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At least 19 recordsLinked to original sources
PubMed1999

Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine.

Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 +/- 1 mL/min, UNaV 7 +/- 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 microgram/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 +/- 4 mL/min, UNaV 47 +/- 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 +/- 10 mL/min, UNaV 8 +/- 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation.

Dopamine↗
PubMed2000

Ornipressin (Por 8): An efficient alternative to counteract hypotension during combined general/epidural anesthesia.

UNLABELLED: We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. IMPLICATIONS: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.

Adolescent↗
PubMed1982

A comparative study of the haemostatic properties and cardiovascular effects of adrenaline and ornipressin in children using enflurane anaesthesia.

In a randomized, double-blind trial, haemostatic and cardiovascular effects of ornipressin and adrenaline were compared in 30 children requiring surgery for "bat-ear" deformity. Mean total blood loss was 14.3 ml with ornipressin and 11.7 ml with adrenaline, this difference being insignificant. There was a significant and progressive reduction in mean heart rate in children who received ornipressin, from 134 to 116 bpm (P less than 0.05), and a significant rise from 127 to 134 bpm (P less than 0.05) with adrenaline. Mean systolic pressure was unaltered by ornipressin but was significantly increased from 97 to 105 mmHg (P less than 0.05) in children receiving adrenaline. Ornipressin is as effective a haemostatic agent as adrenaline and the rises in heart rate and systolic pressure associated with adrenaline, which are factors known to predispose to the onset of ventricular dysrhythmias, do not occur with ornipressin.

Adult↗
PubMedDate not supplied

Hemodynamic effects of endobronchial application of ornipressin versus terlipressin.

BACKGROUND: Ornipressin and terlipressin, two ADH-derivates, are instilled endobronchially for bronchoscopy- related bleeding without sufficient evidence of efficacy, nor safety. OBJECTIVES: To compare the immediate hemodynamic effects of ornipressin and terlipressin used for procedure-related bleeding during flexible bronchoscopy. METHODS: This retrospective study included patients referred for flexible bronchoscopy who needed administration of ornipressin (15 patients) or terlipressin (15 patients) for procedure-related bleeding. Endobronchial ornipressin (5 IU) or terlipressin (0.5 mg) was administered through the bronchoscope when bleeding persisted for 2 min of continuous suction, or when bleeding was considered increasing in time or major. Hemodynamic data were collected before, during and after administration of either drug. RESULTS: Biopsy-associated hemoptysis requiring medical treatment occurred in 110 (4.2%) of 2,592 bronchoscopies. After administration of ornipressin, no significant change in heart rate or blood pressure was observed. Following terlipressin instillation, heart rate increased from 93 +/- 17 to 101 +/- 22 b.p.m. (p = 0.03), and blood pressure decreased from 107 +/- 14 to 101 +/- 17 mm Hg (p = 0.04). Oxygen saturation under supplemental nasal oxygen was not different in both groups. None of the 110 patients died from bronchoscopy-related hemoptysis or needed further intervention to stop bleeding or prolonged monitoring because of hemodynamic instability. CONCLUSIONS: In contrast to ornipressin, administration of terlipressin is associated with significant changes in heart rate and blood pressure. However, these changes are of minor clinical importance, and terlipressin can be safely given for bronchoscopy-associated bleeding.

Adult↗
PubMed1991

Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis. Effects on renal hemodynamics and atrial natriuretic factor.

In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis.

Atrial Natriuretic Factor↗
PubMed1994

Dose-response relation of ornipressin with regard to vasoconstriction in human skin.

We have studied the vasoconstrictor potency of ornipressin in the skin of 30 volunteers. Subjects received intradermal injections (50 microliters) of five different concentrations of ornipressin (10(-4) - 10(0) u. ml-1 in 0.9% saline) and plain 0.9% saline as a control. Immediately before injection, basal cutaneous blood flow in the test field was enhanced with 1% histamine. Capillary flux was measured by laser Doppler flowmetry and the size of pallor was determined. Ornipressin was effective at 10(-4) u. ml-1 and had its largest constrictor effect at concentrations of 10(-2) and 10(-1) u. ml-1. Larger concentrations were less effective in reducing capillary flux. Interindividually, the most effective concentration varied between 10(-3) and 10(-1) u. ml-1. The size of pallor grew in a dose-dependent manner but 10(0) u. ml-1 always caused reddening in its centre. Capacitance vessels (skin colour) were more sensitive to ornipressin than resistance vessels (capillary flux). The shortest latency of vasoconstriction was obtained with concentrations of 10(-2) and 10(-1) u. ml-1. The results of this study suggest that for haemostasis of the skin a concentration of ornipressin 10(-2) u. ml-1 is useful; this low concentration would reduce total dosage and unwanted side effects.

Adult↗
PubMed1990

[Cutaneous blood flow following subcutaneous infiltration of lidocaine with and without the addition of adrenaline or ornipressin].

The addition of ornipressin to local anesthetics increases the duration of regional anesthesia. A dose of 0.1 unit/ml produces an increase in nerve block duration comparable to adrenaline 5 micrograms/ml. In order to suppress intraoperative bleeding higher concentrations of ornipressin have been used in infiltration anesthesia. This study was designed to examine whether an increase in ornipressin concentration above 0.1 unit/ml causes a further reduction in cutaneous blood flow. Twelve volunteers took part in the study. They received intracutaneous infiltrations of 4 ml lidocaine 0.5% in the volar aspects of both forearms (Fig. 1). The solution was either plain (= Lido) or contained adrenaline 5 micrograms/ml (Lido + A), or ornipressin 0.1 unit/ml (Lido + P1) or 0.2 unit/ml (Lido + P2). Blood flow was measured with a laser Doppler flowmeter; before the infiltration the skin was locally heated to 40 degrees C in order to obtain maximal perfusion (Flow 100); this temperature was maintained throughout the measuring period. The minimal flow after infiltration was calculated as a percentage of Flow 100. Lido caused a significant decrease in flow to 59 +/- 25% (M +/- SD). Lido + A, Lido + P1 and Lido + P2 caused further significant flow reductions, to 19 +/- 21%, 23 +/- 16% and 26 +/- 23%, respectively (Figs. 3, 4). The latency of maximal flow reduction did not differ between the four solutions (Fig. 5). The results show that in infiltration anesthesia an increase in ornipressin concentration above 0.1 unit/ml does not improve superficial vasoconstriction.

Anesthetics, Local↗
PubMed1998

Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.

Hepatorenal syndrome is caused by a marked vasoconstriction of the renal circulation. It is suggested that the renal vasoconstriction is related to an overactivity of vasoconstrictor systems secondary to a vasodilation of the arterial circulation that causes a reduction in effective arterial blood volume. To test this hypothesis, 16 cirrhotic patients with hepatorenal syndrome were treated with a combination of ornipressin, a potent vasoconstrictor agent, and plasma volume expansion with albumin to improve effective arterial blood volume. The combined treatment was administered either for 3 or 15 days (8 patients each), and the effects on renal function, vasoactive systems, and systemic hemodynamics were assessed. The 3-day treatment with ornipressin and albumin was associated with a normalization of the overactivity of renin-angiotensin and sympathetic nervous systems, a marked increase in atrial-natriuretic peptide levels, and only a slight improvement in renal function. However, when ornipressin and albumin were administered for 15 days, a remarkable improvement in renal function was observed, with normalization of serum-creatinine concentration, a marked increase in renal plasma flow and glomerular filtration rate, and a persistent suppression in the activity of vasoconstrictor systems. However, 3 of 8 patients on 15-day therapy treatment had to be discontinued because of ischemic complications. In conclusion, the decrease in effective arterial blood volume and the activation of vasoconstrictor systems play a crucial role in the pathogenesis of hepatorenal syndrome. Although the prolonged administration of ornipressin combined with plasma volume expansion reverses hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications.

Adult↗
PubMed1991

Animal test or chromatography? Validated high-performance liquid chromatographic assay as an alternative to the biological assay for ornipressin.

Ornipressin is a peptide drug which is usually assayed by a test on live rats. In order to reduce the animal experiments an alternative method was developed which uses gradient high-performance liquid chromatography (HPLC) on reversed-phase. The HPLC method was validated and shown to be selective and precise. Correlation studies were performed on samples of different dosage strengths and on thermally degraded samples, showing good correlation with the results obtained by the biological assay. The HPLC method was applied on various batches of ornipressin in bulk and in pharmaceutical preparations. HPLC is a rapid and inexpensive method which can replace the animal assay. A new quality control concept is proposed which uses HPLC for the analysis of ornipressin in bulk and in pharmaceutical preparations. With this concept animal testing can be reduced by 90%.

Amino Acid Sequence↗
PubMed1986

The effects of ornipressin and adrenaline on lignocaine nerve blocks.

An electrophysiological method measuring nerve conduction following the electrical stimulation of a sciatic nerve branch in anaesthetised rats was used to evaluate under strictly controlled conditions the effects of 1:100,000 adrenaline and of 0.03 IU X ml-1 ornipressin on the speed of onset, depth and duration of lignocaine anaesthesia. It was shown that compared with plain lignocaine, lignocaine with ornipressin produced shorter onset of anaesthesia and improved its depth and duration. Adding adrenaline to lignocaine merely extended its duration of action. Ornipressin, therefore, even at low concentration, can be considered as a viable alternative vasoconstrictor to adrenaline, the use of which is undesirable in some categories of patients.

Action Potentials↗
PubMed1998

[Successful conservative therapy of hepatorenal syndrome with vasopressin-1-receptor antagonist ornipressin].

A 47-year-old male patient with alcoholic cirrhosis Child-Pugh grade C was admitted to our center for evaluation of liver transplantation. Serum creatinine had increased from 1.6 to 4.3 mg/100 ml within the previous two weeks, creatinine clearance was 12 ml/min, and urinary sodium 12 mmol/24 h. The diagnosis of HRS type I was established. Diuretic treatment was discontinued. Following albumin infusion, central venous pressure was increased to above 10 cm H2O and dopamine (2 micrograms/kg/min) infusion was started. However, renal function did not improve. An i.v. infusion of ornipressin (POR8, Sandoz; 6 IU/h) was started and dopamine infusion continued. During a four-hour interval, urinary volume and sodium excretion doubled. Therefore treatment was continued for three weeks. After 22 days, renal function had normalized (creatinine 1.2 mg/100 ml, creatinine clearance 65 ml/min, urinary sodium 62 mmol/24 h) and diuretic therapy was resumed. No adverse effects were observed. Ornipressin/dopamine infusion was discontinued and renal function remained normal. Three weeks later, the patient underwent liver transplantation with normal renal function. Ornipressin infusion had no effect on circulating endothelin, but decreased the activation of the renin-aldosterone system and of the sympathetic activity. So far, no noninvasive therapy of hepatorenal syndrome has been established. This is the first report of successful medical treatment of HRS type I with a three-week infusion of the vasopressin-l-receptor agonist ornipressin.

Dose-Response Relationship, Drug↗
PubMed1983

Ornipressin as vasoconstrictor in rhinosurgery.

The haemostatic effect of a high concentration of ornipressin 5 IU/10 mls lidocaine was studied in 127 patients undergoing rhinosurgery under two types of general anaesthesia. Under halothane/enflurane anaesthesia blood pressure and heart rate remained nearly constant up to 15 minutes following local injection of ornipressin into the nasal tissues. Good haemostasis was achieved in 86.5 percent of cases. Under diazepam/fentanyl anaesthesia an elevation of blood pressure was observed following infiltration of ornipressin. Thus the high concentration cannot be recommended for cases with blood pressure dyscrasias. The haemostatic effect was either good in only 60 percent of the patients.

Anesthesia, Inhalation↗
PubMed1977

A comparison of ornipressin and adrenaline for local vasoconstriction.

The effectiveness of ornipressin and adrenaline as local vasoconstrictors is compared, with special reference to cleft-lip-and-palate surgery. A latent period of 3 - 5 minutes with the use of ornipressin is advised. A brief review comparing the local and general effects of ornipressin and adrenaline is included.

Cleft Lip↗
PubMed1985

Enhancement of renal function with ornipressin in a patient with decompensated cirrhosis.

An infusion with Ornipressin (8-ornithin vasopressin) in a patient with decompensated alcoholic liver cirrhosis increased urinary volume from 30 ml/h to 500 ml/h, creatinine clearance from 24 to 65 ml/min, and fractional sodium excretion from 0.86% to 11.1%. Free water clearance decreased from -10.2 ml/h to -26.2 ml/h and noradrenaline plasma concentrations dropped from 2.04 to 1.37 ng/ml. After stopping Ornipressin infusion all values returned to initial concentrations. Possible effects are an increase of renal blood flow secondary to an increase in arterial blood pressure, possibly potentiated by the vasodilatory effect of the fall in noradrenaline and/or angiotensin concentration.

Adult↗
PubMedDate not supplied

[The adverse effects induced by ornipressin during oral and maxillofacial surgical interventions under general anesthesia].

There are various methods used in maxillofacial surgery for the control of superficial hemorrhage. The purpose is to achieve a better identification of the anatomical structures and reduce operating times without side effects. Ornipressin has no arrhythmogenic effects in presence of inhalational anesthetics and should therefore be considered safer then adrenalin. The authors examined the cardiocirculatory effects of this drug by means of an invasive hemodynamic study on five patients. The results showed that ornipressin causes worrying increases in blood pressure and peripheral vascular resistances, with reduction in the cardiac output.

Adult↗
PubMed1985

The treatment of resistant hypotension with ornipressin. A case report.

A 50-year-old man underwent emergency aortic valve replacement. He had been treated with five antihypertensive agents before the procedure; this contributed to the development of profound hypotension after induction of anaesthesia. The hypotension did not respond to conventional treatment with an incremental intravenous infusion of phenylephrine HCl, probably due to the direct vasodilator action of the hydralazine group of drugs which renders the peripheral vascular smooth muscle unresponsive to sympathomimetic stimulation. The hypotension did, however, respond rapidly to low-dose infusion of a synthetic vasopressor, ornipressin (POR 8; Sandoz), a drug with a direct action on vascular smooth muscle, especially the capacitance vessels. Ornipressin thus restores vascular smooth-muscle tone even when the integrity of the adrenergic pathways is no longer intact.

Anesthesia, General↗
PubMed1993

[Ornipressin (POR 8)--effect on coronary blood circulation and the peripheral circulation. An animal experimental study].

Ornipressin (POR 8), referred to below as OR, is a synthetic derivative of natural vasopressin. It was introduced into clinical practice to replace epinephrine as a local vasoconstrictor because OR was presumed to produce fewer undesirable side-effects. However, mayor cardiovascular complications following local infiltration of OR have been reported in recent time. Beside increased blood pressure and changes in heart rate, there is evidence that the systemic effects of OR include a distinct vasopressor activity on coronary arteries. This study was planned to investigate the effects of OR in haemodynamics and the coronary vascular system. METHODS. The effects of OR on systemic haemodynamics and coronary circulation were studied in nine anaesthetized closed-chest mongrel dogs. Anaesthesia was administered using N2O/O2 (FiO2:0.33) and enflurane (1.0 vol% endtidal). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a tip catheter manometer. Cardiac output (CO) was determined using thermodilution and coronary sinus blood flow, using a Pitot catheter. Recording of baseline values was followed by bolus injection of OR (0.03 U/kg) and changes in haemodynamics were measured for 90 min at fixed time intervals. Statistical analysis was performed by analysis of variance for repeated measures. A value of P < or = 0.05 was considered to indicate statistical significance. RESULTS. Significant maximum changes occurred within 3-5 min after administration of OR. Systolic and diastolic arterial pressures increased by 33% and 39%, respectively. With only minor changes in heart rate, cardiac output markedly decreased by 44% and total peripheral resistance increased by 159%. Impaired pump function of the left ventricle became obvious by a decrease in maximum dP/dt, a decrease in ejection fraction by 35%, and a concomitant sharp increase in left ventricular enddiastolic pressure by 68% and in endosystolic volume by 41%. At the same time, OR produced a marked impairment of coronary perfusion. Myocardial blood flow fell by 32%, while coronary vascular resistance rose by 112%. Increased myocardial oxygen demand and reduced oxygen supply resulted in very low values of coronary venous oxygen saturation (< 20%). CONCLUSIONS. Systemic effects of OR are characterized by a sharp rise in arterial blood pressure. Concomitantly a decrease of myocardial contractility leads to a compromised left ventricular function with marked increases in left ventricular enddiastolic pressure. These haemodynamic changes are associated with an imbalance of myocardial oxygen demand and delivery due to the distinct OR-induced coronary constriction. With regard to the deterioration of systemic and cardiac haemodynamics the indications and use of ornipressin in clinical practice need to be reevaluated.

Animals↗
PubMed1982

[Value of deliberate normovolemic hemodilution associated with a capillary vasoconstrictor, ornipressin, in surgery of the spine].

This study of sixty-seven children divided in two groups compared the blood loss and the amount of blood transfused during and after the operation. The operations were carried out without haemodilution nor the local injection of vasoconstrictor (twenty-four patients) and following haemodilution and the local injection of vasoconstrictor (forty-three patients). The blood loss during operation was 344 +/- 455 ml per vertebra in the first group, and 151 +/- 54 ml in the second. The blood loss in the post operative period did not seem to be modified by haemodilution, as the level of hemoglobulin was virtually the same in the two groups eleven days after the operation. A mean of seven units of blood were transfused to the first group, whilst only three in the second group. In the post-operative period, both groups received a mean of one unit each. Associating haemodilution and a vasoconstrictor, ornipressin, reduced very significantly the need for homologous blood.

Adolescent↗