Jong-Oh Yang

Association between plasma paraquat level and outcome of paraquat poisoning in 375 paraquat poisoning patients

Objectives. Paraquat poisoning by ingestion is often fatal. Many studies have investigated treatment modalities and predictor parameters, but there is no standard treatment. Plasma paraquat concentration seems a valid predictable parameter of survival. In order to achieve uniform treatment, including extracorporeal elimination and antioxidant therapy, the outcome of paraquat poisoning based on plasma paraquat level needs to be investigated. Methods. This study included 375 paraquat poisoning patients who were diagnosed by means of plasma paraquat concentration within 24 hours after ingestion in the Institute of Pesticide Poisoning of Soonchunhyang University Cheonan Hospital, Korea, from January 2005 to December 2006. All patients were treated according to a uniform protocol including extracorporeal elimination and antioxidant therapy. Plasma paraquat concentration was measured by high-performance liquid chromatography. Results. The mean age of the paraquat-intoxicated patients was 48.42 ± 6.75. One hundred ten patients (29.3%) survived. The upper limit of plasma paraquat concentration in survivors was 2.64 at 3 hour. All patients with plasma paraquat level above 3.44 died. The minimum paraquat level of the deaths was very low (0.12 μg/ml at 5 hours; 0.02 μg/ml at 12 hours; 0.01 μg/ml at 24 hours). Conclusions. Our data showed that plasma paraquat concentration is good predictor of survivors but is not good predictor of non-survivors in the low plasma paraquat level.

Predictors of survival after acute paraquat poisoning.

Acute paraquat poisoning is often fatal. Many studies have investigated successful treatment modalities, but no standard treatment yet exists. The purpose of this study was to determine the predictors of survival after acute paraquat poisoning in 602 patients. The paraquat exposure was assessed based on the amount of ingested paraquat and a semiquantitative measure of the urine level of paraquat. Initial clinical parameters including vital signs, hemoglobin, white-blood-cell count, pH, PaCO2, PaO2, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, total bilirubin, amylase, and glucose were obtained at the time of arrival at the emergency room. Outcomes after acute paraquat poisoning were categorized as survivors and nonsurvivors. Multiple logistic regression analysis was applied to assess the predictors of survival after acute paraquat poisoning. Some patients (55.5%) survived after oral ingestion of paraquat, whereas all those exposed to paraquat percutaneous or inhalational route survived. The amount of paraquat (24.5% concentrate of 1,1′-dimethyl-4,4′-bipyridium dichloride) ingested was 45.69 / 74.1 mL (mean9 / SD). In addition to degree of paraquat exposure, survival after acute paraquat poisoning was associated with age, respiratory rate, pH, PaCO2, hemoglobin, white-blood-cell count, blood urea nitrogen, amylase, and the number of failed organs in multiple logistic regression analysis. In conclusion, young age, percutaneous or inhalational route, exposure to less paraquat, and lesser degrees of leukocytosis, acidosis, and renal, hepatic, and pancreatic failures on admission are good prognostic factors of survival after acute paraquat poisoning.

The clinical features of acute kidney injury in patients with acute paraquat intoxication

BACKGROUND Paraquat (PQ) is a non-selective herbicide that generates reactive oxygen species in vivo. We hypothesized that acute kidney injury (AKI) in patients with acute PQ poisoning would provide a model for the clinical features of ROS-induced AKI. METHODS From January 2007 to December 2007, 278 patients with acute PQ intoxication were included in the study. AKI was defined based on the RIFLE classification. The serial changes of creatinine (Cr), the incidence of AKI and the mortality according to the RIFLE classification were analysed. RESULTS An initial serum Cr >1.2 mg/dL was a significant predictor of mortality [odds ratio 9.00, 95% C.I. (4.747, 17.061), P < 0.01]. The incidence of AKI was 51.4% among the 173 patients who had an initial serum Cr < or =1.2 mg/dL. Among them, 34.7% were the failure group and oliguric AKI was observed in 10 patients. The average peak serum Cr level, among the 13 survivors in the failure group, was 4.38 mg/dL at the fifth day, after ingestion, and their Cr level normalized within 3 weeks. None of the 13 survivors had permanent loss of renal function. The estimated amount of PQ ingestion was a predictor of the incidence of AKI. The mortality risk was significantly higher in the failure group than in the group without failure. CONCLUSION The clinical feature was characterized by fully developed AKI at the fifth day after PQ ingestion and normalized within 3 weeks without exception.

Effect of haemoperfusion on plasma paraquat concentration in vitro and in vivo.

This study was to observe the paraquat (PQ) reduction rate after haemoperfusion (HP) on the groups of a relatively large number: 50 survivors out of 105 patients with acute PQ poisoning. We started off by measuring the clearance of haemodialysis (HD) and HP for the PQ in vitro. At the blood flow of 250 mL/min, the PQ clearance was greater in HP than in HD during the first 90 minutes: 215 versus 175 mL/min at 30 minutes, 213 versus 201 mL/min at 60 minutes, and 199 versus 179 mL/min at 90 minutes. The clearance in HP decreased rapidly after two hours. By the end of the dialysis, however, the final concentration in container decreased to 5.7 mg/mL in HD and 1.5 mg/mL in HP, which implied that although HD was cleared more effectively during the later stages, the overall elimination was greater in HP. Following this preliminary investigation, we performed HP on all the patients in order to assess the extracorporeal elimination. One hundred and five patients who had swallowed one to three mouthfuls of PQ (24.5% w/v) solution were subjected to the in vivo study. The reduction rate of PQ was checked out by measuring the PQ concentration in plasma before and after four hours of HP. Seeing the reduction rate was significantly higher in the survivors group than in the nonsurvivors group (80.39 ± 19.9 versus 67.29 ± 19.2%, P <0.01), we concluded that adequate HP appears to be an indispensable treatment for patients with acute PQ poisoning.

Comparison between Kidney and Hemoperfusion for Paraquat Elimination

The mortality rate of acute paraquat (PQ) poisoning depends on the PQ concentration in the blood. It has been shown that the kidneys eliminate PQ effectively. However, early renal function deterioration is frequently observed in acute PQ intoxication. This study is designed to compare the efficacy of PQ elimination with hemoperfusion (HP) and kidneys, taking into account the functional deterioration of the kidneys. The amount of renal and HP excretion of PQ were measured during the procedure of HP in patients with acute PQ intoxication. The PQ clearance and the actual amount of PQ elimination by the HP cartridge during the HP procedure were 111±11 mL/min (range; 13.2-162.2 mL/min) and 251.4±506.3 mg (range; 4.6-1,655.7) each. While, the renal clearance and actual amount of renal elimination of PQ was 79.8±56.0 mL/min (range; 9.7-177.0) and 75.4±73.6 mg (range; 4.9-245.8). As the creatinine clearance decreased, the PQ elimination by HP was as effective as or more effective than the renal elimination. In conclusion, early HP must be provided for life saving treatment in patients with acute PQ intoxication.

Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication

Background: Glyphosate, one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The purpose of this study was to determine the effect of glyphosate-surfactants (“glyphosate-surfactant toxicity”) in patients with acute glyphosate intoxication. Methods: In all, 107 patients (69 men and 38 women, aged 52.3 ± 15.5 years) with acute glyphosate intoxication were enrolled in this study. From their medical records, we identified the formulation of ingested glyphosate products and derived clinical parameters, which focused on clinical outcome, admission days, duration in the intensive care unit, development of respiratory failure, cardiovascular deterioration, renal failure, altered mental status, and convulsions. The effect of surfactants on clinical complications was also assessed. Results: For surfactant ingestion volumes of 8 mL, the incidence of clinical complications was (in rank order) as follows: hypotension, 47.1%; mental deterioration, 38.6%; respiratory failure, 30.0%; acute kidney injury, 17.1%; and arrhythmia, 10.0%. These complications were influenced by the volume of surfactant and not the type of surfactant-ingredient in the herbicide product. Two patients died of refractory shock, metabolic acidosis, and respiratory failure. However, the final clinical outcomes of the surviving patients were benign, and cardiovascular, respiratory, kidney, and mental functions were fully restored to normal levels. Conclusions: Our results indicate that treatment of patients with acute glyphosate herbicide intoxication should take into account the volume and not the type of surfactants in herbicide formulations.

Factors for Determining Survival in Acute Organophosphate Poisoning

Background/Aims Organophosphate poisoning has a high mortality rate. Recently, differences among organophosphorus insecticides in human self-poisoning were reported. This study investigated the prognostic risk factors and the mortality of different organophosphates following acute organophosphate poisoning. Methods This retrospective study included 68 patients with acute organophosphate poisoning. We investigated patient survival according to initial parameters, including the initial Acute Physiology and Chronic Health Evaluation (APACHE) II score, serum cholinesterase level, and hemoperfusion and evaluated the mortality according to organophosphate types. Results Thirteen of the 68 patients died. The agents responsible for mortality were different. The APACHE II score was a significant predictor of mortality (odds ratio [OR], 1.194; p<0.01; 95% confidence interval [CI], 1.089 to 1.309) and respiratory failure (OR, 1.273; p<0.01; 95% CI, 1.122 to 1.444). The mortality was 0% for dichlorvos, malathion, chlorpyrifos and profenofos. However, other organophosphates showed different mortality (16.7% for O-ethyl-O-4-nitrophenyl phenylphosphonothioate, 25% for phenthoate, 37.5% for phosphamidon, 50% for methidathion). The usefulness of hemoperfusion appears to be limited. Conclusions The initial APACHE II score is a useful prognostic indicator, and different organophosphates have different mortality.

Clinical Outcome of Hemoperfusion in Poisoned Patients

Extracorporeal removal techniques are effective methods for toxin removal from the body. To define the safety and clinical outcomes of hemoperfusion, we evaluated retrospectively clinical outcomes of hemoperfusion over a 3-year period in our clinical center. From January 2006 to December 2008, we analyzed 803 patients. Mortality, catheter-related bleeding, systemic bleeding, hypocalcemia, and thrombocytopenia were investigated. Medical drugs (n = 54) and pesticide toxins (n = 749) were represented. Pesticides included herbicides (n = 598), insecticides (n = 130), mixed herbicides and insecticides (n = 4), and unknown pesticides (n = 17). Among those with herbicide poisoning, 493 cases were caused by paraquat, and among those affected by insecticides, 67 cases were caused by organophosphate insecticides. After hemoperfusion, systemic bleeding complications were observed in 26 cases (3.0%). Systemic bleeding was a greater mortality risk factor than nonsystemic bleeding (OR 2.779, 95% CI 1.07–7.23). Hypocalcemia was observed in 69.1% and thrombocytopenia in 31.1%. Excess mortality was 44.4%. In hemoperfusion cases, systemic bleeding is a major factor to predict adverse outcome.

Clinical implication of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in patients with acute paraquat intoxication

Background. Paraquat (PQ)-induced acute kidney injury (AKI) might show the role for reactive oxygen species (ROS) in AKI. The purpose of this study was to investigate the characteristics of early urinary biomarkers in patients with acute PQ poisoning. We prospectively investigated changes in urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in acute PQ intoxication. Methods. From May 2008 to September 2008, 20 patients were included. Urine KIM-1, NGAL, and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were measured at 6, 12, 24, 48, 72, and 120 h after ingestion. The serum creatinine was measured also at the same intervals. Results. AKI was diagnosed in 11 out of 20 patients. There was a significant difference in the creatinine at 12 h between patients with AKI and those without AKI (0.50 ± 0.15 vs. 1.04 ± 0.53 mg/dL, p = 0.01). Urinary NGAL was higher in patients with AKI compared to patients without AKI at 24 h (2.84 vs. 0.96 ng/mL). Urinary KIM-1 was not different in comparisons between patients with AKI and those without AKI. Regardless of the AKI, the NGAL and KIM-1 were increased at between 24 and 48 h. Conclusion. PQ is a very potent stimulant of NGAL-1 and KIM-1. Therefore, the NGAL might reflect reactive oxygen species-induced kidney injury.

Effect of glutathione on the cadmium chelation of EDTA in a patient with cadmium intoxication

In order to evaluate the efficiency and renal protective effects of glutathione during Ca++-EDTA chelation therapy for chronic cadmium intoxication, we measured the renal excretion of cadmium, β2-microglobulin, proteinuria, and hematuria during intravenous administration of glutathione with Ca++-EDTA in a 54-year-old patient with chronic cadmium intoxication. We administered 500 mg of Ca++-EDTA and 50 mg/kg of glutathione alone or in 1 L of normal saline over the next 24 hours and repeated this over 12 consecutive days. During the first 3 days, the basal levels (only saline administration) were determined; during the second 3 days, Ca++-EDTA only was administered, for the third sequence of 3 days, Ca++-EDTA with glutathione was provided, and for the last 3 days, glutathione alone was given. One month later, the same protocol was repeated. There were six blood and urine samples to analyze in each group. The blood cadmium level was higher when the EDTA was infused together with glutathione (7.44 ± 0.73 µg/L, p < 0.01) compared to the basal level of 4.6 ± 0.44 µg/L. Also, the renal cadmium excretion was significantly higher in the EDTA with glutathione group than in the basal group (23.4 ± 15.81 µg/g creatinine vs 89.23 ± 58.52 µg/g creatinine, p < 0.01). There was no difference in the protein/creatinine and β2-microglobulin/creatinine ratio in the urine (p > 0.05) among the groups. Furthermore, microhematuria and proteinuria did not develop over the observation period of 6 months. These results suggest that glutathione administration with EDTA might be an effective treatment modality for patients with cadmium intoxication.