Eur J Cardio-thorac

Surg (1990) 4: 595-600

Q Springer-Verlag

1990

Postoperative autologous transfusion in cardiac surgery A prospective, randomised study J. Eng,

P. H. Kay, A. J. Murday, I. Shreiti, D. P. Harrison, D. R. Norfolk, I. Barnes, P. M. Hawkey,

Cardiothoracic

Surgical Unit, Leeds General Infirmary,

Leeds, UK

Abstract. To investigate the safety and efficacy of postop-

erative autologous blood transfusion (AT) using the Shiley hardshell venous reservoir, a prospective, randomised, controlled study was carried out in two matched groups of twenty patients undergoing elective coronary artery bypass surgery. The mean volume of shed mediastinal blood reinfused in the first 6 h postoperatively was 371.7k63.23 ml. Use of homologous blood was reduced from 760.5f108.37 ml in the control patients to 466.25 + 87.44 ml m the AT patients, a reduction of 38.7% (p < 0.05). There was no statistically significant difference in the clinical outcome, overall blood loss, use of platelets, fresh frozen plasma and colloids, haematological indices, renal and hepatic functions, or clotting mechanism, although there was a reduction in the fibrinogen level in the patients who received AT (pcO.05). Mediastinal blood did not clot and was defibrinogenated. It contained significant levels of haemoglobin (8.175 kO.506 g/dl), platelets (96.55 f 10.39 per mm3 103), protein (42.5 & 1.13 g/l), calcium (2.385 + 0.054 mmol/l) and was well oxygenated (PO, =20.46* 0.81 kPa). No patients developed bacteraemia or had any AT-related infections. We conclude that postoperative autologous transfusion using the Shiley hardshell venous reservoir is a safe and efficient method for reducing postoperative homologous blood requirement after coronary artery bypass surgery. [Eur J Cardio-thorac Surg (1990) 4: 595-6001 Key words: Autologous

transfusion

- Coronary

by cardiotomy suction and meticulous surgical haemostasis [17]. In coronary artery bypass grafting, the bank blood requirement has been reduced to an average of 328 ml in some centres [19]. However, cardiac surgical patients still remain one of the major groups utilising bank blood, up to 3.7% of hospital need and 2% of community usage [19]. In the United Kingdom, the current average requirement for donor blood for cardiac surgery is five units per operation [14]. The hazards of homologous bank blood use include serum hepatitis, especially hepatitis C, which complicates up to 7.1% of blood transfusions [l]. The possibility of transmission of the human immunodeficiency virus has increased interest in autologous blood transfusion (AT) [13]. In cardiac surgery, postoperative AT of shed mediastinal blood was first described in 1978 using the Sorenson autotransfusion system [15]. This method has since been used successfully in this and other centres [IO, 16, 171. Cardiotomy reservoirs were found to be safe and inexpensive [8]. In the United Kingdom, postoperative AT has not been used routinely in most major cardiac surgical units. In a recent survey of 32 major cardiothoracic surgical centres in the United Kingdom, only four were using AT regularly [14]. We decided to undertake a prospective study to assess the safety of AT and its feasibility in the routine postoperative management of cardiac surgical patients.

artery Patients and methods

surgery

Improvements in cardiac surgical techniques have resulted in reduced requirements for homologous blood transfusion both intraoperatively and postoperatively. Measures include preoperative phlebotomy, bloodless pump prime, intraoperative reinfusion of shed blood removed Received for publication: Accepted for publication:

and T. J. Inglis

December 13, 1989 June 5, 1990

Forty patients undergoing elective coronary artery bypass operations were prospectively randomised into tow groups. The first group (“study”) received postoperative AT while the second group (“control”) was managed in the usual way without AT. Patients undergoing repeat operations were excluded, as were those who underwent concomitant procedures. The study was approved by the Hospital Ethics Committee and informed consent was obtained from each patient entered into the study. Preoperative tests performed included haematological, biochemical, renal and hepatic functions. All patients received cefuroxime prophylaxis commenced with induction of anaesthesia and continued for 48 h postoperatively.

596 Imed

infusion

Pump R

ardshell venous

and incubated in air for 48 h. Two of the aliquots had a /3-lactamase preparation added to them. Blood samples from the patients were cultured using the Oxoid4 signal system. The reservoir was retained to collect further drained matter from the chest until the drains were removed the following day. In both groups of patients, volume replacement using clear colloidal solutions, mainly hetastarch and polygeline, was used, guided by measurements of systemic and filling pressures, peripheral perfusion and urine output. Blood was used only when the haematocrit fell below 25%, haemoglobulin below 9 g/d1 or the blood loss exceeded 500 ml in the first 4 h. Fresh frozen plasma, cryoprecipitate and platelets were used when coagulation abnormalities were detected in patients bleeding excessively (> 100 ml/h) within the first 6 h postoperatively. The total volume of blood loss postoperatively was recorded after removal of the chest drains. In addition to the mediastinal blood, specimens of the patients’ blood were obtained immediately after surgery and on the 1st and 7th postoperative days for haematological, biochemical and bacteriological examinations. The patients’ temperature charts were inspected, and any significant signs of infections recorded. The results were expressed as means f standard errors of the means. Statistical analyses were performed using two-sample t tests

and Mann-Whitneytest for non-parametricmeasurements.A probability of co.05 was taken as the criterion of significance.

Low vacuum pump Fig. 1. Autotransfusion technique. The chest drains are connected to the inlet port of the Shileyhardshellvenous reservoir. The transfusion set is attached to the outlet port and blood is infused via an Imed pump Standard anaestheticand perfusiontechniquesusingnon-blood prime were used in each case. The Shiley M2000 membrane oxygenator 1 was used for all patients in this study. Cardiopulmonary bypass was established between right atria1 basket and the ascending aorta after full systemic heparinisation (3 mg/kg body weight). Anastomoses were performed either by cold cardioplegic arrest of the heart or on a fibrillating heart using intermittent cross clamping technique without cardioplegia. After reversal of heparinisalion with protamine, titrated with measurement of activated clotting time, closure was performed in the standard fashion after the insertion of mediastinal and pleural drains. The latter were used when one or both pleural cavities were opened. At the end of the operation in theatre, the chest drains were connected to the Shiley hardshell venous reservoir using the Shiley chest drainage set. The drainage line was connected to the inlet at the top of the reservoir. The patient was then transferred to the cardiac intensive care unit where low continous suction (-20 cm water) was applied to one of the outer luer ports of the reservoir. Patients randomised to receive postoperative AT had their reservoirs set up for this purpose. The outlet port at the bottom of the reservoir was connected, via an Imed volumetric infusion pump *, to a peripheral transfusion line (Fig. 1). A Pall Ultipor blood transfusion filter 3 was incorporated into the system just distal to the outlet port of the reservoir. After the system was primed and specimens obtained for haematological, biochemical and bacteriological analyses, transfusion of the shed blood was commenced, the rate depending on the amount of drainage, reinfusing the previous hour’s blood loss over the subsequent hour. At the end of 6 h, the AT was discontinued and further specimens were obtained for haematological analyses and bacteriological cultures. Four 5-ml aliquots of shed blood were incorporated into 30 ml blood Agarbac (Oxoid4) 1 ’ 3 4

Shiley Incorporated, Irvine, California, USA Imed, Abington, Oxford, England Pall Biomedical Limited, Portsmouth, England Oxoid, Basingstoke, England

Results There was no hospital mortality in this series. There were no significant differences in the age and sex distribution of patients in the two groups, with a mean age of 55.75 years (range 33-69 years). There were 33 male and 7 female patients. There were no significant differences between the two groups in the preoperative tests on haematological and biochemical indices. The number of bypass grafts per patient averaged 3.5 + 0.11, with the left internal mammary artery used as one of the conduits in 95% of cases. One patient also had the right internal mammary artery harvested and used. Two patients who had previously undergone stripping of both long saphenous veins had their cephalic veins removed to be used as bypass conduits. The overall bypass time was 90.45 _+4.18 min, with no difference between the two groups. Cardioplegia was used in nine patients in the control group and five patients in the study group. The volume of postoperative blood loss and the types of volume replacement used are shown in Fig. 2. The overall blood loss per patient was 845.5 _+81.23 ml. There was no difference between the study and control patients. One patient in the control group had to be returned to theatre for control of excessive haemorrhage (> 200 ml/h for 2 consecutive hours). Use of the shed mediastinal blood in the study patients (mean 371.7k63.23 ml) resulted in a statistically significant reduction (38.7%) in the use of homologous bank blood (~~0.05). Figure 3 shows the number of units of bank blood used in the two groups. A total of 24 units of bank blood was used in the study group (mean 1.2 units/patient) compared to 34 units in the control group (mean 1.7 units/patient). The use of the mediastinal blood therefore resulted in a reduction of 0.5 unit of bank blood per patient. No difference was found in the use of colloids other than blood as postoperative volume replacement.

597 2500

1

2000 -

0

1

2

3

4

Units of blood used Fig. 2. Blood loss and volume replacement

in the two groups. A statistically significant difference was found only in the use of bank blood. A =total blood loss; B= homologous blood used; C= colloid replacement; n = study ; q = control

Table 1. Haematological

data (mean k SE)

Tests

Haemoglobin Study Control Haematocrit Study Control

Fig. 3. Number of units of bank blood used postoperatively. The use of shed mediastinal blood resulted in a reduction of the amount of bank blood used, n = study; EY = control

Preoperative

Immediately postoperative

1st Day

7th Day

(g/dl) 14.65 f 14.87+

0.25 0.28

10.48 f 10.22+

0.34 0.33

10.24* 10.47+

43.19+ 0.78 43.95 + 0.86

30.65f 30.54*

1.13 1.05

29.96 + 0.86 30.50 + 0.74

35.14+ 0.98 34.67 + 0.73

10.35f 10.53+

0.71 1.20

10.37* 9.51 f

0.53 0.67

3.31+ 3.41+

0.09 0.07

3.88* 3.86*

0.12 0.09

0.29 0.25

11.96+ ll.86+

0.33 0.24

(%)

White cell count ( x log/l) Study Control

7.62& 0.34 7.76, 0.57

Red blood cell count ( x 10i2/1) Study Control

4.79+ 0.08 4.81 _t 0.09

Platelet count ( x 109/1) Study Control

265.5 f 17.3 265.9 f 16.1

Table 1 shows the haematological data of the two groups of patients. There was no statistically significant difference between the groups in any of the haematological indices. Table 2 shows the results of tests on the coagulation systems. There was no significant difference in the prothrombin time, activated partial thromboplastin time and thrombin time between the study and control patients either immediately after surgery or at 1 or 7 days postoperatively. On the 1st postoperative day, however, the fibrinogen levels in the study patients were lower than those in the control levels (p < 0.05), although these values were still higher than immediately after surgery. Recovery was such that by the 7th postoperative day no difference remained. There was no significant difference

11.74& 1.27 10.81 _t 0.92

3.52+ 3.44f

0.16 0.13

171.0 * 12.1 163.4 f 9.9

153.5 + 7.3 158.3 + 12.0

368.4 + 26.2 336.3 +21.0

between the factor VIIJc levels of the two groups. Fibrin degradation products (D-dimer) levels were higher in the study group on the 1st postoperative day (p < 0.05) than in the control group. Immediately after surgery, the reverse was true (p < 0.05). These levels are not sufficiently high to suggest disseminated intravascular coagulation. Analyses of renal and hepatic functions were performed at the same intervals. No difference between the study and control patients was detected in the urea, creatinine, bilirubin, alkaline phosphatase and aspartate transaminase levels either preoperatively, immediately after surgery, or on the 1st or 7th postoperative days. Shed mediastinal blood in this series did not clot, the fibrinogen levels being less than 0.1 g/l. The quality of the

598 Table 2. Coagulation

indices (mean + SE) Preoperative

Tests

Immediately postoperative

1st Day

7th Day

PT (ratio) Study Control

0.997 + 0.014 0.971 k 0.016

1.282 + 0.034 1.34 + 0.03

1.356* 0.048 1.246 + 0.046

1.094 If: 0.026 1.076+ 0.018

APTT (ratio) Study Control

1.016+ 0.016 1.023 k 0.025

1.185+ 0.037 1.272 + 0.026

1.394 * 0.039 1.374+ 0.285

1.122& 0.026 1.113* 0.022

TT (ratio) Study Control

1.000 f 0.971+

0.037 0.029

1.091+ 0.041 1.062 + 0.047

1.018+ 0.933 f

0.966* 1.062 f

2.852 f 3.305+

0.167 0.193

1.802+ 2.06 f

2.49 f 0.143* 2.92 + 0.129*

Fibrinogen Study Control

0.042 0.044

0.035 0.036

(g/l)

Factor VIIIc (IU/dl) Study Control Fibrin degradation Study Control PT = prothrombin

112.9 102.8

+ 6.78 k 5.86

105.4 + 52.02 86.36 + 8.06

product (D-dimer) (ng/ml) 186.5 k46.89 168.7 + 26.67

199.1 449.4

time ; APTT = activated partial thromboplastin

Table 3. Haematological

indices of mediastinal

blood (mean + SE) 6h postoperative

Haemoglobulin (g/dl) Haematocrit (%) Red blood cell count

8.175+ 0.566 24.09 _+ 1.65 2.6995 0.188

4.922 _t 0.547 12.77 k1.57 1.385+0.187

W$Z IZLI IL? count (per mm3 103) Platelet count (per mm3 103)

5.45 + 0.826

5.07 +0.603

Table 4. Biochemical indices of mediastinal ter surgery (mean + SE) Sodium (mmol/l) Potassium (mmol/l) Chloride (mmol/l) PH PCO, (kPa) PCO, (kPa) Bicarbonate (mmol/l) Total protein (g/l) Albumin (g/l) Globulin (g/l) Standardised calcium (mmol/l)

88.11 +7.34

blood immediately

*23.2* + 85.7 *

time ; TT = thrombin

Immediately postoperative

96.55 If: 10.39

0.163 0.146

af-

137.9 k2.094 5.935 f0.326 109.6 _t 1.790 7.512+0.042 3.404 + 0.200 20.467 kO.812 15.75 k1.030 42.5 f 1.137 23.8 _+0.986 18.7 kO.715 2.385 kO.054

shed mediastinal blood in its various indices is shown in Tables 3 and 4. Although the haemoglobulin levels deteriorated, platelet counts appeared to be well maintained over the 6 h of AT. The mediastinal blood immediately after surgery contained significant levels of potassium

95.31 i 85.4 f

675.5 426.4

4.168* 0.212 4.299 + 0.177

9.28 6.82

203.3 202.5

k65.49 f 12.56

k90.6 * k61.1 *

514.2 473.6

f 72.83 k86.17

time ; * p < 0.05

and calcium and was well oxygenated with good levels of protein. There was some degree of haemolysis, as shown by a free haemoglobin level of 1328.33 + 595.2 mg/l. No free haemoglobin was detected in the patients’ blood, however, and there was no statistically significant difference between the haptoglobin levels of the two groups. All blood cultures were negative with one exception, in which coagulase-negative staphylococci different from those isolated from the shed blood were obtained. Seven out of 14 samples of mediastinal blood grew bacteria after 48-h incubation. All were grown from samples obtained at the completion of AT. All these samples had had /?-lactamase added to them. No more than four colony forming units per millilitre of blood culture were found. Two patients had coryneform bacteria isolated, one patient Streptococcus viridans, and the remaining four patients coagulase-negative staphylococci. There was thus a potential contamination in 50% of the patients receiving autologous blood postoperatively. Since none of the patients developed clinically significant infections, the clinical significance of this is unclear. There was no statistically significant difference between the two groups in the number of days spent in hospital after surgery, this being 10.8 &-1.55 in the study group and 11.95f2.62 in the control group. Postoperative pulmonary complications detected clinically and radiologically developed in nine patients in the study group and seven in the control group (no significant difference). One patient in each group developed significant sternal wound discharge, with a patient in the control group whose sternum dehisced, requiring resuturing. One patient in the control group developed significant leg wound infection, delaying her discharge from hospital.

599 Discussion Blood conservation is particularly important in cardiac surgery, not only because of the inevitable intra- and postoperative losses from heparinisation and coagulation defects and the unavoidable breaches of myocardial and vascular continuity, but also because methods and expertise for such measures abound in the routine perioperative management of the cardiac surgical patient. In addition, the recent rapid increase in open heart surgery, especially coronary artery bypass grafting, places high demand on limited blood bank resources. Further impetus is provided by the realisation that multiple transfusions in cardiac surgery contributed 27% of all adult patients with transfusion-related AIDS [I 31. Full heparinisation during cardiopulmonary bypass allows spilt blood to be salvaged, filtered and reinfused into the circulation. The lack of clotting, as observed in traumatic haemothorax [2], allows shed blood postoperatively to be reutilised without further addition of anticoagulants. Since its original describtion by Schaff et al. in 1978 [15], postoperative AT has become increasingly popular in cardiac surgery [6, 10, 12,16, 171. The reduction in the use of bank blood of 0.5 unit per patient postoperatively shown in this prospective study is comparable to other published series [lo, 1.51.Evaluation of cost has repeatedly shown this method to be efficient by reducing homologous blood usage [lo, 161. More importantly, the routine use of postoperative autologous transfusion reduces the risk of transmission of infectious diseases [l, 131 and alloimmunization. The Shiley hardshell venous reservoir has two main advantages compared to other systems. Firstly, its salvage after cardiopulmonary bypass reduces costs, since the same reservoir is used during surgery. Secondly, after setting up for postoperative autologous transfusion, a closed system is obtained. This enhances acceptance by the personnel handling it and also reduces the risk of contamination during the transfer of salvaged blood. Incorporation within the reservoir of a 20-urn filter helps by removing debri from the shed mediastinal blood. The flexibility of the technique using the Shiley hardshell venous reservoir is especially attractive. Since many patients do not require blood replacement, either of homologous or of autologous blood [lo, 15, 161, the application of special autotransfusion devices would be wasteful of resources. The easy availability of blood without cross matching, thus eliminating delays in volume replacement, is also valuable, especially for patients with large losses [16]. This method has previously been shown to be life saving in trauma and postpartum haemorrhage [7]. Such utilisation minimises the hazards associated with massive transfusion of stored homologous bank blood. It can also be very useful in patients with rare blood groups and unusual antibodies which make cross matching difficult. This prospective study confirms previous observations that shed mediastinal blood does not clot [8, 151. Its quality compares favourably with bank blood not only in haematological but also biochemical indices, with low potassium content in comparison. Our findings of

platelet counts are higher than those previously reported [IO, 16 - 171. This may be the result of our using a membrane oxygenator as opposed to a bubble oxygenator used in those studies. Membrane oxygenators have been shown to preserve better haemostatic functions after cardiopulmonary bypass [18]. The platelet counts are comparable to those achieved with preoperative donation since withdrawal of fresh blood into the plastic bag results in an immediate reduction in platelet count of 42% (9). The high protein content is superior to that of blood salvaged using a cell saver, which loses protein in its effluent [20]. The good oxygenation achieved with this technique is beneficial. Our findings of the lack of septic complications and negative venous blood cultures have been reassuring, since earlier studies reported the rate of contamination during open heart surgery to be as high as 71% [l 11. Later reports of mediastinal contamination quoted rates of 16.7% - 19.5% [6, 151.All our positive cultures from shed mediastinal blood were those obtained after treatment with jI-lactamase in the culture medium. Ordinary cultures without such treatment were negative. Our prophylactic use of cefuroxime thus prevented the growth of the bacteria isolated from the specially treated culture medium. The clinical correlation of this observation is the lack of septic complications. Shed mediastinal blood has been successfully reinfused in cardiac surgical patients after prosthetic valve replacements without significant septic complications [16]. We believe that with adequate antibiotic prophylaxis, such usage should not pose problems. Each centre is advised to monitor its own protocol, however, to ensure minimal contamination. The average blood utilisation per cardiac surgical patient has been reduced to less than one unit in recent reports [19]. Open heart surgery without the use of homologous blood has been shown to be feasible not only in coronary artery surgery [5] but also in valve replacement [4]. By a combination of methods including preoperative and prebypass donation, bloodless pump prime, intraoperative and postoperative haemodilution [5, 61, and postoperative autologous transfusion as demonstrated in this study, the requirement for homologous blood may be minimised. Other methods, including the use of aprotinin, may reduce this requirement even further [3]. Acknowledgement.

The authors would like to thank junior medical, nursing and perfusion staff for help in the study, Messrs G. Tate and P. Day, and Miss J. Higginson for performing haematological and biochemical analyses.

References 1. Aach RD. Kahn RA (1980) Post transfusion

hepatitis. Current perspectives. Ann Int Med 92: 539-546 2. Barriot P, Riou B, Viars P (1988) Prehospital autotransfusion in life threatening hemothorax. Chest 93: 522-526 3. Bidstrup BP, Royston D, Sapsford RN, Taylor KM (1989) Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol). J Thorac Cardiovast Surg 91: 364-372

600 4. Cooley DA, Bloodwell RD, Beall AC, Hallman GL (1966) Cardiac valve replacement without blood transfusion. Am J Surg 112:743-751 5. Cosgrove DM, Thurer RL, Lytle BW, Gill CG, Peter M, Loop FD (1979) Blood conservation during myocardial revascularization. Ann Thorac Surg 28: 184- 189 6. Dietrich W, Barany A, Dilthey G, Mitto HP, Richter JA (1989) Reduction of blood utilization during myocardial revascularization. J Thorac Cardiovasc Surg 97:213-219 I. Griswold RA, Ortner AB (1943) The use of autotransfusion in surgery of the serous cavities. Surg Gynecol Obstet 77: 167-177 8. Haltz RS, Smith JA, Green D (1988) Autotransfusion after cardiac operations. Assessment of hemostatic factors. J Thorac Cardiovasc Surg 96: 178-182 9. Hardesty RL, Bayer WL, Bahnson HT (1968) A technique for the use of autologous fresh blood during open heart surgery. J Thorac Cardiovasc Surg 56: 683 -688 KR, Preston RA, Hopkins C, 10. Johnson RG, Rosenkrantz Daggett WM (1982) The efficacy of postoperative autotransfusion in patients undergoing cardiac operations. Ann Thorac Surg 36: 173-179 11. Kluge RM, Calia FM, McLaughlin JS, Hornick RB (1974) Sources of contamination in open heart surgery. JAMA 230: 1415-1418 12. Lepore V, Radegran K (1989) Autotransfusion of mediastinal blood in cardiac surgery. Stand J Thorac Cardiovasc Surg 23147-49 13. Peterman TA, Jaffe HW, Feorino PM, Getchell JP, Warlield DT, Haverkos HW, Stoneburner RL, Curran JW (1985) Transfusion associated acquired immunodeficiency syndrome in the United States. JAMA 254:2913-2917

14. Russell GN, Peterson S, Harper SJ, Fox MA (1988) Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom. Br Med J 297: 1390-1391 15. Schaff HV, Hauer JM, Bell WR, Gardner TJ, Donahoo JS, Gott VL, Brawley RK (1978) Autotransfusion of shed mediastinal blood after cardiac surgery. A prospective study. J Thorac Cardiovasc Surg 75: 632-641 16. Schaff HV, Hauer J, Gardner TJ, Donahoo JS, Watkins L, Gott VL, Brawley RK (1979) Routine use of autotransfusion following cardiac surgery: experience in 700 patients. Ann Thorac Surg 27: 493 -499 11. Thurer RL, Lytle SW, Cosgrove DM and Loop FD (1979) Autotransfusion following cardiac operations: a randomised, prospective study. Ann Thorac Surg 27: 500-507 18. Van der Dungen JJAM, Karliczek GF, Breaken U, Van der Heide JNH, Wildevuur CRH (1982). Clinical study of blood trauma during perfusion with membrane and bubble oxygenators. J Thorac Cardiovasc Surg 83: 108- 116 19. Yeh T, Shelton L and Yeh TJ (1978) Blood loss and bank blood requirement in coronary bypass surgery. Ann Thorac Surg 26:11-16 20. Young JN, Ecker RR, Moretti RL, Iverson LIG, Ennix CL, Etheredge SN, Webb RL, Jackson WST, May RD, May IA (1982) Autologous blood retrieval in thoracic, cardiovascular and orthopedic surgery. Am J Surg 14448-52 Mr. J. Eng, MA, MB, FRCS Cardiothoracic Surgical Unit Killingbeck Hospital Leeds LS14 6UQ United Kingdom