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The effect of desmopressin acetate (DDAVP) on postoperative blood loss after cardiac operations in children
J THORAC
CARDIOVASC SURG 1989;98:217-9
The effect of desmopressin acetate (DDAVP) on postoperative blood loss after cardiac operations in children We investigated the effect of an intraoperative desmopressin acetate inf~ion on blood loss after cardiac operation in 60 children, by using a prospective, randomized, double-blind trial. Thirty patients received a desmopressin dose of 0.3 J.Lg/kg intraveno~ly over 15 minutes at the conclusion of cardiac bypass, and 30 received a saline placebo. The two groups were comparable with respect to age, sex, cardiac lesion, presence of cyanosis, and prevalence of Down's syndrome. Results showed no significant difference in postoperative blood loss between the two groups (30.5 ± 37.9 ml/kg in the placebo group versus 40.0 ± 33.1 ml/kg in the desmopressin group). Postoperative bleeding time, total urine output, postinfusion hemodynamics, and postoperative coagulation studies did not differ significantly between the two groups. We conclude that postbypass desmopressin inf~ion does not reduce blood loss in children undergoing cardiac operations.
M. D. Seear, MD, L. D. Wadsworth, MD, P. C. Rogers, MD, S. Sheps, MD, and P. G. Ashmore, MD, Vancouver, British Columbia, Canada
Rtoperative blood loss remains a significant problem after cardiac bypass operations. Apart from surgical trauma, the major cause of bleeding is an acquired coagulopathy produced by extracorporeal circuits.' This is the result of a number of defects including thrombocytopenia, thrombocytopathy, fibrinolysis, un neutralized heparin, and reduced clotting factors. 2 Desmopressin acetate is a synthetic analog of arginine vasopressin. It has a specific antidiuretic hormone action (VI receptor) with almost no smooth muscle effects, for example vasoconstriction and uterine contraction (V 2 receptorj.v' Transnasal or intravenous administration of desmopressin also causes a rapid twofold to threefold increase in plasma levels of all components of the factor VIII molecule.' It has been used successfully to control bleeding in a range of coagulopathies including moderate hemophilia A,5 von Willebrand's disease,' platelet
From the Departments of Pediatrics,Surgery. and Pathology, University of British Columbia. Vancouver. British Columbia, Canada. Supported in part by a grant from the British Columbia Health Care Research Foundation. Received for publication June 29. 1988. Accepted for publication Nov. 22, 1988. Address for reprints: Dr. M. Seear, Intensive Care Unit, British Columbia's Children's Hospital, 4480 Oak St., Vancouver, British Columbia V6H 3V4, Canada.
disorders," and uremia.' Desmopressin has also been used in patients having major operations.v? Salzman and associates" have suggested that desmopressin causes a marked decrease in blood loss after cardiac operations in adults. We investigated this possible effect in children by using a double-blind, randomized, prospective study of desmopressin versus placebo in 60 patients undergoing cardiac bypass operations. Methods The study was conducted in the Intensive Care Unit of British Columbia's Children's Hospital. All operations were performed by the same two cardiac surgeons. Postoperative management was provided by three pediatric intensivists. Ethical approval was obtained from the clinical screening committee of the University of British Columbia. Sixty consecutive patients admitted for cardiac operations were enrolled. All legal guardians were aware of the study and gave informed consent. There were no exclusion criteria and no patients refused to enter the study. We used a desmopressin dose of 0.3 /Lg/kg because it has been shown to produce a maximal rise in factor VIII coagulant and von Willebrand factor activity.' It is a commonly accepted dose for the treatment of hemophilia AS and is also the dose used in the original paper by Salzman and associates.' Using a system of sealed envelopes, we randomly allocated patients to one of two treatment groups: On conclusion of cardiac bypass, 30 received a desmopressin dose of 0.3 /Lg/kg in a saline intravenous infusion over 15 minutes, and 30 received an identical saline placebo. Only the pharmacist was aware of the patient's treatment group. Systemic arterial
217
The Journal of Thoracic and Cardiovascular
2 1 8 Seear et al.
Surgery
Table
Table I. Patient characteristics
Bypass time (min) Heparin (mg/kg) Protamine (rug/kg) Age (mo) Weight (kg) Male/female Down's syndrome Cyanosed Profound hypothermia Repair ASD (primary and secondary) VSD Tetralogy Mustard Fontan AV canal Valvotomy Artificial valves PA conduit Repeat thoracotomy Died
Desmopressin (n = 30)
Placebo (n = 30)
96.4 ± 37.4 2.7 ± 3.0 3.3 ± 4.2 45.9 ± 50J 14.9 ± 13.5 17/13 3 16 10
93.7 ± 47.1 3.1 ± 2.7 3.8 ± 3.1 64.2 ± 60.1 20.1 ± 16.4 18/12 3 14 11
7
6
4 8 3 0 1 2 0 5 I 0
4 6 0 3 2 I 4 4 I 2
ASD. Atrial septal defect: YSD. ventricular septal defect: AY. atrioventricular: PA. pulmonary artery.
Table II. Preoperative hematology Desmopressin (n = 30)
Bleeding time (min) Prothrombin time (sec) Partial thromboplastin time (sec) Fibrinogen (gm/L) Platelets (XlO'/L) Hematocrit Thrombin time (sec)
6.1 ± 2.7 11.0 ± 0.6 32.6 ± 4.8 2.97 290.0 0.355 23.0
± 0.88 ± 82.0 ± 0.076
± 13.0
Placebo (n = 30)
7.5 ± 4.0 11.1 ± 0.5 36.2 ± 5.3 2.29 267.0 0.374 24.5
± 0.56 ± 88.0 ± 0.047 ± 14.0
Results of preoperative coagulation studies: No statistically significant differences were detected between the groups (30 patients in each group. unpaired ( test).
pressure, pulmonary arterial pressure, right atrial pressure, and heart rate were monitored during the infusion and for 15 minutes afterward. Blood samples were drawn for coagulation studies before the operation and then immediately before and 3 hours after desmopressin or placebo infusion. Bleeding time was determined by the simplate technique before the operation and 3 hours after infusion. Hourly blood loss was measured for 24 hours starting from the time of desmopressin or placebo administration. It was calculated by weighing sponges and measuring the volume of chest tube drainage. Urine output was also measured over the same period. Both variables were expressed in milliliters per kilgram because of the wide variation in weights between patients. Statistical analysis was by unpaired t test for comparison of means of parametric data. The individual effects of several
m.
Postoperative hematology (n = 30)
Placebo in = 30)
11.8 ± 5.1 12.2 ± 1.0 40.6 ± 16.4
12.1 ± 5.5 12.1 ± 0.7 41.2 ± 14.7
Desmopressin
Bleeding time (min) Prothrombin time (sec) Partial thromboplastin time (sec) Fibrinogen (grn/L) Platelets (X 10' /L) Hematocrit Thrombin time (sec)
2.03 168.0 0.357 43.0
± 0.50
± 55.0 ± 0.017 ± 18.0
2.02 162.0 0.360 45.8
± 0.36 ± 76.0 ± 0.049 ± 18.0
Results of postoperative coagulation studies: No statistically significant differences were detected between the groups (30 patients in each group. unpaired ( test).
variables on blood loss were assessed by analysis of covariance. The usual level of significance was taken as p = 0.05 except for multiple t tests of postoperative blood loss, in which the level of significance was reduced to p = 0.01.
Results
The characteristics of the two patient groups are shown in Table I. Apart from differences in the type of procedure performed, the groups were comparable with respect to age, sex, presence of cyanosis, proportion with Down's syndrome, duration of bypass, and amounts of heparin and protamine given. Two patients from the placebo group died in the postoperative period of heart failure. There were no deaths in the desmopressin group. Four children had a postoperative blood loss well above 2 standard deviations from the mean. Two of these (one from each treatment group) required a repeat thoracotomy, and the other two (one from each group) were treated conservatively with blood replacement. Table II shows the preoperative coagulation results of the two groups. There were no significant differences between them. The postoperative coagulation studies (Table III) demonstrate the prolonged bleeding time, prolonged thrombin time, and decreased platelet and fibrinogen levels typical of the coagulopathy associated with cardiac bypass operations. Again, there were no significant differences between the two groups. Postoperative blood loss and urine output are presented in Table IV. In each 6-hour block there was a greater blood loss in the desmopressin-treated group. The overall 24-hour blood loss was almost 30% higher than in the placebo group. Because of the large variance, none of these differences achieved statistical significance. Total urine output for the study period did not differ between the two groups (55.0 ± 22.3 ml/kg, desmopressin group; 48.4 ± 19.5 ml/kg, placebo group). During the infusion period, there were no differences in heart rate, right atrial pressure, or pulmonary arterial and systemic arterial blood pressures between the groups.
Volume 98 Number 2 August 1989
Desmopressin acetate in children
2 19
Table IV. Results Desmopressin
Blood loss (rnl/kg) 0-6 hr 6-12 hr 12-18 hr 18-24 hr 24 hr Urine output (rnl/kg) 24 hr
27.2 5.4 4.3 3.1 40.0 55.0
± ± ± ± ± ±
30.3 4.4 3.2 2.7 33.1 22.3
Placebo
p Value
± ± ± ± ± ±
0.20 0.31 0.05 0.02 0.15 0.11
20.7 4.7 3.1 2.0 30.5 48.4
29.5 6.4 2.7 1.6
37.9 19.5
Postoperative blood loss and urine output: No statistically significant differences were detected (30 patients each group, multiple unpaired I tests, level of significance
p = 0.01).
Discussion Much interest was aroused by the report of Salzman and associates' that desmopressin caused a 40% decrease in 24-hour blood loss after cardiac operations (2210 ± 1415 ml, placebo group; 1317 ± 486 ml, desmopressin group). Our study failed to demonstrate this difference. In fact, the desmopressin-treated group had almost 30% greater blood loss than the placebo group (40.0 ± 33.1 nils/kg versus 30.5 ± 37.9 ml/kg), Our study design was similar to Salzman's, but the study population was quite different: The age range was much lower, the majority had congenital heart defects, 50% were cyanosed, and 10% had Down's syndrome. These factors do not readily explain the difference between our results and Salzman's. Any effect that Down's syndrome or cyanosis may have on coagulation was minimized by randomization, since both variables were distributed equally between the treatment groups. By analysis of covariance for total bypass time, age, heparin dose, and protamine dose, only bypass time was strongly predictive of postoperative blood loss. This variable was equally distributed between the groups. The possibility that desmopressin has different actions in adults and children seems unlikely, since desmopressin has been used effectively in pediatric coagulopathies' and has also been shown to increase factor VIII subunits in patients of all ages.' Desmopressin causes a threefold to fourfold rise in tissue plasminogen activator.' This could have produced a fibrinolytic state that might provide an explanation for the increased blood loss found in our desmopressin group. Two other recent studies have also found that desmopressin does not cause a decrease in blood loss after cardiac operations. Rocha and associates" found no effect in 60 adults, and Hackman and colleagues (manuscript in preparation) found no effect in 150 adults. We found no adverse side effects from the use of
desmopressin and believe that it is a safe drug to use before operations in children with a wide range of coagulation disorders. However, we found no hemostatic advantage to its use in normal children undergoing cardiac operations. REFERENCES I. Mammen E, Koets M, Washington B, et al. Hemostasis
2.
3.
4. 5. 6.
7. 8.
9.
10.
changes during cardiopulmonary bypass surgery. Semin Thromb Hemost 1985; II :281-92. Bick R. Hemostasis defects associated with cardiac surgery, prosthetic devices and other extracorporeal circuits. Semin Thromb Hemost 1985; II :249-80. Mannucci P. Desmopressin (DDAVP) for treatment of disordersof hemostasis. Prog Hemost Thromb 1986;8: 1945. Kobrinsky N, Israels E, Gerrard J, et al. Shortening of bleeding time by l-deamino-Svo-arginine vasopressin in various bleeding disorders. Lancet 1984; I:1145-8. Warrier A. Lusher J. DDAVP: a useful alterntive to blood components in moderate hemophilia A and von Willebrand disease. J Pediatr 1983;102:228-33. Kentro T, Lottenberg R, Kitchens C. Clinical efficacy of desmopressin acetate for hemostatic control in patients with primary platelet disorders undergoingsurgery. Am J Hematol 1987;24:215-9. Mannucci P, Remuzzi G, Pusineri F, et al. Deamino8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med 1983;308:8-12. Salzman E, Weinstein M, Weintraub R, et al. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery: a double blind randomized trial. N Engl J Med 1986;314: 1402-6. Kobrinsky N, Letts R, Patel L, et al. I-Deamino8-D-arginine vasopressin (Desmopressin) decreases operative blood loss in patients having Harrington rod spinal fusion surgery. Ann Intern Med 1987;107:446-50. Rocha E, Llorens R, Paramo J, et al. Does desmopressin acetate reduced blood loss after cardiopulmonary bypass surgery? [Abstract]. Thromb Haemost 1987;1:517.
CARDIOVASC SURG 1989;98:217-9
The effect of desmopressin acetate (DDAVP) on postoperative blood loss after cardiac operations in children We investigated the effect of an intraoperative desmopressin acetate inf~ion on blood loss after cardiac operation in 60 children, by using a prospective, randomized, double-blind trial. Thirty patients received a desmopressin dose of 0.3 J.Lg/kg intraveno~ly over 15 minutes at the conclusion of cardiac bypass, and 30 received a saline placebo. The two groups were comparable with respect to age, sex, cardiac lesion, presence of cyanosis, and prevalence of Down's syndrome. Results showed no significant difference in postoperative blood loss between the two groups (30.5 ± 37.9 ml/kg in the placebo group versus 40.0 ± 33.1 ml/kg in the desmopressin group). Postoperative bleeding time, total urine output, postinfusion hemodynamics, and postoperative coagulation studies did not differ significantly between the two groups. We conclude that postbypass desmopressin inf~ion does not reduce blood loss in children undergoing cardiac operations.
M. D. Seear, MD, L. D. Wadsworth, MD, P. C. Rogers, MD, S. Sheps, MD, and P. G. Ashmore, MD, Vancouver, British Columbia, Canada
Rtoperative blood loss remains a significant problem after cardiac bypass operations. Apart from surgical trauma, the major cause of bleeding is an acquired coagulopathy produced by extracorporeal circuits.' This is the result of a number of defects including thrombocytopenia, thrombocytopathy, fibrinolysis, un neutralized heparin, and reduced clotting factors. 2 Desmopressin acetate is a synthetic analog of arginine vasopressin. It has a specific antidiuretic hormone action (VI receptor) with almost no smooth muscle effects, for example vasoconstriction and uterine contraction (V 2 receptorj.v' Transnasal or intravenous administration of desmopressin also causes a rapid twofold to threefold increase in plasma levels of all components of the factor VIII molecule.' It has been used successfully to control bleeding in a range of coagulopathies including moderate hemophilia A,5 von Willebrand's disease,' platelet
From the Departments of Pediatrics,Surgery. and Pathology, University of British Columbia. Vancouver. British Columbia, Canada. Supported in part by a grant from the British Columbia Health Care Research Foundation. Received for publication June 29. 1988. Accepted for publication Nov. 22, 1988. Address for reprints: Dr. M. Seear, Intensive Care Unit, British Columbia's Children's Hospital, 4480 Oak St., Vancouver, British Columbia V6H 3V4, Canada.
disorders," and uremia.' Desmopressin has also been used in patients having major operations.v? Salzman and associates" have suggested that desmopressin causes a marked decrease in blood loss after cardiac operations in adults. We investigated this possible effect in children by using a double-blind, randomized, prospective study of desmopressin versus placebo in 60 patients undergoing cardiac bypass operations. Methods The study was conducted in the Intensive Care Unit of British Columbia's Children's Hospital. All operations were performed by the same two cardiac surgeons. Postoperative management was provided by three pediatric intensivists. Ethical approval was obtained from the clinical screening committee of the University of British Columbia. Sixty consecutive patients admitted for cardiac operations were enrolled. All legal guardians were aware of the study and gave informed consent. There were no exclusion criteria and no patients refused to enter the study. We used a desmopressin dose of 0.3 /Lg/kg because it has been shown to produce a maximal rise in factor VIII coagulant and von Willebrand factor activity.' It is a commonly accepted dose for the treatment of hemophilia AS and is also the dose used in the original paper by Salzman and associates.' Using a system of sealed envelopes, we randomly allocated patients to one of two treatment groups: On conclusion of cardiac bypass, 30 received a desmopressin dose of 0.3 /Lg/kg in a saline intravenous infusion over 15 minutes, and 30 received an identical saline placebo. Only the pharmacist was aware of the patient's treatment group. Systemic arterial
217
The Journal of Thoracic and Cardiovascular
2 1 8 Seear et al.
Surgery
Table
Table I. Patient characteristics
Bypass time (min) Heparin (mg/kg) Protamine (rug/kg) Age (mo) Weight (kg) Male/female Down's syndrome Cyanosed Profound hypothermia Repair ASD (primary and secondary) VSD Tetralogy Mustard Fontan AV canal Valvotomy Artificial valves PA conduit Repeat thoracotomy Died
Desmopressin (n = 30)
Placebo (n = 30)
96.4 ± 37.4 2.7 ± 3.0 3.3 ± 4.2 45.9 ± 50J 14.9 ± 13.5 17/13 3 16 10
93.7 ± 47.1 3.1 ± 2.7 3.8 ± 3.1 64.2 ± 60.1 20.1 ± 16.4 18/12 3 14 11
7
6
4 8 3 0 1 2 0 5 I 0
4 6 0 3 2 I 4 4 I 2
ASD. Atrial septal defect: YSD. ventricular septal defect: AY. atrioventricular: PA. pulmonary artery.
Table II. Preoperative hematology Desmopressin (n = 30)
Bleeding time (min) Prothrombin time (sec) Partial thromboplastin time (sec) Fibrinogen (gm/L) Platelets (XlO'/L) Hematocrit Thrombin time (sec)
6.1 ± 2.7 11.0 ± 0.6 32.6 ± 4.8 2.97 290.0 0.355 23.0
± 0.88 ± 82.0 ± 0.076
± 13.0
Placebo (n = 30)
7.5 ± 4.0 11.1 ± 0.5 36.2 ± 5.3 2.29 267.0 0.374 24.5
± 0.56 ± 88.0 ± 0.047 ± 14.0
Results of preoperative coagulation studies: No statistically significant differences were detected between the groups (30 patients in each group. unpaired ( test).
pressure, pulmonary arterial pressure, right atrial pressure, and heart rate were monitored during the infusion and for 15 minutes afterward. Blood samples were drawn for coagulation studies before the operation and then immediately before and 3 hours after desmopressin or placebo infusion. Bleeding time was determined by the simplate technique before the operation and 3 hours after infusion. Hourly blood loss was measured for 24 hours starting from the time of desmopressin or placebo administration. It was calculated by weighing sponges and measuring the volume of chest tube drainage. Urine output was also measured over the same period. Both variables were expressed in milliliters per kilgram because of the wide variation in weights between patients. Statistical analysis was by unpaired t test for comparison of means of parametric data. The individual effects of several
m.
Postoperative hematology (n = 30)
Placebo in = 30)
11.8 ± 5.1 12.2 ± 1.0 40.6 ± 16.4
12.1 ± 5.5 12.1 ± 0.7 41.2 ± 14.7
Desmopressin
Bleeding time (min) Prothrombin time (sec) Partial thromboplastin time (sec) Fibrinogen (grn/L) Platelets (X 10' /L) Hematocrit Thrombin time (sec)
2.03 168.0 0.357 43.0
± 0.50
± 55.0 ± 0.017 ± 18.0
2.02 162.0 0.360 45.8
± 0.36 ± 76.0 ± 0.049 ± 18.0
Results of postoperative coagulation studies: No statistically significant differences were detected between the groups (30 patients in each group. unpaired ( test).
variables on blood loss were assessed by analysis of covariance. The usual level of significance was taken as p = 0.05 except for multiple t tests of postoperative blood loss, in which the level of significance was reduced to p = 0.01.
Results
The characteristics of the two patient groups are shown in Table I. Apart from differences in the type of procedure performed, the groups were comparable with respect to age, sex, presence of cyanosis, proportion with Down's syndrome, duration of bypass, and amounts of heparin and protamine given. Two patients from the placebo group died in the postoperative period of heart failure. There were no deaths in the desmopressin group. Four children had a postoperative blood loss well above 2 standard deviations from the mean. Two of these (one from each treatment group) required a repeat thoracotomy, and the other two (one from each group) were treated conservatively with blood replacement. Table II shows the preoperative coagulation results of the two groups. There were no significant differences between them. The postoperative coagulation studies (Table III) demonstrate the prolonged bleeding time, prolonged thrombin time, and decreased platelet and fibrinogen levels typical of the coagulopathy associated with cardiac bypass operations. Again, there were no significant differences between the two groups. Postoperative blood loss and urine output are presented in Table IV. In each 6-hour block there was a greater blood loss in the desmopressin-treated group. The overall 24-hour blood loss was almost 30% higher than in the placebo group. Because of the large variance, none of these differences achieved statistical significance. Total urine output for the study period did not differ between the two groups (55.0 ± 22.3 ml/kg, desmopressin group; 48.4 ± 19.5 ml/kg, placebo group). During the infusion period, there were no differences in heart rate, right atrial pressure, or pulmonary arterial and systemic arterial blood pressures between the groups.
Volume 98 Number 2 August 1989
Desmopressin acetate in children
2 19
Table IV. Results Desmopressin
Blood loss (rnl/kg) 0-6 hr 6-12 hr 12-18 hr 18-24 hr 24 hr Urine output (rnl/kg) 24 hr
27.2 5.4 4.3 3.1 40.0 55.0
± ± ± ± ± ±
30.3 4.4 3.2 2.7 33.1 22.3
Placebo
p Value
± ± ± ± ± ±
0.20 0.31 0.05 0.02 0.15 0.11
20.7 4.7 3.1 2.0 30.5 48.4
29.5 6.4 2.7 1.6
37.9 19.5
Postoperative blood loss and urine output: No statistically significant differences were detected (30 patients each group, multiple unpaired I tests, level of significance
p = 0.01).
Discussion Much interest was aroused by the report of Salzman and associates' that desmopressin caused a 40% decrease in 24-hour blood loss after cardiac operations (2210 ± 1415 ml, placebo group; 1317 ± 486 ml, desmopressin group). Our study failed to demonstrate this difference. In fact, the desmopressin-treated group had almost 30% greater blood loss than the placebo group (40.0 ± 33.1 nils/kg versus 30.5 ± 37.9 ml/kg), Our study design was similar to Salzman's, but the study population was quite different: The age range was much lower, the majority had congenital heart defects, 50% were cyanosed, and 10% had Down's syndrome. These factors do not readily explain the difference between our results and Salzman's. Any effect that Down's syndrome or cyanosis may have on coagulation was minimized by randomization, since both variables were distributed equally between the treatment groups. By analysis of covariance for total bypass time, age, heparin dose, and protamine dose, only bypass time was strongly predictive of postoperative blood loss. This variable was equally distributed between the groups. The possibility that desmopressin has different actions in adults and children seems unlikely, since desmopressin has been used effectively in pediatric coagulopathies' and has also been shown to increase factor VIII subunits in patients of all ages.' Desmopressin causes a threefold to fourfold rise in tissue plasminogen activator.' This could have produced a fibrinolytic state that might provide an explanation for the increased blood loss found in our desmopressin group. Two other recent studies have also found that desmopressin does not cause a decrease in blood loss after cardiac operations. Rocha and associates" found no effect in 60 adults, and Hackman and colleagues (manuscript in preparation) found no effect in 150 adults. We found no adverse side effects from the use of
desmopressin and believe that it is a safe drug to use before operations in children with a wide range of coagulation disorders. However, we found no hemostatic advantage to its use in normal children undergoing cardiac operations. REFERENCES I. Mammen E, Koets M, Washington B, et al. Hemostasis
2.
3.
4. 5. 6.
7. 8.
9.
10.
changes during cardiopulmonary bypass surgery. Semin Thromb Hemost 1985; II :281-92. Bick R. Hemostasis defects associated with cardiac surgery, prosthetic devices and other extracorporeal circuits. Semin Thromb Hemost 1985; II :249-80. Mannucci P. Desmopressin (DDAVP) for treatment of disordersof hemostasis. Prog Hemost Thromb 1986;8: 1945. Kobrinsky N, Israels E, Gerrard J, et al. Shortening of bleeding time by l-deamino-Svo-arginine vasopressin in various bleeding disorders. Lancet 1984; I:1145-8. Warrier A. Lusher J. DDAVP: a useful alterntive to blood components in moderate hemophilia A and von Willebrand disease. J Pediatr 1983;102:228-33. Kentro T, Lottenberg R, Kitchens C. Clinical efficacy of desmopressin acetate for hemostatic control in patients with primary platelet disorders undergoingsurgery. Am J Hematol 1987;24:215-9. Mannucci P, Remuzzi G, Pusineri F, et al. Deamino8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med 1983;308:8-12. Salzman E, Weinstein M, Weintraub R, et al. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery: a double blind randomized trial. N Engl J Med 1986;314: 1402-6. Kobrinsky N, Letts R, Patel L, et al. I-Deamino8-D-arginine vasopressin (Desmopressin) decreases operative blood loss in patients having Harrington rod spinal fusion surgery. Ann Intern Med 1987;107:446-50. Rocha E, Llorens R, Paramo J, et al. Does desmopressin acetate reduced blood loss after cardiopulmonary bypass surgery? [Abstract]. Thromb Haemost 1987;1:517.