Cardiorespiratory and microcirculatory effects following volume replacement using a new hydroxyethyl starch preparation]

Volume therapy is often necessary in cardiac surgery to maintain stable haemodynamics. Various different hydroxyethyl starch (HAES) solutions with different concentrations, mean molecular weights, and degrees of substitution are available for this purpose. In determining the ideal type of volume therapy, not only changes in macrohaemodynamics, but also the influence on microcirculatory blood flow have to be taken into account. The efficacy of a new 10% HAES 130/0.5 solution was studied in cardiac surgery patients in comparison to a standard 10% HAES 200/0.5 preparation. METHODS. In patients scheduled for elective aortocoronary bypass grafting who had a pulmonary capillary wedge pressure (PCWP) of less than 4 mm Hg after induction of anaesthesia, either a new 10% HAES 130/0.5 (n = 15) or a standard 10% HAES 200/0.5 solution (n = 15) was infused to double the reduced PCWP; 15 patients without volume therapy served as controls (n = 15). A two-channel laser Doppler skin blood-flux monitor was used to evaluate microcirculatory alterations. Measurements of laser Doppler flux (LDF) was simultaneously performed at the patient's forehead and forearm before and after volume infusion as well as during and after cardiopulmonary bypass (CPB). In addition, changes in gross haemodynamics were documented using a pulmonary artery catheter. Plasma viscosity and various laboratory parameters, including calculation of intrapulmonary right-to-left shunting (Qs/Qt), were also measured. RESULTS. Cardiac index (CI) increased in both volume groups (HAES 130: max. +38%; HAES 200: +55%). The increases in PCWP and CI were maintained at 40 min after volume infusion only in the HAES 200 patients. Systemic vascular resistance (SVR) decreased most markedly after infusion of HAES 200 (-34%; HAES 130: -18%). No further differences in gross haemodynamics could be seen after CPB. Plasma viscosity and colloid osmotic pressure increased in both HAES groups without significant differences. During the entire investigation period, pulmonary gas exchange (paO2) and Qs/Qt did not differ between the groups. Infusion of both HAES solutions resulted in an increase in LDF that was most pronounced after infusion of HAES 200 (forehead LDF: +81%; HAES 130: +18%) and was evident in the post-bypass period only in these patients (LDF: HAES 200: +82%; HAES 130: -20%; control: -43%). No correlation between LDF values and the other haemodynamic and laboratory parameters could be demonstrated. CONCLUSION. The improvement in macrohaemodynamics was of shorter duration after infusion of the new HAES 130 solution than after standard HAES 200. Volume replacement with HAES 200 resulted in an increase in microcirculatory blood flow that was more pronounced and of longer duration than in the HAES 130 patients. Thus, HAES 130 seems to be less effective than HAES 200 for volume replacement; HAES 200 should be preferred in patients undergoing cardiac surgery.     

Compatibility of different colloid plasma expanders with perflubron emulsion: an intravital microscopic study in the hamster

BACKGROUND: Perfluorocarbon-based oxygen carriers have been proposed as an adjunct to autologous blood conservation techniques during elective surgery. To date, the effects of perfluorocarbon emulsions at the microcirculatory level have not been studied extensively. In this study the effects of perflubron emulsion on the microcirculation after acute normovolemic hemodilution (ANH) were investigated using different colloid plasma expanders. METHODS: The dorsal skin fold chamber model and intravital fluorescence microscopy were used for analysis of the microcirculation in the thin striated skin muscle of conscious hamsters (body weight, 40-60 g). Measurements of microvascular perfusion and leukocyte adhesion (n = 6 animals per experimental group) were made before and at 10, 30, and 60 min after ANH (to hematocrit 0.3) with either 6% hydroxyethyl starch 200/0.6 (HES), 3.5% gelatin, 5% human serum albumin (HSA), or 6% dextran 60 (DX-60) followed by intravenous injection of 3 ml/kg body weight of a 60% weight/volume perfluorocarbon emulsion based on perflubron (perfluorooctyl bromide) emulsified with egg yolk lecithin. RESULTS: Acute normovolemic hemodilution with HES, gelatin, or HSA followed by injection of perflubron emulsion elicited no alterations of local microvascular perfusion or leukocyte-endothelium interaction as assessed in arterioles and postcapillary venules. However, ANH with DX-60 followed by injection of perflubron emulsion led to a significant reduction of erythrocyte velocity in postcapillary venules and an increase in venular leukocyte sticking that was never observed with DX-60 alone. CONCLUSIONS: Hydroxyethyl starch, gelatin, and HSA are compatible with perflubron emulsion in the setting of ANH. Only DX-60 appeared to be incompatible with perflubron emulsion, as evidenced by impairment of capillary perfusion.     

The hemodynamic effects of various hydroxyethyl starch solutions in heart surgery patients]

Blood conservation is gaining more and more interest because of the increasing risks involved in homologous blood transfusions. Acute normovolemic hemodilution (ANH) is becoming an established technique even in cardiac surgery patients. The "optimal" kind of volume replacement, however, is still controversial. Thus, this study was carried out to investigate the hemodynamic response of 6 different hydroxyethyl starch (HES) solutions as volume replacement. METHODS. In 60 patients undergoing elective aortocoronary bypass surgery, acute, preoperative hemodilution was performed (10 ml/kg) and HES with different concentrations, molecular weight, and substitution was infused according to a randomized sequence: 1. 6% HES 450,000/0.7; 2. 10% HES 200,000/0.5; 3. 3% HES 200,000/0.5%; 4. 6% HES 40,000/0.5; 5. 6% HES 200,000/0.5; 6. 6% HES 200,000/0.62. All patients were monitored using a new pulmonary artery catheter that allows measurement of the right ventricular ejection fraction (RVEF), right ventricular enddiastolic volume (RVEDV), and right ventricular end systolic volume (RVESV) in addition to standard hemodynamic parameters. RESULTS. Immediately after finishing ANH the typical hemodynamic changes of hemodilution (HD) were apparent (decrease in peripheral resistance and increase in cardiac index (CI]. All 6 solutions investigated were effective in hemodynamic stabilization (no changes in mean arterial pressure (MAP), filling pressures (PCP, RAP), or heart rate (HR]. Forty min after ANH, however (before beginning extracorporeal circulation (ECC], there were significant differences between the groups: in groups 3 and 4 the increase in CI had already disappeared, and SVI in group 3 was even lower than the baseline values (-8%). In the other groups, a higher CI level remained even 40 min after ANH, which was most pronounced in groups 2 (+40%) and 5 (+43%). Right ventricular performance was not changed by ANH (RVEF unchanged in all groups). Forty min after hemodilution RVEDVI (-8%) and RVESVI (-16%) decreased significantly only in group 4, whereas in the other groups these parameters were still elevated. The most pronounced positive fluid balance after the end of ECC was found in group 4 (+850 ml); in these patients paO2 decreased significantly (-150 mmHg). CONCLUSIONS. The guarantee of stable hemodynamic conditions is a prerequisite when performing ANH in coronary surgery patients. The different physiochemical attributes of various HES solutions seem to be important, thus influencing their hemodynamic response. In this study, low-concentration (3% HES 200/0.5) and low-molecular (6% HES 40/0.5) HES solutions were less effective in stabilizing hemodynamics until the beginning of ECC. Additionally, their negative influence on fluid balance during ECC, followed by a deterioration in pulmonary function led to the conclusion that other solutions are preferable; in particular, 10% HES seems to be of advantage in these situations.     

Compatibility of Different Colloid Plasma Expanders with Perflubron Emulsion: An Intravital Microscopic Study in the Hamster

Background: Perfluorocarbon-based oxygen carriers have been proposed as an adjunct to autologous blood conservation techniques during elective surgery. To date, the effects of perfluorocarbon emulsions at the microcirculatory level have not been studied extensively. In this study the effects of perflubron emulsion on the microcirculation after acute normovolemic hemodilution (ANH) were investigated using different colloid plasma expanders.

Methods: The dorsal skin fold chamber model and intravital fluorescence microscopy were used for analysis of the microcirculation in the thin striated skin muscle of conscious hamsters (body weight, 40-60 g). Measurements of microvascular perfusion and leukocyte adhesion (n = 6 animals per experimental group) were made before and at 10, 30, and 60 min after ANH (to hematocrit 0.3) with either 6% hydroxyethyl starch 200/0.6 (HES), 3.5% gelatin, 5% human serum albumin (HSA), or 6% dextran 60 (DX-60) followed by intravenous injection of 3 ml/kg body weight of a 60% weight/volume perfluorocarbon emulsion based on perflubron (perfluorooctyl bromide) emulsified with egg yolk lecithin.

Results: Acute normovolemic hemodilution with HES, gelatin, or HSA followed by injection of perflubron emulsion elicited no alterations of local microvascular perfusion or leukocyte-endothelium interaction as assessed in arterioles and postcapillary venules. However, ANH with DX-60 followed by injection of perflubron emulsion led to a significant reduction of erythrocyte velocity in postcapillary venules and an increase in venular leukocyte sticking that was never observed with DX-60 alone.     

不同程度急性等容量血液稀释对兔小肠粘膜的影响

目的 探讨常温下不同程度急性等容量血液稀释(ANH)对家兔小肠粘膜的影响.方法 选择健康成年家兔32只,体重2.0～2.5 kg,随机分为4组(n=8),对照组(C组)不行血液稀释;其余3组血液稀释的目标Hct分别为24%(H1组)、18%(H2组)和12%(H3组).经股动脉放血:H1组、H2组、H3 组所需放血量=2×体重×每公斤体重所含体液量×(初始Hct-目标Hct)/(初始Hct+目标Hct),股静脉经30 min输入等容量6%羟乙基淀粉200/0.5行ANH.于ANH前(T0)及ANH后8 h(T1)时采集肠系膜上静脉血样0.5 ml,采用酶联免疫吸附法测定血浆TNF-α浓度.于T1时取小肠粘膜组织,观察病理学结果.结果 与T0时比较,T1时H2组、H3组肠系膜上静脉血浆TNF-α浓度升高(P＜0.01),H1组差异无统计学意义(P＞0.05).与C组比较,H2组和H3组肠系膜上静脉血浆TNF-α浓度升高(P＜0.01),H1组差异无统计学意义(P＞0.05).H1组小肠粘膜未见明显损伤,H2组轻度损伤,H3组损伤严重.结论 6%羟乙基淀粉200/0.5行ANH,当Hct为24%时,对家兔小肠粘膜无明显影响;当Hct≤18%时,可诱发小肠粘膜损伤.     

INFLUENCE OF HYPERTONIC VOLUME REPLACEMENT ON THE MICROCIRCULATION IN CARDIAC SURGERY

We have studied the effects of two types of volume replacementon the microcirculation in an open, controlled study in 45 patientsundergoing aorto-coronary bypass grafting whose pulmonary capillarywedge pressure (PCWP) was < 5 mm Hg. Hypertonic saline preparedin hydroxyethylstarch solution (HS-HES, n = 15) and6%HES200/0.5solution(6% HES; n = 15) were infused randomly before operation in orderto double the PCWP. Patients not given an infusion served ascontrols (n = 15). Skin micro-circulatory blood flow was investigatedby laser Doppler flow (LDF) measured simultaneously at the forearmand forehead before and after cardiopulmonary bypass (CPB).Less HS-HES (3.8 (SD 0.3) ml kg^–1) than 6% HES-solution(9.7 (1.5) ml kg^–1) was necessary to double baseline PCWP.There were no differences in heart rate and mean arterial pressure(MAP) between the groups. Cardiac index (Cl) increased significantlyin both volume groups (HS-HES max. +54%; 6% HES max. +30%).Systemic vascular resistance (SVR) decreased after infusionof HS-HES (30%) and after 6% HES(19%) and remained almost unchangedin the control group. Plasma viscosity decreased after infusionof HS-HES and increased slightly in control patients (+4%).In comparison with the 6% HES and particularly with the controlgroup, LDF was significantly greater after infusion of HS-HES(forearm +80%; forehead +28%). LDF during CPB and thereafterwas always greater than baseline values in the HS-HES group,whereas after bypass LDF was reduced in the 6% HES (5%) andparticularly in the control patients (30%). No differences intemperature (oesophageal, rectal, forearm, forehead) occurredbetween groups. Changes in MAP, Cl, SVR, haemoglobin and viscositydid not correlate with skin blood flow. It was concluded thatthe preoperative infusion of HS-HES resulted in a significantimprovement in microcirculation before, during and after CPB.     

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     

Endocrine reactions during acute normovolemic hemodilution

To investigate the influence of acute normovolemic hemodilution (ANH) on endocrine parameters in orthopedic surgery patients, 20 patients scheduled for total prosthetic replacement of the hip under epidural anesthesia with bupivacaine 0.5% were randomly allocated to the following groups: ANH group, (about 7.5 ml/kg body weight within 30 min) during substitution with 6% HES 200/0.5; Control group (without hemodilution). During a period before the onset of anesthesia and on the 1st day after the operation, MAP, HR, plasma concentrations of adrenaline and noradrenaline (by HPLC/ECD), and of ADH, ACTH and cortisol (by RIA) were determined at 8 points, as were glucose, lactate and free glycerol. Biometric data were comparable between the groups. MAP was significantly higher in the ANH group, and the intraoperative decrease was less pronounced. Adrenaline, ACTH, and cortisol revealed no specific influence of ANH and remained within the normal range in both groups. Noradrenaline was above the normal range in both groups and increased slightly (about 20%) during ANH. ADH was significantly higher in the control group. No specific influence of ANH was found with respect to glucose, lactate and free glycerol. In conclusion, ANH had no negative effects on the endocrine stress response during orthopedic surgery under epidural anesthesia. Sympatho-adrenergic reactions were only moderate and tolerable, even for patients with compensated cardiovascular disorders. Slight increases in endocrine parameters in the perioperative period documented adequate stress protection with epidural anesthesia.     

Equivalence of hydroxyethyl starch HES 130/0. 4 and HES 200/0. 5 for perioperative volume replacement in major gynaecological surgery

BACKGROUND: Hydroxyethyl starch solutions (HES) are increasingly used for the compensation of surgical blood loss. The objective of this clinical trial was to compare a novel 6% HES 130/0.4 solution with a favourable pharmacological profile and a standard 6% HES 200/0.5 solution for maintenance of haemodynamic stability in major gynaecological surgery. METHODS: Sixty female patients aged 18-80 years undergoing major gynaecological surgery with indication for perioperative colloidal volume replacement were enrolled in this prospective, randomized double-blinded clinical study. The administration of study medication was dependent on individual requirements to maintain haemodynamic stability. The amount of study medication required from induction of anaesthesia until 6 h postoperatively served as the primary investigative parameter. RESULTS: The two one-sided test procedure by Westlake demonstrated equivalence of mean infused volumes between HES 130/0.4 and HES 200/0.5 during the study period (1224 +/- 544 ml and 1389 +/- 610 ml, respectively, P < 0.05). Perioperatively, haemodynamics did not differ significantly between treatment groups. While none of the mean values of coagulation parameters shifted outside the normal range, the degree of haemodilution revealed reduced haematocrit values in HES 200/0.5 treated patients at 6 h postoperatively (P < 0.05). Moreover, prothrombin time (PT) was higher and consequently international normalized ratio (INR) was lower at the same time point for patients who received HES 130/0.4 (P < 0.05). CONCLUSION: This clinical trial demonstrated therapeutic equivalence of this novel low-substituted HES 130/0.4 solution and a standard HES 200/0.5 solution for perioperative volume replacement. Moreover, both HES preparations were equally well-tolerated and safe.     

腹部手术患者麻醉诱导期间液体治疗对皮肤微循环灌注的影响

目的 观察腹部手术患者麻醉诱导期间静脉输注羟乙基淀粉和乳酸钠林格氏液后皮肤微循环灌注的变化,比较晶体液和胶体液治疗方案对微循环灌注的影响.方法 择期拟行腹部手术患者36例,ASAⅠ或Ⅱ级,年龄18～64岁,随机分为2组(n=18):羟乙基淀粉组(HES组)和乳酸钠林格氏液组(RL组).HES组和RL组分别静脉输注6%羟乙基淀粉130/0.4或乳酸钠林格氏液各7 ml/kg补充麻醉致血管扩容量.同时均静脉输注乳酸钠林格氏液8 ml·kg~(-1)·h~(-1)补充生理需要量和禁食禁饮丢失量.液体治疗后40 min静脉注射异丙酚.罗库溴铵-芬太尼麻醉诱导,气管插管,20 min后开始手术.于液体治疗前(T_0,基础状态)、气管插管后即刻(T_1)、手术开始前即刻(T_2)行动脉血气分析,同时记录患者前额皮肤的微循环灌注量(SMP)和CVP,计算各时点SMP较基础值的变化率(△SMP).结果 与RL组比较,HES组T_1时CVP和△sMP升高(P<0.05或0.01),血气分析各指标差异无统计学意义(P>0.05).与T_0时比较,HES组T_1时△SMP升高(P<0.01),RL组差异无统计学意义(P>0.05),两组T2时△SMP均降低(P<0.01),两组T_(1,2)时CVP和PaO_2/FiO_2升高,Hb降低(P<0.05).与T_1时比较,两组T_2时△SMP均降低(P<0.01).结论 腹部手术患者麻醉诱导期间静脉输注6%羟乙基淀粉130/0.4较乳酸钠林格氏液可更好地改善机体微循环灌注.     

Renal effects of hypotensive anaesthesia in combination with acute normovolaemic haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline

BACKGROUND: Hypotensive anaesthesia (HA) and acute normovolaemic haemodilution (ANH) are used separately to decrease per-operative blood loss. Reducing blood viscosity by adding ANH to HA may appear profitable in a situation with lowered perfusion pressure and concern about organ ischemia. The aim of this study was to clarify the influence of HA in combination with ANH using crystalloid or colloid as replacement fluid on renal function. METHODS: Hypotensive anaesthesia was induced in 11 patients referred to major spine surgery using sevoflurane in combination with fentanyl/remifentanil. Acute normovolaemic haemodilution was carried out by drawing venous blood into standard blood bags and replacing it by isotonic saline 0.9% (Group S) or HES 130/0.4 (Group V). Renal function was evaluated before, during and up to 8 h after hypotension as the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) by means of 51Cr-EDTA and 125I-Hippuran clearances. RESULTS: Lowering mean arterial blood pressure decreased GFR and ERPF in both groups. During hypotension ERPF was lower in Group S (n = 5) than Group V (n = 6). Renal function was normalized postoperatively. We found a positive but non-significant correlation between the relative GFR change and the duration of hypotension. CONCLUSION: In conclusion, our study demonstrated that renal function, assessed by GFR and ERPF, is transiently reduced during the combination of hypotensive anaesthesia and acute normovolaemic haemodilution. A colloid-based fluid regime (HES 130/0.4) used for haemodilution may preserve renal function to a greater extent than a crystalloid-based regime (0.9% saline).     

不同程度急性等容量血液稀释对家兔血清S-100B蛋白浓度和脑氧代谢的影响

目的 探讨常温下不同程度急性等容量血液稀释(ANH)对家兔血清S-100B蛋白浓度和脑氧代谢的影响.方法 健康成年家兔32只,体重2～2.5 kg,随机分为4组(n=8),对照组(Ⅰ组)不行血液稀释;其余3组血液稀释的目标红细胞压积(Hot)分别为24%(Ⅱ组)、18%(Ⅲ组)、12%(Ⅳ组).麻醉下气管插管后行机械通气,维持体温37℃左右.左颈动脉和左颈内静脉穿刺并置管,用于监测血压、采血和血气分析.右颈内静脉穿刺并置管,用于监测中心静脉压.股动脉放血,同时Ⅱ组～Ⅳ组股静脉经30 min输注等量6%羟乙基淀粉200/0.5行ANH至目标Hct.于动脉、静脉穿刺并置管稳定20 min(To)、ANH后2、4、8 h(T1～T3)时,记录血液动力学指标;分别采集左颈动脉和左颈内静脉血样各0.1 ml,行血气分析,计算脑氧摄取率(CERO2);颈动脉取血样,采用ELISA法测定血清S-100B蛋白浓度.ANH后8 h时处死动物,取右侧脑组织,称湿重和干重,计算脑含水量.结果 与T0时比较,Ⅲ组T3时、Ⅳ组T1～T3时CERO2和血清S-100B蛋白浓度升高(P<0.05);Ⅰ组和Ⅱ组各时点CERO2和血清S-100B蛋白浓度比较差异无统计学意义(P>0.05);与Ⅰ组和Ⅱ组比较,Ⅲ组T3时、Ⅳ组T1～T3时CERO2和血清S-100B蛋白浓度升高(P<0.05);与Ⅲ组比较,Ⅳ组T1～T3时CERO2和血清S-100B蛋白浓度升高(P<0.05).各组问脑含水量比较差异无统计学意义(P>0.05).结论 常温下ANH目标Hct为24%时,对家兔脑氧代谢无影响;目标Hct≤18%时,发生脑氧代谢失衡和脑损伤.     

Acute preoperative hemodilution in cardiac surgery: volume replacement with a hypertonic saline-hydroxyethyl starch solution.

Preoperative hemodilution (HD) is a recommended practice in cardiac surgery that conserves blood and reduces the complications of homologous blood transfusion. In 45 patients undergoing myocardial revascularization, HD was performed preoperatively. Withdrawn volume (10 mL/kg) was replaced either by a new hypertonic saline (HS) solution prepared in hydroxyethyl starch (HES) (2,400 mOsm/L, HS-HES group, n = 15) or by a standard low molecular weight hydroxyethyl starch solution (6% HES 200/0.5, HES group, n = 15) to maintain baseline PCWP (acute normovolemic hemodilution [ANH]). Fifteen comparable patients without HD served as controls. Significantly less HS-HES (210 +/- 20 mL) than HES 6% (890 +/- 90 mL) was necessary to sustain hemodynamics during HD. Stable cardiocirculatory conditions were obtained even after termination of bypass. Fluid balance during cardiopulmonary bypass as well as in the postoperative period was significantly lower in HS-HES-treated patients. With regard to hemodynamics, CI increased most in the HS-HES group (+36%), whereas systemic vascular resistance was lower in these patients. Right ventricular ejection fraction increased only in HS-HES patients (+15%). However, sodium concentration as well as osmolarity increased after volume replacement with HS-HES, without exceeding normal values. None of the patients suffered from organ failure. Pulmonary gas exchange (PaO2) was less compromised in the HS-HES patients. There were no renal function differences between the groups. In conclusion, HS solution prepared in HES is an attractive alternative for blood substitution in cardiac patients undergoing acute hemodilution for blood conservation.     

Hydroxyethyl starch (HES) 130/0.4 provides larger and faster increases in tissue oxygen tension in comparison with prehemodilution values than HES 70/0.5 or HES 200/0.5 in volunteers undergoing acute normovolemic hemodilution

Stable hemodynamics and improved rheology are important effects of hemodilution with hydroxyethyl starch (HES) infusions. One clinical indicator of improved rheology is increased tissue oxygen tension (tpO(2)). In this prospective, randomized, double-blinded, crossover study, we examined the effects of acute normovolemic hemodilution with HES 130/0.4 on hemodynamics and skeletal muscle tpO(2) in comparison with conventional HES solutions. Twelve healthy volunteers were randomly enrolled in each group. At an interval of >8 days, volunteers donated 18% of their calculated blood volume within 30 min and randomly received 6% HES 130/0.4, 6% HES 70/0.5, or 6% HES 200/0.5 (crossover design) in a 1:1.2 ratio to their blood loss. Hemodynamic variables, tpO(2) in the quadriceps muscle, hematocrit, plasmatic HES concentrations, plasma viscosity, colloid osmotic pressures, and platelet aggregation were measured until 6 h after the infusion of HES. No differences were found among groups with respect to changes of hemodynamics, hematocrit, or platelet aggregation. With HES 200, colloid osmotic pressures and plasma viscosities were larger than after HES 70 (P < 0.05). HES 130 in comparison with HES 70 and 200 caused the fastest (30 min versus 90 min and 150 min after hemodilution; P < 0.05) and largest increase of tpO(2) in comparison to baseline (+93% versus +33% and 40%; P < 0.05). In healthy volunteers undergoing acute normovolemic hemodilution, the newly designed HES 130/0.4 showed a more pronounced and earlier increase of skeletal muscle tpO(2) in comparison with prehemodilution values than HES 70/0.5 or 200/0.5. IMPLICATIONS: The effects of three different hydroxyethyl starch (HES) solutions on hemodynamics, rheology, and skeletal muscle tissue tension after acute normovolemic hemodilution were examined in awake volunteers. With HES 130/0.4, increases of tissue oxygen tension in comparison to baseline were larger and more rapid than with HES 70/0.5 or HES 200/0.5.     

Variations in superficial renal cortical blood flow and tissue oxygenation: an experimental porcine model

Renal cortical microcirculation and its relation to inulin clearance, central haemodynamics and pulmonary gas exchange were studied in eight pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The animals were studied during six consecutive 30-min periods. Four of the animals were also studied 19 h after the first period. In the superficial renal cortex, regional blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) and tissue oxygenation (PtO2) by surface microelectrode technique. Central haemodynamics and pulmonary gas exchange values were distributed within normal ranges. The importance of stable central haemodynamics in order to perform accurate microcirculatory measurements in the renal cortex was documented. A significant relation between Qsrc and pulmonary capillary wedge pressure (PCWP) was found (P less than 0.0001) despite the fact that PCWP was distributed within a range of only 0.7 kPa (all values were well within the normal range for pigs). No other relationships were found between central haemodynamics or pulmonary gas exchange variables and renal microcirculatory parameters. Concerning renal microcirculation and inulin clearance, at least 2-3 h may be required for stabilization after surgery. The average temporal variability between measurements performed every 30 min in each animal was 6 +/- 7% (s.d.) in the LDF values and 21 +/- 21% in the PtO2 values (mean PtO2). No correlations were found between Qsrc or PtO2 and inulin clearance. Since the haemodynamic parameters, pulmonary gas exchange variables and haematocrit were distributed within narrow ranges, we regard the temporal microcirculatory variability obtained here as normal in this experimental situation, and consider the porcine model well suited for further studies concerning renal microcirculation.     

Effects of acute normovolemic hemodilution on ventriculoarterial coupling in dogs

BACKGROUND: Acute normovolemic hemodilution (ANH) causes a decrease in systemic vascular resistance. Similar to vasodilating drugs, ANH might modify ventriculoarterial coupling. Left ventricular elastance (Ees), effective arterial elastance (Ea), stroke work (SW), and pressure volume area (PVA) were used as indicators to examine the effects of ANH on this coupling. METHODS: After institutional approval eight dogs were anesthetized with isoflurane and subjected to measurements including aortic pressure, left ventricular (LV) pressure, and LV volume. Left ventricular volume was measured with a conductance catheter. Ees was determined as the slope of the end-systolic pressure-volume relationship. Ea was determined as the ratio of LV end-systolic pressure to stroke volume. Ventriculoarterial coupling was evaluated as the ratio of Ees to Ea. Mechanical efficiency, another criterion for ventriculoarterial coupling, was calculated as the ratio of SW to PVA. Data are expressed as mean+/-SD, and P<0.05 was considered significant. RESULTS: Normovolemic exchange of 50 ml kg-1 of blood for 6% hydroxyethyl starch (ANH50) reduced hemoglobin concentration from 12.8+/-3.0 g dl-1 to 6.4+/-1.3 g dl-1. Acute normovolemic hemodilution 50 did not change Ees significantly although it significantly decreased Ea. Left ventricular elastance/Ea did not change after ANH (1.0+/-0.4 at baseline and 1.2+/-0.5 at ANH50). Acute normovolemic hemodilution 50 significantly increased SW and PVA, preventing SW/PVA from changing significantly after ANH (0.57+/-0.10 at baseline and 0.62+/-0.14 at ANH50). CONCLUSION: Before ANH, ventriculoarterial coupling was so matched as to maximize SW at the expense of the work efficiency. This relation was preserved at ANH50.     

In vivo investigation into the effects of haemodilution with hydroxyethyl starch (200/0.5) and normal saline on coagulation

We have investigated the effects of haemodilution with either saline or hydroxyethyl starch (200/0.5) (HES) on blood coagulation in healthy volunteers in vivo. Standard haematological tests (packed cell volume (PCV), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin III, bleeding time and platelet aggregation), and thrombelastography (TEG) were performed before and after administration of either 0.9% saline 1000 ml or HES 1000 ml i.v. over a 30-min period. Dilution of PCV and platelet concentrations as a result of volume load were 9% in the saline group and 19% in the HES group. Reductions in fibrinogen (18.6% and 28.8%) and antithrombin III (25.5% and 37.8%) were significantly greater than could be explained by haemodilution alone in both groups. Indices of platelet aggregation were significantly enhanced by saline haemodilution, but not by HES, which inhibited epinephrine-induced aggregation and prolonged bleeding time. TEG in the saline group showed significantly shortened r and k times (24% and 26%, respectively), and increased alpha angle (24%) and maximum amplitude (MA, 6%). HES haemodilution decreased MA (11%) but did not affect other TEG variables. We conclude that haemodilution of normal blood exerted a procoagulant effect, possibly by enhancement of thrombin formation. Circulating concentrations of antithrombin III were depleted more than could be explained by haemodilution alone, leading to a hypercoagulable state. This effect was offset by an antiplatelet action of HES, which was not seen with saline. The mechanism is unknown.      

羟乙基淀粉行急性等容血液稀释对兔脊髓缺血-再灌注损伤的保护作用

目的 探讨用羟乙基淀粉(HES130/0.4)急性等容血液稀释(ANH)对兔脊髓缺血-再灌注损伤的保护作用.方法 24只新西兰雄性大白兔,随机均分成三组:HES组,生理盐水组(NS组),对照组(C组).HES组和NS组分别用HES130/0.4和生理盐水行ANH,使红细胞压积(Hct)达30%.ANH的方法为:15 min内经股动脉恒速放出计算的血量,同时利用微量输液泵经静脉输注与放血量等量的液体(HES组)或输注3倍于放血量的液体(NS组),放血和输液速度相等,维持术中大白兔的血压和心率恒定.稳定15 min后,行肾下腹主动脉(IRA)阻闭建立脊髓缺血-再灌注损伤模型.分别于稀释前、稀释后和腹主动脉开放后采集动脉血进行血气分析.评估再灌注后4、8、12、24及48 h后肢运动功能,并于48 h处死动物取脊髓(L5)制标本行病理组织学观察.结果 再灌注后48 h.HES组和NS组动物的后肢运动功能比C组明显改善(P＜0.05或P＜0.01);HES组和NS组动物脊髓前角正常运动神经元计数比C组显著增加(P＜0.05或P＜0.01),但两组间差异无统计学意义.结论 HES130/0.4行适度ANH对脊髓缺血-再灌注损伤具有显著地保护作用.     

Continuous haemodynamic monitoring using transoesophageal Doppler during acute normovolaemic haemodilution in patients with coronary artery disease

Transoesophageal Doppler monitoring allows non-invasive assessment of stroke volume. We studied haemodynamic changes during acute normovolemic haemodilution (ANH) in anaesthetised patients with coronary artery disease. Twenty patients were randomly assigned to either ANH or a control group. During ANH, a mean (SD) blood volume of 15.3 (3.4) ml.kg(-1) was withdrawn decreasing systemic oxygen delivery from 12.7 (3.3) to 9.3 (1.8) ml.kg(-1).min(-1) (p < 0.001). In the control group, haemodynamic data remained unchanged, whereas in the ANH group, stroke volume and central venous pressure increased significantly (mean = +21 ml [95% CI: 18-25 ml.min(-1)]; mean = +2.5 mmHg [95% CI: 2.2-2.8 mmHg], respectively) and heart rate decreased (mean = -6 beat.min(-1)[95% CI: 6-8 beat.min(-1)], p < 0.05). According to the Frank-Starling relationship, individual changes in stroke volume compared with central venous pressure fitted a quadratic regression model (R2 > 0.91). A reduced viscosity associated with ANH resulted in improved venous return, higher cardiac preload and increased cardiac output. In summary, this study demonstrated that ANH to a haemoglobin value of 8.6 g.dl(-1) was well tolerated in patients with coronary artery disease.     

The influence of crystalloid and colloid replacement solutions in acute normovolemic hemodilution: a preliminary survey of hemostatic markers

Acute normovolemic hemodilution (ANH), in which blood for autologous use is collected immediately before the onset of surgical blood loss, is a recommended autologous blood procurement technique for blood conservation. Both crystalloid and colloid replacement fluids have been used to maintain normovolemia during ANH, but few data are available to justify the use of a particular replacement fluid. Therefore, we designed a prospective, randomized study to determine if the replacement fluid choice affects various coagulation variables and perioperative blood loss. Forty adult patients, ASA physical status 1-3, scheduled for ANH during radical prostatectomy were randomly assigned to one of four replacement fluid groups: (a) Ringer's lactate, (b) 5% albumin, (c) 6% dextran 70 (DEX), or (d) 6% hetastarch (HES). After the induction of a standardized general anesthetic, all patients underwent ANH to a final hemoglobin level of 9 g/dL. Complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, factors V and VIII levels, bleeding time, and thromboelastography (TEG measurements were obtained at similar time points in the procedure. When compared with baseline, activated partial thromboplastin time decreased and factor VIII levels increased in the postanesthesia care unit in both the Ringer's lactate and 5% albumin groups. The DEX and HES groups demonstrated a decrease in TEG maximum amplitude between preoperative and postanesthesia care unit measurements and TEG alpha (angle) was decreased from baseline in the DEX group. The changes in factor VIII, activated partial thromboplastin time, and TEG measurements indicate that HES and DEX may attenuate the hypercoagulability related to surgery.