carboprost and Hemorrhage

To report a case of cyclophosphamide-induced hemorrhagic cystitis, discuss prevention, and review treatment options, particularly the use of intravesicular prostaglandins.. Literature obtained through a computerized search, with subsequent bibliography scanning. Information on the individual case was obtained from the patient's medical record and the Pharmacy Clinical Research Specialist.. A 29-year-old woman who had a postallogeneic bone marrow transplantation was hospitalized because of graft-versus-host disease. During hospitalization, she developed a cyclophosphamide-induced hematuria that, despite hydration and transfusions of blood products, progressed to refractory hemorrhagic cystitis. A response was prompted ultimately by a regimen consisting of continuous bladder irrigation and intermittent intravesical instillation of carboprost.. The best treatment for hemorrhagic cystitis remains prevention. Therapies for established cystitis are varied; the choice depends on the degree of hematuria present. Therapies are often temporary or ineffective, and themselves cause significant morbidity. One promising treatment option involves the intravesicular administration of prostaglandins. Reports in the literature discuss a variety of products, dosages, and treatment schedules that have been used with some success. The available data on this technique are presented.. Prostaglandins appear to be effective in resolving established hemorrhagic cystitis; however, their place in therapy remains unclear. Before this class can be employed routinely, several basic issues remain. These include optimal dosage, dosing schedule, duration of treatment, and comparative efficacy with other agents.

Topics: Administration, Intravesical; Adult; Bone Marrow Transplantation; Carboprost; Cyclophosphamide; Cystitis; Female; Hematuria; Hemorrhage; Humans; Therapeutic Irrigation

To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation.. Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response.. Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy.. Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered for a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.

Topics: Administration, Intravesical; Adult; Bone Marrow Transplantation; Carboprost; Cystitis; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged

Our purpose was to compare intramyometrial 15-methyl prostaglandin F2 alpha with intravenous oxytocin for controlling blood loss at elective cesarean section.. A double-blind, randomized trial was performed with intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, or intravenous oxytocin, 20 U, in 60 women undergoing elective lower segment cesarean section at 36 to 41 weeks' gestation. Subjective assessment of the operative blood loss and early lochial discharge and objective change in hemoglobin and hematocrit before and 24 hours after delivery and the incidence of side effects were compared by nonparametric statistical tests.. The mean estimated blood loss was similar in both groups, with 645 ml (SD 278, range 400 to 1500) in the 15-methyl prostaglandin F2 alpha group compared with 605 ml (SD 303, range 200 to 1750) in the oxytocin group. The mean fall in hemoglobin and hematocrit was greater in the 15-methyl prostaglandin F2 alpha group than in the oxytocin group, 0.98 gm/dl (SD 0.95) versus 0.65 gm/dl (SD 0.79) for hemoglobin and 2.58% (SD 2.96) versus 2% (SD 2.96) for hematocrit. None of these differences reached statistical significance. There were no differences in side effects and lochial discharge between the treatment groups. In both groups there was a decrease of approximately 1% in maternal arterial oxygen saturation.. Routine intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, does not offer any obvious advantage over intravenous oxytocin, 20 U, in reducing operative blood loss at elective lower-segment cesarean section.

Topics: Adult; Carboprost; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemorrhage; Humans; Injections; Injections, Intravenous; Myometrium; Oxygen; Oxytocin; Pregnancy; Prospective Studies; Treatment Outcome

The influence of intramyometrial injection of 125 micrograms of 15-s-15-methyl prostaglandin F2 alpha (carboprost tromethamine, Prostin/15M) versus 20 U of oxytocin immediately after delivery of placenta on blood loss at cesarean section was investigated by means of a double-blinded, randomized trial. Hematocrit decrease from the day before operation to the third postoperative day was used as an index of blood loss. Decreases in hematocrit were comparable for the oxytocin and carboprost tromethamine groups. Excess blood loss (hematocrit decrease more than 6 vol. %) was significantly associated with the indication for cesarean section (three of four for cephalopelvic disproportion versus 9 of 42 others, p less than 0.01), but not with age, parity, number of prior cesarean sections, or birthweight. Carboprost tromethamine does not appear to be more effective than oxytocin when given by intramyometrial injection at this dose for routine cesarean section; its prophylactic utility in higher doses or in cases at risk for hemorrhage from uterine atony remains to be investigated.

Topics: Adult; Carboprost; Cesarean Section; Double-Blind Method; Female; Hematocrit; Hemorrhage; Hemostatic Techniques; Humans; Injections; Labor Onset; Myometrium; Oxytocin; Postoperative Complications; Pregnancy; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Uterine Contraction

Recently, prostaglandins have been shown to be effective agents for the treatment of cyclophosphamide-induced hemorrhagic cystitis. Among the prostaglandins studied is carboprost tromethamine, a PGF2a analog. To determine the effectiveness of carboprost tromethamine therapy on the urothelium, we induced hemorrhagic cystitis in 81 rats. These were divided into two treatment arms. One arm was treated prophylactically at the time of cyclophosphamide injection, and the other started treatment only after hemorrhagic cystitis was established. Animals were divided equally into groups receiving 0, 0.4, 0.8, and 1.6 mg.% carboprost tromethamine in 0.9% normal saline by continuous bladder irrigation. All bladders were examined grossly for edema and hemorrhage, then histologically for mucosal ulceration, congestion, and perivascular hemorrhage. Results from the prophylactic arm, as compared to those for controls, revealed that all groups except those treated only with 0.9% normal saline had a lower incidence of hemorrhagic cystitis (p less than 0.05). In the established hemorrhagic cystitis arm, the group treated with 1.6 mg.% carboprost tromethamine showed the best response (p less than 0.05), whereas the group treated with 0.9% normal saline showed the poorest response. This study reveals that hemorrhagic cystitis in the rat model may be prevented by prophylactic continuous bladder irrigation with carboprost tromethamine, whereas established hemorrhagic cystitis may be treated effectively with intravesical instillation of carboprost tromethamine. Although the mechanism of action of this prostaglandin on the urothelium is unknown, it appears grossly and histologically to decrease ulceration, perivascular hemorrhage, and congestion in the mucosa and submucosa.

Topics: Animals; Carboprost; Cyclophosphamide; Cystitis; Drug Combinations; Edema; Female; Hemorrhage; Rats; Rats, Sprague-Dawley; Therapeutic Irrigation; Tromethamine; Urinary Bladder Diseases

The treatment of cyclophosphamide-induced hemorrhagic cystitis has been difficult, with overall poor results using intensive and costly therapy. The authors evaluated the treatment of this problem in four patients with prostaglandin intravesical therapy. Each patient had failed to respond to conservative management. Carboprost tromethamine (Hemabate) was instilled into the bladder, with dwell times ranging from 45 to 60 minutes, three to four times a day for 4 to 5 days. Two of the patients required a second course with carboprost tromethamine at an increased concentration. A third patient's treatment was stopped after the first 5-day course because of intractable bladder spasms and persistent hematuria. In the three patients who completed the full course of therapy the hematuria resolved completely. The only side effect noted was bladder spasms, which were controlled in three of the four patients with oxybutynin chloride. This preliminary evaluation suggests that carboprost tromethamine may be a safe and effective bedside treatment of cyclophosphamide-induced hemorrhagic cystitis.

Topics: Adult; Carboprost; Child; Cyclophosphamide; Cystitis; Drug Combinations; Drug Evaluation; Female; Hematuria; Hemorrhage; Humans; Male; Prostaglandins F, Synthetic; Tromethamine

Intravesical instillation of 15 (s) 15-methyl prostaglandin F2-alpha (1 mg in 100 ml of normal saline on days 1 and 2, and 0.5 mg in 50 ml of normal saline on days 3 and 4) controlled massive vesical hemorrhage due to radiation cystitis in a 60-year female with carcinoma of uterine cervix. With the 1 mg dose, she developed severe bladder spasms and mild fever. No cardiac or respiratory side effect was observed.

Topics: Aged; Carboprost; Cystitis; Female; Hematuria; Hemorrhage; Humans; Prostaglandins F, Synthetic; Urinary Bladder Diseases; Uterine Cervical Neoplasms