Sae-Yong Hong

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.

Blockade of Oxidative Stress by Vitamin C Ameliorates Albuminuria and Renal Sclerosis in Experimental Diabetic Rats

Purpose Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney. Materials and Methods Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n = 8) and a vitamin C-treated group (n = 8). Long-Evans Tokushima Otsuka rats (n = 8 ) were used as a control. Results Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats. Conclusion By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy.

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.

Paraquat intoxication in Korea

Abstract In this study, the authors explored acute paraquat intoxication and determined potential factors related to paraquat fatalities. During 1999, 154 patients with paraquat intoxication were admitted to the Institute of Pesticide Poisoning at the Soonchunhyang University Chunan Hospital. The authors assessed paraquat exposure by quantifying the amount of ingested paraquat and by semiquantitative assay of paraquat in urine. Outcomes of paraquat intoxication were categorized as recovery or death. Among all the patients, 139 (90.3%) were transferred from other medical facilities to the Institute of Pesticide Poisoning following a mean exposure time of 20.1 hr (standard deviation = 2.6 hr). Intentional ingestion of paraquat accounted for 73.4% (113/154 patients) of all paraquat poisonings, and it represented a significantly higher fatality rate (53.2%) than did accidental ingestion (19.1 % [p < .001]). The overall paraquat fatality was 43.8%. Multiple logistic-regression analysis revealed that the risk of fatality increased significantly with (1) the quantity of paraquat ingested and (2) a positive urinary paraquat test. The results indicated that paraquat is potentially lethal in humans, and the risk of fatality is directly related to the amount ingested and absorbed.

Angiotensin II receptor blocker attenuates overexpression of vascular endothelial growth factor in diabetic podocytes

VEGF expressed in glomerular podocytes, is known to increase vascular permeability to macromolecules. Angiotensin II can stimulate the release of VEGF, and the protective effects of angiotensin II antagonist against diabetic glomerular injury suggest that the angiotensin II-induced VEGF is an important pathogenetic mechanism in the development of proteinuria during diabetic nephropathy although this mechanism is not fully understood. In this study, the changes of VEGF expression was examined in the experimental diabetic nephropathy to determine whether these changes were modified by renoprotective intervention by blockers of angiotensin II receptors. The streptozotocin- induced diabetic rats were treated with L-158,809, a blocker of angiotensin II receptors, for 12 weeks. Age-matched rats with L-158,809 served as controls. RT-PCR and immunohistochemistry were used to assess and quantify gene and protein expression of VEGF. A progressive increase in urinary protein excretion was observed in diabetic rats. Glomerular VEGF expression was significantly higher in diabetic rats than in the control groups, with a significant reduction in glomerular VEGF expression and proteinuria in L-158,809- treated diabetic rats. VEGF mRNA was also significantly higher in diabetic kidneys than in the control groups, with a significant reduction in VEGF mRNA in L-158,809-treated diabetic kidneys. These results demonstrates that VEGF expression is significantly increased in diabetic podocytes, and angiotensin II receptor antagonist attenuated these changes in VEGF expression and prevented the development of proteinuria in vivo. Attenuation of increased VEGF expression in podocytes could contribute to the renoprotective effects of angiotensin II receptor antagonists in diabetic nephropathy.

Effect of vitamin C on plasma total antioxidant status in patients with paraquat intoxication

This study was conducted to evaluate whether vitamin C (VC) was associated with total antioxidant status (TAS) in human plasma and to determine the usefulness of VC on TAS in the treatment of patients with paraquat poisoning. VC and TAS were measured in 56 healthy subjects. Then, various concentrations (1-100 mg/dl) of VC in pooled plasma from 10 volunteers were constructed in vitro and TAS was measured. The VC and TAS were measured in vivo at 0.5, 1, 2, 3, 5, 7, 9, and 11 h after injection of VC (50 mg/kg) in seven volunteers and pharmacokinetic data were calculated. Finally, various amounts of VC (100, 500, 1000, 3000 mg/day, and 3000 mg/8 h) were given to 10 paraquat-poisoned patients for 5 consecutive days, and blood was taken for TAS 1 h after each injection. The means (SD) of VC and TAS in healthy subjects were 2.22 (0.16) mmol/l and 0.48 (0.10) mg/dl, respectively. Positive correlation between VC and TAS was observed in both in vitro and in healthy volunteers. The pharmacokinetic results in vivo were as follows: means (SD) of distribution volume, area under curve, plasma clearance, half life, C(max), and T(max) were 32.0 (4.4) l, 36.4 (11.3) mg h/dl, 2.13 (1.36) l/h, 10.2 (7.8) h, 17.1 (7.1) mg/dl, and 0.64 (0.24) h, respectively. Estimated loading and maintenance doses of VC were 2278 mg and 146 mg/h, respectively. The means of TAS were increased over 5 consecutive days as 2.26, 2.76, 2.81, 3.18, and 3.58 mmol/l in paraquat patients. All patients were recovered within mean (SD) 21.2 (5.4) admission days. Our data suggested that VC was a significant antioxidant as TAS in human plasma and that increased TAS by high doses of VC could be useful as a free radical scavenger for paraquat poisoned patients.

Paraquat Intoxication in Subjects Who Attempt Suicide: Why They Chose Paraquat

Background/Aims Paraquat (PQ) has been used in suicide attempts; an estimated 2,000 toxic ingestions occur annually, with 60-70% mortality. We sought to determine why PQ is such a common agent for suicide attempts in Korea. Methods We analyzed 250 cases (143 males, 107 females) of attempted suicide by PQ ingestion from January to December 2007. The procurement of the PQ was divided into two categories: purchased and preexisting. Results Men were more likely to have purchased PQ than women (66% vs. 22%, p=0.042). Additionally, men were more likely to be unmarried (n=34, 23.9% vs. n=10, 9.3%) or divorced or separated (n=16, 11.3% vs. n=5, 4.6%) than the women (p<0.001). The group who intentionally selected PQ (38.4%) consisted of 96 cases (54 males, 42 females) and the group who did not intentionally select PQ (61.6%) included 154 cases (89 males, 65 females). The incidence of PQ purchase was higher in the intentional selection PQ group (46.9% vs. 18.2%, p<0.01). Conclusions Only 38% of patients who attempted suicide with PQ intentionally selected PQ. Thus, greater control of PQ availability is needed, especially in patients at risk.

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.