Blood conservation for myocardial revascularization

J

THoRAc CARDIOVASC SURG

1987;93:512-22

Blood conservation for myocardial revascularization Is it cost effective? A total of 284 patients undergoing myocardialrevascularization wereprospectively studiedto determineif (1) the use of intraoperative autotransfusion or intraoperative autotransfusion plus postoperative reinfusion of shed mediastinal blood decreased transfusion requirements and (2) the use of one or both techniques was cost effective. The Haemonetics CeO Saver System was used for intraoperative autotransfusion and theSorensonReceptasealautotransfusionsystem for postoperative reinfusion of shed mediastinalblood.During Phase 1, the CeO Saver System was used for 57 patients and 93 patients served as a control group. During Phase 2, the CeO Saver System plus the autotransfusion system were used in 43 patients and 91 patients were in the control group. Separate parallel analyses to compare the blood conservation groups to control groups were conducted for each phase of the study. The patient groups were comparable with regard to age, sex, preoperative red ceO mass, preoperative hematocrit value, number of bypasses, and use of internal mammary grafts. Blood conservation techniques resulted in significant reductions in the use of bank blood. During Phase 1, CeO Saver System patients received an average of 2.8 units of packed ceUs versus 4.7 units for control patients. Transfusion was avoided entirely in 14% of CeO Saver System patients compared to 3% of control patients. During Phase 2, patients subjected to both the CeO Saver System and the autotransfusion system received an average of 1 unit of packed red ceUs versus 3 units for control patients. Tranfusion was required in only 42 % of patients subjected to both the CeO Saver System and the autotransfusion system compared to 85 % of control patients. Multiple logistic regressionanalysis confirmed that the use of the CeO Saver System in Phase 1 and the CeU Saver System and autotransfusion system in Phase 2 were each independently predictive of decreased transfusion requirements. The total "blood-related costs" (including cost for aD bank blood products plus Receptaseal and CeO Saver System equipment) was slightlylowerfor the bloodconservation patients in both Phase 1 ($555.00 versus $615.00, no significantdifference) and Phase 2 ($373.00versus $426.00, no significant difference). Intraoperative use of the CeU Saver System is associated with substantial savings of bank blood, and the addition of postoperative reinfusion of shed mediastinal blood results in further bank bloodsavings. The use of bloodconservation techniques is cost effective; that is, the costs incurred for the blood conservation equipment are more than offset by the resultant doUar savings for blood products.

Robert H. Breyer, M.D., Richard M. Engelman, M.D., John A. Rousou, M.D., and Stanley Lemeshow, Ph.D., Springfield, Boston, and Amherst, Mass., and Farmington, Conn.

From the Cardiac Surgery Department, Baystate Medical Center, Springfield, Mass.; the Departments of Surgery, Tufts University School of Medicine, Boston. Mass., and the University of Connecticut, Farmington, Conn.; and the School of Public Health, University of Massachusetts, Amherst, Mass. Read at the Twelfth Annual Meeting of The Western Thoracic Surgical Association, Napa, Calif., June 25-29, 1986. Address for reprints: Robert H. Breyer, M.D., Baystate Medical Center, 759 Chestnut St., Springfield, Mass. 01199. Supported in part by the Baystate Cardiac Surgical Research Fund.

512

IncreaSed use of blood conservation techniques during recent years has resulted in a significant decrease in the requirement for transfusion of homologous blood during or after cardiac surgical procedures. I·] These techniques have included preoperative autologous blood donation, intraoperative withdrawal of autologous blood before cardiopulmonary bypass (CPB), complete reinfusion of oxygenator blood, hemodilution during CPB, and acceptance of norrnovolemic anemia both during and after

Volume 93 Number 4 April 1987

operation. Additionally, intraoperative autotransfusion of blood aspirated from the operative field (before and after CPB) and postoperative reinfusion of shed mediastinal blood are major components of successful blood conservation programs. However, the equipment that allows use of these last two techniques adds specific costs that might not be offset by the savings associated with decreased blood bank utilization. Use of these devices has been reported to be associated with decreased homologous blood transfusion requirements at several institutions, I, 4-6 but others have questioned their efficacy7.8 or cost effectiveness.t? or both. We conducted a prospective study in two separate phases to determine if (1) the use of intraoperative autotransfusion or intraoperative autotransfusion plus postoperative reinfusion of shed mediastinal blood decreased transfusion requirements and (2) the use of one or both techniques was cost effective. Methods Phase 1. During a 7 month period (January to July 1985), intraoperative autotransfusion of blood aspirated from the operative field was evaluated in patients undergoing isolated myocardial revascularization. The Cell Saver System* was employed for autotransfusion. With this system, all blood shed in the operative field before or after CPB is aspirated by means of a locally heparinized collecting system. The aspirated blood is centrifuged and the resulting red cell concentrate subsequently reinfused. Assignment to Cell Saver System or control groups was not randomized. The Cell Saver System was used in all patients operated on by one surgeon (Group I) and was not used in any of the patients operated on by two other surgeons (Group II). However, patients were assigned to surgeon on a strictly rotating basis and were not selected on the basis of preoperative characteristics. Consequently, during a given time frame (i.e., Phase 1 or 2), patient groups were expected to be comparable. Phase 2. During a subsequent 5 month period (August to December 1985), the combination of intraoperative use of the Cell Saver System and postoperative reinfusion of shed mediastinal blood was evaluated. The Sorenson Receptaseal autotransfusion system] (ATS) was used for reinfusion of shed mediastinal blood. This system consists of a sterile plastic liner within a reusable rigid canister and provides a constant negative pressure *Haemonetics Corp., Braintree, Mass, tSorenson Research, Salt Lake City, Utah; Division of Abbott Laboratories, North Chicago, Ill.

Blood conservation

5 13

of 20 em H 20. The liner bag contains a 170 J.Lm filter that can be removed from the outer canister and its contents reinfused directly into the patient. For this study, reinfusion was employed if 250 ml or more was collected during a 4 hour period. If the rate of mediastinal bleeding was less than 250 ml over 4 hours, blood was not reinfused. Reinfused blood was passed through a 20 J.Lm Fenwal filter.* Again, patient assignment was according to attending surgeon. Intraoperative autotransfusion (Cell Saver System) and postoperative blood reinfusion (ATS) were employed in all patients operated on by one surgeon (Group III) and not used in patients operated on by two other surgeons (Group IV). During both Phase 1 and Phase 2, consecutive patients undergoing myocardial revascularization were entered into the study. Patients having any additional concomitant procedures, such as valve replacement, and patients with documented preexistent coagulation defects likely to require treatment with blood products were excluded from consideration. Additionally, patients who died in the operating room or immediately after the operation were excluded as the transfusion requirements in these patients might be artificially low. Patients requiring preoperative intra-aortic balloon pump support or havirig second or third revascularization operations were included in the analysis. Operative techniques were largely standardized. Neither preoperative donation of autologous blood nor withdrawal of autologous blood before CPB was used. The Shiley S-lOO bubble oxygenator] was used for primary operations and the Cobe CML membrane oxygenatorf for repeat bypass procedures. The oxygenator was primed with balanced electrolyte solution. Personal preference of the surgeon dictated the choice of blood or crystalloid cardioplegia. All control patients (Groups II and IV) received crystalloid cardioplegia, whereas patients in the blood conservation groups (Groups I and III) received blood cardioplegia. An ultrafilter connected in parallel with the bypass circuit was used to remove excess water from the bypass circuit and thus avoid severe hemodilution in patients receiving large volumes of crystalloid cardioplegic solution (> 1,750 ml). Anticoagulation was established with heparin, 5 mg/kg of body weight, and maintained during bypass with additional doses determined by the activated clotting time. After bypass, protamine dosage was determined according to heparin/protamine titration *Fenwal Laboratories, Deerfield, Ill. tShiley Incorporated, Irvine, Calif, :j:Cobe Laboratories, Inc., Lakewood, Colo.

5 14

The Journal of Thoracic and Cardiovascular Surgery

Breyer et al.

Table I. Patient characteristics Phase I Group I (Cell Saver System) No. of patients Age (yr) Sex Male (%) Female (%) Weight (kg) Preop. hematocrit (%) Preop. red cell mass (ml)

Phase 2 Group II (control)

I

Group III (Cell Saver System

+ ATS)

Group IV (control)

I

57 60.4 ± 1.2

93 62.3 ± 1.0

43 62.1 ± 1.2

91 62.7 ± 1.0

82.5 17.5 81.1 ± 1.5 40.0 ± 0.5 2,104 ± 43

73.1 26.9 77.4 ± 1.5 39.4 ± 0.5 1,980 ± 47

81.4 18.6 79.6 ± 2.1 40.1 ± 0.6 2,085 ± 69

82.4 17.6 80.2 ± 1.8 39.2 ± 0.4 2,029 ± 43

Legend: Continuous variables are expressed as mean ± standard error. ATS, Autotransfusion system.

Table II. Operative characteristics Phase 2

Phase I Group I (Cell Saver System) No. of patients No. of bypasses Internal mammary graft(s) Repeat revascularization Preop. IABP* CPB (min) Cardioplegic arrest (min) Postop. mediastinal drainage (ml) Reop. for bleeding

I

Group II (control)

Group III (Cell Saver System

+ ATS)

57 3.0 ± 0.1 26 (45.6%) 2 (3.5%)

93

43

3.0 ± 0.1 43 (46.2%) 0

96.3 ± 3.68t 46.6 ± 1.80 653 ± 57 2 (3.5%)

83.0 ± 2.78t 45.7 ± 1.50 632 ± 50 4 (4.3%)

2.7 ± 0.2 23 (53.5%) 3 (7.0%) 2 (4.7%) 90.6 ± 4.76+ 39.0 ± 2.50 806 ± 46+ 0(0%)

I

Group IV (control) 91 2.6 ± 0.1 33 (36.3%) 3 (3.3%) 8 (8.8%) 73.1 ± 3.42+ 37.0 ± 1.52 482 ± 44+ 3 (3.4%)

Legend: Continuous variables are expressed as mean ± standard error. ATS, Autotransfusion system. IABP, Intra-aortic balloon pump. CPB, Cardiopulmonary bypass.

•

'Data regarding IABP not available for Group I and Group II patients. 'tp

< 0.01. Group I versus Group II.

:j:p<0.01, Group III versus Group IV.

(Hepcon System 810*). During operation, hematocrit values as low as 18% to 20% were tolerated. Asymptomatic, hemodynamically stable patients were generally not given transfusions postoperatively unless the hematocrit value dropped below 25%. The mediastinum was drained by sump drains connected to high pressure suction for patients in Groups I, II, and IV. Closed mediastinal drainage was used for Group III patients. During Phase 2, our routine standing orders were reviewed and a number of blood tests were eliminated, which resulted in less blood withdrawn for laboratory use. Multiple preoperative and operative variables were recorded and analyzed to confirm that preoperative and operative factors which might affect blood use did not differ between groups. These variables included age, sex, weight, body surface area, number of bypass grafts, use *Hematec, Engelwood, Colo.

of internal mammary artery, primary versus second or third bypass procedure, use of intra-aortic balloon pump (recorded in Phase 2 only), preoperative hematocrit value, estimated preoperative red cell mass, duration of CPB, duration of cardioplegic arrest, postoperative mediastinal drainage, and hematocrit value at hospital discharge. The estimated preoperative red cell mass was calculated as the product of hematocrit multiplied by blood volume estimated from a nomogram." The need for transfusion of homologous red cells, fresh-frozen plasma (FFP), and platelets during the entire operative and postoperative course was recorded. Additionally, the volume of blood salvaged with the Cell Saver System or Sorenson Receptaseal system was noted. Total costs for blood products and blood conservation devices for each group were calculated and compared. The dollar values used for the calculations were the actual costs to the institution: Receptaseal system, $35.00; additional Receptaseal liners, $20.50;

Volume 93

Blood conservation 5 1 5

Number 4

April 1987

Table

m. Blood replacement Phase 2

Phase I Group I (Cell Saver System) No. of patients Cell Saver System reinfusion

57

I

Group /I (control)

93

332 ± 18.8

Group III (Cell Saver System

+ ATS)

43 426 ± 33.2

I

Group IV (control)

91

(rnl)

Receptaseal system reinfusion (ml) Bank blood products Red cells (units'[) Patients transfused (%) Fresh-frozen plasma (units) Patients transfused (%) Platelets (units) Patients transfused (%) Discharge hematocrit (%)

465 ± 35.9*

2.8 ± 0.3:1= 86.011 0.60 ± 0.2 19.3 2.2 ± 0.59 22.8 27.6 ± 0.38

4.7 ± 0.3:1= 96.811 1.23 ± 0.3 28.0 2.3 ± 0.55 21.5 27.7 ± 0.3

1.0 ± 0.2§ 41.9§ 0.23 ± 0.2 4.7~

1.0 ± 0.6 9.3 26.8 ± 0.34

3.2 ± O.3§ 84.6§ 0.7 ± 0.2 20.9~

1.5 ± 0.4 19.8 26.9 ± 0.32

Legend: Continuous variables are expressed as mean ± standard error. Mean value calculations include all patients in each group. ATS, Autotransfusion system *Includes only 33 patients who were actually reinfused. tUnit -225 ml. :j:p < 0.0001 Group I versus Group II. §p < 0.0001 Group III versus Group IV. lip < 0.05 Group I versus Group II. ~p < 0.05 Group III versus Group IV.

disposable reservoir and tubing pack for Cell Saver System, $163.00; and ultrafilter, $70.00. Blood product costswere calculated to be $85.00 per unit of packed red cells (PRCs), $40.00 per unit of FFP, $324.00 per platelet pack (derived from 6 units of blood), and $28.00 per unit of cryoprecipitate.

Statistical analysis Separate, parallel analyses to compare the blood conservation groups to the control groups were conducted for each phase of the study (i.e., Group I versus Group II and Group III versus Group IV). Initial analyses for each phase assessed the relationship between the use of blood conservation techniques and the need for transfusion of bank blood products, defined both in terms of the need for any PRCs, platelets, or FFP and in terms of the number of units of each product required. The chi square test of independence for categorical variables and Student's t test for continuous variables were used to identify potentially confounding patient and operative variables significantly associated with blood conservation or with blood replacement requirements during each of the two phases, and to determine the significance of any differences in cost between the groups. Subsequently, multiple logistic regression analysis was used to determine which variables were the best predictors of bank blood transfusion

(PRCs). This technique made it possible to generate a model for each phase that controlled for other important factors potentially related to transfusion while comparing the likelihood of requiring bank blood replacement of PRCs between the blood conservation group and the control group. The need for homologous PRC transfusion was the dichotomous outcome variable and all potentially related independent variables were permitted to enter the model by a forward stepwise technique. It was of interest to determine whether blood conservation was important enough a predictor to enter the model in the presence of other related factors.

Results A total of 150 patients were entered into the study during Phase 1: Cell Saver System (Group I), 57 patients; control (Group II), 93 patients. During Phase 2, 134 patients were entered into the study: Cell Saver System plus ATS (Group III), 43 patients; control (Group IV), 91 patients. Pertinent details regarding the patients in each group are summarized in Table I. No significant intergroup differences were noted in regard to age, sex, weight, preoperative hematocrit value, or red cell mass. Pertinent information regarding operative variables is summarized for each patient group in Table II. During Phase 1, the Cell Saver System and control groups were

The Journal of Thoracic and Cardiovascular Surgery

Breyer et al.

5 16

500

700

400

600

300

500

Dollars

400

200

Dollars 300

100 0

200 GROUP 1 CS

GROUP II CONTROL

GROUP III CS+ATS

GROUP IV CONTROL

Fig. 1. The actual cost for transfusion of packed red cells is shown for each of the four groups. During Phase I, the costs were significantly higher for Group II patients than for Group I (p = 0.0001). During Phase 2, costs were significantly higher for Group IV than for Group III patients (p = 0.0001). CS. Cell Saver System. ATS. Autotransfusion system.

similar with regard to number of vessels bypassed, use of the internal mammary artery, repeat revascularization procedures, amount of postoperative drainage, and incidence of reoperation for bleeding. Mean duration of CPB was significantly longer (p < 0.05) for Cell Saver System patients than for control patients, but the length of cardioplegic arrest was essentially identical for the two groups. During Phase 2, the mean number of bypasses per patient was slightly lower than during Phase 1, but was again equivalent between the blood conservation (Cell Saver System plus ATS) and control groups. The incidence of mammary artery usage was somewhat higher in the Cell Saver System plus ATS group than in the control groups (53.5% versus 36.3%), but this difference did not quite achieve statistical significance (p = 0.06). The incidences of preoperative intra-aortic balloon use, repeat revascularization procedures, and reoperation for bleeding were similar. Again, the duration of CPB was significantly longer in the blood conservation group than in the control group (90.6 versus 73.1 minutes, p = 0.01). Postoperative mediastinal drainage was also significantly higher in the blood conservation group than in the control group (806 ± 46 versus 482 ± 44 mI, p < 0.01). The volume of autologous blood salvaged with the Cell Saver System alone (Group I) and Cell Saver System plus ATS (Group III) is shown in Table III. During Phase I, an average red cell concentrate of 332 mI was retrieved from the Cell Saver System and reinfused in Group I patients. During Phase 2, an average red cell concentrate of 426 mI was salvaged from the Cell Saver System and reinfused in Group III patients. Thirty-three of the 43 Group III patients had 250 mI of postoperative drainage or more during the

100

GROUP I CS

GROUP II CONTROL

GROUP III CS +ATS

GROUP IV

Fig. 2. The overall "blood-related costs" were calculated to include total expenditure for all blood products plus any expenditures for ultrafilter, Cell Saver System, or Receptaseal disposables. Total blood-related costs were slightly, but not significantly, less in the blood conservation groups during both Phase I and Phase 2. CS, Cell Saver System. ATS. Autotransfusion system.

first 4 hours and consequently met the criteria for reinfusion of shed mediastinal blood. An average of 465 mI of shed blood was reinfused for these 33 patients. The use of blood conservation techniques was associated with significantly decreased bank blood requirements during both Phase 1 and Phase 2 (Tabel III). During Phase 1, Cell Saver System patients received an average of 2.8 ± 0.2 units of homologous PRCs versus 4.7 ± 0.3 units of PRCs for control patients (p < 0.(01). Transfusion of PRCs was avoided entirely in 14.0%of Group I patients, whereas only 3.2%of control patients avoided PRC transfusion entirely (p < 0.05). Requirements for FFP and platelets were similar for Group I and Group II patients, and hematocrit values upon discharge were identical in the two groups. During Phase 2, 84.6% of control patients required transfusion of homologous PRCs whereas only 41.9% of patients in the blood conservation group required transfusion of PRCs (p < 0.0001). Overall, Group III patients received a mean of 1.0 ± 0.2 units of homologous PRCs compared to 3.2 ± 0.3 units of homologous PRCs for Group IV patients (p < 0.(001). The percent of patients receiving FFP was significantly lower in Group III than Group IV (4.7% versus 20.9%, p < 0.05), but the overall average volume of FFP transfused for the two groups was not significantly different. Platelet transfusions were similar in the two groups. Hematocrit values upon discharge were identical in the two groups. The reduced transfusion requirements in Group I and Group III patients resulted in significanlty lower costs

Volume 93 Number 4

Blood conservation 5 1 7

April 1987

Table IV. Univariate analysis of risk factors for blood transfusion Phase 2

Phase I Transfusion Continuous variables Preop. hematocrit (%) Red cell volume (ml) Postop. drainage (ml) Age (yr) Weight (kg) Discrete variables Mammary graft(s) No Yes Repeat operation No Yes Sex Male Female

± ± ± ± ±

I

No transfusion 43.0 2420 498 53.4 86.9

± ± ± ± ±

I

p Value

38.9 1958 549 63.6 78.0

± ± ± ± ±

± ± ± ± ±

p Value

15 (19.2%) 24 (42.9%)

0.003

0.020

90 (70.3%) 5 (83.3%)

38 (29.7%) 1 (16.7%)

0.493

0.246

72 (65.5%) 23 (95.8%)

38 (34.5%) 1 (4.2%)

0.003

1 (1.2%) 10 (14.5%)

0.002

138 (93.2%) 1 (50.0%)

10 (6.8%) 1 (50.0%)

105 (91.3%) 34 (97.1%)

10 (8.7%) 1(2.9%)

41.0 2264 677 59.8 85.0

I

63 (80.8%) 32 (57.1%)

80 (98.8%) 59 (85.5%)

0.4 45 45 0.9 1.8

No transfusion

0.002 0.001 0.100 O.oI8 0.025

0.005 0.001 0.026 0.003 0.033

0.4 35 41 0.8 1.1

I

0.5 49 50 1.3 1.9

0.7 57 51 2.4 3.3

39.3 1996 651 62.2 78.2

Transfusion

Legend: Continuous variables are shown as mean ± standard error. Discretevariables are shown as number of patientsand pereent of patients. The ehi square test of independence was used for categorical variables and the Student's t test for continuous variables.

for homologus PRCs in these groups, as illustrated in Fig. 1. However, use of the Cell Saver System or the Cell Saver System plus the Receptaseal ATS did result in additional equipment costs for Group I and Group III patients. Therefore, we considered the overall "bloodrelated costs" to include the total expenditure for any blood products plus the expenditure for Cell Saver System and Receptaseal equipment. During both Phase I and Phase 2, total blood-related costs were slightly less in the blood conservation groups, but the differences were not statistically significant in either time frame, as shown in Fig. 2. Univariate analysis demonstrated several factors, in addition to use of the Cell Saver System, to be associated with decreased homologous PRC requirements during Phase 1. These variables are listed in Table IV. Preoperative hematocrit value, preoperative red cell volume, and the amount of postoperative mediastinal drainage all influenced the needs for transfusion. The likelihoodof PRC transfusion increased with increasing age and decreased with increasing weight. The incidenceof PRC transfusion was actually lower for patients having repeat procedures than for those having primary procedures, but the number of repeat procedures was only two. Patients having mammary artery grafts had a lower incidence of PRC transfusion than those not having mammary grafts. Evaluation by multiple logistic regression analysis (Table V) revealed that only two of these factors were independently predictive of the need for PRC transfusion. These two factors were

(in order of decreasing importance) preoperative red cell mass and the use of the Cell Saver System. "During Phase 2, univariate analysis again demonstrated that preoperative hematocrit, preoperative red cell volume, age, and weight influenced the need for postoperative homologus PRC transfusion, whereas the amount of postoperative drainage was no longer a significant factor. Female patients were more likely to require PRC transfusion than male patients. PRC transfusions were used less frequently in patients having mammary grafts than in patients not having mammary grafts, but repeat operation was not related to PRC transfusion requirements. A significant relationship between ischemic time and need for PRC transfusion was also noted. As indicated previously, the use of blood conservation techniques (ATS plus Cell Saver System) was associated with a highly significant decrease in the need for PRC transfusion. Evaluation by multiple logistic regression analysis revealed that only two factors were independent predictors of the need for PRC transfusion during Phase 2. These two factors were (in order of decreasing importance) use of blood conservation techniques (Cell Saver System and ATS) and red cell mass (Table V). For example, during Phase 1, patients in the Cell'Saver System group were only 15.8% as likely to require PRC transfusion as control patients, when controlling for red cell mass. During Phase 2, patients in the Cell Saver System plus ATS group were only 11.1% as likely to require PRC transfusion as control patients, when controlling for red cell mass.

The Journal of

5I8

Breyer et aJ.

Thoracic and Cardiovascular Surgery

Table V. Determinants of blood transfusion requirement Predictor

Phase 1 Phase 2

Red Cell Cell Red

cell mass Saver System Saver System plus ATS cell mass

Lower

Upper

Odds ratio

confidence unit

confidence unit

p Value

0.687* 0.158 0.111 0.803*

0.541 0.034 0.044 0.711

0.872 0.742 0.281 0.906

0.001 0.01 0.001 0.001

'Based on I()() unit difference.

Discussion This study demonstrates that the intraoperative use of the Cell Saver System during myocardial revascularization significantly decreases transfusion requirements and that the combined use of postoperative reinfusion of shed mediastinal blood plus intraoperative autotransfusion results in further savings of homologous blood products. The advantages of blood conservation include lower risk of transmission of infectious agents, decreased risk of febrile reaction, and decreased incidence of biosensitization to blood products. Autotransfused blood has a higher level of 2,3-diphosphoglycerate lO and consequently improved oxygen-carrying capacity. Finally, as shown in this study, the use of blood conservation techniques lessens overall blood bank requirements.':' Our study demonstrates that these advantages can be achieved without additional expense. The costs incurred for blood conservation devices are completely offset by savings resulting from decreased use of bank blood products. Although our patients were not randomized to blood conservation or control groups, analysis revealed the patient groups to be identical with regard to multiple patient variables that might affect the need for homologous PRC transfusion. Operative variables that might be associated with increased bleeding were also similar in both blood conservation and control groups except for the increased length of CPB in the blood conservation groups and the increased volume of postoperative mediastinal drainage in the blood conservation group during Phase 2. The longer CPB time merely reflects the differing surgical techniques used by the three surgeons participating in this study. In Group I and Group III patients proximal anastomoses were constructed during CPB. In most of the control patients (Groups II and IV), proximal anastomoses were constructed before CPB and thus the total CPB was shorter. We believe that the increased volume of mediastinal drainage recorded for Group III patients is apparent rather than real. In these patients, blood collecting in the mediastinum during sternal reapproximation and wound closure

was drained into the Receptaseal canister and included in the recorded volume of "postoperative" bleeding. In the control patients, all blood collected during sternal closure was aspirated into suction containers in the operating room and not included in the recorded volume of "postoperative" drainage in the intensive care unit. In any event, if differences in these two variables had any effect on transfusion requirements, the control groups would actually have been favored. However, multiple logistic regression analysis demonstrated that neither the length of CPB nor the volume of postoperative drainage was an independent predictor of blood transfusion requirements. The comparability of our patient groups combined with the results of multiple logistic regression analysis strongly support our conclusion that the decreased need for bank blood seen in Groups I and III can be attributed to the use of blood conservation techniques. It should be noted that the findings of our multiple logistic regression analysis largely confirm findings recently reported by Cosgrove and associates.I They found that red cell volume and age were the only two variables that were independently predictive of the need for transfusion in a group of 441 patients undergoing myocardial revascularization with the benefit of aggressive blood conservation techniques. The safety of the Cell Saver System during cardiac surgical procedures has been previously demonstrated. 5,6, II Moran and associates II noted decreased blood transfusion requirements during the first 48 hours after operation in patients in whom oxygenator contents were centrifuged by the Cell Saver System and reinfused. Both Cordell and Lavender' and Cosgrove and colleagues" have found intraoperative use of the Cell Saver System to be efficacious. However, Winton, Charrette, and Salerno' questioned the efficacy of the Cell Saver System. In a group of 20 patients, they found the mean volume of PRCs salvaged intraoperatively with the Cell Saver System to be only 105 ± 88.7 mI. The authors, however, did not empty the residual oxygenator contents into the Cell Saver System after CPB as was done in this study. During our Phase I studies, use of the Cell Saver

Volume 93 Number 4 April 1987

System alone was associated with a significant decrease in the incidence of homologous PRC transfusion and the overall mean volume of PRCs transfused. In fact, the use of the Cell Saver System was the only independent predictor of the need for transfusion other than preoperative red cell mass. Previous studies5,6,8, 12, 13 have demonstrated that reinfusion of shed mediastinal blood is a safe technique. The shed blood has a hematocrit value ranging from 18% to 25%4.6.8,12 and the platelet count in shed blood has been reported to be over 60,000/mm3. 8,11 The use of this technique has not resulted in derangement of coagulation function or in an increased need for platelets or FFP. 12, 13 Previous studies2, 5, 12 have reported decreased homologous blood transfusion requirements associated with routine autotransfusion of shed mediastinal blood. Although Thurer and associates" could not demonstrate a savings of bank blood when this technique was added to a program of blood conservation in routine cases, a subsequent report from the same institution" did show the value of postoperative autotransfusion in the subgroup of patients who have excessive postoperative bleeding. Similarly, Johnson and co-workers" found significant savings of bank blood in patients with excessive postoperative bleeding although they also could not demonstrate statistically significant savings of blood in the overall group of patients randomized to have postoperative autotransfusion. Our finding that excessive mediastinal drainage was not related to the likelihoodof transfusion in Phase 2 (in contrast to Phase 1) indirectly confirms the particular value of the Receptaseal system in patients with above average postoperative drainage. The criteria for reinfusion in other reports have ranged from 250 to 400 m1 over 4 hours.v" 12, 13 Other investigators have reported that 46% to 83% of their patients met criteria for reinfusion.P 12, 13 In our series, 77% of the patients in the ATS and Cell Saver System group had at least 250 m1 of drainage during the first 4 hours and consequently received a reinfusion. In combination with intraoperative use of the Cell Saver System, this technique was associated with a highly significant decrease in the incidence of transfusion of bank blood products and a highly significant decrease in the overall average volume of blood transfused. Multiple logistic regression analysis demonstrated that the combined use of these two blood conservation techniques was the most important determinant of the need for transfusion. We did not directly evaluate the use of the postoperative autotransfusion alone (i.e., without intraoperative use of the Cell Saver System). However, the mean volume of homologous blood transfused in patients having both intraoperative use of the Cell Saver

Blood conservation 5 1 9

System and postoperative autotransfusion (Phase 2) was reduced to almost one third of the volume received by patients having only intraoperative use of the Cell Saver System (during Phase 1). The percentage of Group III (ATS and Cell Saver System) patients receiving transfusions was dramatically and significantly lower than that of Group I (Cell Saver System alone) during the previous time frame (42% versus 85%, p < 0.0001). It is reasonable to conclude that this difference is due in part to the reinfusion of shed mediastinal blood. With the use of intraoperative and postoperative autotransfusion plus the acceptance of postoperative hematocrit values as low as 25%, we were able to reduce the incidence of blood transfusion to 42% of our patients. This can be compared to the experience of Cosgrove and associates,1 who were able to reduce the incidence of blood transfusion in myocardial revascularization to only 10%. They accepted hematocrit values as low as 15% during CPB and 22% postoperatively compared to our guidelines of 18% to 20% during CPB and 25% postoperatively. We suspect that this tolerance for anemia is one factor responsible for their ability to avoid transfusion in an additional 30% of patients as compared to .our results. Additionally, the patient cohort reported by Cosgrove's group 1 was younger than the patients in this report, and there was a considerably lower percentage of female patients (2.1% versus 21%) than in our current series. Both of these differences would be reflected in an increase in the mean preoperative red cell mass with consequent decreased likelihood of transfusion in Cosgrove's series, independent of any blood conservation efforts. We did note an overall decrease in homologous blood use in the second time frame of this study as compared to the first. For example, control patients received 4.7 units of PRCs in the first time frame but only 3.2 units in the second (p < 0.01). We believe that this change over time is due, in part, to an increased scrutiny regarding the need for routine postoperative blood work with consequent decreased postoperative phlebotomy as well as improved surgical hemostasis because of the attention focused on blood conservation during the study. Additional unrecognized factors may also be operative. In any event, the use of separate analyses for the two time frames should avoid any biases resulting from unrecognized changes over time. In summary, this study of 284 patients undergoing myocardial revascularization demonstrates that the intraoperative use of the Cell Saver System is associated with significant bank blood savings and that the addition of postoperative reinfusion of shed mediastinal blood results in further significant savings of bank blood. The

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use of these blood conservation techniques is cost effective; that is, the cost incurred for the blood conservation equipment is completely offset by the decreased blood bank costs. In an era of increasing financial restraints and malpractice litigation, maximal use of blood conservation techniques during myocardial revascularization allows cost-effective reduction in the use of bank blood and consequently lessens transfusion-related risks.

REFERENCES 1. Cosgrove OM, Loop FD, Lytle BW, et ai. Determinants of blood utilization during myocardial revascularization. Ann Thorac Surg 1985;40:380-4. 2. Schaff HV, Hauer J, Gardner TJ, et ai. Routine use of autotransfusion following cardiac surgery: experience in 700 patients. Ann Thorac Surg 1979;27:493-9. 3. Utley JR, Moores WY, Stephens DB. Blood conservation techniques. Ann Thorac Surg 1981;31:482-90. 4. Carter RF, McArdle B, Morritt GM. Autologous transfusion of mediastinal drainage blood: a report of its use following open heart surgery. Anaesthesia 1981 ;36:54-9. 5. Cordell AR, Lavender SW. An appraisal of blood salvage techniques in vascular and cardiac operations. Ann Thorae Surg 1981;31:421-5. 6. Cosgrove OM, Thurer RL, Lytle BW, Gill CG, Peter M, Loop FD. Blood conservation during myocardial revascularization. Ann Thorac Surg 1979;28:184-9. 7. Winton TL, Charrette EJP, Salerno TA: The Cell Saver during cardiac surgery. Does it save? Ann Thorac Surg 1982;33:379-81. 8. Thurer RL, Lytle BW, Cosgrove OM, Loop FD. Autotransfusion following cardiac operations: a randomized, prospective study. Ann Thorac Surg 1979;27:500-7. 9. Dagher FJ, Lyons JH, Finlayson DC, Shamsai J, Moore FD. Blood volume measurement: a critical study. Prediction of normal values: controlled measurement of sequential changes: Choice of a bedside method. Adv Surg 1965;69-109. 10. Noon GP, Solis RT, Natelson EA. A simple method of intraoperative autotransfusion. Surg Gynecol Obstet 1976;143:65-70. II. Moran JM, Babka R, Silberman S, et ai. Immediate centrifugation of oxygenator contents after cardiopulmonary bypass: role in maximum blood conservation. J THoRAc CARDIOVASC SURG 1978;76:510-7. 12. Schaff HV, Hauer JM, Bell WR, et ai. Autotransfusion of shed mediastinal blood after cardiac surgery: a prospective study. J THORAC CARDIOVASC SURG 1978;75:63241. 13. Johnson RG, Rosenkrantz KR, Preston RA, Hopkins C, Daggett WM. The efficacy of postoperative autotransfusion in patients undergoing cardiac operations. Ann Thorac Surg 1983;36:173-9.

Discussion DR. W. GERALD RAINER Denver. Colo.

This subject is timely, not only because of the factors that Dr. Breyer mentioned, but also because of the prevalent anxiety in many areas concerning the administration of homologous blood and blood products. This multivariate analysis examines an enormous number of factors concerning blood utilization. A few arbitrary decisions were made in this particular study design that might flaw the outcome: (1) the use of different surgeons with consequent different techniques; (2) the exclusion of operative or immediate postoperative deaths, especially if they were related to blood loss or hemorrhage; (3) use of different oxygenators-bubble oxygenators for primary cases and membrane oxygenators for reoperations; (4) the use of suction on the mediastinal tubes during the sternal closure in one group and eliminating that blood loss in another group. The deviation from protocol that concerned me the most, and Dr. Breyer touched on this in his presentation, was the elimination of patients who had been receiving preoperative medications that might affect the coagulation mechanisms. Additionally, the exclusion of these criteria may negate any benefit derived from transposing the study results to everyday practice. I have two comments concerning our techniques and one question to ask of Dr. Breyer. We use a Y-connector immediately proximal to the aortic cannula to eliminate air at the time of cannulation and to transfuse aliquots of blood back to the patient during the post-decannulation period. This is also a convenient method for returning any residual blood into the Cell Saver System for processing. Additionally, we have been looking at the use of serial Sonoclot determinations. These determinations may be very helpful in patients who have shown no preoperative coagulation deficits on the routine laboratory tests but may have some obscure platelet dysfunction. Our initial results with this test appear to be extremely helpful and we are optimistic about their continued help in the future. A comment about cost: Our costs are reasonably similar in every respect to those presented by Dr. Breyer with the exception that the cost of platelets in Denver is about half that cited by Dr. Breyer. The costs that we refer to are the costs to the patient. My belief is that even if the costs were moderately higher in your blood conservation group, it would still be worthwhile to eliminate or minimize the risk of exposure to extraneous blood and blood elements. One question: If you have included all the patients that were left out, would not the benefits of using your blood conservation techniques be even more significant? DR. BREYER Thank you for your comments, Dr. Rainer. We accept the limitations due to the fact that our study was not totally randomized. However, the demonstration by multiple logistic regression that these patients were entirely comparable in all regards largely negates that limitation of the study. This study

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was actually initiated to justify to our operating room committee the expenditure for blood conservation devices, and was done consequently for very practical nonacademic reasons initially.There were some compromises to get quick institution and compliance from three surgeons who do not always have the same inherent biases at the outset. We did exclude 7% of the patients who had coronary bypasses during this time period. I think the results, had they been included, would have been the same. However, we were afraid that if we had a few too many valve replacements in one of the other groups, none of which were very large, or one or two operative deaths for which no blood products would have been used (i.e., death from pump failure in the operating room), we may have skewed the results. I do not think the inclusion of those patients would have changed our final conclusions. We do not have any experience with the Sonoclot device, but certainly, especially now, we are interested in all modalities that can help us to conserve blood.

drainage bags and tubing for less than $100. I did not see that you had a comparison of autotransfusion alone versus autotransfusion and the Cell Saver System. If there was truly a significant difference in those patients, there may be another reason that you could eliminate some costs. Whether or not the Cell Saver System is that much of an advantage over autotransfusion alone remains a question.

DR. BENSON B. ROE

Costs and charges are different, and although you talk about costs there may be a significant magnification of savings when this translates as charges. Another point that has been alluded to by Drs. Rainer and Roe is the unwritten cost of a situation of AIDS or of hepatitis. In those circumstances, cutting down on blood utilization is important. I would recommend to all of you consideration of two other kinds of programs: The first is autotransfusiontaking blood in elective situations from the patient preoperatively to be used for him intraoperatively. The second is the use of specifically designated or directed donors who are known and whose health histories are well documented. If you were to have one case of hepatitis, or certainly one case of AIDS, this study would become irrelevant, because the costs would be enormous! I think these are two very safe and meaningful kinds of ways to use blood products better.

San Francisco. Calif.

Dr. Breyer is to be thanked for substantiating the economic aspect of this modality in this cost-conserving era. However, particular emphasis should be on safety, because there is no such thing as a perfect crossmatch. There appears to be some benefit from minimizing the use of homologous blood, which is highlighted in the seeming paradox of how well Jehovah's Witness patients do. I was similarly impressed by the benign course of Donald Ross's patients at the National Heart Hospital, who are allowed to become very anemic before they receive any blood. Let us recognize that blood conservation is both economical and safe. The latter issue is particularly sensitive in San Francisco, where the risk of acquired immune deficiency syndrome (AIDS) is added to the risk of hepatitis. DR. RICHARD ZOLLINGER Charlotte. N. C.

We use a similar technique, and I have been reviewing this with our series of patients. Do you use a cardiotomy with your setup? I understand that the Cleveland Clinic group sets up an ATS and transports it with the patient to the unit. Do you routinely type and crossmatch your patients? Originally, when I was in training we routinely typed and crossmatched, and the overall cost of that in the New Orleans area was $40 to $45 a unit. We now just routinely type and screen our patients at a cost of $30 and with a transfusion rate of 0.8 units per patient. That is another saving. We do not routinely use the Cell Saver System. We maximally autotransfuse before we remove the aortic cannula and any remaining blood that is available the perfusionists drain off in a bag and anesthesia gives it. In your series might it not be useful to look at the cost of a series in which only autotransfusion was used postoperatively compared to autotransfusion and the Cell Saver System, with the Cell Saver System cost being $150 to $180 versus your two Sorenson

DR. BREYER As you mentioned, we did not have a third group that merely had postoperative reinfusion. We do drain the cardiotomy contents into the Cell Saver System. This has the advantage of removing 85% of the heparin, which would remain if the blood were drained into a bag and reinfused. As we demonstrated, the use of the Cell Saver System alone did result in a savings equaling the cost of the device. We will stand by that conclusion. DR. JACK M. MATLOFF Los Angeles. Calif.

DR. BREYER I want to go on the record as saying that it is a given that less blood is better than more. I do not mean for our talk to imply that we are only concerned with cost. Avoidance of blood transfusions is desirable. For clarification, the costs that we considered were the true costs-not the charges to the patient, but the actual costs received by the hospital. DR. RICHARD G. FOSBURG La Jolla. Calif.

Currently I am sensitized about the problem of intra-aortic air. All of the discussants have indicated retention of the aortic cannula in place and reinfusion of shed volumes. There is a very successful alternative. A not uncommon problem is that when the aortic cannula is removed the stitch breaks or the anastomosis leaks and more blood is shed at that time. Some of you might want to take under consideration Dr. Shumway's longstanding technique of having the aortic cannula removed, the arterial line broken, and using one remaining venous line for reinfusion of any shed products.

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Manuscript reviewer's comment Acquired immune deficiency syndrome (AIDS), which has now reached pandemic proportions, has focused the attention of the lay and surgical communities on the complications associated with the transfusion of homologous blood. Worldwide, 100,000 persons have AIDS and I million more have AIDS-related disorders. Up to 10 million persons are infected with the AIDS virus and presumably are capable of spreading it. The emergence of a new strain of AIDS virus that is not detectable by currently employed antihuman immunodeficiency virus antibody testing has renewed concern for transmission of AIDS by blood transfusion. The 5% to 27% risk of transmission of non-A, non-B hepatitis from blood or blood products with its attendant potential for late hepatic failure is a less dramatic but more common complication.' In addition, economic pressures have encouraged reduced use of this expensive commodity. Currently, the total cost of transfusion of I unit of packed cells approaches $100 and seven platelet packs cost $280. These issues have made blood conservation increasingly important in cardiac operations. Generally practiced blood conservation techniques include crystalloid oxygenator prime, autotransfusion via the cardiotomy reservoir, transfusion of all oxygenator contents, and an acceptance of intraoperative and postoperative normovolemic anemia. Unfortunately, preoperative deposit of autologous blood has not been widely implemented because of logistic considerations such as unstable angina, hemodynamic instability, or hospital proximity. Attention has been focused on retrieval of shed blood to further reduce blood requirements. The Haemonetics Cell Saver System was the first widely applied device to salvage blood intraoperatively. It employs a regionally heparinized collection system and retransfusion of washed red cells. Reports attest to the safety and efficacy of this method and it has been widely applied in cardiac operations.' ] Because the hardware costs $17,500 and the disposable equipment $165 per patient setup, a significant reduction in transfusion requirements must be realized to be cost effective. Clinical studies evaluating its cost show mixed results.' The second method of retrieval of shed blood involves postoperative reinfusion of shed mediastinal blood. Defibrinated by the action of the heart and lungs, nonprocessed blood can be safely autotransfused.v" The Sorenson A TS was the first commercially available device. Despite its documented safety and ability to reduce transfusion requirements, transfusion of shed mediastinal blood has not become standard practice. Awkward technology and increased costs have contributed to its slow acceptance by cardiac surgeons. Breyer and associates have addressed the important issues of intraoperative and postoperative blood salvage to reduce blood transfusion requirements and increase cost effectiveness. They demonstrated that both intraoperative salvage with a Haemonetics Cell Saver System and postoperative autotransfusion of shed mediastinal blood with the Sorenson ATS decreased blood requirements. The expense of doing this was offset by the decreased use of blood and blood products. The strict cost accounting method employed underestimates the

cost of homologous blood transfusion by failing to take into consideration the huge expense of morbidity and mortality resulting from transfusion transmitted diseases. The economic advantages of intraoperative and postoperative blood salvage can be further enhanced by reducing the costs of the equipment. Using an inexpensive Sorenson ATS for the regionally anticoagulated salvage device ($36.00) and processing only when a significant blood volume has accumulated avoid the obligatory cost of Haemonetics Cell Saver System disposable equipment. If a significant volume is collected, processing may be done in the blood banks without additional expense for equipment or personnel.' Converting the cardiotomy reservoir for collection of mediastinal drainage for autotransfusion ($10.00) eliminates the cost of a chest drainage system and has the advantage of being accepted by Jehovah's Witnesses." These techniques reduce the cost of intraoperative and postoperative blood salvage and retransfusion to less than half the current cost of typing, cross-matching, and transfusing I unit of packed red cells. It is apparent that salvage and autotransfusion of blood is safe and effective. It not only is cost effective but results in financial savings. As society places increasing pressure on the cardiac surgical community to provide a safer operation at a lower cost, blood conservation by intraoperative and postoperative salvage of red cells is a method to accomplish both objectives.

Delos M. Cosgrove. M.D. The Cleveland Clinic Foundation Cleveland, Ohio 44106 REFERENCES I. Koziol DE, Holland PV, Alling DW, et al, Antibody to hepatitis B core antigen as a paradoxical marker for non-A, non-B hepatitis agents in donated blood. Ann Intern Moo 1986;104:488-95. 2. Messick KD, Gibbons GA, Fosburg RG, Nolan PC. Intraoperative use of the Haemonetics Cell Saver. Proceedings of the Blood Conservation Institute, 1978 3. Cosgrove DM, Thurer RL, Lytle BW, Gill CC, Peter M, Loop FD. Blood conservation during myocardial revascularization. Ann Thorac Surg 1979;28:184-9. 4. Winton TL, Charrette EJP, Salerno T A. The Cell Saver during cardiac surgery: Does it save? Ann Thorac Surg 1982;33:379-81. 5. Schaff HV, Hauer JM, Bell WR, et al. Autotransfusion of shed mediastinal blood after cardiac surgery. J THORAC CARDIOVASC SURG 1978;75:632-41. 6. Thurer RL, Lytle BW, Cosgrove DM, Loop FD. Autotransfusion following cardiac surgery: a randomized, prospective study. Ann Thorac Surg 1979;27:500-7. 7. Cosgrove DM, Loop FD, Lytle BW. Blood conservation in cardiac surgery. In: Brest AN. Cardiovascular therapy. Cardiovascular clinics. 12th ed. Philadelphia: FA Davis, 1982:165-75. 8. Cosgrove DM. An improved technique for autotransfusion of shed mediastinal blood. Ann Thorac Surg 1985;40:51920.