Effect Of Desmopressin Research Articles

The role of desmopressin in reducing blood loss during lumbar fusions

The effectiveness of desmopressin (1-desamino-8-D-arginine vasopressin) in reducing intraoperative blood loss during lumbar fusions was investigated in 42 patients (52 operations) and compared with a control group of 55 patients (63 operations). The mean hemoglobin and hematocrit levels on admission and discharge were identical for both groups. Patients receiving desmopressin required less than one-half the number of autologous transfusions than the control group. Desmopressin was effective in reducing blood loss in operations in which intraoperative bleeding was greater than 1,000 milliliters, but it is probably not necessary for anticipated losses less than this amount. It may have a role in operations performed on short notice when autologous blood is usually unavailable.

Blood loss and safety with desmopressin or placebo during aorto-iliac graft surgery

In a double blind, placebo controlled study in 50 patients undergoing aorto-iliac graft surgery, we studied the effects of desmopressin given prior to surgery on blood loss and blood transfusion requirements. Desmopressin reduced the number of patients with clinically significant bleeding. Blood loss volumes and transfusion requirements were lower in the desmopressin group, but this could not be verified statistically. Even if our study population has a high incidence of generalised arteriosclerotic disease, there were no clinical manifestations of venous thromboembolism, no increase of graft occlusions and no myocardial infarction during the operative or early postoperative period. Desmopressin may be used in patients with excessive peroperative bleeding or a prolonged preoperative bleeding time. In patients where desmopressin is considered to be haemostatically efficacious, it may be used with a maintained margin of safety.

Effect of desmopressin on vein graft patency in a microvascular model

Desmopressin acetate decreases blood loss after cardiac surgery by activating platelets. We studied whether this effect was detrimental to small-caliber vein grafts in rats. Thirty minutes before femoral artery grafting with 0.75-mm-diameter reverse autogenous saphenous vein grafts, 20 rats received desmopressin acetate intravenously at 1.0 micrograms/kg over 10 minutes, and 20 control rats received normal saline intravenously over 10 minutes. In each group, 10 rats received a 6-mm-long graft and 10 an 18-mm-long graft. Graft patency was evaluated at 20 minutes, 24 hours, and 30 days. Intimal thickening was assessed by light and scanning electron microscopy. At 30 days, 9 short grafts and 8 long grafts in the desmopressin-treated group were patent, whereas only 8 short control grafts and only 6 long control grafts were patent. Intimal thickening and platelet deposition were the same in both groups. These data show no detrimental effects of desmopressin acetate on saphenous vein graft patency.

The effect of desmopressin on massive gastrointestinal bleeding in hereditary telangiectasia unresponsive to treatment with cryoprecipitate

The effect of desmopressin on massive gastrointestinal bleeding in hereditary telangiectasia unresponsive to treatment with cryoprecipitate

The Effect of Desmopressin on Massive Gastrointestinal Bleeding in Hereditary Telangiectasia Unresponsive to Treatment With Cryoprecipitate

A patient with hereditary hemorrhagic telangiectasia and reduced levels of von Willebrand factor had severe recurrent gastrointestinal bleeding. Treatment with either desmopressin acetate or cryoprecipitate normalized both bleeding time and kaolin-activated partial thromboplastin time. Hematochezia (five episodes) continued, however, for a week despite daily treatment with cryoprecipitate, whereas treatment with desmopressin at the onset of three later episodes of hematochezia resulted in the prompt cessation of bleeding. After an episode of life-threatening gastrointestinal bleeding, desmopressin administration allowed a total colectomy without excessive bleeding. During the 3 years after colectomy, no further gastrointestinal bleeding occurred. In the past year, however, three episodes of severe epistaxis responded promptly to intravenous infusion of desmopressin. We conclude that desmopressin may be useful in the management of bleeding in patients with hereditary hemorrhagic telangiectasia with or without von Willebrand factor deficiency.

Desmopressin is a Potent Vasorelaxant of Aorta and Pulmonary Artery Isolated from Rabbit and Rat

Hypotension related to the intraoperative use of desmopressin acetate to improve platelet function following cardiopulmonary bypass has recently been reported. To investigate the direct vascular actions of this drug as a potential mechanism of its induced hypotension, cumulative, dose-dependent (3.7 X 10(-10) to 1.2 X 10(-7) M) effects of desmopressin were studied in isolated phenylephrine precontracted rings of rat and rabbit thoracic aorta and rabbit pulmonary artery. Desmopressin was a potent vasodilator of all vessel types studied with significant (P less than 0.05) vasodilation beginning at 7.5 X 10(-9) M. Vascular relaxation of all vessels was greater when the vascular endothelium was intact (P less than 0.05). Indomethacin potentiated (P less than 0.05) vascular relaxation in rat and rabbit aortic rings and partially inhibited (P less than 0.05) relaxation in rabbit pulmonary artery rings. Selective antagonists of vasopressin V1 (d(CH2)5-Tyr(Me)AVP, 1 X 10(-6) M) and V2 (d(CH2)5[D-Ile2,Ala-NH2(9)] AVP, 1 X 10(-6) M) receptors and of histamine H1 (diphenhydramine, 1 X 10(-5) M) and H2 (cimetidine 1 X 10(-5) M) receptors had no effect on desmopressin-induced relaxation of rat aortic rings. Chlorobutanol, the diluent in which desmopressin is supplied, was devoid of vascular effects. To study the effects of desmopressin on vascular cyclic GMP and cyclic AMP concentrations, a cultured bovine aortic smooth muscle--rat vascular smooth muscle coculture model was employed. Desmopressin (1 X 10(-7) and 1 X 10(-8) M) did not significantly alter control values of either cyclic nucleotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate

Patients who receive desmopressin acetate (dDAVP) after cardiopulmonary bypass bleed less during operation and in the first 24 hours after operation than do patients who receive a placebo. To study the mechanism of improved hemostasis in bypass patients, we examined the relationship between von Willebrand factor (vWF) and blood loss in 70 cardiopulmonary bypass patients, one-half of whom received desmopressin intraoperatively. vWF concentration and multimeric composition were analyzed before and after bypass, after drug treatment, and 24 hours after operation. Before operation, patients with valvular disease had lower percentages of vWF high-mol-wt multimers (HMWMs) than did healthy subjects or patients with coronary artery disease, but subsequent blood loss, vWF activity, and bleeding times were not related to this finding. Irrespective of drug treatment, patients who had low preoperative vWF and who had a net loss of the protein during bypass bled more after bypass than did similar patients who had a net increase of vWF during bypass. HMWMs rose to above normal levels after bypass regardless of desmopressin infusion. Differences in the concentration of vWF between desmopressin and placebo patients after receipt of the drug, although small, were better correlated with reduced blood loss than were differences in HMWM distribution. We conclude that the beneficial effect of desmopressin on hemostasis following cardiopulmonary bypass cannot be attributed to a drug-induced change in HMWM distribution but may be related to an increase in overall vWF concentration.

Changes in von Willebrand Factor During Cardiac Surgery: Effect of Desmopressin Acetate

Patients who receive desmopressin acetate (dDAVP) after cardiopulmonary bypass bleed less during operation and in the first 24 hours after operation than do patients who receive a placebo. To study the mechanism of improved hemostasis in bypass patients, we examined the relationship between von Willebrand factor (vWF) and blood loss in 70 cardiopulmonary bypass patients, one-half of whom received desmopressin intraoperatively. vWF concentration and multimeric composition were analyzed before and after bypass, after drug treatment, and 24 hours after operation. Before operation, patients with valvular disease had lower percentages of vWF high-mol-wt multimers (HMWMs) than did healthy subjects or patients with coronary artery disease, but subsequent blood loss, vWF activity, and bleeding times were not related to this finding. Irrespective of drug treatment, patients who had low preoperative vWF and who had a net loss of the protein during bypass bled more after bypass than did similar patients who had a net increase of vWF during bypass. HMWMs rose to above normal levels after bypass regardless of desmopressin infusion. Differences in the concentration of vWF between desmopressin and placebo patients after receipt of the drug, although small, were better correlated with reduced blood loss than were differences in HMWM distribution. We conclude that the beneficial effect of desmopressin on hemostasis following cardiopulmonary bypass cannot be attributed to a drug-induced change in HMWM distribution but may be related to an increase in overall vWF concentration.

Pharmacokinetics and haematological effects of desmopressin.

The pharmacokinetics and haematological effects of 1-deamino-8-D-arginine vasopressin (desmopressin, DDAVP) after intravenous, subcutaneous and intranasal administration has been studied in man. Using a sensitive, specific radioimmunoassay for DDAVP, the AUC was determined for each route of administration. It was not significantly different for the i.v. and s.c. routes. There was no effect of the route on the plasma half-life of DDAVP which ranged from 2.7 to 4.6 h. Absorption of DDAVP after intranasal (i.n.) administration was poor. Based on AUC data, bioavailability via the two s.c. methods and the i.n. route was 112%, 94% and 2%, respectively. DDAVP has a pronounced effect on coagulation and fibrinolytic parameters, causing a 4.0- (i.v.), 2.9- (s.c.), 3.1- (s.c.; 40 micrograms/ml) and 1.2- (i.n.) fold increase in factor VIII: Ag. The corresponding effect on tissue-type plasminogen activator (t-PA) was 1.9- (i.v.), 1.3- (s.c.), 2.2- (s.c.; 40 micrograms/ml) and 1.0- (i.n.) increase over the basal value. There was also a 1.4- to 1.6-fold increase in leukocyte count 4 h after s.c. and i.v. DDAVP. At plasma DDAVP levels greater than 300 pg/ml no correlation was found between the AUC and the maximum plasma DDAVP and biological response, which indicates a ceiling limit for exogenous stimulation of the coagulation and fibrinolytic systems.

Treatment of severe platelet dysfunction and hemorrhage after cardiopulmonary bypass: Reduction in blood product usage with desmopressin

Impairment of platelet function commonly occurs after cardiopulmonary bypass, and may result in substantial bleeding. Because desmopressin acetate (a synthetic analogue of vasopressin) shortens bleeding time in a variety of platelet disorders, a controlled clinical trial of intravenous desmopressin was performed in 39 patients with excessive mediastinal bleeding (greater than 100 ml/h) and a prolonged template bleeding time (greater than 10 minutes) more than 2 hours after termination of cardiopulmonary bypass. Twenty-three desmopressin recipients and 16 control patients (no desmopressin) were similar in surgical procedure, pump time, platelet count, template bleeding time and amount of bleeding before therapy (p = NS). Compared with the control group, the patients receiving desmopressin (20 micrograms; mean 0.3 micrograms/kg) utilized fewer blood products (29 +/- 19 versus 15 +/- 13 units/patient; p less than 0.05), especially platelets (12 +/- 9 versus 4 +/- 7 units/patient; p = 0.004), while achieving a similarly effective reduction in mediastinal bleeding (4.8- and 4.3-fold, p = 0.001 for both). Severe platelet dysfunction was partially corrected within 1 hour after desmopressin infusion, during which interval no blood products were administered: the template bleeding time shortened (from 17 to 12.5 minutes, p less than 0.05), whereas the platelet count remained unchanged (at 96 +/- 35 and 105 +/- 31 X 10(3)/mm3, p = NS). The plasma levels of two factor VIII components increased: procoagulant activity (VIII:C) from 0.97 +/- 0.43 to 1.52 +/- 0.74 units/ml (p less than 0.05) and von Willebrand factor (VIII:vWF) from 1.28 to 1.78 units/ml (p less than 0.05); these increases correlated with the shortening of the bleeding time (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

A pilot study; desmopressin (DDAVP) in the treatment of deep venous thrombosis

In a pilot study on 9 patients with acute deep venous thrombosis of the leg the fibrinolytic response and the possible thrombolysic effect of desmopressin (DDAVP); when given supplementary to standard heparin treatment, was examined. Six injections of 0.3-0.4 ug DDAVP/kg b.w. at 12 hours intervals were given. No serious side effects were observed. The fibrinolytic variables that followed showed that plasma levels of t-PA increased significantly and most pronounced after the first injection. Rephlebography 4–7 days after hospitalization showed partial thrombolysis in 7 out of 9 patients. The phlebographic score according to Marder was reduced from 22.7 ± 12.1 to 18.4 ± 10.1 (p = 0.018); corresponding to a thrombus size reduction of 19%. No correlation between the level of the fibrinolytic variables measured and the degree of thrombolysis in the individual patients, could be demonstrated in this small number of patients.

Venous Thrombosis Following Diagnostic Transvenous Catheterization by Percutaneous Catheter Insertion: An Evaluation of Desmopressin as a Thromboprophylactic Agent

The preventive effect of desmopressin with respect to catheter induced thrombosis was studied in a randomized double-blind trial, consisting of 30 patients undergoing percutaneous transcubital right heart catheterization. Phlebography of the catheterized arm was performed after five days. The frequency of post-catheterization thrombosis was reduced by 33 per cent, from 86 per cent in the treatment group to 53 per cent in the control group (0.1 less than p less than 0.2). This effect was restricted to minor thrombi, whereas major thrombosis could not be prevented. Patient materials such as that of the present study, may become useful in preliminary investigations of thromboprophylactic agents.

Effect of desmopressin on normal and impaired memory.

In view of the reported influence of vasopressin on the memory process of animals, trials were carried out on normal subjects and patients with memory disorders using the vasopressin analogue desmopressin. No beneficial effects could be demonstrated.

88 DESMOPRESSIN THERAPY FOR ENURESIS

To determine the effectiveness of desmopressin (DDAVP, a vasopressin analogue) for treating enuresis, we performed a double-blind crossover study at three medical centers. Subjects (N=43) ranged from 6 to 16 years old, had normal renal function and denied polyuria, polydipsia and daytime incontinence. The study encompassed four consecutive two-week periods: pre-treatment, treatment with placebo or DDAVP (40 mcg intranasally at 8 PM), crossover treatment, and post-treatment. DDAVP did not produce adverse side effects or significantly alter blood pressure, body weight, serum osmolality or urine osmolality. The results were as follows:Thirteen of 43 children responded to DDAVP (number of wet nights <6). In 6 of the responders, the drug effect persisted into the next study period. Only 2 of 24 children responded to placebo during the first treatment period. In conclusion, DDAVP appears safe for treating enuresis. A child's response to the drug can be determined by a two-week therapeutic trial.

Studies on Kidney Function in Subjects Exposed to Organic Solvents

The renal concentrating ability was studied in 11 subjects by means of 14-16 hours of fluid deprivations, alone and in combination with the vasopressin analogue desmopressin. The effect of desmopressin without fluid deprivation on urinary osmolality was also studied. The combination of desmopressin and fluid deprivation was not superior to fluid deprivation alone for the production of concentrated urine. Desmopressin alone was inferior to the other two methods. No difference in renal concentrating ability could be demonstrated after 14 hours of fluid deprivation, when comparing 118 subjects exposed to various organic solvents with 48 controls.