联合大黄为主中药组方序贯治疗急性百草枯中毒患者的前瞻性临床研究

Effect of rhubarb as the main composition of sequential treatment in patients with acute paraquat poisoning：a prospective clinical research

目的：观察以大黄为主的中药组方对急性百草枯中毒（APP）患者的治疗作用。方法采用前瞻性随机对照研究方法，选择2011年3月至2013年12月河北衡水哈励逊国际和平医院收治的128例APP患者，按随机数字表法分为西医对照组（64例）和联合中药组（64例）。所有患者入院后给予反复洗胃并口服白陶土。西医对照组用20%甘露醇和（或）硫酸镁导泻，入院8 h内进行血液灌流（HP），同时给予常规药物综合治疗。联合中药组在西医对照组治疗基础上洗胃后口服百草枯中毒解毒一号方〔组成：生大黄（后下）10 g，芒硝10 g，仙鹤草12 g，甘草6 g〕导泻，2 h 1次，待停止排绿便后改服百草枯中毒解毒二号方（组成：熟大黄10 g，人参6 g，仙鹤草15 g，川芎10 g，甘草6 g），每日1次，连续14 d。观察两组患者服毒剂量、首次口服药物时间、首次灌流时间、首次排便时间、末次排绿便时间、血浆毒物清除时间、白细胞计数（WBC）、C-反应蛋白（CRP）、动脉血气、血乳酸（Lac）、肝肾功能、心肌酶谱、胸部CT、不良反应及住院时间和病死率；于治疗前和中毒12 h测定血浆和尿中的百草枯含量。出院后60 d回访胸部CT，观察肺纤维化情况。结果两组服毒剂量、首次口服药物时间、首次灌流时间比较差异均无统计学意义。与西医对照组比较，联合中药组首次排便时间（h：3.94±1.14比6.17±1.52）、末次排绿便时间（h：36.90±4.10比51.63±4.91）、血浆毒物清除时间（h：19.48±3.63比23.84±3.29）均明显提前（均P＜0.01）；WBC、CRP、丙氨酸转氨酶（ALT）、尿素氮（BUN）、血肌酐（SCr）于入院后逐渐升高，5 d达峰值〔WBC（＆#215;109/L）：15.35±2.17比17.47±2.09，CRP （mg/L）：32.62±2.76比39.51±2.45，ALT（U/L）：270.88±11.06比334.67±7.85，BUN（mmol/L）：13.29±1.90比17.63±1.42，SCr（μmol/L）：203.54±18.40比251.53±14.38，均P＜0.05〕，随后下降；Lac于入院后逐渐升高，7 d时达峰值（mmol/L：3.53±0.21比3.82±0.14，P＜0.05），随后下降；心肌酶谱于入院后逐渐升高，3 d达峰值〔肌酸激酶（CK，U/L）：192.09±16.26比216.20±11.96，肌酸激酶同工酶（CK-MB，U/L）：39.03±3.75比47.22±5.84，均P＜0.05〕，随后逐渐下降；动脉血氧分压（PaO2）、剩余碱（BE）于入院后逐渐下降，7 d降至谷值〔PaO2（mmHg：1 mmHg＝0.133 kPa）：87.04±2.37比84.93±2.44，BE（mmol/L）：-7.31±2.31比-9.18±2.49，均P＜0.05〕，随后升高。中毒12 h后，联合中药组血和尿中百草枯含量均明显低于西医对照组〔血浆（ng/L）：0.83±0.08比0.96±0.10，尿（ng/L）：0.88±0.09比0.97±011，均P＜0.05〕。联合中药组入院14 d内肺损伤程度明显轻于西医对照组，且治疗过程中未发现与中药相关的严重不良反应，住院时间明显缩短（d：20.46±6.07比29.73±9.16，P＜0.01），病死率明显降低〔35.9%（23/64）比45.3%（29/64），P＜0.05〕。60 d回访CT示，联合中药组肺纤维化程度轻于西医对照组。结论以大黄为主组方的百草枯中毒解毒一、二号方序贯治疗APP，可有效清除体内百草枯，减少毒物吸收，阻断中毒后所导致的多器官损伤，缩短住院时间，改善患者预后。

ObjectiveTo observe the effect of rhubarb as the main composition in the therapy for patients with acute paraquat poisoning （APP）.MethodsA prospective randomized controlled trial was conducted. 128 patients with APP admitted to Harrison International Peace Hospital from March 2011 to December 2013 were randomly divided into western medicine control group （n = 64） and western medicine and traditional Chinese medicine＆amp;nbsp;（TCM） combination group （n = 64）. All the patients were treated with repeated gastric lavage and oral kaolin. The patients in western medicine control group were given 20% mannitol and （or） magnesium sulfate for catharsis, early （within 8 hours of admission） hemoperfusion （HP）, and also given the routine combined therapy. In TCM combination group, in addition to the above treatment patients were given oral paraquat poisoning detoxification prescription No.1 every 2 hours for catharsis, which was composed of rhubarb 10 g, glauber salt 12 g, agrimony 12 g, and licorice 6 g. When green stool disappeared, detoxification therapy was changed to No. 2 compound once a day for 14 days, which was consisted of rhubarb 10 g, ginseng 6 g, agrimony 15 g, rhizoma chuanxiong 10 g, licorice 6 g. The poison volume, first dose of oral drug, time for the first HP, time of the first defecation, the time of last green stool, decontamination time, white blood cell count （WBC）, C-reactive protein （CRP）, arterial blood gas analysis, blood lactic acid （Lac）, liver and kidney functions, myocardial enzyme spectrum, chest CT, adverse reaction, days of hospitalization, and mortality rate were observed in both groups. The levels of paraquat in plasma and urine were determined before treatment and 12 hours after poisoning in both groups. Sixty days after discharge, chest CT was taken for observation of pulmonary fibrosis. ResultsThere were no significant differences in the poison volume, ingestion time and the time for the first HP between the two groups. Compared with western medicine control group, the first defecation time （hours： 3.94±1.14 vs. 6.17±1.52）, the last time of green stool （hours： 36.90±4.10 vs. 51.63±4.91）, and poison clean-up time from plasma （hours： 19.48±3.63 vs. 23.84±3.29） in combination with TCM group were significantly earlier （allP〈 0.01）. WBC, CRP, alanine aminotransferase （ALT）, blood urea nitrogen （BUN）, and serum creatinine （SCr） levels were gradually increased after admission in combination with TCM group, and they peaked on 5th day [WBC （＆#215;109/L）： 15.35±2.17 vs. 17.47±2.09, CRP （mg/L）： 32.62±2.76 vs. 39.51±2.45, ALT （U/L）： 270.88±11.06 vs. 334.67±7.85, BUN （mmol/L）： 13.29±1.90 vs. 17.63±1.42, SCr （μmol/L）： 203.54±18.40 vs. 251.53±14.38, allP〈 0.05], and then they declined; Lac after admission was gradually increased, and peaked at 7 days （mmol/L： 3.53±0.21 vs. 3.82±0.14, P〈 0.05）, and then it was decreased. Myocardial enzyme spectrum was increased after admission, and peaked on 3rd day [creatine kinase （CK, U/L）： 192.09±16.26 vs. 216.20±11.96, creatine kinase isoenzyme enzyme （CK-MB, U/L）：39.03±3.75 vs. 47.22±5.84, bothP〈 0.05）, and then they declined gradually. Arterial partial pressure of oxygen （PaO2） and base excess （BE） were gradually decreased after admission, down to trough on the 7th day after admission [PaO2 （mmHg, 1 mmHg = 0.133 kPa）： 87.04±2.37 vs. 84.93±2.44, BE （mmol/L）： -7.31±2.31 vs. -9.18±2.49, bothP〈 0.05], and then they were increased. At 12 hours after poisoning, paraquat contents in plasma and urine in combination with TCM group were significantly lower than those of the western medicine control group [plasma （ng/L）：0.83±0.08 vs. 0.96±0.10, urine （ng/L）： 0.88±0.09 vs. 0.97±011, bothP〈 0.05]. The injury to lung tissue was significantly improved in combination with TCM group compared with that in the western medicine control group, and no serious adverse reactions was found, and the hospital stay time （days： 20.46±6.07 vs. 29.73±9.16） was significantly shortened （P〈 0.01）, and the mortality rate [35.9% （23/64） vs. 45.3% （29/64）] was significantly lowered compared with western medicine control group （P〈 0.05）. In the combination with TCM group pulmonary fibrosis was lighter than that in the western medicine control group during the 60-day follow-up. ConclusionThe sequential treatment of No. 1 and No. 2 detoxification of APP, using rhubarb as the main drug, can effectively eliminate paraquat, reduce absorption of the toxin, prevent the development of multiple organ dysfunction syndrome （MODS） induced by the toxin, shorten the hospital stay days, and improve the prognosis of APP.