Paraquat Poisoning: A Retrospective Study of 55 Patients From a Tertiary Care Center in Southern India

INTRODUCTION

Paraquat is a commonly used herbicide in India.¹ Suicides due to paraquat (PQ) are an important cause of morbidity and mortality, especially due to the absence of specific antidote. Metabolism of PQ generates free radicals that damage the cellular organelles and membranes, causing damage to many organs, especially the pulmonary alveolar epithelium.²

Consumption of PQ > 40 mg/kg causes acute multiorgan failure with death within the first 2 days, while %3C; 20 mg/kg of PQ causes mild symptoms and most survive.³

Paraquat of 20–40 mg/kg causes severe mucosal damage followed by multiorgan failure. The few, who survive, die within 2–4 weeks due to lung fibrosis. The pulmonary alveolar cells selectively accumulate polyamines that are required for cellular functions. Being structurally similar to polyamines, PQ gets accumulated in these cells, causing selective delayed lung injury.⁴

Although there is no specific antidote, most patients receive steroids/cyclophosphamide/antioxidants to reduce free radical damage.

Although PQ is commonly used in India, except for one large study,⁵ data on PQ poisoning are restricted to case reports and small case series. Hence, this study was undertaken to know the clinical features and outcome following PQ poisoning. We also briefly report the relevant Indian data on PQ poisoning.

MATERIALS AND METHODS

This was a retrospective study of case records of patients with PQ poisoning admitted to medicine wards over a period of 5 years (January 2014 to December 2018).

All consecutive patients of age more than 12 years were included in this study. Diagnosis was based on history of PQ intake and/or identifying the container with PQ. Those with prior renal/hepatic or lung diseases were not excluded.

Institute Scientific Committee and Ethics Committee approvals were obtained.

A pro forma was used to collect data regarding the demographics, symptoms, complications, outcomes, treatment with immunosuppression, laboratory, and radiological findings. Amount of PQ ingested was classified as mild (<10 mL), moderate (10–20 mL), and severe (%3E;20 mL).⁴

Lung involvement was diagnosed based on hypoxemia and infiltrates on chest X-ray. Kidney injury was diagnosed by raising creatinine/oliguria/need for dialysis. The use of steroids and cyclophosphamide was decided on case-to-case basis by the treating units, and no specific protocol was used for the same.

Mortality included patients who were taken against medical advice, when they deteriorated due to refractory hypotension/multiorgan failure. Postmortem records were analyzed to know the organs involved and their histological features.

RESULTS

A total of 55 patients were included in this study (Table 1).

Most of them were males (65.4%) and the median age was 28 years. Many patients (54.5%) presented by 6–12 hours after ingestion of PQ and 54.5% had consumed moderate amount of PQ. Hypotension was documented in 32.7%. Lung injury was documented in 61.8% and 18.1% needed mechanical ventilation. Of the 35 who had undergone chest X-ray, 10 had lung infiltrates. Computed tomography chest was done for two patients, which was normal. Paraquat tongue was documented in six patients.

Acute kidney injury was documented in 81.8%, and 56.3% had undergone dialysis.

Details of liver function tests were available for 45 patients, of whom 33.3% had bilirubin > 2 mg/dL. Elevation of (more than two times the upper normal limit) aspartate (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) was reported in 46.4%, 46.4%, and 24.4%, respectively. Acute hepatic failure was not noted in anyone.

Thirty-nine patients (70.9%) had received steroids (pulse methyl prednisolone: 29, hydrocortisone: 6, prednisolone: 3, and dexamethasone: 1) and cyclophosphamide (750 mg intravenously for 1–2 days, along with steroids) in 30.9%. The use of steroids and cyclophosphamide did not lead to a decrease in mortality rate (suppl. Tables S1 and S2).

Outcome: During hospitalization, 35 died and 5 were discharged against medical advice (mortality rate of 72.7%). All patients died within 3 days of PQ consumption. Most common cause of death was acute lung and kidney injury. Those who were discharged were later contacted by phone. Increased quantity of PQ consumed had higher mortality, while the time of presentation did not affect the mortality rate (suppl. Table S3 and S4). Presence of lung injury had higher mortality rate, while kidney injury did not have any correlation with mortality rate (suppl. Tables S5 and S6).

Of the 15 survivors, 7 could not be contacted, 5 were alive, and 3 died later elsewhere (within 2 months, likely due to delayed pulmonary fibrosis).

Autopsy was done on 30 patients (Table 2). Lungs, liver, and kidneys were sent for histopathological analysis. Lung was involved in all cases, with pulmonary edema and hemorrhage being the most common findings. Chronic venous congestion of the liver and renal acute tubular necrosis were the other important findings (Fig. 1). No characteristic histological findings were observed that suggested PQ poisoning.

DISCUSSION

In this retrospective study of 55 patients, most were males in the age-group of 20–40 years. Acute lung and renal involvement led to high mortality rate of 72.5%, with at least three more dying after discharge due to delayed lung fibrosis. The use of immunosuppression did not affect the outcome.

We tried to compare our data with other studies from India. Except for one study by Rao et al.,⁵ most of the reported data are limited to small series of less than 10 patients or case reports (Table 3). Of the 101 patients studied by Rao et al., the mortality rate was 61.4% which is less than that in our study. This may be because patients who left against medical advice were excluded. Also, delayed mortality due to lung fibrosis has not been reported in any of the Indian studies, while 3 of the 15 of our patients died due to lung fibrosis. This suggests that the so-called survivors should be kept on close follow-up and the overall mortality rates could be higher than reported.

LIMITATIONS

Since this is a retrospective study, laboratory data were not available for some patients. Biochemical confirmation at bedside was not done. This study was not powered to assess the efficacy of cyclophosphamide in PQ poisoning. Follow-up data were missing for seven patients.

CONCLUSION

Our study showed a very high in-hospital mortality rate of 72.7%. The amount of PQ consumed and the presence of lung injury had correlation with mortality rate, while the use of steroids/cyclophosphamide did not lead to reduced mortality rate.

In the absence of effective antidote and specific treatment, PQ continues to cause very high mortality rates. In many countries (Sri Lanka, South Korea), PQ has been banned,^2,13 which were followed by reduction in pesticide-associated mortality rates. We hope that this study will help clinicians in the management of PQ poisoning.

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