6%羟乙基淀粉130/0.4和6%羟乙基淀粉200/0.5急性高容量血液稀释对全麻患者凝血功能的影响

目的 评价6%羟乙基淀粉130/0.4(6% HES130/0.4)和6%羟乙基淀粉20010.5(6% HES200/0.5)急性高容量血液稀释(AHHD)对全麻患者凝血功能的影响.方法 择期全麻手术患者60例,ASA Ⅰ或Ⅱ级,年龄18～64岁,随机分为3组(n=20):对照组(C组)、6%HES200/0.5组(H组)及6%HES130/0.4组(V组).H组和V组于麻醉诱导前90 min分别静脉输注6% HES200/0.5或6% HES130/0.4,速率20 ml·kg-1·h-1,扩容量20ml/kg;C组仅静脉输注乳酸钠林格氏液6～8 ml·kg-1·h-1.于AHHD前、AHHD后即刻及AHHD后1 h采血,进行下述指标的测定:血小板计数、凝血酶原时间(PT)、血小板最大聚集率和Sonoclot玻璃珠激活全血凝固时间(gbACT)、凝结速率(CR)、血小板功能(PF)和曲线达峰时间.H组和V组同时还测定活化部分凝血活酶时间(APTT)、凝血因子Ⅷ活性(FⅧ:C)、von Willebrand因子(vWF)水平.结果 与AHHD前比较,H组和V组AHHD后PT和APTY均延长,FⅧ:C下降(P＜0.05),但2组AHHD后1 h FⅧ:C高于AHHD后即刻(P＞0.05);H组和V组AHHD后血小板最大聚集率降低,但AHHD后1 h高于AHHD后即刻(P＜0.05).与H组比较,V组AHHD后CR降低(P＜0.05),其他凝血功能指标比较差异无统计学意义(P＞0.05).结论 6%HES130/0.4和6% HES200/0.5(20 ml/kg)AHHD对全麻患者凝血功能的抑制作用较轻;两者对凝血功能的影响无明显差异.     

Plasma substitution effects of a new hydroxyethyl starch HES 130/0.4 compared with HES 200/0.5 during and after extended acute normovolaemic haemodilution

Background. The volume expansion effect of a recently introducedhydroxyethyl starch, HES 130/0.4, was compared with the commonlyused HES 200/0.5 after rapid infusion of a single large dose(up to 2 litres) administered during acute normovolaemic haemodilution(ANH). Methods. This prospective, randomized, double-blind study included40 patients scheduled for major abdominal surgery with no contraindicationto ANH. Patients were randomized to undergo ANH with eitherHES 130/0.4 (n=20) or HES 200/0.5 (n=20). Blood was collectedto reach a target haemoglobin level of about 8.0 g dl^–1and simultaneously replaced by the same volume of colloid (HES130: 1825 [SD 245] ml; HES 200: 1925 [183] ml). Heart rate,mean arterial pressure, cardiac filling pressure, and cardiacoutput were measured before induction of anaesthesia (baseline),10 min after completion of ANH, before surgery, at the end ofsurgery and on the following morning (postoperative day 1; POD1).ANH blood was systematically retransfused during surgery orbefore POD1. Results. Exchange of about 40% of blood volume resulted in similarhaemodynamic changes in both groups. Filling pressures increasedsignificantly, while cardiac index remained unchanged (HES 130:from 3.3 [0.4] to 3.2 [0.7] litre min^–1 m^–2; HES200: from 3.0 [0.6] to 3.1 [0.7] litre min^–1 m^–2).Need for crystalloids and colloids was similar between the groupsduring surgery and on POD1. Total blood loss (HES 130: median2165 ml, range 660–2970 ml; HES 200: median 2464 ml, range640–19 380 ml) and amount of allogeneic red blood cellstransfused (HES 130: median 0, range 0–4 units; HES 200:median 0, range 0–18 units) were comparable in the twogroups. Conclusions. This study demonstrates a good immediate and medium-termplasma volume substitution effect of HES 130 compared with HES200. HES 130 could represent a suitable synthetic colloid forplasma volume substitution during extensive ANH. Br J Anaesth 2003; 91: 196–202     

Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5

Hydroxyethyl starch (HES) solutions are effective plasma volume expanders. Impairment of coagulation occurs with large HES volumes infused perioperatively. Therefore, a lower substituted novel HES (Voluven; Fresenius Kabi, Bad Homburg, Germany) was developed to minimize hemostatic interactions, and was compared with HAES-steril (Fresenius Kabi) (pentastarch) regarding safety and efficacy. We performed a prospective, randomized, double-blinded study in 100 major orthopedic surgery patients. Because the 95% confidence interval (-330 mL; +284 mL) for the treatment contrast Voluven-HAES-steril was entirely included in the predefined equivalence range (+/- 500 mL), comparable efficacy was established. Voluven interfered significantly less than HAES-steril with coagulation factor VIII levels and partial thromboplastin time postoperatively. Total amounts of red blood cells transfused were comparable between the Voluven and HAES-steril groups, but a significantly reduced need for homologous red blood cells was observed in the Voluven group. We conclude that in large-blood-loss surgery, Voluven has a comparable efficacy with HAES-steril and may reduce coagulation impairment, possibly leading to a smaller number of allogeneic blood transfusions. IMPLICATIONS: Hydroxyethyl starches are common plasma volume expanders, but may interfere with coagulation at large doses. We tested a novel hydroxyethyl starch specification (Voluven; Fresenius Kabi, Bad Homburg, Germany) which was developed to reduce hemostatic interactions while preserving its efficacy in restoring plasma volume in comparison to HAES-steril (pentastarch; Fresenius Kabi) in major orthopedic surgery.     

Effects of two different hydroxyethyl starch solutions (HES200/0.5 vs. HES130/0.4) on the expression of platelet membrane glycoprotein

BACKGROUND: There are various hydroxyethyl starch (HES) solutions with different degrees of hydroxylation and different molecular weights. HES200/0.5 solution is most commonly used. HES130/0.4 is a new HES solution and is the 'state-of-the-art' in volume substitution. However, the mechanism of the observed anticoagulation action of HES has not been fully delineated. The objective of this study was to further investigate the effect of HES200/0.5 and HES130/0.4 on platelet coagulation. METHODS: Sixty ASA I-II patients undergoing elective minor surgery were randomly allocated to receive an intravenous infusion (20 ml/kg) of lactated Ringer's solution (group L), HES200/0.5 (group H) or HES130/0.4 (group V) after the induction of anesthesia. The expression of CD42b, CD41/61 and CD62p in vivo was assessed on non-stimulated platelets and adenosine diphosphate (ADP) agonist-activated platelets using flow cytometry. RESULTS: Resting glycoprotein expression of the non-stimulated platelets was observed. HES200/0.5 and HES130/0.4 reduced the CD42b, CD41/61 and CD62p expression of ADP-agonist-activated platelets at 15 min after intravenous infusion. At 6 h after intravenous infusion, the trend of decreasing expression of activated CD42b, CD41/61 and CD62p was maintained in group H. However, CD42b, CD41/61 and CD62p expression returned to the pre-operative level in group V. CONCLUSION: This study showed that both HES200/0.5 and HES130/0.4 can inhibit platelet coagulation. Platelet dysfunction experienced a faster recovery after the infusion of HES130/0.4 than after HES200/0.5. Liquid resuscitation with HES130/0.4 may decrease the risk of hemorrhage in the operative period.     

The influence of two different hydroxyethyl starch solutions (6% HES 130/0.4 and 200/0.5) on blood viscosity

We performed the current study to investigate the influence of 2 different hydroxyethyl starch (HES) solutions, the novel medium molecular weight HES 130/0.4 (6%) and HES 200/0.5 (6%), on plasma and whole blood viscosity in vitro and ex vivo in patients with severe head injury. For the in vitro experiments, blood was incubated with increasing concentrations (0%-50% vol/vol plasma) of either 6% HES 130/0.4 or 6% HES 200/0.5 solution. Plasma viscosity and whole blood viscosity (hematocrit [Hct] 45%) at high (94.5 s(-1)) and low (0.1 s(-1)) shear rates were determined. Both HES solutions increased plasma viscosity, but HES 130/0.4 to a lesser extent than HES 200/0.5. Whole blood viscosity was significantly less with HES 130/0.4 than with HES 200/0.5 at concentrations of 37.5% and larger. In the ex vivo study on 31 patients with severe cranio-cerebral trauma treated randomly with either HES 130/0.4 or HES 200/0.5 over several days, frozen plasma samples were thawed and plasma viscosity was determined. Blood was reconstituted with normal erythrocytes (0, Rh neg, Hct 45%) for whole blood viscosity measurements. In both groups plasma and blood viscosity tended to increase over time without statistical significance. Although the prominent effects found in vitro are not in keeping with the ex vivo data, they are likely to reflect the true clinical situation during repetitive, large-dose HES administration. We therefore conclude that HES 130/0.4 may have hemorheological advantages over conventional HES 200/0.5 when used in large quantities.     

羟乙基淀粉200/0.5和羟乙基淀粉130/0.4术前急性高容量血液稀释对结肠癌根治术患者血液流变学的影响

目的 评价6%羟乙基淀粉(HES)200/0.5和6%HES 130/0.4术前急性高容量血液稀释(AHH)对结肠癌根治术患者血液流变学的影响.方法 择期在全麻下行结肠癌根治术患者40例,ASA Ⅰ或Ⅱ级,随机分为2组(n=20),麻醉诱导期间于30 min内静脉输注15 ml/kg HES 200/0.5(Ⅰ组)或HES 130/0.4(Ⅱ组),AHH结束后开始手术.分别于麻醉诱导前(基础状态,T0)、AHH后即刻(T1)、AHH结束后1 h(T2)和术后1 h(T3)时抽取静脉血样,检测全血粘度、血浆粘度、红细胞聚集指数、血小板聚集指数和红细胞压积(Hct).结果 与T0时比较,Ⅰ组T1时全血低切粘度和红细胞聚集指数降低,T1-3时全血中切粘度、全血高切粘度、血浆粘度、血小板聚集指数和Hct降低,Ⅱ组T1-3时全血低切粘度、全血中切粘度、全血高切粘度、血浆粘度、红细胞聚集指数和Hct降低(P<0.05);与Ⅰ组比较,Ⅱ组T2,3时全血低切粘度和红细胞聚集指数降低,T1-3时血小板聚集指数升高(P<0.05).结论 6%HES 200/0.5与6%HES 130/0.4(15 ml/kg)术前AHH均能改善结肠癌根治术患者围术期血液流变学,其中6% HES 130/0.4的效果较好.     

The effects of in vitro hemodilution with 6% hydroxyethyl starch (HES) (130/0.4) solution on thrombelastograph analysis in patients undergoing liver transplantation

Bang SR, Kim YH, Kim GS. The effects of in vitro hemodilution with 6% hydroxyethyl starch (HES) (130/0.4) solution on thrombelastograph analysis in patients undergoing liver transplantation.
Clin Transplant 2011: 25: 450–456. © 2010 John Wiley & Sons A/S. Abstract: Introduction: The aim of this study was to determine the effects of in vitro hemodilution with 6% HES (130/0.4) solution on thrombelastograph^® (TEG) parameters in whole blood samples from patients with end‐stage liver disease (ESLD). Methods: Enrollment consisted of 95 patients with ESLD undergoing liver transplantation. Blood was diluted by 11%, 22%, and 33% with 6% HES (130/0.4) solution. Normal saline was used as a control diluent. Results: When blood was diluted by 33% with normal saline, only the reaction time (r) was increased (p < 0.0001) compared to the baseline value. When blood was diluted with 6% HES (130/0.4), 11% dilution decreased maximum amplitude (MA) (p = 0.003) compared to baseline. At 33% dilution, the r (p < 0.0001, vs. baseline) and K (p < 0.0001, vs. baseline; p < 0.0001, vs. normal saline) increased, and the MA, alpha angle, and coagulation index (p < 0.0001, vs. baseline; p < 0.0001, vs. normal saline) decreased. Conclusion: Hemodilution with 6% HES (130/0.4) solution results in TEG abnormalities even with 11% hemodilution, in whole blood samples of patients with ESLD undergoing liver transplantation.     

不同羟乙基淀粉急性高容量血液稀释对大面积烧伤患者围术期凝血功能的影响

目的 评价羟乙基淀粉130/0.4(HES 130/0.4)与羟乙基淀粉200/0.5(HES 200/0.5)急性高容量血液稀释(AHH)对大面积烧伤患者围术期凝血功能的影响.方法 拟行早期切痂术的大面积烧伤患者40例,年龄18～49岁,ASAⅡ级,随机分为HES 200/0.5组(HES 200组)与HES 130/0.4组(HES 130组),每组20例,另选20名健康志愿者为正常对照组(C组).麻醉诱导开始时HES 200组和HES 130组经30 min分别静脉输注HES 200/0.5、HES 130/0.4 15 ml/kg,行AHH,C组不予任何处理.于麻醉诱导前(T0)、AHH结束即刻(T1)、AHH后1 h(T2)、术后1 h(T3)时采用流式细胞仪检测血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa)、CD62P的表达水平,采用血栓弹力图描记仪测定以下指标:反应时间(R).凝血时间(K)、α角、最大振幅(MA)和凝血指数(CI).结果 与C组比较,HES 200组和HES 130组血小板GPⅡb/Ⅲa、CD62P表达上调,R、K缩短,α角、MA、CI增大(P<0.05);与HES 200组比较,HES 130组血小板GPⅡb/Ⅲa、CD62P表达上调,R缩短,α角、MA和CI增大(P<0.05);与T0时比较,HES 200组AHH后血小板GPⅡb/Ⅲa、CD62P表达下调,R、K延长,α角、MA、CI减小(P<0.05),HES 130组R、K延长,α角、CI减小(P<0.05),MA和血小板GPⅡb/Ⅲa、CD62P差异无统计学意义(P>0.05).结论 HES 200/0.5 AHH可抑制大面积烧伤患者围术期血小板过度活化,其减轻血液高凝状态的效应强于HES 130/0.4.     

Evaluation of a new hydroxyethyl starch solution (HES 130/0.4) in patients undergoing preoperative autologous blood donation.

STUDY OBJECTIVE: To compare the tolerance and efficacy of the new hydroxyethyl starch (HES) 130/0.4 with a current HES solution (HES 200/0.5) in patients undergoing preoperative autologous blood donation as a model of surgical blood loss. HES 130/0.4 is expected to be a plasma substitute as efficacious as current HES solutions while offering such advantages as more complete renal elimination and reduced tissue storage. DESIGN: Controlled, randomized, double-blind, phase II clinical trial. SETTING: 1500-bed university hospital. PATIENTS: 60 ASA physical status II and III patients scheduled for elective cardiac and noncardiac surgery, and meeting selection criteria for autologous blood donors. INTERVENTIONS: Collection of 500 mL of blood with simultaneous intravenous (IV) infusion of 500 mL of either HES 130/0.4 or HES 200/0.5 (mean molecular weight 130 kD and 200 kD, degree of substitution 0.4 and 0.5, respectively). MEASUREMENTS: Noninvasive measurements of heart rate and arterial blood pressure were obtained every 5 minutes until 1 hour after blood donation and infusion of the study drugs; laboratory studies (complete blood counts, electrolytes, markers of renal and liver function) were performed; and follow-up assessment of adverse events was undertaken by questionnaire 24 hours after blood donation and infusion of the study drugs. MAIN RESULTS: Both hemodynamics and laboratory test results did not differ significantly between the groups at any time. Hemodynamics remained stable in each group, and no adverse event was observed in any patient until one hour after blood donation and infusion of the study drugs. Adverse events elicited by postphlebotomy questionnaire were mild and probably unrelated to HES infusion. CONCLUSIONS: Intravenous infusion of 500 mL of the new HES 130/0.4 was tolerated well and maintained cardiovascular stability in patients undergoing preoperative autologous blood donation. HES 130/0.4 proved equivalent to HES 200/0.5 in every measured respect. Its pharmacokinetic profile may render HES 130/0.4 an attractive alternative to current HES solutions.     

6％羟乙基淀粉130／0．4在小儿腹部手术中容量治疗的临床应用

目的 探讨6％羟乙基淀粉130／0．4在小儿腹部手术中容量治疗的应用效果。方法60例拟行腹部手术的患儿随机分为观察组和对照组,每组各30例。观察组术中容量治疗使用6％羟乙基淀粉130／0．4及晶体液;对照组未使用6％HES130／0．4,所使用的晶体液与观察组相同,可选用胶体液为浓缩红细胞。观察两组患儿手术前后心率、血压．总输液量及晶体液、胶体液、浓缩红细胞输入量等。记录观察组因输注6％羟乙基淀粉可能出现的不良反应,如：过敏（包括低血压、皮疹等）。结果两组输液总量无显著性差异。观察组与对照组相比：胶体液用量、晶体液用量、浓缩红细胞用量均有显著性差异,（P〈0．05）。观察组未发现因输注6％羟乙基淀粉130／0．4而出现的不良反应。结论6％羟乙基淀粉130／0．4可安全、有效的用于小儿腹部大手术中的容量治疗。     

Large-dose Hydroxyethyl Starch 130/0.4 Does Not Increase Blood Loss and Transfusion Requirements in Coronary Artery Bypass Surgery Compared with Hydroxyethyl Starch 200/0.5 at Recommended Doses

Background: Hydroxyethyl starch (HES) 130/0.4 may impair blood coagulation less than other HES solutions and, thus, may be used at larger doses without increasing the risk of postoperative bleeding. This study tested the hypothesis that volume replacement with 6% HES 130/0.4 at a dose of up to 50 ml/kg does not increase blood loss and transfusion requirements in elective coronary artery bypass surgery compared with 6% HES 200/0.5 at a dose of up to 33 ml/kg.

Methods: One hundred twenty adult patients scheduled for elective coronary artery bypass surgery were randomized to receive up to 50 ml/kg of 6% HES 130/0.4 or up to 33 ml/kg of 6% HES 200/0.5 for volume replacement during surgery and until 24 h thereafter. Volume requirements in excess of the respective maximum dose of HES were treated with gelatin. Colloid use was at the discretion of the attending physicians and not dictated by protocol. The primary outcome variable was chest tube drainage volume during the first 24 h after surgery.

Results: The data from 117 patients (HES 130/0.4, 59 patients; HES 200/0.5, 58 patients) who completed the study according to protocol were analyzed. The median volumes of HES administered were 49 and 33 ml/kg in the HES 130/0.4 and HES 200/0.5 groups, respectively (P < 0.001). Consequently, patients in the HES 130/0.4 group required less gelatin in addition to HES than those in the HES 200/0.5 group (medians: 7 ml/kg vs. 20 ml/kg, P < 0.001). The combined volumes of HES and gelatin were similar for both groups (P = 0.21). The 24-h chest tube drainage (medians: 660 ml vs. 705 ml, P = 0.60) did not differ significantly between the groups, nor did transfusion outcome.     

羟乙基淀粉130/0.4急性高容量血液稀释对骨科手术患者内环境的影响

目的探讨硬膜外复合全身麻醉下6%羟乙基淀粉130/0.4急性高容量血液稀释对骨科手术患者内环境的影响。方法选择ASAⅠ或Ⅱ级择期骨科手术患者28例,随机均分为急性高容量血液稀释组(AHH组)和对照组(C组)。均采用硬膜外阻滞复合全身麻醉。AHH组硬膜外阻滞起效后开始血液稀释,快速输入6%羟乙基淀粉130/0.420ml/kg,速率50ml/min;C组常规输液。术中连续监测MAP、HR、SpO2、CVP、ECG和PETCO2。分别于稀释前即刻(T0)、稀释后5min(T1)、120min(T2)采取桡动脉血进行电解质、乳酸(Lac)、血糖(BG)、尿素氮(BUN)、Hct及Hb测定,计算血浆渗透浓度(Posm)。结果AHH组Hct及Hb血液稀释后下降约20%。与C组相比,AHH组患者的MAP、HR较平稳,术中输液量、尿量增多。与T0相比,AHH组T1时CVP升高,T2时pH值降低(P<0.05)。两组患者的BG在T2时增高,且C组高于AHH组(P<0.05)。两组各时点血电解质、Lac、BUN、HCO3-、BE、Posm等各指标差异均无统计学意义。结论硬膜外复合全身麻醉下6%羟乙基淀粉130/0.4急性高容量血液稀释能维持内环境的相对稳定。     

Large-dose hydroxyethyl starch 130/0.4 does not increase blood loss and transfusion requirements in coronary artery bypass surgery compared with hydroxyethyl starch 200/0.5 at recommended doses

BACKGROUND: Hydroxyethyl starch (HES) 130/0.4 may impair blood coagulation less than other HES solutions and, thus, may be used at larger doses without increasing the risk of postoperative bleeding. This study tested the hypothesis that volume replacement with 6% HES 130/0.4 at a dose of up to 50 ml/kg does not increase blood loss and transfusion requirements in elective coronary artery bypass surgery compared with 6% HES 200/0.5 at a dose of up to 33 ml/kg. METHODS: One hundred twenty adult patients scheduled for elective coronary artery bypass surgery were randomized to receive up to 50 ml/kg of 6% HES 130/0.4 or up to 33 ml/kg of 6% HES 200/0.5 for volume replacement during surgery and until 24 h thereafter. Volume requirements in excess of the respective maximum dose of HES were treated with gelatin. Colloid use was at the discretion of the attending physicians and not dictated by protocol. The primary outcome variable was chest tube drainage volume during the first 24 h after surgery. RESULTS: The data from 117 patients (HES 130/0.4, 59 patients; HES 200/0.5, 58 patients) who completed the study according to protocol were analyzed. The median volumes of HES administered were 49 and 33 ml/kg in the HES 130/0.4 and HES 200/0.5 groups, respectively (P < 0.001). Consequently, patients in the HES 130/0.4 group required less gelatin in addition to HES than those in the HES 200/0.5 group (medians: 7 ml/kg vs. 20 ml/kg, P < 0.001). The combined volumes of HES and gelatin were similar for both groups (P = 0.21). The 24-h chest tube drainage (medians: 660 ml vs. 705 ml, P = 0.60) did not differ significantly between the groups, nor did transfusion outcome. CONCLUSION: Six percent HES 130/0.4 at a median dose of 49 ml/kg did not increase blood loss and transfusion requirements in coronary artery bypass surgery compared with 6% HES 200/0.5 at a median dose of 33 ml/kg.     

The influence of intravascular volume therapy with a new hydroxyethyl starch preparation (6% HES 130/0.4) on coagulation in patients undergoing major abdominal surgery

A new hydroxyethyl starch (HES) preparation with a mean molecular weight of 130,000 daltons and a degree of substitution of 0.4 shows favorable pharmacokinetic properties. We conducted a study of the influence of the new HES specification on coagulation and compared it with another colloidal intravascular volume replacement regimen using gelatin. According to a prospective, random sequence, 42 patients undergoing major abdominal surgery received either HES 130/0.4 (n = 21) or gelatin (n = 21) until the first postoperative day (POD) to keep central venous pressure between 10 and 14 mm Hg. From arterial blood samples, standard coagulation variables were measured, and modified thrombelastogram (TEG) measurements using different activators were performed. A total of 2830 +/- 350 mL of gelatin and 2430 +/- 310 mL of HES 130/0.4 were administered until the morning of the first POD. The use of allogeneic blood/blood products and standard coagulation variables did not differ significantly between the two groups. After induction of anesthesia, all TEG data for both groups were within normal range. Coagulation time and maximum clot firmness did not change significantly in any TEG measurements during the study period. The kinetics of clot formation (clot formation time) significantly increased immediately after surgery, but without showing significant group differences. On the morning of the first POD, the clot formation time returned to almost normal levels, except for aprotinin-activated TEG(R). We conclude that administration of moderate doses of the new HES 130/0.4 preparation in patients undergoing major abdominal surgery results in similar coagulation alterations as those after using an established gelatin-based volume-replacement regimen. IMPLICATIONS: We compared the effects of infusion of a new hydroxyethyl starch preparation (6% hydroxyethyl starch; mean molecular weight 130,000 daltons; degree of substitution 0.4) on coagulation with a gelatin-based intravascular volume replacement regimen in patients undergoing major abdominal surgery. After moderate doses of hydroxyethyl starch (2430 +/- 310 mL until the morning of the first postoperative day), coagulation monitoring, including modified thrombelastography, did not show impaired hemostasis.