Terlipressin

Vasoactive drug therapy (somatostatin, octreotide, or terlipressin) to stop or slow bleeding is routinely employed early in patient management to allow stabilization of the patient and to permit endoscopy to proceed under more favorable conditions. These agents decrease splanchnic blood flow and reduce portal and variceal pressures, without significant adverse effects. 

Hepato-renal syndrome rapid progressive (type I) with rising serum creatinine levels, or non-progressive and less severe (type II) impairment of renal function, often consequent on bacterial peritonitis, with persistent ascites responds to vasoconstrictor treatment, typically with terlipressin through constriction of splanchnic vessels and improved renal perfusion. Withdrawal of treatment does not seem to lead inevitably to recurrence. Haemodialysis may also stabilise patients. 

During the past decade, vasopressin has proved beneficial in the treatment of vasodilatory shock states, at least in part by virtue of its Vi agonist activity. Terlipressin (triglycyl lysine vasopressin), a synthetic vasopressin analog that is converted to lysine vasopressin in the body, is also effective. It may have advantages over vasopressin because it is more selective for Vi receptors and has a longer half-life. 

Lange M, Ertmer C, Westphal M Vasopressin vs. terlipressin in the treatment of cardiovascular failure in sepsis. Intensive Care Med 2008 34 821. [PMID 18066524]... 

Terlipressin is a vasopressin analog that appears to have similar efficacy to vasopressin with fewer adverse effects. Although this agent is available in other countries, it has never been approved for use in the USA. 

Terlipressin, a long-acting vasopressin analogue, is metabolized to the active drug lysine vasopressin. The use of terlipressin to treat acute variceal bleeding has been reviewed (2,3). 

A review has suggested that terlipressin has fewer adverse effects than vasopressin however, the studies on which this was based were rated as low in quality (4). 

The use of vasopressin and terlipressin for the management of septic shock has been reviewed a maximum dose of 0.04 U/minute is recommended (5). Vasopressin 0.23 U/minute in patients with hepatorenal syndrome did not appear to be associated with the adverse effects that occur at the lower doses that are used to treat other critically ill patients (6). 

Terlipressin has similar, but less pronounced, systemic hemodynamic effects to vasopressin, including increases in mean arterial pressure and reduced heart rate (9). Of 105 patients who had continuous terlipressin infusions for... 

Of 86 cirrhotic patients treated with terlipressin 10 developed a tachycardia, four developed atrial fibrillation, and one developed ventricular tachycardia. Four patients in the same study developed hypertension (11). In another study, tachycardia occurred in 23% of patients randomized to pitressin for acute variceal bleeding and 8% developed transient hypertension (12). 

Myocardial ischemia has been associated with terlipressin (13). 

A 61-year-old man with coronary artery stenosis became hypotensive during elective surgery, refractory to ephedrine (cumulative dose of 36 mg over 45 minutes). Immediately after terlipressin 1 mg, he developed hypertension and bradycardia, with evidence of myocardial ischemia. 

One of 21 patients with hepatorenal syndrome developed finger ischemia on the fourth day of intermittent intravenous terlipressin and recovered after terlipressin was stopped (14). 

An elderly patient (over 70 years old) with cirrhosis and hepatorenal syndrome developed severe bronchospasm and died after intravenous terlipressin administration the mechanism was not determined (15). 

Six unselected patients (four women), mean age 27 years, with acute liver failure and grade IV hepatic encephalopathy received terlipressin 0.005 mg/kg as a single intravenous bolus (16). There was an increase in cerebral blood flow 1 hour after the bolus, which returned to baseline at 5 hours, and an increase in intracranial pressure at 1 hour, which returned to baseline at 2 hours. The authors speculated that terlipressin could have a deleterious effect on cerebral hemodynamics in patients with severe hepatic encephalopathy. 

High-dose terlipressin (1 mg intravenously every 4 hours for 5 days) was associated with severe hyponatremia and loss of consciousness in one of 45 cirrhotic patients in a randomized trial (11). Of course, cirrhosis itself is associated with hyponatremia. 

Mild lymphangitis was reported in one of 105 patients in a multicenter study of the effects of terlipressin (10). 

It has also been suggested that terlipressin has vasoconstrictor activity within the splanchnic vascular territory (21). Hypotension developed under general anesthesia in 32 patients undergoing carotid endarterectomy treated with renin-angiotensin inhibitors (22). They were randomized to received terlipressin 1 mg (n = 16) or noradrenaline infusion. Compared with baseline those who received terlipressin had reduced gastric mucosal perfusion for at least 4 hours. There was also reduced oxygen delivery and oxygen consumption index at 30 minutes and 4 hours in those who received terlipressin. 

Skin necrosis is often reported after vasopressin therapy. In a retrospective study, two of five patients treated with a continuous infusion of terlipressin developed skin necrosis at the infusion site and a third developed scrotal necrosis (15). 

Bullous necrosis developed within 48 hours of starting an infusion of terlipressin in a 44-year-old man (28). There have been only four previous reports of skin necrosis. 

Delmas A, Leone M, Rousseau S, Albanese J, Martin C. Clinical review vasopressin and terlipressin in septic shock patients. Crit Care 2005 9 212-22. 

Romero G, Kravetz D, Argonz J, Bildozola M, Suarez A, Terg R. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. J Hepatol 2000 32(3) 419-25. 

Escorsell A, Ruiz del Arbol L, Planas R, Albillos A, Banares R, Cales P, Pateron D, Bernard B, Vinel JP, Bosch J. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding the TEST study. Hepatology 2000 32(3) 471-6. 

Bruha R, Marecek Z, Spicak J, Hulek P, Lata J, Petrtyl J, Urbanek P, Taimr P, Volfova M, Dite P. Double-blind randomized, comparative multicenter study of the effect of terlipressin in the treatment of acute esophageal variceal and/or hypertensive gastropathy bleeding. Hepatogastroenterology 2002 49(46) 1161-6. 

Medel J, Boccara G, Van de Steen E, Bertrand M, Godet G, Coriat P. Terlipressin for treating intraoperative hypotension can it unmask myocardial ischemia Anesth Analg 2001 93(l) 53-5. 

Ortega R, Gines P, Uriz J, Cardenas A, Calahorra B, De Las Heras D, Guevara M, Bataller R, Jimenez W, Arroyo V, Rodes J. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome results of a prospective, nonrandomized study. Hepatology 2002 36(4 Pt l) 941-8. 

Halimi C, Bonnard P, Bernard B, Mathurin P, Mofredj A, di Martino V, Demontis R, Henry-Biabaud E, Fievet P, Opolon P, Poynard T, Cadranel JF. Effect of terlipressin... 

Shawcross DL, Davies NA, Mookcrjcc RP, Hayes PC, Williams R, Lee A, Jalan R. Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy. Hepatology 2004 39 471-5. 

Fellahi JL, Benard P, Daccache G, Mourgeon E, Gerard JL. Vasodilatory septic shock refractory to catecholamines is there a role for terlipressin Ann Fr Anesth Reanim 2003 22 631 1. 

Morelli A, Tritapepe L, Rocco M, Conti G, Orecchioni A, De Gaetano A, Picchini U, Pelaia P, Reale C, Pietropaoli P. Terlipressin versus norepinephrine to counteract anesthesia-induced hypotension in patients treated with renin-angiotensin system inhibitors effects on systemic and regional hemodynamics. Anesthesiology 2005 102 12-19. 

Kam PCA, Williams S, Yoong FFY. Vasopressin and terlipressin pharmacology and its clinical relevance. Anaesthesia 2004 59 993-1001. 

Tomassini E, Guiot P, Poussel JF, De Cubber J, Schnitzler B. Bullous disease following intravenous terlipressin infusion. Reanim Urgences 20(X) 9 313—4. 

Rolla D, Cannella G, Ravetti JL. Toxic rhabdomyolysis induced by terlipressin infusion in a uraemic patient suffering from AA-type amyloidosis. Nephron 1999 83(2) 167-8. 

The next day the patient had decreased respiratory rate, became tired with falling blood sugar and acidosis. She had acute renal failure with urine output <30 mL/h and was in fluid overload. The doctors started her on terlipressin 2 mg q.d.s. and HAS (Human Albumin Solution) 20% to maintain central venous pressure 8-12 mmHg and prevent hepatorenal syndrome. Terlipressin is a prodrug for vasopressin. 

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