The effects of hydroxyethyl starch solutions on thromboelastography in preoperative male patients

BACKGROUND: Hydroxyethyl starches (HES) have been shown to decrease clot strength and to increase coagulation times assessed by thromboelastography (TEG). HES with minimal anticoagulant side-effects is beneficial for plasma volume expansion in the perioperative setting. A comparison of the in vivo effects of high, middle and low molecular weight HES solutions on TEG variables has not been performed so far. METHODS: Blood was obtained before and after intravenous infusion (10 ml kg-1) of either saline, HES 70/0.5/4 (molecular weight in kDa/degree of substitution/C2:C6 ratio), HES 130/0.4/9, HES 200/0.6/9.4, or HES 450/0.7/4.6 in 50 otherwise healthy patients. Thromboelastography was performed in 360 micro l of 1% celite activated citrated whole blood after recalcification. RESULTS: HES 450/0.7/4.6 prolonged reaction time indicating impairment of the plasmatic coagulation system. TEG parameters indicative for platelet function, including angle alpha, maximum amplitude and coagulation time, deteriorated after infusion of HES 450/0.7/4.6 and HES 70/0.5/4. HES 200/0.6/9.4 and HES 130/0.4/9 impaired platelet contribution to hemostasis only partially, decreasing two or one TEG platelet parameters, respectively. CONCLUSION: Infusion of HES 450/0.7/4.6 compromises TEG parameters more than the other solutions tested, whereas HES 130/0.4/9 has the smallest effect. Further outcome-related studies are needed in order to assess the clinical relevance of our findings.     

羟乙基淀粉对明胶对体外循环心内直视术病人凝血和肾功能的影响

目的　比较 6%羟乙基淀粉 (HES)与 4 %改良琥珀明胶 (MFG)用作心肺转流 (CPB)预充液及术中容量补充对凝血指标及肾功能的影响。方法　随机选择CPB心内直视术患者 4 0例 ,根据人工心肺机预充液配方分为两组。Ⅰ组 :MFG5 0 0ml +晶体 13 0 0ml;Ⅱ组 :HES5 0 0ml +晶体13 0 0ml。每组晶体均为甘露醇 5ml/kg +碳酸氢钠 2 5ml/kg +复方乳酸钠液。CPB中若容量不足 ,则分别输注MFG和HES ,总量均≤ 2 0ml/kg(包括预充液用量 ) ,超此量时则改用血浆。 结果　 ( 1)与术前相比 ,两组患者CPB2 0分钟时WBC均显著下降 (P <0 0 1) ,术毕及术后 18小时WBC均显著上升(P <0 0 1) ,但MFG组高于HES组 (P <0 0 1)。与术前相比 ,两组患者CPB2 0分钟、停机、术毕及术后 18小时RBC、Hb、Hct及Pt均显著下降 (P <0 0 1)。 ( 2 )凝血功能指标组间组内均无差异 (P >0 0 5 )。 ( 3 )术毕时明胶组尿素氮有显著上升 (P <0 0 1)。肌酐值组内组间均无差异 (P >0 0 5 )。结论　HES与MFG均适用于CPB心内直视术病人 ,对凝血指标及肾功能无明显影响 ;但HES组白细胞数的上升较MFG组少 ,炎症反应较轻。     

The effects of high molecular weight hydroxyethyl starch solutions on platelets

Physicochemical characteristics of hydroxyethyl starch (HES) molecules determine their side effects on hemostasis. Our aim in the present experiments was to test the antiplatelet effect of novel high molecular weight HES. Citrated whole blood was hemodiluted in vitro (0% and 20%) with either HES 550 (Hextend), HES 600 (6%Hetastarch-Baxter), HES 200 (Eloh?st), or the solvent of Hextend in its commercially available solution. The availability of glycoprotein IIb-IIIa was assessed on nonstimulated and on agonist-induced platelets using flow cytometry. Glycoprotein IIb-IIIa availability increased significantly after hemodilution with Hextend and its solvent by 23% and 24%, respectively, but decreased in the presence of 6% Hetastarch-Baxter and Eloh?st by 18% and 15%, respectively, with no significant difference between the latter two colloids. This study shows that Hextend does not inhibit platelet function as anticipated by its high molecular weight and degree of substitution. The unexpected platelet stimulating effect of Hextend is unique among the currently available HES preparations and may, at least in part, be induced by its solvent containing calcium chloride dihydrate (2.5 mmol/L). The platelet-inhibiting effect of 6%Hetastarch-Baxter was not significantly different from that of medium molecular weight HES 200.     

The effects of hydroxyethyl starch solution in critically ill patients

AIM: In the treatment of the critically ill patients an adequate fluid therapy appears to be essential to optimize hemodynamics and to get a suitable tissue perfusion. In this study we have evaluated the effects of volume replacement, carried out with 2 different solutions: hydroxyethyl starch 6% (HAES) and albumin 20% (HA). METHODS: Twenty patients suffering from sepsis were recruited and randomized into 2 groups. The first group was treated with hydroxyethyl starch 6% ( HAES treated group), and the second with albumin 20% (HA treated group). The volume of colloids was given to maintain pulmonary capillary wedge pressure (PCWP) between 15 and 18 mmHg. Daily, both hemodynamic parameters and blood gas analyses were monitored. RESULTS: Groups were homogeneous for age, sex and pathology. During the treatment we observed that cardiac index (CI), right ventricular ejection fraction (RVEF), oxygen consumption index (VO(2)I), oxygen delivery index (DO(2)I), and rate between arterial oxygen pressure and fraction of inspired oxygen (PaO(2)/FiO(2)) were increased significantly only in HAES treated group (P<0.05). APACHE II score decreased significantly only in HAES treated group (P<0.05), contrarily to the HA treated group, in which we observed a non significant increase. CONCLUSIONS: Since hydroxyethyl starch induced a hemodynamic and clinical improvement, these effects translated into an improvement of sensorium and a reduction of APACHE II score, without causing pulmonary edema, we can conclude that hydroxyethyl starch 6% ws 130,000 dalton ms 0.4 (Voluven) is an effective fluid for resuscitation of hypovolemic patients and represent an attractive alternative to albumin.     

两种羟乙基淀粉行急性高容量血液稀释对小儿血液流变学和凝血功能的影响

目的探讨两种分子量和取代级的6%羟乙基淀粉(HES)130/0·4(万汶)和6%HES200/0·5(贺斯)行急性高容量血液稀释(AHH)对手术患儿的血液流变学、血小板和凝血功能等的影响。方法40例1~12岁的手术患儿随机分为6%HES130/0·4组(V组)和6%HES200/0·5组(H组),术前1h分别输入6%HES130/0·4或6%HES200/0·510ml/kg,测定输液前后血液流变学、血小板功能和凝血功能,并进行比较。结果两组患儿输液后全血粘度低切、中切、高切参数和红细胞压积均显著下降(P<0·01)。V组患儿全血还原粘度低切和高切参数在输液后显著降低(P<0·05)。V组红细胞聚集指数在输液后显著降低(P<0·01)且与H组比较差异有显著意义(P<0·05);两组红细胞电泳指数在输液后显著增加(P<0·05)。两组患儿1min血小板聚集率(PAG1)和最大血小板聚集率(PAGM)在输液前后无显著改变,但是两组间差异有显著意义(P<0·05)。两组患儿输液后凝血酶原时间(PT)均显著延长(P<0·01),但均在正常范围。结论两种不同分子量和取代级的羟乙基淀粉用于1~12岁患儿进行术前AHH,均改善血液流变性,6%HES130/0·4对凝血功能的影响比6%HES200/0·5更小,对血液流变学的改善更好。     

In vitro effects of gelatin solutions on platelet function: a comparison with hydroxyethyl starch solutions

The aim of this study was to investigate the effects of various gelatin and hydroxyethyl starch solutions on platelet reactivity. Citrated whole blood was obtained from 20 healthy volunteers. Expression of glycoprotein (GP) IIb-IIIa and p-selectin were determined using whole blood flow cytometry on both resting and agonist-activated platelets before and after in vitro haemodilution (20% and 40%) using oxypolygelatin, modified gelatin, urea-linked gelatin, hydroxyethyl starch (HES) 130 (mean molecular weight in kDa), HES 200, HES 450 and HES 550. High degrees of haemodilution using oxypolygelatin had no significant effect, similar to HES 130, whereas modified gelatin inhibited GP IIb-IIIa expression, similar to HES 200 and HES 450. Urea-linked gelatin significantly increased the expression of GP IIb-IIIa, similar to HES 550. p-selectin expression remained unchanged in all samples. The present in vitro study indicates that chemical characteristics of colloidal solutions modulate their influence on platelet reactivity.     

胃肠道手术后应用羟乙基淀粉的临床研究

目的:探讨羟乙基淀粉溶液对胃肠道手术患者术后恢复的影响。方法:将2009年1月—12月行胃肠道手术的患者90例,随机分为羟乙基淀粉(HES)组,白蛋白(ALB)组和对照组。术后3 d内,均给予相同能量的静脉营养,另外HES组每日补充羟乙基淀粉(130/0.4)500 mL,ALB组每日补充白蛋白10 g,对照组补充适当晶体液。测定术前和术后第1,4,7天血清白蛋白浓度,C反应蛋白(CRP)水平,并观察术后并发症发生率、住院天数。结果:3组术前临床资料、术前白蛋白水平、手术时间及术中出血量均具有可比性(均P>0.05)。术后第1天,3组间血清白蛋白和CRP水平差异无统计学意义(均P>0.05);术后第4天,对照组血清白蛋白浓度明显低于HES组和ALB组(均P<0.05),而HES组和ALB组血清白蛋白浓度无明显差异(P>0.05)。HES组CRP水平明显低于ALB组和对照组(均P<0.05),而对照组和ALB组血清CRP水平无明显差异(P>0.05);术后第7天,3组间血清白蛋白与CRP水平差异无统计学意义(均P>0.05)。3组并发症发生率差异无统计学意义(P>0.05)。对照组术后住院时间明显长于HES组和ALB组(均P<0.05),而HES组和ALB组间差异无统计学意义(P>0.05)。结论:羟乙基淀粉在胃肠道手术后早期应用可以有效节约白蛋白的用量,控制术后的炎症反应,缩短住院时间。     

Experience with using of solutions of hydroxyethyl starch (refortan and voluven) in neuroanesthesiology]

The investigation has shown that solutions of hydroxyethyl starch included in complex infusion therapy facilitate stabilization of hemodynamics in neurosurgical patients during surgery. Refortan exerts a more pronounced effect on the indices of hemodynamics as compared with voluven, but its modifying action on the hemostasis system is also more pronounced. These medicines used in doses 6-8 ml/kg fail to have substantial effects on efficiency of hemostasis in the brain wound and do not increase risk of postoperative hemorrhagic complications.     

Pharmacology of low molecular weight hydroxyethyl starch]

In the last ten years, the practice of plasma volume expansion has changed significantly. Most clinicians have put a stop to the use of fresh frozen plasma because of growing concerns about hepatitis and AIDS transmission. Today, natural and synthetic colloids and crystalloids are used to a great extent. Although clinical practice varies from one institution to another, the most widely observed change was a major increase in the administration of human serum albumin (HSA). As a result, the cost of plasma volume expansion became so high that it justified finding safe and cheaper alternatives to HSA. Low molecular weight, hydroxyethylstarch (HES) are the synthetic colloids which are closest to HSA. HES are modified natural polymers whose physico-chemical properties are defined by their molecular weight and molar substitution ratio. Average molecular weights of these poly-dispersed solutions are approximately 200 to 250 kd (in weight) and 60 kd (in number). Hydroxyethylation, which slows down hydrolysis by alpha-amylase, is best quantified by the molar substitution ratio between the proportions of hydroxyethyl-ether and glucose. HES have pharmacokinetic properties which are independent of molecular weight and directly related to the molar substitution ratio. The two HES available in France are Elohes and Lomol, Elohes, at a concentration of 6%, has a colloid-osmotic effect close to that of plasma. It induces an initial plasma volume expansion greater than that of the infused volume, and has a long lasting effect (24 h) related to its molar substitution ratio (0.62). Lomol, at a concentration of 10%, is hyperoncotic.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of platelet function by hydroxyethyl starch solutions in chronic pain patients undergoing peridural anesthesia

The use of hydroxyethyl starch (HES) solutions as a fluid replacement before peridural blockade may compromise blood coagulation, thus increasing the risk of neuraxial bleeding. In this prospective, double-blind, placebo-controlled, crossover study, we compared the influence of HES 130 (molecular weight in kilodalton), HES 200, and lactated Ringer's solution on platelet function and hemodynamics in chronic low back pain patients scheduled for peridural blockades. Patients received 3 test infusions of 10 mL/kg each administered IV for 30 min. Collagen/epinephrine and collagen/adenosine diphosphate were used as agonists for assessment of platelet function analyzer-closure times. Arterial blood pressure, heart rate, platelet counts, and hemoglobin levels were documented. Platelet function analyzer-closure times remained stable after lactated Ringer's solution but were significantly prolonged after HES. The platelet-inhibiting effect of HES 200 was more than that of HES 130. Hemodynamic stability was sufficiently maintained by all test infusions. In contrast to previous observations, a relevant antiplatelet effect of both low and medium molecular weight HES solutions was found in this study in chronic pain patients undergoing peridural anesthesia. Because hemostasiological competence is a prerequisite for safe neuraxial blockade, the decision of HES for intravascular fluid administration before blockade should be critically made.     

Effects of hydroxyethyl starch in critically ill patients

Editor—The Sepsis Occurrence in Acutely ill Patients (SOAP)trial group have published another analysis from their database¹on hydroxyethyl starch (HES) and its effects on renal function.²However, we are concerned that the methods used were not adequate,and the conclusion drawn ‘that HES had no influence onrenal function or the need for renal replacement therapy (RRT)’must therefore be viewed with caution. Our main concerns areas follows.

1. Cohort studies must be planned in such a way thatavailabledata about potential confounding factors are of goodquality.To ensure this, outcome events must be clearly pre-specifiedin the protocol and the data which will be     

老年患者术中6%羟乙基淀粉急性高容量血液稀释的可行性

目的 探讨急性高容量血液稀释(AHH)在老年患者术中应用的可行性。方法 选择肝脏择期手术的成年病人24例,ASA I-Ⅱ级,无心肺疾患。根据年龄分成A组(n=12,年龄≥65岁)和B组(n=12,年龄≤55岁)。两组患者均在硬膜外复合全麻下实施AHH,常规全麻诱导后,经中心静脉输注预温的6％羟乙基淀粉(6％HES,200/0.5)15 ml/kg。用HemoSonicTM100血液动力学监测仪连续监测CO、SV、HR、SVR和血流加速度(ACC);并监测MAP、CVP、ECG、SpO2、乳酸、COP、Hct、T和动脉血气的变化。分别在麻醉平稳后5 min,AHH后即刻及术毕记录上述数据,同时记录术中输液量、失血量及输血量,术后第一天复查血常规。结果 AHH后,两组患者的MAP、HR、和ACC与血液稀释前相比无显著性改变,而CO、SV及CVP明显升高,SVR明显下降(P<0.05)。A和B组CO、SV、CVP变化幅度差异无显著性(P>0.05)。动脉血pH值、乳酸及COP在AHH前后无明显改变,其组间比较P>0.05。两组患者术中输液量及失血量差异亦无显著性。结论 年龄并不是影响AHH实施的主要因素;一般情况良好、无心肺疾患的老年患者,在硬膜外复合全麻下,用6％HES按15ml/kg行快速扩容实施AHH是安全可行的。