血液灌流与持续静脉-静脉血液滤过在治疗百草枯中毒中疗效观察

目的：总结血液灌流（HP）与持续静脉-静脉血液滤过（CVVH）对百草枯（PQ）中毒患者的疗效,以便探讨更加有效的治疗模式。方法：回顾性分析了54例PQ中毒患者,分成对照（常规治疗）组（14例）及试验组（40例）,两组均给予常规治疗,试验组加予血液灌流（HP）或CVVH或血液灌流＋持续血液滤过（HP＋CVVH）,比较生存率、死亡生存天数、MODS发生率、肺纤维化发生率的情况。结果：试验组较对照组死亡生存天数明显增加,以HP＋CWH组增加最为显著;4h内行HP治疗组的生存率高于4h组,而MODS的发生率降低。结论：CVVH能明显延长PQ中毒患者的生存时间,有效降低早期死亡率,并有望降低整体死亡率;早期、足够的HP治疗能够改善PQ中毒患者的预后,提高生存率;合理的HP及CVVH联合使用有望提高PQ中毒患者的整体救治成功率。     

Drug dosing during continuous arteriovenous hemofiltration

An overview of continuous arteriovenous hemofiltration (CAVH), which is an alternative to hemodialysis and peritoneal dialysis in the management of acute renal failure, is provided, and literature concerning drug clearance via hemofiltration is reviewed. CAVH is a slow, continuous process that removes, by convective mass transport, non-protein-bound solutes smaller than 10,000 daltons from blood diverted through an extracorporeal filter. The system provides a creatinine clearance of approximately 10 mL/min. The sieving coefficient of a particular compound reflects its ability to permeate the filter membrane and is primarily influenced by protein binding. Clearance of a compound depends on its sieving coefficient and the ultrafiltration rate. Methods for estimating drug clearance, the amount of drug removed per time interval, and appropriate drug dosages are discussed. Many drugs commonly used in an intensive-care setting, including aminoglycosides, cephalosporins, acyclovir, vancomycin, phenobarbital, ranitidine, and theophylline, can be expected to have a limited but clinically important clearance during CAVH. CAVH substantially enhances the current treatment of acute renal failure; although limited data for specific drugs are available in the literature, drug dosages may be adjusted based on the methods outlined in this review.     

连续性静脉-静脉血液滤过联合血液灌流对百草枯中毒疗效的研究

目的 探讨连续性静脉-静脉血液净化(CVVH)对口服百草枯急性中毒的疗效,及其对百草枯中毒患者血清炎性因子的影响.方法 回顾分析2010年1月至2016年6月福州总医院第一附属医院急诊科诊治的急性口服百草枯中毒患者62例的临床资料.所有患者均给予包括血液灌流在内的常规治疗(对照组30例),在此基础上给予CVVH治疗的32例为观察组,比较2组患者一般临床资料和预后,分析2组患者血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、动脉血氧分压、血清肌酐(Cr)和丙氨酸氨基转移酶(ALT)的变化.结果 与对照组相比,观察组第3、7天时TNF-α、Cr和ALT降低(P＜0.05);观察组IL-6、动脉血氧分压在第3天时差异无统计学意义(P＞0.05),第7天差异有统计学意义(P＜0.05).观察组和对照组治疗总有效率分别为71.9％、56.7％(P＞0.05),2组治疗结果为痊愈、好转、有效和死亡人数构成比上差异无统计学意义(P＞0.05).结论 CVVH对急性百草枯中毒患者能清除炎性因子TNF-α和IL-6,可提高百草枯中毒患者治疗总有效率.     

Pharmacokinetics of cefmenoxime in renal-failure patients undergoing continuous arteriovenous hemofiltration

We investigated the pharmacokinetics of cefmenoxime (CMX) administrated to renal-failure patients undergoing continuous arteriovenous hemofiltration (CAVH). CAVH was carried out with a filter (0.5 m2) employing a PAN-50P (hollow fiber type) made of polyacrylonitrile membrane, with a blood flow rate of 100 ml/min and a filtration rate of 1,200 ml/hr. At 5 and 300 minutes after the CMX administration, the concentrations of CMX in the serum were 126.8 mg/L and 31.5 mg/L, respectively. The T1/2 beta was 3.55 hours. In 300 minutes after the administration of CMX, the total amount of CMX contained in the filtrate corresponded to 11.6% of the administered dose.     

血液灌流联合连续性静脉-静脉血液滤过救治重度急性中毒的疗效观察

目的探讨血液灌流（HP）联合连续性静脉-静脉血液滤过（CVVH）救治重度急性中毒的临床效果。方法在彻底洗胃、导泻、利尿、保肝等综合治疗的基础上,治疗组采用HP联合CVVH治疗,对照组采用单纯HP治疗。结果治疗组患者的昏迷时问[（9．12±2．21）h]、平均住院时间[（11．46±3．50）d]明显短于对照组[（18．85±4．28）h、（22．27±2．90）d]（P〈0．05）,死亡率明显低于对照组（10．63％US36．13％,P〈0．05）,治愈率明显高于对照组（89．37％vs63．87％,P〈0．05）。两组患者治疗前后格拉斯哥昏迷量表评分比较,治疗组明显提高,差异有统计学意义（P〈0．05）;急性生理学与慢性健康状况Ⅱ（APACHEⅡ）评分比较,治疗组明显降低,差异有统计学意义（P〈0．05）。结论HP联合CVVH是治疗重度急性毒物中毒更有效的方法之一。     

The pharmacokinetic profile of voriconazole during continuous high-volume venovenous hemofiltration in a critically ill patient

In critically ill patients, dosage adjustment of voriconazole could be helpful when high-volume continuous venovenous hemofiltration is needed. Voriconazole pharmacokinetics were studied in an anuric critically ill patient, under high-volume continuous venovenous hemofiltration, over an interval period after a 4-mg/kg dose of voriconazole. Arterial and effluent voriconazole concentrations were measured after liquid phase extraction using a high-pressure liquid chromatography. The extrapolate area under the curve(0-12h) of voriconazole was 65 mg/h/L. The total body clearance of voriconazole was 5.4 L/h with a half-life of 16.5 hours and a distribution volume of 128.6 L. The estimated sieving coefficient was 0.58 and the filtration clearance 1.39 L/h. High-volume continuous venovenous hemofiltration could affect voriconazole disposition in contrast with other techniques. Besides, we observed voriconazole accumulation consequence of the saturation of the metabolic clearance resulting from multiple organ failure. Dosage adjustment seems to be required in these conditions, but this observation must be confirmed by a clinical study.     

血液灌流联合血液透析抢救百草枯中毒12例疗效观察

目的：观察血液灌流（HP）和血液透析（HD）联合治疗百草枯中毒疗效。方法：35例百草枯中毒患者，按照他们所接受治疗方法的不同分成3组，其中接受常规综合治疗的13例为对照组，在常规综合治疗的基础上联合使用HP的10例为HP组，联合使用HP＋HD的12例为HP＋HD组，将他们的临床资料进行比较分析。结果：经血液净化治疗后抢救成功率明显提高，而且接受HP＋HD联合治疗的患者病死率较接受另外两种方法治疗的患者病死率下降。结论：对百草枯严重中毒的患者应尽早行血液净化治疗。且HP＋HD联合治疗可能是抢救百草枯中毒的一种较好方法。     

兔急性草乌中毒血液灌流后的毒代动力学研究

目的：建立高效液相色谱．质谱检测兔血浆乌头碱、次乌头碱和新乌头碱的方法,研究兔急性草乌中毒血液灌流后的毒代动力学。方法：普通级健康成年雄性日本大耳白兔8只,体重（2．5±0．2）kg,予草乌酒1．0mL／kg灌胃（i．g．）染毒,染毒后0．25h予血液灌流2h。分别于染毒后0．5、1、1．5、2、3、4、6、12、24h取血浆。以高效液相色谱．质谱法检测血浆新鸟头碱、乌头碱、次乌头碱的浓度。应用DAS2．0程序计算毒代动力学参数。结果：急性草乌中毒血液灌流后,新乌头碱毒代动力学参数为：tmax（3．1±0．8）h、Cmax（11．5±2．1）μg／L、Ka（1．6±0．9）h、Ke（0．13±0．05）h、t1/2（5．9±1．7）h、V/F（85．4±20．9）L／kg、CL／F（10．28±1．46）L·h～·kg～;乌头碱毒代动力学参数为：tmax（3．2±0．5）h、Cmax（18．7±5．5）μg／L、Ka（1．2±0．4）h、Ke（0．10±0．03）h、t1/2（7．5±2．4）h、V/F（2．7±1．0）L／kg、CL／F（0．25±0．08）L·h^-1·kg^-1;次乌头碱毒代动力学参数为：tmax（3．0±0．8）h、Cmax（14．6±11．0）μg／L、Ka（1．4±1．2）h、Ke（0．09±0．03）h、t1/2（8．3±2．1）h、V／F（10．7±6．9）L／kg、CL／F（0．85±0．38）L·h^-1·kg^-1。结论：急性草乌中毒兔血液灌流治疗后的毒代动力学呈一级吸收的一室模型。     

血液灌流联合连续性血液滤过治疗急性中毒合并多器官功能障碍的临床观察

目的探讨血液灌流联合连续性血液滤过治疗急性中毒引起多器官功能障碍的治疗效果。方法对7例急性中毒合并多器官功能障碍的患者给予血液灌流（HP）联合连续性血液滤过（CRRT）治疗,观察治疗前后生化指标。结果 6例抢救成功,1例患者家属放弃治疗。患者治疗前后生化指标明显好转（P〈0.05）。结论血液灌流（HP）联合连续性血液滤过（CRRT）治疗急性中毒合并多器官功能障碍效果显著。     

血液灌流串联血液透析救治急性百草枯中毒的临床研究

目的研究血液灌流串联血液透析治疗急性百草枯中毒的临床效果。方法临床按照不同中毒剂量区别治疗,分别分为治疗组：常规治疗＋HP串联HD;对照组：单纯常规治疗。结果不同中毒剂量的治疗组与对照组死亡率不同,死亡患者中的存活时间治疗组较对照组长（P〈0．05）。结论急性百草枯中毒服毒量越大死亡率越高（P〈0．05）,服毒量≤100ml中毒患者HP串联HD治疗可明显降低死亡率（P〈0．05）,临床可以使用血液灌流串联血液透析治疗百草枯中毒的患者,提高患者存活率。     

Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach

Aims

Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive therapy in hospitalized paraquat-intoxicated patients. The aim of this analysis was to characterize the toxicokinetics and toxicodynamics of paraquat in this population.

Methods

A non-linear mixed effects approach was used to perform a toxicokinetic/toxicodynamic population analysis in a cohort of 78 patients.

Results

The paraquat plasma concentrations were best fitted by a two compartment toxicokinetic structural model with first order absorption and first order elimination. Changes in renal function were used for the assessment of paraquat toxicodynamics. The estimates of toxicokinetic parameters for the apparent clearance, the apparent volume of distribution and elimination half-life were 1.17 l h⁻¹, 2.4 l kg⁻¹ and 87 h, respectively. Renal function, namely creatinine clearance, was the most significant covariate to explain between patient variability in paraquat clearance.This model suggested that a reduction in paraquat clearance occurred within 24 to 48 h after poison ingestion, and afterwards the clearance was constant over time. The model estimated that a paraquat concentration of 429 μg l⁻¹ caused 50% of maximum renal toxicity. The immunosuppressive therapy tested during this study was associated with only 8% improvement of renal function.

Conclusion

The developed models may be useful as prognostic tools to predict patient outcome based on patient characteristics on admission and to assess drug effectiveness during antidote drug development.     

血液灌流治疗百草枯急性重度中毒疗效分析

目的:观察血液灌流治疗百草枯急性重度中毒的临床疗效.方法:总结我院31例急性重度百草枯中毒患者的临床资料.根据收治时间、是否进行血液灌流分为非灌流组16例和灌流组15例,非灌流组为百草枯中毒常规急救治疗,灌流组为百草枯中毒常规急救治疗基础上应用血液灌流进行抢救处理.结果:灌流组总有效率(53.3％)显著高于非灌流组(12.5％),组间比较差异有统计学意义(x2=5.907,P＜0.05).灌流组急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)、多器官衰竭(MOF)发生率显著低于非灌流组;死亡病例生存时间显著高于非灌流组.灌流组治疗12h后ALT、AST、CK、CKMB、LDH显著低于于非灌流组;氧分压显著高于非灌流组;无栓塞、休克等并发症发生.结论:血液灌流可降低百草枯对急性重度中毒患者重要脏器的损害,提高治疗有效率、降低并发症的发生.     

Continuous arteriovenous hemofiltration of aminoglycoside antibiotics in critically ill patients

The effect of continuous arteriovenous hemofiltration on the clearance of either tobramycin or gentamicin (mean dose, 1.65 +/- 0.36 mg/kg) was studied in eight critically ill patients. Mean aminoglycoside clearance by hemofiltration was 3.47 +/- 1.93 mL/min and total body clearance was 11.92 +/- 3.51 mL/min. Hemofiltration clearance (HFCL) was directly correlated with hemofiltration flow rate (HFQR): HFCL (mL/min) = 1.03 HFQR (mL/min)-0.88 (R = .89). Mean volume of distribution was 0.31 +/- 0.08 L/kg, and the elimination rate constant was 0.020 +/- 0.01 hr-1. Continuous arteriovenous hemofiltration was responsible for the removal of between 3% and 36% of each aminoglycoside dose in 24 hours. In critically ill patients with changing hemofiltration flow rates, measurement of multiple serum aminoglycoside concentrations is necessary to accurately assess dosing requirements and avoid ototoxicity and nephrotoxicity.     

血浆置换联合血液灌流治疗百草枯中毒的临床应用

目的 探讨血浆置换联合血液灌流(PE/HP)治疗百草枯中毒的疗效.方法 系统回顾2011年5月～2012年8月本院急救中心收治的22例百草枯中毒患者资料,在综合性内科治疗的基础上加用血浆置换(plasma exchange,PE)及血液灌流(Hemoperfusion,HP).观察治疗前后临床症状、生化指标的变化.结果 22例百草枯中毒患者经PE联合HP治疗后,临床症状显著减轻,总有效率为77.3％.结论 PE/HP是抢救百草枯中毒患者的有效措施之一,治疗效果良好,应尽早使用.     

Changes in plasma antiproteases in paraquat poisoned rats using micro two-dimensional electrophoretic analysis.

Rats were subjected to subacute paraquat (PQ) exposure (7 mg/kg sc daily for 6-9 administrations). They were divided into a group that died from subacute toxicity, a group that recovered from the subacute toxicity and progressed to pulmonary fibrosis, and a group that showed no effects from the PQ. The rats with subacute fatal toxicity had a remarkable increase in a2M-1. Those which progressed to pulmonary fibrosis had remarkable decreases in a2M-2, a2M-3, and a2M-4 and a1AT. The rats that showed no effects from the PQ had relative increases in all molecular species of a2M. Increases in major a2M molecular species, a2M-1 and a2M-4, and a minor molecular species, a2M-3, were characteristically observed.     

血液灌流联合血液透析治疗急性百草枯中毒的临床分析

目的：探讨血液灌流加血液透析治疗百草枯中毒的疗效。方法：选择确诊的百草枯中毒患者16例,在常规内科综合治疗同时,采用血液灌流加血液透析治疗。结果：16例急性百草枯中毒患者治愈9例,好转4例,死亡3例。抢救百草枯中毒除常规内科综合治疗外,尽早强化血液透析加血液灌流,抢救成功率明显提高。结论：对百草枯中毒用血液透析与血液灌流联合进行且要尽早进行。