RESUMO
BACKGROUND & AIMS: Studies of variceal bleeding have shown that a hemodynamic response to treatment of portal hypertension is appropriate when the hepatic venous pressure gradient (HVPG) decreases below 12 mmHg or by > 20% from baseline. However, in primary prophylaxis, many nonresponders do not bleed and 2 invasive procedures are needed to assess response. We investigated the long-term prognostic value of an acute response to beta-blockers and whether the target reduction in HVPG can be improved in primary prophylaxis. METHODS: An initial hemodynamic study was performed in patients with large varices and without previous bleeding. After baseline measurements were made, propranolol was administered intravenously and measurements were repeated 20 minutes later. Patients were given nadolol daily and a second hemodynamic study was performed. RESULTS: Of 105 patients, 15% had variceal bleeding. Using receiver operating characteristic curve analysis, a decrease of HVPG > or = 10% was the best value to predict bleeding. In the initial study, 75 patients (71%) were responders (HVPG decreased to < or = 12 mmHg or by > or = 10%) and had a lower probability of first bleeding than nonresponders (4% vs 46% at 24 months; P < .001). Acute responders also had a lower risk of developing ascites (P = .001). Chronic responders had a lower probability of bleeding than nonresponders (P < .001). There was a correlation between acute and chronic changes in HVPG (r = 0.62; P = .01). CONCLUSION: The acute hemodynamic response to beta-blockers can be used to predict the long-term risk of first bleeding. An HVPG reduction > 10% from baseline is the best target to define response in primary prophylaxis.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Hemodinâmica/efeitos dos fármacos , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Nadolol/uso terapêutico , Propranolol/uso terapêutico , Idoso , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/mortalidade , Varizes Esofágicas e Gástricas/fisiopatologia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/fisiopatologia , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/mortalidade , Hipertensão Portal/fisiopatologia , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/efeitos dos fármacos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: The currently recommended treatment for acute variceal bleeding is the association of vasoactive drugs and endoscopic therapy. However, which emergency endoscopic treatment combines better with drugs has not been clarified. This study compares the efficacy and safety of variceal ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin. METHODS: Patients admitted with acute gastrointestinal bleeding and with suspected cirrhosis received somatostatin infusion (for 5 days). Endoscopy was performed within 6h and those with esophageal variceal bleeding were randomized to receive either sclerotherapy (N=89) or ligation (N=90). RESULTS: Therapeutic failure occurred in 21 patients treated with sclerotherapy (24%) and in nine treated with ligation (10%) (RR=2.4, 95% CI=1.1-4.9). Failure to control bleeding occurred in 15% vs 4%, respectively (P=0.02). Treatment group, shock and HVPG >16 mmHg were independent predictors of failure. Side-effects occurred in 28% of patients receiving sclerotherapy vs 14% with ligation (RR=1.9, 95% CI=1.1-3.5), being serious in 13% vs 4% (P=0.04). Six-week survival probability without therapeutic failure was better with ligation (P=0.01). CONCLUSIONS: The use of variceal ligation instead of sclerotherapy as emergency endoscopic therapy added to somatostatin for the treatment of acute variceal bleeding significantly improves the efficacy and safety.
Assuntos
Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/cirurgia , Hormônios/administração & dosagem , Escleroterapia , Somatostatina/administração & dosagem , Doença Aguda , Idoso , Pressão Sanguínea , Terapia Combinada , Serviços Médicos de Emergência , Endoscopia Gastrointestinal , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Hipertensão Portal/complicações , Ligadura , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Falha de TratamentoRESUMO
OBJECTIVES: High dose of somatostatin infusion achieves a greater reduction of hepatic venous pressure gradient (HVPG) than the usual dose, and terlipressin decreases HVPG through mechanisms other than somatostatin. Our aim was to assess the hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. METHODS: Hemodynamic studies were performed in 80 patients with cirrhosis and variceal bleeding during the first 3 days of admission. After baseline measurements, somatostatin was administered (250 microg/h with an initial bolus of 250 microg). Patients were considered responders when the HVPG decreased by >10% from baseline (n = 31). Nonresponders were randomized under double-blind conditions to a control group (n = 7), or to receive terlipressin (2 mg IV bolus, n = 22), or high dose of somatostatin (500 microg/h, n = 20). Final measurements were obtained 30 min later. RESULTS: Terlipressin caused a decrease in HVPG (from 22.2 +/- 5 to 19.1 +/- 5.2, p < 0.01) and heart rate (p < 0.01), while mean arterial pressure increased (p < 0.01). High somatostatin dose also reduced HVPG (from 21.8 +/- 3.4 to 19.6 +/- 3.1, p < 0.01), although this decrease was more pronounced with terlipressin (15%+/- 9%vs 10%+/- 6% from baseline, p= 0.05). Both terlipressin and high somatostatin dose achieved a significantly higher rate of response than that in the control group. A decrease in HVPG >20% was observed in 36% of cases with terlipressin versus 5% with high somatostatin dose (p= 0.02). CONCLUSIONS: In nonresponders to usual somatostatin dose, both terlipressin and high-dose of somatostatin infusion significantly decreased HVPG and increased the rate of hemodynamic responders. Such effects were greater with terlipressin. Both treatments may be an alternative when standard somatostatin fails.
Assuntos
Varizes Esofágicas e Gástricas/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Lipressina/análogos & derivados , Lipressina/farmacologia , Somatostatina/administração & dosagem , Vasoconstritores/farmacologia , Idoso , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Circulação Hepática/efeitos dos fármacos , Lipressina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Terlipressina , Vasoconstritores/administração & dosagem , Pressão Venosa/efeitos dos fármacosRESUMO
BACKGROUND/AIMS: Following treatment with beta blockers in patients with cirrhosis and portal hypertension, reduction of hepatic venous pressure gradient (HVPG) to <12 mmHg or by >20% of baseline induces an extremely low risk of variceal bleeding. However, several factors such as compliance to therapy or alcohol abstinence may change the initial response after a long follow-up, and the effect of response on other complications of cirrhosis is less clear. The aim of this study was to assess the long-term maintenance of hemodynamic response and its influence on complications of cirrhosis. METHODS: One hundred and thirty two cirrhotic patients received nadolol and isosorbide mononitrate to prevent variceal rebleeding. HVPG was measured at baseline, after 1 to 3 months under treatment and again 12 to 18 months later. RESULTS: Sixty four patients were responders. After a longer follow-up, earlier response did not change in 81% of cases. Changes of response were mainly related to modifications in medication dose or in alcohol intake. As compared with poor-responders, responders had a lower probability of developing ascites (P<0.001) and related conditions, a greater improvement of Child-Pugh score (P=0.03), and a lower likelihood of developing encephalopathy (P=0.001) and of requiring liver transplantation (P=0.002). Eleven responders and 22 poor-responders died (P=0.029). CONCLUSIONS: Hemodynamic response to treatment of portal hypertension is usually sustained after a long-term follow-up. Response decreases the probability of developing complications of cirrhosis and the need for liver transplantation, and significantly improves survival.