Effect of hemodilution on the adequacy of cerebral perfusion under hypothermic cardiopulmonary bypass

OBJECTIVE: Open heart surgery without transfusion has been performed even in children. However, the critical limit of the hemoglobin level has not yet been ascertained. Here, we have assessed experimentally the effect of the hemoglobin level on brain metabolism under hypothermic cardiopulmonary bypass. METHODS: Brain tissue pH was measured in 14 rabbits that were put on bypass with a different degree of hemodilution. Cardiopulmonary bypass was started at 37 degrees C and cooled down to 25 degrees C. After maintaining the bypass at 25 degrees C for 60 minutes, the animal was rewarmed to 37 degrees C for 30 minutes and then kept on-bypass for another 30 minutes. The perfusion flow was maintained as 10 ml/kg/min. RESULTS: The lowest hemoglobin level in each rabbit was from 2.5 through 8.5 g/dl. During hypothermic bypass, brain tissue pH increased from 7.21 +/- 0.16 (mean +/- SD, at the normothermic baseline) to 7.55 +/- 0.27 except 2 cases (6.91 +/- 0.16) whose hemoglobin level was lower than 3.0 g/dl. The brain tissue pH after 60 minutes on hypothermic bypass had a good correlation with the hemoglobin level (r = 0.831). After rewarming for 60 minutes, the brain tissue pH was decreased to 7.18 +/- 0.31. In 4 rabbits with less than 4.0 g/dl of hemoglobin, the brain tissue pH (6.67 +/- 0.24) was lower than the baseline level. In the other 10 rabbits, the brain tissue pH (7.22 +/- 0.16) was almost the same as the baseline level. The correlation coefficient between the brain tissue pH and the hemoglobin level after rewarming for 60 minutes was 0.778. CONCLUSIONS: These results indicated that severe hemodilution in cardiopulmonary bypass promoted acidosis in brain even during hypothermia.     

Correlation between cerebral and mixed venous oxygen saturation during moderate versus tepid hypothermic hemodiluted cardiopulmonary bypass

OBJECTIVE: This study was undertaken to compare cerebral oxygen saturation (RsO(2)) and mixed venous oxygen saturation (SvO(2)) in patients undergoing moderate and tepid hypothermic hemodiluted cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTINGS: University hospital operating room. PARTICIPANTS: Fourteen patients undergoing elective coronary artery bypass graft surgery using hypothermic hemodiluted CPB. INTERVENTIONS: During moderate (28 degrees -30 degrees C) and tepid hypothermic (33 degrees -34 degrees C) hemodiluted CPB, RsO(2) and SvO(2) were continuously monitored with a cerebral oximeter via a surface electrode placed on the patient's forehead and with the mixed venous oximeter integrated in the CPB machine, respectively. MEASUREMENTS AND MAIN RESULTS: Mean +/- standard deviation of RsO(2), SvO(2), PaCO(2), and hematocrit were determined prebypass and during moderate and tepid hypothermic phases of CPB while maintaining pump flow at 2.4 L/min/m(2) and mean arterial pressure in the 60- to 70-mmHg range. Compared with a prebypass value of 76.0% +/- 9.6%, RsO(2) was significantly decreased during moderate hypothermia to 58.9% +/- 6.4% and increased to 66.4% +/- 6.7% after slow rewarming to tepid hypothermia. In contrast, compared with a prebypass value of 78.6% +/- 3.3%, SvO(2) significantly increased to 84.9% +/- 3.6% during moderate hypothermia and decreased to 74.1% +/- 5.6% during tepid hypothermia. During moderate hypothermia, there was poor agreement between RsO(2) and SvO(2) with a gradient of 26%; however, during tepid hypothermia, there was a strong agreement between RsO(2) and SvO(2) with a gradient of 6%. The temperature-uncorrected PaCO(2) was maintained at the normocapnic level throughout the study, whereas the temperature-corrected PaCO(2) was significantly lower during the moderate hypothermic phase (26.8 +/- 3.1 mmHg) compared with the tepid hypothermic phase (38.9 +/- 3.7 mmHg) of CPB. There was a significant and positive correlation between RsO(2) and temperature-corrected PaCO(2) during hypothermia. CONCLUSIONS: During moderate hypothermic hemodiluted CPB, there was a significant increase of SvO(2) associated with a paradoxic decrease of RsO(2) that was attributed to the low temperature-corrected PaCO(2) values. During tepid CPB after slow rewarming, regional cerebral oxygen saturation was increased in association with an increase with the temperature-corrected PaCO(2) values. The results show that during hypothermic hemodiluted CPB using the alpha-stat strategy for carbon dioxide homeostasis, cerebral oxygen saturation is significantly higher during tepid than moderate hypothermia.     

Cerebral response to hemodilution during hypothermic cardiopulmonary bypass in adults.

We examined the cerebral response to changing hematocrit during hypothermic cardiopulmonary bypass (CPB) in 18 adults. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and cerebral oxygen delivery (CDO2) were determined using the nitrous oxide saturation technique. Measurements were obtained before CPB at 36 degrees C, and twice during 27 degrees C CPB: first with a hemoglobin (Hgb) of 6.2 +/- 1.2 g/dL and then with a Hgb of 8.5 +/- 1.2 g/dL. During hypothermia, appropriate reductions in CMRO2 were demonstrated, but hemodilution-associated increases in CBF offset the reduction in CBF seen with hypothermia. At 27 degrees C CPB, as the Hgb concentration was increased from 6.2 to 8.5 g/ dL, CBF decreased. CDO2 and CMRO2 were no different whether the Hgb was 6.2 or 8.5 g/dL. In eight patients in whom the Hgb was less than 6 g/dL, CDO2 remained more than twice CMRO2. IMPLICATIONS: This study suggests that cerebral oxygen balance during cardiopulmonary bypass is well maintained at more pronounced levels of hemodilution than are typically practiced, because changes in cerebral blood flow compensate for changes in hemoglobin concentration.     

The Brain Uses Mostly Dissolved Oxygen During Profoundly Hypothermic Cardiopulmonary Bypass

Background. During profoundly hypothermic cardiopulmonary bypass, cerebral venous oxygen saturation increases (eg, to 98% at 15°C). We reanalyzed results of clinical studies to learn why.

Methods. One hundred sixty-eight cerebral oxygen transport measurements were available from 96 infants and children undergoing profoundly hypothermic cardiopulmonary bypass during repair of congenital heart defects.

Results. Dissolved oxygen accounted for 2% to 17% of arterial oxygen content, depending on the arterial oxygen partial pressure and hemoglobin concentration. The fraction of the cerebral metabolic rate for oxygen obtained from dissolved oxygen depended on pump flow, temperature, hemoglobin concentration, and arterial oxygen partial pressure (all p < 10⁻³). For “full-flow” cardiopulmonary bypass, temperatures less than 18°C, and arterial oxygen partial pressure measurements more than 180 mm Hg, the mean ± standard deviation of the fraction of cerebral metabolic rate for oxygen obtained from dissolved oxygen equaled 77% ± 19%.

Conclusions. Dissolved oxygen satisfies most of the brain's oxygen requirements during profound hypothermic cardiopulmonary bypass. This result reflects four properties of profound hypothermic cardiopulmonary bypass: (1) increases in hemoglobin's oxygen affinity due to profound hypothermia (which impairs oxygen transfer from hemoglobin to cerebral tissue), (2) use of hemodilution, (3) use of high arterial oxygen partial pressure, and (4) low cerebral metabolic rate of oxygen.     

Evaluation of cerebral oxygen balance during normothermic cardiopulmonary bypass using jugular oxygen saturation

BACKGROUND: Previous studies suggest that normothermic cardiopulmonary bypass(CPB) impairs cerebral oxygen balance. We studied the effect of normothermic CPB on cerebral oxygen balance evaluated by continuous measurement of oxygen saturation in the jugular vein (SjO2). METHODS: Eleven patients undergoing coronary artery bypass grafting with normothermic CPB were studied. A 4 Fr oxymetry catheter was inserted into the internal jugular bulb for SjO2 monitoring. We measured mean arterial pressure (MAP), SjO2 and hemoglobin (Hgb) concentration at five time points-1) pre CPB, 2) 3) 4) 5, 30, 60 min after the onset of CPB, respectively, 5) 5 min after the end of CPB. RESULTS: MAP decreased significantly 30 min (47 +/- 9 mmHg) and 60 min (48 +/- 9 mmHg) after the onset of CPB compared with the pre CPB (80 +/- 14 mmHg) value. Hgb also decreased significantly 5 min (7.8 +/- 1.1 g x dl(-1)) and 30 min (7.1 +/- 1.0 g x dl(-1)) and 60 min (7.1 +/- 0.8 g x dl(-1)) after the onset of CPB compared with the pre CPB (11 +/- 1.0 g x dl(-1)) value. However, SjO2 showed no significant change throughout the study period. No significant correlation was observed between MAP and SjO2. CONCLUSIONS: Cerebral oxygen balance assessed by SjO2 was not impaired during normothermic CPB, and was unaffected by hypotension and hemodilution.     

Rapid Rewarming Causes an Increase in the Cerebral Metabolic Rate for Oxygen that Is Temporarily Unmatched by Cerebral Blood Flow: A Study during Cardiopulmonary Bypass in Rabbits

Background: Jugular venous hemoglobin desaturation during the rewarming phase of cardiopulmonary bypass is associated with adverse neuropsychologic outcome and may indicate a pathologic mismatch between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). In some studies, rapid rewarming from hypothermic cardiopulmonary bypass results in greater jugular venous hemoglobin desaturation. The authors wished to determine if rewarming rate influences the temperature dependence of CBF and CMRO2.

Methods: Anesthetized New Zealand white rabbits, cooled to 25 degrees Celsius on cardiopulmonary bypass, were randomized to one of two rewarming groups. In the fast group (n = 9), aortic blood temperature was made normothermic over 25 min. Cerebral blood flow (microspheres) and CMRO2 (Fick) were determined at baseline (25 degrees C), and at brain temperatures of 28 degrees, 31 degrees, 34 degrees, and 37 degrees Celsius during rewarming.

Results: Systemic physiologic variables appeared similar between groups. At a brain temperature of 28 degrees C, CMRO2 was 47% greater in the fast rewarming group than in the slow group (2.2 +/-0.5 vs. 1.5+/-0.2 ml O2 *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.01), whereas CBF did not differ (48+/-18 vs. 49+/-8 ml *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.47). Throughout rewarming, CBF increased as a function of brain temperature but was indistinguishable between groups. Cerebral metabolic rate for oxygen differences between groups decreased as brain temperatures increased.     

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.     

Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

OBJECTIVES: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass. METHODS: Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass. RESULTS: The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin. CONCLUSIONS: These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.     

Hematological effects of a low-prime neonatal cardiopulmonary bypass circuit utilizing vacuum-assisted venous return in the porcine model

Limiting hemodilution in neonates is difficult when extracorporeal circuits require priming volumes that are 2 to 3 times the blood volume of the newborn patient. This extreme hemodilution contributes to the development of significant postbypass coagulation disturbances. The purpose of this project was to design a low-prime neonatal bypass circuit and evaluate the coagulation status after reduced hemodilution. The null hypothesis stated there is no significant difference in the measured coagulation parameters between the low-prime circuit and the standard high-prime circuit. Four neonatal piglets (2-4 kg) were divided into two groups and placed on cardiopulmonary bypass using either a low- (200 ml) or high-prime (500 ml) circuit. Both groups were cooled to 20 degrees C, and, following cardioplegic arrest, underwent circulatory arrest for 20 minutes. The low-prime circuit used vacuum-assisted venous drainage, which permitted the circuit to be at the patient level. The high-prime circuit required fresh washed donor red blood cells to maintain the hematocrit in the desired range of 15-20%. The platelet count on bypass decreased by 60 +/- 1.0% in the low-prime group versus 79.6 +/- 0.1% in the high-prime group. Following bypass, the platelet count was reduced by 38.3 +/- 14.3% in the low-prime versus 60.2 +/- 2.6% in the high-prime group. During rewarming, the mean heparinase activated clotting time (ACT) increased 5.1% above baseline in the low-prime group and 53.5% above baseline in the high-prime group. Mean plasma-free hemoglobin levels increased 40.4 mg/dl in the low-prime group versus 62.1 mg/dl in the high-prime group during bypass. This laboratory evaluation of a low-prime neonatal circuit demonstrates that coagulation disturbances often present in neonates can be reduced with the use of a low-prime circuit.     

Acute normovolemic hemodilution improves oxygenation in ischemic flap tissue

BACKGROUND: The flaps used in reconstructive surgery are prone to ischemia and hypoxia, which imply a considerable risk of wound-healing complications. During normovolemic hemodilution, the oxygenation may further deteriorate because of the lack of erythrocytes or improve because of increased microcirculatory blood flow. The aim of this study was to investigate the net effect of normovolemic hemodilution of various degrees on the microcirculation and oxygenation in ischemic flap tissue in adult minipigs. METHODS: A rectangular flap was raised in the middle of the epigastrium, consisting of an adequately perfused portion and a partly ischemic portion. The animals were randomly assigned to either the control group (n = 10) or the experimental group (n = 10) receiving graded normovolemic hemodilution with 6% hydroxyethyl starch 200-0.5. RESULTS: Normovolemic hemodilution caused a significant linear increase in total blood flow to the flap (measured by transit time flowmetry). In the ischemic flap tissue, both oxygen tension (measured by polarographic cells) and venous base excess were transiently improved during hemodilution (F = 4.79 and P = 0.019 for the regression of tissue oxygen tension on hemoglobin and hemoglobin squared, and F = 4.18 and P = 0.029 for base excess). The expected values reached a peak at hemoglobin concentrations of 9.1 and 8.5 g/dl, respectively. The measured values at this level of hemodilution were 17 +/- 10.7 mmHg (mean +/- SD) versus 7.6 +/- 1.9 mmHg (baseline) for oxygen tension and -1.7 +/- 3.4 versus -5.6 +/- 4.1 mM for venous base excess. CONCLUSIONS: Our results suggest that the oxygenation in ischemic and hypoxic flap tissue may be improved by normovolemic hemodilution. The maximal benefit may be expected at a hemoglobin concentration at or slightly less than 9 g/dl.     

Effect of cardiopulmonary bypass and hypothermia on pancreatic endocrine function and peripheral utilization of glucose.

Extracorporeal circulation has been reported to produce abnormalities of glucose, metabolism. Pancreatic endocrine function and peripheral glucose utilisation were studied in 11 nondiabetic patients who underwent myocardial revascularization. Nonpulsatile flow with hemodilution and moderate hypothermia to 28 degrees C were used in each case. Following the onset of cardiopulmonary bypass, serum glucose values rose rapidly to a mean of 972 mg/dl (54.0 mmol/l) and were associated with high circulating concentrations of insulin in the range of 216 microU/ml [1549.8 pmol/l]. High circulating concentrations for both insulin and glucose were maintained throughout the bypass period. These returned to normal postoperatively when the patient was in the recovery room. The results of this study indicate that both the pancreatic endocrine response and the peripheral utilization of glucose are impaired during cardiopulmonary bypass with hemodilution and moderate hypothermia to 28 degrees C.     

Effect of temperature during cardiopulmonary bypass on gastric mucosal perfusion

The purpose of our study was to prospectively study the splanchnic response to hypothermic and tepid cardiopulmonary bypass (CPB) using alphastat management of arterial blood-gas tensions. Twenty-four patients for elective CABG surgery were allocated randomly to tepid (35- 36 degrees C) or hypothermic (30 degrees C) bypass groups. Measurements were made at four times: (1) baseline, (2) stable during CPB (inflow temperature = nasopharyngeal temperature) 30 degrees C for hypothermic patients, bypass +20 min for tepid patients, (3) 10 min before the end of bypass, (4) after bypass, skin closure. Both groups demonstrated a significant reduction in gastric intramucosal pH (pHim) from time 1 to time 4 and there was no difference in the incidence of a low pHim between the tepid and cold groups (4/12 vs 3/12; ns) at time 4. pHim was significantly lower in the tepid groups at time 3 (P = 0.03) but this discrepancy may have been because of an artefactually high pHim in the cold group. There was a significantly higher incidence of postoperative non-cardiac complications in patients who had a low pHim at time 4 (P = 0.0008). Therefore, we conclude that although the temperature during CPB had a transient effect on pHim it is unlikely to be a major determinant in the pathogenesis of gut mucosal hypoperfusion after bypass.      

Higher bypass temperature correlates with increased white cell activation in the cerebral microcirculation

OBJECTIVE: Cardiopulmonary bypass induces a systemic inflammatory response, which in turn promotes a cascade of leukocyte and endothelial cell activity. We investigated whether differences in bypass temperature and flow rate affect endothelial cell and leukocyte adhesion in the cerebral microcirculation. METHODS: Thirty-six piglets (13.0 +/- 1.1 kg) had a cranial window placed over the parietal cortex to evaluate the microcirculation by means of intravital microscopy. Animals were cooled to a temperature of 15 degrees C, 25 degrees C, or 34 degrees C on cardiopulmonary bypass with hematocrit levels of 20% or 30% by using pH-stat management, followed by 60 minutes of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules. RESULTS: Higher bypass temperature correlated with significantly more adherent and rolling leukocytes during the full 60 minutes of low-flow bypass (P <.05). Poisson regression revealed more adherent leukocytes at 34 degrees C than at 15 degrees C and at a flow rate of 10 mL.kg(-1).min(-1) compared with a flow rate of 50 mL.kg(-1).min(-1). There was an inverse correlation between flow rate and the number of adherent and rolling leukocytes at 30, 45, and 60 minutes of low-flow bypass (P <.05). Temperature was a multivariable predictor of histologic score, with greater neurologic damage found after bypass at 34 degrees C (P <.01). CONCLUSIONS: Leukocyte activation in cerebral microcirculation is increased with higher temperature and lower flow rate, suggesting that these variables influence the inflammatory response during cardiopulmonary bypass.     

High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants.

Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants.     

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.     

High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg—Safe limits of hemodilution in cardiopulmonary bypass in infants

Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m²/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and impaired venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants.     

The oxygen transporting capability of neo red cells (NRC) evaluated under total cardiopulmonary bypass

The oxygen transporting capability of an artificial oxygen carrier NRC was evaluated by employing it as a perfusate for total cardiopulmonary bypass. NRC is a type of liposome encapsulated hemoglobin. It has a particle size of approximately 220 nm, with a hemoglobin concentration of 5.6 g/dl and its P₅₀ is controlled to 45 Torr. Male beagles were used in the experiment. Approximately 80% of the estimated circulatory volume was exchanged with NRC and total cardiopulmonary bypass was initiated. Arterial oxygen tension and carbon dioxide tension were controlled to 400 Torr and 40 Torr respectively. The perfused we heated to 37°C. The rate of flow was altered during the experiment. Oxygen consumption reached a plateau at 9.3 ml/kg/min where oxygen delivery was 14.9 ml/kg/min. At this point the oxygen consumed per gram of hemoglobin from NRC was equivalent to that from dog red blood cells. This indicated that almost an equal amount of oxygen was consumed from NRC in comparison to red blood cells. Regarding oxygen transporting capability, NRC could be considered a candidate for perfusate in cardiopulmonary bypass.     

Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery

BACKGROUND: This observational study sought to determine whether the degree of hemodilution during cardiopulmonary bypass is independently related to perioperative acute renal failure necessitating dialysis support. METHODS: Data were prospectively collected on consecutive patients undergoing cardiac operations with cardiopulmonary bypass from 1999 to 2003 at a tertiary care hospital. The independent relationship was assessed between the degree of hemodilution during cardiopulmonary bypass, as measured by nadir hematocrit concentration, and acute renal failure necessitating dialysis support. Multivariate logistic regression was used to control for variables known to be associated with perioperative renal failure and anemia. RESULTS: Of the 9080 patients included in the analysis, 1.5% (n = 134) had acute renal failure necessitating dialysis support. There was an independent, nonlinear relationship between nadir hematocrit concentration during cardiopulmonary bypass and acute renal failure necessitating dialysis support. Moderate hemodilution (nadir hematocrit concentration, 21%-25%) was associated with the lowest risk of acute renal failure necessitating dialysis support; the risk increased as nadir hematocrit concentration deviated from this range in either direction (P = .005). Compared with moderate hemodilution, the adjusted odds ratio for acute renal failure necessitating dialysis support with severe hemodilution (nadir hematocrit concentration <21%) was 2.34 (95% confidence interval, 1.47-3.71), and for mild hemodilution (nadir hematocrit concentration >25%) it was 1.88 (95% confidence interval, 1.02-3.46). CONCLUSIONS: Given that there is an independent association between the degree of hemodilution during cardiopulmonary bypass and perioperative acute renal failure necessitating dialysis support, patient outcomes may be improved if the nadir hematocrit concentration during cardiopulmonary bypass is kept within the identified optimal range. Randomized clinical trials, however, are needed to determine whether this is a cause-effect relationship or simply an association.     

Hemoglobin levels and weight gain after coronary bypass grafting by use of intraoperative hemodilution and autologous blood transfusion

We investigated the relationship between the degree of hemodilution during cardiopulmonary bypass (CPB) and weight gain after coronary bypass grafting by use of intraoperative hemodilution and autologous blood transfusion. There is no significant difference in weight gain between the higher hemoglobin group (Hb > or = 6 g.dl-1) and the lower hemoglobin group (Hb < 6 g.dl-1). Furthermore, there is no significant correlation between hemoglobin levels during CPB and weight gain after operation. We conclude that slightly excessive hemodilution than usual during CPB does not influence weight gain when cardiac and renal functions are fair.     

The effect of hematocrit on cerebral blood flow velocity in neonates and infants undergoing deep hypothermic cardiopulmonary bypass.

Varying degrees of hemodilution are used during deep hypothermic cardiopulmonary bypass. However, the optimal hematocrit (Hct) level to ensure adequate oxygen delivery without impairing microcirculatory flow is not known. In this prospective, randomized study, cerebral blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography in 35 neonates and infants undergoing surgery with deep hypothermic cardiopulmonary bypass. Patients were randomized to low Hct (aiming for 20%) or high Hct (aiming for 30%) during cooling on cardiopulmonary bypass (CPB). Systolic (V(s)), mean (Vm), and diastolic (Vd) cerebral blood flow velocity, as well as pulsatility index (PI = [V(s) - Vd]/Vm) and resistance index (RI = [V(s) - Vd]/V(s)) were recorded at six time points: postinduction, at cannulation, after 10 min cooling on CPB, rewarmed to 35 degrees C on CPB, immediately off CPB, and at skin closure. Vm was significantly lower in the high Hct group compared with that in the low Hct group during cooling (P < 0.01). Postinduction, the high Hct group demonstrated significantly lower Vd immediately off CPB (P < 0.01) and significantly lower Vm and V(s) at skin closure (P < 0.001). We conclude that there is an inverse relation between hematocrit and cerebral blood flow velocity during deep hypothermic cardiopulmonary bypass in neonates and infants. Implications: There is an inverse relation between hematocrit and cerebral blood flow velocity during deep hypothermic cardiopulmonary bypass in neonates and infants. Further studies correlating Hct and cerebral blood flow velocity with cerebral metabolic rate and neurologic outcome are necessary to determine the optimal Hct during deep hypothermic cardiopulmonary bypass.