Joaquim Balanzó

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.

A Nationwide Study of Mortality Associated with Hospital Admission Due to Severe Gastrointestinal Events and Those Associated with Nonsteroidal Antiinflammatory Drug Use

BACKGROUND:The worst outcome of gastrointestinal complications is death. Data regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or aspirin use are scarce.AIM:To determine mortality associated with hospital admission due to major gastrointestinal (GI) events and NSAID/aspirin use.METHODS:The study was based on actual count of deaths from two different data sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198 people. Study 2 used a database from 197 general hospitals, representative of the 269 hospitals in the Spanish National Health System. Information regarding gastrointestinal complications and deaths was obtained throughout the Minimum Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed to NSAID/aspirin use were estimated on the basis of prospectively collected data from hospitals of study 1.RESULTS:The incidence of hospital admission due to major GI events of the entire (upper and lower) gastrointestinal tract was 121.9 events/100,000 persons/year, but those related to the upper GI tract were six times more frequent. Mortality rate was 5.57% (95% CI = 4.9–6.7), and 5.62% (95% CI = 4.8–6.8) in study 1 and study 2, respectively. Death rate attributed to NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively, or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin deaths can be attributed to low-dose aspirin use.CONCLUSION:Mortality rates associated with either major upper or lower GI events are similar but upper GI events were more frequent. Deaths attributed to NSAID/ASA use were high but previous reports may have provided an overestimate and one-third of them can be due to low-dose aspirin use.

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.

Acute Hemodynamic Response to β-Blockers and Prediction of Long-term Outcome in Primary Prophylaxis of Variceal Bleeding

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.

Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis

BACKGROUND/AIMS Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats. METHODS Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage. RESULTS Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water (P<0.05). CONCLUSIONS Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.

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)

Prediction of therapeutic failure in patients with bleeding peptic ulcer treated with endoscopic injection

Endoscopic injection therapy was performed in a consecutive series of 233 patients admitted for a bleeding peptic ulcer with active arterial hemorrhage or a nonbleeding visible vessel disclosed at emergency endoscopy. Further bleeding occurred in 57 cases (24.5%). The present study was conducted to evaluate whether any clinical or endoscopic features could identify the patients at high risk of therapeutic failure. Multiple logistic regression analysis showed that failure was significantly related to: (1) the ulcer location on the posterior wall (P=0.004) or superior wall (P=0.003) of the duodenal bulb, (2) the ulcer size (P=0.011), and (3) the existence of associated diseases (P=0.012). The validity of the prediction rule based on these factors was evaluated by receiver-operating characteristic curves and was confirmed and prospectively validated in an independent sample of 81 patients with a bleeding peptic ulcer treated by endoscopic injection. We conclude that once the initial control of bleeding has been achieved by injection therapy, the present prediction rule can be used to identify candidates for alternative treatment.

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.

Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy

Background  Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to β‐blockers ± nitrates has not been clarified.

Hemodynamic Effects of Terlipressin and High Somatostatin Dose during Acute Variceal Bleeding in Nonresponders to the Usual Somatostatin Dose

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 μg/h with an initial bolus of 250 μg). 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 μg/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.