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Clinical Toxicology (2008) 46, 515–518
Copyright Informa Healthcare USA, Inc.
ISSN: 1556-3650 print / 1556-9519 online
DOI: 10.1080/15563650701549403
Association between plasma paraquat level and outcome of paraquat poisoning in 375 paraquat poisoning patients Paraquat level in 375 paraquat poisoning patients HYO-WOOK GIL, MUN-SOO KANG, JONG-OH YANG, EUN-YOUNG LEE, and SAE-YONG HONG Soonchunhyang Cheonan Hospital, Department of Internal Medicine, Cheonan, Republic of Korea Objectives. Paraquat poisoning by ingestion is often fatal. Many studies have investigated treatment modalities and predictor parameters, butthere is no standard treatment. Plasma paraquat concentration seems a valid predictable parameter of survival. In order to achieve uniformtreatment, including extracorporeal elimination and antioxidant therapy, the outcome of paraquat poisoning based on plasma paraquat levelneeds to be investigated.
Methods. This study included 375 paraquat poisoning patients who were diagnosed by means of plasma paraquat concentration within 24 hours after ingestion in the Institute of Pesticide Poisoning of Soonchunhyang University Cheonan Hospital, Korea,from January 2005 to December 2006. All patients were treated according to a uniform protocol including extracorporeal elimination andantioxidant therapy. Plasma paraquat concentration was measured by high-performance liquid chromatography.
Downloaded By: [Hong, Sae-Yong] At: 15:34 29 June 2008 the paraquat-intoxicated patients was 48.42 ± 6.75. One hundred ten patients (29.3%) survived. The upper limit of plasma paraquatconcentration in survivors was 2.64 at 3 hour. All patients with plasma paraquat level above 3.44 died. The minimum paraquat level of thedeaths was very low (0.12 μg/ml at 5 hours; 0.02 μg/ml at 12 hours; 0.01 μg/ml at 24 hours).
Conclusions. Our data showed that plasma paraquat concentration is good predictor of survivors but is not good predictor of non-survivors in the low plasma paraquat level.
of absorption in the gastrointestinal tract (6), removal from theblood stream (7), prevention of accumulation in the lungs (8), Paraquat (1,1′-dimethyl-4,4′-bipyridium dichloride) was intro- scavenging oxygen free radicals (9,10), and prevention of lung duced in 1962 as an effective herbicide that had low chronic toxicity because of its rapid deactivation upon soil contact (1).
Unfortunately, most of these methods have proven inef- However, it has since become notorious throughout the world fective, with the outcome already determined by the degree as a potent human poison (2). In spite of the decreasing num- of exposure to paraquat. However, in most previous studies bers in the agricultural population of Korea, the incidence of the results have been severely compromised by their rela- paraquat poisoning is rapidly increasing (3).
tively small sample size, making it hard to detect small In humans, intentional or accidental ingestion of paraquat changes in the efficiency of the individual treatment is frequently fatal, as a result of multiorgan failure (4). Inges- modality. The number of patients in such investigation tion of large amounts is considered to be uniformly fatal, should be large enough to ensure statistical significance in resulting in death from multi-organ failure and cardiogenic shock within 1–4 days (5). After ingestion of smaller quanti- The plasma levels of paraquat have an excellent prognostic ties, paraquat is specially taken up into and accumulates in value on previous reports (12–15). Patients whose plasma the lung. Subsequent redox cycling and free radical genera- paraquat levels are less than 2.0, 0.6, 0.3, 0.16, and 0.1 mg/L tion triggers a neutrophil-mediated inflammatory response in at 4, 6, 10, 16, and 24 hours are likely to survive (15).
the lungs, which initiates an irreversible fibrotic process that In this regard, the enhancement of extracorporeal elimina- kills the majority of patients within several weeks (5).
tion of paraquat seems to be effective treatment because Over the past 30 years, several methods for modifying the hemoperfusion reduces paraquat levels. Contrary to our toxicity of paraquat have been examined, including prevention expectation, the current consensus is that hemoperfusion doesnot change clinical outcomes in patients with acute paraquatpoisoning (16). There are, in addition, no clinical outcomestudies proving that antioxidant therapy changes outcome.
Received 15 April 2007; accepted 2 July 2007.
But antioxidant therapy might reduce oxidation injury after Address correspondence to Sae-Yong Hong, MD, Dept. Internal paraquat poisoning in pathophysiology, because paraquat Medicine, Soonchunhyang Hospital, 23–20 Bongayung-Dong, CheonanCity, Choongnan 330–721, Korea. E-mail: [email protected] injury evoked many oxidant processes that injure many organs.
It is unclear why the clinical effect of antioxidant ther- Table 1. Summary of treatment guidelines for paraquat in-
apy and extracorporeal elimination is below theoretical toxication, depending on the time lag after paraquat ingestion expectations. In previous reports, all proposed interventions Emergency treatment protocol and treatment after admission.
have been based on case reports or small case series, and inmost studies the therapy varied. The vigorous therapy, 1. Gastric lavage, if within 2 hr of ingestion2. Urine test for paraquat including extracorporeal elimination and antioxidant therapy, 3. Fuller’s earth, 100gm in 200ml mannitol if may improve the survival of paraquat intoxicated patients.
intoxication had occurred within the past 12 hr.
Our center has admitted about 300 paraquat poisoning patients annually (3,17). Our patients were treated according to uniform treatment protocol. The key to our treatment is as follows. First, fuller’s earth was given within 12 hours after paraquat ingestion to reduce absorption in the gastrointestinal tract. Second, intensive extracorporeal elimination therapy, especially hemoperfusion, was performed if the urine paraquat test was positive. Third, intensive antioxidant ther- apy (N-acetylcysteine, glutathione, vitamin C) was given in 5. Emergency hemoperfusion if admitted within the hope that it may scavenge oxidants.
24 hours after ingestion and urine paraquat test is The purpose of this study was to investigate the plasma paraquat level of survivors and non-survivors according to uniform therapy and to examine the upper limit concentration of plasma paraquat for survival and the lower limit concentra- Downloaded By: [Hong, Sae-Yong] At: 15:34 29 June 2008 Liver function test, electrolytesRenal function testX-ray Study population
The study subjects were acute paraquat poisoning patientswho were admitted to the Institute of Pesticide Poisoning ofSoonchunhyang University Cheonan Hospital, Cheonan,Korea, from January 2005 to December 2006. If the patient arrived at the emergency room. Blood samples were stored was intoxicated according to history but the plasma at −70°C until analysis. Plasma paraquat was measured concentration was less than 0.01 μg/ml, the patient was quantitatively by high-performance liquid chromatography excluded. Patients who were admitted within 24 hours of (HPLC) (18). The amount of ingestion was classified < 1 paraquat ingestion were included. Soonchunhyang Cheonan mouthful, 1 – 2mouthful, or >2 mouthful on history. After Hospital’s Investigational Review Board approved this study.
admission, all patients were admitted to the intensive careunit. High resolution computer tomography (HRCT) wasperformed on the 7th day after ingestion. If there was an Data collection
abnormal finding on HRCT, follow up HRCT was done 1 Trained physicians treated the patients and recorded all week later. A survivor was defined as a patient who sur- information on standardized data-collection forms. Stan- vived more than 4 weeks after paraquat ingestion and who dardized medical emergency procedures were conducted fit the following criteria; 1) On lung HRCT, there was in accordance with the treatment guidelines for paraquat consolidation of less than 30% of lung volume on the first intoxication prepared by the IPP, a specialized institute for HRCT obtained 7 days after paraquat ingestion with no pesticide poisoning in Korea (Table 1). Briefly, gastric progression on the second HRCT obtained 14 days after lavage was performed on all subjects seen within 2 hours paraquat ingestion. 2) On arterial blood gas analysis, PaO2 of paraquat ingestion, and 100 g of fuller’s earth in 200 ml never fell below 70 mmHg during the admission period. 3) of 20% mannitol was given if the intoxication had On laboratory chemistry, serum creatinine, liver function, occurred within the previous 12 hours. Hemoperfusion and pancreatic enzyme normalized or was being normal- was performed if a urinary paraquat test was positive ized at 14 days after paraquat ingestion.
within 24 hours. All these procedures were conducted withthe subjects’ permission and informed consent. Urinary Statistical analysis
paraquat was measured semiquantitatively by a dithionitemethod (1). A blood sample for measuring plasma Data are presented as mean ± SD values. A probability of paraquat concentration was collected as soon as patients p < 0.05 was considered to indicate statistical significance, Paraquat level in 375 paraquat poisoning patients with all statistical analyses performed using SPSS for Win- showed a nomogram of the probability of survival (12,13).
dows (version 12.0, Chicago, Illinois, USA).
Sherman reported that the survival rate was 36%, but thestudy included only 53 patients within 24 hours after inges-tion and the blood paraquat level was not checked (14). Ike- buchi reported that the survival rate (n=128) was 16%(19,20). Most studies were data collected from individual Five hundred and two paraquat ingestion patients presented cases, but many studies included only a small number and the between January 2005 to December 2006, but only 375 patients were included in this study because 127 patients were visited after Our center recently reported initial laboratory parame- 24 hours or had less than 0.01μg/ml of plasma paraquat level.
ters related to the prognosis of patients with acute paraquat The mean age (standard deviation = SD) of paraquat-intoxicated poisoning (3,17). The plasma paraquat concentration patients was 48.42(SD = 16.75). Males were intoxicated more fre- seems likely to be the most useful marker of exposure and quently than females (231 versus 144). 29.3% of the severity. The extracorporeal elimination of paraquat poi- patients (110/375) survived (FIG. 1). The mean interval soning seems to be a cornerstone of the initial treatment between paraquat ingestion and arrival on IPP was 6.22 hours modality, because the elimination reduced plasma (SD = 4.67). One hundred thirty eight (36.8) was classified < 1 paraquat level. In pathophysiology, paraquat evoked oxi- mouthful; 24(12.5%) was classified 1–2 mouthfuls; 185 dative injury, so antioxidant therapy may be an effective (49.3) was classified >2 mouthfuls. The plasma paraquat concen- treatment. Nonetheless, contrary to our expectation, the tration of <1 mouthful was 5.29(SD = 18.39); 1–2 mouthfuls was current consensus is that extracorporeal elimination and 11.55(SD = 21.27); >2 mouthfuls was 32.56(SD = 40.61). The >2 antioxidant do not change clinical outcomes in patients mouthfuls group was greater than <1 and 1–2 mouthfuls patients with acute paraquat poisoning (22). But we presume that were statistically significant by ANOVA. There was no difference the patients’ survival rate and the maximal paraquat level Downloaded By: [Hong, Sae-Yong] At: 15:34 29 June 2008 between <1 mouthful and 1–2 mouthfuls. The paraquat level of all for survival might be improved when patients are treated 375 patients was drawn before hemoperfusion. The upper limit of with concurrent hemoperfusion and antioxidant therapy.
plasma paraquat concentration in the survivors was showed in The number of patients in such an investigation should be Table 2. The lower limit of plasma paraquat concentration in non- large enough to ensure statistical significance in the survivors was shown in Table 2. The minimum paraquat level of results. Paraquat poisoning is associated with high mortal- the non-survivors was 0.01 μg/ml measured at 24 hours.
ity, resulting in a low proportion of survivors. Our resultsincluded 375 patients and showed the survival rate(29.6%) according one treatment protocol in one institute Discussion
of pesticide poisoning center. If patients were suspected ofparaquat poisoning on their history but the plasma Many studies reported a link between the results of investiga- paraquat level was lesser than 0.01 μg/ml, the patients tions and outcomes (3, 12–15,17,19–21). Proudfoot and Hart were excluded. The patients who arrived more than 24hours after paraquat ingestion were excluded.
Our data suggested that patients above the maximum concen- tration in our study cannot survive, and the patients with verylow plasma concentration (0.12 μg/ml at 5hour; 0.02 μg/ml at12hour; 0.01 μg/ml at 24hour) may die. The outcome may beinfluenced by several factors, including individual sensitivityto paraquat (10). Clinicians keep in mind that paraquat intox-icated patients with a low level of paraquat concentration candie. It means that the minimum fatal paraquat concentrationcan be very low in practice (FIG. 1). Individual sensitivity toparaquat varied. Plasma paraquat level seems to be not agood predictor of death.
Plasma paraquat concentration did not predict death in thisstudy and is likely not a good parameter to use since deathsoccurred at such low concentrations. Thus, further studies are Fig. 1. Plasma paraquat concentration related to time of ingestion
needed to investigate the factors affecting individual sensitiv- Table 2. The distribution of 375 paraquat poisoning patients according to hours of ingestion and maximum paraquat level
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