Prophylaxis Of Variceal Bleeding Research Articles

Nonocclusive Mesenteric Ischemia Associated with Propranolol Overdose

SummaryWe describe a case of massive propranolol overdose in a healthy 19‐year‐old woman associated with isolated mesenteric ischemia following shock. We postulate that endogenous catecholamine release from shock combined with massive β‐adrenergic blockade led to severe splanchnic vasoconstriction from unopposed α‐adrenergic activity. This case supports current thinking regarding the effect of vasoactive mediators on the gastrointestinal tract in humans and might be relevant to the mechanism of action of propranolol in the prophylaxis of variceal bleeding.

Nonocclusive Mesenteric Ischemia Associated with Propranolol Overdose

We describe a case of massive propranolol overdose in a healthy 19-year-old woman associated with isolated mesenteric ischemia following shock. We postulate that endogenous catecholamine release from shock combined with massive beta-adrenergic blockade led to severe splanchnic vasoconstriction from unopposed alpha-adrenergic activity. This case supports current thinking regarding the effect of vasoactive mediators on the gastrointestinal tract in humans and might be relevant to the mechanism of action of propranolol in the prophylaxis of variceal bleeding.

Prophylactic Therapy for Variceal Hemorrhage Revisited

The high mortality of a first variceal bleed in cirrhotic patients even in very recent studies makes some effective form of primary prophylaxis desirable. Controlled studies of shunt and nonshunting surgery have shown that these operations can prevent variceal hemorrhage only at the expense of increased morbidity and mortality. Therefore, this type of surgery has no place in the primary prophylaxis of variceal bleeding. Liver transplantation, however, is becoming a real therapeutic alternative for many patients with chronic liver disease. Obviously, it will prevent bleeding in many patients, but primary prophylaxis of bleeding itself is not an indication for a transplant. The radically different results of randomized controlled trials of prophylactic sclerotherapy indicate that it is either very helpful and will save many lives or very harmful and will lead to death in patients who would otherwise survive. The cumulative evidence from the trials that took appropriate care of effective treatment for the acute bleed and that had no major problems with complications of the procedure itself suggests that prophylactic sclerotherapy is neither helpful nor very harmful. Thus, there is also no indication for prophylactic sclerotherapy in clinical routine. Personally, I even doubt that it should be used in future controlled trials in the light of the positive results of the prophylactic trials of beta-blockers. If there is an indication for prophylactic treatment, it should be the last invasive treatment available. In the near future, work should focus on the confirmation and further development of endoscopic or other simple and safe means to predict the risk of first bleeding; on the development and characterization of effective drugs; and on development of methods to identify at an early stage responders and nonresponders. If I presently had large varices that had not yet bled, I would like to join one of my senior colleagues and look for admission to the Control group of an ongoing randomized beta-blocker trial.

Inv dup (15)

<h3>Objective</h3> Non-selective β-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥20% or to values &lt;12 mm Hg). <h3>Design</h3> Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80–160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25–50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders. <h3>Results</h3> 36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol non-responders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): −19±10% versus −12±11% (p&lt;0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% (p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group. <h3>Conclusions</h3> Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.