Terlipressin has Stood the Test of Time

Clinical Overview in 2020 and Future Perspectives

Anand V. Kulkarni; Juan Pablo Arab; Madhumita Premkumar; Carlos Benítez; Sowmya Tirumalige Ravikumar; Pramod Kumar; Mithun Sharma; Duvvuru Nageshwar Reddy; Douglas A. Simonetto; Padaki Nagaraja Rao


Liver International. 2020;40(12):2888-2905. 

In This Article

Reported Adverse Events of Terlipressin

The adverse effects of terlipressin and its management are described in Table 4. The most common adverse effects are abdominal pain and diarrhoea, which occur in about 20% of the patients.[3] Terlipressin is also known to cause dysrhythmia and ischaemic cardiovascular events.[22] Patients on terlipressin should be frequently examined to detect peripheral ischaemia, cyanosis, livedo reticularis or skin necrosis of the fingers or extremities, which are more common in high MELD and ACLF patients.[96] Terlipressin leads to vasoconstriction and, hence, cyanosis is a common occurrence. N-acetyl cysteine, a potent antioxidant, has been reported to improve the cyanosis caused by intense peripheral vasoconstriction by increasing NO-mediated vasodilation.[97] Anaphylaxis, bronchospasm and mesenteric ischaemia have been reported with terlipressin therapy.[2] Terlipressin increases the afterload and end-diastolic volume with a concurrent reduction in cardiac index.[98] This may unmask the pre-existing cardiac dysfunction in cirrhosis and lead to volume overload and pulmonary oedema, particularly if large amounts of albumin are given as in HRS. In a recent randomised study of terlipressin alone vs dobutamine with terlipressin, dobutamine reversed the cardio-suppressive effect of terlipressin without any change in GFR/renal functions.[99] However, dobutamine reduced the peripheral vascular resistance and activated renin-angiotensin-aldosterone system (RAAS) which may preclude its use in decompensated cirrhosis patients with HRS who already have pre-existing hyperaldosteronism.

Hyponatremia has been described more commonly in the setting of acute variceal bleed, which can be overcome with albumin infusion.[64,100–102] Hyponatremia is more often noted in patients whose bleed is controlled with terlipressin.[100] Serum albumin, sCr and duration of hyponatremia predict the development of severe hyponatremia (serum sodium <125 mmol/L).[101] Continuous infusion of terlipressin in AVB may reduce the incidence of hyponatremia as a result of lower dose requirements. Adverse effects are more common in patients with diabetes mellitus, peripheral vascular disease and smokers who have a high risk of vasculopathy. Pre-existing cardiovascular diseases is a strict contraindication. Prior cerebrovascular event, asthma, chronic obstructive airway disease, severe peripheral arterial disease, age >70 years and pregnancy are some of the contraindications for terlipressin therapy.[1]