Splanchnic Oxygen Consumption Is Impaired during Severe Acute Normovolemic Anemia in Anesthetized Humans

Background: In conscious humans, reduction in hemoglobin concentration to 5 g/dl did not produce inadequate systemic oxygenation. However, systemic measures of inadequate oxygenation may not be sufficiently sensitive to detect inadequate oxygenation in individual organs such as splanchnic organs. The authors tested the hypothesis that acute normovolemic anemia to hemoglobin less than 6.0 g/dl in anesthetized humans reduces splanchnic oxygen consumption because of diminished whole body oxygen delivery.

Methods: Elective spine (n = 12) and abdominal (n = 7) surgery patients underwent acute normovolemic anemia to decrease the hemoglobin concentration close to 6.0 g/dl. The authors assessed the development of supply-dependent conditions in systemic and regional vascular beds by two primary measures before and after acute normovolemic anemia: oxygen consumption and surrogate biochemical markers of anaerobic metabolism, including plasma lactate, regional lactate kinetics, and ketone body ratio.

Results: When hemoglobin was reduced from 13.6 +/- 1.2 to 5.9 +/- 0.3 g/dl, oxygen supply dependency occurred in the splanchnic and preportal tissues but not at the systemic level. Regional supply dependency was accompanied by biochemical markers of anaerobic metabolism.     

Cardiovascular and Metabolic Response to Acute Normovolemic Anemia: Effects of Anesthesia

Background: The maintenance of adequate tissue oxygenation during acute anemia depends on an increase in both cardiac output and tissue oxygen extraction. This study tested the hypothesis that anesthesia blunts the cardiac output response associated with acute normovolemic hemodilution.

Methods: Forty patients undergoing major abdominal surgery were prospectively randomized to undergo acute normovolemic hemodilution (ANH) either awake (awake group, n = 20) or with fentanyl-nitrous oxide-isoflurane anesthesia (anesthetized group, n = 20). Radial and pulmonary artery catheters were placed in all patients. After hemodynamic measurements were taken, patients in the two groups underwent hemodilution to decrease their hemoglobin concentration from 13 to 8 g/dl. A total of 1,875 +/- 222 ml (mean +/- SD) of blood was collected and simultaneously replaced by the same volume of medium molecular weight hydroxyethylstarch in both groups.

Results: In the awake group, ANH resulted in a significant increase in cardiac index (from 3.1 +/- 0.5 to 4.8 +/- 1.0 l [middle dot] min-1 [middle dot] m-2) related to both an increase in heart rate and stroke index. Oxygen delivery remained unchanged, but oxygen consumption increased significantly, resulting in an increase in oxygen extraction ratio. In the anesthetized group, ANH resulted in a significantly smaller increase in cardiac index (from 2.3 +/- 0.5 to 3.1 +/- 0.7 l [middle dot] min-1 [middle dot] m-2) related solely to an increase in stroke index. Oxygen delivery decreased but oxygen consumption was maintained as oxygen extraction increased.     

Influence of crystalloid and colloid replacement solutions on hemodynamic variables during acute normovolemic hemodilution

STUDY OBJECTIVE: To determine whether, in maintaining normovolemia during acute normovolemic hemodilution, replacement fluid choice influences intraoperative hemodynamic variables. DESIGN: Prospective, randomized, single-blinded study. SETTING: Operating room of a tertiary-care university hospital. PATIENTS: 40 adult, ASA physical status I, II, and III patients scheduled for acute normovolemic hemodilution during radical prostatectomy. INTERVENTIONS: Patients were randomly assigned to four replacement fluid groups to receive 1) Ringer's lactate, 2) 5% albumin, 3) 6% dextran 70, or 4) 6% hetastarch. A standardized general anesthetic was used, and patients underwent moderate hemodilution to a target hemoglobin of 9 gm/dL. MEASUREMENTS: Hemodynamic variables were recorded using standard monitors, 5-lead electrocardiography, radial arterial catheter, and pulmonary artery catheter. Red blood cell loss for the entire hospitalization was calculated. MAIN RESULTS: Demographic and clinical outcome data were similar among the groups. During acute normovolemic hemodilution, heart rate and pulmonary capillary wedge pressure were unchanged from baseline in all groups, but patients receiving Ringer's lactate or albumin had greater declines in mean arterial pressure at the end of acute normovolemic hemodilution. Cardiac and oxygen consumption indexes were stable during acute normovolemic hemodilution, but oxygen extraction increased. CONCLUSIONS: During hemodilution, anesthetized patients maintain whole body oxygenation by increasing oxygen extraction. The administration of hetastarch or dextran as the replacement fluid during acute normovolemic hemodilution is associated with a more stable mean arterial pressure, but overall acute normovolemic hemodilution is well tolerated irrespective of the replacement fluid used.     

Hyperoxic ventilation reduces 6-hour mortality at the critical hemoglobin concentration

BACKGROUND: Acute normovolemic hemodilution reduces the circulating erythrocyte mass and, thus, the hemoglobin concentration. After extreme acute normovolemic hemodilution to the critical hemoglobin concentration (Hbcrit), oxygen demand of the tissues is no longer met by oxygen supply, and death occurs with increasing oxygen debt. The aim of the current study was to investigate whether ventilation with 100% oxygen (fraction of inspired oxygen [FiO2] = 1.0; hyperoxic ventilation) initiated at Hbcrit could restore adequate tissue oxygenation and prevent death. METHODS: Fourteen anesthetized pigs ventilated with room air (FiO2 = 0.21) were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual Hbcrit was reached. Hbcrit was defined as the onset of oxygen supply dependency of oxygen consumption and was identified with indirect calorimetry. For the next 6 h, animals were either ventilated with an FiO2 of 0.21 (n = 7) or an FiO2 of 1.0 (n = 7). RESULTS: All animals in the 0.21 FiO2 group died within the first 3 h at Hbcrit (i.e., 6-h mortality 100%). Death was preceded by an increase of serum concentrations of lactate and catecholamines. In contrast to that, six of the seven animals of the 1.0 FiO2 group survived the complete 6-h observation period without lactacidosis and increased serum catecholamines (i.e., 6-h mortality 14%; FiO2 0.21 vs. FiO2 1.0, P < or = 0.05). After 6 h at Hbcrit, the FiO2 was reduced from 1.0 to 0.21, and five of the six animals died within the next 3 h. CONCLUSION: In anesthetized pigs submitted to lethal anemia, hyperoxic ventilation enabled survival for 6 h without signs of circulatory failure.     

Cardiovascular and metabolic response to acute normovolemic anemia. Effects of anesthesia

BACKGROUND: The maintenance of adequate tissue oxygenation during acute anemia depends on an increase in both cardiac output and tissue oxygen extraction. This study tested the hypothesis that anesthesia blunts the cardiac output response associated with acute normovolemic hemodilution. METHODS: Forty patients undergoing major abdominal surgery were prospectively randomized to undergo acute normovolemic hemodilution (ANH) either awake (awake group, n = 20) or with fentanyl-nitrous oxide-isoflurane anesthesia (anesthetized group, n = 20). Radial and pulmonary artery catheters were placed in all patients. After hemodynamic measurements were taken, patients in the two groups underwent hemodilution to decrease their hemoglobin concentration from 13 to 8 g/dl. A total of 1,875 +/- 222 ml (mean +/- SD) of blood was collected and simultaneously replaced by the same volume of medium molecular weight hydroxyethylstarch in both groups. RESULTS: In the awake group, ANH resulted in a significant increase in cardiac index (from 3.1 +/- 0.5 to 4.8 +/- 1.0 l. min-1. m-2) related to both an increase in heart rate and stroke index. Oxygen delivery remained unchanged, but oxygen consumption increased significantly, resulting in an increase in oxygen extraction ratio. In the anesthetized group, ANH resulted in a significantly smaller increase in cardiac index (from 2.3 +/- 0.5 to 3.1 +/- 0.7 l. min-1. m-2) related solely to an increase in stroke index. Oxygen delivery decreased but oxygen consumption was maintained as oxygen extraction increased. CONCLUSIONS: Anesthesia significantly reduces the cardiac output response associated with ANH. This could be related to the effects of the anesthetic drugs on the autonomic and the cardiovascular systems.     

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.     

Monitoring of allogenic red blood cell transfusions

Careful assessment of risks and benefits has to precede each decision on allogenic red blood cell (RBC) transfusion. Physicians work to establish more appropriate transfusions of blood components according to the guidelines issued by the Ministry of Health, Welfare, and Labor in Japan. For many years the so-called "10/ 30 rule" was used as a hemoglobin/hematocrit transfusion trigger. However, this rule does not take into account the individual anemia tolerance of a patient nor its individual compensatory mechanisms. RBC transfusions should not be dictated by a single hemoglobin transfusion trigger, but instead should be on the patient's risk of developing complications of inadequate oxygenation. Therefore, transfusion decisions should be primarily based on an individual patient's need for global and regional oxygen supply as indicated by signs of inadequate global and regional oxygenation. However, a hemoglobin transfusion trigger may be useful if matched with some other makers of inadequate tissue perfusion. Therefore, RBC transfusion is recommended under the following circumstances: for hemoglobin levels < 6 g x dl(-1) and for physiologic signs of inadequate oxygenation.     

Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia

Background: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia.

Methods: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test.

Results: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia.     

Oxygen reverses deficits of cognitive function and memory and increased heart rate induced by acute severe isovolemic anemia

BACKGROUND: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia. METHODS: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test. RESULTS: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia. CONCLUSION: The authors confirmed that acute isovolemic anemia subtly slows human reaction time, degrades memory, increases heart rate, and decreases energy level. The findings of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater by breathing oxygen reverses all of these effects of acute anemia except for decreased energy.     

Acute severe isovolemic anemia impairs cognitive function and memory in humans

BACKGROUND: Erythrocytes are transfused to prevent or treat inadequate oxygen delivery resulting from insufficient hemoglobin concentration. Previous studies failed to find evidence of inadequate systemic oxygen delivery at a hemoglobin concentration of 5 g/dl. However, in those studies, sensitive, specific measures of critical organ function were not used. This study tested the hypothesis that acute severe decreases of hemoglobin concentration alters human cognitive function. METHODS: Nine healthy volunteers, age 29 +/- 5 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and after acute isovolemic reduction of their hemoglobin to 7, 6, and 5 g/dl and again after transfusion of their autologous erythrocytes to return their hemoglobin concentration to 7 g/dl. To control for duration of the experiment, each volunteer also completed the same tests on a separate day, without alteration of hemoglobin, at times of the day approximately equivalent to those on the experimental day. RESULTS: No test showed any change in reaction time or error rate at hemoglobin concentration of 7 g/dl compared with the data at the baseline hemoglobin concentration of 14 g/dl. Reaction time, but not error rate, for horizontal addition and digit-symbol substitution test (DSST) increased at hemoglobin 6 g/dl (mean horizontal addition, 19%; 95% confidence interval [CI], 4-34%; mean DSST, 10%; 95% CI, 4-17%) and further at 5 g/dl (mean horizontal addition, 43%; 95% CI, 6-79%; mean DSST, 18%; 95% CI, 4-31%). Immediate and delayed memory was degraded at hemoglobin 5 g/dl but not at 6 g/dl. Return of hemoglobin to 7 g/dl returned all tests to baseline, except for the DSST, which significantly improved, and returned to baseline the following morning after transfusion of all autologous erythrocytes. CONCLUSION: Acute reduction of hemoglobin concentration to 7 g/dl does not produce detectable changes in human cognitive function. Further reduction of hemoglobin level to 6 and 5 g/dl produces subtle, reversible increases in reaction time and impaired immediate and delayed memory. These are the first prospective data to demonstrate subtle degraded human function with acute anemia of hemoglobin concentrations of 6 and 5 g/dl. This reversibility of these decrements with erythrocyte transfusion suggests that our model can be used to test the efficacy of erythrocytes, oxygen therapeutics, or other treatments for acute anemia.     

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.     

Fresh Blood and Aged Stored Blood Are Equally Efficacious in Immediately Reversing Anemia-induced Brain Oxygenation Deficits in Humans

Background: Erythrocytes are transfused to treat or prevent imminent inadequate tissue oxygenation. 2,3-diphosphoglycerate concentration decreases and oxygen affinity of hemoglobin increases (P50 decreases) with blood storage, leading some to propose that erythrocytes stored for 14 or more days do not release sufficient oxygen to make their transfusion efficacious. The authors tested the hypothesis that erythrocytes stored for 3 weeks are as effective in supplying oxygen to human tissues as are erythrocytes stored for less than 5 h.

Methods: Nine healthy volunteers donated 2 units of blood more than 3 weeks before they were tested with a standard, computerized neuropsychological test (digit-symbol substitution test [DSST]) on 2 days, 1 week apart, before and after acute isovolemic reduction of their hemoglobin concentration to 7.4 and 5.5 g/dl. Volunteers randomly received autologous erythrocytes stored for either less than 5 h ("fresh") or 3 weeks ("stored") to return their hemoglobin concentration to 7.5 g/dl (double blinded). Erythrocytes of the alternate storage duration were transfused on the second experimental day. The DSST was repeated after transfusion.

Results: Acute anemia slowed DSST performance equivalently in both groups. Transfusion of stored erythrocytes with decreased P50 reversed the altered DSST (P < 0.001) to a time that did not differ from that at 7.4 g/dl hemoglobin during production of acute anemia (P = 0.88). The erythrocyte transfusion-induced DSST improvement did not differ between groups (P = 0.96).     

Fresh blood and aged stored blood are equally efficacious in immediately reversing anemia-induced brain oxygenation deficits in humans

BACKGROUND: Erythrocytes are transfused to treat or prevent imminent inadequate tissue oxygenation. 2,3-diphosphoglycerate concentration decreases and oxygen affinity of hemoglobin increases (P50 decreases) with blood storage, leading some to propose that erythrocytes stored for 14 or more days do not release sufficient oxygen to make their transfusion efficacious. The authors tested the hypothesis that erythrocytes stored for 3 weeks are as effective in supplying oxygen to human tissues as are erythrocytes stored for less than 5 h. METHODS: Nine healthy volunteers donated 2 units of blood more than 3 weeks before they were tested with a standard, computerized neuropsychological test (digit-symbol substitution test [DSST]) on 2 days, 1 week apart, before and after acute isovolemic reduction of their hemoglobin concentration to 7.4 and 5.5 g/dl. Volunteers randomly received autologous erythrocytes stored for either less than 5 h ("fresh") or 3 weeks ("stored") to return their hemoglobin concentration to 7.5 g/dl (double blinded). Erythrocytes of the alternate storage duration were transfused on the second experimental day. The DSST was repeated after transfusion. RESULTS: Acute anemia slowed DSST performance equivalently in both groups. Transfusion of stored erythrocytes with decreased P50 reversed the altered DSST (P < 0.001) to a time that did not differ from that at 7.4 g/dl hemoglobin during production of acute anemia (P = 0.88). The erythrocyte transfusion-induced DSST improvement did not differ between groups (P = 0.96). CONCLUSION: Erythrocytes stored for 3 weeks are as efficacious as are erythrocytes stored for 3.5 h in reversing the neurocognitive deficit of acute anemia. Requiring fresh rather than stored erythrocytes for augmentation of oxygen delivery does not seem warranted.     

Hyperoxic Ventilation Reduces 6-Hour Mortality at the Critical Hemoglobin Concentration

Background: Acute normovolemic hemodilution reduces the circulating erythrocyte mass and, thus, the hemoglobin concentration. After extreme acute normovolemic hemodilution to the critical hemoglobin concentration (Hbcrit), oxygen demand of the tissues is no longer met by oxygen supply, and death occurs with increasing oxygen debt. The aim of the current study was to investigate whether ventilation with 100% oxygen (fraction of inspired oxygen [Fio2] = 1.0; hyperoxic ventilation) initiated at Hbcrit could restore adequate tissue oxygenation and prevent death.

Methods: Fourteen anesthetized pigs ventilated with room air (Fio2 = 0.21) were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual Hbcrit was reached. Hbcrit was defined as the onset of oxygen supply dependency of oxygen consumption and was identified with indirect calorimetry. For the next 6 h, animals were either ventilated with an Fio2 of 0.21 (n = 7) or an Fio2 of 1.0 (n = 7).

Results: All animals in the 0.21 Fio2 group died within the first 3 h at Hbcrit (i.e., 6-h mortality 100%). Death was preceded by an increase of serum concentrations of lactate and catecholamines. In contrast to that, six of the seven animals of the 1.0 Fio2 group survived the complete 6-h observation period without lactacidosis and increased serum catecholamines (i.e., 6-h mortality 14%; Fio2 0.21 vs. Fio2 1.0, P <= 0.05). After 6 h at Hbcrit, the Fio2 was reduced from 1.0 to 0.21, and five of the six animals died within the next 3 h.     

Critical oxygen delivery in conscious humans is less than 7.3 ml O2 x kg(-1) x min(-1)

BACKGROUND: The "critical" level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2. METHODS: With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19-25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a beta-adrenergic antagonist, esmolol. RESULTS: Reduction of hemoglobin from 12.5+/-0.8 g/dl to 4.8+/-0.2 g/dl (mean +/- SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0+/-2.9 to 9.9+/-20 ml O2 x kg(-1) x min(-1); all P<0.001). Oxygen consumption (VO2; 3.0+/-0.5 to 3.4+/-0.6 ml O2 x kg(-1) x min(-1); P<0.05) and plasma lactate concentration (0.50+/-0.10 to 0.62+/-0.16 mM; P<0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3+/-1.4 ml O2 x kg(-1) x min(-1); all P<0.01 vs. before esmolol). VO2 (3.2+/-0.6 ml O2 x kg(-1) x min(-1); P>0.05) and plasma lactate (0.66+/-0.14 mM; P>0.05) did not change further. No value of plasma lactate exceeded the normal range. CONCLUSIONS: A decrease in DO2 to 7.3+/-1.4 ml O2 x kg(-1) min(-1) in resting, healthy, conscious humans does not produce evidence of inadequate systemic oxygenation. The critical DO2 in healthy, resting, conscious humans appears to be less than this value.     

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.     

Effects of Enflurane on Splanchnic Circulation

A brief summary of the anatomy and physiology of the splanchnic circulation is presented. The influence of 1 MAC enflurane anaesthesia on splanchnic circulation and oxygenation was studied in 10 dogs. Superior mesenteric arterial, portal venous and hepatic arterial blood flows decreased less than mean arterial blood pressure, due to reductions in superior mesenteric arterial, preportal vascular and hepatic arterial resistances. It is suggested that these reactions within the splanchnic circiilarion are mainly dependent on normal autoregulative responses elicited by the fall in blood pressure. Oxygen consumption of the preportal tissues and the liver was unchanged as a result of increased extraction of oxygen.     

Vermeidbarkeit von Fremdblut trotz extremen Blutverlustes

We report the case of a 22-year-old woman who underwent two-step scoliosis surgery without allogeneic transfusion, although the intraoperative blood loss (3500 ml) during the first procedure was higher than the calculated blood volume (3250 ml). Preoperatively the patient had donated four units of autologous blood. Intraoperatively blood-saving methods were combined. During the first operation acute normovolemic hemodilution (target hemoglobin 9.0 g/dl) was applied and during the second operation controlled hypotension (systolic blood pressure 80 mmHg). Intraoperative autotransfusion was used in both procedures. During the first operation severe normovolemic anemia (minimal hemoglobin 3.5 g/dl) was accepted while the patient was ventilated with FiO₂ 1.0. The hemoglobin concentration was 8.6 g/dl after the first procedure and had increased to 11.6 g/dl 4 weeks after the second procedure. No severe complications occurred during the postoperative phase. This case report shows that also in surgical procedures with extreme blood loss any allogeneic transfusion can be avoided by the combination of blood-saving methods, acceptance of low intraoperative transfusion trigger and ventilation with 100% oxygen.     

The hemodynamic and metabolic effects of shivering during acute normovolemic hemodilution

To assess the hemodynamic and metabolic effects of shivering during extreme normovolemic hemodilution, we anesthetized 16 pigs with fentanyl-midazolam-pancuronium. Mild hypothermia (36.5 degrees +/- 0.1 degrees C) was induced by surface cooling, and the animals were randomized to either a control group (hemoglobin 118 +/- 3 g/L) or a hemodilution group (hemoglobin 52 +/- 2 g/L). In the latter group, blood was replaced with an isotonic Ringer's acetate/dextran 70 solution. Shivering was allowed to occur by a controlled decrease in the infusion rate of pancuronium. Shivering increased oxygen consumption (VO(2)) in both groups (P < 0.001). Initially, this was predominantly compensated for by an increased oxygen extraction ratio (ER), but when VO(2) was 2.3 +/- 0.2 times baseline, critical levels of mixed venous oxygenation (SVO(2) = 18% +/- 2%; PVO(2) = 22.5 +/- 1.5 mm Hg) and ER (82% +/- 3%) were recorded in anemic animals. Control animals did not reach critical levels until VO(2) was maximal (3.7 +/- 0.3 times baseline). Maximal attained VO(2) was less (2.9 +/- 0.1 times baseline) in the anemic animals (P = 0.01), and at this stage two of these pigs had myocardial lactate production, one of which died in ventricular fibrillation. Coronary perfusion pressure was significantly less (P < 0.001) in the anemic animals. We conclude that in this experimental model, maximal shivering as measured by VO(2) was limited in hemodiluted animals, and left ventricular oxygen balance was marginal, as evidenced by a decreased lactate uptake and extraction. IMPLICATIONS: The effect of acute increases in oxygen consumption (shivering) on severely anemic individuals has not been evaluated. In this experimental model, left ventricular oxygen balance was marginal, as evidenced by decreased lactate extraction.     

Mild hypothermia has minimal effects on the tolerance to severe progressive normovolemic anemia in Swine

BACKGROUND: The benefits of hypothermia during acute severe anemia are not entirely settled. The authors hypothesized that cooling would improve tolerance to anemia. METHODS: Eight normothermic (38.0 +/- 0.5 degrees C) and eight hypothermic (32.0 +/- 0.5 degrees C) pigs anesthetized with midazolam-fentanyl-vecuronium-isoflurane (0.5% inspired concentration) were subjected to stepwise normovolemic hemodilution (hematocrit, 15%, 10%, 7%, 5%, 3%). Critical hemoglobin concentration (Hgb(CRIT)) and critical oxygen delivery (DO(2CRIT)), i.e., the hemoglobin concentration (Hgb) and oxygen delivery (DO2) at which oxygen consumption (VO2, independently measured by indirect calorimetry) was no longer sustained, and Hgb at the moment of death, defined prospectively as the point when VO2, decreased below 40 ml/min, were used to assess the tolerance of the two groups to progressive isovolemic anemia. RESULTS: At hematocrits of 15% and 10% (Hgb, 47 and 31 g/l), VO2 was maintained in both groups by an increase (P < 0.001) in cardiac output (CO) and extraction ratio (ER; P< 0.001) with unchanged mean arterial lactate concentration (L(art)). At hematocrit of 7% (Hgb, 22 g/l), all normothermic but no hypothermic animals had DO2-dependent VO2. No normothermic and three hypothermic animals survived to 5% hematocrit (Hgb, 15 g/l), and none survived to 3%. Hgb(CRIT) was 23 +/- 2 g/l and 19 +/- 6 g/l (mean +/- SD) in normothermic and hypothermic animals, respectively (P = 0.053). Hgb at death was 19 +/- 3 g/l versus 14 +/- 4 g/l (P = 0.015), and DO(2CRIT) was 8.7 +/- 1.7 versus 4.6 +/- 0.8 ml x kg(-1) x min(-1) (P < 0.001). CONCLUSION: During progressive normovolemic hemodilution in pigs, hypothermia did not significantly change Hgb(CRIT), but it decreased the Hgb at death, i.e., short-term survival was prolonged.