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THE PROPHYLACTIC USE OF FRESH FROZEN PLASMA AFTER EXTRACORPOREAL CIRCULATION
THE PROPHYLACTIC USE OF FRESH FROZEN PLASMA AFTER EXTRACORPOREAL CIRCULATION A. S. Trimble, M.D.* J. J. Oshorn, M.D., W. ]. Kerth, M.D., and F. Gerbode, M.D., San Francisco and Palo Alto, Calif.
E
bleeding after extracorporeal circulation was a catastrophic event during the pioneering years in this field. The infrequent appearance of this syndrome in the present era is a tribute to the efforts of hematologists and surgeons in defining and treating the etiologic factors. 1 ' 2 In spite of these ad vances, routine postoperative blood losses in these patients are significant and occasional bleeding problems do arise. Fresh frozen plasma ( F P P ) , equivalent to fresh blood as a source of the plasma clotting factors I I and V to X, has been used in the treatment of a number of hemorrhagic diatheses, including hemophilia.3 This study was carried out to establish whether the routine use of fresh frozen plasma would measurably decrease postoperative bleeding after open-heart surgery. Because of the great variation in bleeding and in operative procedure, from one patient to another, the study was carried out by "blind" random sampling in a consecutive series of patients. XCESSIVE
PLAN OF THE STUDY
Fifty-three consecutive patients, with a variety of congenital and acquired heart defects, were included in the study. Each had an open-heart operation with the use of a large-disc oxygenator. 4 The patients were divided into two groups by reference to a list of random numbers. 5 The random allocation of each patient to one group or the other was carried out before the patient's entry into the hospital, and without knowledge of the detailed diagnosis. The surgeons and attending staff did not know in which group any patient fell. The treatment of the two groups was therefore similar except that one group received fresh frozen plasma as described below. From the Department of Cardiovascular Surgery, Presbyterian Medical Center, The Insti tute of Medical Sciences, San Francisco. Calif., and the Department of Surgery, Stanford University School of Medicine, Palo Alto, Calif. Aided in part by grants from the U. S. Public Health Service. Received for publication March 5, 1964. *R. Samuel McLaughlin Fellow, University of Toronto, Toronto, Canada.
314
Vol. 48. No. 2 August, 1964
PROPHYLACTIC USE OF FROZEN PLASMA
315
SURGICAL MANAGEMENT
Preoperative coagulation studies have not been a routine at this center. Heparin (3 mg./Kg.) was administered prior to bypass with additional incre ments during prolonged runs. No hemodilution was used, but mannitol was added to the priming blood in alternate patients as part of another study. At the termination of bypass, neutralization of heparin with protamine (3 mg./Kg.) was followed by a heparin titration to ensure adequate dosage.1 Careful surgical hemostasis was obtained while fresh frozen plasma, 1 unit (250 c.c.) for children and 2 units (500 c.c.) for adults, was administered immediately on thawing over a period of 30 minutes. Chest drainage was recorded over arbitrary intervals. The first period ran till 7 :00 A.M. of the first postoperative day, a period of 12 to 18 hours, and in 24 hour periods subsequently. RESULTS
For analysis the group was divided into children under 15 years of age and adults (Tables I and I I ) . In the children (Table I ) , the mean age and perfusion time in the group receiving F F P was lower than the controls, 5y2 years and 1 hour and 5 min. as against 8V2 years and IV2 hours. The difference is not significant. There was no difference in the postoperative blood loss between these groups. TABLE I. POSTOPERATIVE BLEEDING IN 13 CHILDREN AFTER EXTRACORPOREAL CIRCULATION
PERFUSION TIME
PERFUSION TEMP. ( ° C.)
CHEST DRAINAGE UNTIL 7 : 0 0 A.M. (C.C.)
CHEST DRAINAGE FIRST 24 HR. (C.C.)
FFP
NO.
AGE
Yes
6
5.5* 3tol2t
1 hr. 5 min. 35 min. to 1 hr. 50 min.
29 27 to 32
400 210 to 900
120 25 to 335
Not
7
8.5* 2tol5t
1 hr. 30 min. 35 min. to 2 % hr.
27 19.5 to 33
470 225 to 900
135 10 to 335
•Mean value. tRange. JOne patient reoperated upon—technical factor.
TABLE I I . POSTOPERATIVE BLEEDING IN 40 ADULTS AFTER EXTRACORPOREAL CIRCULATION CHEST DRAINAGE FFP
NO.
Yes
15
Not
AGE
PERFUSION TIME
42* 1 hr. 27 min. 20 to 581 30 min. to 2 hr. 45 min.
PERFUSION TEMP. ( ° C.)
UNTIL 7 :00 A.M. (C.C.)
28 25 to 33
1,040 400 to 1,925
29 1,055 43* 2 hr. 11 min. 400 to 3,950 22 to 33 18 to 631 25 min. to 5 hr. 35 min. •Mean value. tRange. ÎThree patients were re-explored—technical factor. 25
1ST 24 HR. 1 2ND 24 HR. (c.c.) | (c.c.) 400 100 90 to 900 25 to 300 500 75 to 3,700
290 10 to 950
316
TRIMBLE E T AL.
J. Thoracic and Cardiovas. Surg.
The findings were similar in the adult group (Table I I ) . Although the perfusion times in the control group were longer, on the average 2 hours and 11 min. as against 1 hour and 27 min., there was no reduction in bleeding in the group receiving F F P . Four patients in the group of 53 were re-explored for excessive bleeding (Tables I and I I ) . In each case the causative vessel was successfully ligated. DISCUSSION
This study effectively demonstrates the lack of response to F F P in these patients. This is not surprising. Extracorporeal circulation can, but need not necessarily, produce a wide range of deficiencies in the various factors of the clotting mechanism. 1 ' 2 If no defect is produced, little beneficial result could be expected from the use of F F P . The defects in the plasma components that have been reported are often complex and, in many instances, do not delay hemostasis.2 If any defects were present in this group of patients, they did not appear clinically important, and the routine use of F F P in this dosage was unnecessary or ineffective in correcting them. CONCLUSION
The routine use of fresh frozen plasma to reduce bleeding after extra corporeal circulation is ineffective and not recommended. If blood losses be come excessive, hematological investigation should be followed by appropriate specific treatment. SUMMARY
While hemorrhagic diatheses have become an uncommon complication of extracorporeal circulation, postoperative blood losses in these patients are significant. To assess the effect of fresh frozen plasma in reducing these losses, 53 consecutive patients received F F P in the post-perfusion period. There was no decrease in chest drainage in this group. The routine use of F F P postoperatively is not recommended. REFERENCES 1. Perkins, H. A., Osborn, J . J., and Gerbode, F . : The Management of Abnormal Bleeding Following Extracorporeal Circulation, Ann. I n t . Med. 5 1 : 658, 1959. 2. Kendall, A. G., and Lowenstein, L.: Alterations in Blood Coagulation and Hemostasis During Extracorporeal Circulation, Canad. M. A. J . 87: 786, 1962. 3. Grove-Rasmussen, M., Lesses, M. F . , and Anstall, H . B . : Transfusion Therapy, New England J . Med. 264: 1034, 1961. 4. Osborn, J. J., Bramson, M. L., and Gerbode, F . : A Rotating Disc Blood Oxygenator and I n t e g r a l H e a t Exchanger of Improved Inherent Efficiency, J . THORACIC & CARDIOV. SURG. 39: 427,
1960.
5. Hill, C. B.: Principles of Medical Statistics, The Lancet, 1955.
E
bleeding after extracorporeal circulation was a catastrophic event during the pioneering years in this field. The infrequent appearance of this syndrome in the present era is a tribute to the efforts of hematologists and surgeons in defining and treating the etiologic factors. 1 ' 2 In spite of these ad vances, routine postoperative blood losses in these patients are significant and occasional bleeding problems do arise. Fresh frozen plasma ( F P P ) , equivalent to fresh blood as a source of the plasma clotting factors I I and V to X, has been used in the treatment of a number of hemorrhagic diatheses, including hemophilia.3 This study was carried out to establish whether the routine use of fresh frozen plasma would measurably decrease postoperative bleeding after open-heart surgery. Because of the great variation in bleeding and in operative procedure, from one patient to another, the study was carried out by "blind" random sampling in a consecutive series of patients. XCESSIVE
PLAN OF THE STUDY
Fifty-three consecutive patients, with a variety of congenital and acquired heart defects, were included in the study. Each had an open-heart operation with the use of a large-disc oxygenator. 4 The patients were divided into two groups by reference to a list of random numbers. 5 The random allocation of each patient to one group or the other was carried out before the patient's entry into the hospital, and without knowledge of the detailed diagnosis. The surgeons and attending staff did not know in which group any patient fell. The treatment of the two groups was therefore similar except that one group received fresh frozen plasma as described below. From the Department of Cardiovascular Surgery, Presbyterian Medical Center, The Insti tute of Medical Sciences, San Francisco. Calif., and the Department of Surgery, Stanford University School of Medicine, Palo Alto, Calif. Aided in part by grants from the U. S. Public Health Service. Received for publication March 5, 1964. *R. Samuel McLaughlin Fellow, University of Toronto, Toronto, Canada.
314
Vol. 48. No. 2 August, 1964
PROPHYLACTIC USE OF FROZEN PLASMA
315
SURGICAL MANAGEMENT
Preoperative coagulation studies have not been a routine at this center. Heparin (3 mg./Kg.) was administered prior to bypass with additional incre ments during prolonged runs. No hemodilution was used, but mannitol was added to the priming blood in alternate patients as part of another study. At the termination of bypass, neutralization of heparin with protamine (3 mg./Kg.) was followed by a heparin titration to ensure adequate dosage.1 Careful surgical hemostasis was obtained while fresh frozen plasma, 1 unit (250 c.c.) for children and 2 units (500 c.c.) for adults, was administered immediately on thawing over a period of 30 minutes. Chest drainage was recorded over arbitrary intervals. The first period ran till 7 :00 A.M. of the first postoperative day, a period of 12 to 18 hours, and in 24 hour periods subsequently. RESULTS
For analysis the group was divided into children under 15 years of age and adults (Tables I and I I ) . In the children (Table I ) , the mean age and perfusion time in the group receiving F F P was lower than the controls, 5y2 years and 1 hour and 5 min. as against 8V2 years and IV2 hours. The difference is not significant. There was no difference in the postoperative blood loss between these groups. TABLE I. POSTOPERATIVE BLEEDING IN 13 CHILDREN AFTER EXTRACORPOREAL CIRCULATION
PERFUSION TIME
PERFUSION TEMP. ( ° C.)
CHEST DRAINAGE UNTIL 7 : 0 0 A.M. (C.C.)
CHEST DRAINAGE FIRST 24 HR. (C.C.)
FFP
NO.
AGE
Yes
6
5.5* 3tol2t
1 hr. 5 min. 35 min. to 1 hr. 50 min.
29 27 to 32
400 210 to 900
120 25 to 335
Not
7
8.5* 2tol5t
1 hr. 30 min. 35 min. to 2 % hr.
27 19.5 to 33
470 225 to 900
135 10 to 335
•Mean value. tRange. JOne patient reoperated upon—technical factor.
TABLE I I . POSTOPERATIVE BLEEDING IN 40 ADULTS AFTER EXTRACORPOREAL CIRCULATION CHEST DRAINAGE FFP
NO.
Yes
15
Not
AGE
PERFUSION TIME
42* 1 hr. 27 min. 20 to 581 30 min. to 2 hr. 45 min.
PERFUSION TEMP. ( ° C.)
UNTIL 7 :00 A.M. (C.C.)
28 25 to 33
1,040 400 to 1,925
29 1,055 43* 2 hr. 11 min. 400 to 3,950 22 to 33 18 to 631 25 min. to 5 hr. 35 min. •Mean value. tRange. ÎThree patients were re-explored—technical factor. 25
1ST 24 HR. 1 2ND 24 HR. (c.c.) | (c.c.) 400 100 90 to 900 25 to 300 500 75 to 3,700
290 10 to 950
316
TRIMBLE E T AL.
J. Thoracic and Cardiovas. Surg.
The findings were similar in the adult group (Table I I ) . Although the perfusion times in the control group were longer, on the average 2 hours and 11 min. as against 1 hour and 27 min., there was no reduction in bleeding in the group receiving F F P . Four patients in the group of 53 were re-explored for excessive bleeding (Tables I and I I ) . In each case the causative vessel was successfully ligated. DISCUSSION
This study effectively demonstrates the lack of response to F F P in these patients. This is not surprising. Extracorporeal circulation can, but need not necessarily, produce a wide range of deficiencies in the various factors of the clotting mechanism. 1 ' 2 If no defect is produced, little beneficial result could be expected from the use of F F P . The defects in the plasma components that have been reported are often complex and, in many instances, do not delay hemostasis.2 If any defects were present in this group of patients, they did not appear clinically important, and the routine use of F F P in this dosage was unnecessary or ineffective in correcting them. CONCLUSION
The routine use of fresh frozen plasma to reduce bleeding after extra corporeal circulation is ineffective and not recommended. If blood losses be come excessive, hematological investigation should be followed by appropriate specific treatment. SUMMARY
While hemorrhagic diatheses have become an uncommon complication of extracorporeal circulation, postoperative blood losses in these patients are significant. To assess the effect of fresh frozen plasma in reducing these losses, 53 consecutive patients received F F P in the post-perfusion period. There was no decrease in chest drainage in this group. The routine use of F F P postoperatively is not recommended. REFERENCES 1. Perkins, H. A., Osborn, J . J., and Gerbode, F . : The Management of Abnormal Bleeding Following Extracorporeal Circulation, Ann. I n t . Med. 5 1 : 658, 1959. 2. Kendall, A. G., and Lowenstein, L.: Alterations in Blood Coagulation and Hemostasis During Extracorporeal Circulation, Canad. M. A. J . 87: 786, 1962. 3. Grove-Rasmussen, M., Lesses, M. F . , and Anstall, H . B . : Transfusion Therapy, New England J . Med. 264: 1034, 1961. 4. Osborn, J. J., Bramson, M. L., and Gerbode, F . : A Rotating Disc Blood Oxygenator and I n t e g r a l H e a t Exchanger of Improved Inherent Efficiency, J . THORACIC & CARDIOV. SURG. 39: 427,
1960.
5. Hill, C. B.: Principles of Medical Statistics, The Lancet, 1955.