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.     

Splanchnic perfusion during controlled hypotension combined with acute hypervolemic hemodilution: a comparison with combination of acute normovolemic hemodilution-gastric intramucosal pH study

STUDY OBJECTIVE: To evaluate the effect of controlled hypotension combined with acute hypervolemic or normovolemic hemodilution on the splanchnic perfusion in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 28 ASA physical status I and II patients scheduled for total hip arthroplasty.Interventions: Patients were randomly divided into two groups. Group A (n = 14) received controlled hypotension with acute normovolemic hemodilution (ANH). Group B (n = 14) received controlled hypotension with acute hypervolemic hemodilution (HHD). ANH was produced by drawing approximately 1000 mL of blood and replacing it with the same amount of 6% hydroxyethyl starch solution (HES). HHD was produced by preoperative infusion of 1000 mL of 6% HES without removing blood. The final hematocrit values were 24+/-2% (mean +/- SD) in Group A and 25+/-3% in Group B. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS: Measurements included the gastric pH (pHi), the arterial blood pH (pHa), and plasma lactate. These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, 60 minutes after recovery from hypotension, and on the first postoperative day. The value of pHi was measured by tonometric method. MAIN RESULTS: The pHa and lactate values showed no change in either group A or group B throughout the time course. Gastric pHi values in group A showed a significant decrease from 7.424+/-0.033 to 7.335+/-0.038 (p<0.05) after hemodilution, whereas it showed no further decrease at 80 minutes after starting hypotension and 60 minutes after recovery from hypotension. The pHi values in group B showed no significant decrease after hemodilution and no further change at 80 minutes after starting hypotension. CONCLUSIONS: HHD does not impair splanchnic perfusion, whereas ANH might cause impairment. Controlled hypotension with prostaglandin E1 would not impair splanchnic perfusion in combination with either HHD or ANH.     

Influence of volume replacement with different HES–solutions on microcirculatory blood flow in cardiac surgery

A variety of hydroxyethyl starch (HES) preparations with different molecular weight average (Mw) and molar substitution (MS) is available for volume replacement during acute normovolemic haemodilution (ANH). Particularly with regard to microcirculation, the ideal solution for volume therapy has not been found. A 5th group without ANH served as a control (10 patients in each group). In addition to systemic haemodynamics and various laboratory parameters, skin capillary blood flow was measured by laser Doppler flowmetry. Laser Doppler flow (LDF) was monitored simultaneously at the patient's forehead and forearm. Changes in systemic haemodynamics were similar in all ANH–patients. Systemic vascular resistance (SVR) was lowest after infusion of HES 200/0.5. The most pronounced increase in plasma viscosity was in patients of group 1 (450/0.7) (P<0.05) and plasma viscosity remained highest during the entire investigation period in these patients. After ANH, skin capillary blood flow measured at the forehead decreased in all patients except in patients of group 2 (200/0.5: max. + 18%). Group 3 (200/0.62) showed the highest decrease in forehead–LDF. During CPB, forehead–LDF decreased significantly in groups 3 (200/0.62) and 4 (40/0.5). At the end of the operation, LDF was most reduced in groups 1 (– 32%) and 3 (– 33%). Forearm–LDF increased in all ANH–patients. Immediately after ANH this increase was lowest in group 3 (200/0.62). In the further course of the investigation, no more differences were seen in any HES patients. The different HES preparations showed a different microcirculatory response. 6% HES 200/0.5 seems to be overall most suitable for volume replacement in cardiac surgery patients undergoing acute normovolemic haemodilution (ANH) due to the best effects on microcirculatory skin perfusion assessed by laser Doppler flow. HES 6% 200/0.62 showed the overall least positive effects with regard to skin capillary blood flow in this situation.     

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.     

Perflubron Emulsion Delays Blood Transfusions in Orthopedic Surgery

Background: Fluorocarbon emulsions have been proposed as temporary artificial oxygen carriers. The aim of the present study is to compare the effectiveness of perflubron emulsion with the effectiveness of autologous blood or colloid infusion for reversal of physiologic transfusion triggers.

Methods: A multinational, multicenter, randomized, controlled, single-blind, parallel group study was performed in 147 orthopedic patients. Patients underwent acute normovolemic hemodilution with colloid to a target hemoglobin of 9 g/dl with an inspiratory oxygen fraction (FIO2) of 0.40. Patients were then randomized into one of four treatment groups after having reached any of the protocol-defined transfusion triggers including tachycardia (heart rate > 125% of posthemodilution rate or > 110 bpm), hypotension (mean arterial pressure < 75% of posthemodilution level or <= 60 mmHg), elevated cardiac output (> 150% of posthemodilution level) or decreased mixed venous oxygen partial pressure (PvO2; < 38 mmHg). Treatments in the four groups were 450 ml autologous blood harvested during acute normovolemic hemodilution given at FIO2 = 0.40; 450 ml colloid at FIO2 = 1.0; 0.9 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0; and 1.8 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0. The primary endpoint was duration of transfusion-trigger reversal. A secondary endpoint was percentage of transfusion-trigger reversal.

Results: Perflubron emulsion was well tolerated with no serious adverse event attributed to drug treatment. Duration of reversal was longest in the 1.8 g/kg perflubron group (median, 80 min; 95% confidence interval, 60-100 min;P = 0.014 vs. autologous blood, P < 0.001 vs. colloid) followed by the 0.9 g/kg perflubron group (median, 59 min; 95% confidence interval, 40-90 min), the autologous blood group (median, 55 min; 95% confidence interval, 30-70 min) and the colloid group (median, 30 min; 95% confidence interval, 27-60 min). Percentage of reversal was also highest in the 1.8 g/kg perflubron group (97%;P < 0.001 vs. autologous blood;P = 0.014 vs. colloid), followed by 0.9 g/kg perflubron (82%), colloid (76%), and autologous blood (60%).     

Perflubron emulsion delays blood transfusions in orthopedic surgery. European Perflubron Emulsion Study Group.

BACKGROUND: Fluorocarbon emulsions have been proposed as temporary artificial oxygen carriers. The aim of the present study is to compare the effectiveness of perflubron emulsion with the effectiveness of autologous blood or colloid infusion for reversal of physiologic transfusion triggers. METHODS: A multinational, multicenter, randomized, controlled, single-blind, parallel group study was performed in 147 orthopedic patients. Patients underwent acute normovolemic hemodilution with colloid to a target hemoglobin of 9 g/dl with an inspiratory oxygen fraction (FIO2) of 0.40. Patients were then randomized into one of four treatment groups after having reached any of the protocol-defined transfusion triggers including tachycardia (heart rate > 125% of posthemodilution rate or > 110 bpm), hypotension (mean arterial pressure < 75% of posthemodilution level or < or = 60 mmHg), elevated cardiac output (> 150% of posthemodilution level) or decreased mixed venous oxygen partial pressure (PVO2; < 38 mmHg). Treatments in the four groups were 450 ml autologous blood harvested during acute normovolemic hemodilution given at FO2 = 0.40; 450 ml colloid at FIO2 = 1.0; 0.9 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0; and 1.8 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0. The primary endpoint was duration of transfusion-trigger reversal. A secondary end-point was percentage of transfusion-trigger reversal. RESULTS: Perflubron emulsion was well tolerated with no serious adverse event attributed to drug treatment. Duration of reversal was longest in the 1.8 g/kg perflubron group (median, 80 min; 95% confidence interval, 60-100 min; P = 0.014 vs. autologous blood, P < 0.001 vs. colloid) followed by the 0.9 g/kg perflubron group (median, 59 min; 95% confidence interval, 40-90 min), the autologous blood group (median, 55 min; 95% confidence interval, 30-70 min) and the colloid group (median, 30 min; 95% confidence interval, 27-60 min). Percentage of reversal was also highest in the 1.8 g/kg perflubron group (97%; P < 0.001 vs. autologous blood; P = 0.014 vs. colloid), followed by 0.9 g/kg perflubron (82%), colloid (76%), and autologous blood (60%). CONCLUSIONS: Perflubron emulsion (1.8 g/kg) combined with 100% oxygen ventilation is more effective than autologous blood or colloid infusion in reversing physiologic transfusion triggers.     

Comparison between intermittent and continuous measurement of cardiac output after acute normovolemic hemodilution in pigs

Continuous cardiac output (CO) and mixed venous oxygen saturation (SvO2) determined through the pulmonary artery catheter may be helpful in monitoring hemodynamic conditions in critically ill patients. This study aimed to evaluate CO and SvO2 in a model of acute normovolemic hemodilution (ANH), analyzing the accuracy of the continuous versus intermittent method for CO and SvO2 measurement in pigs. Twenty-three pigs were enrolled to three groups: control, ANH with 6% hydroxyethyl starch (HES), or ANH with lactated Ringer's (LR) solution. After hemodilution, we showed that SvO2 was reduced in both groups, mainly in LR animals (P < 0.05). Regarding the evaluation of CO, we showed an increase in both groups submitted to ANH (P < 0.05). Through Bland-Altman analysis, we showed that the continuous CO catheter presented lower values than the intermittent method after hemodilution, mainly with HES (P < 0.001), and there was no difference in the measurement of SvO2. The ANH promoted a decrease in SvO2 and an increase in CO values, mainly in animals submitted to hemodilution with HES. The use of continuous and intermittent (laboratory) measurement of SvO2 showed clinical applicability and good agreement, an effect not reproduced by the CO measurement. New studies are needed to further investigate the agreement between the continuous and intermittent methods for the measurement of CO in adverse hemodynamic conditions such as ANH.     

Exakte Messung des Volumeneffektes von 6%iger Hydroxyethylstärke 130/0,4 (Voluven®) während präoperativer akuter normovolämer Hämodilution

Background

What is the effect of preoperative acute normovolemic hemodilution (ANH) with 6% hydroxyethyl starch (HES) 130/0.4 (Voluven^®) on blood volume?

Methods

In 10 patients undergoing radical hysterectomy, ANH was performed to a hematocrit of 21% using 6% HES 130/0.4 (Voluven^®) whereby a replacement of blood with 115% of colloid was planned. Plasma volume (indocyanine green dilution technique) and hematocrit were determined before, 30 and 60 min after ANH. Red cell volume (labelling erythrocytes with fluorescein) was determined before and 30 min after ANH.

Results

After removal of 1,431±388 ml of blood and simultaneous replacement with 1,686±437 ml of colloid, blood volumes were 218±174 ml higher than before (at 105±4%). The volume effect was 98±12%, 30 min after ANH. Even 60 min after ANH, mean blood volumes were with 4,228±986 ml slightly higher than before ANH (102±5%). The hematocrit decreased disproportionally in relation to the residual intravascular volume. Consequently, estimating the volume effect from the changes in hematocrit led to an overestimation (about +30%).

Conclusion

Double label measurements of blood volume demonstrated that the volume effect of 6% HES 130/0.4 (Voluven^®) is about 100% in the course of ANH. The reason for the disproportionally large decrease in hematocrits could be the mobilization of a fraction of the plasma volume which was retained within the endothelial glycocalyx.     

Small volume hypertonic hydroxyethyl starch reduces acute microvascular dysfunction after closed soft-tissue trauma

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL. In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by approximately 50%. Erythrocyte flux in NS-treated animals decreased to 90 +/- 8% (mean SEM), whereas values in the HS/HES group significantly increased to 137 +/- 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 +/- 0.02) was significantly decreased compared with the NS-group (1.12 +/- 0.01). HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction.     

Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs

BACKGROUND: Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. METHODS: Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. RESULTS: Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. CONCLUSION: High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.     

Acid-Base Changes Caused by 5% Albumin versus 6% Hydroxyethyl Starch Solution in Patients Undergoing Acute Normovolemic Hemodilution: A Randomized Prospective Study

Background: Preoperative acute normovolemic hemodilution (ANH) is an excellent model for evaluating the effects of different colloid solutions that are free of bicarbonate but have large chloride concentrations on acid-base equilibrium.

Methods: In 20 patients undergoing gynecologic surgery, ANH to a hematocrit of 22% was performed. Two groups of 10 patients each were randomly assigned to receive either 5% albumin or 6% hydroxyethyl starch solutions containing chloride concentrations of 150 and 154 mm, respectively, during ANH. Blood volume (double label measurement of plasma and red cell volumes), pH, Paco2, and serum concentrations of sodium, potassium, chloride, lactate, ionized calcium, phosphate, albumin, and total protein were measured before and 20 min after completion of ANH. Strong ion difference was calculated as serum sodium plus serum potassium minus serum chloride minus serum lactate. The amount of weak plasma acid was calculated using a computer program.

Results: After ANH, blood volume was well maintained in both groups. ANH caused slight metabolic acidosis with hyperchloremia and a concomitant decrease in strong ion difference. Plasma albumin concentration decreased after hemodilution with 6% hydroxyethyl starch solution and increased after hemodilution with 5% albumin solution. Despite a three-times larger decrease in strong ion difference after ANH with 6% hydroxyethyl starch solution, the decrease in pH was nearly the same in both groups.     

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.     

Albumin or hetastarch improves neurological outcome and decreases volume of brain tissue necrosis but not brain edema following closed-head trauma in rats.

The present study examined whether hemodilution with 20% human serum albumin (HSA) or 10% hydroxyethyl starch (HES) improved the outcome from closed-head trauma (CHT) in rats. Rats anesthetized with halothane were given one of three hemodilution solutions (i.e., 20% HSA, 10% HES, or control [0.9% saline]) after CHT or sham surgery. CHT was delivered using a weight drop impact of 0.5 J onto the closed cranium. The hemodilution solution (volume = 1% of body weight) was given just after determining the neurological severity score (NSS) at 1 hour following CHT. The NSS was determined again at 24, 48, and 72 hours following CHT. At 72 hours, brains were removed, and brain edema and brain tissue necrosis volume were determined. Solutions of 20% HSA and 10% HES significantly improved brain tissue necrosis volume (143 +/- 72 mm3 and 104 +/- 53 mm3 as compared to 271 +/- 65 mm3 in controls, mean +/- SD) and NSS (12 +/- 2 and 9 +/- 2 as compared to 15 +/- 2 in controls at 72 hours, median +/- range) but not brain edema. The hematocrit decreased similarly in all groups during hemodilution. Hemodilution with 20% HSA and 10% HES following CHT in rats did not decrease brain edema but did decrease brain tissue necrosis volume and NSS (improved neurological function), suggesting that the beneficial effect of hemodilution resulted not from decreased edema formation but rather from effects not measured in this study such as improved perfusion of the salvageable brain tissue surrounding the core injury.     

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.     

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.     

Effect of High- and Low-molecular-weight Low-substituted Hydroxyethyl Starch on Blood Coagulation during Acute Normovolemic Hemodilution in Pigs

Background: Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution.

Methods: Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml [middle dot] kg-1 [middle dot] body weight-1 of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters.

Results: Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle [alpha] (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations.     

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.     

Hemostasis and hemodilution: a quantitative mathematical guide for clinical practice

Quantitative changes of hemostasis during hemodilution remain unclear. With the increasing popularity of artificial blood substitutes (ABS), which solely provide oxygen-transport capacity, this issue becomes even more complex. We developed a mathematical model to quantitatively analyze hemostasis during hemodilution and validated it by recalculating patient data. We calculated and compared maximal allowable blood losses (MABL) related to minimal acceptable hematocrit, platelet concentration, and plasma fibrinogen concentration. MABL is the maximal blood loss that can be tolerated without any additional blood products. The variable with the smallest MABL thus limits hemodilution foremost. Hemodilution included isovolemic replacement of blood loss with colloid or acute normovolemic hemodilution (ANH) followed by isovolemic replacement of blood loss with colloid and ABS. We also related our findings to preoperative patient data (n = 204). The decline in platelet concentrations rarely (<2% of all patients) limits hemodilution. By contrast, critical plasma fibrinogen (< or =100 mg/dL) concentrations can often (< or =20% of all patients) limit hemodilution if their initial concentrations are within the lower normal range (<300 mg/dL). These findings become more frequent if ANH is combined with ABS. Under those circumstances ANH blood products are solely required for stabilization of hemostasis, thereby defeating the original purpose of combining ANH with ABS. IMPLICATIONS: The causes of quantitative changes of hemostasis during hemodilution, as well as their clinical effect and relevance, remain unclear. Using a validated, realistic mathematical model, we demonstrate that hemostasis, especially plasma fibrinogen, can limit the extent of hemodilution. This phenomenon is particularly prominent when acute normovolemic hemodilution is combined with artificial blood substitutes.     

Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections

BACKGROUND: Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH). METHODS: The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population. RESULTS: During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups. CONCLUSIONS: Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood.     

Changes in blood volume during acute normovolemic hemodilution with 5% albumin or 6% hydroxyethylstarch and intraoperative retransfusion

Question. What is the impact of acute preoperative normovolemic hemodilution (ANH) on blood volume, intravascular colloid, and loss of red cells in the perioperative period? Methods. In 20 patients undergoing radical hysterectomy, preoperative ANH was performed to a hematocrit of 22% using 5% albumin (albumin group; n=10) or 6% hydroxyethylstarch solution (HES group; n=10). Intraoperative retransfusion of ANH blood was started at a hematocrit of 18%. Plasma volume (indocyanine green-dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labelling erythrocytes with fluorescein) was determined before and after ANH and postoperatively. In the HES group hydroxyethylstarch concentrations were measured in plasma and urine. Results. After removal of about 1,500 ml of blood and replacement with 15% more colloid solution, the blood volume was maintained in both groups after ANH. After a mean blood loss of about 1,800 ml, an average of 150 ml of red cells were saved due to ANH in both groups. Conclusions. Double label measurements of blood volume demonstrated that with the colloids used a surplus of 15% of colloid infusion in relation to blood removal was necessary to generate isovolemia after ANH.