Acute Paraquat Poisoning Research Articles

Factors associated with refusing hemoperfusion in patients with acute paraquat poisoning.

Paraquat poisoning remains a critical public health issue with no established effective treatment. Hemoperfusion (HP) has been recognized for its potential to remove toxins and is widely employed in several developing countries for managing acute paraquat poisoning cases. However, the reluctance of some patients to undergo this recommended treatment has been observed but not thoroughly investigated. This study aimed to explore the factors associated with the refusal of HP in patients suffering from paraquat intoxication. In this retrospective study, data of 358 patients with acute paraquat poisoning were analyzed in Xi'an, China. The outcome of our study was mortality, and the influential factors were age, gender, marital status, educational level, symptoms at presentation, and laboratory findings. A logistic regression model was utilized to explore the independent risk factors. In a total of 358 paraquat-poisoned patients, the significant differences were found between patients who underwent HP and those who did not, particularly regarding mean age (48.02 years vs. 42.32 years; P = 0.01), mental disorders (15.6% vs. 6.1%; P = 0.01), poisoning severity score (2.36 vs. 2.57; P = 0.03), organ failure (10.9% vs. 23.5%; P = 0.02), and mechanical ventilation (18.8% vs. 33.3%; P = 0.02). Patients who refused HP exhibited a higher mortality (20.3% vs. 10.9%; P = 0.03) compared to those who received HP. Age (odds ratio (OR), 1.76; 95% confidence interval (CI): 1.01-3.82; P = 0.01) and history of mental disorders (OR, 2.81; 95% CI: 1.19-6.61; P = 0.02) were identified as significant independent predictors for the refusal of HP. The results of this study showed that elderly individuals and those with a history of mental disorders were independently associated with refusing HP in patients with acute paraquat poisoning.

A hospital management algorithm for acute poisoning by Paraquat® in a pediatric population, a series of cases

Paraquat®, or N,N′-dimethyl-4,4′-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of patients with acute paraquat poisoning

This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective observational cohort study included 724 patients with acute paraquat poisoning whose clinical data were collected within 24 h of admission. The primary outcome was in-hospital mortality. Patients were randomly divided into training and validation cohorts (7/3 ratio). In the training cohort, the least absolute shrinkage and selection operator regression models were used for data dimension reduction and feature selection. Multivariate logistic regression was used to generate a predictive nomogram for in-hospital mortality. The prediction model was assessed for both the training and validation cohorts. In the training cohort, decreased level of consciousness (Glasgow Coma Scale score < 15), neutrophil-to-lymphocyte ratio, alanine aminotransferase, creatinine, carbon dioxide combining power, and paraquat plasma concentrations at admission were identified as independent predictors of in-hospital mortality in patients with acute paraquat poisoning. The calibration curves, decision curve analysis, and clinical impact curves indicated that the model had a good predictive performance. It can be used on admission to the emergency department to predict mortality and facilitate early risk stratification and actionable measures in clinical practice after further external validation.

A Meta-analysis of the predictive value of peripheral blood neutrophil to lymphocyte ratio in mortality of patients with acute paraquat poisoning

Objective: To evaluate the predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) in mortality of patients with acute paraquat poisoning. Methods: In March 2022, all literatures about the studies on NLR assessing the mortality of patients with acute paraquat poisoning were searched in the National Library of Medicine PubMed, Embase, Cochrane Library Database, Web of Science, CNKI, Wanfang Medicine Database, Weipu Database, China Biology Medicine disc (SinoMed). The data updated by March 2022, without the limitation of languages. Two researchers extracted literature information independently and conducted literature quality evaluation using QUADAS-2. And the data extracted from the literatures were analyzed with Stata 16 software. Results: A total of 9 studies were included in this Meta-analysis, including 967 patients. And the Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.77 (95%CI: 0.72-0.82, P<0.05), 0.83 (95%CI: 0.74-0.90, P<0.05), 4.63 (95%CI: 2.99-7.15, P<0.05), 0.27 (95%CI: 0.22-0.34, P<0.05) and 17.06 (95%CI: 10.22-28.48, P<0.05), and the area under the curve (AUC) of the summary receiver operator characteristics curve (SROC) was 0.85 (95%CI: 0.81-0.88) . Conclusion: NLR has predictive value in 30-day mortality of patients with acute paraquat poisoning.

A Forensic Case of Suicide Ingestion of Paraquat Herbicide: New Histological Insights and Revision of the Literature.

Paraquat (PQ) is one of the most widely used herbicides in the world, and poisoning is generally associated with accidental, suicidal, or homicidal events. Therefore, in the forensic context, PQ could be in various ways involved as a possible cause of death of a subject. However, even though its systemic toxicity is known, the biological effects exerted on individual viscera have been explored only to some extent, especially in case of victim's survival. Therefore, a case concerning a suicidal ingestion of PQ with survival of 3 days was deemed of interest. Clinical toxicological analyses confirmed acute PQ intoxication, and after the death of the victim, an autopsy was performed showing local and systemic signs of ingestion of a caustic substance. Histologic examination revealed marked cellular damage to the major viscera, particularly the gastroesophageal tract, liver, kidneys, and lungs, with initial alveolar fibrosis noted despite the patient's short survival. This finding represents a new element in the context of PQ lung injury, as it has not been previously documented in the literature. Thus, histological findings in lethal intoxications after survival can reveal specific peculiarities still unknown and, therefore, assume transversal relevance not only at forensic but also clinical level.

Prognostic Value of the Average Lung CT Number in Patients with Acute Paraquat Poisoning.

The chest computed tomography (CT) examination is an important clinical examination in the diagnosis and monitoring of paraquat- (PQ-) induced lung injury. The aim of this study was to explore the prognostic value of the average lung CT number acquired by quantitative CT techniques in patients with acute paraquat poisoning in the early stages of the disease. 46 patients who suffered from acute PQ poisoning in the emergency department of the Nanjing Drum Tower Hospital from January 2015 to June 2020 were enrolled in the present study. The patients were divided into survival group (n = 21) and nonsurvival group (n = 25). Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. The average lung CT numbers of each patient were obtained by quantitative CT techniques. Receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of average lung CT number in patients with acute paraquat poisoning. The average CT numbers of the middle-lung, lower-lung, and whole lung fields in the nonsurvival group were significantly higher than those of the survival group (p < 0.0001). However, the upper-lung field was not significantly different between the two groups (p = 0.7765). The AUCs of different levels ranged from 0.554 to 0.977, among which the lower-lung field presented the largest AUC of 0.977 (95% CI: 0.943∼1; cut-off value: -702Hu; sensitivity 96%; specificity, 90.5%; YI: 0.865), followed by the whole lung field 0.914 (95% CI: 0.830∼0.999; cut-off value: -727Hu; sensitivity 76%; specificity, 95.2%; YI: 0.712) and the middle-lung field 0.87 (95% CI: 0.768∼0.971; cut-off value: -779Hu; sensitivity 80%; specificity, 85.7%; YI: 0.657). The present study indicated that the average lung CT number could be used to evaluate the relationship between the severity of PQ-induced lung injury and prognosis, especially in the lower-lung field. However, further research is needed to draw a clear conclusion.

The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction.

Acute lung injury (ALI) is the primary cause of death among patients with acute paraquat (PQ) poisoning, whereby peroxidative damage is an important mechanism underlying PQ-induced lung injury. There is a lack of effective interventional drugs for patients with PQ poisoning. Oxaloacetic acid (OAA) participates in multiple in vivo metabolic processes, whereby it facilitates the clearance of reactive oxygen species (ROS) and improves mitochondrial function. The study aimed to assess the protective effects of OAA on PQ-induced ALI and elucidate the underlying molecular mechanism. Our data demonstrated that OAA treatment significantly alleviated PQ-induced ALI and improved the survival rate of PQ-poisoned mice, and also alleviated PQ-induced cellular oxidative stress and mitochondrial dysfunction. OAA-mediated alleviation of PQ-induced mitochondrial dysfunction depends on the following mechanisms which may explain the above findings: 1) OAA effectively cleared intracellular ROS, inhibited ROS accumulation, and mitochondrial depolarization; 2) OAA inhibited the downregulation of L-OPA1 and MFN2 caused by PQ and promoted a dynamic balance of mitochondrial fusion and fission, and 3) the expression of PGC-1α, TFAM, COX2, and COX4I1, increased significantly following OAA intervention which improved mitochondrial respiratory functions and promoted its biogenesis and energy metabolism in damaged cells. In conclusion, OAA effectively cleared ROS and improved mitochondrial dysfunction, thereby significantly improving ALI caused by PQ poisoning and the animal survival rate. Therefore, OAA may be a potential drug for the treatment of PQ poisoning.

Risk factors and optimal predictive scoring system of mortality for children with acute paraquat poisoning

BACKGROUNDThere is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication (APP).AIMTo optimize a predictive scoring system for mortality in children with APP.METHODSA total of 113 children with APP from January 1, 2010 to January 1, 2020 were enrolled in this study. These patients were divided into survivors and non-survivors. We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors. The survival rates of patients with different values of the pediatric critical illness score (PCIS) were assessed using kaplan-meier survival analysis. The best scoring system was established by using the area under the receiver operating characteristic curve analysis.RESULTSThe overall mortality rate was 23.4%. All non-survivors died within 20 days; 48.1% (13/27) died within 3 days, and 70.3% (19/27) died within 7 days. Compared to survivors, the non-survivors were older, had higher white blood cell count, alanine aminotransferase (ALT), aspartate aminotransferase, serum creatinine, blood urea nitrogen, glucose, and pediatric early warning score, and had lower platelet count, albumin, Serum sodium (Na+) and PCIS. ALT and PCIS were the independent prognostic risk factors for children with APP. The survival rate of children classified as extremely critical patients (100%) was lower than that of children classified as critical (60%) or noncritical (6.7%) patients. The specificity of ALT was high (96.51%), but the sensitivity was low (59.26%). The sensitivity and specificity of ALT combined with PCIS were high, 92.59% and 87.21%, respectively. The difference in mortality was significantly higher for ALT combined with PCIS (area under the receiver operating characteristic: 0.937; 95%CI: 0.875-0.974; P < 0.05).CONCLUSIONIn our study, ALT and PCIS were independent prognostic risk factors for children with APP. ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP.

Plasma Concentration After the First Hemoperfusion has a High Predictive Value in Medium Level Acute Paraquat-Poisoned Patients.

Paraquat ( PQ) is very poisonous to humans and animals and there is no effective clinical antidote . The efficacy of hemoperfusion (HP) treatment for PQ poisoning remains controversial. To explore new ways to predict the prognosis of patients with acute PQ poisoning and assist in the development of better hemopurification treatment strategies. The clinical data of patients who were intoxicated with PQ through contact were diagnosed with PQ poisoning by high-performance liquid chromatography. Samples were collected by the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from January 2012 to November 2016. Based on the prognosis, the patients were grouped into survival and death groups. Comparisons of the differences in the clinical indexes were performed, including the initial concentration of PQ at admission, PQ concentration after first HP, the number of HP cartridges used for the first hemoperfusion, whether HP was combined with continuous renal replacement therapy, and the number of concurrent organ injuries between the 2 groups. In addition, data were analyzed using multivariate logistic regression models and receiver operating characteristic curves. Moreover, prognostic factors in patients with acute PQ poisoning were analyzed. Overall, 128 patients with acute PQ poisoning were enrolled in this study. The median plasma PQ concentrations of the patients at admission were 21 and 834 ng/mL (range: 50-1,099,118 ng/mL). The multiple logistic regression model revealed that the initial concentration of PQ and the PQ concentration after the first perfusion were independent risk factors for death in patients with acute PQ poisoning. The PQ concentration in the survival group after the first HP was <516 ng/mL and was mainly distributed at approximately 100 ng/mL. The percentage of patients whose concentration after the first HP was <516 ng/mL in the death group was only 19%. The initial plasma PQ concentration after admission and PQ concentration after the first HP are risk factors for death in patients with acute PQ poisoning. Moreover, PQ concentration after the first HP had a high predictive value for death. When the initial plasma PQ concentration after admission ranges from 50 ng/mL to 5000 ng/mL, the rapid reduction in plasma PQ concentration after HP treatment could improve the prognosis of patients with acute PQ poisoning.

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.

The acute paraquat poisoning mortality (APPM) score to predict the risk of death in paraquat-poisoned patients

Context Mortality prediction in paraquat poisoning is a major issue since most prediction rules are inapplicable if the exact ingestion time cannot be determined and/or the serum paraquat concentration is not readily available, as in most countries. Therefore, we aimed to develop and validate a new prediction rule not requiring these two parameters. Methods We designed a 10-year observational cohort study including all consecutive paraquat-poisoned patients managed in two Taiwanese hospitals. We built one cohort to define and one cohort to validate this prediction rule. Parameters independently related to mortality determined using a multivariate analysis were used to formulate the Acute Paraquat Poisoning Mortality (APPM) score. Results Overall, 321 paraquat-poisoned patients were included, 156 in the derivation and 165 in the validation cohort. Mortality rates in the derivation and validation cohorts were 73% and 81%, respectively (p = 0.20). The three parameters chosen of 28-day mortality at presentation were urine paraquat level >10 ppm (using a colorimetric sodium dithionite-based test; odds ratio (OR), 12.70; 95% confidence interval (CI), 2.64–61.24), white blood cells >13.0 G/L (OR, 5.50; CI, 1.41–21.48) and blood glucose >140 mg/dL [7.8 mmol/L] (OR, 7.45; CI, 1.70–32.86). In the derivation cohort, the area under the ROC curve (AUC-ROC) of the APPM score did not significantly differ from AUC-ROCs of serum paraquat (0.95, p = 0.25) and the Severity Index of Paraquat Poisoning (0.95, p = 0.33). AUC-ROCs of the APPM score in the derivation and validation cohorts were 0.91 and 0.94, respectively. Conclusion We built and validated a reliable score to predict 28-day mortality in paraquat-poisoned patients at presentation, independently from the ingestion time and serum paraquat measurement.

Alveolar-arterial partial pressure difference as an early predictor for patients with acute paraquat poisoning.

ObjectiveParaquat (PQ) is associated with high mortality rates in acute poisoning. This study aimed to determine the importance of the alveolar–arterial partial pressure difference (A-aDo2) in the expected consequences of acute PQ poisoning.MethodsPatients who were hospitalized for PQ poisoning in 2018 were enrolled in this retrospective study. A-aDo2 data were collected. Multivariate analysis was performed using binary logistic regression to determine whether A-aDo2 is an independent risk factor for mortality from PQ.ResultsA total of 352 cases were analyzed. The mean PQ dose was 36.84 ± 50.30 mL (0.3–500 mL). There were 185 survivors and 167 non-survivors. The mean A-aDo2 was not significantly correlated between survivors and non-survivors on day 1. However, there were significant differences in A-aDo2 between survivors and non-survivors on days 3, 7, 14, and 21. Increased A-aDo2 values were correlated with an increased mortality rate. The mean A-aDo2 on day 14 showed the most significant difference between survivors and non-survivors.ConclusionOur study suggests that A-aDo2 plays an important role as a reference index, which could be a useful predictor in assessing acute PQ poisoning, especially on the 14th day after onset of poisoning.

Bacopaside-I Alleviates the Detrimental Effects of Acute Paraquat Intoxication in the Adult Zebrafish Brain

Paraquat (PQ), an environmental neurotoxicant, causes acute fatal poisoning upon accidental or intentional ingestion (suicidal cases) worldwide. To date, an effective remedy for PQ toxicity is not available. In this study, we have evaluated the therapeutic efficacy of Bacopaside-I (BS-I), an active compound found in the plant extract of Bacopa monnieri (Brahmi), against acute PQ intoxication using zebrafish as a model organism. Adult zebrafish were injected with a dose of either 30mg/kg or 50mg/kg PQ. PQ-intoxicated zebrafish showed an increased rate of mortality and oxidative imbalance in their brain. Also, the proliferation of neural cells in the adult zebrafish brain was inhibited. However, when BS-I pretreated zebrafish were intoxicated with PQ, the toxic effects of PQ were ameliorated. PQ treatment also affected the expression of particular genes concerned with the apoptosis and dopamine signaling, which was not altered by BS-I administration. Our results highlight the efficiency of BS-I as a novel therapeutic agent for PQ intoxication. It further compels us to search and evaluate the molecular mechanisms targeted by BS-I to develop a potent therapy for acute PQ intoxication.

Clinical research of the differences between hematocrit and serum albumin for evaluating the severity of acute paraquat poisoning

To investigate the clinical values of the differences between hematocrit and serum albumin (HCT-ALB) for evaluating the severity of patients with acute paraquat (PQ) poisoning. Patients with acute PQ poisoning admitted to the Second People's Hospital of Yunnan Province from January 2018 to December 2019 were enrolled, and healthy voluteers during the same period were selected as the control. The general information, poisoning dose and poisoning time of patients, as well as the HCT and serum ALB levels before blood product infusion, intravenous infusion, or hemopurification at admission were collected, and the HCT-ALB was calculated. According to the results of rapid semiquantitative test of PQ in urine at admission, the patients were divided into PQ low concentration group (0-10 mg/L) and PQ high concentration group (30-100 mg/L). The relationship between poisoning time, poisoning dose, HCT-ALB and the degree of acute PQ poisoning were analyzed, and Spearman method was used to analyze the grade correlation. A total of 295 patients with acute PQ poisoning were enrolled, including 118 cases in PQ low concentration group and 177 cases in PQ high concentration group, and another 200 healthy persons matched with PQ patients in gender and age (healthy control group). The poisoning time of PQ low concentration group was significantly longer than that of PQ high concentration group [hours: 11.0 (6.0, 60.0) vs. 8.0 (5.0, 20.5), P < 0.01], but the poisoning dose was significantly lower than that of PQ high concentration group [mL: 10.0 (5.8, 15.0) vs. 40.0 (20.0, 80.0), P < 0.01]. The HCT and HCT-ALB in PQ low and high concentration groups were significantly higher than those of the healthy control group [HCT: (43.14±4.41)%, (43.54±5.40)% vs. (42.14±2.15)%, HCT-ALB: 3.59±6.26, 5.94±7.80 vs. -7.26±3.55, all P < 0.01], but ALB was significantly lower than that of the healthy control group (g/L: 39.54±5.74, 37.60±7.15 vs. 49.40±3.41, both P < 0.01). With the increase of urine PQ concentration, the HCT and HCT-ALB further increased, and ALB further decreased. There were significant differences between PQ high concentration group and PQ low concentration group [HCT: (43.54±5.40)% vs. (43.14±4.41)%, HCT-ALB: 5.94±7.80 vs. 3.59±6.26, ALB (g/L): 37.60±7.15 vs. 39.54±5.74, all P < 0.05]. The poisoning severity of patients with acute PQ poisoning were negatively correlated with poisoning time and ALB (r values were -0.195 and -0.695, respectively, both P < 0.01), there were positively correlated with poisoning dose, HCT, and HCT-ALB (r values were 0.650, 0.256, 0.737, respectively, all P < 0.01), and the correlation between HCT-ALB and poisoning severity was the strongest. The HCT-ALB can reflect the poisoning severity of patients with acute PQ poisoning and indirectly reveal the pathological changes of microvessels in patients with acute PQ poisoning.

Hemodynamic and electromechanical effects of paraquat in rat heart.

Paraquat (PQ) is a highly lethal herbicide. Ingestion of large quantities of PQ usually results in cardiovascular collapse and eventual mortality. Recent pieces of evidence indicate possible involvement of oxidative stress- and inflammation-related factors in PQ-induced cardiac toxicity. However, little information exists on the relationship between hemodynamic and cardiac electromechanical effects involved in acute PQ poisoning. The present study investigated the effects of acute PQ exposure on hemodynamics and electrocardiogram (ECG) in vivo, left ventricular (LV) pressure in isolated hearts, as well as contractile and intracellular Ca2+ properties and ionic currents in ventricular myocytes in a rat model. In anesthetized rats, intravenous PQ administration (100 or 180 mg/kg) induced dose-dependent decreases in heart rate, blood pressure, and cardiac contractility (LV +dP/dtmax). Furthermore, PQ administration prolonged the PR, QRS, QT, and rate-corrected QT (QTc) intervals. In Langendorff-perfused isolated hearts, PQ (33 or 60 μM) decreased LV pressure and contractility (LV +dP/dtmax). PQ (10-60 μM) reduced the amplitudes of Ca2+ transients and fractional cell shortening in a concentration-dependent manner in isolated ventricular myocytes. Moreover, whole-cell patch-clamp experiments demonstrated that PQ decreased the current amplitude and availability of the transient outward K+ channel (Ito) and altered its gating kinetics. These results suggest that PQ-induced cardiotoxicity results mainly from diminished Ca2+ transients and inhibited K+ channels in cardiomyocytes, which lead to LV contractile force suppression and QTc interval prolongation. These findings should provide novel cues to understand PQ-induced cardiac suppression and electrical disturbances and may aid in the development of new treatment modalities.

Development and Validation of a Radiomics Nomogram for Prognosis Prediction of Patients with Acute Paraquat Poisoning: A Retrospective Cohort Study.

Objective To evaluate the efficiency of a radiomics model in predicting the prognosis of patients with acute paraquat poisoning (APP). Materials and Methods Chest computed tomography images and clinical data of 80 patients with APP were obtained from November 2014 to October 2017, which were randomly assigned to a primary group and a validation group by a ratio of 7 : 3, and then the radiomics features were extracted from the whole lung. Principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) regression were used to select the features and establish the radiomics signature (Rad-score). Multivariate logistic regression analysis was used to establish a radiomics prediction model incorporating the Rad-score and clinical risk factors; the model was represented by nomogram. The performance of the nomogram was confirmed by its discrimination and calibration. Result The area under the ROC curve of operation was 0.942 and 0.865, respectively, in the primary and validation datasets. The sensitivity and specificity were 0.864 and 0.914 and 0.778 and 0.929, and the prediction accuracy rates were 89.5% and 87%, respectively. Predictors included in the individualized predictive nomograms include the Rad-score, blood paraquat concentration, creatine kinase, and serum creatinine. The AUC of the nomogram was 0.973 and 0.944 in the primary and validation datasets, and the sensitivity and specificity were 0.943 and 0.955, respectively, in the primary dataset and 0.889 and 0.929 in the validation dataset, and the prediction accuracy was 94.7% and 91.3%, respectively. Conclusion The radiomics nomogram incorporates the radiomics signature and hematological laboratory data, which can be conveniently used to facilitate the individualized prediction of the prognosis of APP patients.

A novel simple risk model to predict the prognosis of patients with paraquat poisoning

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.

Identify the Early Predictor of Mortality in Patients with Acute Paraquat Poisoning.

Background Paraquat is a widely used nonselective and fast-acting contact herbicide worldwide. This study identified the early predictor of mortality in patients with acute paraquat poisoning. Methods Twenty-nine patients with acute paraquat poisoning admitted at Nanjing Drum Tower Hospital from January 2018 to August 2020 were included in this study. The early predictor of mortality in patients with acute paraquat poisoning based on the blood tests was identified by correlation, logistic regression, and receiver operating characteristic (ROC) analyses. Result 15 of the 29 patients died after poisoning. Compared to the survivors, the neutrophilic granulocyte ratio, leukocyte count, ALB, and Crea of the nonsurvivors were significantly higher with p value < 0.05, while the lymphocyte ratio and eGFR(MDRD) of the nonsurvivors were remarkably lower with p value < 0.01. Moreover, the neutrophil-to-lymphocyte ratio (NLR) was remarkably upregulated in the nonsurvivors. The area under the ROC curve (AUC) of the neutrophilic granulocyte ratio, lymphocyte ratio, leukocyte count, ALB, Crea, eGFR(MDRD), and NLR to predict the mortality in patients with acute paraquat poisoning was 0.8905 (95% CI: 0.7589-1.022), 0.8643 (95% CI: 0.7244-1.004), 0.8500 (95% CI: 0.7133-0.9867), 0.7286 (95% CI: 0.5338-0.9233), 0.8167 (95% CI: 0.6620-0.9713), 0.8714 (95% CI: 0.7330-1.010), and 0.8667 (95% CI: 0.7277-1.006), respectively. More interestingly, we also evaluated the diagnostic values of the different combinations of six blood test biomarkers by logistic regression analysis. According to the results of the logistic regression analysis, the AUCs for the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) were the largest with 0.986 (95% CI: 0.952-1), and the sensitivity and specificity were 100% and 100%. Conclusion This study demonstrated that the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) could serve as an ideal early predictor of mortality in patients with acute paraquat poisoning. However, further research is needed to draw a clear conclusion.

Does Hemoperfusion Increase Survival in Acute Paraquat Poisoning? A Retrospective Multicenter Study.

The efficacy of hemoperfusion (HP) in patients with acute paraquat poisoning (PQ) remains controversial. We conducted a multi-center retrospective study to include acute PQ-poisoned patients admitted to two tertiary medical centers between 2005 and 2015. We used the Severity Index of Paraquat Poisoning (SIPP) to stratify the severity of PQ-poisoned patients. The indication to start HP was a positive result for the semiquantitative urine PQ test and presentation to the hospital was within 24 h. Early HP was defined as the first session of HP performed within five hours of PQ ingestion. A total of 213 patients (100 HP group, 113 non-HP group) were eligible for the study. The overall 60-day mortality of poisoned patients was 75.6% (161/213). Multivariate Cox regression analysis showed no statistically significant difference in 60-day survival between HP and non-HP groups (95% confidence interval (CI): 0.84–1.63, p = 0.363). Further subgroup analysis in the HP group showed early HP (95% CI: 0.54–1.69, p = 0.880), and multiple secessions of HP (95% CI: 0.56–1.07, p = 0.124) were not significantly related to better survival. Among acute PQ-poisoned patients, this study found that HP was not associated with increased 60-day survival. Furthermore, neither early HP nor multiple secessions of HP were associated with survival.