Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

Poor outcomes with treatment of hepatorenal syndrome type 1 with splancnic vasoconstrictors and albumin: report of seven cases and review of the literature / Resultados adversos com o emprego de vasoconstritores esplâncnicos e albumina para tratamento da síndrome hepatorrenal do tipo 1: relato de sete casos e revisão da literatura

CONTEXT: Treatment of hepatorenal syndrome type 1 (HRS-1) with splancnic vasoconstrictors and high-dose albumin has been associated with reversal of renal failure in approximately 60 percent to 80 percent of the cases in pilot or uncontrolled studies. OBJECTIVE: To evaluate the results of treatment of HRS-1 with terlipressin and high-dose albumin. METHODS: All patients with HRS-1 that underwent treatment with terlipressin and high-dose albumin at our unit were retrospectively reviewed. Outcomes including reversal of renal failure and death were recorded and compared to baseline clinical and laboratory parameters. RESULTS: Seven subjects (median age 64 [47-69] years, 5 males) with median Child-Pugh and MELD scores of 12 [10-15] and 22 [17-38], respectively, hospitalized with decompensated chronic liver disease secondary to tense ascitis and infections, who exhibited criteria for HRS-1, were submitted to therapy with terlipressin and high-dose albumin according to a predefined standard protocol. Baseline creatinine levels were 2.9 [2.3-4.0] mg/mL. None of the patients achieved reversal of HRS-1 and five subjects died on-treatment due to sudden-death (n = 1), multiple organ dysfunction associated with end-stage liver failure (n = 2) and sepsis (n = 2). CONCLUSIONS: Treatment of HRS-1 with terlipressin and high-dose albumin was not associated with reversal of renal failure, but most of the treated subjects had severe end-stage liver disease with high MELD scores as well as high baseline creatinine values, parameters previously associated with bad outcomes.

CONTEXTO: O tratamento da síndrome hepatorrenal do tipo 1 (SHR-1) com vasoconstritores esplâncnicos e albumina intravenosa tem se associado, em relatos de caso e estudos piloto não-controlados, à reversão da insuficiência renal em 60 por cento-80 por cento dos pacientes tratados. OBJETIVO: Avaliar os resultados do tratamento da SHR-1 com terlipressina e albumina. MÉTODOS: Foram avaliados, retrospectivamente, todos os pacientes hospitalizados com o diagnóstico de SHR-1 que se submeteram a tratamento com terlipressina associada à albumina em altas doses. As frequências de reversão de insuficiência renal e óbito foram comparados com parâmetros clínicos e laboratoriais pré-tratamento. RESULTADOS: Sete pacientes (5 homens, idade mediana 64 [47-69] anos) com mediana de pontuação Child-Pugh e MELD respectivamente de 12 [10-15] e 22 [17-38], admitidos na unidade de terapia intensiva por desconforto respiratório secundário à ascite tensa ou por infecções, que apresentaram critérios para SHR-1 e eligibilidade para o transplante de fígado foram submetidos a tratamento com terlipressina e albumina, de acordo com protocolo pré-definido. Níveis de creatinina prévios ao tratamento foram de 2.9 [2.3-4.0] mg/mL. Nenhum paciente apresentou reversão da SHR-1 e cinco faleceram por morte súbita (n = 1), disfunção de múltiplos órgãos associada a falência hepática (n = 2) e sepse (n = 2), a maioria antes de completar o tratamento. CONCLUSÕES: O tratamento da SHR-1 com terlipressina e albumina, em altas doses, não foi associado à reversão da insuficiência renal em nenhum dos pacientes tratados, mas a maioria dos pacientes apresentava doença hepática em fase avançada, com altos valores de MELD, e níveis elevados de creatinina pré-tratamento, parâmetros previamente associados com pior resposta e prognóstico mais reservado.

Emerging role of vasopressin.

Ionotropic agents are frequently used in vasodilatory shock like conditions of septic or nonseptic origin. Conventional catecholamines such as norepinephrine are used at a very high dose with possibility of adverse effects in many patients. One often encounters refractoriness to these drugs. Infusion of vasopressin (VP) which is detectable at inappropriately low level in advanced phase of septic shock might allow withdrawal of catecholamines, as it maintains adequate mean arterial pressure (MAP), improves urine output and leaves perfusion of vital organs unhindered. Vasopressin has been found to be superior to epinephrine in animal models and some human trials, especially in patients with resistant ventricular fibrillation (VF) while doing cardiopulmonary resuscitation (CPR). Analogues of VP have also been used for diuresis in patients of hepatorenal syndrome.

A Case of Peripheral Ischemic Complication after Terlipressin Therapy / 대한소화기학회지

Hepatorenal syndrome is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin is a nonselective V1 vasopressin agonist. When comparing with ornipressin, it is known to have a similar vasoconstricting potency, but much less ischemic complication. We report a case of gangrene on toes and necrosis on the infusion site of left hand which developed after the use of terlipressin due to hepatorenal syndrome in a 41-year-old-man with liver cirrhosis. Ischemic complication of terlipressin is rare and there has been no case report in Korea. Although it is rare, we must pay attention to the peripheral ischemic complication of terlipressin.

Problemas renales de la cirrosis

Cirrhosis of the liver is a common entity frequently seen by the clinician only after initiation of edema or ascitis. Renal problems have been described for many years associated to all types of cirrhosis, and are responsible for many abnormalities of water and electrolytes seen in these patients. One of the most remarkable renal abnormalities is sodium retention, with urinary excretion (Una V) of less than 10 mEq/1. This fact explains the common appearance of edema and ascitis even in the early states of cirrhosis. For many years two main theories have been postulated in order to explain this avid sodium retention: 1) The "underfill theory" states that the initial event is a state of peripheral vasodilatation that causes ineffective plasma volume and sodium retention by the kidney, meaning that the sodium retention is a secondary event. 2) the "overflow theory" in contrast, emphasizes that the primary event is sodium retention by the kidney, with secondary expansion of plasma volume and associated sequestration of fluid in the abdomen due to portal hypertension and a reduction of the colloid-osmotic pressure. Recent evidence is suggestive that both theories play a significant role in the avid sodium retention of cirrhosis. In order to explain the sodium retention by the kidney the following humoral factors have been postulated: increased secretion and decreased degradation of aldosterone, decreased production of prostaglandin E, increased secretion of catecholamines, decreased response to the natriuretic atrial factor and abnormalities of the kalikrein-kinin system. Although some studies have shown abnormalities in the handling of water by the kidney, most of the evidence suggest that it is due to the sodium retention...