Bloodless open heart surgery with atraumatic extracorporeal circulation F.N. McKenzie, md; R.O. Heimbecker, md; K.T.N. Barnicoat, md; A. Robert, cp; N.F. Gergeley, md; R. Del Maestro, md; W. Wall, md

Summary: With careful refinements in the pump oxygenator and a nonblood prime, bloodless open heart surgery may be performed almost routinely. In our series these measures reduced blood trauma, with a remarkable preservation of blood elements, especially platelets, and a corresponding elimination of postoperative bleeding. The mean hematocrit value decreased from 38 to 27% and recovered to 33% in the first 3 hours of postoperative diuresis. Mannitol and furosemide were rarely needed. Of 61 adult patients who underwent open heart surgery for aortocoronary bypass or valve replacement, the last 43 had a bloodless procedure. Of the 43, 26 (60%) required no bank blood postoperatively (in the operating room or the intensive care unit). In these 26 the operative mortality was 4% (1 patient). Bloodless techniques are invaluable during periods of bank blood shortage. They avoid the dangers of hepatitis and transfusion reaction, and they may minimize the incidence of postperfusion lung syndrome as well as renal

complications. Resume: La chirurgie a coeur ouvert sans transfusion sanquine utiiisant une circulation extracorporelle atraumatique Aujourd'hui, grace aux perfectionnements apportes aux oxygenateurs et a I'amorcage de l'appareil coeur-poumon avec un liquide physiologique autre que le sang, on peut

a coeur ouvert sans utilisation de sang presque couramment. Dans notre serie ces nouveaux procedes permettent de reduire le dommage cause au sang, lui conservant de facon remarquable ses elements, notamment les plaquettes, d'ou elimination d'hemorragie postoperatoire. L'hematocrite moyen est tombe de 38 a 27%, mais est remonte a 33% dans les 3 premieres heures qui ont suivi la diurese postoperatoire. On n'a du recourir que rarement au mannitol et au furosemide. Sur les 61 malades adultes qui ont subi une intervention a coeur ouvert (pour un pontage aortocoronarien ou le remplacement d'une valvule) les 43 derniers operes ont eu une operation sans transfusion sanguine. Vingt-six de ces 43 (60%) n'ont pas eu besoin de transfusion du sang de banque apres I'operation (ni dans la salle d'operation

pratiquer des interventions

Supported in part by the Ontario Heart Foundation, the Bickell Foundations, the Nelson Hyland Foundation and the Medical Research Council of Canada.

Reprint requests to: Dr. R.O. Heimbecker, University Hospital, 339 Windermere Rd., London, Ont. N6G 2K3

ni dans le service des soins intensifs). Sur ces 26 malades la mortalite operatoire a ete de 4% (1 malade). Ces techniques operatoires sans transfusion sanguine sont tres precieuses en periodes de penurie du sang de banque. Elles evitent les risques d'hepatite et de reactions transfusionnelles et peuvent minimiser la frequence des problemes pulmonaires consecutifs aux perfusions et les complications renales.

Many authors have described the obvious advantages of bloodless open heart surgery.13 Cooley and associates4 and Beall and colleagues5 have so managed quite large series of JehovarTs Witnesses. Hallowell and colleagues6 have used fresh autologous blood taken after induction of anesthesia but before the patient was heparinized, whereas Litwak and associates7 have achieved similar results by drawing blood 6 days preoperatively and then returning it to the patient at the time of surgery. The limitations of these techniques have prevented their wide use in other medical centres. We postulated that further refinements in technique might permit wider use and thus reduce blood bank requirements, and would pre¬ vent serum hepatitis, which has been reported from Amer¬ ican institutions to occur in 18.3% of patients who have received transfusions. In spite of 18 years of engineering refinement, trauma to blood elements, with subsequent erythrocyte and platelet loss, remains one of the principal hazards of extracorporeal circulation. We have examined ways in which trauma to the blood could be reduced and have studied the effect on indices of erythrocyte and platelet survival in two groups of patients undergoing open heart surgery. Materials and methods Patients

Sixty-one patients were studied. In the control group of 18 patients 5 underwent valve replacement and 13 aorto¬ coronary bypass. In the study group of 43 patients 15 underwent valve replacement and 28 aortocoronary bypass. Laboratory investigations Hematologic and coagulation values were determined routinely before surgery. No patient was excluded from the series on the basis of these results. Prothrombin time, partial thromboplastin time and plasma fibrinogen concentration were

measured in

venous

blood diluted 9:1 with 3.8%

CMA JOURNAL/MAY 3, 1975/VOL. 112 1073

sodium citrate. Platelet counts were done by Coulter count¬ er. These measurements, together with hemoglobin, hemato¬ crit and blood gas values, were obtained before operation, during operation (towards the end of bypass) and after operation (the same afternoon and daily for the next 3 days). Further measurements were obtained at intervals until the patient was discharged. All chemical measurements (blood gas, acid-base and electrolyte values) were made on the blood samples drawn from the patient during perfusion, 1 hour after perfusion and on postoperative days 1, 2, 3 and 5.

Perfusion techniques

Cardiopulmonary bypass was carried out with a dispo¬ sable bubble oxygenator (Bentley Laboratories Inc, Irvine, California) primed with up to 2 litres of Ringer's lactate to which was added 88 meq of sodium bicarbonate solution and 40 meq of potassium chloride. Patients were routinely

cooled to 32°C. The measured flow rate was 4 to 5 1/min (2 to 2.5 1/m2 body surface area per minute) and was mon¬ itored by central venous pressure. A Po2 analyzer (Bentley) was always used on the arterial line to monitor constantly arterial Po2 and keep it between 150 and 250 mm Hg to avoid the risks of de novo oxygen emboli. Patients in the control group were perfused according to standard methods. Fresh homologous blood, 500 ml, was added to the priming solution. No special effort was made to minimize cardiotomy suction. Left heart (ventricular) venting was usually used and a disposable filter (Pall) was used in the arterial line. Further bank blood was given to equal the blood loss as determined intraoperatively by weighing sponges, and postoperatively by measuring chest

drainage hourly. In the study group of 43 patients perfusion technique were made:

several refinements in

1. A filter was not used in the arterial line. 2. Perfusion lines were cut as short as possible. 3. Cardiotomy suction and left heart venting were avoided where possible. 4. At the end of perfusion all blood in the pump re¬ servoir was returned to the patient either in the operating room or in the intensive care unit (ICU) during the first few postoperative hours. 5. A bloodless prime of Ringer's lactate was always used for hemodilution and no blood was given intraoperatively or postoperatively unless there was an inadequate per¬ fusion pressure despite administration of Ringer's solution in the ICU. For each group of patients a detailed record of fluid intake and output was kept before, during and after per¬ fusion and in the postoperative period (from arrival in the ICU until 48 hours later). Mannitol was only occasionally used intraoperatively and furosemide was occasionally used postoperatively to promote diuresis. No patient received Table I.Data of Current surgical

procedure Coronary bypass

human

serum

albumin at any time

during

the

study.

Results Mean perfusion time in the control group was 63 minutes and in the study group 58 minutes. Of the 43 study pa¬ tients, in whom a bloodless prime was used, 26 (60%) required no blood postoperatively (in the operating room or the ICU). About 10% (6 of 61) of patients in both groups had had previous cardiac surgery and yet were readily managed and did not have excessive postoperative bleeding. Three patients who had had previous surgery underwent bloodless

techniques (Table I). Hemoglobin and hematocrit changes (Figs. 1 and 2) In the control group the mean hemoglobin value de¬ creased from 14 g/dl preoperatively to 9 g/dl intraopera¬ tively. The postoperative diuresis and homologous blood transfusion combined to increase the hemoglobin value to 12.3 g/dl in the first hours postoperatively, and there¬ after it gradually stabilized to reach a mean of 11.5 g/dl at the time of discharge. In the study group the mean preoperative hemoglobin value and the magnitude of decrease of the value during bypass were similar to those in the control group. Rapid diuresis of the pump priming fluid produced a return to a mean value of 12 g/dl in the first few hours after opera¬ tion. The hemoglobin values in this group were somewhat lower for the next 3 days because blood transfusions were carefully avoided during this period. However, despite this, the mean hemoglobin value at the time of discharge in the study group was close to that of the control group (Fig. 1). Changes in hematocrit value in both groups (from

Mh

X

7-15

FIG. 1.Mean study groups.

hemoglobin values (in g/dl) in control

and

patients with previous cardiac surgery and pericardial adhesions Patient

No. of units of blood transfused

Amount of fresh frozen plasma received

and aneurysm

Mitral valve

replacement ?Severe thrombocytopenic purpura preoperatively (30 000/mm3), with improvement under steroid therapy. 1074 CMA JOURNAL/MAY 3, 1975/VOL. 112

Amount of

platelet

concentrates received

Mean blood loss from chest drainage in first 12 postoperative hours 200 1400 250 250 500 500

40i

rzz

about 40% to 27%) closely followed those of hemoglobin. At the time of discharge the mean hematocrit values in the two groups were almost identical, at about 33%.

30h

20

CONTROL o.o STUDY ...

o

X

10

-I

J_L I

0P0

2

3

7-15

DAYS FIG. 2.Mean hematocrit values in control and

study

groups.

500r-

Platelet counts (Fig. 3) The most notable differences between the two groups of patients were changes in platelet counts. For both groups the mean preoperative value was about 250 000/mm3. In the control group the count decreased to 100 000/mm3 intraoperatively and to 70 000/mm3 on the 1st postopera¬ tive day, thereafter slowly recovering. In the study group the mean decrease was much less to 180 000/mm* during the operation and increasing to 190 000 by the 1st postoperative day; thereafter a progressive thrombocytosis was observed, in keeping with previous reported observa¬ tions. This improvement can be attributed to several factors. The avoidance of homologous blood in the study group is undoubtedly of importance. Elimination of the filter from the arterial line is probably of great importance. Yates and colleagues910 have stressed the importance of placing a filter in the arterial line, but we believe the commercial filters currently available do far more harm than good: when placed in the arterial line with flow rates of 3 to 5 1/min they become the site of removal of platelets and fibrin. Perhaps these disposable filters are unable to take such high flow rates and should only be used in the cardi¬ otomy suction line.

Scanning electron microscopy (Fig. 4)

OLI_1_I_I_L -I OP I 2 3

4-6

7-15

DAYS FIG. 3.Mean

platelet

counts in control and

study

groups.

FIG. 4A.Control group. Arterial line disposable filter; perfusion rate, 5 1/min for 1 hour. Note heavy paving with amorphous layer to cause complete occlusion of the mesh in some areas and subsequent rupture of the layer in others.

At the end of bypass the disposable filters were opened and the mesh was gently irrigated with saline, then prepared for study under the electron microscope. Fig. 4A shows the tremendous deposition of platelets and fibrin that invariably occurs in the mesh when flows of 3 to 5 1/min are forced through such a filter. In contrast, when such a filter is placed in the cardiotomy suction line at flow rates of 0 to 0.3 1/min the deposition is sparse (Fig. 4B).

FIG. 4B.Study group. Similar disposable filter in cardiotomy suction line; perfusion rate, 0 to 0.3 1/min for 1 hour. Note sparse deposition of platelets and fibrin. CMA JOURNAL/MAY 3, 1975/VOL. 112 1075

Postoperative

be available for insertion should ventricular distension be

course

The postoperative course of these two groups of patients is summarized in Table II. The mean perfusion time was similar in the two groups. The mean blood loss from chest drainage tubes in the first 12 postoperative hours was much greater in the con¬ trol group. Subsequent drainage was mostly serous and was similar in volume in the two groups. There were no renal complications. Urinary plasma hemoglobin values remained very low. Renal shutdown

oliguria was never a problem postoperatively, although patients were oliguric and uremic preoperatively. Pulmonary complications were minimal, with only one patient requiring ventilation for more than 24 hours. None required tracheostomy. The overall operative mortality was 5% (3 of 61), but was only 2.3% (1 of 43) in the study group. or

three

Discussion The use of crystalloid solutions as a substitute for whole blood to prime the extracorporeal pump oxygenator has greatly reduced the amount of homologous blood required in open heart surgery. The refinements of technique, as undertaken in the study group, are as follows: Avoidance of arterial line filter The present disposable filters seem unable to deal with such large blood flows (pump flow, 3 to 5 1/min). The turbulence, cavitation and filter vibration that can result at these flow rates are probably the cause of platelet and fibrin deposition on the filter (Fig. 4A) and the subsequent increase in risk of postoperative bleeding. A similar filter on the cardiotomy suction line only handles 0 to 0.5 1/min, quite within its capabilities, and will remove important pieces of thrombus, suture material, valve debris, micro¬ scopic gas bubbles, ete. (Fig. 4B). Under these conditions platelet counts are well preserved, with a corresponding reduction in incidence of postoperative bleeding (Fig. 3). Minimal cardiotomy suction Cardiotomy suction must be performed at low flow rates and with great care to prevent occlusion of the suction tip against the cardiac wall. The negative pressure so resulting will destroy erythrocytes, for they are most sensitive to negative pressure. With minimal flow rates there will be no excess air in the suction line, which would further contribute to blood turbulence. Venting of the left side of the heart has been widely advocated as an important part of surgery in coronary bypass and in mitral and aortic valve replacement.1112 In coronary bypass we have found venting to be usually un¬ necessary: it is never necessary in left coronary artery lesions, rarely in right coronary artery lesions, and only occasionally in circumflex lesions. Vents should always Table II.Data from postoperative

period

?Eight of these patients received packed red cells shortly before discharge. 1076 CMA JOURNAL/MAY 3, 1975/VOL. 112

observed, but with careful caval cannulation the latter is

distinctly

uncommon.

Prime of crystalloid A Ringer's lactate prime of about 2000 ml seems to produce an ideal amount of hemodilution in the average adult patient. In this series the mean hematocrit value reached a minimum of 27% during bypass (Fig. 2). This is of great benefit to overall tissue oxygenation because of enhanced capillary perfusion, as has been noted by others,13 and is probably due to decreased viscosity of the blood and therefore a more rapid transit of the erythrocyte across the capillary bed, especially with routine hypothermia to 32°C and the resulting increase in blood viscosity. As the patient returns to normothermia, a rapid diuresis occurs and the hematocrit reading returns to a mean value of 35% within the first few hours postoperatively (Fig. 2). Recovery of oxygenator blood The oxygenator and the arterial and venous lines should be carefully emptied of all blood. Much of this can be reinfused into the patient while the chest is being closed. The remainder can be put into blood transfusion bottles to be reinfused during the first few hours in the ICU, as indicated by measurements of central venous pressure. In this way the patient achieves a maximum recovery of erythrocytes, plasma, fibrinogen, platelets, ete, his own blood constituents being much more valuable to him than the best a blood bank can provide. It appears that this auto¬ logous blood is as valuable as blood removed from the patient immediately before operation and returned to him at the conclusion of bypass, as suggested by Dodrill et al14 and Hallowell et al.6 The absence of serious postoperative lung complications was a most notable finding. It was perhaps entirely due to the avoidance of homologous blood, thus preventing the sequestration and stagnation of foreign cells as de¬ scribed in the homologous blood-lung syndrome.15 The absence of serious renal complications further sup¬ ports the view that the avoidance of homologous blood minimizes erythrocyte sequestration and agglutination in the kidney.16 Further studies are now under way to clarify this con¬

cept.

Conclusion The routine use of a bloodless prime in open heart sur¬ gery together with the use of an atraumatic pump circuit with no arterial line filter has been very rewarding. The avoidance of cardiotomy suction and venting where possible greatly simplifies management, reduces blood requirements, reduces the incidence of postoperative bleeding and min¬ imizes overall morbidity. With these techniques we have completely avoided postoperative bleeding, have reduced the volume of postoperative chest drainage by 200%, have eliminated the need for fresh frozen plasma and platelet concentrates, and have reduced the requirements for homo¬ logous blood by more than 500%. Indeed, in 60% (26 of 43) of study patients we have avoided homologous blood completely in the intraoperative and ICU periods; the oper¬ ative mortality in these 26 patients was 4%. The use of serum albumin and blood substitutes as de¬ scribed in the literature is unnecessary and undesirable. The authors are grateful to Dr. J.C. Coles, department of sur¬ gery, and Dr. D. Hodgson, department of anesthesia, for their interest; also to Drs. R. M. Barr and R.K. Stuart, department of hematology; and to Mr. Razzo Smith, department of dentistry, University of Western Ontario, for his beautiful scanning elec¬

tron

micrographs.

Addendum Since the preparation of this paper we have obtained equally impressive results with additional patients, bringing the total series to 100 operations. References I. GOLLUB S, BAILEY CP: Management of major surgery blood loss without blood transfusion. JAMA 198: 149, 1966 2. COOLEY DA, BLOODWELL RD, BEALL AC JR, et al: Cardiac valve replacement without blood transfusion. Am / Surg 112: 743, 1966 3. EvAI.Is-PaossER CDG, SMITH GH, ROBERTSON DS: Ringer lactate solution as a priming fluid for the disc oxygenator. Thorax 21: 545, 1966 4. COOLEY DA, CRAWFORD ES, HOWELL JF, et al: Open heart surgery in Jehovah's Witnesses. Am J Cardiol 13: 779, 1964 5. BEALL AC JR, YoW EM JR, BLOODWELL RD, et al: Open heart surgery without blood transfusion. Arch SurF 94: 567, 1967 6. HALLOWELL P, BLAND JHL, BucKLEY MJ, et al: Transfusion of fresh autologous blood in open heart surgery. / Thorac Cardiovasc Surg 64: 941, 1972 7. LITWAK RS, JURADO RA, LUEBAN SB, et al: Perfusion without donor blood. Ibid, p 714

8. ALLEN JG, DAWSON D, SAYMAN WA, Ct al: Blood transfusions and serum hepatitis: use of monochioroacetate as an antibacterial agent in

plasma. Ann Surg 150: 455, 1959 9. YATES RA, OLDERMAN GM: Hematological effects of extracorporeal filtration: a comparison of the woven screen and variable pore foam

filters. New Brunswick NJ, Johnson & Johnson, 1973 10. YATES RA, KUBANEK GR: Physiological effects of extracorporeal filtration. Presented at the annual. meeting of the American Society of Extracorporeal Technology, New York, 1972 11. Filtoit WB, DsAs F: Intracardiac pressures during induced ventricular fibrillation and anoxic arrest. Can J Surg 17: 89. 1974

12. ZwART HH, BRAINARD JZ, DEWALL RA: Ventricular fibrillation without venting; hemodynamic observations in humans. Presented at the annual meeting of the Society of Thoracic Surgeons, Montreal, Jan. 21, 1975 13. MESSMER K: 02 supply to the tissue during limited normovolemic hemodilution. Res Exp Med (Berlin) 159: 152, 1973

14. DODRILL FD, MARSHALL N, NYsOER J, et al: The use of the heart

lung apparatus in human cardiac surgery. J Thorac Cardiovasc Surg 33: 60. 1957 15. VEITH FJ, HAOSTEOM JWC, PANOSSIAN A, et al: Pulmonary microcirculatory response to shock, transfusion and pump-oxygenator procedures: a unified mechanism underlying pulmonary damage. Surgery 64: 95. 1968

16. HEIMBEcKER RO, BIGELOw WG: Intravascular agglutination of erythrocytes (sludged blood) and traumatic shock. Surgery 28: 461, 1950

Retrospect Cancer prophylaxis Accordingly, we may divide this prophylaxis in the following way: - A general prophylaxis, and a special prophylaxis. The general prophylaxis will deal, as a matter of course with the general health of the body; with nutrition, or over-nutrition; and the factors that conspire toward a premature senescence. Diet i. a factor here, in respect of both quantity and quality, and the vegetarian does not escape. If this diet contain or manifest a noxious irritant, it falls into the second division of special prophylaxis which will concern itself with body-hygiene, within or without, and the possible escape from all persistent irritation. I shall first deal, very shortly, with general prophylaxis. The rules for guidance here may be summed up in the one phrase, "a simple life," of maintaining a sound mind in a diligent and useful body. Dr. Hindhede of Copenhagen, asserts that "in civilized countries, the higher standard of living during the last fifty years has been attended by a marked increase in the cancer death-rate"; and he also states that "in England there is a higher death-rate from cancer in classes that indulge in high living, than in those who live frugally." He says of his own country, Denmark, that "cancer is the cause of death for every fifth person .t'ho dies after the age of forty-five; there is no other country in which there are so many fat men and fat women, and in no other country is the daily fare so rich." The death-rate from cancer is high in fat people. Dr. Hindhede lays special stress on the over-consumption of meat. Speaking of America, Dr. C. W. Saleeby, the noted publicist, observes that "over-eating is now almost the only physiological sin generally committed in the United States." As regards our women he might have said, over-eating and lack of exercise. Now, all this over-eating (or over-drinking), this over-loaded nutrition, means inevitably a premature old age, a lowering of resistance, and a disturbance of balance between the tissues. We have indicated the way in which this bodydegeneration may induce a cancer-influence, and the remedy thereof is not only simple, but self-evident. Special prophylaxis is concerned with the avoidance and removal of all possible forms of chronic irritation. Billroth stated many years ago that, "without previous chronic inflammation cancer does not exist, and we are all agreed that frequently, it is the immediate cause, the occasion, of this disease." You are all familiar with these irritants, their name is legion, and their number increases from year to year. They affect chiefly the skin-surface, the alimentary tube, and the urino-genital canal. As regards the alimentary tube, one or two facts are of special interest. The frequency-curve of cancer in men and women crosses at the level of the stomach. In men, cancer is more frequent in front of the stomach, in the oesophagus and in the buccal cavity, and we can guess the reason; while in women, it is more frequent behind the stomach, in the bowel, and here the irritating agent is constipation. In China, rice is eaten very hot by the men. who are served first by the women; in consequence, the latter get their rice cold, and the reward of their service is an escape from cancer of the oesophagus, so common in the men. - Chipman WW: An address on cancer prophylaxis. Can Med Assoc J 15: 467, 1925 CMA JOURNAL/MAY 3, 1975/VOL. 112 1077