Diagnostic and Therapeutic Approach for Acute Paraquat Intoxication

Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic factor is the time required to achieve a negative urine dithionite test. Patient survival is a 100% when the area affected by ground glass opacity is <20% of the total lung volume on high-resolution computed tomography imaging 7 days post-PQ ingestion. The incidence of acute kidney injury is approximately 50%. The average serum creatinine level reaches its peak around 5 days post-ingestion, and usually normalizes within 3 weeks. We obtain two connecting lines from the highest PQ level for the survivors and the lowest PQ level among the non-survivors at a given time. Patients with a PQ level between these two lines are considered treatable. The following treatment modalities are recommended to preserve kidney function: 1) extracorporeal elimination, 2) intravenous antioxidant administration, 3) diuresis with a fluid, and 4) cytotoxic drugs. In conclusion, this review provides a general overview on the diagnostic procedure and treatment modality of acute PQ intoxication, while focusing on our clinical experience.

The Time between Paraquat Ingestion and a Negative Dithionite Urine Test in an Independent Risk Factor for Death and Organ Failure in Acute Paraquat Intoxication

To identify a prognostic marker that is less sensitive to variations in the elapsed time since paraquat ingestion, we assessed the time between paraquat ingestion and a negative dithionite urine test as a prognostic parameter in patients with acute paraquat intoxication. Forty-one patients with acute paraquat intoxication were enrolled in this study and analyzed to verify significant determinants of mortality and organ dysfunction. The amount of paraquat ingested, paraquat plasma levels, and the time to a negative urine dithionite test were significant independent risk factors predicting mortality. The amount of paraquat ingestion, and the time to a negative urine dithionite test were independent risk factors predicting organ dysfunction. With a cut-off value of 34.5 hr for the time to negative conversion of the urine dithionite test, the sensitivity and specificity for mortality were 71.4% and 75.0%, respectively. The incidence of acute kidney injury and respiratory failure above 34.5 hr were 100% and 85.0%, respectively. In conclusion, the time to a negative urine dithionite test is the reliable marker for predicting mortality and/or essential organ failure in patients with acute paraquat intoxication, who survive 72 hr.

Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication

To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication.

The Area of Ground Glass Opacities of the Lungs as a Predictive Factor in Acute Paraquat Intoxication

Even though plasma paraquat (PQ) levels have known to be an informative predictor, many patients succumb at low PQ levels in acute PQ intoxication. This study was designed to see whether the high resolution computerized tomography (HRCT) of the lungs would be a predictive measure in acute PQ intoxication. HRCT of the lungs was obtained from 119 patients with acute PQ intoxication on 7 days after PQ ingestion. The areas with ground glass opacities (GGOs) were evaluated at five levels with the area measurement tool of the picture archiving and communication systems. Among 119 patients, 102 survived and 17 died. The plasma PQ levels were significantly higher in the non-survivors than in the survivors (2.6+/-4.0 microgram/mL vs. 0.2+/-0.4 microgram/mL, P=0.02). The area with GGOs was 2.0+/-6.4% in the survivors and 73.0+/- 29.9% in the non-survivors (P<0.001). No patients survived when the area with GGOs was more than 40% but all of the patients survived when the area affected by GGOs was less than 20%. In conclusion, the area of GGOs is a useful predictor of survival in acute PQ intoxication, especially in patients with low plasma PQ levels.

Fatal paraquat poisoning: a light microscopic study in eight autopsy cases.

Eight autopsy cases of paraquat poisoning from 1980 to 1990 were studied by light microscopy. An attempt was made to correlate the severity of poisoning, as assessed by the blood paraquat concentrations and the time between ingestion and treatment, with the survival periods and pathological changes. Six of the patients were male. The mean age was 21 years (range 12-33 years). The blood paraquat concentrations on admission ranged from 0.04 to 4.27 micrograms/ml. The survival periods were between 26 hours and 59 days. The main causes of death included circulatory collapse in one patient with 26 hours survival, and acute alveolar injury of the lungs and acute tubular necrosis or diffuse cortical necrosis of the kidneys in 4 patients who survived less than 7 days. Pulmonary proliferative changes leading to respiratory failure were detected in the remaining patients, who survived 11, 17, and 59 days. The liver revealed bile duct injury in the portal areas, centrolobular cholestasis, fatty metamorphosis, and inconspicuous centrolobular hepatic necrosis. The adrenal glands showed diffuse cortical necrosis in 3 severe cases. Mild acute pancreatitis was evident in one case. The brain was edematous with or without focal minimal hemorrhages. Toxic myocarditis, myositis, and aplasia of erythropoiesis, as previously described, were not present in this study. The severity of poisoning seems to correlate reversely with the survival periods and directly with degrees of pulmonary damage and adrenal cortical necrosis.