Comparison of 12-hour with 72-hour terlipressin therapy for bleeding esophageal varices

Objective: To determine the efficacy of 12-hour of Terlipressin therapy as compared to 72-hour therapy in preventing rebleeding after endoscopic therapy

Study Design: Interventional study

Place and Duration of Study: Department of Gastroenterology and Hepatology, Shaikh Zayed Hospital, Lahore, from January to March 2016

Methodology: Cirrhotic patients presenting to our hospital with Gl [gastrointestinal] bleeding received Terlipressin 2 mg intravenous bolus, followed by 1mg 6-hourly until undergoing endoscopy.;Those with esophageal varices as the source of bleeding underwent band ligation and were recruited. Of the 93 enrolled patients, 90 remained and were randomized into 25 [27.8%] in control Group-A and 65 [72.2%] in test Group-B. Group-A received 72-hour of Terlipressin while Group-B received it for 12-hour. Both groups were monitored for rebleeding for 5 days

Results: Rebleeding occurred in 1 [4%] patient in Group-A and 3 [4.6%] in Group-B during the 5-day period. All 4 [4.4%] underwent repeat endoscopy. The Group-A patient and 2 [3%] of 3 Group-B patients showed ulcers over band ligation sites as source of bleed. The third Group-B patient showed varices requiring repeat banding. One [4%] patient [Group-A]

died due to persistent encephalopathy. No drug related adverse effects were seen

Conclusion: A 12-hour duration of Terlipressin as an adjunct to endoscopic band ligation shows similar results to 72-hour therapy

Noradrenaline vs terlipressin for hepatorenal syndrome (no to hepatorenal syndrome): A meta-analysis

INTRODUCTION: Hepatorenal syndrome (HRS) is a functional renal impairment associated with advanced cirrhosis. The best treatment is liver transplantation; however, many patients die before this can be done. Terlipressin improves renal function in HRS, but recent studies have shown similar effects with the cheaper and more readily available norepinephrine. This review included randomized trials comparing noradrenaline to terlipressin for patients with type 1 HRS, as defined by the International Ascites Club. OBJECTIVE: To determine the safety and effectiveness of noradrenaline in the management of HRS in terms of 1) reducing mortality, 2) reversal and 3) occurrence of adverse events METHODOLOGY: For this meta-analysis paper, the researchers utilized an electronic search of databases and manual scanning of reference lists were performed. Standardized eligibility assessment was performed independently by three reviewers. Review Manager 5.0.23 was used to calculate odds ratios (OR) with 95% confidence intervals (CIs) as well as I2 values for inter-trial heterogeneity. Standardized eligibility assessment was performed independently by three reviewers. RESULTS: Thirty-six articles were found after electronic and manual searching. Three were assessed for validity and included in the final analysis. The total number of patients across all trials was 95. Noradrenaline was found not to differ from terlipressin in terms of 15-day survival rate (OR 01.17; 95% CI: 0.51-2.66), reversal of HRS (OR1.07; 95% CI: 0.47-2.44), and a post-hoc analysis on disease-free survival (OR 0.78; 95% CI: 0.34-1.79). Results of sensitivity analysis were consistent with the previous findings (15-day survival: OR=1.21 95% CI = 0.52-2.83; HRS reversal: OR= 1.33, 95% CI = 0.56-3.13; disease-free survival: 1.35, CI =0.56-3.25). Only transient adverse effects were noted with either drugs. CONCLUSION: There is inconclusive evidence that noradrenaline and terlipressin are significantly different in the reversal of HRS and reduction of mortality. Larger trials on noradrenaline or a non-inferiority trial may be needed to establish the equivalence of noradrenaline with terlipressin.

A comparative study of high-or low-dose terlipressin therapy in patients with cirrhosis and type 1 hepatorenal syndrome / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To perform an analysis and comparative study of the clinical data for patients with cirrhosis and type 1 hepatorenal syndrome (HRS) who received treatment with terlipressin using high-or low-dose regimens.</p><p><b>METHODS</b>A total of 56 patients with cirrhosis and type 1 HRS who presented for treatment to the Wuhan Medical Treatment Center and Taizhou Central Hospital between March 2010 and October 2012 were enrolled in the study. The patients were randomly assigned to the terlipressin treatment groups for receipt of the high-dose regimen (1 mg/6-8 h;n =27) or low-dose regimen (1 mg/12 h;n =29). All patients were assessed for 24-hour urine volume, serum blood urea nitrogen (BUN) and creatinine (Cr) levels, therapeutic effect and prognosis, and adverse reactions. Measurements were made before and after the treatment, and on post-treatment days 3, 7 and 14. Inter-group differences were assessed by statistical analyses.</p><p><b>RESULTS</b>The high-dose group showed an increase in 24-hour urine volumes from post-treatment day 3 (1112 ± 262 ml) to day 7 (1938 ± 312 ml), and the volumes on both days were significantly better than those of the low-dose group (day 3:986 ± 162 ml and day 7:1760 ± 300 ml, t =1.500, 1.830, P=0.038, 0.041). The high-dose group also showed a significantly better decreases in serum BUN levels (35.1 ± 8.6 to 30.2 ± 6.3 mmol/L vs.low-dose group: 43.2 ± 10.9 to 35.1 ± 7.6 mmol/L, t =3.200, 5.901, P =0.043, 0.047) and in serum Cr values (219.0 ± 35.1 to 128.2 ± 41.6 vs.low-dose group: 230.3 ± 82.1 to 151.5 ± 38.7, t =2.997, 5.765, P =0.036, 0.046).On post-treatment day 14 the 24-hour urine volume of patients in the high-dose group decreased (to 720+/-136 ml), but the difference from that of the low-dose group was not significant (vs. 620 ± 164 ml, t =1.855, P =0.069). The serum BUN level increased in the high-dose group (to 54.4 ± 15.0 mmol/L), which was statistically different from that in the low-dose group (vs .57.7 ± 17.3 mmol/L, t=5.166, P =0.022); the same trend was seen for the serum Cr value (397.8 ± 127.4 mumol/L vs. 480.3 ± 179.8 mumol/L, t =5.638, P =0.047). No statistically significant differences were observed for the groups in regard to significant efficiency, efficiency or 2-week survival rate (x2 =2.314, 1.767, 0.678, P =0.128, 0.128, 0.410 respectively), but the total efficiency was significantly different between the two groups (x² =5.793, P =0.016). In addition, no serious adverse reactions (including precordial pain, myocardial infarction or intestinal necrosis) were observed in either group.</p><p><b>CONCLUSION</b>Terlipressin therapy at both high and low dosages can lead to significant beneficial effects within as little as 3 days after the treatment; however, the high-dose appears to produce a better lasting efficacy (at day 14 after the treatment). The difference in doses does not appear to markedly affect significant efficiency, efficiency, nor the 2-week survival rate.</p>

Hemorragia variceal: terapia con drogas vasoactivas ¿siempre o en casos seleccionados? / Variceal hemorrhage: pharmacological therapy: always or in selected cases only?

One of the most relevant complications of portal hypertension in cirrhosis is the development of gastroesophageal varices. They are present in 50 percent of patients with cirrhosis at the diagnosis. The risk of bleeding depends on the degree of portal hypertension and the severity of liver disease. Variceal hemorrhage is the most common lethal complication of cirrhosis. In the last decades there had been numerous clinical trials involving different treatment options for variceal bleeding (pharmacological, endoscopic and surgery) trying to establish the best treatment strategy. Since the rise in portal pressure is the cause of variceal rupture, therapies that can decrease portal pressure have a theoretical rationale for their use. Endoscopic treatment, although effective, has no effect on portal pressure. Vasoactive agents (vasopressin and its analogue terlipressin, somatostatin and its analogue octreotide) cause splanchnic vasoconstriction and decrease portal pressure. Pharmacological treatments have the advantage that they can be easily administered, and started as soon as the diagnosis of variceal bleeding is suspected. This makes pharmacological treatment especially attractive for centers that have no chance of emergency endoscopy. At this moment there is sufficient evidence to recommend combined treatment with vasoactive drugs and endoscopy for the control of variceal hemorrhage.

Una de las principales complicaciones de los pacientes cirróticos con hipertensión portal es el desarrollo de várices gastroesofágicas. Éstas están presentes al momento del diagnóstico en alrededor de 50 por ciento de los pacientes con cirrosis. La hemorragia variceal es la complicación letal más frecuente en los pacientes cirróticos. En las últimas décadas se han realizado múltiples esfuerzos para lograr definir la mejor combinación de técnicas (endoscópicas, farmacológicas y quirúrgicas) para disminuir la morbimortalidad asociada a la hemorragia variceal. Dado que la causa de la ruptura de las várices es un aumento de la presión portal, todas las medidas que logren disminuirla son medidas racionales para lograr detener la hemorragia. El tratamiento endoscópico, si bien efectivo, no afecta la fisiopatología de la hemorragia variceal. Las drogas vasoconstrictoras (vasopresina y su derivado terlipresina o somatostatina y su derivado octreotide) actúan a nivel de la circulación esplácnica, disminuyendo el flujo sanguíneo. El tratamiento farmacológico tiene la ventaja de ser fácilmente administrado, incluso antes de realizar una endoscopia, toda vez que se sospecha una hemorragia variceal, lo que hace particularmente atractivo su uso en centros en que no se cuenta con endoscopia de urgencia. Actualmente, existe suficiente evidencia para recomendar el uso de estos fármacos como terapia adicional a la endoscopia ante la sospecha de una hemorragia variceal.

Effects of terlipressin and naloxone compared with epinephrine in a rat model of asphyxia-induced cardiac arrest

OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n = 7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses were tested: 50 µg/kg (TP50; n = 7), 100 µg/kg (TP100; n = 7) and 150 µg/kg (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial pressure values in the TP50 group were higher than those in the epinephrine group at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119 vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30 (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat model of asphyxia-induced cardiac arrest, terlipressin and naloxone were effective vasopressors in cardiopulmonary resuscitation and presented better metabolic profiles than epinephrine. Terlipressin provided better hemodynamic stability than epinephrine. .

A case of peripheral gangrene and osteomyelitis secondary to terlipressin therapy in advanced liver disease

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.

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.

A eficácia da terlipressina versus adrenalina na ressuscitação cardiopulmonar em suínos / The efficacy of terlipressin versus adrenaline in swine cardiopulmonary resuscitation / La eficacia de la terlipresina versus adrenalina en la resucitación cardiopulmonar en cerdos

JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar a eficácia da terlipressina (TP) versus adrenalina (ADR) em aumentar a pressão de perfusão coronariana (PPC) e o retorno da circulação espontânea (RCE) na RCP em suínos. MÉTODOS: Sob anestesia cetamina/tiopental, induziu-se fibrilação ventricular em 44 porcos fêmeas imaturos, permanecendo não assistida por 10 min, seguidos de 2 min de RCP-manual (100 compressões/10 ventilações/min com ar). Os animais foram então alocados em quatro grupos, recebendo: 1) ADR (45 µg.kg-1); 2) salina-placebo (10 mL); 3) TP (20 µg.kg-1); 4) TP (20 µg.kg-1) + ADR (45 µg.kg-1). Desfibrilação foi realizada 2 min após, observando-se os animais sobreviventes por um período de 30 min. ECG, PA sistêmica, PAD e PetCO2 foram monitorados continuamente. RESULTADOS: A TP não diferiu do placebo quanto aos efeitos na PPC, com baixas taxas de RCE em ambos os grupos (1/11 vs.2/11; p = NS). A ADR aumentou a PPC de 13 ± 12 para 54 ± 15 mmHg (p < 0,0001), efeito similar a TP + ADR (de 21 ± 10 para 45 ± 13 mmHg; p < 0,0001), com altas taxas de RCE/sobreviventes em ambos os grupos (10/11 vs.9/11, respectivamente). Entre os sobreviventes, maior PAM foi observada no grupo TP + ADR vs.ADR (105 ± 19 mmHg vs.76 ± 21 mmHg; p = 0,0157). CONCLUSÕES: ADR e TP + ADR foram efetivas para aumentar a PPC/RCE neste modelo experimental, mas a TP, isolada, não foi diferente do placebo. Contudo, nos animais sobreviventes do grupo TP + ADR observou-se maior estabilidade hemodinâmica após a RCE, sugerindo que a TP possa ser uma medicação útil no manuseio da hipotensão pós-RCP.

BACKGROUND AND OBJECTIVES: The objective of the present study was to evaluate the efficacy of terlipressin (TP) vs.adrenaline (ADR) in increasing coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) in swine CPR. METHODS: Under anesthesia with ketamine/thiopental, ventricular fibrillation was induced in 44 female immature pigs, remaining unassisted for 10 minutes, followed by 2 minutes of manual CPR (100 compression/10 ventilations/min with air). Animals were, then, divided into four groups: 1) ADR (45 µg.kg-1); 2) saline-placebo (10 mL); 3) TP 20 µg.kg-1); and TP (20 µg.kg-1) + ADR (45 µg.kg-1). Defibrillation was performed after 2 minutes, observing surviving animals for a 30-minute period. Electrocardiogram, systemic BP, DBP, and PetCO2 were monitored continuously. RESULTS: Terlipressin did not differ from placebo regarding the effects on CPP, with low rates of ROSC in both groups (1/11 vs.2/11; p = NS). Adrenaline increased CPP from 13 ± 12 to 54 ± 15 mmHg (p < 0.0001), similar effect to TP + ADR (from 21 ± 10 to 45 ± 13 mmHg; p < 0.0001), with high rates of ROSC/survivors in both groups (10/11 vs.9/11, respectively). Among survivors, greater MAP was observed in the TP + ADR group vs.ADR (105 ± 19 mmHg vs.76 ± 21 mmHg; p = 0.0157) groups. CONCLUSIONS: Adrenaline and TP + ADR were effective on maintaining CPP/ROSC in this experimental model, but isolated TP did not differ from placebo. However, in surviving animals in the TP + ADR group, greater hemodynamic stability was observed after ROSC, suggesting that TP can be a useful medication in the management of post-CPR hypotension.

JUSTIFICATIVA Y OBJETIVOS: El objetivo de este estudio fue evaluar la eficacia de la terlipresina (TP) versus adrenalina (ADR) en aumentar la presión de perfusión coronaria (PPC) y el retorno de la circulación espontánea (RCE) en la RCP en cerdos. MÉTODOS: Bajo la anestesia ketamina/tiopental, se indujo la fibrilación ventricular en 44 cerdos hembras no adultos, permaneciendo no asistida por 10 min, seguidos de 2 min de RCP-manual (100 compresiones/10 ventilaciones/min con aire). Los animales se ubicaron entonces en cuatro grupos, recibiendo: 1) ADR (45 µg.kg-1); 2) salina-placebo (10 mL); 3) TP (20 µg.kg-1); 4) TP (20 µg.kg-1) + ADR (45 µg.kg-1). La desfibrilación fue realizada 2 min después, haciendo el seguimiento de los animales sobrevivientes por un período de 30 min. ECG, PA sistémica, PAD y PetCO2 fueron monitorizados continuamente. RESULTADOS: La TP no fue diferente del placebo en cuanto a los efectos en la PPC, con bajas tasas de RCE en ambos grupos (1/11 vs.2/11; p = NS). La ADR aumentó la PPC de 13 ± 12 para 54 ± 15 mmHg (p < 0,0001), efecto similar a TP + ADR (de 21 ± 10 para 45 ± 13 mmHg; p < 0,0001), con altas tasas de RCE/supervivientes en ambos grupos (10/11 vs.9/11, respectivamente). Entre los supervivientes, se observó una mayor PAM en el grupo TP + ADR vs.ADR (105 ± 19 mmHg vs.76 ± 21 mmHg; p = 0,0157). CONCLUSIONES: La ADR y TP + ADR fueron efectivas para aumentar la PPC/RCE en este modelo experimental, pero la TP aislada, no fue diferente del placebo. Sin embargo, en los animales supervivientes del grupo TP + ADR, vimos una mayor estabilidad hemodinámica después de la RCE, lo que nos indica que la TP puede ser una medicación útil en el manejo de la hipotensión post-RCP.

Efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na ressuscitação cardiopulmonar: estudo experimental, randomizado e controlado / Hemodynamic and metabolic effects of terlipressin or naloxone in cardiopulmonary resuscitation: an experimental, randomized and controlled trial

Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base...

Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo...

Type 2 Hepatorenal Syndrome in a Cirrhotic Patient Who Underwent Gastric Cancer Surgery / 대한소화기학회지

No abstract available.

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.

Hyperkalemia accompanies hemorrhagic shock and correlates with mortality

OBJECTIVE: This study was designed to evaluate the effects of terlipressin versus fluid resuscitation with normal saline, hypertonic saline or hypertonic-hyperoncotic hydroxyethyl starch, on hemodynamics, metabolics, blood loss and short-term survival in hemorrhagic shock. METHOD: Twenty-nine pigs were subjected to severe liver injury and treated 30 min later with either: (1) 2 mg terlipressin in a bolus, (2) placebo-treated controls, (3) 4 mL/kg 7.5% hypertonic NaCl, (4) 4 mL/kg 7.2% hypertonic-hyperoncotic hydroxyethyl starch 200/0.5, or (5) normal saline at three times lost blood volume. RESULTS: The overall mortality rate was 69%. Blood loss was significantly higher in the hypertonic-hyperoncotic hydroxyethyl starch and normal saline groups than in the terlipressin, hypertonic NaCl and placebo-treated controls groups (p<0.005). Hyperkalemia (K>5 mmol/L) before any treatment occurred in 66% of the patients (80% among non-survivors vs. 22% among survivors, p=0.019). Post-resuscitation hyperkalemia occurred in 86.66% of non-survivors vs. 0% of survivors (p<0.001). Hyperkalemia was the first sign of an unsuccessful outcome for the usual resuscitative procedure and was not related to arterial acidemia. Successfully resuscitated animals showed a significant decrease in serum potassium levels relative to the baseline value. CONCLUSION: Hyperkalemia accompanies hemorrhagic shock and, in addition to providing an early sign of the acute ischemic insult severity, may be responsible for cardiac arrest related to hemorrhagic shock.

Clinical Features and Treatment Outcomes of Upper Gastrointestinal Bleeding in Patients with Cirrhosis

With recent progress in treatment modalities, mortality from upper gastrointestinal (UGI) bleeding has decreased appreciably. The aim of this study was to establish how UGI bleeds are managed in Korean patients with cirrhosis and to evaluate treatment outcomes. A total of 479 episodes of acute UGI bleeding in 464 patients with cirrhosis were included during a six-month period at nine tertiary medical centers. Treatment outcomes were assessed by failure to control bleeding, rebleeding and mortality. The source of bleeding was esophagogastric varices in 77.7% of patients, nonvariceal lesions in 15.9%, and undefined in 6.5%. For control of bleeding, endoscopic and pharmacologic treatments were used in 74.7% and 81.9% of patients, respectively. Variceal ligation was a major technique for endoscopic treatment (90%), and terlipressin and somatostatin were the main pharmacologic agents used (96.4%). Initial hemostasis was achieved in 86.8% of cases, but rebleeding occurred in 3.8% and 16.8% of cases within five days and six weeks of hemorrhage, respectively. Five-day and six-week mortality were 11.3% and 25.9%, respectively. Survival of patients with variceal bleeding seems to be remarkably improved than previous reports, which may suggest the advances in hemostatic methods for control of variceal hemorrhage..

A Case of Ischemic Skin Necrosis after Glypressin Therapy in Liver Cirrhosis / 대한소화기학회지

Terlipressin is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion. Thus, it has a less adverse reaction than vasopressin. We report a case of ischemic skin complication in a cirrhotic patient treated with terlipressin. A 71-year-old man with liver cirrhosis was admitted because of hematemesis and melena. He was commenced on terlipressin at a dose 1 mg every 6 hours for the treatment of varicieal bleeding. After 36 hours of treatment, skin blistering and ecchymosis was noted on the skin of his upper thigh, scrotal area and trunk. We found that terlipressin was a possible cause of ischemic skin complication based on the skin biopsy finding. Terlipressin may induce a complication of the ischemic event. In spite of rarity, special attention needs to paid on the peripheral ischemic complication of terlipressin.

Corrlation of adjusted blood requirement index with treatment intervention and outcome in patients presenting with acute variceal bleeding

To determine the correlation of ABRI with treatment intervention and outcome as discharged or expired in patients of acute variceal bleed. Cross-sectional study Records of all the patients admitted in Medical Unit-IV, Civil Hospital Karachi with acute variceal bleeding during January 2004 to October 2006 were retrieved. Use of vasoactive agents [Terlipressin/Octreotide], endoscopic band ligation [EBL] and outcome [Discharged/Expired] were noted. ABRI was calculated by the following formula: ABRI= Blood Units Transfused/ [[Final Hematocrit - Initial Hematocrit] + 0.01] Mean ABRI were compared by Student's 't' test according to vasoactive therapy, EBL and outcome. Correlation of ABRI with the same variables was also studied by plotting Receiver Operative Curves [ROC]. Seventy six patients fulfilling inclusion criteria were selected. No statistically significant difference was observed in the mean ABRI scores when compared according to vasoactive drug administration, EBL and outcome. Significant correlation with mortality was seen on ROC plot with significantly larger area under the curve. ABRI correlated significantly with mortality in this study. Larger prospective studies with appropriate power are required to evaluate its association with other variables