Paraquat Poisoning in a Female in the Fourth Decade of Life

ABSTRACT


INTRODUCTION
Paraquat is a bipyridyl herbicide that acts by contact, it is presented in liquid form in concentrations of 20% for agricultural use. Its chemical name is 1-1'-dimethyl-4-4-4bipyridyl 1-2 . It is frequently used in agricultural areas. It has been available to farmers for more than 40 years and is the second most sold agrochemical in the world. Paraquat's herbicidal properties were discovered in 1955 and the active ingredient was introduced on world markets in 1962 under the brand name GRAMOXONE®, available as a 20 or 40% aqueous solution 2,3,4 The lungs are the first target of paraquat, and pulmonary effects represent the most lethal and least treatable manifestation of toxicity. However, inhalation toxicity is rare. The primary mechanism is the generation of free radicals that oxidize lung tissue .5-6 Although acute pulmonary edema and lung damage can occur within hours after severe acute exposures 7,8 the delayed toxic injury of pulmonary fibrosis, the usual cause of death, most commonly occurs 7 to 14 days after ingestion. 9 In some patients who ingested a large amount of concentrated form (20%), they died more rapidly due to circulatory failure (within 48 hours). Both type I and II pneumatocytes appear to selectively accumulate paraquat. Biotransformation of paraquat in these cells generates free radicals, resulting in lipid peroxidation and cell damage. Hemorrhage, edema fluids and leukocytes infiltrate the alveolar spaces, after which fibroblast proliferation immediately appears. There is a progressive decrease in arterial oxygen tension and CO2 diffusion capacity. Such a deterioration in gas exchange causes the progressive proliferation of fibrous connective tissue in the alveoli causing finally death by asphyxia and tissue anoxia. 10

CLINICAL CASE
Female patient in her fourth decade of life began her current illness on March 28th during the afternoon with conscious consumption of paraquat herbicide of approximately 300 ml, immediately presented nausea and abdominal pain, 4 hours later she presented vomiting on 10 occasions of gastrointestinal content and 10 liquid evacuations, Afterwards, he consumed a medicinal herb known as (crucetillo) as an antidote, asthenia, adynamia and sialorrhea were added to the clinical picture, as he did not show improvement he went to the emergency area of the hospital 8 hours after ingestion, on admission treatment was started with analgesic, fluid therapy and proton pump inhibitor, a referral to the intensive care unit was requested, which referred the patient to the gastroenterology department, which evaluated the patient and mentioned that he would not benefit from Corresponding Author: Mayra Evelyn Quiñones Martinez endoscopy due to the time of evolution and risk of perforation, During her stay on the internal medicine floor we were able to see elevation of liver enzymes in the first two days, acute renal injury after ingestion, she was kept hydrated, because she did not have a window period for the use of activated carbon, she was treated conservatively. At 48 hours of laboratory evolution we observed an increase in hepatic transaminases, acute kidney injury grade 3, since there is an increase of more than three times the baseline value, clinically the patient already had icteric coloration in skin and integuments, as well as pain at the level of the hepatic border at mid and deep palpation, the patient had hydration and use of steroid via vein.
At 96 hours post-exposure is when we found the maximum point of elevation of hepatic transaminases, with persistence of acute renal injury, at this time the patient begins with febrile peaks >39c, reaching convulsions on 2 occasions. After 144 hours post ingestion of paracuat, a decrease in hepatic transaminase levels and improvement in the azotemia were observed, but clinically the patient continued to be clinically unstable, with persistent fever, requiring the use of supplemental oxygen.
On the 8th day of intrahospital stay, a central blood culture was performed where they found the presence of Staphylococcus haemolyticus, sensitive to tetracyclines, the patient was in very good health, although laboratorially there was a significant decrease in hepatic transaminations and renal function, due to the high morbidity that this type of intoxication has, taking into account the amount that the patient took, she died on the 10th day of intrahospital stay . A B Figure 1

DISCUSSION
Paraquat dichloride is an effective and widely used herbicide that has a proven safety record when properly applied to kill weeds. However in recent decades numerous deaths have occurred mainly through accidental or voluntary ingestion 10 In the context of paracuat poisoning, most cases are suicidal ingestion, some accidental, which have been seen in children or adults in a state of inebriation, but homicidal etiology is always important to rule out 11 .
The WHO recommended classification of pesticides by hazard was approved by the 28th World Health Assembly in 1975 and has since gained wide acceptance. The original guidelines approved by the World Health Assembly in 1975 were followed unchanged until 2009, when the World Health Organization classified Paraquat as a "Moderately hazardous technical grade active ingredient (Class II) in pesticides" 12. Just one teaspoon of concentrated Paraquat can cause death in an adult human being, since the estimated minimum lethal Corresponding Author: Mayra Evelyn Quiñones Martinez dose is about 30mg/kg or 3-6g of Paraquat ion, which is equivalent to 10-20ml of 20% solution 13 . Medical experience has elaborated an approximate doseeffect ratio scale by which the prognosis of cases of paraquat ingestion can be made: -Less than 20 mg of ionic paraquat per kg body weight (less than 7.5 ml of 20% w/v paraquat concentrate). No symptoms or only gastrointestinal symptoms are present. Recovery is likely.
-20 to 40 mg ionic paraquat per kilogram body weight (7.5 to 15.0 ml 20% [w/v] paraquat concentrate).lung fibroplasia appears. In most cases death ensues, which may be delayed for 2 to 3 weeks.
-More than 40 mg of ionic paraquat per kilogram body weight (more than 15.0 ml at 20% [w/v] paraquat concentrate). Multiple organ damage occurs as in class II, but progresses more rapidly. It is often characterized by marked ulceration in the oropharynx. Mortality is generally 100%, within 1 to 7 days 14 . Most Paraquat poisonings result from ingestion. Paraquat is known to be absorbed very rapidly, apparently associated with the transporter-mediated choline transport system in the brush border membrane, although this absorption from the gastrointestinal tract is low. Absorption occurs mainly in the small intestine (little of the stomach) and is estimated to be 1 to 5% in humans over a period of 1 to 6 hours. Any recent ingestion of food may decrease the amount of systemic absorption. Although the maximum plasma time is not known with certainty in humans, paraquat can be detected in urine as soon as 1 h after ingestion10. Paraquat is rapidly but incompletely absorbed and then eliminated largely unchanged in the urine within 12 to 24 hours. Paraquat-induced toxicity and its clinical characteristics are due to its ability to undergo redox cycling and subsequent generation of intracellular reactive oxygen species that cause cellular damage through lipid peroxidation, nuclear factor kappa B activation, mitochondrial damage and apoptosis, since the generation of highly reactive oxygen species and nitrite produces toxicity in most organs, but toxicity is particularly severe in the lungs, as paraquat is absorbed against a concentration gradient in the lung leading to pneumonitis and pulmonary fibrosis. Paraquat also damages the heart, kidneys, liver, adrenal glands, central nervous system, muscles and spleen, leading to multi-organ failure 13,14. Despite the proposed treatment variation, the reported lethality is very high in all centers, and mortality varies between 50% and 90%, but in cases of intentional autointoxication with concentrated formulations, mortality approaches 100% 14 .