Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
APACHE score, Severity Index of Paraquat Poisoning and serum lactic acid concentration in the prognosis of paraquat poisoning of Chinese Shuyun Xu1,Hai Hu1,Zhen Jiang1,Shiyuan Tang1,Yuangao Zhou2,Jie Sheng1,Jinggang Chen1, Yu Cao1 1. Department of Emergency, West China Hospital, Sichuan University, No 37 Guoxuexiang / Wuhou District, Chengdu, Sichuan, 610041, PR China; 2. Department of Laboratory Medicine, Sichuan University, West China Hospital, No 37 Guoxuexiang / Wuhou District, Chengdu, Sichuan, 610041, PR China. Corresponding authors: Yu Cao, Department of Emergency, West China Hospital, Sichuan University, No 37 Guoxuexiang / Wuhou District, Chengdu, Sichuan Province, 610041, P. R. China. E-mail: [email protected] Tel: +86-28-85164011 Fax: +86-28-85164024 Abstract Background: Many prognostic indictors had been studied to evaluate the prognosis of paraquat poisoning. However, the optimal indicator remains unclear. Objective: To determine the value of the Acute Physiology and Chronic Health Evaluation (APACHE-II) score, Severity Index of Paraquat Poisoning (SIPP) and serum lactate levels in the prognosis of paraquat poisoning, we performed a prospective study consisting of 143 paraquat patients. Methods: Data were collected from patients (161) at West China Hospital in Chengdu, China, including the details about the patients’ general conditions, laboratory examinations, and treatment. Receiver operating characteristic (ROC) curves for predicting inpatient mortality of APACHE II , SIPP and lactate were generated. To analyze the best cut-off values for lactate level, APACHE II and SIPP in predicting the prognosis of paraquat poisoning, the initial parameters on admission and 7 days survival curves of patients with lactate level ≥ 2.95 mmol/L, SIPP ≥ 15.22 h·mg/L and APACHE II score ≥ 5.50 at the time of Westchina Hospital (WCH) arrival were compared using one-way analysis of variance (ANOVA) and log-rank test. Results: The SIPP (5.45 ± 3.67 versus 11.29 ± 4.31 hr•mg/L ), APACHE II score (2.78 ± 1.89 versus 7.63±2.46) and lactate level (2.78 ± 1.89 versus 7.63 ± 2.46 mmol/l) were significantly lower in survivors (77) after oral ingestion of paraquat compared with nonsurvivors (66). The APACHE II score, SIPP and lactate level had different AUC of ROC (0.789, 0.847 and 0.916 , respectively) and accuracy (0.64, 0.84 and 0.89, respectively). Respiratory rate (RR), serum creatinine, PaCO2 and mortality rate at 7 days after admission in patients with lactate level ≥ 2.95 mmol/L were markedly different compared to others (P<0.05). Conclusions: The predictive value of lactic acid was superior to APACHE II Score and SIPP for acute oral paraquat poisoning. Key Words: paraquat poisoning, Receiver operating characteristic, lactate levels; 1. Introduction Paraquat is an organic heterocyclic contact defoliant and herbicide, which has gained worldwide 1 popularity [1-3]. The widespread use of paraquat in the villages of developing countries, such as China, has led to an increase in the number of paraquat poisoning cases [2]. It is reported that the number of poisonings cases have reached for an estimated 877 000 every year(World Health Organization, 2003), and many health officials consider paraquat a public health threat because of its high toxicity [4,5]. The ingestion of 40 mg of paraquat ion/kg body weight is associated with a mortality rate of up to 100% [1]. The clinical manifestations of paraquat poisoning varies depending on a number of factors, including dosage and route of entry [2, 6], which also affects the prognosis. There have been reports of survival from mild poisonings with no intervention, but highly toxic doses (35 mg/kg) are almost always fatal despite aggressive interventions, such as hemodialysis and renal replacement therapy [7]. Hence, an accurate prognostic indicators is very necessary. Appropriate prognostic indicators can aid physicians in evaluating the severity of poisoning and predicting overall outcome. At present, most primary health care institutional guideline lacks a favorable prognostic indicators for paraquat poisoning. Therefore, most physicians predict the outcome of the condition by the clinical signs and symptoms [8]. However, the time to the onset of symptoms after acute paraquat poisoning can require a period of time, and by then the poisoning can become irreversible or fatal. Thus, a simple and easy to obtain prognostic indicator for acute paraquat poisoning is crucially important. Many prognostic indictors had been studied to evaluate the prognosis of paraquat poisoning, but the optimal indictors remains unclear. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is a scoring systems based on 12 parameters of acute physiology and chronic health [9]. This scoring system is commonly used for the assessment of the severity and prognosis of diseases [10], especially in the intensive care unit (ICU) [11]. The APACHE II is also used to predict the severity and prognosis of poisoning, but Chinese physicians rarely use it for acute paraquat poisoning cases. The Severity Index of Paraquat Poisoning (SIPP) is also a potentially valuable prognostic indicator, which is calculated by multiplying the time since the ingestion (hr) of paraquat by the paraquat concentration in plasma (mg/L) [12,13]. Studies have suggested that patients with a SIPP of less than 10 h·mg/L have a good chance of survival, whereas those between 10-50 h·mg/L frequently dies because of interstitial pulmonary fibrosis secondary to paraquat poisoning, and those with values greater than 50 h·mg/L dies rapidly owning to circulatory collapse [14,15]. Though promising, but the plasma paraquat level is not widely available in China. Other studies have shown that acidosis was an important prognostic indicator for acute paraquat poisoning [16, 17], particularly the serum lactic acid concentration, which was the primary cause of acidosis. To determine the value of the APACHE II, SIPP and serum lactate concentration in the prognosis of paraquat poisoning, a prospective study consisting of 143 patients with paraquat poisoning was performed. 2 Data and Method 2.1 Study population Patients with acute oral paraquat poisoning were consecutively selected among those who were referred to the Emergency Department (ED) of Sichuan University (Chengdu, China) between January 2011 and January 2012 (n=143) according to the following exclusion criteria: transcutaneous or intravenous exposure and undetectable levels of paraquat in the blood. In addition, individuals were also ineligible if they had concomitant diseases including cancer, cardiac disease, pulmonary disease, renal disease and liver disease, or if the patient refused to 2 participate in the study. Signed informed consent was obtained from the patients, family members, or legal guardians. 2.2 Data collection All data was collected by experienced emergency doctors, including the details of the patients’ general conditions, laboratory examinations, and treatment. On admission, each patient’s age, gender and other demographic data, past medical history, amount of paraquat ingested (including other toxic substances ingested) and poisoned time was documented. On admission, vital signs were recorded and blood samples were collected for the purpose of the following tests: blood routine, liver and renal function, other biochemical blood examination, and arterial blood gas examination. To ensure inter-rater reliability, a 20% sample of data were screened by a second reviewer. The Glasgow Coma Scale (GCS) score and the APACHE II score was calculated, and the serum lactate level and plasma paraquat concentration was determined. All specimens were collected at 1 hour after admission. Complete blood cell count, biochemistry, and lactic acid level were measured using an autoanalyzer (Roche modular P800, Mannheim, Germany). Plasma paraquat concentration was measured by high performance liquid chromatographic (HPLC) system (Shimadzu, Japan). The elapsed time (hours) from ingestion of paraquat to arrival and serum paraquat levels was recorded to calculate SIPP (mean elapsed time (hour) × serum paraquat level in the ED (mg/L)). Deaths which occurred in the hospital were recorded, and those discharged from the hospital was followed by telephone or letter. The 60 days mortality were used to determine the efficacy of individual prognostic indicators, and the results were summarized by an expert of toxicology. 2.3 Treatment As summarized in Table 1, all patients presenting within 6 hours of paraquat ingestion received a gastric lavage followed by 200ml of 20% mannitol via gastric tube. The patients who presented within 12 hours of ingestion received hemoperfusion every 12 hours until serum paraquat levels dropped below 200 ppm. In addition, they also received a pulse therapy daily via intravenous infusion with 1 gram of methylprednisolone, 400mg of cyclophosphamide (CTX), antioxidants vitamins C (2g/d) and E (300mg/d), and cysteine (1.2g/d). Supplemental oxygen therapy was administered if the oxygen partial pressure was less than 50mmHg. Hemodialysis was performed if the patients had severe metabolic acidosis, hyperkalemia, or heart failure. 2.4 Statistical analysis Collected data were presented as mean ± standard deviation for continuous variables and frequency for categorical variables. A P-value of < 0.05 was considered statistically significant, with all statistical analyses performed using SPSS18.0. Differences in covariates between survivors and nonsurvivors were tested by Student’s t-test for continuous variables and chi-square test or Fisher exact probability method for categorical variables. To investigate which prognostic indicator (APACHE II, SIPP, and serum lactic acid level) were the most valuable predictor of prognosis for acute paraquat poisoning, receiver operating characteristic (ROC) curves for predicting inpatient mortality were generated. The area under the curve (AUC), sensitivities, specificities, cut-off values, accuracy, and an indicator of the predictive value of a test were calculated using GraphPad Prism V4.0. To analyze the best cut-off values for APACHE II score, SIPP and lactate level for predicting the prognosis in paraquat poisoning, one-way analysis of variance (ANOVA) assessed for differences in initial parameters at the time of WCH arrival of paraquat poisoning patients of lactate level ≥ 2.95 mmol/L, APACHE II score ≥ 15.22 and SIPP ≥ 3 5.50 h·mg/L. In addition, with one another, the 7 days survival curves of lactate level ≥ 2.95 mmol/L, APACHE II score ≥ 15.22, and SIPP ≥ 5.50 h·mg/L were compared. 3. Result 3.1 Patient characteristics During the study period, 161 patients fulfilled the acute oral poisoning criteria. Eighteen of these patients were excluded because of missing data or loss of follow-up. The remaining 143 patients were included in the study analysis. The median age of the patients in this study was 30.65 ± 12.75 years old. The mean time interval between exposure and WCH arrival (hours) was 8.95 ± 6.15 h. The mean ingested amount of paraquat dichloride (24.5% concentrate neat) as estimated through history was 65.66 ± 14.01 ml. Forty-seven (32.86%) patients had comorbid diseases, of which 25 (17.48%) patients had psychiatric conditions. Only 1 patient had concomitant alcohol ingestion. 77 (53.85%) of patients survived after oral ingestion of paraquat, whereas 66 patients died within 60 days. The overall 60-day mortality rate was 46.15%. The general characteristics of all patients, the survivors and nonsurvivors are summarized in Table 1. The SIPP (5.45 ± 3.67 versus 11.29 ± 4.31 hr•mg/L), APACHE II score (2.78±1.89 versus 7.63±2.46) and lactate level (2.78±1.89 versus 7.63±2.46 mmol/l) in survivors were significantly lower compared to nonsurvivors. Table 1. General characteristics of 143 oral paraquat poisoning patients at the time of WCH arrival Number of patientsa Age (year)b Sexa Time between exposure and WCH arrival (hours)b Estimated amount of paraquat dichloride (24.5% concentrate) exposure (mL)b Comorbid diseasea Pyschiatric conditiona underlying diseasea Concomitant alcohol ingestiona Serum lactates (mmol/l)b APACHE II scoreb SIPP (hr•mg/L)b All patients Survivors Non-survivors P value 143 30.6±12.7 54/89 9.9±5.1 77 28.0±12.9 28/49 11.2±4.3 66 33.6±11.9 26/40 7.4±6.9 0.190 0.666 0.106 65.6±14.1 50.1±21.2 76.9±18.2 0.227 47 25 7 1 5.29±2.54 8.65±4.63 81.07 ± 67.42 27 16 5 1 2.78±1.89 5.45±3.67 15.39 ± 10.6 20 9 2 0 7.63±2.46 11.29±4.31 147.85 ± 78.56 0.546 0.262 0.35 1.000 <0.001 <0.001 <0.001 Results are expressed as a number of patients or b mean ± SD. 3.2 The prognostic value of lactate level、APACHE II score、SIPP Of all patients, 143 with a history of acute oral paraquat poisoning were included. Receiver operating characteristic (ROC) curves were calculated for APACHE II score, SIPP and lactate level on admission. The APACHE II score, SIPP and lactate level all had different ROC area under the curves (AUC). The lactate level was as good as the SIPP or APACHE II score (AUC 0.916 vs 4 0.847, 0.789) at predicting the patient outcome, and level of consciousness had the utmost contribution to the APACHE II score or SIPP (Fig 1 A, Table 2). All 3 predictive indicators was useful in predicting the outcome in oral paraquat poisoning patients, with patents with lactate level equal > 2.95 (mmol/l) having a sensitivity of 0.87, specificity of 0.91 and accuracy of 0.89 for predicting death, SIPP > 15.22(h•mg/L) having a sensitivity of 0.78, specificity of 0.91 and accuracy of 0.84 for predicting death, and APACHE II score > 5.50 having sensitivity, specificity and accuracy of 0.95, 0.50 and 0.64, respectively. Fig. 1. A: shows the ROC curves comparing lactate level,APACHE II score, SIPP for prediction 60-day mortality of f acute oral paraquat poisoning mortality. B: 7 days survival curves after admission of paraquat-poisoning patients of lactate level≥2.95 mmol/L, APACHE II score≥15.22 and SIPP≥5.50 h·mg/L. Table 2 Comparisons of initial parameters in paraquat poisoning patients with SIPP ≥ 15.22 h·mg/L, APACHE II score ≥ 5.50, and lactate level ≥ 2.95 mmol/L at the time of WCH arrival Number of patients SBP (mmHg) DBP (mmHg) HR (/min) RR (/min) BT (℃) Hemoglobin (g/dL) WBC (×103/mm3) pH PaCO2 (mmHg) PaO2 (mmHg) 5 lactate level≥2.95 mmol/L SIPP≥15.22 h·mg/L APACHE II score ≥ 5.50 64 117.42±19.42 79.46±20.73 87.68±16. 52 27.08±3.06 36.89±0.44 15.75±2.32 18.28±6.04 7.31±0.08 27.77±4.2 95.23±24.02 59 126.63±20.58 81.0±11.57 83.55±13.62 26.38±3.36 36.86±0.47 14. 47±3.03 16.89±5.97 7.38±0.12 29.63±5.9 91.46±32.13 91 121.72±23.61 80.5±14. 68 95.59±10.09 22.23±2.14 36.94±0.52 16.24±1.83 17.23±6.18 7.45±0.10 32.26±5.0 99.74±30.03 BUN (mg/dL) Creatinine (mg/dL) AST (IU/L) ALT (IU/L) Total bilirubin (mg/dL) Amylase (IU/L) Glucose (mg/dL) 23.84±4.27 2.54±0.3 76.52±9.28 62.38±11.27 1.78±0.65 515.39±162.53 147.37±21.48 21.63±3.68 2.04±0.4 75.95±10.31 63.62±10.68 1.88±0.43 490.51±157.01 159.69±17.83 20.05±4.70 1.84±0.3 77.47±11.25 67.57±8.25 1.84±0.74 413.18±188.22 162.76±23.62 Results are expressed as mean ± SD. SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; RR, respiratory rate; BT, body temperature; WBC, total white blood cell; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase. 3.3 Comparison of best cut-off values for lactate level, APACHE II score and SIPP The initial parameters of patients with lactate level ≥ 2.95 mmol/L, SIPP ≥ 15.22 h·mg/L and APACHE II score ≥ 5.50 at the time of WCH arrival are shown in Table 2. On average, respiratory rate (RR) and serum creatinine amylase values (RR: 27.8 ± 3.0 /min and creatinine: 2.54 ± 0.3 mg/dL) in patients with lactate level ≥ 2.95 mmol/L were higher than patients with SIPP ≥ 15.22 h·mg/L (RR: 26.38±3.3 /min; and creatinine: 2.04±0.4 mg/dL) and APACHE II score ≥ 5.50 (RR: 22.23 ± 2.1 /min and creatinine: 1.84 ± 0.3 mg /dL) at the time of WCH arrival (P<0.05). In contrast, blood PaCO2 values (27.77±4.2 mmHg) in patients with lactate level ≥ 2.95 mmol/L was lower than patients with SIPP ≥ 15.22 h·mg/L (29.63±5.9 mmHg) and APACHE II score ≥ 5.50 (32.26 ± 5.0 mmHg) (P<0.05). Further analysis revealed a significant difference in the 7 days survival curves in patients with lactate level ≥ 2.95 mmol/L, SIPP ≥ 15.22 h·mg/L and APACHE II score ≥ 5.50 (Fig. 1 B). The paraquat poisoning patients with lactate level ≥ 2.95 mmol/L or SIPP ≥15.22 h·mg/L had a significant higher 7-day mortality after admission, 54 of the 64 deaths (84.38%) in the patients of lactate level≥2.95 mmol/L and 49 of 59 (83.05%) in the patients of SIPP≥5.50 h·mg/L compared with 46 of 91 deaths (50.55%) in the patients of APACHE II score≥5.50, (P<0.05) ( Fig. 1 B) 4. Discussion For a long time, one of the many problems which puzzled clinical doctors was how to uncover a good prognostic indictor. A good prognostic indictor is able to identify the high risks patients, and can facilitate the doctor-patient communications [18], acquired from the blood. In addition, it must have an appropriate half-life period, not only does it have to respond in the early phase, but also has to have enough window phase [19], easy to be acquired and expanded, and is helpful for clinical doctors to predict the prognosis [20]. The number of paraquat poisoning cases in western China has increased dramatically in recent years. West China Hospital of Sichuan University (Chengdu, China) is the first-line poisoning treatment referral center in western China, and our center has developed an algorithms for measurement and diagnosis of paraquat levels to ensure the consistent intervention measures. Though our practice, we have found that the APACHE II score, lactic acid and SIPP maybe correlated with the prognosis of paraquat poisoning. The present study has investigated the correlation of 3 indicators (APACHE II score, lactic acid and SIPP) and the prognosis of acute paraquat poisoning. The lactic acid had the largest ROC area under the curves (AUC) compared with SIPP and APACHE II. The lactic acid was more specific 6 and accurate at predicting the prognosis of acute paraquat poisoning. This implies that the predictive value of lactic acid was superior to SIPP and APACHE II., which accords with our past clinical observations. The most common clinical manifestations of paraquat poisoning were anoxia and ARDS (acute respiratory distress syndrome) which are caused by acute lung injury [21,22], and were the primary cause of death in patients with a short survival. The serum lactic acid concentration is an indicator of histanoxia, which can reflect the severity of patient's condition. In addition, because of its sensitivity for anoxia, it can also reflect the severity of paraquat poisoning. Our results showed that the serum lactate concentration correlates with the prognosis, and demonstrated that it is a good prognostic indicator, which can indicate physicians of the necessity for early treatment, and is very important for high risk patients. Through comparisons of initial parameters and survival curves of patients with lactate level ≥ 2.95 mmol/L, SIPP ≥ 15.22 h·mg/L and APACHE II score ≥ 5.50 at the time of WCH arrival, we had found that the hypoxic symptoms were more severe in patients with lactate level ≥ 2.95 mmol/L. In addition, these patients also had a poorer renal function and shorter survival. These results can explain why the serum lactic acid concentration was on overall a better indicator than SIPP and APACHE II Score at predicting the mortality of acute paraquat poisoning. The results of this study was comparable to the results from past literatures, which concluded that SIPP was related to prognosis of paraquat poisoning [12-15]. When the cutoff value was 15.22 h·mg/L, the accurancy of SIPP at predicting mortality was 84%. When available, the plasma paraquat concentration should be tested, and appropriate treatment should be administer accordingly. Because the plasma paraquat concentration only reflex the distribution in blood, the tissue damage for patients unable to direct reaction. This may be the reason that the predictive value of SIPP was lower than serum lactic acid concentration. In addition, the results of our study also showed that the APACHE II score is not as good a prognostic indicator as lactic acid and SIPP. The AUC of APACHE II was 0.789, degree of accurancy was only 64%, and the cutoff value was 5.50 , which is not comparable to the result of past literature [23]. Possible reasons for its decrease in reliability include the fact that acute paraquat poisoning symptoms can take from a few days to weeks to manifest [23,24], and since the APACHE II score is generally calculated during the early stages, and therefore it may not be able to truly reflect the severity of the poisoning. As a result, the APACHE II score may not provide the best prognostic information. In conclusion, serum lactic acid level, SIPP and APACHE II score all were correlated with prognosis of acute paraquat poisoning. The elevation of serum lactic acid level had great inferred value for the severity and prognosis of acute paraquat poisoning. Serum lactic acid ≥ 2.95mmol/L and SIPP ≥15.22 h·mg/L was a simple and easy to acquire prognostic indicator of acute paraquat poisoning, and was better than SIPP. In the future, serum lactic acid concentration accompany with SIPP for predicting the prognosis of acute paraquat poisoning should be the area of interest for investigators. Because of the delay of symptom after acute paraquat poisoning, APACHE II score maybe inaccurate at the early course of paraquat poisoning, but whether it can be used to predict the prognosis at several days after poisoning should also be investigated in the future. Financial disclosure:No current external funding sources for this study Reference 1. Vale JA, Meredith TJ, Buckley BM. Paraquat poisoning: clinical features and immediate 7 general management. Hum Toxicol. 1987;6:41–7. 2. Eddleston M. Patterns and problems of deliberate selfpoisoning in the developing world. Q J Med. 2000; 93:715-731. 3. Goldfrank LR, Flomenbaum NE, Lewin NA,Howland MA,et al. Goldfrank's toxicologic emergency, 7th edition,McGraw Hill, 2002: 1396-1402. 4. Bertolote JM,Fleischmann A. Deaths from pestieide Poisoning:A global resPons[J].Br J Psyehiatry.2006,189(l):201-203. 5. SittiPunt C.Paraquat poisoning[J].ResPir Care.2005,50(3):383-385. 6. United States Environmental Protection Agency. Reregistration eligibility decision (RED), Paraquat dichloride. 1997, Office of Prevention,Pesticides and Toxic Substances. 7. Juanwen Zhang, Guocai Lv, Ying Zhao. The significance of serum xanthine oxidase and oxidation markers in acute paraquat poisoning in humans. Clinical Biochemistry.2011,44 : 221–225 8. Huh JW, Hong SB, Lim CM, et al. Sequential radiologic and functional pulmonary changes in patients with paraquat intoxication. Int J Occup Environ Health. 2006;12:203–8. 9. Knaus WA, Draper EA, Wagner DP, et al. An evaluation of outcome from intensive care in major medical centers. Ann intern Med, 1986, 104: 410 - 418. 10. KnausWA, Draper EA,Wagner DP, et al. APACHEⅡ: a severity of disease classification system[ J ]. Crit Care Med, 1985, 13 (10) : 818-829. 11. Stephanie L. Taylor, Daniel L. Morgan, Kent D. Denson,et al. A comparison of the Ranson, Glasgow, and APACHE II scoring systems to a multiple organ system score in predicting patient outcome in pancreatitis. The American Journal of Surgery .2005,89:219–222 12. Proudfoot AT, Stewart MJ, Levitt T, Widdop B. Paraquat poisoning: significance of plasma paraquat concentration. Lancet. 1979;2:330–2. 13. Senarathna L, Eddleston M, Wilks MF, et al. Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration[J]. QJM. 2009, 102(4): 14. Yamamoto I, Saito T, Harunari N, et al. Correlating the severity of paraquat poisoning with specific hemodynamic and oxygen metabolism variables. Crit Care Med. 2000;28: 1877–83. 15. Sawada Y, Yamamoto I, Hirokane T, et al. Severity index of paraquat oisoning[J].Lancet.1988: 1333,251-259. 16. Ragoucy-Sengler C, Pileire B. A biological index to predict patient outcome in paraquat poisoning[J].Hum ExpToxicol.1996, 15(3): 265-268. 17. Huang C, Zhang X. Prognostic significance of arterial blood gas analysis in the early evaluation of paraquat poisoning patients[J]. ClinToxicol.2011, 49(8): 734-738. 18. Christopher R. Carpenter, Samuel M. Keim, Suneel Upadhye,et al.Risk stratification of the potentially septic patient in the emergency department: the mortality in the emergency department sepsis (MEDS)score. The Journal of Emergency Medicine.2009,( 37): 319–327 19. Alan E. Jones, James F. Fiechtl, Michael D. Brown, , et al. Procalcitonin Test in the Diagnosis of Bacteremia:A Meta-analysis.Annals of Emergency Medicine.2007;50:34-41 20. Jason Phua, Evelyn S. C. Koay, and Kang Hoe Lee. Lactate ,procalcitonin, and amino-terminal pro-B-type natriuretic peptide versus cytokine measurements and clinical severity scores for prognostication in septic shock . SHOCK. 2008,29,(3): 328-333, 21. Venkatesan N. Pulmonary protective effects of currum in against Paraquat toxicity[J].Life Sci.2000.66(2):21-28. 8 22. Mohammadi-Karakani A , Ghazi-Khansari M, Sotoudeh M. Lisinopril ameliorates Paraquat-induced lung fibrosis.Clin Chim Acta.2006,367(1-2):170-174. 23. Dinis-Oliveira,R.J.,Duarte,J.A.,Sánchez-Navarro, A., Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit. Rev. Toxicol. 2008,38, 13–71. 24. Jen-Pi Tsai1, Ru-Ping Lee2, Chih-Hsien Wang3,et al.A Clinical Study of Prognosis and Glucocorticoid Pulse Treatment in Patients with Acute Paraquat Intoxication. TZU CHI MED J ,2009 Vol 21 No 2:156-160 9