphorus insecticides are by far the leading cause of morbidity and mortality in these self-poisonings, other pesticides are important in specific regions and countries [2,3]. Paraquat (1,1′-dimethyl-4,4′-bipyridinium dichloride) is a nonselective contact herbicide that has been widely used in many countries since the 1960s. Following ingestion of large amounts of concentrated formulation, the rapid development of multi-organ failure and cardiogenic shock is almost universally fatal. When smaller amounts are ingested, paraquat is actively taken up into pulmonary epithelial cells where redox cycling and free radical generation trigger a fibrotic process that may lead to death [4–7].

Information was collected by the nine study hospitals on 774 patients over the study period. The numbers of participants eligible for the primary analysis and sensitivity analyses broken down by formulation are given in Table 2. The primary study population included 297 confirmed cases of standard formulation ingestion admitted before 1 October 2004 and 289 confirmed, probable and possible cases of INTEON ingestion. For sensitivity analyses all confirmed or probable cases were used (382 standard formulation and 206 INTEON cases).

In Sri Lanka, pesticides are the most common means of self poisoning, with case fatality ratios more than 10-fold higher than those from self-poisoning in industrialised countries [15]. Although not the most common cause of pesticide death, paraquat has a higher case fatality ratio than other commonly ingested pesticides [16]. We have shown in this study that the development of a new formulation that turns to a gel in the stomach, slowing absorption and increasing the time available for effective emesis, increases estimated 3-mo survival from 27.1% for patients ingesting the standard formulation to 36.7% with the INTEON product. In individual terms this equates to approximately 30 lives saved within the survey due to the introduction of INTEON.



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