Plasma Paraquat Concentration Research Articles

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.

Dose ingested, vomiting, and outcome in patients ingesting a standard paraquat 20SL formulation

Background FAO specifications for liquid paraquat dichloride SL formulations require the use of an emetic agent to stimulate vomiting within 30 min of ingestion. To date, there is no high-quality evidence of efficacy, despite use of the PP796 emetic since 1979. We first examined the validity of patients’ self-reported dose of paraquat ingested by examining the relationship with blood paraquat concentration and time to death for patients ingesting the standard paraquat SL formulation in a Sri Lankan cohort. As a secondary outcome, we assessed whether ingestion resulted in vomiting within 30 min and whether vomiting was associated with good outcome. Methods Patients presenting with paraquat SL self-poisoning were prospectively studied in ten Sri Lankan hospitals in 2003–08. Data on reported dose ingested, incidence and timing of vomiting after ingestion, treatment received, plasma paraquat concentration, and outcome were collected prospectively on presentation to hospital. Time between ingestion and blood sampling was incorporated by covariate adjustment. Results 441 patients were recruited to the case series, presenting a median (IQR) of 3.0 (1.5–8.1] h post ingestion. Outcome was known for 435 patients of whom 322 (74.0%) died within 42 days, a median of 1.3 (0.6–4.4) days post ingestion. Median reported dose ingested was 15 to <30 mL. There was a highly significant linear trend between log plasma paraquat and reported dose ingested (p < .001); adjustment for the log of the time from ingestion to sampling further improved the model fit. Case fatality and median time to death also showed good agreement with estimated ingestion amount. 347/438 patients (79.2%) were stated to have vomited before reaching the study hospital with 300 (68.5%) vomiting within 30 min of ingestion; time to vomiting was unknown for a further 12 (2.7%). The proportion vomiting was strongly associated with reported dose ingested (p < .001); of note the proportion vomiting within 30 min only increased to 83.3% for the highest ingestion group. Patients vomiting within 30 min had higher plasma paraquat concentrations (p = .008), and higher hazard ratio in the adjusted Cox regression model of 2.01 (95% CI 1.45–2.77) compared to those who did not. Vomiting within 30 min was associated with a higher case fatality (241/295 [81.7%] vs 68/125 [54.4%], p < .001). Forty-three (47.3%) of the 91 patients who did not vomit before reaching hospital died (one had unknown outcome). Conclusion Importantly, we found good agreement between reported dose ingested and plasma paraquat concentration, case fatality, and time to death, suggesting that the reported dose is a valid marker for the dose ingested. Vomiting occurred within 30 min for 68.5% of patients, exceeding the characteristics for a purported effective emetic in the FAO specifications. However, vomiting within 30 min was associated with approximately double the risk of death compared to those who did not vomit, larger paraquat ingestions, and higher blood paraquat concentrations. In addition, death occurred in many patients who did not vomit, and the proportion vomiting within 30 min only reached 82.1% for the highest ingested dose group. Overall, we found no evidence of benefit resulting from incorporation of the emetic, suggesting that the current FAO specification is not effective at preventing deaths after ingestion of the paraquat SL formulation.

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.

Evaluation of gastric lavage efficiency and utility using a rapid quantitative method in a swine paraquat poisoning model.

Gastric lavage (GL) is one of the most critical early therapies for acute paraquat (PQ) poisoning; however, details of the treatment protocol remain to be established. A rapid quantitative method involving sodium dithionite testing was developed. It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL, or without. The vital signs, laboratory testing, and PQ plasma concentrations were collected for therapeutic effect evaluation. The reaction conditions of the test were optimized for two types of samples. Early GL at one hour (H1) could improve the signs and symptoms after acute PQ poisoning at 24 hours (H24). In contrast, GL at 6 hours (H6) could only partially relieve the vital signs. The H1 GL group effectively reduced the peak of the plasma PQ concentration. In addition, the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24. Moreover, there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups. However, the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate. GL only at early stage may it benefit PQ poisoning in an animal model. The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate. The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.

Metabolomics Analysis in Acute Paraquat Poisoning Patients Based on UPLC-Q-TOF-MS and Machine Learning Approach.

Most paraquat (PQ) poisoned patients died from acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects. The initial PQ plasma concentrations of PQ poisoned patients were >1000 ng/mL, and the blood samples were collected at before first hemoperfusion (HP), after first HP, and after last HP. The results showed that PQ poisoned patients all differed from healthy subjects, whatever they were before or after first HP or after last HP. The efficient machine learning approaches selected key metabolites from three UPLC/Q-TOF-MS data sets which had the highest classification performance in terms of classification accuracy, Matthews Correlation Coefficients, sensitivity, and specificity, respectively. The mass identification revealed that the most important metabolite was adenosine, which sustained in low level, regardless of whether PQ poisoned patients received HP treatment. In conclusion, decreased adenosine was the most important metabolite in PQ poisoned patients. The metabolic disturbance caused by PQ poisoning cannot be improved by HP treatment even the PQ was cleared from the blood.

Increased 90-Day Mortality in Spontaneously Breathing Patients With Paraquat Poisoning: In Addition to Disease Severity, Lung Strain May Play a Role.

1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. Prospective study. A university hospital ICU. One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. A standardized treatment protocol. Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021-3.296; p < 0.001) was most strongly associated with mortality, such that neither blood paraquat concentration nor PaO2 provided any additional prognostic information. The ratio of residual volume to total lung capacity as a percentage of the predicted value (adjusted hazard ratio, 1.041; 95% CI, 1.026-1.057; p < 0.001) was the only variable that added prognostic value to Exp(%Wpoor/15). While controlling for Exp(%Wpoor/15) and percentage of predicted residual volume/total lung capacity, increases in dynamic strain (adjusted hazard ratio, 2.041/0.1 U; 95% CI, 1.283-3.248; p = 0.003) and/or decreases in respiratory system reactance at 5 Hz (adjusted hazard ratio, 1.19/0.1 U; 95% CI, 1.03-1.386; p = 0.02) were independently associated with increased 90-day mortality. In patients with paraquat poisoning, Exp(%Wpoor/15) and percentage of residual volume/total lung capacity are independent prognostic indicators. Higher dynamic strain and increased ventilation heterogeneity during unassisted spontaneous breathing were associated with worsened survival independent of Exp(%Wpoor/15) and percentage of residual volume/total lung capacity.

A retrospective analysis of leucocyte count as a strong predictor of survival for patients with acute paraquat poisoning.

The aim of this study is the identification of a reliable predictor of prognosis to optimize the treatment of acute paraquat (PQ) poisoning patients. We performed a retrospective analysis on 96 patients with acute PQ poisoning to evaluate leucocyte count as a predictor of 90-day survival. These patients were admitted to the emergency department from May 2012 to February 2017. Kaplan–Meier method was used to compare the 90-day survival. Cox proportional hazard models were utilized to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Receiver operating characteristic (ROC) analysis was conducted to analyze the discriminatory potential of leucocyte with respect to 90-day survival. Result showed that leucocyte was significantly higher among nonsurvivors than that among survivors (p<0.001). Leukocyte was also an independent predictor of survival according to the multivariate Cox analysis (HR 1.103; 95%CI: 1.062–1.146; p<0.001). The area under the curve (AUC) for leucocyte (AUC 0.911; 95%CI: 0.855–0.966; p<0.001) showed a discriminatory potential similar to that of the plasma PQ concentration (AUC 0.961; 95%CI: 0.926–0.997; p<0.001) in predicting 90-day survival. The leucocyte count is a strong predictor of survival in patients with acute PQ poisoning.

Effect of activated charcoal hemoperfusion on renal function in patients with paraquat poisoning.

The present study retrospectively analyzed 19 patients diagnosed with paraquat (PQ) poisoning with the aim to investigate the effect of activated charcoal hemoperfusion on renal function and PQ elimination. The results indicated that 7 patients died and 12 survived. Non-oliguric renal failure occurred in all of the 7 patients who died. Among the 12 surviving patients, 10 had normal renal function and 2 developed non-oliguric renal failure. There was a linear correlation between plasma and urine paraquat concentration prior to and during activated charcoal hemoperfusion. The equation parameters together with the correlation coefficient on admission were as follows: Y=0.5820+1.7348X (R2=0.678; F=35.768; P<0.0001). The equation parameters together with the correlation coefficient were as follows during activated charcoal hemoperfusion: Y=0.6827+1.2649X (R2=0.626; F=50.308; P<0.0001). Therefore, it was concluded that in patients with normal renal function, the elimination kinetics of PQ by the kidneys were only associated with the plasma PQ concentration. Activated charcoal hemoperfusion had little effect on avoiding acute kidney injury in patients with severe PQ poisoning.

A new machine-learning method to prognosticate paraquat poisoned patients by combining coagulation, liver, and kidney indices.

The prognosis of paraquat (PQ) poisoning is highly correlated to plasma PQ concentration, which has been identified as the most important index in PQ poisoning. This study investigated the predictive value of coagulation, liver, and kidney indices in prognosticating PQ-poisoning patients, when aligned with plasma PQ concentrations. Coagulation, liver, and kidney indices were first analyzed by variance analysis, receiver operating characteristic curves, and Fisher discriminant analysis. Then, a new, intelligent, machine learning-based system was established to effectively provide prognostic analysis of PQ-poisoning patients based on a combination of the aforementioned indices. In the proposed system, an enhanced extreme learning machine wrapped with a grey wolf-optimization strategy was developed to predict the risk status from a pool of 103 patients (56 males and 47 females); of these, 52 subjects were deceased and 51 alive. The proposed method was rigorously evaluated against this real-life dataset, in terms of accuracy, Matthews correlation coefficients, sensitivity, and specificity. Additionally, the feature selection was investigated to identify correlating factors for risk status. The results demonstrated that there were significant differences in the coagulation, liver, and kidney indices between deceased and surviving subjects (p<0.05). Aspartate aminotransferase, prothrombin time, prothrombin activity, total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, urea nitrogen, and creatinine were the most highly correlated indices in PQ poisoning and showed statistical significance (p<0.05) in predicting PQ-poisoning prognoses. According to the feature selection, the most important correlated indices were found to be associated with aspartate aminotransferase, the aspartate aminotransferase to alanine ratio, creatinine, prothrombin time, and prothrombin activity. The method proposed here showed excellent results that were better than that produced based on blood-PQ concentration alone. These promising results indicated that the combination of these indices can provide a new avenue for prognosticating the outcome of PQ poisoning.

Elimination effect of haemoperfusion on different initial level of plasma paraquat concentration in vivo and in vitro

Elimination effect of haemoperfusion on different initial level of plasma paraquat concentration in vivo and in vitro

Value of base excess in predicting the prognosis of patients with paraquat poisoning

Objective: To explore prognostic factors of acute paraquat poisoning (APP) , analyze the correlation between base excess (BE) and plasma concentration of paraquat (C-PQ) and discuss BE level in evalua-tion of prognosis of acute paraquat poisoning patients. Methods: We retrospectively selected 84 APP patients who admitted to Emergency Intensive Care Unit (EICU) of our hospital from 2009.9.1 to 2015.8.31.Clinical data from 84 APP patients were analyzed. BE、C-PQ、time of gastric lavagesince ingestion、time of hemoperfusion since ingestion、severity index of paraquat poisoning (SIPP) 、white blood cell (WBC) 、percentage of neutrophils (N%) 、hemoglobin (HB) 、creatinine (Cr) 、alanine aminotransferase (ALT) 、aspartate aminotransferase (AST) 、partial pressure of oxygen (PaO(2)) 、partial pressure of carbon dioxide (PaCO(2)) and other laboratory parameters were measured. A total of 41 patients in non-survivors died during the 30 days after admission and 43 patients in survivors survived during the 30 days. The factors of prognosis in paraquat poisoining and the role of BE in evalu-ating prognosis was analyzed, as well as the correlation between BE and C-PQ. Results: 1.Logistic regression analyses showed BE、C-PQ、ALT、AST、Cr was of prognostic significance[odds ratio (OR) of BE: 0.511, 95%CI 0.267, 0.978; C-PQ:-=0.999, 95%CI 0.999, 1.000; both P<0.05] ; 2.The area under the receiver operating characteristic curve (ROC curve) of BE、C-PQ and prognosis were 0.775、0.927 respectively, BE≤-1.7 mmol/L was the best cut-off value, the sensitivity、specificity for predicting were 82.9%、62.8%, the evaluation value was lower to C-PQ>3 273.935 ng/ml (AUC 0.927, 78.0%、95.3%) ; 3.BE negative correlated with C-PQ[-1.100 (-4.100, -0.200) , -5.900(-8.650, -2.500) , both P<0.05]. (r=-0.4, P<0.01). Conclusion: These results suggest that BE may be useful for the prediction of prognosis in PQ poisoning and BE negative correlated with C-PQ.

Elimination effects of gastric lavage in swine model of paraquat poisoning

Objective To evaluate the elimination effect of gastric lavage (GL) in the swine model of paraquat (PQ) poisoning by using the determination of PQ plasma concentration. Methods A total of 17 healthy female domestic swine were randomly divided into PQ group (n=6), PQ+ 1 h GL group (n=6) and PQ+ 6 h GL group (n=5). A dose of 60 mg /kg PQ in 40% PQ solution was administered in all animals through gastric tube. Swine of PQ+ 1 h GL group and PQ+ 6 h GL group were treated with gastric lavage by using 20 L warm water at 1 h and 6 h after ingestion of PQ, respectively. Vital signs and PQ plasma concentration were monitored continuously for 24 h. LC-MS device was used to measure the PQ concentrations in lavage fluid and plasma, and HPLC was performed to measure the fluid drug concentration. Results The 24 h survival rates of PQ group, PQ+ 6 h GL group and PQ+ 1 h GL group were 66.7%, 80% and 100%, respectively. The peak plasma PQ concentration in PQ group was (5.12±3.38)μg/mL, in PQ+ 6 h GL group was (3.99±1.24)μg/mL, and in PQ+ 1 h GL group was (1.96±1.83)μg/mL. The percentage of the total amount of PQ ingested in the gastric lavage fluid in PQ+ 1 h GL group was (24.46±6.49)% and in PQ+ 6 h GL group was (30.72±9.86)% (P>0.05). Alternatively, the gastric lavage process was divided into two successive procedures with 10 L warm water in each instead of 20 L water in one procedure . The content of PQ in lavage fluid from the first 10 L warm water was (20.44±5.59)% and that from the second 10 L warm water was (4.02±1.82)% in PQ+ 1 h GL group (P<0.01), whereas (26.17±7.19)% PQ in gastric lavage fluid from the first 10 L warm water and (7.03±4.29)% PQ in gastric lavage fluid from the second 10 L warm water, in PQ+ 6 h GL group (P<0.01). Conclusions Gastric lavage process carried out in two successive procedures with 10 L warm water in each can eliminate PQ effectively, thus reducing the mortality. The early gastric lavage (1 h) can cause significantly decrease in plasma PQ peak concentration. However, the clearance rate of gastric lavage process is significantly lower in the second procedure in comparison with the first procedure of gastric lavage. Key words: Paraquat; Gastric lavage; Drug concentration; Clearance ratio

Prognosis and survival analysis of paraquat poisoned patients based on improved HPLC-UV method

Paraquat (PQ) has caused deaths of numerous people around the world. In order to assess the lethal plasma concentration, the patients who acquired acute PQ intoxication were analyzed by plasma concentration monitoring. The plasma PQ concentrations were determined by high performance liquid chromatography (HPLC) which used 5-bromopyrimidine as internal standard and trichloroacetic acid-methanol (1:9) as protein precipitant. The liver, kidney and coagulation function were determined by automatic biochemical analyzer. According to plasma PQ concentration, 90 patients were divided into four groups: trace PQ group (<50ng/mL), low PQ group (<1000ng/mL), medium PQ group (1000–5000ng/mL) and high PQ group (>5000ng/mL). The clinical data from the four groups was statistically analyzed. The results showed the developed HPLC methods exhibited a high degree of accuracy and good linearity within 50–25000ng/mL (R=0.9998). The Spearman's correlation analysis showed PQ concentration had a strong relationship to total bilirubin, direct bilirubin, aspartic transaminase, urea nitrogen, prothrombin time, prothrombin activity, and international normalized ratio (P<0.01). The cured or survival PQ poisoned patients among the trace PQ group, the low PQ group, the medium PQ group, and the high PQ group were 19/19 (100%), 19/21 (90.47%), 11/25 (44.0%), and 0/25 (0%) respectively. The mean hospital days were (10.37±8.04), (18.76±12.06), (16.76±14.44), and (4.04±5.41) days respectively. The Cox regression analysis indicated that plasma PQ concentration was highly related to prognosis (P<0.05). In conclusion, no patient presenting with a PQ concentration over 5000ng/mL survived. The plasma PQ level is related to liver, kidney and coagulation function, which can be used as an important clinical index to judge the prognosis of PQ poisoned patients. Chemical compoundsParaquat (PubChem CID: 15938), 5-bromopyrimidine (PubChem CID: 78344), acetonitrile (PubChem CID: 6342), sodium dihydrogen phosphate (PubChem CID: 23672064), sodium heptanesulfonate (PubChem CID: 23672332), methylprednisolone (PubChem CID: 6741), cyclophosphamide (PubChem CID: 2907).

Toxicokinetics of paraquat in Korean patients with acute poisoning.

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1±6.8 h. Cmax and AUCinf were 20.8±25.7 mg/l and 172.5±160.3 h·mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9±61.3 l/kg and 173.4±111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Therapeutic effects of gastric lavage with fuller earth combined with QingyiII catharsis in treatment of oral paraquat poisoning in rabbits

To observe the therapeutic effects of gastric lavage with fuller earth combined with Qingyi II catharsis in treatment of oral paraquat poisoning in rabbits. Thirty healthy adult Japanese white rabbits were randomly divided into five groups: namely control group, model group, gastric lavage group (lavage of 10% fuller earth suspension), catharsis group (Qingyi II catharsis), and combination group (10 minutes after gastric lavage of fuller earth suspension liquid, giving Qingyi II for catharsis), with 6 rabbits in each group. All groups were challenged with paraquat (100 mg/kg) diluted to 5 mL with normal saline by lavage to reproduce the model of acute poisoning, while the control group was given 5 mL of normal saline instead. Each treatment group was treated accordingly at 1 hour after gavages of paraquat, and treatment continued for 3 days. The animal survival rate was observed. Venous blood samples were collected from ear marginal vein to determine the plasma concentration of paraquat by ultraviolet spectrophotometer at 1, 2, 4, 8 and 24 hours after the poisoning. The animals were sacrificed by intravenous air injection on the 8th day after the poisoning, and the right lower lobe of lung was harvested to observe the lung tissue pathological changes with hematoxylin-eosin (HE) staining. (1) Survival rate: the surviving rate of the combination group (6 rabbits) was higher than that of gastric lavage group (5 rabbits), catharsis group (2 rabbits) and model group (0 rabbit) on the 2nd day with statistically significant difference (P < 0.001). The survival rate on the 7th day in combination group (5 rabbits) was higher than that of gastric lavage group (3 rabbits), and catharsis group (0 rabbit ) with statistically significant difference (P = 0.003). (2) Plasma concentrations of paraquat: plasma paraquat concentration in all groups peaked at 2 hours after intoxication, and its levels in the gastric lavage, catharsis and combination groups were significantly lower than that of the model group ( mg/L: 1.830 ± 0.068, 1.890 ± 0.048, 1.800 ± 0.052 vs. 1.960 ± 0.063, all P < 0.01). As the time prolonged, the plasma concentration of paraquat was lowest in combination group than that of gastric lavage group and catharsis group (all P < 0.01). Gastric lavage and catharsis had interaction at 4 hours in combination group [F = 5.194, P = 0.034; the concentrations of paraquat (mg/L) was 0.670 ± 0.057 vs. 1.010 ± 0.018, 1.210 ± 0.052]. (3) Lung histopathology: obvious expansion and hyperemia of the alveolar capillary, widened alveolar septum, a large number of inflammatory cell infiltrations were observed in model group and catharsis group. Lung histopathology was more improved in combination group and gastric lavage group, and it was improved more obviously in combination group than that in gastric lavage group. Early start of gastric lavage with fuller earth combined with Qingyi II catharsis, can reduce the animal plasma concentrations of paraquat in oral paraquat poisoning rabbits. At the same time, it can alleviate the degree of lung injury and significantly improve survival rates compared with the single gastric lavage or catharsis alone. Gastric lavage with fuller earth combined with Qingyi II catharsis can improve the prognosis of animal synergistically.

Intensity of hemoperfusion in acute paraquat-poisoned patients and analysis of prognosis

To evaluate the influence of different hemoperfusion (HP) intensity on 7-day and 28-day mortality for patients with paraquat (PQ) poisoning, and examine the factors that may affect the decision of the clinicians to prescribe a high intensity HP. A retrospective cohort study was conducted. The patients admitted to the department of critical care medicine of Anhui Provincial Hospital Affiliated to Anhui Medical University with the diagnosis of PQ poisoning from August 2012 to August 2014, fulfilling the following criteria were enrolled in the study: older than 18 years, interval from ingestion PQ to hospital admission shorter than 12 hours, and receiving HP treatment within 24 hours, and expecting surviving time exceeding 24 hours after admission, and data of the patients available for at least 28 days after admission. Depending on the intensity of HP, patients were assigned to either lower intensity HP group (LHP, defined as receiving HP for less than 4 hours, 2 columns) or higher intensity HP group (HHP, defined as receiving HP longer than 6 hours, 3 columns). Patients' data were retrieved from hospital's electronic database after hospital admission, and the results at 7th day and 28th day were recorded. Multiple logistic regression model was used to determine factors with which the clinician decided to choose the intensity of HP for the patients, and Cox regression model was used to evaluate 7-day and 28-day mortality. Data of 60 patients was finally available for this study. LHP group consisted of 28 patients, with a 7-day mortality of 53.6% ( 15 patients ) and 28-day mortality of 64.3% ( 28 patients ); 32 patients were assigned to HHP group with 7-day mortality of 43.8% ( 14 patients) and 28-day mortality of 62.5% (20 patients). Twenty-eight patients constituted as the HHP group, with higher PQ concentration in plasma, higher incidence of respiratory alkalosis and acute kidney injury (AKI), and higher level of lactate (Lac) compared with LHP group. However, a lower 7-day mortality was observed in the HHP group. Multiple logistic regression model indicated that at admission, interval from ingestion PQ to hospital admission longer than 4 hours [ odds ratio (OR) = 1.461, 95% confidence interval (95%CI) = 1.132-1.435, P < 0.001], younger than 50 years old (40-49 years old: OR = 1.397, 95%CI = 1.251-1.703, P = 0.002; < 40 years old: OR = 1.701, 95%CI = 1.253-1.836, P < 0.001), PQ plasma concentration ≥ 2 mg/L (OR = 3.140, 95%CI = 1.511-3.091, P < 0.001), white blood cell (WBC) > 10 × 10⁹/L (OR = 1.222, 95%CI = 1.032-1.275, P = 0.018), Lac > 2.0 mmol/L (OR = 2.392, 95%CI = 2.090-2.734, P < 0.001 ), AKI on admission (stage 2: OR = 2.350, 95%CI = 2.160-3.910, P < 0.001; stage 3: OR = 2.821, 95%CI = 1.932-3.651, P < 0.001), accompanying hypoxia (OR = 2.420, 95%CI = 2.131-2.662, P = 0.003 ) were more likely to receive higher intensity of HP. Furthermore when compared with patients survived for 28 days, patients who were older, with higher levels of PQ concentration at admission or after 4 hours of HP, accompanied by AKI, increased serum creatinine (SCr), WBC, Lac, and acute physiology and chronic health evaluation II (APACHEII) score, lower arterial partial pressure of carbon dioxide (PaCO₂) and lower pH value were more likely to die. After adjusted for con-variables in COX regression model, HHP was associated with lower 7-day mortality after admission [ hazard ratio (HR) = 0.843, 95%CI = 0.732-0.971, P = 0.032], but devoid of lowering effect on 28-day mortality rate (HR = 0.930, 95%CI = 0.632-1.411, P = 0.423). In addition, age > 50 years old (HR = 1.282, 95%CI = 1.050-1.530, P = 0.043), PQ concentration increased by 1 mg/L (HR = 2.521, 95%CI = 2.371-3.825, P = 0.012), AKI on admission (HR = 3.850, 95%CI = 2.071-5.391, P < 0.001), WBC>10 × 10⁹/L (HR = 1.932, 95%CI = 1.782-2.171, P = 0.006 ), Lac > 2.0 mmol/L ( HR = 2.981, 95%CI = 2.210-3.792, P = 0.002 ), and PaCO2 < 35 mmHg ( HR = 1.772, 95%CI = 1.483-2.516, P = 0.008; 1 mmHg = 0.133 kPa ) were independent risk factors for 28-day mortality. Though HHP was helpful in lowering mortality rate in patients with PQ poisoning within 7 days, it did not influence on 28-day mortality. Clinicians' decisions on HP intensity need further investigation, and more perfect clinical evaluation system is required for reasonable use of expensive medical resources such as HP.

The value of assessment of area of ground glass opacity in lungs cast by high-resolution computed tomography on the prognosis of patients with acute paraquat intoxication

To assess the value of the area of ground glass opacities (GGOs) in lungs displayed by high-resolution computed tomography (HRCT) in paraquat (PQ) poisoned patients in evaluating prognosis. Clinical and imaging data of 137 patients with acute PQ poisoning admitted to Affiliated Hospital of the Medical College of Chinese People's Armed Police Forces from January 2012 to August 2014 were analyzed retrospectively. The plasma concentration of PQ on admission and the area of GGOs were compared between two groups. The lung HRCT within 10 days of poisoning was performed every 3 days, and the areas of GGOs were evaluated on five levels, including aortic arch, aortic pulmonary window, left upper lobe bronchial, right inferior pulmonary vein, and left diaphragmatic dome. Receiver operating characteristic curve (ROC) was plotted to evaluate the value of all the parameters for prognosis. Among 137 patients, 45 died within 28 days after poisoning, with the mortality rate of 32.85%. The plasma PQ level in the non-survivors was significantly higher than that in the survivors (mg/L: 7.06 ± 0.67 vs. 3.51 ± 0.34, t = 5.280, P = 0.000). The areas of GGOs at three time points in the non-survivors were significantly higher than those in the survivors [ 1-3 days: (32.0 ± 5.0)% vs. (2.5 ± 0.4)%, t = 7.860, P = 0.000; 4-6 days: (45.5 ± 5.7)% vs. (2.8 ± 0.5)%, t = 12.420, P = 0.000; 7-10 days: (68.0 ± 4.8)% vs. (3.0 ± 0.6)%, t = 23.950, P = 0.00 ]. ROC analysis demonstrated that the area under the ROC curve (AUC) of GGOs in 7-10 days was 1.000, which could be used to determine the prognosis, but it was too late for the treatment. The AUC of GGOs in 4-6 days was 0.979, with the threshold of > 12.0%, the specificity of 96.15%, the sensitivity of 85.19%, the positive predictive value of 88.46%, and the negative predictive value of 94.94%, which presented good effect in predicting prognosis in the early stage of acute PQ intoxication. But plasma PQ concentration was relatively poor for determining prognosis, AUC was 0.821, with the threshold of > 1.95 mg/L, the specificity of 34.52%, the sensitivity of 88.64%, the positive predictive value of 41.49%, and the negative predictive value of 85.29%. The area of GGOs displayed by HRCT can be used to evaluate the fully developed acute PQ lung injury, and it is superior to plasma PQ concentration. The area of GGOs displayed by HRCT 4-6 days after intoxication can be used for the evaluation of PQ induced pulmonary injury in the early stage and the evaluation of clinical prognosis.

The volume ratio of ground glass opacity in early lung CT predicts mortality in acute paraquat poisoning.

BackgroundPulmonary injury is the main cause of death in acute paraquat (PQ) poisoning. However, whether quantitative lung computed tomography (CT) can be useful in predicting the outcome of PQ poisoning remains unknown. We aimed to identify early findings of quantitative lung CT as predictors of outcome in acute PQ poisoning.MethodsLung CT scanning (64-slide) and quantitative CT lesions were prospectively measured for patients after PQ intoxication within 5 days. The study outcome was mortality during 90 days follow-up. Survival curves were derived by the Kaplan-Meier method, and mortality risk factors were analyzed by the forward stepwise Cox regression analysis.ResultsOf 97 patients, 41 (42.3%) died. Among the eight different types of lung CT findings which appeared in the first 5-day of PQ intoxication, four ones discriminated between survivors and non-survivors including ground glass opacity (GGO), consolidation, pneumomediastinum and “no obvious lesion”. With a cutoff value of 10.8%, sensitivity of 85.4% and specificity of 89.3%, GGO volume ratio is better than adopted outcome indicators in predicting mortality, such as estimated amount of PQ ingestion, plasma or urine PQ concentration, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. GGO volume ratios above 10.8% were associated with increased mortality (hazard ratio, 5.82; 95% confidence interval, 4.77-7.09; P < 0.001).ConclusionsThe volume ratio of GGO exceeding 10.8% is a novel, reliable and independent predictors of outcome in acute PQ poisoning.

Metabolic changes in paraquat poisoned patients and support vector machine model of discrimination.

Numerous people die of paraquat (PQ) poisoning every year in the world. Although several studies regarding paraquat (PQ) poisoning have been conducted, the metabolic changes in plasma remain unknown. In this study, the metabolomics of 15 PQ poisoned patients with plasma PQ concentrations in excess of 0.1 µg/mL and 16 healthy volunteers were investigated. The plasma samples were evaluated through the use of gas chromatography-mass spectrometry (GC/MS) and analyzed by partial least-squares discriminant analysis (PLS-DA). Based on the metabolomics data, a support vector machine (SVM) discrimination model was developed. The results showed the plasma levels of urea, glucose oxime and L-phenylalanine decreased and cholesterol increased in PQ poisoned patients in comparison to healthy volunteers. The SVM discrimination model was developed, and performed with a high degree of accuracy, to distinguish PQ poisoned patients from healthy volunteers. In conclusion, metabolic pathways including the urea cycle, and amino acid, glucose, and cholesterol metabolism were impaired after PQ poisoning. An SVM discrimination model, based on metabolomics data, was established and may become a new powerful tool for the diagnosis of PQ poisoning.

Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach

Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive therapy in hospitalized paraquat-intoxicated patients. The aim of this analysis was to characterize the toxicokinetics and toxicodynamics of paraquat in this population. A non-linear mixed effects approach was used to perform a toxicokinetic/toxicodynamic population analysis in a cohort of 78 patients. The paraquat plasma concentrations were best fitted by a two compartment toxicokinetic structural model with first order absorption and first order elimination. Changes in renal function were used for the assessment of paraquat toxicodynamics. The estimates of toxicokinetic parameters for the apparent clearance, the apparent volume of distribution and elimination half-life were 1.17 l h(-1) , 2.4 l kg(-1) and 87 h, respectively. Renal function, namely creatinine clearance, was the most significant covariate to explain between patient variability in paraquat clearance.This model suggested that a reduction in paraquat clearance occurred within 24 to 48 h after poison ingestion, and afterwards the clearance was constant over time. The model estimated that a paraquat concentration of 429 μg l(-1) caused 50% of maximum renal toxicity. The immunosuppressive therapy tested during this study was associated with only 8% improvement of renal function. The developed models may be useful as prognostic tools to predict patient outcome based on patient characteristics on admission and to assess drug effectiveness during antidote drug development.