Continuous Terlipressin Infusion Research Articles

Hemodynamic effects of continuous versus bolus infusion of terlipressin for portal hypertension: A randomized comparison

The hemodynamics of patients with portal hypertension within 4 h after a single injection of terlipressin has been studied. However, the hemodynamics in a longer phase under different infusion styles is unknown. This study aims to compare the effects of bolus and continuous infusion of terlipressin on systemic and hepatic hemodynamics in patients with portal hypertension. Twenty patients who underwent transjugular intrahepatic portosystemic shunt procedure were randomly assigned to be treated with either intravenous bolus infusion of terlipressin (1 mg) followed by a continuous infusion (4 mg/24 h, n = 10), or intravenous bolus injection of terlipressin (2 mg) followed by intermittent injections (1 mg/6 h, n = 10). The mean arterial pressure, heart rate, and portal venous pressure (PVP) were monitored and recorded at baseline, 1 min, 5 min, 10 min, 30 min, and then once an hour. Serum renin activity, serum angiotensin II, and aldosterone levels were measured prior to and 24 h after the administration of terlipressin. PVP dropped rapidly in both groups, and reduced 16.46% and 28.22%, respectively, at the 1-h time point. Thereafter, PVP remained stable in continuous group while rebounded obviously in intermittent group. One hour after the start of drug administration, heart rate decreased significantly in both groups (84.1 ± 12.8 vs 73.8 ± 12.6 in intermittent group and 86.7 ± 11.5 vs 77.1 ± 13.6 in continuous group, P < 0.005), and mean arterial pressure increased in both groups, although no statistical differences were found. Continuous infusion of terlipressin reduces PVP stably and may become an alternative to traditional bolus injection.

Terlipressin in the treatment of late phase catecholamine-resistant septic shock.

Norepinephrine, but also dopamine and epinephrine are recommended as first line vasopressors in the treatment of septic shock. In some patients, septic shock deteriorates and becomes to be resistant to catecholamines. In this situation, addition of vasopressin or terlipressin can be advantageous. The aim of our pilot study was to evaluate the impact of terlipressin on open label norepinephrine requirements and mortality. In a randomized, controlled, single centre study we assigned patients with late advanced septic shock refractory to catecholamines (norepinephrine >0.6µg/kg/min for more than 24h) to receive either continuously terlipressin 4mg/24h for 72 hours in addition to open label norepinephrine (TERLI group) or to continue therapy only with catecholamines (CON group). All vasopressor infusions were titrated to maintain a target blood pressure. We enrolled 30 patients, of whom 13 were assigned to terlipressin and in 17 we continued in catecholamine therapy. There was no significant difference in norepinephrine consumption between the groups. Open label norepinephrine infusion rates decreased significantly in the TERLI group as compared with initial consumption, but the decrease we observed only in 7 (54%) patients. There was no significant difference between groups in the rate of death at day 28 (77% in TERLI group and 94% in CON group; p=0.18) or at day 90 (91% vs. 94%; p=0.85). Continuous terlipressin infusion was not effective in reducing norepinephrine consumption or in the mortality of patients, if administered in late phase of catecholamine refractory septic shock.

Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia

To test the hypothesis that a continuous infusion of the vasopressin analog terlipressin is associated with less organ dysfunction as compared to intermittent bolus infusion in an ovine sepsis model. Twenty-seven adult female sheep. All sheep were subjected to a Salmonella typhosa endotoxin infusion (10 ng/kg/min). After 16 h of endotoxemia, the surviving animals (n = 24) were randomized to (1) an untreated control group, (2) a continuous terlipressin group (2 mg/24 h), or (3) a terlipressin bolus group (1 mg/6 h). Hemodynamic variables were measured and blood was withdrawn at specific time points for the assessment of organ functions. Continuous terlipressin infusion was associated with improved surrogate parameters of myocardial, renal, and hepatic function as compared with terlipressin bolus infusion. Reduced vascular hyperpermeability was evidenced by an attenuated decrease in plasma protein concentrations in sheep treated with continuous terlipressin infusion as compared to bolus injection or no treatment. Continuous infusion of low-dose terlipressin preserved several surrogate parameters of organ function better than intermittent bolus injections in sheep with systemic inflammation.

Continuous Terlipressin Infusion as Rescue Treatment in a Case Series of Children with Refractory Septic Shock

Despite intensive therapy, refractory pediatric septic shock has a high rate of morbidity and mortality. Additional treatments are needed to improve outcomes in such cases. To report the clinical effects of continuous terlipressin infusion as rescue treatment for children with septic shock refractory to high catecholamine doses. Sixteen episodes of catecholamine-resistant septic shock were recorded in 15 children (aged from newborn to 15 years) who received compassionate rescue treatment with terlipressin at 6 pediatric intensive care units. Terlipressin treatment consisted of a loading dose (20 μg/kg) followed by continuous infusion at a rate of 4-20 μg/kg/h. Terlipressin was titrated at increases of 1 μg/kg/h to maintain mean arterial pressure (MAP) in normal range for age and to reduce catecholamine dosage. The main outcome was survival of the episode. Secondary outcomes included hemodynamic effects, ischemia, and terlipressin-related adverse events. Terlipressin increased median MAP from 48 (range 42-63) to 68 (45-115) mm Hg 30 minutes after terlipressin administration (p < 0.01). MAP was subsequently sustained, which allowed for the reduction of norepinephrine infusion from 2 μg/kg/min (1-4) at baseline to 1.5 μg/kg/min (0.4-4) at 1 hour, 1.3 μg/kg/min (0-8) at 4 hours, 1 μg/kg/min (0-2) at 12 hours, 0.45 μg/kg/min (0-1.4) at 24 hours, and 0 μg/kg/min (0-0.6) at 48 hours (p < 0.05 vs baseline in all cases). In 8 (50%) of the 16 septic shock episodes the patients survived, 7 (44%) without sequelae. One patient survived with sequelae (minor amputation and mild cutaneous ischemia). Eight patients had signs of ischemia at admission; terlipressin induced reversible ischemia in another 4 patients. Meningococcal infection, prior ischemia, and MAP were risk factors for mortality. Continuous terlipressin infusion may improve hemodynamics and survival in some children with refractory septic shock. Terlipressin could contribute to tissue ischemia.

Vasopressin vs. terlipressinin the treatmentof cardiovascular failure in sepsis

Arginine vasopressin (AVP) and terlipressin (TP) are increasingly used as adjunct vasopressors in the treatment of septic shock. Despite important pharmacological differences between the two drugs (e.g., receptor selectivity, effective half-life) the use of either substance is determined mainly by local availability and institutional inventory. We briefly describe the pathophysiology and pharmacology of septic shock relevant to the treatment with vasopressin analogues. In addition, differences in pharmacokinetics and pharmacodynamics between AVP and TP are discussed. The current literature suggests that neither AVP nor TP should be administered in high doses in patients with septic shock. Furthermore, increasing evidence indicates that early administration of vasopressin analogues may improve outcome as compared to a last-resort treatment. Low-dose infusion of AVP (0.6-2.4 U/h) has been demonstrated to be a safe adjunct in the management of septic shock. The V2 agonistic effects of AVP may exert favorable effects on hepatosplanchnic, renal, pulmonary, and coronary perfusion. However, the higher V1 receptor selectivity of TP may prove more potent in restoring arterial blood pressure and avoiding rebound hypotension, while carrying the risk of sustained global and regional vasoconstriction after bolus injection. Evidence from experimental studies and initial clinical reports suggests that continuous low-dose infusion of TP may stabilize hemodynamics in septic shock with reduced side effects. However, randomized, controlled trials are necessary to determine the role of bolus or continuous infusion of TP in the treatment of septic shock before this approach can be recommended for routine clinical use.

CONTINUOUS VERSUS BOLUS INFUSION OF TERLIPRESSIN IN OVINE ENDOTOXEMIA

In patients with sepsis, hemodynamic support is often complicated by a tachyphylaxis against conventional vasopressor agents. Bolus infusion of terlipressin, a vasopressin analog, has been reported to increase mean arterial pressure in patients with catecholamine-resistant septic shock. However, bolus infusion of terlipressin may be associated with severe side effects, including pulmonary vasoconstriction and impairment of oxygen delivery. We hypothesized that continuous low-dose infusion of terlipressin may reverse sepsis-related systemic arterial hypotension with reduced side effects as compared with the traditional concept of bolus administration. Twenty-seven adult sheep were instrumented for chronic study. After a baseline measurement, Salmonella typhosa endotoxin (10 ng.kg-1.min-1) was continuously administered for the next 40 h. After 16 h of endotoxemia, the surviving sheep (n = 24) were randomly assigned to be treated with either a continuous infusion of terlipressin (2 mg for 24 h), bolus injections of terlipressin (1 mg every 6 h), or placebo (normal saline; each n = 8). Continuous infusion of terlipressin permanently reversed endotoxin-induced systemic arterial hypotension (P < 0.001) and improved left ventricular stroke work index in all sheep (P < 0.05). Intermittent bolus injections of terlipressin were linked to decreases in heart rate and cardiac index and increases in pulmonary vascular resistance index (each, P < 0.001). These unwanted side effects were prevented by continuous low-dose infusion of the drug. In conclusion, continuous infusion of terlipressin stabilized hemodynamics and improved myocardial performance in endotoxemic ewes without obvious side effects. Continuous low-dose terlipressin infusion may represent a useful alternative treatment of arterial hypotension related to sepsis and systemic inflammatory response syndrome.

Continuous terlipressin infusion in patients with persistent septic shock and cirrhosis of the liver

Continuous terlipressin infusion in patients with persistent septic shock and cirrhosis of the liver

Continuous terlipressin infusion in patients with septic shock: less may be best, and the earlier the better?

Continuous terlipressin infusion in patients with septic shock: less may be best, and the earlier the better?

The Role of Terlipressin in Pediatric Septic Shock: A Review of the Literature and Personal Experience

Vasopressin and its synthetic analog terlipressin are potent vasopressors that could be useful in vasodilatory septic shock. In septic adults, vasopressin-terlipressin have been shown to increase mean arterial pressure and to decrease the necessity for catecholamines. Moreover, low doses of vasopressin, or terlipressin, increase urine output and ameliorate oxygenation. Although pediatric septic shock is more often hypodynamic, both vasopressin and terlipressin have proved to be effective in restoring blood pressure or increasing the diuresis in this setting. The purpose of this review is to summarize the physiology of vasopressin and to report the available evidence for the use of vasopressin or terlipressin in pediatric septic shock in order to make best use in this population. We also report our experience with the continuous infusion of terlipressin in two pediatric patients who developed catecholamine refractory septic shock.

Rescue therapy with terlipressin by continuous infusion in a child with catecholamine-resistant septic shock

A 2-month-old female infant presented with septic shock, refractory to high doses of catecholamines. Continuous infusion of terlipressin at a rate of 10 mcg/kgh produced a significant increase in the mean arterial pressure that was evident within half and hour, so allowing a reduction in the rate of catecholamine infusion. However, 18 h later, the blood pressure fell again and finally the patient died. This case shows the potential value of terlipressin infusion to restore normal mean arterial pressure in children with vasodilatory shock and hypotension refractory to catecholamines.

Choc septique réfractaire aux catécholamines : y a-t-il une place pour la terlipressine ?

We report two patients in vasodilatory septic shock refractory to catecholamines in which a continuous infusion of terlipressin was associated with a dramatic increase in systemic arterial blood pressure and short-term survival. Low doses of terlipressin were sufficient in both cases (0.01–0.0 mg h –1) to restore blood pressure by increase of systemic vascular resistances. The haemodynamic response was immediate, long-acting, dose-dependent and reversible in a few hours when the drug administration was stopped. A further increase in terlipressin dose regimen markedly decreased cardiac performance. Terlipressin simultaneously induced vasoconstriction within the cutaneous vascular territory, leading to local skin necrosis. The splanchnic vascular territory seemed to be constricted in the same way. Further studies are needed to better understand and precise the role of terlipressin in the treatment of vasodilatory septic shock refractory to catecholamines.