Effects of different plasma expanders on rats subjected to severe acute normovolemic hemodilution

Background:Plasma expanders are widely used for acute normovolemic hemodilution(ANH).However,existing studies have not focused on large-volume infusion with colloidal plasma expanders,and there is a lack of studies that compare the effects of different plasma expanders.Methods:The viscosity,hydrodynamic radius(Rh)and colloid osmotic pressure(COP)of plasma expanders were determined by a cone-plate viscometer,Zetasizer and cut-off membrane,respectively.Sixty male rats were randomized into five groups with Gelofusine(Gel),Hydroxyethyl Starch 200/0.5(HES200),Hydroxyethyl Starch 130/0.4(HES130),Hydroxyethyl Starch 40(HES40),and Dextran 40(Dex40),with 12 rats used in each group to build the ANH model.ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders.Acid-base,lactate,blood gas and physiological parameters were detected.Results:Gel had a lower intrinsic viscosity than HES200 and HES130(P<0.01),but at a low shear rate in a mixture of colloids,red cells and plasma,Gel had a higher viscosity(P<0.05 or P<0.01,respectively).For hydroxyethyl starch plasma expanders,the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of Rh from 10.7 nm to 20.2 nm.A severe ANH model,with the hematocrit of 40%of the baseline level,was established and accompanied by disturbances in acid-base,lactate and blood gas parameters.At the end of ANH and 60 min afterward,the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups.The systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)decreased significantly in all groups at the end of ANH.The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH.During the process of ANH,the Dex40 group showed a drop and recovery in SBP,DBP and MAP.The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points(P<0.05 or P<0.01).Conclusions:Gel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates.Rh and COP showed a strong correlation among hydroxyethyl starch plasma expanders.Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders.During the process of ANH,Dex40 displayed a V-shaped recovery pattern for blood pressure,and HES200 had the advantage in sustaining the DBP and MAP at some time points.

Evaluation of modified hemodilution combined therapy in the treatment of acute ischemic stroke in the elderly

BACKGROUND： Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal. OBJECTIVE： To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method. DESIGN： 1：1 paired grouping according to gender and controlled observation SETTING： Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University. PARTICIPANTS： Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items. According to 1：1 paired principle in gender, 90 enrolled patients were assigned into treated group （n=45） and control group （n=45）. There were 39 male and 6 female in the treatment group, and they were aged （76±6）years, ranging from 71 to 84 years, and hospitalized at the 14^th to 76^th hours after onset. There were 39 male and 6 female in the control group, and they were aged （76±6）years , ranging from 70 to 82 years, and hospitalized at the 16^th to 72^th hours after onset. METHODS： Therapeutic method： Patients of treated group received modified hemodilution combined therapy. 200 mL whole blood of patients was exchanged with 500 mL dextran-40 （including 20 mL danshen parenteral solution and 32 mg heparin） at the beginning of therapy; From the 2^nd day, compound huangqi tea bag （Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid） was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6^th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton（Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ） and 50 g/L glucose of 500 mL, 75 mg acetosal was taken orally, once a day, 14 days in total. ② Measurement and observation of index： Blood coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference （1995） was used to evaluate the recovery of neurological function of the patients in two groups at the 3rd, 5^th, 7^th and 14^th days after therapy. ③Therapeutic effect and adverse effect were observed at the same time. MAIN OUTCOME MEASURES ： ① Changes of coagulation index, blood lipid level and hemorheology; ② Blood flow rate of middle cerebral artery and NDS of patients with acute ischemic stroke in two groups; ③Adverse effect of drug. RESULTS： Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died of severe pulmonary infection. The rest 88 patients entered the stage of result analysis. ① Change of coagulation index and platelet aggregation rate： prothrombin time （PT）, activated partial thromboplastin time （APTT） and thrombin time （TT） of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group： （18.4±1.9）, （41.8±2.1）, （19.7±1.7） s, Before therapy in treated group： （13.4±1.3）, （35.8±1.3）, （12.5±0.9） s, After therapy in control group： （16.9±1.5）, （39.1±1.1）, （11.9±2.1） s, P〈 0.05]：Concentration of fibrinogen （Fbg） after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group： （3.4±0.4） g/L; Before therapy in treated group： （4.3±0.7） g/L; After therapy in control group：（4.0±0.6） g/L; P 〈 0.05]. Platelet aggregation rate decreased from （37.92 ±0.85）% before therapy to （26.42±1.01）% after therapy （P 〈 0.01）. ②Change of blood lipid level： Levels of total cholesterol （TC）, triacylglycerol（TG） and low density lipoprotein cholesterol （LDL-C） of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group： （5.2±0.9）, （1.9±0.9）, （2.08±1.1） mmol/L, before therapy in treated group： （5.9±1.2）, （2.8±0.9）, （3.94±0.5） mmol/L, After therapy in control group： （6.0±1.1）, （2.6±0.8）, （3.84±0.9） mmol/L, P 〈 0.05]. ③Change of hemorheology index： Hematocrit of patients of treated group was significantly lower after therapy than before therapy [Before therapy： （43.84±4.55）% ;After therapy： （40.48±4.02）%;P 〈 0.05]. Blood flow rate of middle cerebral artery of patients of treated group was significantly lower before therapy than after therapy [（90±1.2）, （97±2.1） cm/s,P〈 0.01]. ⑤NDS of patients in treated group was significantly lower than of control group 14 days after therapy. The total effective rate after therapy was significantly higher in the treated group than in the control group （93%,78%, P 〈 0.05）. ⑥There was no obvious adverse effect. CONCLUSION： Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit, increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid.

Acute Normovolemic Hemodilution: A Practical Approach

Justifications: Perioperative allogeneic blood transfusion can be reduced or even completely avoided by using a set of different strategies: meticulous hemostasis, the use of pharmaceutical agents that assist in the process of coagulation/ fibrinolysis, the use of blood substitutes, induced hypotension, preoperative autologous blood donation, collection and reinfusion of autologous blood during the operation, as well as from acute normovolemic hemodilution (ANH). Contents: ANH consists of taking a percentage of the patient’s blood volume and a concurrent infusion of acellular fluids in order to maintain normovolemia. As a consequence, a hemodiluted patient will lose less blood cells for each blood volume that is lost during the surgical procedure. The aim of this study is to clarify doubts and provide practical information relative to the procedure of ANH through the author’s own experiences as well as literary examples. Conclusions: ANH is an easy and cheap technique performed during the intraoperative period useful to reduce the use of hemoderivatives.

Effect of Hemodilution on Fluctuation of Cerebral Oxygen Saturation during Cardiopulmonary Bypass in Children with Cyanotic Congenital Heart Disease

Background:In patients with cyanotic congenital heart disease(CHD),cerebral oxygenation may be maintained by elevations in hematocrit(Hct).Hemodilution accompanying cardiopulmonary bypass(CPB),however,can disrupt cerebral oxygen balance,leading to fluctuations in cerebral oxygen saturation(ScO_(2)).The present study investigated the effects of Hct changes on the fluctuation of ScO_(2)during CPB in cyanotic CHD using performance measurement(PM).Methods:Children with CHD(51 acyanotic and 46 cyanotic)who had undergone cardiac surgery using CPB were enrolled.Median performance error(MDPE),median absolute performance error(MDAPE),and wobble parameters of ScO_(2)were calculated before(reference value),during,and after CPB.Correlations of PM parameters with Hct and reductions in Hct(ΔHct)were also evaluated.Results:Before CPB,patients with cyanotic CHD had lower MDPE and larger wobble than those with acyanotic CHD,although mean ScO_(2)did not differ significantly between the two groups.During CPB,ScO_(2)of acyanotic CHD increased asΔHct increased,but PM variables were not associated withΔHct.In cyanotic CHD,MDPE(r=−0.324,p=0.032)and MDAPE(r=0.339,p=0.024)correlated significantly withΔHct during CPB.After CPB,MDPE(r=0.574,p=0.025)and MDAPE(r=−0.543,p=0.036)were significantly correlated with Hct in children with cyanotic CHD who underwent palliative surgery.Conclusion:Therefore,ScO_(2)fluctuation during CPB in children with cyanotic CHD may be affected by the decrease in Hct,suggesting that excessive hemodilution can negatively influence the maintenance of cerebral oxygenation in these patients.

Safety and efficacy of acute normovolemic hemodilution during liver surgery: a Meta-analysis

Objective The aim of this study was to evaluate the safety and efficacy of acute normovolemic hemodilution(ANH) during liver surgery.Methods Structured searches of the Pub Med,Chinese Biological Medicine Database,and Cochrane Library electronic databases were performed,followed by a meta-analysis of outcomes,including intraoperative blood transfusion(s),intraoperative bleeding,postoperative hematocrit(Hct) levels,postoperative prothrombin time(PT),and number of patients who underwent transfusions during liver surgery.Results In total,14 eligible studies were included in the meta-analysis,which revealed that ANH for liver resection was associated with a reduction in intraoperative blood transfusions [weighted mean difference(WMD)-1.99;95% confidence interval(CI)-2.82 to -1.16;P<0.00001].The ANH group experienced less intraoperative bleeding(WMD -72.81;95% CI -136.12 to -9.50;P<0.00001) and exhibited a lower postoperative Hct level(WMD -3.38;95% CI -7.14 to -0.67;P<0.00001) than the control group.Moreover,meta-analysis revealed that postoperative prothrombin time was not affected by ANH(WMD -0.02;95% CI -0.18 to -0.32;P=0.65).Finally,the number of patients requiring allogeneic transfusion was significantly smaller in the ANH group than in the control group(odds ratio 0.13;95% CI 0.09 to 0.18;P=0.24).Conclusion Results of the present meta-analysis indicated that ANH can reduce intraoperative bleeding and the need for blood transfusions.In addition,ANH did not negatively affect the coagulation system after surgery;therefore,ANH appears to be safe and effective during liver surgery.

The role of acute normovolemic hemodilution in reducing allogeneic blood transfusion in glioblastoma surgery:a case-control study

Background Acute normovolemic hemodilution(ANH)was first introduced in glioblastoma surgery,and its role in reducing allogeneic blood transfusion was investigated in this study.Methods This study enrolled supratentorial glioblastoma patients who received total resection.In the ANH group,the patients were required to draw blood before the operation,and the blood will be transfused back to the patient during the operation.The association between ANH and clinical features was investigated.Results Sixty supratentorial glioblastoma patients were enrolled in this study,25 patients were allocated in the ANH group,and another 35 patients were included in the control group.ANH dramatically reduced the need for allogeneic blood transfusion(3[12%]vs 12[34.3%],P=0.049),and the blood transfusion per total of patients was dramatically decreased by the application of ANH(0.40±1.15 units vs 1.06±1.59 units,P=0.069).Furthermore,ANH also markedly reduced the requirement of fresh frozen plasma(FFP)transfusion(2[8%]vs 11[31.4%],P=0.030)and the volume of FFP transfusion per total of patients(32.00±114.46 mL vs 115.71±181.00 mL,P=0.033).The complication rate was similar between the two groups.Conclusions ANH was a safe and effective blood conservation technique in glioblastoma surgery.

Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis

Background Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis （SAP）. In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. Methods One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution （hematocrit （HCT） 〈35%, n=56） or slow hemodilution （HCT 〉35%, n=-59） within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. Results The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution （P 〈0.05） on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution （（7.4±1.9） days） compared with the slow hemodilution group （（10.2±2.3） days）, and the incidence of sepsis （78.6%） was higher in the rapid group compared to the slow （57.6%） in the first 28 days. The survival rate of the slow hemodilution group （84.7%） was better than the rapid hemodilution （66.1%. P 〈0.05）. Conclusions Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.

Responsiveness of stroke volume variation and central venous pressure during acute normovolemic and hypervolemic hemodilution

Background Stroke volume variation （SW） is a robust indicator of fluid responsiveness during volume change. We compared the sensibility of SW by Vigileo/Flotrac to central venous pressure （CVP） when volume changes in patients undergoing intraoperative acute normovolemic hemodilution （ANH） and acute hypervolemic hemodilution （AHH）. Methods Forty patients were randomly divided into an ANH group （n=20） and an AHH group （n=20）. All patients received general anesthesia and were mechanically ventilated. Data were collected from 7 different time-points in the ANH group： baseline, after withdrawal of 5%, 10%, and 15% of the estimated blood volume （EBV） and after replacement with an equal volume of 6% hydroxyethyl starch 130/0.4 （HES） in 5% EBV increments to baseline. There were four time points in the AHH group： baseline, after 5%, 10%, and 15% expansion of the EBV with 6% HES. At each time-point, CVP, SW and other hemodynamic parameters measurements were obtained. Results After removal of 10% and 15% EBV, SVV significantly increased from 10.9±3.0 to 14.1±3.4 and 10.9±3.0 to16.0±3.3 （P 〈0.01）, and returned to a final value of 10.6±3.4 after volume replacement. The CVP value was unchanged after removal and replacement of 15% of the EBV. There were no significant changes in SW after 5%, 10% whereas there was a significant reduction after 15% （8.2±1.7） expansion of the EBV compared with baseline （9.9±1.8） （P=0.033）. However, there was a significant increase in CVP after10% （10.3±2.4）, 15% （11.3±2.2） expansion of the EBV compared with baseline （8.2±2.7） （P 〈0.01）. Conclusion SW is a more sensitive parameter for volume than CVP during hypovolemia, on the contrary CVP is more sensitive than SW during hypervolemia.

Prolonged hypervolemic hemodilution decreases functional capillary density of ileal mucosa in pigs revealed by sidestream dark-field imaging

Objective:Hemodilution changes the physical properties of blood by reducing its hematocrit and blood viscosity.We tested whether prolonged hypervolemic hemodilution (HHD) impairs functional capillary density (FCD) of ileal mucosa in healthy mechanically-ventilated pigs and if there is any correlation between changes in FCD of ileal and sublingual mucosas during HHD.Methods:Sixteen domestic female pigs were anesthetized,mechanically-ventilated,and randomly assigned to the HHD (20 ml/(kg·h) Hartmann's solution for 3 h) or fluid restrictive (5 ml/(kg·h) Hartmann's solution for 3 h) group.Microcirculations of sublingual and ileal mucosas via ileostomy were visualized using sidestream dark-field (SDF) imaging at baseline conditions (t=0 h) and at selected time intervals of fluid therapy (t=1,2,and 3 h).Results:A significant decrease of ileal FCD (285 (278-292) cm/cm 2) in the HHD group was observed after the third hour of HHD when compared to the baseline (360 (350-370) cm/cm 2) (P<0.01).This trend was not observed in the restrictive group,where the ileal mucosa FCD was significantly higher after the third hour of fluid therapy as compared to the HHD group (P<0.01).No correlation between microhemodynamic parameters obtained from sublingual and ileal mucosas was found throughout the study.Conclusions:Prolonged HHD established by crystalloid solution significantly decreased ileal villus FCD when compared to restrictive fluid regimen.An inappropriate degree of HHD can be harmful during uncomplicated abdominal surgery.

Effects of infusion of different fluids during controlled hypotension on gastric intramucosal pH and postoperative gastroenterological function

The present study was aimed to investigate the effects of infusion of different fluids combined with control-led hypotension on gastric intramucosal pH （pHi） and postoperative gastrointestinal function in patients undergo-ing hepatocarcinoma surgery. Forty-five patients （ASAⅡ） scheduled for surgical resection of hepatocarcinoma undergoing controlled hypotension were randomly assigned to three groups and received infusion of 20 mL/kg Ringer’s solution （R group）, 6% HAES（H group） or 6% Voluven group （W group）. Intragastric PgCO2, pHi, he-matocrit and hemoglobin were measured. The significant decrease of pHi and increase of PgCO2 were produced at 1 and 2 h after controlled hypotension in the R group （P 0.05 or P 0.01）. The time of bowel movement af-ter operation was shorter in the W group than the R group. Meanwhile, we also did not find obvious difference in blood gas indexes among the three groups. The infusion of HAES and Voluven during controlled hypotension could improve gastrointestinal perfusion and accelerate the recovery of postoperative gastrointestinal function.

急性高容量血液稀释联合七氟醚吸入用于脊柱手术患者的血液保护效果观察

目的探讨急性高容量血液稀释(AHH)联合七氟醚吸入对脊柱手术患者的血液保护效果。方法择期行脊柱手术的患者60例,性别不限,年龄34～67岁,体质指数18.5～27.8 kg/m2,ASA分级Ⅱ或Ⅲ级,随机分为对照组(C组)和急性高容量血液稀释联合七氟醚吸入组(A组),各30例。A组于麻醉诱导后行AHH(以25 ml/min)的速率输注6%羟乙基淀粉15 ml/kg),同时持续吸入1.0%～3.0%七氟醚行控制性降压。C组为空白对照组,不做任何处理。连续监测血流动力学指标(HR,MAP,CVP和SpO2),并于麻醉诱导前(T0,基础值)、切皮时(T1)、手术开始后60 min(T2)和术毕时(T3)采集动脉血样,测定凝血酶原时间(PT)、凝血活酶时间(APTT)和动脉血乳酸(Lac),记录术中出血量、异体输血量和尿量。结果与C组比较,A组T1～T2时点MAP明显下降(P<0.05),T1～T3时点CVP明显升高(P<0.05),各时点HR、SpO2、PT、APTT和Lac差异无统计学意义(P>0.05)。A组术中出血量、异体输血例数和输血量明显少于C组(P<0.05)。结论 AHH联合七氟醚吸入可减少术中出血量和异体输血量,且不影响凝血功能和微循环灌注,可安全用于脊柱手术的血液保护。

Effects of Phentolamine on Hemorrheology and Hemodynamics in Dogs with Acute Liver Damage

The effects of phentolamine on hemorrheology and hemodynamics were studied in dogs with acute liver damage induced by acetaminophen. After 1 h of phentolamine application , the viscosity of plasma and whole blood was significantly diminished. The hematocrit readings followed the same pattern as the alterations in viscosity. The portal venous resistance and the value of K were remarkably decreased and the portal venous blood flow was obviously increased. It can be assumed , therefore , that the decrease in viscosity induced by phentolamine results from internal hemodilution and phentolamine may improve hepatic blood circulation through the decrease of portal venous resistance caused by the reduction of blood viscosity and the dilation of portal vascular beds.