Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning

OBJECTIVE: Paraquat is widely used in the world, and all treatments for paraquat poisoning have been unsuccessful. Many patients have died of paraquat poisoning in developing countries. A novel anti-inflammation method was developed to treat severe paraquat-poisoned patients with >50% to <90% predictive mortality: initial pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 2 days), followed by dexamethasone 20 mg/day until Pao2 was >11.5 kPa (80 mm Hg) and repeated pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 1 day), which was repeated if Pao2 was <8.64 kPa (60 mm Hg). DESIGN: Randomized controlled trial. SETTING: Academic medical center in Taiwan. PATIENTS: Twenty-three paraquat-poisoned patients with >50% and <90% predictive mortality assessed by plasma paraquat levels were prospectively and randomly assigned to the control and study groups at a proportion of 1:2. INTERVENTIONS: The control group received conventional therapy and the study group received the novel repeated pulse treatment with long-term steroid therapy. MEASUREMENTS AND MAIN RESULTS: We measured patient mortality during the study period. There was not a different distribution of basal variables between the two study groups. The mortality rate (85.7%, six of seven) of the control group was higher than that of the study group (31.3%, five of 16; p = .0272). CONCLUSIONS: The novel anti-inflammatory therapy reduces the mortality rate for patients with severe paraquat poisoning.     

糖皮质激素早期大剂量冲击联合小剂量长时间递减维持治疗对重度百草枯中毒的疗效观察

目的 探讨糖皮质激素早期大剂量冲击联合小剂量长时间递减维持治疗重度百草枯中毒的疗效.方法 实验选取2010年1月到2012年1月我院收治的重度百草枯中毒患者76例,实验组给予甲泼尼龙15mg·kg-1·d-1冲击治疗3天,后逐渐减量,每3天减为原来剂量的1/2,直到40 mg/d,之后改为口服泼尼松片,每7天减少5mg,直至5mg/d;对照组给予现行临床上的常规治疗方案,8 mg·kg-1·d-1,连续冲击3～5天,比较2周存活率,对存活超过2周的患者于2、4、6和12周行肺功能检查.结果 实验组2周生存率为52.6％,对照组2周生存率为28.9％(log rank检验,x2=5.902,P＜0.05).在2、4、6、12周,1秒用力呼气容积(FEV1)实验组为(76.40±5.54)％、(82.50±3.75)％、(83.30±4.22)％、(83.30±3.38)％,对照组为(64.80±3.90)％、(76.80±3.35)％、(77.20±3.75)％、(77.60±3.50)％;用力肺活量(FVC)在实验组为(69.60±5.74)％、(76.10±7.30)％、(75.00±6.04)％、(76.50±5.38)％,对照组为(62.40±1.52)％、(69.60±5.30)％、(68.60±5.32)％、(70.80±4.27)％;一氧化碳弥散量(DLco)在实验组为(64.20±6.76)％、(68.40±5.27)％、(68.90±4.70)％、(71.10±5.53)％,对照组为(56.00±4.30)％、(62.00±3.39)％、(62.60±2.41)％、(65.40±3.05)％.两组FEV1、FVC及DLco均呈逐渐增高趋势,FEV1、FVC及DLco在组间、不同时点差异有统计学意义(P＜0.05或＜0.01),但在组间与不同时点的交互作用差异无统计学意义(P＞0.05).结论 糖皮质激素的早期大剂量冲击联合小剂量长时间递减维持方案救治重度百草枯中毒患者能够提高生存率,且对远期的肺功能有益.     

血必净和环磷酰胺治疗百草枯中毒疗效比较研究

目的 比较血必净和环磷酰胺治疗百草枯中毒的疗效.方法 对125例确诊为百草枯口服中毒患者进行前瞻性研究,将患者随机分为治疗组(n=66)和对照组(n=59).治疗组给予血必净注射液300～400 mL/d,1周后根据患者CT表现逐渐减量;对照组给予环磷酰胺注射液500 mg/d,连用3 d后停药.两组患者均给予洗胃、导泻、白陶土、甲基强的松龙、血液灌流等治疗.观察患者临床变化,于治疗前及治疗后第3、7、14天分别检测各组患者血中白细胞计数(WBC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(STB)、血肌酐(SCr)水平,并每天检测患者动脉血氧分压(PaO2)、血乳酸(Lac),于入院第1天及每隔3 d拍1次胸部CT(1、4、8、12、30 d)了解肺部情况.同时通过2个月后随访或患者复查比较两组的生存率等.结果 ①治疗组2个月后生存率为59.1%,对照组生存率为35.6%,两组之间差异具有统计学意义(P＜0.05);②治疗组第14天生化指标优于对照组第14天的生化指标,差异有统计学意义;治疗组第14天生化指标优于第3天时,差异有统计学意义(P＜0.05);③胸部CT治疗组患者较对照组患者肺部病变改善较明显.结论 甲基强的松龙联合血必净注射液治疗百草枯中毒疗效优于联合环磷酰胺注射液.     

血液灌流联合环磷酰胺救治百草枯中毒临床分析

目的 探讨血液灌流联合环磷酰胺对急性百草枯中毒的疗效.方法该研究对我院2007-07～2010-02确诊的急性百草枯中毒患者病历资料进行回顾性分析,将患者分成三组,A组为常规治疗,B组为常规治疗加血液灌流治疗,C组为常规治疗加血液灌流联合环磷酰胺治疗.比较各组患者肝肾功能、中毒性心肌炎和MODS发生率及死亡率等变化.三组间均数比较采用方差分析或秩和检验,两两比较采用ISD法.多个率比较采用非校正x2检验.结果该研究人选患者104例,三组患者年龄、性别及服药剂量分布差异无统计学意义(P>0.05).C组患者的肝肾功能、中毒性心肌炎发生率及死亡病例存活时间等指标明显优于B组和A组,而B组患者的各项指标又优于A组(P<0.05).结论应用血液灌流联合环磷酰胺治疗可以减轻百草枯对患者各个器官的损害,降低患者的死亡率.     

早期血液灌流救治急性百草枯中毒患者临床疗效分析

目的 分析168例急性百草枯中毒患者的临床资料,探讨早期反复血液灌流(HP)的疗效.方法 收集2010年1月至2011年2月中国医科大学附属第一医院急诊监护室(EICU)收治的接受早期反复HP(服毒24h内接受HP≥2次)的81例急性百草枯中毒患者(A组)的临床资料,与2008年1月至2009年12月收治的87例患者(B组)进行对照研究,对早期反复HP的疗效进行分析.A组与B组除HP外接受统一的综合救治方案.应用SPSS 13.0软件包,计量数据以均数±标准差((-x)±s)表示,组间比较采用成组t检验,对计数资料进行x2检验.结果 168例患者均为口服百草枯农药急性中毒,A组81例,病死率64.2％,B组87例,病死率78.2％,两组病死率比较差异具有统计学意义(x2 =4.01,P=0.042).A组患者服毒至首次HP时间(3.6±3.3)h,服毒24h内平均接受HP(2.9±1.4)次.中毒后第2天开始,A组和B组患者SOFA评分均高于来诊时,中毒第3天、第4天A组患者的SOFA评分低于同日B组患者,差异具有统计学意义(P＜0.05).A组和B组的患者比较,B组患者中ALT＞ 80 U/L和TBIL＞ 34.2 μmol/L的出现时间早于A组,差异具有统计学意义(P＜0.05).B组患者中肌酐＞177 μmol/L,PaO2＜60mm Hg(1mm Hg=0.133 kPa)的患者所占的比例高于A组,且出现时间早于A组,差异具有统计学意义(P＜0.05).B组患者ALT、TBIL、肌酐、AMY、肌酸激酶MB同工酶(CK-MB)的最高值比A组患者高,而B组患者PaO2最低值比A组患者低,差异具有统计学意义(P＜0.05).结论 早期反复HP可以延迟急性百草枯中毒后脏器损伤并减轻损伤程度,为进一步采取治疗措施赢得时间.     

Combined methylprednisolone and dexamethasone therapy for paraquat poisoning

OBJECTIVE: To report a severe case of paraquat poisoning successfully treated with repeated-pulse therapy of methylprednisolone. DESIGN: Case study. SETTING: University Hospital, Lin-Kou Medical Center, Taipei, Taiwan, Republic of China. PATIENTS: A 60-yr-old man with paraquat poisoning with severe acute renal failure (serum creatinine level of 11.8 mg/dL and serum paraquat level of 3.66 microg/mL at 10 hrs after ingestion) and severe hypoxemia (Pao2, 66.6 mm Hg). INTERVENTION: Repeated 3-day pulse therapy with methylprednisolone, one course of 2-day cyclophosphamide, and a high dose of dexamethasone for 33 days. MEASUREMENTS AND MAIN OUTCOME: Arterial blood gas analysis was obtained regularly. A chest radiography was obtained every week. The arterial blood oxygen concentrations dramatically elevated from 66 mm Hg to 97 mm Hg, and the chest radiographs markedly improved after repeated-pulse therapy with anti-inflammatory agents and cyclophosphamide. CONCLUSIONS: We successfully treated a severe paraquat poisoned patient with repeated methylprednisolone pulse therapy and prolonged dexamethasone treatment. This case demonstrates that the severe inflammation, not the fibrosis, of the lungs plays a major role in the lethal hypoxemia of patients with paraquat poisoning during the subacute period and confirms our previous hypotheses. Clearly, the use of anti-inflammatory therapy to treat paraquat-poisoned patients needs further evaluation; however, anti-inflammatory therapy may be an effective treatment after failure of standard therapies.     

血液灌流联合环磷酰胺救治百草枯中毒疗效观察

目的 探讨血液灌流(HP)联合环磷酰胺对急性百草枯中毒的疗效.方法 回顾性分析本院2007年7月至2010年2月确诊的104例急性百草枯中毒患者病历资料,将患者按治疗方法不同分成3组,常规治疗组(A组,37例),常规治疗加HP组(B组,33例),常规治疗加HP联合环磷酰胺治疗组(C组,34例).治疗3周后观察患者肝、肾、心功能指标,评价器官损害情况及预后.结果 3组患者性别、年龄及服药剂量比较差异无统计学意义(均P>0.05).A组死亡31例,B组死亡15例,C组死亡12例(P=0.00);B组、C组死亡病例存活时间明显长于A组[(8.13±4.03) d、(9.67±4.12) d比(2.99±2.10) d,均P<0.01],B组与C组比较差异无统计学意义(P>0.05).B组肝、肾、心功能损害发生率明显低于A组(P<0.05或P<0.01);C组略低于B组,但差异无统计学意义(P>0.05).结论 采用HP联合环磷酰胺治疗可以减轻百草枯对患者各器官的损害,降低患者病死率.     

长期存活急性百草枯中毒患者肺功能的随访研究

目的 通过随访长期存活急性PQ中毒患者在中毒后6个月的肺功能以进一步了解PQ中毒致肺损伤的转归.方法 回顾河北医科大学第二医院急诊科于2010年9月至2012年7月收治的50例PQ中毒患者,按临床及肺CT表现分为轻型组和重型组,在中毒后6个月时测定VC％、FVC％、FEV1.0％、FEV1.0/FVC％、MMEF％,应用SPSS 20.0软件进行统计分析,观察两组肺功能的差别.结果 轻型组VC％为(93.28±7.11)％,FVC％为(94.24±7.17)％,FEV1.0％为(96.48±8.85)％,FEV1.0/FVC％为(97.83±8.21)％,MMEF％为(102.82±9.52)％;重型组VC％为(97.13±12.18)％,FVC％为(98.94±12.22)％,FEV1.0％为(99.52±12.84)％,FEV1.0/FVC％为(90.18±7.88)％,MMEF％为(91.48±11.80)％.轻型组与重型组限制性、阻塞性通气障碍异常率的比较均差异无统计学意义(P＞0.05);轻型组与重型组肺功能各检测指标异常率的比较均差异无统计学意义(P＞0.05);轻型组与重型组FEV1.0/FVC％、MMEF％比较差异有统计学意义(P＜0.05),其他指标均差异无统计学意义(P＞0.05).结论 百草枯中毒可对存活至6个月的部分患者的肺功能造成一定损伤,对重型患者小气道造成的损伤程度较轻型患者为重,但这种差异未能使阻塞性通气障碍异常率差异具有统计学意义.     

Efficacy of single or repeated hemoperfusion in a canine model of paraquat poisoning

Although hemoperfusion has been used to treat paraquat poisoning, its efficacy has been widely debated. This study examines the kinetic and pathologic correlates of paraquat toxicity and hemoperfusion and the efficacy of hemoperfusion in four groups of four dogs. This species was chosen because the kinetics and toxicity of paraquat are similar to those in the human. All dogs given a lethal dose of paraquat dichloride producing 100% mortality as a 2-hr infusion (7.48 mg of paraquat ion per kg) developed the typical clinical, laboratory and pathologic features of paraquat toxicity and died within 5 to 7 days. All dogs given paraquat and hemoperfused for 8 hr daily, beginning at 12 hr, died within 3 to 6 days. Two of four dogs which were hemoperfused once, beginning at 2 hr, survived. One dog in the repeated hemoperfusion only group died from blood loss. Negligible amounts of paraquat (0.4-2.0% of the total dose) were adsorbed during repeated hemoperfusion because of extensive excretion of paraquat in urine and sequestration in peripheral tissues from which redistribution was slow. The efficacy in the single early hemoperfusion group can be attributed to removal of 25% of the dose by the procedure in the two survivors. We conclude that single hemoperfusion may have some clinical application in patients who present within a few hours of the ingestion and have not ingested a dose of paraquat that is multiples of the lethal dose producing 100% mortality. It is doubtful if there is any role for repeated hemoperfusion.     

姜黄素治疗急性百草枯中毒的临床研究

目的:探讨姜黄素治疗急性百草枯口服中毒的临床疗效。方法:选择2007年3月-2010年3月在院救治的急性百草枯口服中毒患者74例,分为常规治疗组、激素治疗组和姜黄素治疗组。3组均常规对症治疗,激素治疗组在此基础上给予地塞米松25mg,静脉注射,每日1次。姜黄素治疗组在此基础之上给予姜黄素500mg/kg,口服,每日1次。在治疗第3天、7天、21天进行疗效评价,并对各组患者所出现的并发症进行统计。常规治疗组、激素治疗组和姜黄素治疗组均根据服毒量分组比较(20%原液或相当量<50ml组和≥50ml组)。结果:中毒治疗第3天,7天,21天,各组相比较,激素治疗组和姜黄素治疗组存活率均明显比常规治疗组高(均P<0.05),而姜黄素治疗组生存率与激素治疗组相比差异无统计学意义(P>0.05)。各组并发症发生率,即肺纤维化、急性肾功能衰竭、肝功能衰竭、MODS、DIC等并发症在激素治疗组和姜黄素治疗组均明显低于常规治疗组(均P<0.05),而激素治疗组与姜黄素治疗组之间比较差异无统计学意义(P>0.05)。结论:对急性百草枯口服中毒患者给予姜黄素治疗,其存活率和严重并发症发生率得到一定程度的改善,初步显示较好的疗效。     

Serum paraquat concentration detected by spectrophotometry in patients with paraquat poisoning

BACKGROUND:

Paraquat (PQ) is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ.

METHODS:

The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second-derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 μg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student''s t test or Fisher''s exact test.

RESULTS:

The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4–8.0 μg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer''s law with r=0.996. The average recovery rates of PQ were within a range of 95.0% to 99.5%, relative standard deviation (RSD) was within 1.35% to 5.41% (n=6), and the lower detection limit was 0.05 μg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC (r=0.995, P<0.0001). The survival rate was 22.2% in patients whose PQ concentration in serum was more than 1.8 μg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6%, 55.6% and 77.8%, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 μg/mL (P<0.05).

CONCLUSIONS:

For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second-derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 μg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.KEY WORDS: Spectrophotometry, Derivative spectrophotometry, Paraquat, Poisoning, Serum, Concentration     

强化血液灌流治疗急性百草枯中毒患者临床分析

目的探讨强化血液灌流和普通血液灌流治疗急性百草枯中毒患者的疗效。方法回顾分析百草枯中毒患者52例,根据治疗方式分为两组:A组为强化灌流组(n=28),每日行2次血液灌流,持续一周;B组为普通灌流组(n=24),每日行1次血液灌流治疗,持续一周;除了血液灌流外,两组患者的常规治疗均相同。对两组患者的死亡率和各个器官的并发症发生率进行比较;对两组患者的血白细胞、动脉血氧分压、C反应蛋白、肌酐、视黄醇结合蛋白的水平进行比较。结果 A组和B组的死亡率、急性肾损伤发生率、急性呼吸窘迫综合征发生率比较,差异有统计学意义(χ2分别=6.39、7.08、6.39,P均<0.05)。A组的血白细胞及C反应蛋白水平明显低于B组(t分别=5.06、5.57,P均<0.05),氧分压明显升高(t=7.02,P<0.05),血肌酐和视黄醇结合蛋白水平明显下降(t分别=3.61、10.81,P均<0.05)。结论和普通血液灌流相比,强化血液灌流可进一步降低百草枯中毒患者的死亡率,减少心肺和肾脏并发症的发生率。此外,强化灌流还可进一步降低白细胞及C反应蛋白水平,改善氧合。     

百草枯中毒肺部MSCT表现分析

目的总结百草枯中毒不同剂量、不同时期肺部MSCT表现特点。方法收集我院2012年1月~2014年12月64例百草枯中毒患者的临床及肺部MSCT资料,根据中毒剂量分为三组,分别是小剂量组(小于20 mg)12例,中剂量组(20~40 mg)36例,大剂量组(大于40 mg)16例;并根据病程在第1、3、7天(早期)、第15天(中期)和第30、90天(晚期)行多层螺旋CT肺部检查,对不同剂量不同病程患者的MSCT肺内表现及肺部并发症进行分析。结果百枯中毒肺部MSCT表现包括肺纹理增强、肺泡渗出、肺实变及肺纤维化。在中毒的不同时期有不同的表现,早期第1天时主要表现为肺纹理增强(26/49)、第3天以渗出为主(36/38),第7天则演变为以渗出(26/31)和实变(7/31)为主;中期(15 d)发展为渗出(18/22)、实变(10/22)和纤维化(10/22);晚期(30 d)表现为肺实变(8/14)、肺纤维化(11/14);晚期(90 d)转变为肺实变(2/6),肺纤维化(6/6)。不同剂量的中毒者也有不同的表现特点,其中小、中剂量组早期第1天以正常(11/33)或肺纹理增强(22/33)表现为主,大剂量组早期第1天即可以出现渗出改变(5/13);百草枯中毒可出现并发症,包括纵隔气肿(16/64)、胸腔积液(13/64)、胸膜增厚(14/64)、气胸(5/64)及支气管扩张(1/64)。结论不同剂量、不同时期百草枯中毒肺部MSCT表现具有一定的特点及演变规律。     

3例百草枯中毒患儿的护理

回顾分析血浆置换治疗3例百草枯中毒患儿的护理.护理要点包括:呼吸道、消化道、肾脏、肝脏的监测,在血浆置换过程中管道的护理与并发症的观察.本组2例好转出院,1例死亡.     

百草枯中毒的肺部X线表现及临床价值

目的探讨百草枯中毒的胸部X线表现及其临床价值。方法回顾分析11例临床确诊为百草枯中毒的胸部X线影像学特征。结果病变时期的不同,导致了影像学表现的多样化,典型的影像学表现为肺门向肺内散在分布的斑点状片状阴影7例（63．64％）,粟粒状阴影4例（36．36％）以及克氏B线2例和磨玻璃状影1例。结论本病的胸部X线影像学表现不具有特征性,但认识其影像学表现结合临床综合分析,对百草枯中毒肺损伤的诊断与鉴别诊断具有重要意义。     

血液灌流治疗急性百草枯中毒笔谈

急性百草枯（PQ）中毒的病死率极高,血液灌流（HP）作为PQ中毒救治的推荐方法,已经在我国得到了广泛应用,但对于HP强度以及是否合并血液透析等治疗方案目前仍无定论。最新的《2013百草枯诊治国内专家共识》推荐的方法,是HP时使用1个或多个灌流器、重复数次。而在临床实践中,临床医师多依据临床经验进行判断,随意性较大。本文就HP治疗PQ中毒的时机、模式、重复次数、以及其他合并治疗作一笔谈,以期对将来临床治疗和临床研究有所帮助。     

百草枯中毒患者的抢救与护理12例

通过对12例百草枯中毒患者的抢救与护理,总结出血液灌流和综合护理的重要性。     

百草枯中毒的研究进展

随着百草枯(PQ)的广泛应用,PQ中毒事件数量逐年增加,已成为我国第二位的农药中毒事件。PQ对人有剧毒,中毒后致多脏器严重损害,病死率极高,其中毒机制尚不完全明确,氧自由基产生学说为大多数学者认可。PQ中毒暂无特效解毒药,临床上主要采取综合治疗的办法,如洗胃、导泻、吸附体内毒素、应用激素及免疫抑制剂、清除氧自由基、保护各脏器功能等,同时结合有效的血液净化手段,本文旨在对相关进展做一简要综述。