Càndid Villanueva

Transfusion Strategies for Acute Upper Gastrointestinal Bleeding

BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. RESULTS A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. CONCLUSIONS As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).

Nadolol plus Isosorbide Mononitrate Compared with Sclerotherapy for the Prevention of Variceal Rebleeding

BACKGROUND Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.

Norfloxacin Prevents Bacterial Infection in Cirrhotics With Gastrointestinal Hemorrhage

To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.

Value of second-look endoscopy after injection therapy for bleeding peptic ulcer: A prospective and randomized trial

A prospective and randomized trial involving 104 patients was performed to assess whether second-look endoscopy could improve the efficacy of injection therapy for bleeding ulcers. The inclusion criteria were the presence of active arterial bleeding or a non-bleeding visible vessel at emergency endoscopy. All the patients received emergency injection of 1:10,000 adrenaline and were subsequently randomized (52 patients in each group) according to whether or not they would receive a second elective endoscopy within the first 24 hours with repeated injection if a visible vessel was still identified. Both groups were well matched for clinical and endoscopic data. A tendency towards better results was noted in the group that received a second-look endoscopy; the two groups were compared in regard to further bleeding (21% versus 29%, 95% confidence interval of the difference = -24.3 to 8.5), need for emergency surgery (8% versus 15%, 95% confidence interval of the difference = -19.9 to 4.5), transfusion requirements (1.7 +/- 1.9 versus 2.5 +/- 2.5 units, 95% confidence interval of the difference = -1.6 to 0.07), length of hospital stay (9.3 +/- 8.6 versus 11.8 +/- 10.8 days, 95% confidence interval of the difference = -6.2 to 1.4), and mortality rate (2% versus 4%). Although these trends did not achieve statistical significance, a type II error cannot be ruled out. However, according to our results, several hundred patients would be required to demonstrate statistically these relatively small differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: a multicentre randomised controlled trial

Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n = 78) or combined with EBL (Drug+EBL; n = 80). HVPG measurements were performed at randomisation and after 4–6 weeks on medical therapy. Results: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p = 0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction ⩾20% or ⩽12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL. Conclusions: Adding EBL to pharmacological treatment did not reduce recurrent bleeding, the need for rescue therapy, or mortality, and was associated with more adverse events. Furthermore, associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders. ISRCTN26221020

Development of Ascites in Compensated Cirrhosis With Severe Portal Hypertension Treated With β-Blockers

OBJECTIVES:In compensated cirrhosis, a threshold value of hepatic venous pressure gradient (HVPG) ≥10 mm Hg is required for the development of decompensation. However, whether the treatment of portal hypertension (PHT) can prevent the transition into development of ascites once this level has been reached is unclear. Our aim was to assess the relationship between changes in HVPG induced by β-blockers and development of ascites in compensated cirrhosis with severe PHT.METHODS:Eighty-three patients without any previous decompensation of cirrhosis, with large esophageal varices and HVPG ≥12 mm Hg were included. After baseline hemodynamic measurements nadolol was administered and a second hemodynamic study was repeated 1–3 months later.RESULTS:During 53±30 months of follow-up, decompensation occurred in 52 patients (62%) and in 81% of them ascites was the first manifestation. Using receiver operating characteristic curve analysis a decrease in HVPG ≥10% was the best cutoff to predict ascites. As compared with nonresponders, patients with an HVPG decrease ≥10% had a lower probability of developing ascites (19% vs. 57% at 3 years, P<0.001), refractory ascites (P=0.007), and hepatorenal syndrome (P=0.027). By Cox regression analysis hemodynamic nonresponse was the best predictor of ascites. By stepwise logistic regression, development of ascites was independently associated with nonresponse, whereas refractory ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis were not.CONCLUSIONS:In patients with compensated cirrhosis and large varices treated with β-blockers, an HVPG decrease ≥10% significantly reduces the risk of developing ascitic decompensation and other related complications such as refractory ascites or hepatorenal syndrome.

Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol.

In a prospective randomized trial involving 63 patients with bleeding peptic ulcer, we assessed whether the addition of 1% polidocanol improved the results achieved by 1/10(4) adrenaline alone for injection therapy. The inclusion criterion was the presence of active arterial bleeding or a nonbleeding visible vessel at emergency endoscopy. Thirty patients were treated with 1/10(4) adrenaline (group A) and 33 with adrenaline plus 1% polidocanol (group B). Initial hemostasis was achieved in 97% of cases in both groups and permanent hemostasis in 87% patients in group A and in 76% in group B (p = NS). Mortality was 6% in group A and 3% in group B. There were no differences between the two groups regarding requirements for emergency surgery, the number of transfusions, or the length of hospital stay. One patient in group B had a perforation. No other relevant complications were noted. In conclusion, combined therapy does not improve the results achieved with adrenaline alone.

Esophageal balloon tamponade versus esophageal stent in controlling acute refractory variceal bleeding: A multicenter randomized, controlled trial

Balloon tamponade is recommended only as a “bridge” to definitive therapy in patients with cirrhosis and massive or refractory esophageal variceal bleeding (EVB), but is frequently associated with rebleeding and severe complications. Preliminary, noncontrolled data suggest that a self‐expandable, esophageal covered metal stent (SX‐ELLA Danis; Ella‐CS, Hradec Kralove, Czech Republic) may be an effective and safer alternative to balloon tamponade. We conducted a randomized, controlled trial aimed at comparing esophageal stent versus balloon tamponade in patients with cirrhosis and EVB refractory to medical and endoscopic treatment. Primary endpoint was success of therapy, defined as survival at day 15 with control of bleeding and without serious adverse events (SAEs). Twenty‐eight patients were randomized to Sengstaken‐Blakemore tube (n = 15) or SX‐ELLA Danis stent (n = 13). Patients were comparable in severity of liver failure, active bleeding at endoscopy, and initial therapy. Success of therapy was more frequent in the esophageal stent than in balloon tamponade group (66% vs. 20%; P = 0.025). Moreover, control of bleeding was higher (85% vs. 47%; P = 0.037) and transfusional requirements (2 vs 6 PRBC; P = 0.08) and SAEs lower (15% vs. 47%; P = 0.077) in the esophageal stent group. TIPS was used more frequently in the tamponade group (4 vs. 10; P = 0.12). There were no significant differences in 6‐week survival (54% vs. 40%; P = 0.46). Conclusion: Esophageal stents have greater efficacy with less SAEs than balloon tamponade in the control of EVB in treatment failures. Our findings favor the use of esophageal stents in patients with EVB uncontrolled with medical and endoscopic treatment. (Hepatology 2016;63:1957‐1967)

Recomendaciones para el diagnóstico y el tratamiento de la hemorragia digestiva alta aguda no varicosa

Se define como hemorragia digestiva alta aquella que se origina en una lesión situada por encima del ángulo de Treitz. Clínicamente, se manifiesta en forma de hematemesis de sangre fresca o en «poso de café», de melenas, de ambas o, con menor frecuencia, como hematoquecia. La causa más frecuente de hemorragia digestiva alta no varicosa es la úlcera péptica gastroduodenal, que representa alrededor del 70% de los casos, pero también puede ser debida a lesiones agudas de la mucosa gástrica, esofagitis, síndrome de Mallory-Weiss, tumores o lesiones vasculares. La hemorragia digestiva alta no varicosa es una emergencia médica frecuente, con una incidencia anual que oscila entre 50 y 150 casos por 100.000 habitantes1. Ello representa un elevado número de ingresos anuales y un consumo muy elevado de recursos sanitarios. A pesar de los importantes avances de los últimos años, la mortalidad asociada a la hemorragia digestiva alta no varicosa todavía es elevada en algunas series (10%)2,3, aunque en estudios más recientes ha descendido hasta valores del 2%4. La reducción de la mortalidad observada en las series más recientes se debe, principalmente, al mejor conocimiento de los factores pronósticos en la hemorragia digestiva alta2,3,5-9 y, sobre todo, a la introducción y el desarrollo de diferentes técnicas de terapéutica endoscópica que ha condicionado un notable descenso de la incidencia de recidiva de la hemorragia y de la necesidad de tratamiento quirúrgico10. No obstante, existen otros factores que han contribuido a este descenso de mortalidad, y entre ellos debemos destacar el tratamiento de estos pacientes en «unidades de sangrantes». En ellas, los pacientes son atendidos por un equipo médico multidisciplinario (formado por gastroenterólogo, cirujano, endoscopista y radiólogo) y personal de enfermería especializado y altamente cualificado en el manejo de la hemorragia digestiva alta. Estas unidades también favorecen la concentración de recursos terapéuticos y la aplicación de protocolos que conducirán a un manejo más homogéneo de los pacientes. En cualquier caso, es fundamental tratar a los pacientes con hemorragia digestiva alta en centros que dispongan del personal y los recursos necesarios para tratar adecuadamente a estos pacientes. La hemorragia digestiva alta no varicosa es una entidad idónea para la confección de una guía clínica, porque tiene una elevada incidencia y ocasiona un importante consumo de recursos. A pesar de la abundante información acumulada en los últimos años sobre su pronóstico y tratamiento, todavía existe una importante heterogeneidad en el manejo de los pacientes, lo que puede ocasionar resultados clínicos diferentes. En este sentido, un estudio realizado recientemente en hospitales universitarios de nuestro país11 pone de manifiesto el diferente manejo de la hemorragia digestiva en función del servicio de ingreso del paciente (gastroenterología, cirugía o medicina interna). Si bien no se observan diferencias significativas en la mortalidad, la estancia media y el coste de la hospitalización fueron significativamente inferiores en los pacientes ingresados en el servicio de gastroenterología, que en los de cirugía o medicina interna. Estos hechos ponen de manifiesto la necesidad de una guía clínica para la hemorragia digestiva alta no varicosa, que permita homogeneizar la conducta, mejorar la calidad de la asistencia que reciben los pacientes y optimizar la utilización de recursos sanitarios. Por iniciativa de la Junta de Gobierno de la Societat Catalana de Digestologia, se constituyó un grupo de trabajo formado por 11 especialistas con amplia experiencia en el diagnóstico y el tratamiento de la hemorragia digestiva, entre los cuales había gastroenterólogos, endoscopistas y cirujanos, con el objetivo de confeccionar una guía clínica para la hemorragia digestiva alta aguda no varicosa. Cada uno de los miembros del grupo desarrolló diferentes temas de la guía, que fueron discutidos conjuntamente en las 10 reuniones de trabajo que se realizaron a lo largo de algo más de un año. Las recomendaciones que se exponen a continuación son fruto de la revisión de la mejor evidenCorrespondencia: Dr. F. Feu. Servicio de Gastroenterología. Hospital Clínic. Villarroel, 170. 08036 Barcelona. España. Correo electrónico: ffeu@clinic.ub.es

Cognitive dysfunction in cirrhosis is associated with falls: a prospective study.

Falls are frequent among patients with debilitating disorders and can have a serious effect on health status. Mild cognitive disturbances associated with cirrhosis may increase the risk for falls. Identifying subjects at risk may allow the implementation of preventive measures. Our aim was to assess the predictive value of the Psychometric Hepatic Encephalopathy Score (PHES) in identifying patients likely to sustain falls. One hundred and twenty‐two outpatients with cirrhosis were assessed using the PHES and were followed at specified intervals. One third of them exhibited cognitive dysfunction (CD) according to the PHES (<−4). Seventeen of the forty‐two patients (40.4%) with CD had at least one fall during follow‐up. In comparison, only 5 of 80 (6.2%) without CD had falls (P < 0.001). Fractures occurred in 4 patients (9.5%) with CD, but in no patients without CD (P = 0.01). Patients with CD needed more healthcare (23.8% versus 2.5%; P < 0.001), more emergency room care (14.2% versus 2.5%; P = 0.02), and more hospitalization (9.5% versus 0%; P = 0.01) as a result of falls than patients without CD. Patients taking psychoactive treatment (n = 21) had a higher frequency of falls, and this was related to an abnormal PHES. In patients without psychoactive treatment (n = 101), the incidence of falls was 32.4% in patients with CD versus 7.5% in those without CD (P = 0.003). In the multivariate analysis, CD was the only independent predictive factor of falls (odds ratio, 10.2; 95% confidence interval, 3.4‐30.4; P < 0.001). The 1‐year probability of falling was 52.3% in patients with CD and 6.5% in those without (P < 0.001). Conclusion: An abnormal PHES identifies patients with cirrhosis who are at risk for falls. This psychometric test may be useful to promote awareness of falls and identify patients who may benefit from preventive strategies. (HEPATOLOGY 2012;55:1922–1930)