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Intraoperative normovolemic hemodilution
JOURNAL
OF SURGICAL
RESEARCH
31, 375-38 1 ( t 98 1)
lntraoperative DAVID ROSE, M.D.,**’
Normovolemic
Hemodilution
AND THEODORE COUTSOFTIDES, M.D.?
Departments of *Anesthesiology and tsurgery, University of California, Irvine. California 92664, and *Surgical Intensive Care Unit and fDepartment of Colon and Rectal Surgery, Veterans Administration Medical Center, Long Beach, California 90822 Submitted for publication December 26, 1980 We have studied the cardiopulmonary hemodynamics of acute hemodilution in a group of patients with cancer. The majority of patients had multisystem disease; including chronic lung disease, liver disease, sepsis, and malnutrition. The only patients who were excluded were those with a recent history of myocardial ischemia. Acute intraoperative hemodilution to a hematocrit of 22% was well tolerated provided blood volume was maintained with crystalloid solution. Hemodilution led to improved cardiac output by enhancing venous return which helped to compensate for the diminished oxygen content of the blood. There were no adverse cardiopulmonary effects in hemodiluted patients compared to patients undergoing similar operations without hemodilution. Acute normovolemic hemodilution is an effective clinical means of reducing the use of bank blood and avoiding the risks of blood transfusion in patients undergoing major surgery.
Intraoperative hemodilution is used in cardiac surgery to avoid the adverse consequences of homologous blood transfusion and to conserve supplies of banked blood. Also, the reports by Cooley et al. [2] and Ochsner et al. [8] suggest that hemodilution may improve cardiac function by reducing blood viscosity. Anaphylactic shock, bacterial contamination, and hemolytic reactions are rare complications of blood transfusion, but posttransfusion hepatitis is a persistent problem which at the present time can be prevented only by avoiding the use of banked blood. The reported incidence of hepatitis after bank blood transfusion varies greatly depending on the population studied and techniques used to identify the disease. Despite the routine screening of donor blood for the hepatitis type B surface antigen in the United States, post-transfusion hepatitis develops in approximately 7% of blood recipients at the present time [ 11. In an attempt to deal with this problem there is a trend ’ To whom requests for reprints should be sent at: Department of Anesthesiology, VA Medical Center, 5901 E. Seventh St., Long Beach, Calif. 90822.
toward all-volunteer donors that has placed a premium on supplies of banked blood. There are several methods available to conserve banked blood, but each has its disadvantages. Autologous blood may be collected and frozen, but the delay in preparing such units for use is unacceptable for emergency cases and the loss of platelets is undesirable. Mechanical autotransfusion using suction devices to collect blood from the operative field has been used successfully, but requires an investment in equipment and personnel, is destructive to cells and has only limited technical application. Intraoperative normovolemic hemodilution is a technique which is readily available to reduce transfusion needs when a blood loss of less than 2000 ml is expected. This technique was suggested as early as 1957 by Dodrill et al. [3] and has been used extensively in cardiac surgery. Earlier studies sug gested that the major hemodynamic response to hemodilution was an increase in cardiac output sufficient to maintain systemic oxygen delivery at adequate levels [ 61. The present study was undertaken to delineate precisely the hemodynamics of acute hemodilution in elderly patients with mul-
375
0022-4804/81/110375-07301.00/O Copyright 8 1981 by Academic Press, Inc. All rights of reprcduction in any form reserved.
376
JOURNAL OF SURGICAL RESEARCH: VOL. 31, NO. 5, NOVEMBER
1981
tisystem disease undergoing elective operation.
two controls appeared cachectic despite intravenous hyperalimentation. Blood from all patients was typed and cross-matched in the usual manner in the event that unexpected MATERIALS AND METHODS hemorrhage developed. Twenty-one consenting patients with an Patients were brought to the operating age of 60 f 4 years undergoing abdominal room unpremeditated and were anesthetized cancer surgery with an expected blood loss with intravenous thiopental 3 mg/kg for inof 1000-2000 ml were observed. Six of these duction and halothane and oxygen for mainpatients were randomly chosen to serve as tenance. Neither nitrous oxide nor adjuvant controls and were monitored in an identical drugs were administered. The inspired halofashion, but did not undergo intraoperative thane concentration was maintained behemodilution. None of the patients had tween 0.5 and 1%. Patients were mechanianemia or renal disease preoperatively, but cally ventilated through endotracheal tubes multisystem diseasewas prevalent (Table 1). to maintain normal pH and P,COI. Prior to induction a radial artery cannula, Twelve of the fifteen study patients and three of the six controls had abnormal pulmonary a thermistor-tipped triple-lumen pulmonary function tests; 6 of the 15 study patients and artery catheter, a Foley catheter, and a 14three of the six controls had a history of gauge venous catheter were inserted. Meamyocardial disease. Six study patients and surements were made during the control pe-
TABLE 1 PATIENT POPULATION Patient
8 9 10 11 12 13 14 15 16 17 18 19 20 21
Age
wt.
Procedure
46 54 52 69 64 61
68 66 51 59 68 78
Colectomy Colectomy A-P Reset. Colectomy Colectomy A-P Reset.
PFT, PFT, LFT, PFT,
57 69 64 52 49 65 71 60 60 55 67 81 52 53 57
66 73 74 55 63 61 77 57 62 72 66 53 47 82 75
Colectomy Colectomy Colectomy A-P Reset. A-P Reset. Colectomy A-P Reset. A-P Reset. A-P Reset. A-P Reset.
PFT PFT, LFT, MD PFT, LFT PFT, MD, HA, Ma1
A-P Reset. A-P Reset. A-P Reset. Colectomy
Multisystem disease” LFT MD HA, MD, Ma1 LFT, HA, MD, Ma1
MD PFT, LFT HA, Ma1 PFT, MD, PFT PFT, LFT, PFT, LFT, PFT, MD, PFT, LFT PFT, MD,
HA, Ma1 HA, Ma1 Ma1 Ma1 LFT
“PFT, abnormal pulmonary function tests; LFT, abnormal liver function tests; HA, hyperalimentation; MD, history of myocardial disease; Mal, malnutrition.
ROSE AND COUTSOFTIDES:
INTRAOPERATIVE
riod, which was 15 min after induction, and then every 30 min thereafter. These included blood pressure, heart rate, pulmonary artery, central venous, and pulmonary artery occluded pressures, arterial and venous blood gases, cardiac output, and large vessel hematocrit. Arterial blood gaseswere analyzed immediately in the operating room using an instrumentation laboratory 8 13 automated analyzer and cardiac outputs were determined in triplicate using the thermodilution technique and an Edwards Laboratory Model 95A computer. Then, blood was withdrawn from the large venous catheter into standard citrate-phosphate-dextrose blood storage bags which were numbered and maintained at room temperature. Simultaneously, lactated Ringer’s solution was infused in a ratio of 3 ml of crystalloid for every 1 ml of blood withdrawn. Hemodilution was continued until the large vessel hematocrit was 20-25%, then blood withdrawal was stopped and crystalloid solution was given at a rate sufficient to maintain pulmonary artery occlusion pressure between 10 and 15 Torr. Blood was reinfused if the hematocrit fell below 20%. In effect crystalloid solution was given to maintain circulatory stability and blood was given to maintain oxygen carrying capacity. When all major bleeding had been controlled, crystalloid infusion was stopped and the patients’ own blood was reinfused at a rate commensurate with cardiac filling pressures and clinical state. Autologous blood was reinfused in the reverse order of its collection so that the units with the lowest hematocrit were given back first. Furosemide was given intravenously, 1 mg/kg, if filling pressures were elevated and reinfusion was not complete. In all cases reinfusion was completed in the operating room without delaying the termination of the operation. All patients were extubated in the operating room and observed in the surgical intensive care unit overnight. Coagulation studies and platelet counts were done immediately postoperatively and every day for 3 days. The calculated and derived cardiopulmonary data included the following:
NORMOVOLEMIC
HEMODILUTION
377
1. Arterial oxygen content, C,O, = (Hgb x 1.34) &O, + zJao* x 0.003). 2. Physiologic shunt,
cc02 - GO2
QdQt= cco2- c&2. 3. Oxygen utilization coefficient,
02uc = C@;--y *
. 2
The control group was anesthetized and monitored in an identical fashion but without hemodilution. Whole blood was given to keep the hematocrit at the preoperative level and crystalloid was given to maintain the PAOP at lo- 15 Torr. Measured and derived data were accumulated identically in both groups. Statistical significance within groups was determined by comparing baseline data with subsequent values using a paired t test. Differences between groups were determined by a nonpaired t test. RESULTS
The preoperative hematocrit averaged 39 f 4 in the hemodiluted group and 38 + 3 in the nonhemodiluted group. The hematocrit was reduced to a minimum of 22 f 4 with dilution and was held constant in the group given whole blood. The postoperative hematocrit was 35 f 3 in the hemodiluted group compared to 37 + 4 in the nonhemodiluted group. The volume of blood removed averaged 2700 + 600 ml and the volume of crystalloid infused over the course of the operation averaged 10.3 liters. No patient in the hemodilution group received banked blood while an average of 2.4 units of whole blood was required in the control group. The amount of banked blood needed by the control patients ranged from 2 to 4 units. Heart rate was comparable between the two groups during the control period (Fig. 1). It was well maintained in the dilution
378
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VOL. 31, NO. 5, NOVEMBER
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FIG. 1. Heart rate was maintained in the hemodilution
groupand tended to decrease in the control group. group rising insignificantly from a baseline level of 88 + 3 beats/min to a maximum of 93 k 4 beats/min. Heart rate was maximal at 60 min after hemodilution when cardiac output and mean arterial pressure were at their lowest levels. The control group experienced an insignificant decrease in heart rate from a control level of 84 k 4 beats/ min to a minimum of 72 + 4 beats/min midway through the procedure. There was a tendency for the rate to return toward baseline level in both groups by the end of the operation. Heart rate was not significantly different between the two groups in the postoperative period and tachycardia was not a clinically significant problem postoperatively. Cardiac output was similar in both groups during the control period averaging 6.1 +- 1 liter in the hemodiluted group and 5.7 f 1.5 liters in the control group (Fig. 2). Cardiac output increased 16% in the diluted patients and decreased 18% in the nonhemodiluted patients (P < 0.05). In both groups cardiac output returned toward baseline levels by the end of the procedure. Mean arterial blood pressure was well
C
8
I
D
30
60
1981
90
120
150
180
FIG. 3. Mean arterial pressure did not differ between the two groups.
maintained in both groups decreasing a maximum of 10 Torr in the hemodilution group at 1 hr (Fig. 3). There were no significant changes in the MAP of the control group. Pulmonary capillary wedge pressure was held constant in both groups at lo- 15 Torr. Pulmonary artery pressure did not deviate from baseline values in either group at any time during the procedure. Figure 4 shows the percentage change in cardiac output, arterial oxygen content, and arterial-venous oxygen content during the baseline period, at maximal hemodilution and in the postoperative period. The decrease in arterial oxygen content, which is the major effect of hemodilution, is offset by the increase in cardiac output so that arterial-venous oxygen content remains unchanged. Cardiac output remains slightly elevated in the postoperative period as would be expected in most patients due to the stress of surgery. Oxygen consumption was not affected greatly by hemodilution. It decreaseda maximum of 9% midway through the operation although this was not statistically signifil 301
-301 Control
C
D306090
120
I50
I60
FIG. 2. Cardiac output increased with hemodilution and fell in the control group.
Dilurm
End
FIG. 4. The increase in cardiac output with hemodilution offset the decrease in arterial oxygen content so that arterial-venous oxygen content was well maintained.
ROSE AND COUTSOFTIDES
INTRAOPERATIVE
cant, and returned to baseline levels at the end of the procedure. There was no statistical difference in oxygen consumption between the two groups. Arterial-venous oxygen content difference was narrowed in the hemodiluted patients, but was not significantly different from the control group. The oxygen utilization coefficient, the supplydemand ratio for oxygen in the body, stayed within the normal range at all times for both groups. It averaged 24% in the diluted patients and 21% in the control group. Arterial oxygenation was similar in the two groups before, during, and after the op eration. P,O, was 380 + 75 Torr with a 12% intrapulmonary shunt during the baseline period in the hemodilution group and 374 +- 101 Torr with a 12% shunt in the nonhemodiluted group. After induction of anesthesia intrapulmonary shunt rose to 23 j, 5% in the dilution group and 26 +- 5% in the control group. Shunt remained constant throughout the procedure in both groups. P,O, was 390 f 100 Torr with a 12.8% shunt after extubation in the hemodilution group and 3 19 + 48 with a 14% shunt in the control group. All shunt data were calculated on an FIOz of 1.0. All patients had serum electrolytes and routine coagulation studies, including prothrombin time, partial thromboplastin time, and platelet count performed daily for 3 days postoperatively and there were no clinically significant changes in any patient. All patients were warm and well perfused and all maintained excellent urine output both intra- and postoperatively. Most study patients had a brisk diuresis which lasted 12-18 hr before urine output slowed to a more normal amount. There were no postoperative complications related to either the surgery or the hemodilution technique. DISCUSSION
Banked blood is in short supply, is costly, and is associated with a significant degree of morbidity [ 111. Acute intraoperative hemodilution is a technique to reduce the use
NORMOVOLEMIC
HEMODILUTION
379
of banked blood with its many adverse consequences and to make surgery safer for those who must avoid homologous blood for either religious or medical reasons. Some Jehovah’s Witnesses will accept autologous blood and it offers a safer alternative than volume expansion alone for those needing surgery. Also, for those who are difficult to cross-match or for those such as renal transplant patients who must avoid banked blood, this technique is well suited. We have assessedthe cardiopulmonary hemodynamics of acute hemodilution in a group of elderly patients with cancer. The majority of patients had multisystem disease, including chronic lung disease, sepsis, malnutrition, and liver disease.The only patients who were excluded were those with a recent history of myocardial ischemia. This study showed that the major compensatory factor in acute normovolemic hemodilution was an increase in cardiac output and that hemodilution to hematocrit levels of 20% was well tolerated. The increase in cardiac output to a mean of 16% above baseline without a significant heart rate change agrees with the work of Glick et al. who reported the same findings of an increased cardiac output resulting from an increased stroke volume in dogs subjected to hemodilution [4]. The increased cardiac output is unlikely to be related to changes in blood volume because right atria1 and pulmonary capillary wedge pressures remain stable during hemodilution. Because acute reduction in hematocrit will reduce viscous resistance and resistance to flow, venous return will increase if driving pressure remains constant. Guyton and Richardson showed that venous return and thus cardiac output increased significantly when hematocrit is isovolemically reduced [ 51. In normal volunteers undergoing gradual hemorrhage without volume replacement the major compensatory response is a decrease in arterialvenous oxygen content difference without an increase in cardiac output [ 121.The reduced viscosity associated with hemodilution may play the major role in the increased cardiac output and maintenance of the C,&,. By
380
JOURNAL
OF SURGICAL
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maintaining cardiac filling pressures we found a stable oxygen consumption and oxygen utilization coefficient and no widening of the Ca-&, which indicates the importance of adequate volume replacement in the presenceof an acute reduction in hematocrit. Mean arterial pressure was well maintained throughout the operation, although it decreased an average of 10 Torr when hemodilution was maximal at 1 hr. This slight drop in pressure was most likely due to the reduction in systemic vascular resistance associated with dilution. An important effect of hemodilution is the reduction in viscosity from decreasing the hematocrit. This prevents the formation of aggregates and makes rouleaux less stable and more easily disaggregated with less increase in shear [7]. This reduction in viscosity has been shown to increase flow through the microcirculation which may be of particular benefit in patients with vascular disease [9]. There is also a decrease in myocardial work associated with a decrease in systemic vascular resistance. Oxygen utilization coefficient (OJJC) is an index of the demand-supply ratio for the body and reflects the adequacy of cardiac output in relation to peripheral tissue needs. When correlated with other parameters of perfusion, such as color, temperature and urine output, it gives an excellent index of the ability of the myocardium to supply the metabolic needs of the body. With hemodilution the oxygen carrying capacity is reduced becauseof the lowered hematocrit and cardiac output is increased because of a lowered viscosity and peripheral resistance. The normal range of OzUC is between 20 and 3096,meaning that 20-30s of the available oxygen is consumed. An increase in the OJJC reflects a disparity between total body oxygen consumption and oxygen delivery. With hemodilution, not only did OJJC remain without normal limits, but the C,&, and total body oxygen consumption remained constant even with a reduced hemoglobin level. Oxygen delivery was evidently sufficient to meet metabolic demands
VOL. 31, NO. 5, NOVEMBER
1981
at a hematocrit of 20% when intravascular volume was maintained. Extensive volume expansion with crystalloid solution does not appear to involve the pulmonary parenchyma to a degree sufficient to affect arterial oxygenation [lo]. Although serum oncotic pressure was not measured in this study, it would obviously be lowered by the hemodilution technique we employed; whole blood was withdrawn and replaced with a balanced salt solution. Despite the low albumin levels and massive volume replacement, no evidence of altered pulmonary function was seen in any patient. All patients were extubated in the operating room and maintained adequate arterial blood gasesin the postoperative period. There were no respiratory complications. Serum electrolytes and a coagulation screen were done postoperatively and every day for 3 days and there were no abnormalities noted in any patient. There was a tendency for the platelet count to be transiently depressed in the immediate postoperative period, but this was not clinically significant. Clinically the patients were warm and well perfused despite a low hematocrit and there were no significant arrhythmias. The patients seemed to tolerate hemodilution well. Because of the large volume of crystalloid employed, the patients had a large diuresis both intra- and postoperatively. Most patients exhibited a brisk diuresis toward the end of the procedure as the shed blood was reinfused. It was common to have a urine output of 500 cc/hr or greater for the first few hours postoperatively. Approximately one-third of the patients required a diuretic because myocardial filling pressures were elevated and reinfusion was not complete. In every case the use of furosemide, 1 mg/ kg, resulted in a satisfactory diuresis and decrease in filling pressures to allow for the completion of the retransfusion. Urine output was occasionally sluggish early in the procedure because infusion of crystalloid often lagged behind the withdrawal of blood. When filling pressures in the myocardium
ROSE AND COUTSOFTIDES:
INTRAOPERATIVE
were optimized urine output was always adequate. Diuresis was usually complete by the following morning when urine output returned to normal. Clinically, fluid overload was never a problem as evidenced by arterial blood gases,chest X-ray, or filling pressures. There were no postoperative complications in this group of patients. There is much controversy over the use of crystalloid versus colloid for volume replacement in the surgical patient. In the present study fluids were titrated to maintain left heart filling pressures at 10-l 5 Torr. This resulted in a cardiac output greater than the preoperative level and adequate urinary output. Despite the 10.3~liter average intraoperative fluid requirement there was no abnormality in physiologic shunt, chest X-ray, or ventilatory parameters. Virgilio ef al., using crystalloid volume replacement in a manner similar to ours for patients undergoing aortic surgery showed a 40% decrease in colloid oncotic pressure from preoperative levels without any detrimental physiological effects on lung function when fluids were titrated to physiologic endpoints [IO]. Because the cost of albumin can be 50 times as great as Ringer’s lactate solution it is difficult to justify the use of colloid solutions for this technique. This technique is used at our hospital without the use of a pulmonary artery catheter or an overnight stay in the intensive care unit, although we do insert a central venous catheter both to monitor volume replacement and to serve as access to the central circulation. We have used it for Jehovah’s Witnesses, for patients difficult to crossmatch, and for portal caval shunts where fresh whole blood may be beneficial to control bleeding at the end of the operation. The results of our study indicate that acute normovolemic hemodilution is a feasible technique to reduce intraoperative blood loss and the need for homologous blood
NORMOVOLEMIC
HEMODILUTION
38 1
transfusion. Hemodilution saved an average of 2.4 units of blood when compared to nonhemodiluted patients. This represents not only a monetary savings, but a conservation of a scarce resource and the avoidance of a product with a significant incidence of side effects. REFERENCES 1. Aach, R. D., and Kahn, R. A. Post-transfusion hepatitis: Current perspectives. Ann. Intern. Med 92: 539, 1980. 2. Cooley, D., Beall, A., and Grondin, P. Open-heart operations with disposable oxygenators, 5 percent dextrose prime, and normothermia. Surgery 52: 713, 1962. 3. Dodrill, F., Marshall, N., Nyboer, J. et al. The use of the heart-lung apparatus in human cardiac surgery. J. Thoruc. Surg. 33: 60, 1957. 4. Glick, C., Plauth, W., and Braunwald, E. Role of the autonomic nervous system in the circulatory response to acutely induced anemia in unanesthetized dogs. J. Clin. Invest. 43: 2112, 1964. 5. Guyton, A., and Richardson, T. Effect of hematocrit on venous return. Circ. Res. 9: 157, 1961. 6. Laks, H., Pilon, R. N., Klovekorn, W. P. et al. Acute hemodilution: Its effects on hemodynamics and oxygen transport in anesthetized man. Ann. slug. 180: 103, 1974. 7. Messmer, K., Sunder-Plassman. L., and Klovekorn, W. Circulatory significance of hemodilution: Rheologic changes and limitations. Advan. Microcirc. 4: 1, 1972. 8. Ochsner, J., Mills, N., Leonard, G., and Lawson, N. Fresh autologous blood transfusions with extracorporeal circulation. Ann. Surg. 177: 811, 1973. 9. Replogle, R., and Merrill, E. Experimental polycythemia and hemodilution. Physiologic and rheologic effects. J. Thorac. Cardiovasc. Surg. 4: 582, 1970. 10. Virgilio, R., Rice, C., Smith, D. et al. Crystalloid versus colloid resuscitation: Is one better? Surgery 85: 129, 1979. 11. Walsh, J. Purcell, R., Morrow, A. er al. Posttransfusion hepatitis after open heart operations: Incidence after the administration of blood from commercial and volunteer donor populations. JAMA 212: 261, 1970. 12. Watkins, G., Bevilacqua, R., Brennar, M. er al. Controlled anemia in normal man: Cardiac output, oxygen transport and extraction. Surg. Form 1: 187, 1972.
OF SURGICAL
RESEARCH
31, 375-38 1 ( t 98 1)
lntraoperative DAVID ROSE, M.D.,**’
Normovolemic
Hemodilution
AND THEODORE COUTSOFTIDES, M.D.?
Departments of *Anesthesiology and tsurgery, University of California, Irvine. California 92664, and *Surgical Intensive Care Unit and fDepartment of Colon and Rectal Surgery, Veterans Administration Medical Center, Long Beach, California 90822 Submitted for publication December 26, 1980 We have studied the cardiopulmonary hemodynamics of acute hemodilution in a group of patients with cancer. The majority of patients had multisystem disease; including chronic lung disease, liver disease, sepsis, and malnutrition. The only patients who were excluded were those with a recent history of myocardial ischemia. Acute intraoperative hemodilution to a hematocrit of 22% was well tolerated provided blood volume was maintained with crystalloid solution. Hemodilution led to improved cardiac output by enhancing venous return which helped to compensate for the diminished oxygen content of the blood. There were no adverse cardiopulmonary effects in hemodiluted patients compared to patients undergoing similar operations without hemodilution. Acute normovolemic hemodilution is an effective clinical means of reducing the use of bank blood and avoiding the risks of blood transfusion in patients undergoing major surgery.
Intraoperative hemodilution is used in cardiac surgery to avoid the adverse consequences of homologous blood transfusion and to conserve supplies of banked blood. Also, the reports by Cooley et al. [2] and Ochsner et al. [8] suggest that hemodilution may improve cardiac function by reducing blood viscosity. Anaphylactic shock, bacterial contamination, and hemolytic reactions are rare complications of blood transfusion, but posttransfusion hepatitis is a persistent problem which at the present time can be prevented only by avoiding the use of banked blood. The reported incidence of hepatitis after bank blood transfusion varies greatly depending on the population studied and techniques used to identify the disease. Despite the routine screening of donor blood for the hepatitis type B surface antigen in the United States, post-transfusion hepatitis develops in approximately 7% of blood recipients at the present time [ 11. In an attempt to deal with this problem there is a trend ’ To whom requests for reprints should be sent at: Department of Anesthesiology, VA Medical Center, 5901 E. Seventh St., Long Beach, Calif. 90822.
toward all-volunteer donors that has placed a premium on supplies of banked blood. There are several methods available to conserve banked blood, but each has its disadvantages. Autologous blood may be collected and frozen, but the delay in preparing such units for use is unacceptable for emergency cases and the loss of platelets is undesirable. Mechanical autotransfusion using suction devices to collect blood from the operative field has been used successfully, but requires an investment in equipment and personnel, is destructive to cells and has only limited technical application. Intraoperative normovolemic hemodilution is a technique which is readily available to reduce transfusion needs when a blood loss of less than 2000 ml is expected. This technique was suggested as early as 1957 by Dodrill et al. [3] and has been used extensively in cardiac surgery. Earlier studies sug gested that the major hemodynamic response to hemodilution was an increase in cardiac output sufficient to maintain systemic oxygen delivery at adequate levels [ 61. The present study was undertaken to delineate precisely the hemodynamics of acute hemodilution in elderly patients with mul-
375
0022-4804/81/110375-07301.00/O Copyright 8 1981 by Academic Press, Inc. All rights of reprcduction in any form reserved.
376
JOURNAL OF SURGICAL RESEARCH: VOL. 31, NO. 5, NOVEMBER
1981
tisystem disease undergoing elective operation.
two controls appeared cachectic despite intravenous hyperalimentation. Blood from all patients was typed and cross-matched in the usual manner in the event that unexpected MATERIALS AND METHODS hemorrhage developed. Twenty-one consenting patients with an Patients were brought to the operating age of 60 f 4 years undergoing abdominal room unpremeditated and were anesthetized cancer surgery with an expected blood loss with intravenous thiopental 3 mg/kg for inof 1000-2000 ml were observed. Six of these duction and halothane and oxygen for mainpatients were randomly chosen to serve as tenance. Neither nitrous oxide nor adjuvant controls and were monitored in an identical drugs were administered. The inspired halofashion, but did not undergo intraoperative thane concentration was maintained behemodilution. None of the patients had tween 0.5 and 1%. Patients were mechanianemia or renal disease preoperatively, but cally ventilated through endotracheal tubes multisystem diseasewas prevalent (Table 1). to maintain normal pH and P,COI. Prior to induction a radial artery cannula, Twelve of the fifteen study patients and three of the six controls had abnormal pulmonary a thermistor-tipped triple-lumen pulmonary function tests; 6 of the 15 study patients and artery catheter, a Foley catheter, and a 14three of the six controls had a history of gauge venous catheter were inserted. Meamyocardial disease. Six study patients and surements were made during the control pe-
TABLE 1 PATIENT POPULATION Patient
8 9 10 11 12 13 14 15 16 17 18 19 20 21
Age
wt.
Procedure
46 54 52 69 64 61
68 66 51 59 68 78
Colectomy Colectomy A-P Reset. Colectomy Colectomy A-P Reset.
PFT, PFT, LFT, PFT,
57 69 64 52 49 65 71 60 60 55 67 81 52 53 57
66 73 74 55 63 61 77 57 62 72 66 53 47 82 75
Colectomy Colectomy Colectomy A-P Reset. A-P Reset. Colectomy A-P Reset. A-P Reset. A-P Reset. A-P Reset.
PFT PFT, LFT, MD PFT, LFT PFT, MD, HA, Ma1
A-P Reset. A-P Reset. A-P Reset. Colectomy
Multisystem disease” LFT MD HA, MD, Ma1 LFT, HA, MD, Ma1
MD PFT, LFT HA, Ma1 PFT, MD, PFT PFT, LFT, PFT, LFT, PFT, MD, PFT, LFT PFT, MD,
HA, Ma1 HA, Ma1 Ma1 Ma1 LFT
“PFT, abnormal pulmonary function tests; LFT, abnormal liver function tests; HA, hyperalimentation; MD, history of myocardial disease; Mal, malnutrition.
ROSE AND COUTSOFTIDES:
INTRAOPERATIVE
riod, which was 15 min after induction, and then every 30 min thereafter. These included blood pressure, heart rate, pulmonary artery, central venous, and pulmonary artery occluded pressures, arterial and venous blood gases, cardiac output, and large vessel hematocrit. Arterial blood gaseswere analyzed immediately in the operating room using an instrumentation laboratory 8 13 automated analyzer and cardiac outputs were determined in triplicate using the thermodilution technique and an Edwards Laboratory Model 95A computer. Then, blood was withdrawn from the large venous catheter into standard citrate-phosphate-dextrose blood storage bags which were numbered and maintained at room temperature. Simultaneously, lactated Ringer’s solution was infused in a ratio of 3 ml of crystalloid for every 1 ml of blood withdrawn. Hemodilution was continued until the large vessel hematocrit was 20-25%, then blood withdrawal was stopped and crystalloid solution was given at a rate sufficient to maintain pulmonary artery occlusion pressure between 10 and 15 Torr. Blood was reinfused if the hematocrit fell below 20%. In effect crystalloid solution was given to maintain circulatory stability and blood was given to maintain oxygen carrying capacity. When all major bleeding had been controlled, crystalloid infusion was stopped and the patients’ own blood was reinfused at a rate commensurate with cardiac filling pressures and clinical state. Autologous blood was reinfused in the reverse order of its collection so that the units with the lowest hematocrit were given back first. Furosemide was given intravenously, 1 mg/kg, if filling pressures were elevated and reinfusion was not complete. In all cases reinfusion was completed in the operating room without delaying the termination of the operation. All patients were extubated in the operating room and observed in the surgical intensive care unit overnight. Coagulation studies and platelet counts were done immediately postoperatively and every day for 3 days. The calculated and derived cardiopulmonary data included the following:
NORMOVOLEMIC
HEMODILUTION
377
1. Arterial oxygen content, C,O, = (Hgb x 1.34) &O, + zJao* x 0.003). 2. Physiologic shunt,
cc02 - GO2
QdQt= cco2- c&2. 3. Oxygen utilization coefficient,
02uc = C@;--y *
. 2
The control group was anesthetized and monitored in an identical fashion but without hemodilution. Whole blood was given to keep the hematocrit at the preoperative level and crystalloid was given to maintain the PAOP at lo- 15 Torr. Measured and derived data were accumulated identically in both groups. Statistical significance within groups was determined by comparing baseline data with subsequent values using a paired t test. Differences between groups were determined by a nonpaired t test. RESULTS
The preoperative hematocrit averaged 39 f 4 in the hemodiluted group and 38 + 3 in the nonhemodiluted group. The hematocrit was reduced to a minimum of 22 f 4 with dilution and was held constant in the group given whole blood. The postoperative hematocrit was 35 f 3 in the hemodiluted group compared to 37 + 4 in the nonhemodiluted group. The volume of blood removed averaged 2700 + 600 ml and the volume of crystalloid infused over the course of the operation averaged 10.3 liters. No patient in the hemodilution group received banked blood while an average of 2.4 units of whole blood was required in the control group. The amount of banked blood needed by the control patients ranged from 2 to 4 units. Heart rate was comparable between the two groups during the control period (Fig. 1). It was well maintained in the dilution
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FIG. 1. Heart rate was maintained in the hemodilution
groupand tended to decrease in the control group. group rising insignificantly from a baseline level of 88 + 3 beats/min to a maximum of 93 k 4 beats/min. Heart rate was maximal at 60 min after hemodilution when cardiac output and mean arterial pressure were at their lowest levels. The control group experienced an insignificant decrease in heart rate from a control level of 84 k 4 beats/ min to a minimum of 72 + 4 beats/min midway through the procedure. There was a tendency for the rate to return toward baseline level in both groups by the end of the operation. Heart rate was not significantly different between the two groups in the postoperative period and tachycardia was not a clinically significant problem postoperatively. Cardiac output was similar in both groups during the control period averaging 6.1 +- 1 liter in the hemodiluted group and 5.7 f 1.5 liters in the control group (Fig. 2). Cardiac output increased 16% in the diluted patients and decreased 18% in the nonhemodiluted patients (P < 0.05). In both groups cardiac output returned toward baseline levels by the end of the procedure. Mean arterial blood pressure was well
C
8
I
D
30
60
1981
90
120
150
180
FIG. 3. Mean arterial pressure did not differ between the two groups.
maintained in both groups decreasing a maximum of 10 Torr in the hemodilution group at 1 hr (Fig. 3). There were no significant changes in the MAP of the control group. Pulmonary capillary wedge pressure was held constant in both groups at lo- 15 Torr. Pulmonary artery pressure did not deviate from baseline values in either group at any time during the procedure. Figure 4 shows the percentage change in cardiac output, arterial oxygen content, and arterial-venous oxygen content during the baseline period, at maximal hemodilution and in the postoperative period. The decrease in arterial oxygen content, which is the major effect of hemodilution, is offset by the increase in cardiac output so that arterial-venous oxygen content remains unchanged. Cardiac output remains slightly elevated in the postoperative period as would be expected in most patients due to the stress of surgery. Oxygen consumption was not affected greatly by hemodilution. It decreaseda maximum of 9% midway through the operation although this was not statistically signifil 301
-301 Control
C
D306090
120
I50
I60
FIG. 2. Cardiac output increased with hemodilution and fell in the control group.
Dilurm
End
FIG. 4. The increase in cardiac output with hemodilution offset the decrease in arterial oxygen content so that arterial-venous oxygen content was well maintained.
ROSE AND COUTSOFTIDES
INTRAOPERATIVE
cant, and returned to baseline levels at the end of the procedure. There was no statistical difference in oxygen consumption between the two groups. Arterial-venous oxygen content difference was narrowed in the hemodiluted patients, but was not significantly different from the control group. The oxygen utilization coefficient, the supplydemand ratio for oxygen in the body, stayed within the normal range at all times for both groups. It averaged 24% in the diluted patients and 21% in the control group. Arterial oxygenation was similar in the two groups before, during, and after the op eration. P,O, was 380 + 75 Torr with a 12% intrapulmonary shunt during the baseline period in the hemodilution group and 374 +- 101 Torr with a 12% shunt in the nonhemodiluted group. After induction of anesthesia intrapulmonary shunt rose to 23 j, 5% in the dilution group and 26 +- 5% in the control group. Shunt remained constant throughout the procedure in both groups. P,O, was 390 f 100 Torr with a 12.8% shunt after extubation in the hemodilution group and 3 19 + 48 with a 14% shunt in the control group. All shunt data were calculated on an FIOz of 1.0. All patients had serum electrolytes and routine coagulation studies, including prothrombin time, partial thromboplastin time, and platelet count performed daily for 3 days postoperatively and there were no clinically significant changes in any patient. All patients were warm and well perfused and all maintained excellent urine output both intra- and postoperatively. Most study patients had a brisk diuresis which lasted 12-18 hr before urine output slowed to a more normal amount. There were no postoperative complications related to either the surgery or the hemodilution technique. DISCUSSION
Banked blood is in short supply, is costly, and is associated with a significant degree of morbidity [ 111. Acute intraoperative hemodilution is a technique to reduce the use
NORMOVOLEMIC
HEMODILUTION
379
of banked blood with its many adverse consequences and to make surgery safer for those who must avoid homologous blood for either religious or medical reasons. Some Jehovah’s Witnesses will accept autologous blood and it offers a safer alternative than volume expansion alone for those needing surgery. Also, for those who are difficult to cross-match or for those such as renal transplant patients who must avoid banked blood, this technique is well suited. We have assessedthe cardiopulmonary hemodynamics of acute hemodilution in a group of elderly patients with cancer. The majority of patients had multisystem disease, including chronic lung disease, sepsis, malnutrition, and liver disease.The only patients who were excluded were those with a recent history of myocardial ischemia. This study showed that the major compensatory factor in acute normovolemic hemodilution was an increase in cardiac output and that hemodilution to hematocrit levels of 20% was well tolerated. The increase in cardiac output to a mean of 16% above baseline without a significant heart rate change agrees with the work of Glick et al. who reported the same findings of an increased cardiac output resulting from an increased stroke volume in dogs subjected to hemodilution [4]. The increased cardiac output is unlikely to be related to changes in blood volume because right atria1 and pulmonary capillary wedge pressures remain stable during hemodilution. Because acute reduction in hematocrit will reduce viscous resistance and resistance to flow, venous return will increase if driving pressure remains constant. Guyton and Richardson showed that venous return and thus cardiac output increased significantly when hematocrit is isovolemically reduced [ 51. In normal volunteers undergoing gradual hemorrhage without volume replacement the major compensatory response is a decrease in arterialvenous oxygen content difference without an increase in cardiac output [ 121.The reduced viscosity associated with hemodilution may play the major role in the increased cardiac output and maintenance of the C,&,. By
380
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maintaining cardiac filling pressures we found a stable oxygen consumption and oxygen utilization coefficient and no widening of the Ca-&, which indicates the importance of adequate volume replacement in the presenceof an acute reduction in hematocrit. Mean arterial pressure was well maintained throughout the operation, although it decreased an average of 10 Torr when hemodilution was maximal at 1 hr. This slight drop in pressure was most likely due to the reduction in systemic vascular resistance associated with dilution. An important effect of hemodilution is the reduction in viscosity from decreasing the hematocrit. This prevents the formation of aggregates and makes rouleaux less stable and more easily disaggregated with less increase in shear [7]. This reduction in viscosity has been shown to increase flow through the microcirculation which may be of particular benefit in patients with vascular disease [9]. There is also a decrease in myocardial work associated with a decrease in systemic vascular resistance. Oxygen utilization coefficient (OJJC) is an index of the demand-supply ratio for the body and reflects the adequacy of cardiac output in relation to peripheral tissue needs. When correlated with other parameters of perfusion, such as color, temperature and urine output, it gives an excellent index of the ability of the myocardium to supply the metabolic needs of the body. With hemodilution the oxygen carrying capacity is reduced becauseof the lowered hematocrit and cardiac output is increased because of a lowered viscosity and peripheral resistance. The normal range of OzUC is between 20 and 3096,meaning that 20-30s of the available oxygen is consumed. An increase in the OJJC reflects a disparity between total body oxygen consumption and oxygen delivery. With hemodilution, not only did OJJC remain without normal limits, but the C,&, and total body oxygen consumption remained constant even with a reduced hemoglobin level. Oxygen delivery was evidently sufficient to meet metabolic demands
VOL. 31, NO. 5, NOVEMBER
1981
at a hematocrit of 20% when intravascular volume was maintained. Extensive volume expansion with crystalloid solution does not appear to involve the pulmonary parenchyma to a degree sufficient to affect arterial oxygenation [lo]. Although serum oncotic pressure was not measured in this study, it would obviously be lowered by the hemodilution technique we employed; whole blood was withdrawn and replaced with a balanced salt solution. Despite the low albumin levels and massive volume replacement, no evidence of altered pulmonary function was seen in any patient. All patients were extubated in the operating room and maintained adequate arterial blood gasesin the postoperative period. There were no respiratory complications. Serum electrolytes and a coagulation screen were done postoperatively and every day for 3 days and there were no abnormalities noted in any patient. There was a tendency for the platelet count to be transiently depressed in the immediate postoperative period, but this was not clinically significant. Clinically the patients were warm and well perfused despite a low hematocrit and there were no significant arrhythmias. The patients seemed to tolerate hemodilution well. Because of the large volume of crystalloid employed, the patients had a large diuresis both intra- and postoperatively. Most patients exhibited a brisk diuresis toward the end of the procedure as the shed blood was reinfused. It was common to have a urine output of 500 cc/hr or greater for the first few hours postoperatively. Approximately one-third of the patients required a diuretic because myocardial filling pressures were elevated and reinfusion was not complete. In every case the use of furosemide, 1 mg/ kg, resulted in a satisfactory diuresis and decrease in filling pressures to allow for the completion of the retransfusion. Urine output was occasionally sluggish early in the procedure because infusion of crystalloid often lagged behind the withdrawal of blood. When filling pressures in the myocardium
ROSE AND COUTSOFTIDES:
INTRAOPERATIVE
were optimized urine output was always adequate. Diuresis was usually complete by the following morning when urine output returned to normal. Clinically, fluid overload was never a problem as evidenced by arterial blood gases,chest X-ray, or filling pressures. There were no postoperative complications in this group of patients. There is much controversy over the use of crystalloid versus colloid for volume replacement in the surgical patient. In the present study fluids were titrated to maintain left heart filling pressures at 10-l 5 Torr. This resulted in a cardiac output greater than the preoperative level and adequate urinary output. Despite the 10.3~liter average intraoperative fluid requirement there was no abnormality in physiologic shunt, chest X-ray, or ventilatory parameters. Virgilio ef al., using crystalloid volume replacement in a manner similar to ours for patients undergoing aortic surgery showed a 40% decrease in colloid oncotic pressure from preoperative levels without any detrimental physiological effects on lung function when fluids were titrated to physiologic endpoints [IO]. Because the cost of albumin can be 50 times as great as Ringer’s lactate solution it is difficult to justify the use of colloid solutions for this technique. This technique is used at our hospital without the use of a pulmonary artery catheter or an overnight stay in the intensive care unit, although we do insert a central venous catheter both to monitor volume replacement and to serve as access to the central circulation. We have used it for Jehovah’s Witnesses, for patients difficult to crossmatch, and for portal caval shunts where fresh whole blood may be beneficial to control bleeding at the end of the operation. The results of our study indicate that acute normovolemic hemodilution is a feasible technique to reduce intraoperative blood loss and the need for homologous blood
NORMOVOLEMIC
HEMODILUTION
38 1
transfusion. Hemodilution saved an average of 2.4 units of blood when compared to nonhemodiluted patients. This represents not only a monetary savings, but a conservation of a scarce resource and the avoidance of a product with a significant incidence of side effects. REFERENCES 1. Aach, R. D., and Kahn, R. A. Post-transfusion hepatitis: Current perspectives. Ann. Intern. Med 92: 539, 1980. 2. Cooley, D., Beall, A., and Grondin, P. Open-heart operations with disposable oxygenators, 5 percent dextrose prime, and normothermia. Surgery 52: 713, 1962. 3. Dodrill, F., Marshall, N., Nyboer, J. et al. The use of the heart-lung apparatus in human cardiac surgery. J. Thoruc. Surg. 33: 60, 1957. 4. Glick, C., Plauth, W., and Braunwald, E. Role of the autonomic nervous system in the circulatory response to acutely induced anemia in unanesthetized dogs. J. Clin. Invest. 43: 2112, 1964. 5. Guyton, A., and Richardson, T. Effect of hematocrit on venous return. Circ. Res. 9: 157, 1961. 6. Laks, H., Pilon, R. N., Klovekorn, W. P. et al. Acute hemodilution: Its effects on hemodynamics and oxygen transport in anesthetized man. Ann. slug. 180: 103, 1974. 7. Messmer, K., Sunder-Plassman. L., and Klovekorn, W. Circulatory significance of hemodilution: Rheologic changes and limitations. Advan. Microcirc. 4: 1, 1972. 8. Ochsner, J., Mills, N., Leonard, G., and Lawson, N. Fresh autologous blood transfusions with extracorporeal circulation. Ann. Surg. 177: 811, 1973. 9. Replogle, R., and Merrill, E. Experimental polycythemia and hemodilution. Physiologic and rheologic effects. J. Thorac. Cardiovasc. Surg. 4: 582, 1970. 10. Virgilio, R., Rice, C., Smith, D. et al. Crystalloid versus colloid resuscitation: Is one better? Surgery 85: 129, 1979. 11. Walsh, J. Purcell, R., Morrow, A. er al. Posttransfusion hepatitis after open heart operations: Incidence after the administration of blood from commercial and volunteer donor populations. JAMA 212: 261, 1970. 12. Watkins, G., Bevilacqua, R., Brennar, M. er al. Controlled anemia in normal man: Cardiac output, oxygen transport and extraction. Surg. Form 1: 187, 1972.