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Proton pump inhibitors versus H2-antagonists: a meta-analysis of their efficacy in treating bleeding peptic ulcer.

PURPOSE: To evaluate whether proton pump inhibitors are more effective than H2-antagonists (H2-A) for the treatment of bleeding peptic ulcer. DATA SOURCES: PubMed database until January 2000. STUDY SELECTION: Comparative randomized trials of proton pump inhibitors (omeprazole, lansoprazole, or pantoprazole) vs. H2-A (cimetidine, ranitidine or famotidine). DATA EXTRACTION: Meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). OUTCOMES EVALUATED: Persistent or recurrent bleeding, need for surgery, or mortality. DATA SYNTHESIS: Eleven studies fulfilled the inclusion criteria and contained data for at least one of the planned comparisons. Persistent or recurrent bleeding was reported in 6.7% (95% CI: 4.9-8.6%) of the patients treated with proton pump inhibitors, and in 13.4% (95% CI: 10.8-16%) of those treated with H2-A (OR 0.4; 95% CI: 0.27-0.59) (chi2-homogeneity test, 18; P=0.09). Surgery was needed in 5.2% (95% CI: 3.4-6.9%) of the patients treated with proton pump inhibitors, and in 6.9% (95% CI: 4.9-8.9%) of the patients treated with H2-A (OR 0.7; 95% CI: 0.43-1.13). Respective percentages for mortality were 1.6% (95% CI: 0.9-2.9%) and 2.2% (95% CI: 1.3-3.7%) (OR 0.69; 95% CI: 0.31-1.57). SUB-ANALYSIS: Five studies evaluated the effect of both therapies given in bolus injections on persistent or recurrent bleeding rate, which was 6% (95% CI: 3.6-8.3%) and 8.1% (95% CI: 5.3-10.9%), respectively (OR, 0.57; 95% CI: 0.31-1.05). Persistent or recurrent bleeding in high risk patients (Forrest Ia, Ib and IIa) occurred in 13.2% (95% CI: 7.9-8%) of the patients treated with proton pump inhibitors and in 34.5% (27-42%) of those treated with H2-A (OR 0.28; 95% CI: 0.16-0.48). In patients not having endoscopic therapy, persistent or recurrent bleeding was reported, respectively, in 4.3% (95% CI: 2.7-6.7%) and in 12% (95% CI: 8.7-15%) (OR 0.24; 95% CI: 0.13-0.43). Less marked differences were observed in patients having adjunct endoscopic therapy: 10.3% (95% CI: 6.7-13.8%) and 15.2% (11.1-19.3%) (OR 0.59; 95% CI: 0.36-0.97). Moreover, the significance disappeared in this group when a single outlier study was excluded. CONCLUSIONS: Proton pump inhibitors are more effective than H2-A in preventing persistent or recurrent bleeding from peptic ulcer, although this advantage seems to be more evident in patients not having adjunct sclerosis therapy. This beneficial effect seems to be similar or even more marked in patients with Forrest Ia, Ib or IIa ulcers. However, proton pump inhibitors are not more effective than H2-A for reducing surgery or mortality rates. Nevertheless, the data are too scarce and heterogeneous to draw definitive conclusions, and further comparative trials are clearly warranted.

Anti-Ulcer Agents↗

Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin.

AIM: To evaluate the role of Helicobacter pylori infection and other clinical factors in the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. SUBJECTS AND METHODS: A case-control study was carried out of consecutive current users of low-dose aspirin admitted because of upper gastrointestinal bleeding. Within a cohort of 695 patients with upper gastrointestinal bleeding, 98 patients had taken low-dose aspirin and no other non-steroidal anti-inflammatory drug. Controls were 147 low-dose aspirin users without upper gastrointestinal bleeding of similar age, sex and extent of aspirin use as cases. H. pylori infection was determined by CagA/VacA serology and 13C-urea breath test in all cases and controls. Adjusted odds ratios (OR) are provided. RESULTS: H. pylori infection was identified as an independent risk factor of upper gastrointestinal bleeding in this population (OR, 4.7; 95% confidence interval (95% CI), 2.0-10.9), but the presence of CagA-positive serology was not. Other risk factors identified were a previous ulcer history (OR, 15.2; 95% CI, 3.8-60.1), alcohol use (OR, 4.2; 95% CI, 1.7-10.4) and use of calcium channel blockers (OR, 2.54; 95% CI, 1.25-5.14). Antisecretory therapy (OR, 0.1; 95% CI, 0.02-0.3) and nitrovasodilators (OR, 0.2; 95% CI, 0.1-0.6) decreased the risk of bleeding. CONCLUSIONS: H. pylori infection is a risk factor for upper gastrointestinal bleeding in low-dose aspirin users, which might have therapeutic implications in high-risk patients.

Aged↗

Protein Z in healthy human individuals and in patients with a bleeding tendency.

Protein Z is a vitamin-K-dependent plasma glycoprotein; its physiological function is not clear. Low protein Z levels were found in patients with otherwise unexplained bleeding disorders. It was therefore suggested that low protein Z levels might be associated with a bleeding diathesis. In the present study we measured protein Z levels in plasma samples of 48 patients with a suspected bleeding disorder and in plasma samples of 200 healthy adult individuals. We found protein Z to have a wide normal range in healthy men and women. Significantly lower protein Z levels were observed in women compared to men, whereas no correlation was found with age or other vitamin-K-dependent coagulation proteins. None of the 48 patients with a bleeding disorder had a protein Z level below the normal range. However, protein Z was significantly lower in the group of male patients with a bleeding history as compared to healthy men. In conclusion, our data indicate that low-normal protein Z levels are not associated with a bleeding tendency. However, it remains to be determined whether a low protein Z level is a weak cofactor associated with an increased bleeding tendency and whether decreased or absent protein Z (conditions not detected in our patients) might constitute a haemorrhagic diathesis.

Adolescent↗

Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids.

BACKGROUND: Patients with acute bleeding from internal haemorrhoids often have to be referred by the general practitioner to the surgeon for definitive treatment with invasive outpatient procedures. At the initial consultation, patients frequently seek postponement of immediate surgery to a more convenient time. Effective and rapid non-invasive control of acute bleeding could be of practical use in scheduling surgery to a time convenient to both patient and surgeon. METHODS: In a 90-day randomized, double-blind study treatment with a micronized purified flavonoid fraction (MPFF) was compared with placebo, in 100 outpatients who presented for treatment of acute internal haemorrhoids of less than 3 days' duration. The primary endpoint was cessation of bleeding on the third day of treatment. RESULTS: Of 50 patients randomized to each group, acute bleeding ceased by the third day in 40 (80 per cent) who received MPFF compared with 19 (38 per cent) who had placebo (P < 0.01). Mean(s.d. ) duration of acute bleeding from onset to cessation of 4.9(1.6) days was 2.1 (95 per cent confidence interval 1.2-2.9) days less than that in patients receiving placebo (P < 0.01). Continued treatment in patients with no bleeding prevented a relapse in 30 of 47 patients, compared with 12 of 30 receiving placebo (P < 0.05). CONCLUSION: Patients with acute internal haemorrhoids treated with MPFF had rapid cessation of bleeding and a reduced risk of relapse. This could be of value in the more convenient timing of treatment with invasive outpatient procedures.

Acute Disease↗

Controlling acute bleeding episodes with recombinant factor VIIa in haemophiliacs with inhibitor: continuous infusion and bolus injection.

The efficacy of recombinant activated factor VII (rFVIIa, NovoSeven) in five Haemophiliacs (four Haemophilia A, one Haemophilia B), with high inhibitors ranging from 70 to 1900 Bethesda units, was evaluated. The treatment regimen was divided into two groups: group I, continuous infusion of 16.5 microg h-1 kg-1 body weight (bw) after the initial bolus of 90 microg kg-1 bw in three episodes of severe bleeding and group II, bolus injection 80-150 microg kg-1 bw every 3 hours for a maximum of four doses in six haemarthroses. The bleeding was effectively controlled within 1 to 48 h in five of nine bleeding episodes. One patient in group I, who had active arterial bleeding requiring sutures, had an ineffective response and three patients in group II had partially effective responses because the rFVIIa was given after the onset of bleeding at 36, 44 and 72 h, respectively. The prothrombin time was shortened and the FVII:C levels were successfully achieved at approximately 10 U mL-1. The continuous infusion reduced the total dose of rFVIIa by 50%. Recurrent bleeding episodes were found in three patients; two occurred at the same site after ceasing rFVIIa for 51 h and while receiving rFVIIa at 144 h and one occurred at a new site after ceasing rFVIIa for 12 h. Our experience would suggest that rFVIIa is effective in controlling acute bleeding episodes in Haemophiliacs with high inhibitors either by continuous infusion or bolus injection.

Adult↗

The relation between nailfold bleeding and capillary microscopic abnormality in patients with connective tissue diseases.

BACKGROUND: Patients with connective tissue diseases, mainly scleroderma, show nailfold bleeding and nailfold capillary abnormality. An attempt was made to determine the possible relation between nailfold bleeding and nailfold capillary abnormality. METHODS: The correlation between nailfold bleeding and nailfold capillary abnormality was studied using quantitative nailfold capillary microscopy. RESULTS: The frequencies of nailfold bleeding in scleroderma, mixed connective tissue disease, dermatomyositis/polymyositis, and secondary Raynaud's phenomenon were significantly higher than those of normal controls. The distributions of abnormal values of capillary parameters in scleroderma, mixed connective tissue disease, dermatomyositis/polymyositis, systemic lupus erythematosus, primary Sjögren's syndrome, secondary Raynaud's phenomenon, primary Raynaud's phenomenon, and diabetes mellitus were significantly higher than those of normal controls. In normal controls, scleroderma, mixed connective tissue diseases, dermatomyositis/polymyositis, systemic lupus erythematosus, primary Sjögren's syndrome, primary Raynaud's phenomenon, and diabetes mellitus, all nailfold bleeding was observed in subjects with nailfold capillary abnormality. The distribution of nailfold bleeding in secondary Raynaud's phenomenon with abnormal values of capillary parameters was significantly higher than that with normal values. CONCLUSIONS: There is a close relationship between nailfold bleeding and nailfold capillary abnormality.

Adolescent↗

Plasma gastrin activity and the diagnosis of bleeding abomasal ulcers in cattle.

The present study was designed to evaluate the usefulness of plasma gastrin determinations as a diagnostic aid and to review the clinical and haematological findings in cattle with bleeding abomasal ulcers. Twenty-nine cows with bleeding abomasal ulcers and six healthy cows were used. Clinical and laboratory examinations, including plasma gastrin levels, were performed. Anorexia, depression, dark-coloured to black faeces, pale mucous membranes, abdominal pain, moderate tachycardia and tachypnoca were the most pronounced clinical symptoms in the cattle with bleeding abomasal ulcers. Plasma gastrin concentration was significantly higher (P < 0.05) in the cattle with bleeding abomasal ulcers than in healthy cows. The mean plasma gastrin concentration in healthy cattle was 103.2 pg/ml, while the mean plasma gastrin concentrations in cattle with bleeding abomasal ulcers were found to be 213.6 pg/ml. Haemoglobin levels, packed cell volume, total white blood cell count and mean corpuscular volume were significantly lower (P < 0.05) in the cows with bleeding abomasal ulcer than in the healthy cattle. The results of this study show that measurement of plasma gastrin can be useful in the diagnosis of bleeding abomasal ulcers in cattle.

Abomasum↗

Effect of intragastric pH on control of peptic ulcer bleeding.

BACKGROUND: We have performed series studies to investigate the effect of intragastric pH on control of peptic ulcer bleeding. In laboratory and animal studies, both platelet aggregation and gastric mucosal bleeding time were shown to be extremely sensitive to different pH levels. Platelet aggregation decreased significantly at pH > or = 6.8 and gastric mucosal bleeding time fell significantly at pH > or = 6.4. In a prospective clinical trial, primed infusions of different dosages of omeprazole (8 or 4 mg/h) after a bolus (40 mg) produced consistently high intragastric pH values in patients with bleeding duodenal ulcer. These results were not significantly different from that obtained from omeprazole 40 mg bolus treatment every 12 h (P > 0.05). However, primed injection with cimetidine (800 mg/12 h) was less effective (P < 0.05). METHODS: In a retrospective analysis, 303 patients with bleeding peptic ulcer who were treated with cimetidine and 326 patients who were treated with omeprazole were compared. RESULTS: The emergency surgery (4.91%) and mortality rates (1.84%) in the omeprazole group were not significantly different (P > 0.05) from those (7.28 and 1.99%) in the cimetidine group. However, the standardized emergency surgery rate of the omeprazole group (3.28%) was significantly lower than that (9.28%) of the cimetidine group (P < 0.05). CONCLUSION: We conclude that increased intragastric pH to at least 6.4 with omeprazole is helpful in controlling peptic ulcer bleeding. Chinese patients require a lower dose of omeprazole than their Western counterparts to control ulcer bleeding.

Adolescent↗

Endoscopic hemostasis of a bleeding marginal ulcer: hemoclipping or dual therapy with epinephrine injection and heater probe thermocoagulation.

BACKGROUND AND AIMS: Endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation have been proven effective in the hemostasis of bleeding peptic ulcers. However, the hemostatic efficacy has not been investigated in bleeding marginal ulcers. The aim of this study is to investigate the hemostatic efficacy of endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation in bleeding marginal ulcers. METHODS: From November 1997 to July 2000, 50 patients with active marginal ulcer bleeding underwent either hemoclipping (20 patients) or dual therapy (30 patients) for hemostasis. The demographic data, clinicopathological characteristics, endoscopic findings, initial hemostatic rates, rebleeding rates, amount of blood transfusion, the need of surgery, and mortality rates were collected and analyzed. RESULTS: Marginal ulcers were located at the anastomotic site (64%), saddle portion (22%), efferent loop (10%), or at the afferent loop (4%). The bleeding stigmata were classified into spurting artery (32%), oozing vessel (38%), visible vessel (20%), and blood clot adhesion (10%). The overall therapeutic results in 50 patients were initial hemostasis (100%), rebleeding rate (22%), need for surgery (4%), and hospital mortality rate (4%). There was no significant difference in demographic data and clinicopathological characteristics between the two modes of treatments, whereas recurrent bleeding developed in 5% in the hemoclipping group and 33% in the dual therapy group. No complication related to the procedure occurred in either mode of therapy. The hospital mortality rates were 0 and 6.7%, respectively. CONCLUSION: Endoscopy is effective in achieving initial hemostasis from bleeding marginal ulcers. However, the rebleeding rate remains high and repeated endoscopy may be needed to arrest the hemorrhage.

Adrenergic Agonists↗

Retrospective study of the utility of nuclear scintigraphic-labelled red cell scanning for lower gastrointestinal bleeding.

BACKGROUND: The aim of the present study was to evaluate the utility of nuclear scintigraphic-labelled red cell scanning in the management of bleeding in patients with acute lower gastrointestinal haemorrhage (GIH) who require surgery. METHODS: A prospective database was used to source data on all patients with lower GIH who underwent technetium-99m (99mTc)-labelled red cell scanning over a 10-year period. A subgroup was identified from cross-reference with the medical records identifying only those patients who continued to bleed and subsequently required laparotomy for further detailed retrospective study. One key question was asked: did the labelled red cell scan influence the type of operation performed by the operating surgeon? RESULTS: The study identified 249 patients who underwent 287 labelled red cell scans for GIH. Forty patients (16%) underwent laparotomy for ongoing bleeding; 28/40 (70%) of the red cell scans were positive for bleeding. Six patients (15%) died postoperatively, none because of continued bleeding. The 99mTc-labelled red cell scan was deemed to have been unhelpful in 22 (55%) cases. Twelve of the 22 scans were negative and 10 of the 22 scans were positive but were ignored by the surgeon. The 99mTc-labelled red cell scan influenced the choice of operation in 18 out of 40 patients (45% of the operated group but only 7.2% of the total scanned group). Of these, 15 patients underwent colonic resection and three patients underwent small bowel resection. CONCLUSION: The present study demonstrates that labelled red cell scanning has only a small role to play in managing lower GIH. The 99mTc-labelled red cell scanning should be used much more selectively. Its use should be limited to patients who continue to bleed after conservative management; it may allow these patients to be effectively treated by segmental bowel resection. Its most critical role, however, is probably to prevent suspected small bowel bleeding from being missed at operation.

Acute Disease↗

Risk of gastrointestinal bleeding associated with Helicobacter pylori infection in patients with hemophilia or von Willebrand's syndrome.

BACKGROUND: Many episodes of bleeding in the upper gastrointestinal tract are caused by Helicobacter pylori infection. Because these episodes present a life-threatening complication in patients with bleeding disorders, we prospectively investigated the prevalence of H. pylori infection in patients with hemophilia A or B and with the von Willebrand syndrome. METHODS: Seventy patients (54 men, 16 women, ages 40 +/- 11 years) and 100 age-related volunteers (63 men, 37 women, ages 39 +/- 9 years) were tested for H. pylori infection using the 13C urea breath test. Fifty-four patients with hemophilia and 16 patients with von Willebrand syndrome participated. RESULTS: Thirty-three (33%) of the controls and 24 (34.3%) of the patients showed positive 13C urea breath tests (p = .97). Nineteen (35.2%) patients with hemophilia and 5 (31.3%) patients with von Willebrand syndrome were positive for H. pylori. History of dyspeptic symptoms (28% vs. 26%) were not different in patients and controls (p = .91). Gastric ulcers (20% vs. 5%) and duodenal ulcers (7% vs. 5%) were diagnosed more often in patients with bleeding disorders. Fourteen of the patients (20%), but none of the controls had a history of gastrointestinal bleeding (p < .001). CONCLUSIONS: The rate of H. pylori infection and dyspepsia in patients with bleeding disorders is similar to the prevalence in the normal population. Due to increased bleeding complications, H. pylori screening and therapy appears mandatory in patients with bleeding disorders.

Adult↗

Lack of efficacy of tranexamic acid in thrombocytopenic bleeding.

A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. Our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia.

Anemia, Aplastic↗

The role of Doppler ultrasound in gastrointestinal bleeding.

The management of acute gastrointestinal bleeding is the domain of endoscopy. More than half of all episodes of upper gastrointestinal bleeding are attributed to bleeding peptic ulcers, and it is important to assess the risk of recurrent bleeding and to determine the appropriate treatment. However, the visual assessment of lesions (Forrest classification) is not always accurate and shows high interobserver variability (especially for visible vessels at the ulcer base, associated with a high rate of re-bleeding). Doppler ultrasound was thus introduced, and several studies have demonstrated that, with Doppler examination, these vessels can be identified. Doppler ultrasound is also used to monitor the effects of endoscopic therapy. In a prospective randomized trial, Doppler ultrasound proved superior to the Forrest classification. Treatment based on this technique resulted in significantly lower rates of re-bleeding and mortality. The Doppler classification may be able to contribute to a safer and more cost-effective management of patients with acute peptic ulcer bleeding.

Blood Flow Velocity↗

Obscure digestive bleeding.

Obscure digestive bleeding is defined as recurrent bleeding for which no definite source has been identified by routine endoscopic or barium studies. Mucosal vascular abnormality or 'angioectasia' is the most common course of obscure bleeding, especially in elderly patients. Small bowel tumours are more frequent in patients younger than 50 years. However, missed or underestimated upper and lower gastrointestinal lesions at the initial endoscopic investigation may be the source of a so-called obscure intestinal bleeding. The various radiological procedures, including enteroclysis, visceral angiography and CT scan as well as radioisotope bleeding scans have limitations in the case of obscure gastrointestinal bleeding. Recent developments in magnetic resonance imaging are promising. The different methods of enteroscopy have a similar diagnostic yield, reaching approximately 40-65%. Endoscopic cauterization of small bowel angioectasias seems to be efficacious but randomized trials are needed. Efficacy of hormonal therapy is very controversial. The extent of diagnostic and therapeutic strategies must be based on a number of factors including the patient's parameters, bleeding characteristics and also the result of previous work-up.

Acute Disease↗

Effects of isosorbide-5-mononitrate compared with propranolol on first bleeding and long-term survival in cirrhosis.

BACKGROUND & AIMS: Isosorbide-5-mononitrate (Is-5-Mn) exerts beneficial hemodynamic effects in portal hypertension, yet the long-term clinical value is uncertain. The aim of this study was to determine the long-term effects of Is-5-Mn vs. propranolol (Pro) on first bleeding, complications, and death in cirrhosis. METHODS: One hundred eighteen patients included in a previously published randomized trial comparing Is-5-Mn (20 mg three times daily) with Pro were followed up for up to 7 years (range, 2-91 months). Fifty-seven patients received Is-5-Mn and 61 received Pro. RESULTS: Thirty episodes of first upper bleeding occurred; 16 were in the Is-5-Mn group. Actuarial probability of bleeding did not differ between the two groups. Endoscopic variceal red signs were the only independent predictors of early bleeding. Of the 52 patients who died, 28 were in the Is-5-Mn group. The likelihood of death was greater among patients assigned to Is-5-Mn than to Pro, but only in patients older than 50 years (72% vs. 48% at 6 years; P = 0.006). Child-Pugh score, bleeding, age, and assignment to Is-5-Mn were independent predictors of death. The likelihood of death without bleeding was also higher (P = 0.05) in the Is-5-Mn group. CONCLUSIONS: Is-5-Mn is as effective as Pro in preventing early bleeding but is associated with higher long-term mortality.

Adrenergic beta-Antagonists↗

Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding.

BACKGROUND AND AIMS: During acute variceal bleeding, several factors may lead to elevations of hepatic venous pressure gradient (HVPG), which may precipitate further hemorrhage. Whether somatostatin can suppress these increments is unknown. This study monitored somatostatin effects on HVPG during acute bleeding and assessed whether the changes affect outcome. METHODS: In 40 patients with acute variceal bleeding treated with sclerotherapy, a catheter was placed into a main hepatic vein for 24-hour serial measurements of HVPG. After baseline measurements, patients received somatostatin (N = 25) or placebo (N = 15) under double blind conditions. RESULTS: Somatostatin but not placebo produced a sustained decrease in HVPG (from 20.7 +/- 3.7 mm Hg to 17.7 +/- 2.7, P < 0.01). In patients receiving placebo, HVPG increased after a test meal (P = 0.018) and after blood transfusion (P = 0.034). Somatostatin completely prevented these increments. HVPG decreased significantly only in patients without further bleeding. One of 27 patients with HVPG <20 mm Hg at baseline or decreased >10% rebled vs. 9 of 13 who had neither of these 2 criteria (P < 0.0001). Both criteria had independent prognostic value for further bleeding. CONCLUSIONS: During acute variceal bleeding, somatostatin produces a significant and sustained decrease in HVPG and prevents secondary elevations. Monitoring HVPG may stratify further bleeding risk and discriminate treatment response.

Double-Blind Method↗

The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis.

In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was </=12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow-up was significantly higher in poor responders (41%) than in good responders (7%; P =.0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow-up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (beta = 1.91; SE(beta) = 0.80; P =.01). During follow-up 11 patients died of hepatic causes. Survival was related to Child-Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta-blockers or beta-blockers plus nitrates.

Adrenergic beta-Antagonists↗

A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices.

Gastric variceal bleeding is a catastrophic event. Both cyanoacrylate injection and banding ligation have been proven to be effective in the management of bleeding gastric varices. This study was performed to compare the efficacy and complications of both the modalities. Cirrhotic patients with a history of gastric variceal bleeding were randomized to 2 groups. The group receiving endoscopic obturation (group A) comprised 31 patients and the group receiving band ligation (group B) comprised 29 patients. Butyl cyanoacrylate and pneumatic-driven ligator were applied, respectively. Treatment was repeated regularly until obliteration of gastric varices. Active bleeding occurred in 15 patients in group A and 11 patients in group B. Initial hemostatic rate (defined as no bleeding for 72 hours after treatment) was 87% in group A and 45% in group B (P = .03). The sessions required to achieve variceal obliteration and obliteration rates were similar in both the groups. However, rebleeding rates were significantly higher in group B (54%) than group A (31%) (P = .0005). Treatment-induced ulcer bleeding occurred in 2 patients (7%) in group A and 8 patients (28%) in group B (P = .03). The amount of blood transfusions required were also higher in group B than group A (4.2 +/- 1.3 vs. 2.6 +/- 0.9 units, respectively) (P < .01). Nine patients of group A and 14 patients of group B died (P = .05). In conclusion, endoscopic obturation using cyanoacrylate proved more effective and safer than band ligation in the management of bleeding gastric varices.

Adult↗