Treatment Of Paraquat Poisoning Research Articles

Anthrahydroquinone-2,6-disulfonate alleviates paraquat-induced kidney injury via the apelin-APJ pathway in rats

Objective: To explore the protective effects of anthrahydroquinone- 2,6-disulfonate (AH2QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH2QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH2QDS group was given AH2QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL- 6, TNF-α, apelin-APJ (the apelin-angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH2QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH2QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH2QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH2QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH2QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH2QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH2QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH2QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH2QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH2QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

Therapeutic Strategies in Managing Acute Paraquat Poisoning: A Review Study

Background: Paraquat is an extremely toxic herbicide that causes such severe adverse effects as acute lung injury, pulmonary fibrosis, metabolic acidosis, cardiogenic shock, acute renal failure, and even death. Regarding the high prevalence and mortality rate without a specific antidote in paraquat poisoning, we explored managing acute paraquat poisoning. Methods: In this study, required articles were searched using the following keywords: “paraquat poisoning” and “treatment” on an electronic database, such as Pubmed and Google Scholar from January 2013 to December 2020. Results: This article examined pharmacokinetic, clinical, and laboratory findings, complications, diagnosis, prognostic factors, and the treatment of paraquat poisoning. Then, the medical management and therapeutic procedures of paraquat poisoning were discussed. Conclusion: Although there exists no antidote for paraquat poisoning, numerous therapeutic methods have been suggested for treating paraquat poisoning. However, their efficacy remains undiscovered. An interesting finding in one study indicating that endotracheal intubation is an inappropriate procedure for managing paraquat poisoning; further studies are required in this regard. For these reasons, preventing poisoning and using other herbicides with less toxicity than paraquat are recommended.

PARAQUAT INDUCED BILATERAL SPONTANEOUS PNEUMOTHORAX-DAISLEY BARTON SYNDROME – A CASE REPORT

Paraquat (1,1-dimethyl-4, 4-bipyridylium dichloride) is an effective herbicide which is widely used all over the world and India is no exception. It is toxic to humans due to its redox activity which produces superoxide anions. Accidental or suicidal poisoning causes ulceration over the mouth and gastrointestinal tract and the majority of patients die of acute renal failure, hepatic failure and acute lung injury causing mainly lung brosis and consolidation. Treatment of paraquat poisoning is extremely difcult as it does not have any specic antidote. Treatment is mainly symptomatic. Very few patients may develop spontaneous pneumothorax, known as Daisley Barton syndrome, which further impairs survival of the patient Here we present a patient of paraquat induced spontaneous bilateral pneumothorax who survived with conservative treatment.

Isorhynchophylline ameliorates paraquat-induced acute kidney injury by attenuating oxidative stress and mitochondrial damage via regulating toll-interacting expression

Isorhynchophylline (IRN) is an alkaloid with anti-inflammatory and anti-oxidative activities in cardiovascular and brain diseases, but its role in paraquat (PQ)-induced acute kidney injury (AKI) is yet unknown. The model of PQ-induced AKI in rats was established by intraperitoneal injection of PQ (25 mg/kg). We found that the tail vein injection of IRN (4 mg/kg) significantly increased the survival rate of PQ-intoxicated rats. IRN administration alleviated PQ-induced renal injury and renal dysfunction in rats, as evidenced by decreased apoptosis in renal cortex and reduced serum creatinine, serum BUN, and urine NGAL levels. Furthermore, IRN treatment improved the PQ-triggered oxidative stress in renal cortex by increasing the levels of anti-oxidant indicators (SOD activity, GSH/GSSG ratio, levels of Nrf-2, NQO-1, and HO-1 in renal cortex) and decreasing the levels of oxidative stress indexes (ROS and MDA levels in renal cortex). Interestingly, toll-interacting protein (Tollip), a negative regulator of interleukin 1 receptor associated kinase 1 (IRAK1) phosphorylation, was demonstrated to be increased by IRN injection in the renal cortex of PQ-intoxicated rats. In vitro experiments revealed that IRN protected renal tubular epithelial cells against PQ toxicity through suppressing oxidative stress and mitochondrial damage, and these protective effects were reversed by Tollip shRNA. Collectively, the present study demonstrated that IRN ameliorated PQ-induced AKI by attenuating oxidative stress and mitochondrial damage through upregulating Tollip, which provides new insights into the pathogenesis and treatment of PQ poisoning.

Efficacy of hemoperfusion combined with continuous veno-venous hemofiltration on the treatment of paraquat poisoning: a Meta-analysis

To evaluate the efficacy of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) on the treatment of acute paraquat (PQ) poisoning. Prospective randomized controlled trials and retrospective studies on the efficacy of HP combined CVVH in patients with oral PQ poisoning (poisoning time ≤ 24 hours) were found by searching from PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI and Wanfang databases before November 1st, 2019. The experimental group was treated with HP+CVVH, and the control group was treated with HP. Data included the general information of the literature, mortality, survival time, the incidence of respiratory failure and circulatory failure. The bias risk and the data were analyzed using the RevMan 5.3 software. A total of 1 041 literatures were retrieved, and 7 literatures were finally enrolled, including 1 199 patients, with 735 patients in the control group and 464 patients in experimental group. Meta-analysis showed that compared with HP alone, HP+CVVH could significantly reduce the short-term mortality [4-day mortality: hazard ratio (HR) = 0.52, 95% confidence interval (95%CI) was 0.38-0.71, P < 0.000 1], but no significant improvement in long-term mortality was found (28-day or 30-day mortality: HR = 0.68, 95%CI was 0.39-1.21, P = 0.19; 90-day mortality: HR = 1.13, 95%CI was 0.61-2.10, P = 0.07; total mortality: HR = 0.96, 95%CI was 0.72-1.29, P = 0.78). The survival time of patients treated with HP+CVVH was significantly longer than that of HP patients [mean difference (MD) = 2.02, 95%CI was 0.81-3.22, P = 0.001], but the heterogeneity between studies was large. According to the type of literature, a subgroup analysis showed that the survival time of patients treated with HP+CVVH in prospective randomized controlled trials and retrospective studies were significantly longer than that of HP patients (prospective studies: MD = 1.53, 95%CI was 0.94-2.12, P < 0.000 01; retrospective studies: MD = 2.40, 95%CI was 0.08-4.73, P = 0.04). Compared with HP group, HP+CVVH could significantly reduce the incidence of circulatory failure [relative risk (RR) = 0.40, 95%CI was 0.30-0.52, P < 0.00 01], but the incidence of respiratory failure significantly increased (RR = 2.75, 95%CI was 2.18-3.48, P < 0.000 01). HP combined with CVVH can reduce the short-term mortality and the incidence of circulatory failure, prolong the survival time, and save time for further rescue, but it can't improve the long-term prognosis of patients.

Systematic review and meta-analysis of the efficacy and safety of immunosuppressive pulse therapy in the treatment of paraquat poisoning.

Paraquat (PQ), a highly effective herbicide, is widely used worldwide. PQ poisoning can cause multiple organ failure, in which the lung is the primary target organ. After PQ poisoning, the patient mortality rate is as high as 90%, and there is currently no specific antidote. The main clinical treatment is the use of glucocorticoids and cyclophosphamide for pulse therapy, but its effectiveness and safety are still uncertain. We investigated the effectiveness and safety of immunosuppressive pulse therapy with glucocorticoids and cyclophosphamide to evaluate the treatment value in patients with acute PQ poisoning. This meta-analysis, combined with seven trials that enrolled a total of 426 patients, showed that immunosuppressive pulse therapy with glucocorticoids and cyclophosphamide for PQ poisoning significantly reduced mortality of the study group (59.3%, 134/226) compared with the control group (81.0%, 162/200). There was no significant difference of hepatitis or renal failure between the control and study groups, indicating that immunosuppressive pulse therapy was relatively safe. Several patients were reported to have leukopenia and returned to normal after 1-2 weeks without any abnormalities. Two cases of non-fatal sepsis were reported and considered to be a side effect of the immunosuppressive pulse therapy. Thus, immunosuppressive pulse therapy can efficiently reduce the mortality of PQ poisoning and it is relatively safe.

Rapamycin reduces mortality in acute-stage paraquat-induced toxicity in zebrafish

Paraquat (PQ) intoxication is frequently associated with a high mortality rate. No specific treatment has been shown to reduce mortality in victims within the first 72 hours. We investigated the protective effects of rapamycin (Rapa) against PQ-induced toxicity in a zebrafish model. To determine the maximum nonlethal concentration (MNLC) and lethal concentration 50 (LC50) of Rapa, zebrafish were treated at 2-5 days post fertilisation (dpf) and their mortality was recorded every 24 hours. At 5 dpf, the zebrafish were treated with PQ 100 µg/mL or PQ+Rapa (MNLC, 1/3 MNLC or 1/9 MNLC) for 72 hours, and the rate of survival was recorded every 24 hours. Reverse transcription-polymerase chain reaction was used to test the signalling pathway of mTOR (mammalian target of rapamycin). MNLC and LC50 of Rapa were determined to be 6.7 µg/mL and 28.9 µg/mL, respectively. At 48 hours, the PQ+Rapa groups had much lower mortality than the PQ group. The rates of survival of the PQ+Rapa groups were 43.33% (MNLC), 53.89% (1/3 MNLC) and 44.45% (1/9 MLNC), as compared to 19.45% in the PQ group, with the 1/3 MNLC group showing the highest rate of survival (p < 0.001). atg1 was slightly activated in the PQ group. In the PQ+Rapa groups, the expression of atg1 was markedly increased, suggesting strengthening of the autophagy process. Rapa can increase the rate of survival of PQ-intoxicated zebrafish by inhibiting mTOR complex 1 and activating autophagy. Rapa could be an alternative first-line drug in the treatment of PQ poisoning.

Clinical effect of haemoperfusion combined with continuous veno-veno haemofiltration in treatment of paraquat poisoning: a Meta-analysis

To systematically analyze the effect of haemoperfusion (HP) combined with continuous veno-veno haemofiltration (CVVH) in the treatment of the patients with paraquat poisoning (PQP). Words of paraquat, poisoning, continuous venous hemofiltration, hemoperfusion, hemodiafiltration in Chinese and paraquat, poisoning, intoxication, haemofiltration, continuous venovenous haemofiltration, haemoperfusion in English were chosen as keywords, the Chinese and English literatures about acute PQP treated with HP combined with CVVH published in Wanfang database, CNKI, CBM, VIP database, PubMed, Embase, Cochrane Library were searched by computer, and the retrieval time was from the establishment of the database to July 2018. The experimental group was treated with HP combined with CVVH, while the control group was treated with HP alone. Besides, the outcome indicators included mortality, survival time of dead patients (the patient's time from exposure to poison to death), serum creatinine (SCr), alanine aminotransferase (ALT), arterial partial pressure of oxygen (PaO2), and incidence of circulatory and respiratory failure. The literature data were extracted by two researchers independently, the quality of the literature was evaluated according to the modified Jadad score table or Newcastle-Ottawa scale (NOS), and the Meta-analysis was carried out by RevMan 5.3 software; and the stability of the results of Meta-analysis was tested by sensitivity analysis. Further, the publication bias was analyzed through drawing a funnel diagram. Finally, 20 articles were included, with 18 in Chinese and 2 in English. Among them, 6 were randomized controlled trial (RCT) and 14 were case-control studies. Furthermore, a total of 2 870 patients were involved, with 1 558 in the control group and 1 312 in the experimental group. Meta-analysis showed that the mortality rate of patients in the experimental group was significantly lower than that in the control group [odds ratio (OR) = 0.55, 95% confidence interval (95%CI) = 0.42 to 0.73, P < 0.000 1], the patients' time from toxin exposure to death was significantly longer than that in the control group [standard mean difference (SMD) = 2.16, 95%CI = 1.46 to 2.86, P < 0.000 01). In the course of treatment, the peak value of SCr in the experimental group was significantly lower than that in the control group (SMD = -0.53, 95%CI = -0.65 to -0.42, P < 0.000 01), and the peak value of ALT was also decreased (SMD = -0.72, 95%CI = -0.99 to -0.44, P < 0.000 01). Besides, there was no significant difference in PaO2 between the two groups on the 3rd day of treatment (SMD = 0.15, 95%CI = -0.19-0.49, P = 0.40), but on the 7th day, PaO2 in the experimental group was significantly higher than that in the control group (SMD = 0.23, 95%CI = 0.29 to 0.98, P = 0.000 3). Furthermore, the incidence of circulatory failure in the experimental group was significantly lower than that in the control group (OR = 0.26, 95%CI = 0.19 to 0.37, P < 0.000 01), but the incidence of respiratory failure was significantly higher than that in the control group (OR = 4.14, 95%CI = 3.00 to 5.72, P < 0.000 01). The influence of heterogeneity on statistical results was excluded in the sensitivity analysis, and funnel plot diagram was applied to indicate the publication bias of mortality and survival time of the dead patients. Combined with HP alone, HP combined with CVVH could better improve liver and kidney function and oxygenation state of PQP patients, reduce the incidence of early circulatory failure, prolong the survival time and reduce the death rate of PQP patients.

Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies.

BackgroundParaquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.MethodsThe electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.ResultsEleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.ConclusionMSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.

Continuous venovenous hemofiltration in the management of paraquat poisoning: A meta-analysis of randomized controlled trials.

Paraquat (PQ) poisoning is a widespread occurrence, especially in underdeveloped areas. The treatment of PQ poisoning has always been difficult, and there is currently no definite effective treatment. Continuous venovenous hemofiltration (CVVH) treatment for PQ poisoning has been widely used in clinical practice; however, its effect remains uncertain. Accordingly, the purpose of this meta-analysis was to evaluate the efficacy of CVVH in the treatment of PQ poisoning. We searched for relevant trials using PubMed, Embase, the Cochrane Library, and 3 Chinese databases, the Chinese BioMedical Literature Database, National Knowledge Infrastructure Database, and Wanfang Database. We included all qualified randomized controlled trials (RCTs) of CVVH treatment for patients with PQ poisoning. The primary outcome was mortality, while the secondary outcomes included the survival time and constituent ratios of death due to respiratory failure and circulatory failure. Three RCTs involving 290 patients were included. The mortality rates of the intervention and control groups were 57.9% and 61.0%, respectively. Pooled analysis demonstrated no significant difference in mortality between the CVVH treatment and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.78-1.15, P = .56), with a low level of heterogeneity (X = 1.75, I = 0%). However, the CVVH group was associated with a longer survival time compared to the control group (weighted mean difference 1.73, 95% CI: 0.56-2.90, P = .004). Respiratory failure as the cause of death was more common in the CVVH group, as compared with the control group (RR 1.66, 95% CI: 1.24-2.23, P = .0008), whereas patients in the control group were more likely to die from circulatory failure than in the CVVH group (RR 0.56, 95% CI: 0.40-0.81, P = .002). Although CVVH treatment might not noticeably reduce mortality for patients with PQ poisoning, it can prolong the survival time of the patients and improve the stability of the circulatory system, thereby enabling further treatment.

The prevention and therapeutics effect of sodium bicarbonate with gastric lavage, atomization inhalation and intravenous injection on the patients with paraquat poisoning and pulmonary fibrosis induced by paraquat poisoning

To observe the prevention effects of patients with lung exudation and pulmonary fibrosis induced by paraquat poisoning in sodium bicarbonate (SB) with gastric lavage, atomization inhalation and intravenous injection. To collect 38 patients with paraquat poisoning in hospital, after poison immediately with gastric lavage of 1.5% SB, and atomization inhalation of 5% SB 10~15 ml twice daily and intravenous injection of 5% SB twice a day, continuous application of 5~7 days. and the HRCT score and liver and kidney function was performed on patients with lung after treatment. And the extraction of 38 SB patients with previously untreated with SB for comparison. Lung HRCT average score in 72 h, 7 d, 30 d on patients with paraquat poisoning untreated with SB reached 2.87, 3.12, 2.13, HRCT display shows that the appearance of the wear glass shadow, grid shadow, honeycomb shadow, and other signs of fibrosis. Average HRCT reached 1.95, 2.20, 1.67 on patients treated with SB,signs of lung exudation and fibrosis was significantly reduced,compare two groups,there was statistically significance (P<0.01). And compared to the control group, activity of serum alanine aminotransferase (ALT) and aspartic acid transaminase (AST) decreased significantly in group of paraquat poisoning with triple application of SB, the level of serum urea nitrogen (BUN) and creatinine (Cr) significantly decreased, the difference is statistically significant (P<0.01). The triple application of SB can reduced the pulmonary fibrosis and effusion induced by paraquat poisoning,and protective effect on the function of liver and kidney is obvious, suggesting that the method for treatment of paraquat poisoning, prevention of paraquat lung and improve survival rate has the exact effect.

Effect of Pulse Therapy with Glucocorticoids and Cyclophosphamide in Patients with Paraquat Poisoning

Introduction Paraquat (PQ) is a widely used herbicide with a high mortality rate when ingested. The aim of the present study was to assess the effectiveness of repeated cyclosphosphamide (CP) and methylprednisolone (MP) combination in the treatment of PQ poisoning. Design Randomised, double-blinded, placebo-controlled trial. Methods Eligible participants were 47 patients with moderate to severe PQ poisoning within 24 hours of hospitalisation. Patients were allocated in a random fashion, 24 as the intervention and 23 as the control group. All patients received two cycles of eight hours of haemoperfusion with charcoal, and underwent emergency haemodialysis. After the dialysis, the intervention group received 15 mg/kg CP for two days and 1g MP for three days. The control group received routine supportive care. Outcome parameters, including mortality, incidence of hypoxia, hepatitis and renal failure were compared between the two groups. Results There were no significant differences between the two groups with regard to age, sex, baseline liver function test, creatinine, time from poisoning to dialysis, and time from poisoning to the hospitalisation. Although the incidence of hepatitis and acute renal failure did not differ significantly between the two groups, the incidence of hypoxia and mortality rate was lower in the intervention group. The number need-to-treat to reduce one mortality was 2.8. Conclusion The results suggest that CP and MP repeated treatment can reduce the mortality rate in moderate to severe PQ intoxication.

Pillar[6]arene/Paraquat Molecular Recognition in Water: High Binding Strength, pH-Responsiveness, and Application in Controllable Self-Assembly, Controlled Release, and Treatment of Paraquat Poisoning

The complexation between a water-soluble pillar[6]arene (WP6) and paraquat (G1) in water was investigated. They could form a stable 1:1 [2]pseudorotaxane with an extremely high association constant of (1.02 ± 0.10) × 10(8) M(-1) mainly driven by electrostatic interactions, hydrophobic interactions, and π-π stacking interactions. This molecular recognition has not only high binding strength but also pH-responsiveness. The threading and dethreading processes of this [2]pseudorotaxane could be reversibly controlled by changing the solution pH. This novel recognition motif was further used to control the aggregation of a complex between WP6 and an amphiphilic paraquat derivative (G2) in water. The reversible transformations between micelles based on G2 and vesicles based on WP6⊃G2 were realized by adjusting the solution pH due to the pH-responsiveness of WP6. The controlled release of water-soluble dye molecules from the vesicles could be achieved by the collapse of the vesicles into the micelles upon changing the solution pH to acidity. Additionally, the high binding affinity between WP6 and paraquat could be utilized to efficiently reduce the toxicity of paraquat. After the formation of a stable host-guest complex between WP6 and paraquat, less opportunity was available for paraquat to interact with the reducing agents in the cell, which made the generation of its radical cation more difficult, resulting in the efficient reduction of paraquat toxicity.

Efficacy of deferoxamine on paraquat poisoning

Background: Paraquat is known to induce oxidant injury that results in multiorgan failure and lung fibrosis. Iron has been considered to play a key role in paraquat-induced oxidant lung injury. This study examined the effect of deferoxamine, an iron-chelating agent, in the treatment of paraquat poisoning. Methods: From September, 2001 to April, 2005, 28 patients with paraquat poisoning who were admitted at a medical intensive care unit of a University-affiliated hospital, were enrolled in this study. Sixteen patients were treated according to the paraquat poisoning treatment guidelines and 12 received an intravenous infusion of deferoxamine in addition to the treatment guidelines. Results: There were no differences between the two groups in terms of age, gender, severity of paraquat poisoning, and the time elapsed from ingestion to presentation at hospital. There was no difference in overall mortality between the two groups but the incidence of respiratory failure in the deferoxamine group was higher than in the conventional group(4/7 versus 0/9, p=0.019). Conclusion: Deferoxamine seems to have no clinical benefit compared with the conventional treatment.

High-dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective study.

Between March 1986 and March 1988, 47 consecutive patients, whose paraquat intoxication was confirmed by urine testing, were enrolled in a prospective study on the treatment of paraquat poisoning. Fourteen received a standard treatment regimen consisting of fluid replacement and oral absorbents, and 33 received high-dose cyclophosphamide and dexamethasone, in addition to standard therapy. The case fatality rate in both treatment groups (63 and 61%) was similar. In addition, all 26 patients whose paraquat serum concentrations were measured and who had a probability of survival of less than 65% according the survival curve of Hart et al. died, regardless of therapy. These included four in the cyclophosphamide/dexamethasone group and two in the standard treatment group who had prior survival probabilities between 50 and 65%. This indicated that the cut-off curve relating mortality and paraquat serum concentrations was similar in both treatment groups. High-dose cyclophosphamide/dexamethasone treatment is unlikely to improve the prognosis of paraquat poisoning.

In vitro adsorption removal of paraquat by activated carbon and cation exchange resin.

With the modernization of agriculture, environmental pollution and accidental poisoning by agricultural chemicals have become a great social problem. With the remarkable increase in the amount of paraquat used, the number of deaths by swallowing of paraquat has also increased in recent years. Presently, an effective antidote and treatment for paraquat poisoning is not available. For primary treatment, administration of an adsorbent is done at the same time as gastrointestinal lavage. As an adsorbent for paraquat poisoning, the efficacy of activated carbon, Fuller's Earth, bentonite, and a cation exchange resin have been reported. In this work, the authors discuss the adsorption characteristics of paraquat in artificial gastric juice and normal saline solution.

Treatment of paraquat poisoning in man: methods to prevent absorption.

Theoretically, absorption of an ingested dose of paraquat may be reduced by gastric lavage, induced emesis, whole-gut lavage or by the oral administration of absorbent substances. Animal experiments suggest that paraquat is absorbed poorly from the stomach and absorbed incompletely (less than 5%) from the small intestine over a 1-6 h period. Although gastric lavage would therefore seem a logical way to ameliorate the toxicity of an ingested dose of paraquat, peak plasma concentrations are attained rapidly and evidence for the efficacy of gastric lavage in man is poor. In 1977, a potent emetic (PP796) was added to liquid and solid formulations of paraquat because experiments in primates had demonstrated a fivefold reduction in toxicity. In man, ingestion of formulations containing an emetic is more likely to cause spontaneous vomiting within 30 min than non-emetic preparations. However, definite evidence of benefit, as judged by improved patient prognosis, has yet to be established. Gut lavage has been shown to remove only a small proportion of an ingested dose of paraquat. At the flow rates employed in man (75 ml/min), approximately 0.5-1.0 litres of lavage fluid/h may be absorbed across the intestinal wall. Since there is a theoretical risk of increasing paraquat absorption, the use of whole-gut lavage cannot be recommended. Bipyridilium herbicides are absorbed by soil and clay minerals, and montmorillonite in particular has been shown to be a strong binding agent in vitro. Accordingly, the use of Fuller's Earth (calcium montmorillonite) and Bentonite (sodium montmorillonite) for the treatment of poisoning has been investigated in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of paraquat poisoning by suppression of leucocytes with dexamethasone and cyclophosphamide

Treatment of paraquat poisoning by suppression of leucocytes with dexamethasone and cyclophosphamide

Prognosis and treatment of paraquat poisoning: a review of 28 cases.

Paraquat poisoning is very severe. When it is ingested, this herbicide may be responsible for causative lesions of the digestive tract, cytolytic hepatitis, renal tubular necrosis, circulatory failure, and/or pulmonary fibrosis. Since a very low dose (as little as one mouthful) is potentially lethal, it is important to understand why 11 of our 28 patients who entered our department for paraquat poisoning survived. The main prognostic factors appear to be the following: Route of administration. Of four patients who had inhaled paraquat aerosols and/or contaminated their skin with the herbicide, all survived. Ingested amount. Above 50 mg/kg, patients died of circulatory failure within 72 h; between 35 and 50 mg/kg, a progressive pulmonary fibrosis occurred. Delay between ingestion and the last meal. Paraquat is adsorbed and neutralized by foodstuffs. Caustic gastric lesions revealed by early endoscopic examination. The occurrence of an organic renal failure. The plasma paraquat concentrations within the first 24 h. Patients whose plasma concentrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg/L at 4, 6, 10, 16, and 24 h, respectively, are likely to survive. The different treatments that have been tested (fuller's earth, forced diarrhea, furosemide, hemodialysis, hemoperfusion, artificial ventilation with hypoxic breathing mixtures) did not modify the initial prognosis. The 11 survivals are only linked to the circumstances of the poisonings (route of administration, ingested amount, delay between ingestion and the last meal, etc.). The treatments did not modify the outcome.

Paraquat中毒に対する吸着剤の効果に関する研究

Paraquat中毒に対する吸着剤の効果に関する研究