- Darren M Roberts, MBBS, PhD, FRACP
Darren M Roberts, MBBS, PhD, FRACP
- Clinical Toxicologist, Royal Prince Alfred Hospital
- Nephrologist, Canberra Hospital
- Associate Professor, Australian National University
- Nicholas A Buckley, MD, FRACP
Nicholas A Buckley, MD, FRACP
- Professor of Clinical Pharmacology
- University of Sydney Medical School
- Clinical Toxicologist
- Royal Prince Alfred Hospital
- Section Editors
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Michele M Burns, MD, MPH
Michele M Burns, MD, MPH
- Section Editor — Pediatric Toxicology
- Assistant Professor of Pediatrics
- Harvard Medical School
Paraquat ingestion is a leading cause of fatal poisoning in many parts of Asia, Pacific nations, and the Americas . Paraquat is a rapidly-acting, nonselective herbicide that is relatively inexpensive. These characteristics contribute to its widespread use in much of the developing world.
Paraquat is reasonably safe to use in agriculture: dermal or spray exposure generally causes only limited, localized injury . However, accidental or deliberate ingestion has an extremely high case-fatality rate . Largely for this reason, paraquat has been restricted in many parts of the world. In the rural areas of countries where it remains readily available, it is a common method for intentional self-poisoning .
Diquat is a related herbicide that is often formulated with paraquat. There are relatively few reports of diquat poisoning, but it appears to involve mechanisms and manifest clinical features similar to those of paraquat . While evidence is limited, the treatment of diquat poisoning is generally the same as that for paraquat poisoning.
The presentation and management of paraquat poisoning will be reviewed here. General approaches to the assessment of the poisoned patient are discussed separately. (See "General approach to drug poisoning in adults" and "Initial management of the critically ill adult with an unknown overdose".)
PHARMACOLOGY AND CELLULAR TOXICOLOGY
Chemically, paraquat and diquat are classified as bipyridyl compounds. After absorption, paraquat is concentrated inside many cells where it undergoes redox cycling, a process involving repetitive enzyme-mediated cycling between paraquat and paraquat radicals. A by-product of this process is a superoxide radical, a highly reactive oxygen species, which can cause direct cellular damage or react further to form other reactive oxygen species and nitrite radicals . Redox cycling consumes NADPH, one of the cell’s key antioxidant defenses. The resultant oxidative stress created by the production of free radicals and the depletion of NADPH directly causes cell damage (via lipid peroxidation, mitochondrial dysfunction, necrosis and apoptosis) and triggers a pronounced secondary inflammatory response.
- Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health 2007; 7:357.
- Lock EA, Wilks MF. Paraquat. In: Handbook of Pesticide Toxicology, 3rd ed, Krieger RI (Ed), Academic Press, San Diego 2010.
- Senarathna L, Eddleston M, Wilks MF, et al. Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration. QJM 2009; 102:251.
- Jones GM, Vale JA. Mechanisms of toxicity, clinical features, and management of diquat poisoning: a review. J Toxicol Clin Toxicol 2000; 38:123.
- Suntres ZE. Role of antioxidants in paraquat toxicity. Toxicology 2002; 180:65.
- Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol 2011; 72:745.
- Houzé P, Baud FJ, Mouy R, et al. Toxicokinetics of paraquat in humans. Hum Exp Toxicol 1990; 9:5.
- Wunnapuk K, Mohammed F, Gawarammana I, et al. Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach. Br J Clin Pharmacol 2014; 78:855.
- Wilks MF, Tomenson JA, Fernando R, et al. Formulation changes and time trends in outcome following paraquat ingestion in Sri Lanka. Clin Toxicol (Phila) 2011; 49:21.
- Kim JH, Gil HW, Yang JO, et al. Serum uric acid level as a marker for mortality and acute kidney injury in patients with acute paraquat intoxication. Nephrol Dial Transplant 2011; 26:1846.
- Gawarammana IB, Dawson AH. Peripheral burning sensation: a novel clinical marker of poor prognosis and higher plasma-paraquat concentrations in paraquat poisoning. Clin Toxicol (Phila) 2010; 48:347.
- Zhou CY, Kang X, Li CB, et al. Pneumomediastinum predicts early mortality in acute paraquat poisoning. Clin Toxicol (Phila) 2015; 53:551.
- Ragoucy-Sengler C, Pileire B. A biological index to predict patient outcome in paraquat poisoning. Hum Exp Toxicol 1996; 15:265.
- Roberts DM, Wilks MF, Roberts MS, et al. Changes in the concentrations of creatinine, cystatin C and NGAL in patients with acute paraquat self-poisoning. Toxicol Lett 2011; 202:69.
- Mohamed F, Endre Z, Jayamanne S, et al. Mechanisms underlying early rapid increases in creatinine in paraquat poisoning. PLoS One 2015; 10:e0122357.
- Mohamed F, Buckley NA, Jayamanne S, et al. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion. Toxicol Lett 2015; 237:140.
- Kim SJ, Gil HW, Yang JO, et al. The clinical features of acute kidney injury in patients with acute paraquat intoxication. Nephrol Dial Transplant 2009; 24:1226.
- Suzuki K, Takasu N, Arita S, et al. A new method for predicting the outcome and survival period in paraquat poisoning. Hum Toxicol 1989; 8:33.
- Lee Y, Lee JH, Seong AJ, et al. Arterial lactate as a predictor of mortality in emergency department patients with paraquat intoxication. Clin Toxicol (Phila) 2012; 50:52.
- Jiang Z, Xu SY, Cao Y, et al. [Prognostic significance of serum lactic acid in evaluation of acute paraquat poisoning patients]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2013; 25:519.
- Scherrmann JM, Houze P, Bismuth C, Bourdon R. Prognostic value of plasma and urine paraquat concentration. Hum Toxicol 1987; 6:91.
- Berry DJ, Grove J. The determination of paraquat (I,I'-dimethyl-4,4'-bipyridylium cation) in urine. Clin Chim Acta 1971; 34:5.
- Koo JR, Yoon JW, Han SJ, et al. Rapid analysis of plasma paraquat using sodium dithionite as a predictor of outcome in acute paraquat poisoning. Am J Med Sci 2009; 338:373.
- Vohra R, Salazar A, Cantrell FL, et al. The poison pen: bedside diagnosis of urinary diquat. J Med Toxicol 2010; 6:35.
- Sawada Y, Yamamoto I, Hirokane T, et al. Severity index of paraquat poisoning. Lancet 1988; 1:1333.
- Kuan CM, Lin ST, Yen TH, et al. Paper-based diagnostic devices for clinical paraquat poisoning diagnosis. Biomicrofluidics 2016; 10:034118.
- Bradberry SM, Proudfoot AT, Vale JA. Glyphosate poisoning. Toxicol Rev 2004; 23:159.
- Bradberry SM, Watt BE, Proudfoot AT, Vale JA. Mechanisms of toxicity, clinical features, and management of acute chlorophenoxy herbicide poisoning: a review. J Toxicol Clin Toxicol 2000; 38:111.
- Twinem G, Monaghan D, McGovern S. Respiratory distress, pneumonic changes on chest X-ray, hypoxaemia, oral candidiasis in a homosexual male: not always Pneumocystis carinii pneumonia. Eur J Emerg Med 2006; 13:175.
- Pond SM, Rivory LP, Hampson EC, Roberts MS. Kinetics of toxic doses of paraquat and the effects of hemoperfusion in the dog. J Toxicol Clin Toxicol 1993; 31:229.
- Hong SY, Yang JO, Lee EY, Kim SH. Effect of haemoperfusion on plasma paraquat concentration in vitro and in vivo. Toxicol Ind Health 2003; 19:17.
- Gosselin S. “Paraquat”. In: AACT SYMPOSIUM: EXTRACORPOREAL THERAPIES IN ACUTE POISONING. Proceedings of the 11th Scientific Congress of the Asia-Pacific Association of Medical Toxicology, Hong Kong, November 2012.
- Wu WP, Lai MN, Lin CH, et al. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study. PLoS One 2014; 9:e87568.
- Li A, Li W, Hao F, Wang H. Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study. Blood Purif 2016; 42:93.
- Gawarammana I, Buckley NA, Mohammed F, et al. A randomised controlled trial of high-dose immunosuppression in paraquat poisoning. Clin Toxicol 2012; 50:278.
- Li LR, Sydenham E, Chaudhary B, et al. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database Syst Rev 2014; :CD008084.
- Deng J, Huo D, Wu Q, et al. Xuebijing for paraquat poisoning. Cochrane Database Syst Rev 2013; :CD010109.
- Dinis-Oliveira RJ, Sousa C, Remião F, et al. Full survival of paraquat-exposed rats after treatment with sodium salicylate. Free Radic Biol Med 2007; 42:1017.
- Dinis-Oliveira RJ, Sousa C, Remião F, et al. Sodium salicylate prevents paraquat-induced apoptosis in the rat lung. Free Radic Biol Med 2007; 43:48.
- Bismuth C, Garnier R, Baud FJ, et al. Paraquat poisoning. An overview of the current status. Drug Saf 1990; 5:243.
- Duan Y, Wang Z. To explore the characteristics of fatality in children poisoned by paraquat--with analysis of 146 cases. Int J Artif Organs 2016; 39:51.
- PHARMACOLOGY AND CELLULAR TOXICOLOGY
- CLINICAL FEATURES OF POISONING
- Physical examination and basic monitoring
- LABORATORY EVALUATION AND DIAGNOSTIC IMAGING
- General testing
- Specific testing for paraquat exposure
- DIFFERENTIAL DIAGNOSIS
- Initial resuscitation
- Gastrointestinal decontamination
- Topical and inhalation exposure
- Specific treatments and antidotal therapy
- - Indications for extracorporeal therapies
- - Antiinflammatory and immunosuppressive therapy
- - Antioxidant therapy
- Ongoing management
- Medical management versus palliative care
- PEDIATRIC CONSIDERATIONS
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS