Clinical, hemodynamic, and hemorheological effects of isovolemic hemodilution in acute cerebral infarction

The effect of isovolemic hemodilution on regional cerebral blood flow (rCBF) and neurological symptoms in 35 patients with acute ischemic stroke was evaluated. Twenty-one patients had internal carotid artery occlusion, and 14 had middle cerebral artery occlusion. Isovolemic hemodilution combined with venesection and the administration of fresh plasma to reduce the hematocrit (Hct) to 33% was performed within 72 hours of the onset of symptoms. The Hct decreased by 27% and was correlated directly with whole blood viscosity (WBV) at a shear rate of 10 sec-1 after the hemodilution. The cardiac output increased by 29% after hemodilution without significant alterations in cerebral perfusion pressure and showed a good inverse correlation with the Hct and the WBV. The rCBF of the area supplied by the ischemic middle cerebral artery (MCA) increased by 30% and was related inversely to the Hct and the WBV. The cerebrospinal fluid pressure increased by 16%, but no symptoms of raised intracranial pressure were observed. The N20 peak latency of the sensory evoked potential decreased by 5%, and the neurological score was improved by 12%. Isovolemic hemodilution thus resulted in an increase of the rCBF in the area supplied by the affected MCA, leading to significant neurological improvement.     

Aging: impact upon local cerebral oxygenation and blood flow with acute isovolemic hemodilution

Data from the neurosurgical critical care arena demonstrate a correlation between cerebral oxygenation, survival, and cognitive function. Transfusion may increase and hemodilution decrease cerebral oxygenation. Both acute and chronic anemia have been associated with cognitive dysfunction. Aggressive blood conservation protocols have been instituted across all age groups without conclusive evidence for their impact upon outcome. Aged subjects are at the greatest risk of cognitive sequelae after major surgery associated with significant blood loss. We hypothesize that cerebral physiologic changes associated with "normal" aging may compromise cerebral oxygenation in the presence of severe anemia.Fischer 344 rats, the NIH National Institute of Aging normal aging rat model, underwent a stepwise isovolemic hemodilution protocol. Age groups (Age Grp) studied were as follows: Age Grp-A (3 months), n=14; Age Grp-B (9 to 12 months), n=14; and Age Grp-C (24 months), n=14. Brain oxygen tension (PBrO2), laser Doppler flow, and mean arterial pressure were measured. Final hemoglobin averaged 6.1+/-0.9 g/dL. PBrO2 levels decreased from a baseline of 18.1+/-4.1 to 17.5+/-6.8 mm Hg (P=0.49), and laser Doppler flow increased by 18+/-20% (P<0.0001) after hemodilution. Employing repeated measures multiple regression, Age Grp (P=0.30) was not a significant controlling covariate of PBrO2 in response to isovolemic hemodilution. PBrO2 levels were actually higher in Age Grp-C animals at all time points of the hemodilution protocol, although this was not statistically significant. Aged animals were also fully capable of mounting a robust local cerebral hyperemic response to the anemic challenge that was not separable from the response of younger animals.     

控制性低血压联合血液稀释对兔肾小球滤过率的影响

目的 观察急性等容血液稀释和控制性低血压联合应用对肾小球滤过功能的影响。方法 选择40只家兔，随机分为对照组，控制性低血压组，血液稀释组和血液稀释联合控制性低血压组。采用氟烷－芬太尼维持麻醉；静脉注射0.02%的硝普钠进行控制性低血压，将MAP维持在35－40mm Hg；通过动脉放血和静脉输注乳酸钠林格氏液进行血液稀释，将Hct降低至20%-25%；采用分光光度法测定血浆菊糖的血浓度，以菊糖清除率来反映肾脏的滤过功能。结果 与对照组比较，控制性低血压组的菊糖排泄率明显降低（P＜0.01)，而联合组则无明显差异（P＞0.05)。结论 单纯控制性低血压可使肾小球滤过率明显降低，而联用血液稀释则可改善控制性低血压下的肾脏微循环灌注。     

The effects of acute isovolemic hemodilution on oxygenation during one-lung ventilation

Data on the effects of isovolemic hemodilution (IH) on oxygenation during one-lung ventilation (OLV) are lacking. We studied 47 patients with hemoglobin >14 g/dL who were scheduled for lung surgery (17 with normal lung function [group NL], 17 with chronic obstructive pulmonary disease [COPD] [group COPD], and 13 with COPD as control for time/anesthesia effects [group CTRL]). Anesthesia was standardized. The tracheas were intubated with a double-lumen tube. Ventilatory settings and fraction of inspired oxygen remained constant. The study was performed with patients in the supine position before surgery. OLV was initiated for 15 min. Two-lung ventilation was reinstituted, and IH was performed (500 mL); an identical volume of hydroxyethyl starch was administered. Subsequently, OLV was again performed for 15 min. In group CTRL, the same sequences of OLV were performed without IH. At the end of each period of OLV, pulmonary mechanics and blood gases were recorded. Data were analyzed by analysis of variance (mean +/- sd). In group NL and group CTRL, the arterial oxygen partial pressure remained constant, whereas it decreased in group COPD from 119 +/- 21 mm Hg before IH to 86 +/- 16 mm Hg after IH (P <0.01). Mild IH impairs gas exchange during OLV in COPD patients, but not in patients with normal lung function.     

Beneficial effects of isovolemic hemodilution using a perfluorocarbon emulsion in a stroke model.

In a clinically applicable cat stroke model, 16 purpose-bred adult animals were used to evaluate the beneficial effects of two treatment regimens: isovolemic hemodilution with either a perfluorocarbon emulsion or dextran 40 (a glucose polymer). Animals that received these treatment regimens were then compared with a control group of untreated animals. Focal cerebral infarctions were produced by transorbital ligation of the left middle cerebral artery. The randomly allocated treatment arms of the study were instituted 3 hours after ligation of the middle cerebral artery, thereby simulating a human clinical situation. In vivo mitochondrial metabolic activity of the peri-infarct cerebral tissue was continually assessed by means of a multiwavelength near-infrared spectrophotometer. This allowed measurement of cellular oxygenation at the cytochrome aa3 level, the terminal member of the cytochrome chain. Sequential proton-based magnetic resonance imaging was used to measure intracerebral water in vivo. Cardiac output, oxygen consumption/delivery, chemical, histologic, and rheologic parameters were also assessed. The data collected were analyzed by group means and standard statistical analyses, which revealed that the group treated with the perfluorocarbon emulsion had both less brain edema in the early post-infarct period (p less than 0.05), as well as a higher level of oxidation of cytochrome aa3 (p less than or equal to 0.025). This evidence supports the premise that isovolemic hemodilution with an oxygen-carrying hemodiluent may be beneficial in the treatment of ischemic strokes.     

急性等容量血液稀释结合控制性降压用于全髋置换术的临床研究

目的　了解控制性降压结合急性等容量血液稀释在全髋置换术中对出血量和术后血红蛋白的影响。方法　择期全髋置换术病人 2 0例 ,随机分成对照组 (组 ,n=10 )和降压组 (组 ,n=10 )。组 采用硬膜外阻滞 ,组 在硬膜外阻滞加全麻下手术 ,术前进行等容量血液稀释 ,术中施行控制性降压。比较两组病人的出血量、输血量和术后血红蛋白。结果　组 病人术中平均出血 ( 4 90±88) ml,比组 病人 ( 94 5± 15 9) ml减少 4 8.1% ;组 病人术中平均输血 ( 62 0± 14 8) ml,而组 病人则完全避免输异体血。两组病人术后均有轻度贫血 ,但仍在安全水平以上 ,且组间差异无显著性意义 ( P>0 .0 5 )。结论　急性等容量血液稀释结合控制性降压用于全髋置换术可明显减少术中出血量 ,对有指征的病人使用可避免输异体血。     

Cerebral effects of isovolemic hemodilution with a hypertonic saline solution

In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR: Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 +/- 6 mEq/liter and 320 +/- 5 mOsm/kg, respectively, mean +/- standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 +/- 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 +/- 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.     

Tolerance to acute isovolemic hemodilution. Effect of anesthetic depth

BACKGROUND: Acceptance of a lower transfusion trigger in the perioperative period requires study of the effects of anesthetic depth on the tolerance to acute isovolemic anemia. Anesthetic agents with negative effects on the cardiovascular system may exert proportionately greater depressant effects on cardiac output response than on tissue oxygen demand, reducing tolerance to acute isovolemic anemia. METHODS: In the first study, animals were anesthetized with halothane (n = 14; 23.8 +/- 4.8 kg, mean +/- SD). In a second study, animals were anesthetized with ketamine (n = 14; 24.3 +/- 4.7 kg). In each study, dogs were randomly allocated to receive either low or high concentrations of anesthetic. Oxygen delivery and oxygen consumption were determined from independent measurements during a stepwise isovolemic hemodilution protocol. In each dog, critical oxygen delivery was determined from a plot of oxygen consumption versus oxygen delivery using a least-sum-of-squares technique. Critical hemoglobin (hemoglobin) was determined from a plot of hemoglobin versus oxygen consumption using the same method. RESULTS: With both agents, the higher anesthetic concentration was associated with decreased oxygen consumption, resulting in a lower critical oxygen delivery. However, critical hemoglobin was significantly higher in the animals receiving the higher anesthetic dosage (1.5 vs. 1.0 minimum alveolar concentration of halothane: 4.1 +/- 1.3 vs. 2.3 +/- 0.5 g/dl, P < 0.05; high- vs. low-dose ketamine: 3.7 +/- 1.4 vs. 2.5 +/- 0.6 g/dl, P < 0.05). This was related to a marked blunting of the cardiac output response to hemodilution in the animals receiving the higher anesthetic dosage. CONCLUSIONS: Increased anesthetic depth with halothane or ketamine resulted in a decreased tolerance to acute anemia, as reflected by a significant increase in critical hemoglobin concentration.     

Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans

BACKGROUND: Controversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. METHODS: Fifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 +/- 1.2 to 5.2 +/- 0.5 g/dl (mean +/- SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. RESULTS: During hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5-7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. CONCLUSION: With acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms.     

急性中度等容性血液稀释对潘库溴铵量—效关系的影响

选择ＡＳＡＩ级行整形外科手术患者３０例随机分成两组：对照组（Ｃ）和血液稀释组（Ｈ）。在麻醉平稳后，手术开始前对Ｈ组患者行急性血液稀释达中度（血球压积平均２８．０４％）。试验中选用加速度仪的四个成串刺激（ＴＯＦ）形式监测神经肌肉功能，用小样本累积给药技术测定两组患者的潘库溴铵量-效关系的变化。结果表明：Ｃ组的潘库溴铵ＥＤ５０、ＥＤ９０、和ＥＤ９５、分别平均为２２．８５±６．９８、４５．２０±７．５１和４７．９９±７·６９μｇ／ｋｇ，Ｈ组的相应数值分别比Ｃ组增加了３２．４２％、２５．５５％和２５．１５％。急性中度等容性血液稀释使潘库溴争的量－效曲线有移，药效明显减弱。     

Subcutaneous perfusion and oxygen during acute severe isovolemic hemodilution in healthy volunteers

HYPOTHESIS: Acute severe isovolemic anemia (to a hemoglobin [Hb] concentration of 50 g/L) does not decrease subcutaneous wound tissue oxygen tension (PsqO(2)). SETTING: University hospital operating room and inpatient general clinical research center ward. SUBJECTS: Twenty-five healthy, paid volunteers. METHODS: Subcutaneous oxygen tension and subcutaneous temperature (Tsq) were measured continuously during isovolemic hemodilution to an Hb level of 50 g/L. In 14 volunteers (initially well-perfused), "normal" perfusion (Tsq >34.4 degrees C) was achieved by hydration and systemic warming prior to starting isovolemic hemodilution, while in 11 volunteers (perfusion not controlled [PNC]), no attempt was made to control perfusion prior to hemodilution. MAIN OUTCOME MEASURES: Measurements of PsqO(2), Tsq, and relative subcutaneous blood flow (flow index). RESULTS: While PsqO(2), Tsq, and flow index were significantly lower in PNC vs well-perfused subjects at baseline, there was no significant difference between them at the Hb of 50 g/L (nadir). Subcutaneous PO(2) did not decrease significantly in either group. Arterial PO(2) was not different between the groups, and did not change significantly over time; Tsq and flow index increased significantly from baseline to nadir Hb in both groups. CONCLUSIONS: The level of PsqO(2) was maintained at baseline levels during hemodilution to Hb 50 g/L in healthy volunteers, whether they were initially well-perfused or mildly underperfused peripherally. Given the significant increase in Tsq and flow index, this resulted from a compensatory increase in subcutaneous blood flow sufficient to maintain oxygen delivery. Wound healing depends to a large extent on tissue oxygen delivery, and these data suggest that even severe anemia by itself would not be sufficient to impair wound healing. Thus, transfusion of autologous packed red blood cells solely to improve healing in surgical patients with no other indication for transfusion is not supported by these results.     

Myocardial and systemic hemodynamics during isovolemic hemodilution alone and combined with nitroprusside-induced controlled hypotension

Myocardial and systemic effects of isovolemic hemodilution alone and combined with controlled hypotension induced with sodium nitroprusside (SNP) were studied in halothane-anesthetized, open-chest dogs. Regional blood flow was measured with radioactive microspheres and used to compute regional oxygen (O2) supply. Values for regional blood flow in myocardium were used to compute myocardial O2 (MVO2) and lactate uptake (MVLAC) using the Fick equation. Hemodilution to hematocrit 50% of baseline increased aortic blood flow and decreased systemic vascular resistance, although other systemic hemodynamic values were not changed. Twofold increases in myocardial blood flow were accompanied by no change in MVO2, MVLAC, or coronary sinus PO2. Hemodilution increased regional blood flow sufficiently in the pancreas, liver, duodenum, skeletal muscle, skin, and brain to preserve O2 supply whereas unchanged blood flow in the spleen and kidney reduced O2 supply. Under hemodilution, 15 min of intravenous SNP sufficient to reduce mean arterial pressure by 50% caused parallel reductions in aortic blood flow, dP/dt max, and left ventricular end-diastolic pressure; systemic vascular resistance was unaffected. Myocardial blood flow and MVO2 decreased proportionally, whereas MVLAC and coronary sinus PO2 did not change. Regional blood flow and O2 supply decreased in the kidney, spleen, liver, and skin. Extending SNP infusion to 60 min increased myocardial blood flow and MVO2, but other hemodynamic values were unchanged. Comparing previous results with adenosine-induced hypotension inferred that coronary vasodilator reserve was greatly reduced at this time. In conclusion, although myocardial O2 supply versus demand balance was well maintained during SNP-induced hypotension under hemodiluted conditions, diminished coronary vasodilator reserve suggests increased vulnerability to ischemia if stresses of augmented cardiac work demand or impaired arterial oxygenation were superimposed. The decrease in O2 supply in the kidney during combined hemodilution and SNP-induced hypotension also warrants concern. These latter findings suggest the need for extensive clinical monitoring when SNP is used for controlled hypotension under hemodiluted conditions.     

急性等容血液稀释用于全髋置换术的临床观察

目的 了解急性等容量血液稀释在全髋置换术中对减少输异体血量的影响。方法 择期全髋置换术病人１６例,随机分成对照组（Ｉ组,ｎ＝８）和稀释组（Ⅱ组,ｎ＝８）,两组皆采用硬膜外阻滞。Ⅱ组术前进行等容量血液稀释,比较两组病人所输异体血量和术后血红蛋白变化。结果 Ⅱ组有４例完全避免输异体血,余４例各输异体血２００ｍｌ;Ⅰ组每例病人均输异体全血量４００～８００ｍｌ,显著多于Ⅱ组（Ｐ〈０．０１）,两组病人术后虽有轻度贫血,但仍在安全范围。结论 急性等容量血液稀释可使全髋置换术病人少输或不输异体血。     

Clinical analysis of combined revascularization in treating ischemic Moyamoya disease in adults

Objective

The aim of this study was to investigate the clinical efficacy of superficial temporal artery-middle cerebral artery anastomosis (STA-MCA) + encephalo-duro-myo-synangiosis (EDMS) in treating ischemic Moyamoya disease (IMD) in adults.

Blood gas analysis of mixed venous blood during normoxic acute isovolemic hemodilution in pigs

Mixed venous oxygen saturation of hemoglobin (SvO2) and mixed venous oxygen tension (PvO2) may reflect the overall balance between oxygen consumption and delivery. Because of the potential value of monitoring SvO2 and PvO2 as indications of the state of tissue oxygenation, the aim of this study was to determine, during normoxic acute isovolemic hemodilution in pigs, the critical PvO2, critical SvO2, and critical oxygen extraction ratio (ER) at which oxygen uptake starts to decline during further induced hemodilution. During stepwise induced isovolemic hemodilution, a gradual decline in SvO2 and PvO2 was observed in all animals. The mean +/- SD of the critical PvO2 of six animals was 32.3 +/- 3.1 mm Hg. The mean +/- SD of the critical SvO2 was 44.2% +/- 7.9%. The ER increased gradually. At an ER of 0.57 +/- 0.08, oxygen uptake started to decline. A significant correlation was found between changes in SvO2 and changes in ER. These degrees of hemodilution were accompanied by an increase in cardiac index, pulmonary wedge pressure, heart rate, and left ventricular stroke work index. Only a slight decrease in systemic vascular resistance was observed. We conclude that measurements of PvO2 and SvO2 can be used as indicators of the critical point of hemodilution and that the SvO2 during hemodilution reflects the overall balance between oxygen uptake and oxygen delivery, confirmed by the strong correlation found between SvO2 and oxygen extraction ratio.     

Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model

BACKGROUND: During severe isovolemic hemodilution, determination of critical hematocrit levels for the microvascular oxygenation of different organs might provide more insight into the effect of the redistribution of blood flow and oxygen delivery on the oxygenation of different organs. The effect of an increased amount of dissolved oxygen on tissue oxygenation during severely decreased hematocrit levels is not clear. METHODS: Fifteen anesthetized pigs were randomized between an experimental group (n = 10), in which severe isovolemic hemodilution was performed with 6% hydroxyethylstarch (1:1), and a time-matched control group (n = 5). Systemic, intestinal, and cerebral hemodynamic and oxygenation parameters were monitored. Microvascular oxygen partial pressure (muPo(2) ) was measured in the cerebral cortex and the intestinal serosa and mucosa, using the oxygen-dependent quenching of Pd-porphyrin phosphorescence. In the final phase of the experiment, fraction of inspired oxygen was increased to 1.0. RESULTS: Hemodilution decreased hematocrit from 25.3 +/- 3.0 to 7.6 +/- 1.2% (mean +/- SD). Systemic and intestinal oxygen delivery fell with the onset of hemodilution; intestinal oxygen consumption deceased at a hematocrit of 9.9%, whereas the systemic oxygen consumption decreased at a hematocrit of 7.6%. During hemodilution, the intestinal and cerebral oxygen extraction ratios increased from baseline with 130 and 52%, respectively. Based on the intersection of the two best-fit regression lines, determined by a least sum of squares technique, similar critical hematocrit levels were found for systemic oxygen consumption and the cerebral and intestinal mucosa muPo(2); the intestinal serosa muPo(2) decreased at an earlier stage (P < 0.05). Hyperoxic ventilation improved the muPo(2) values but not systemic or intestinal oxygen consumption. CONCLUSIONS: During isovolemic hemodilution, the diminished oxygen supply was redistributed in favor of organs with a lower capacity to increase oxygen extraction. It is hypothesized that redirection of the oxygen supply within the intestines resulted in the preservation of oxygen consumption and mucosal muPo(2) compared with serosal muPo(2).     

Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis.

Dextran of different molecular weight (Dx 40, Dx 60/70) has often been evaluated as adjunct treatment of experimental acute pancreatitis. A beneficial effect has been documented by a decrease in its lethality. However, the mechanism of action is poorly understood. A specific effect on the pancreatic microcirculation generally has not been documented and differentiation from unspecific improvement of pancreatic blood flow due to volume expansion has been difficult. This investigation was designed to quantify the effect of dextran on the impairment of pancreatic microcirculation during acute biliary pancreatitis by means of intravital microscopy. Dextran 60 (Dx 60, molecular weight 60,000) was chosen in light of the increase in vascular permeability in the early stage of pancreatitis as demonstrated previously in the same model. Isovolemic hemodilution, i.e., exchange of whole blood for Dx 60 was used as a mode of administration to achieve instantaneous onset of therapy without changes in intravascular volume. In the control group a progressive reduction of pancreatic capillary perfusion commenced 30 minutes after induction of acute pancreatitis, resulting in cessation of nutritive tissue perfusion after 3 hours. In the animals subjected to hemodilution, stabilization of the pancreatic microcirculation was accomplished throughout the observation period of 6 hours. Because volume-related effects could be excluded by the protocol and by monitoring central venous pressure and hematocrit, a specific effect of hemodilution with DX 60 on the pancreatic microcirculation is indicated by our results.