| [Purpose] To observe the clinical effects of high dose methylprednisolone in combination with cyclosporin A pulse therapy and continuous venovenous hemofiltration (CVVH) upon patients with paraquat intoxication, aiming at finding an effective treatment for paraquat poisoning.[Method]1. All paraquat poisoning patients:This is a single-center, prospective and randomized controlled study of patients with acute paraquat intoxication admitted to Emergency Department of307Hospital of PLA between July2009and December2011. All patients received blood or/and urine paraquat concentration examinations. All patients were randomly divided into three groups:the control group (methylprednisolone group), experimental group1(methylprednisolone plus cyclosporin A group) and experimental group2(methylprednisolone plus cyclosporin A plus CVVH group). Inclusion criteria:the subjects who orally took>5ml of commercially available20%paraquat herbicide, aged from12to75years, who were admitted to our hospital within24h after paraquat poisoning were enrolled in this clinical trial. All participants must comply with the treatment. Those who discontinued therapy when prognosis remained unclear were regarded as automatic drop-out. In the control group, patients underwent conventional treatment including early vomiting, gastric lavage, purgation of gastrointestinal tract toxins by cathartic intervention, clearance of absorbed poisons by blood perfusion, resisting oxidative damages by administering high dose vitamin C (lOg/d) plus reduced glutathione, methylprednisolone pulse therapy (15mg/kg×3d,7.5mg/kg×2d,3.75mg/kg×2d), prevention and treatment of infection, maintaining water-electrolyte and acid-base balance, protecting vital organs and alternative symptomatic treatments, etc. In the experimental group1, patients further received cyclosporin A treatment (5mg/kg,8h pumping by a micropump;7.5mg/kg,24h pumping by a micropump) on the basis of treatment in the control group. In the experimental group2, patients also received CVVH therapy besides treatments in the control group and experimental group1. After admission, the patients underwent CVVH treatment as early as possible according to individual status of disease:anticoagulation by heparin for (30±6) h each time, flow volume of150ml to200ml, ultrafiltration of50ml to100ml (based on patients’ regulation of fluid balance). Monitoring indexes included routine blood tests, liver and kidney function, arterial blood gas analysis, chest CT scan, superoxide dismutase (SOD) and reduced glutathione (GSH) levels measurement. IBM SPSS Statistics19software package was employed for statistical analysis. Among the three groups,3-d,3to7-d and7-d mortality were statistically compared and a variety of indexes including overall mortality, survival time of the death, incidence of hypoxemia within and after1week, incidence of organ injuries within1week after treatment, the correlation between organ injury and death, oxidation-antioxidation indexes, comparison on the changing trends between CVVH and non-CVVH treatments, etc.2. Patients with moderate to severe paraquat poisoning:according to the grading method proposed by Dinis-Oliveira et al., a stratified analysis was conducted for all intoxicated patients and divided into mild paraquat poisoning namely asymptomatic or mild gastrointestinal tract symptom occurred. Moderate to severe paraquat poisoning referred to incidence of organ function injury including liver, kidney and lung within several days to weeks after intoxication, pulmonary fibrosis was the most commonly seen and respiratory failure was the primary cause of death. Fulminant paraquat poisoning: extremely high dose oral intake of paraquat, multi-organ failure such as liver, kidney and lung within several hours to days, incidence of spasm and other central nervous system injury, multi-organ failure was the primary cause of death. The same treatment was adopted as mentioned above. IBM SPSS Statistics19software package was utilized to statistically analyze the general information and mortality of mild and fulminant paraquat poisoning among three groups, and compare the general information, mortality, incidence of liver and kidney injuries, incidence of hypoxemia, onset date and peak value of organ injury, mortality of patients with organ injury, cause of death, survival time of the death and30-d survival curve of moderate to severe paraquat intoxicated patients among all three groups.[Results]1. All paraquat poisoning patients:a total of216cases of acute paraquat poisoning were included in this trial,95male and121female (male-female ratio:1:1.27). All subjects were randomly divided into the control group (n=74,7drop-outs), experimental group1(n=76,5drop-outs) and experimental group2(n=66,18drop-outs). Finally,186patients participated in this investigation. The median quantity of orally-taken paraquat was50ml in all groups. The time from poisoning and admission in the experimental group2was the longest and statistical significance was noted among the three groups (5.5h vs5.5h vs7.7h; F=5.290, p=0.006). The overall mortality in the experimental group2was significantly lower compared with those in the other groups but no statistical significance was observed when either two groups were compared (56.7%(38/67) vs57.7%(41/71) vs45.8%(22/48)). The median survival time of the death was3d,4d and9d, respectively and significant difference was found when either two groups were compared (F=4.549, p=0.013). The incidence of MODS post-intoxication in the experimental group2was lower compared with those in the other groups but no statistical significance was observed (53.7%(36/67) vs56.3%(40/71) vs41.7%(20/48); p=0.264). The incidence of7-d hypoxemia was50.7%(34/67),43.7%(31/71) and25.0%(12/48) and significance difference existed when either two groups were statistically compared (x2=7.88, p=0.019). CVVH treatment increased SOD level with a significant increase within48h after poisoning and decreased MDA level with a significant decrease both at24h and48h post-intoxication (p<0.05).2. Patients with moderate to severe paraquat poisoning:85cases were diagnosed as moderate to severe poisoning (n=26for the control group, n=31for the experimental group1and n=28for the experimental group2). The sex ratio, time of admission, quantity of paraquat taken and blood concentration of paraquat did not significantly differ among the three groups (p>0.05). In the experimental group2, CVVH treatment was conducted twice (IQR:1to3) for61.8h (IQR:36.2to108) and the time from admission to CVVH was17.8h (IQR:7.5to32.4). Only adverse events including limb hematoma and decrease in red blood cell count were observed with a rate of21.4%. The mortality was69.2%(18/26),58.1%(18/31) and42.9%(12/28). No significant difference was found when either two groups were compared while statistical significance was noted between the experimental group2and control group (p=0.05). The median survival time of the death with moderate to severe paraquat poisoning was4,7and9d and statistical significance was noted when either two groups were compared (F=7.126, p=0.002). In addition,30-d survival curve analysis revealed that30-d survival rate significantly differed among the three groups (x2=8.183, Log-Rank p=0.004). The survival time and30-d survival rate in the experimental group2were the highest. In the control group, MODS was the primary cause of death, MODS and respiratory failure in the experimental group1and respiratory failure in the experimental group2. Significant difference was found among the three groups (x2=14.545, p=0.0007). The therapies in the experimental groups1and2significantly prolonged the incidence time of liver, kidney injuries and hypoxaemia (F=0.733, p=0.483; F=13.682, p=0.000; F=6.591, p=0.003) compared with those in the control group. Statistical significance was observed in terms of reducing the incidence of kidney injury (x2=10.04, p=0.007) while no significant difference regarding decreasing the incidence of hypoxaemia (χ2=1.99, p=0.369; x2=2.919, p=0.232). The treatments in the experimental group2lowered the peak values of ALT and Cre while alleviating liver and kidney injury while no significant difference existed among the three groups (F=0.733, p=0.483and F=2.199, p=0.117).[Conclusion] The multimodal therapy of high dose methylprednisolone, cyclosporin A pulse therapy and CVVH can prolong the survival time of patients who died from paraquat intoxication, enhance the survival rate of patients with liver and kidney injury and reduce the mortality of patients with acute paraquat intoxication, especially for patients with moderate to severe paraquat poisoning. |
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