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PubMed1995

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Aged↗
PubMed1996

The effects of epoprostenol on drug disposition. I: A pilot study of the pharmacokinetics of digoxin with and without epoprostenol in patients with congestive heart failure.

The influence of epoprostenol on the pharmacokinetics of drugs administered concurrently to patients with congestive heart failure (CHF) receiving epoprostenol was evaluated as a secondary objective of a Phase II pilot study. A total of 278 blood samples were collected from 30 patients with end-stage CHF receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of oral clearance (Cl), volume of distribution, and absorption rate constant of digoxin were generated from plasma digoxin concentrations using nonlinear mixed effects modeling, and the effect of epoprostenol on Cl of digoxin was evaluated by univariate analysis. Additional factors that were evaluated by univariate analysis included age, obesity, time since study entry, cardiac output, concomitant use of angiotensin-converting enzyme (ACE) inhibitor, concomitant dobutamine, and estimated creatinine clearance. Backward elimination was used to arrive at a final model that included concomitant epoprostenol as a covariate. The final model revealed an approximate 15% decrease in Cl of digoxin in response to short-term administration of epoprostenol that was no longer apparent by the end of the 12-week treatment phase. Simulations revealed that this effect, although statistically significant, would not be clinically significant in most patients; however, the potential exists for short-term elevation of digoxin concentrations in response to concurrent administration of epoprostenol.

Adult↗
PubMed1996

The effects of epoprostenol on drug disposition. II: A pilot study of the pharmacokinetics of furosemide with and without epoprostenol in patients with congestive heart failure.

The effect of epoprostenol on the pharmacokinetics of furosemide was investigated in 23 patients with end-stage congestive heart failure (CHF) receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of the apparent oral clearance, volume of distribution, and absorption rate constant for furosemide were generated from 198 serum furosemide concentrations using nonlinear mixed effects modeling (NONMEM). Univariate analyses were performed to assess the effects of patient factors on the apparent oral clearance of furosemide. The final multivariate model determined by backwards elimination included concomitant digoxin therapy. When concomitant epoprostenol therapy was included in the final model, there was a 13% decrease in the apparent oral clearance of furosemide in response to short-term administration of epoprostenol. However, the effect of concomitant epoprostenol therapy was not statistically significant and was no longer apparent by the end of the 12-week study. These data suggest that epoprostenol may have a slight short-term effect on the pharmacokinetics of furosemide; the interaction between epoprostenol and furosemide is not clinically significant, however.

Diuretics↗
PubMed1988

Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).

Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results indicate that clinically tolerable doses of intracoronary epoprostenol do not significantly dilate the epicardial coronary arteries. This route of administration is therefore unlikely to be of use during coronary angioplasty, although the antiplatelet action of intravenous epoprostenol might help to prevent restenosis.

Coronary Angiography↗
PubMed2000

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.

Adult↗
PubMed1993

Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension.

OBJECTIVE: To determine whether epoprostenol (prostacyclin, PGI2) or heart-lung transplantation (HLT), or both improves survival of patients with severe pulmonary hypertension. DESIGN: This was a prospective study where the effects of epoprostenol were compared with conventional treatment. Also, the benefits of epoprostenol and HLT were assessed by comparing survival in this group with that of 120 patients at the Mayo Clinic before HLT and epoprostenol treatment became available. PATIENTS AND INTERVENTIONS: Forty four patients were studied; 25 received continuous epoprostenol over a four year period (mean (SD) cardiac index 1.8 (0.4) 1 min-1 m-2 and mean (SD) pulmonary artery pressure (PAP) 70 (16) mm Hg) and 19 did not (cardiac index 2.1 (0.6) 1 min-1 m-2 and PAP 64 (13) mm Hg). Ten patients underwent HLT: seven had received epoprostenol, and three had not. RESULTS: The therapeutic intervention with epoprostenol, or HLT, or both improved survival compared with the Mayo clinic patients (p = 0.05). Most of the benefit was conferred by epoprostenol, which prolonged survival twofold from a median time of eight to 17 months and doubled the changes of successful HLT. The improved survival with epoprostenol was not related to its immediate capacity to cause pulmonary vasodilation. Those patients who had limited acute pulmonary vasodilation when treated with epoprostenol showed the greatest improvement in survival. CONCLUSIONS: These preliminary results indicate that those pulmonary hypertensive patients with the poorest chance of survival can be helped by epoprostenol and by HLT.

Adult↗
PubMed1984

A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man.

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Cost implications of using inhaled nitric oxide compared with epoprostenol for pulmonary hypertension.

OBJECTIVE: To compare the cost of using intravenous epoprostenol with that of inhaled nitric oxide (NO) for treating episodes of pulmonary hypertension in children with congenital heart disease. DESIGN: An analysis of the cost of epoprostenol and NO use over the previous 18 months was performed. Three 6-month periods were identified, two in which epoprostenol was used and the third in which inhaled NO was introduced for the treatment of pulmonary hypertension. SETTING: A 10-bed pediatric cardiac intensive care unit, Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England. SUBJECTS: Children with congenital heart disease and persistently elevated pulmonary artery pressure following cardiac surgery. MAIN OUTCOME MEASURES: The total duration of use of epoprostenol and inhaled NO was documented. The costs per hour for epoprostenol and inhaled NO were calculated and the annual cost of each agent was estimated. RESULTS: In the two 6-month periods prior to the introduction of inhaled NO, epoprostenol was used on 14 occasions (5 in the first period, 3 in the second). In the last 6-month period, nine children required pulmonary vasodilator therapy on 14 occasions. All nine children were treated successfully with inhaled NO; none were given or needed epoprostenol, as NO always was effective in providing pulmonary vasodilatation. For resistant pulmonary hypertension, increasing the concentration of NO would have been the next therapeutic option. The cost for the two 6-month periods using epoprostenol was $19,483.48 for the drug and $283.25 for equipment costs (total cost $19,766.73). There was no expenditure on epoprostenol in the final 6-month period. The cost of NO was $465. However, the total expenditure, including the delivery and monitoring system, was $4,722.85. CONCLUSIONS: Using inhaled NO in our pediatric cardiac intensive care unit abolished the use of epoprostenol during the reported monitoring period. The cost savings were significant, amounting to 12% of the annual drug budget for the unit. The cost of setting up the inhaled NO delivery system is recouped rapidly. The ease of delivery and measurement of inhaled NO also may have contributed to its increased clinical use.

Child↗
PubMed1996

Epoprostenol increases plasma level of atrial natriuretic peptide in humans.

1. In a placebo-controlled, randomized dose-response study the effect of the prostaglandin analogue epoprostenol (Flolan) on the plasma level of atrial natriuretic peptide has been investigated in 14 healthy control subjects. 2. During epoprostenol infusion, atrial natriuretic peptide increased significantly in a dose-dependent manner, while it remained unchanged during placebo infusion [2 ng min-1 kg-1: epoprostenol 13.2% versus placebo -2.9%; 4 ng min-1 kg-1: epoprostenol 13.4% versus placebo -6.1%; 8 ng min-1 kg-1: epoprostenol 40.7% versus placebo -7.8% (medians), P < 0.01 for all]. 3. Mean blood pressure and heart rate increased significantly after epoprostenol, but were unchanged during placebo infusion [8 ng min-1 kg-1; mean blood pressure: epoprostenol -5.6% versus placebo 3.2%; heart rate: epoprostenol 32.7% versus placebo 3.1% (medians), P < 0.01]. 4. It is concluded that epoprostenol given intravenously increases the plasma level of atrial natriuretic peptide. The results support the hypothesis of an interaction between the prostaglandin system and atrial natriuretic peptide.

Adult↗
PubMed2004

The influence of VIP and epoprostenol on platelet CD62P expression and primary haemostasis in vitro.

Human vasoactive intestinal peptide (VIP) and epoprostenol (prostacyclin) have vasodilatative effects in the pulmonary circulation. Both VIP and epoprostenol are successfully used to treat pulmonary hypertension in humans and experimental animal models. The positive effects of epoprostenol on the course of this disease are achieved through vasodilatation and inhibitory effects on platelet activity. Since VIP also binds specifically to platelets, we compared the in vitro effects of VIP and epoprostenol on platelet P-Selectin (CD62P) expression and primary haemostasis. Anti-aggregative effects of VIP (10(-6) mol and 10(-8) mol) and epoprostenol (50, 5 and 0.5 ng/ml) on platelets were determined by agonist-induced CD62P expression and in vitro bleeding time (PFA-100 trade mark system). Blood from healthy individuals was either incubated with epoprostenol, VIP or saline control and was analysed by whole blood flow cytometry and the PFA-100 trade mark. Prior to flow cytometric analysis, the platelets were stimulated with either arachidonic acid (AA) or adenosine diphosphate (ADP). Whole blood flow cytometry analysis showed that epoprostenol inhibited dose-dependently agonist-induced CD62P expression, whereas VIP did not inhibit CD62P expression. PFA analysis revealed substantial closure time prolongation by epoprostenol and again no effects of VIP. These results indicate that VIP, in contrast to epoprostenol, has no effect on platelet CD62P expression and primary haemostasis.

Adenosine Diphosphate↗
PubMed2000

Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus.

OBJECTIVE: Pulmonary hypertension with pathological changes similar to those observed in primary pulmonary hypertension occurs in patients with systemic lupus erythematosus (SLE). The efficacy of chronic epoprostenol therapy in SLE has not been well described. The objective of this paper is to describe our experience with long-term epoprostenol therapy in patients with pulmonary hypertension associated with SLE. DESIGN: Case series of six patients with SLE and associated pulmonary hypertension receiving chronic treatment with epoprostenol. RESULTS: All 6 patients had severe pulmonary hypertension. Mean pulmonary artery pressure (mPAP) was 57 +/- 9 mm Hg (mean +/- SD), and pulmonary vascular resistance was 14 +/- 7 units before beginning therapy with epoprostenol. In 4 patients who underwent repeat hemodynamic evaluation (9 to 16 months after starting epoprostenol), mean pulmonary artery pressure decreased by 38 +/- 21% and pulmonary vascular resistance by 58 +/- 12%. Clinically, all patients improved from New York Heart Association class III or IV to class I or II. Doses of epoprostenol ranged from 4 to 46 ng/kg/min, and the longest duration of therapy has been 2.5 years. Side effects from epoprostenol have not differed from those seen in patients with primary pulmonary hypertension, and except for one patient, there has been no exacerbation of SLE. CONCLUSION: Epoprostenol was effective for the treatment of pulmonary hypertension in this small group of patients with SLE. Further evaluation of epoprostenol therapy for patients with SLE and other diseases associated with pulmonary hypertension is warranted.

Adult↗
PubMed2003

Successful withdrawal of long-term epoprostenol therapy for pulmonary arterial hypertension.

BACKGROUND: IV epoprostenol treatment of pulmonary arterial hypertension (PAH) has been believed to require an indefinite duration of therapy OBJECTIVE: To describe the successful discontinuation of long-term epoprostenol therapy in four patients DESIGN: Case reports SETTING: Outpatient clinic, tertiary-care hospital PATIENTS: Four patients with acutely nonvasoreactive, World Health Organization (WHO) functional class IV PAH received long-term epoprostenol therapy. All patients subsequently demonstrated normalization of pulmonary arterial pressures on epoprostenol treatment. These patients were selected for epoprostenol withdrawal INTERVENTION: Down-titration and discontinuation of epoprostenol RESULTS: All four patients were safely transitioned from epoprostenol to oral therapies and have maintained WHO functional class I-II for a mean of 11 months (range, 8 to 16 months). The duration of epoprostenol therapy prior to discontinuation averaged 5.7 years (range, 2.4 to 13.5 years) CONCLUSION: Epoprostenol may sufficiently reverse the pathogenic process in select patients with PAH to allow a transition to less complex and less invasive treatment modalities.

Adult↗
PubMedDate not supplied

Role of prostacyclin (epoprostenol) as anticoagulant in continuous renal replacement therapies: efficacy, security and cost analysis.

BACKGROUND: Heparin remains the drug most commonly used for anticoagulation in continuous renal replacement therapies (CRRTs). However, in patients with hypercoagulability, heparin is insufficient or, in cases with an increased risk of bleeding or thrombocytopenia, it may be contraindicated. Epoprostenol, a potent vasodilator, antithrombotic and antiplatelet agent, could be an alternative. PATIENTS AND METHODS: We studied the records of patients treated under continuous venovenous hemodiafiltration in an academic tertiary hospital of 900 beds, between January 2000 and June 2003. Epoprostenol was prescribed to patients with (i) filter hypercoagulability, defined as consumption of 2 or more filters in the last 24 hours; (ii) low platelet count; or (iii) recent severe hemorrhage. RESULTS: Thirty-eight out of 248 (15%) patients who were under CRRT received epoprostenol for more than 72 hours. Epoprostenol was indicated due to filter hypercoagulability in 48%, thrombocytopenia in 68% (7 patients both) and hemorrhage in 3% of cases. The overall time for epoprostenol therapy was 9,749 hours. The mean filter duration previous to epoprostenol was 23 +/- 12 hours and after administering this drug 38.2 +/- 11.9 hours (p = 0.0001). In 6 patients, heparin and epoprostenol were simultaneously administered. The adverse effects were hemorrhage, which presented in 7 patients (18%) and a fall in blood pressure in another 7 (18%), which recovered in the next 24 hour after starting treatment. Cost analysis demonstrates some advantage with epoprostenol in patients with increased tendency to clotting. CONCLUSIONS: Epoprostenol may be safely used to prevent clotting of the extracorporeal circuits, either alone in patients with thrombocytopenia and/or increased risk of bleeding, or in combination with heparin in states of hypercoagulability.

Anticoagulants↗
PubMed1999

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension.

Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as "portopulmonary hypertension." Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (-34% +/- 18%), MPAP (-16% +/- 10%), and cardiac output (CO) (+21 +/- 18%), were statistically significant (P <.01). Long-term use of epoprostenol further lowered PVR (-47% +/- 12% from baseline and -31% +/- 22% from the acute change; P <.05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.

Adult↗
PubMedDate not supplied

Intravenous epoprostenol sodium does not increase hepatic microsomal enzyme activity in rats.

Previous studies have indicated that epoprostenol may increase hepatic microsomal enzyme activity both in animals and humans. However, interpretation of the results of these studies may be confounded by the route of epoprostenol administration or small sample sizes. The primary objective of the present investigation was to evaluate the effects of epoprostenol (given as a continuous intravenous infusion) on hepatic microsomal enzyme activity in rats. Male Sprague Dawley rats (220-290 g) received infusions of either vehicle (glycine buffer, 1 mL/hr) or 0.2 microgram/kg/min epoprostenol through a jugular vein cannula for 24 hr or 7 days. At the end of the infusion, a 25 mg/kg i.v. bolus of antipyrine was administered and blood samples were collected over 6 hr. Serum antipyrine concentrations were determined by HPLC. Twenty-four hr post-infusion, hepatic microsomes were prepared, and cytochrome P-450 content was determined by difference spectroscopy. Cytochrome P-450 content and antipyrine clearance values determined from serum antipyrine concentration-time profiles were not significantly different between treatment groups. Antipyrine clearance [mean (SD)] in the 24-hr vehicle-treated group was 3.68 (0.49) mL/min/kg versus 4.35 (1.1)mL/min/kg in the epoprostenol-treated group. In the 7-day vehicle-treated rats, antipyrine clearance was 5.43 (1.0) mL/min/kg compared to 4.68 (0.61) mL/min/kg in epoprostenol-treated rats. A statistically significant effect of infusion duration was observed in the control group, i.e., antipyrine clearance in rats treated with vehicle for 7 days was significantly greater than that observed in rats treated with vehicle for 24 hr. However, the increase was less than 50%. These data suggest that when epoprostenol is administered as an intravenous infusion to rats, no significant alterations in hepatic microsomal enzyme activity occur. Based on these data, long term changes in hepatic metabolism in response to chronic epoprostenol administration are not expected.

Animals↗
PubMed2006

[Use of isolated epoprostenol or associated to heparin for the maintenance of the patency of the continuous renal replacement technical circuits].

OBJECTIVE: At present, there is no consensus on the best anticoagulant regimen for the maintenance of extrarenal clearance circuits (RRTC). We present our experience with the isolated use of epoprostenol in patients at risk of bleeding or associated to non-fractionated heparin (nFH) in patients with problems of early coagulation of the filters. DESIGN: Prospective study of cohorts on all the RRTC filters used in our service since 1994. SCOPE: Forty-two-bed polyvalent ICU in a tertiary hospital. INTERVENTIONS: Anticoagulation was administered in prefilter perfusion, at doses of 5-7 U/kg/hour for nFH or 4-5 ng/kg/min for epoprostenol. The combined use was done with equal doses of epoprostenol and nFH at 2,5 U/kg/hour. VARIABLES OF MAIN INTEREST: We analyzed the duration of each filter, reason for removing the filter, existence of coagulopathy, platelet count, appearance of bleeding, anticoagulant used and dose. RESULTS: We analyzed the use of 2,322 filters (66,957 hours) in 389 patients, 54% of whom had a clot. nFH was used in 74% of the filters for a median of 39 hours (interquartile range: 19-75), epoprostenol in 6% for 32 hours (interquartile range: 17-48) and combined therapy in 4% for 27 hours (interquartile range: 19-41). In the epoprostenol group, we detected a decrease in blood pressure in only two filters that became normal when the dose was decreased. The filters that were initially anticoagulated with nFH had a 14-hour survival as a median versus 27 hours in combined therapy (p < 0.001). In absence of coagulopathy or thrombopenia, we observed mild bleeding in 8%, moderate in 1% and serious in 1% in the 1,170 filters treated with nFH. We only observed mild bleeding in 3% in 66 filters with epoprostenol. CONCLUSIONS: Isolated epoprostenol in patients at risk of bleeding provided a similar duration of the filters to nFH, decreasing the risk of bleeding. The use of epoprostenol plus low dose nFH significantly increases their duration in patients with early coagulation.

Acute Kidney Injury↗
PubMed2002

Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival.

OBJECTIVES: We sought to determine the factors associated with long-term survival in patients with primary pulmonary hypertension (PPH) treated with continuous epoprostenol infusion. BACKGROUND: Epoprostenol improves survival in patients with PPH in New York Heart Association (NYHA) functional class III or IV. However, some patients do not benefit from epoprostenol and must be considered for lung transplantation. The best timing for listing these patients on a lung transplantation program is currently unknown. METHODS: Between December 1992 and January 2001, 178 patients with PPH in NYHA functional class III or IV were treated with epoprostenol. The 6-min walk test (WT) and right-sided heart catheterization were performed at baseline, after three months on epoprostenol and thereafter once a year. RESULTS: Overall survival rates at one, two, three, and five years were 85%, 70%, 63%, and 55%, respectively. On univariate analysis, the baseline variables associated with a poor outcome were a history of right-sided heart failure, NYHA functional class IV, 6-min WT or=12 mm Hg, and mean pulmonary artery pressure <65 mm Hg. On multivariate analysis, including both baseline variables and those measured after three months on epoprostenol, a history of right-sided heart failure, persistence of NYHA functional class III or IV at three months, and the absence of a fall in total pulmonary resistance of >30%, relative to baseline, were associated with poor survival. CONCLUSIONS: Survival of patients with PPH treated with epoprostenol depends on the severity at baseline, as well as the three-month response to therapy. These findings suggest that lung transplantation should be considered in a subset of patients who remain in NYHA functional class III or IV or in those who cannot achieve a significant hemodynamic improvement after three months of epoprostenol therapy, or both.

Adult↗
PubMed1999

Epoprostenol in primary pulmonary hypertension.

OBJECTIVE: To review briefly the epidemiology, pathophysiology, and current treatment of primary pulmonary hypertension (PPH) and review the available clinical data on epoprostenol in PPH. DATA SOURCES: A MEDLINE search (January 1966-August 1998) was used to identify case reports and clinical studies pertaining to epoprostenol in PPH. Bibliographic lists were also used. STUDY SELECTION: All English-language clinical studies of epoprostenol in PPH were included. Incomplete study descriptions (abstracts) were not included. DATA EXTRACTION: Study design, population, methods, clinical outcomes, and adverse effects were evaluated. DATA SYNTHESIS: PPH is a relatively rare disease that results in symptoms of congestive heart failure and has a five-year survival rate of 34%. Therapy has consisted of vasodilators, anticoagulation, oxygen, and ultimately lung transplantation. Epoprostenol, which has recently become available as an integral pharmacotherapeutic option, has been shown to improve hemodynamic parameters such as cardiac output, pulmonary artery pressure, and pulmonary vascular resistance. It has been shown to improve exercise parameters, New York Heart Association (NYHA) functional class, and survival. Epoprostenol is indicated for patients with severe disease (NYHA class III or IV) who do not respond to acute vasodilator challenge or chronic calcium-channel blocker therapy. Its chronic administration is challenging as it requires continuous infusion via central venous catheter and a special infusion pump. Administration is further complicated by the 48-hour expiration of reconstituted epoprostenol and the need to refrigerate the reconstituted drug. CONCLUSIONS: Epoprostenol improves hemodynamics and clinical outcome in patients with severe PPH. Epoprostenol therapy requires intensive patient education and medical monitoring, but it can improve well-being and delay the need for lung transplantation.

Antihypertensive Agents↗