S. A. Jenkins

A prospective randomised controlled trial comparing the efficacy of somatostatin with injection sclerotherapy in the control of bleeding oesophageal varices.

Since previous reports have suggested that somatostatin may be of value in the control of acute variceal haemorrhage, we compared its efficacy with that of injection sclerotherapy in a randomised controlled clinical trial. Eighty consecutive patients with endoscopically-proven severe variceal bleeding were randomised to injection sclerotherapy (n = 41) or somatostatin (n = 39) given as a continuous infusion of 250 micrograms/h for 5 days plus daily bolus administration of 250 micrograms. The efficacy of injection sclerotherapy and somatostatin infusion in controlling haemorrhage and preventing rebleeding (censored at 5 days), mortality (censored at 28 days) and complications was compared. The aetiology of the portal hypertension and transfusion requirements was similar between the two groups, but there were more patients with severe liver disease (Childs C) in the somatostatin group. There was no significant difference between the two treatments in the initial (p = 1.0) or overall control of bleeding (p = 0.58). Furthermore, somatostatin was as effective as injection sclerotherapy in controlling bleeding in patients with severe liver disease or in those actively bleeding at the time of their endoscopy. The relative risk of rebleeding whilst receiving somatostatin compared to injection sclerotherapy was 1.39 [95% Confidence Interval (CI) 3.73; 0.52], but this was reduced to 0.98 (95% CI 0.37; 2.67) when readjusted for Childs grading, the only prognostic factor shown to be of significance. Mortality was not significantly different between the two groups of patients (p = 0.31). The relative risk of dying whilst receiving somatostatin compared to injection sclerotherapy was 1.6 (95% CI 3.93; 0.66) but was reduced to 1.03 (95% CI 0.47; 2.47) when adjusted for Childs grading, the only significant prognostic factor. Complications in the somatostatin group were minor and less frequent than after injection sclerotherapy. The results of this study indicate that somatostatin is a safe treatment, which is as effective an endoscopic injection sclerotherapy for acute variceal bleeding.

Effects of Somatostatin on Hepatic Haemodynamics in the Cirrhotic Rat

Reports on the effects of somatostatin on hepatic haemodynamics in the cirrhotic patient have provided conflicting results. Therefore, we studied the effects of different modes and rates of somatostatin administration on hepatic haemodynamics in the cirrhotic rat. Portal pressure (PP), wedged hepatic venous pressure (WHVP), portal venous flow (PVF), liver blood flow (LBF) and systemic blood pressure were measured in rats with dimethylnitrosamine-induced cirrhosis. Somatostatin was administered as a rapid injection, a continuous infusion or as a bolus dose followed by a constant infusion. One group of rats with a previously constructed portacaval shunt received a bolus dose of somatostatin followed by a constant infusion. A rapid injection of somatostatin was attended by a rapid and significant fall in all the haemodynamic parameters measured (p less than 0.01). Continuous infusion of somatostatin [4 or 8 micrograms/kg body weight (BW) h] resulted in a gradual but significant reduction in PP, WHVP, PVF and LBF (p less than 0.05), but had no effect on systemic blood pressure. A bolus dose of somatostatin (2, 4 or 8 micrograms/kg BW over 2 min) resulted in a rapid decrease in PP, WHVP, PVF and LBF (p less than 0.01), the decreases being maintained by continuous infusion. In rats with a portacaval shunt a bolus dose of somatostatin (8 micrograms/kg BW) resulted in a rapid fall in WHVP and LBF, the decrease being maintained by a continuous infusion (8 micrograms/kg BW/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Alcohol on Hepatic Haemodynamics in the Rat

The effects of varying rates of alcohol infusion (0.015-0.12 mg/g body weight/min) on hepatic haemodynamics were studied in male Wistar rats. An infusion of 0.015 mg/g body weight/min alcohol had no significant effect on portal pressure (PP) or wedged hepatic venous pressure (WHVP). However, increasing rates of infusion of alcohol (0.03-0.12 mg/g body weight/min) progressively increased PP and WHVP, the maximum increase in PP occurring following an infusion of 0.12 mg/g body weight/min (6.5 +/- 0.5 - 10.3 +/- 0.6 mm Hg). The effect of varying rates of alcohol infusion on portal venous flow and liver blood flow was biphasic. Thus following an infusion of 0.03 mg/g body weight/min alcohol, liver blood flow (40.6 +/- 4.9 - 54.3 +/- 5.8 ml/100 g/min) and portal venous flow (28.6 +/- 2.9 - 41.3 +/- 4.1 ml/min) were increased. However, following infusions of 0.06 and 0.12 mg/g body weight/min alcohol, liver blood flow and portal venous flow were decreased. The results suggest that previous conflicting reports on the effects of alcohol on hepatic haemodynamics may be related to the dose of alcohol administered.

The management of gastrointestinal haemorrhage by somatostatin after apparently successful endoscopic injection sclerotherapy for bleeding oesophageal varices

Twenty-two patients who experienced a severe haemorrhage from either oesophagitis (n = 8) or ulcers (n = 14) following injection sclerotherapy of their oesophageal varices were treated with intravenous administration of somatostatin (250 micrograms/h). Somatostatin was effective in controlling haemorrhage and preventing rebleeding in all eight patients bleeding from oesophagitis and in 12 of the 14 patients bleeding from oesophageal ulcers. In two patients with ulcers, haemorrhage persisted despite two periods of concominant balloon tamponade and somatostatin infusion and bleeding was eventually controlled by repeated hourly bolus injections of the hormone for 24 h superimposed on the continuous infusion. The results of this study suggest that somatostatin is an effective and safe treatment for the control of bleeding from either oesophagitis or ulcers following injection sclerotherapy of oesophageal varices.

The Effects of Arterialisation of the Portal Stump on Liver Function and Hepatic Haemodynamics in Cirrhotic Rats with a Portacaval Shunt

Liver blood flow (xenon-133 clearance method) and wedged hepatic venous pressure were studied in cirrhotic rats immediately after and 3 weeks following portacaval shunting (PCS), PCS and arterialisation of the portal stump with the left gastric artery (PCS-ART) or sham operation. Liver weight and function were compared 3 weeks after operation. Liver blood flow and wedged hepatic venous pressure were significantly reduced immediately after and 3 weeks following PCS. PCS-ART maintained liver blood flow and wedged hepatic venous pressure within the pre-operative range and prevented the liver atrophy and deterioration in liver function observed in rats with PCS. The results suggest that arterialisation of the portal vein with an artery which does not significantly increase sinusoidal pressure may be of benefit in preventing the early undersirable sequelae of PCS in man.

EFFECTS OF TOTAL AND SELECTIVE PORTASYSTEMIC SHUNTING ON HEPATIC HAEMODYNAMICS AND SOME ASPECTS OF LIVER FUNCTION IN THE CIRRHOTIC RAT

1. The effects of total and selective portasystemic shunting on hepatic haemodynamics and some aspects of liver function were studied in rats with dimethylnitro‐samine‐induced cirrhosis.

A COMPARISON OF THE EFFECTS OF END-TO-SIDE PORTACAVAL SHUNTING AND SIDE-TO-SIDE MESOCAVAL SHUNTING ON HEPATIC HAEMODYNAMICS IN THE DOG

1. Functional liver blood flow and hepatic artery flow were measured before and after either end‐to‐side portacaval or side‐to‐side mesocaval shunting in dogs.

The effects of vasopressin on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat.

ZusammenfassungDie Leberdurchblutung (Xenon133 clearance Methode) sowie der portale Fluß werden nach Vasopressin-Infusion verschiedener Geschwindigkeiten, an cirrhotischen und nicht cirrhotischen Ratten gemessen. Bei langsamer Infusion hatte Vasopressin keine signifikante Wirkung auf den portal-venösen oder auf den Leberblutfluß in cirrhotischen oder nicht cirrhotischen Ratten. Die Infusion von Vasopressin mit einer Geschwindigkeit von 0,08 μU/g KG/min in nicht cirrhotischen Ratten und mit 0,04 bzw. 0,08 μU/g KG/min in cirrhotischen Ratten reduziert den portal venösen aber steigert den Leberblutfluß. Bei höherer Infusionsrate (0,2 μ,U/g KG/min in nicht cirrhotischen Ratten und 0,16 μU/g KG/min in cirrhotischen Ratten) wurde dieser Effekt umgekehrt. Darüber hinaus konnte eine VasopressinInfusion von 0,08 μU/g KG/min den portalen Druck bei cirrhotischen Ratten signifikant senken. Dagegen wurde der portale Druck durch Infusion von 0,16 μU/g KG/min Vasopressin nicht signifikant beeinflußt. Die Bedeutung dieser Befunde für eine mögliche deletäre Wirkung hoher Raten von Vasopressin-Infusion in der Behandlung der portalen Hypertension mit blutenden Oesophagus-Varicen wird diskutiert.SummaryLiver blood flow (xenon-133 clearance method) and portal venous flow were mesured in cirrhotic and non cirrhotic rats following the infusion of vasopressin at varying rates. At low rates of infusion, vasopressin had no significant effect on portal venous flow or liver blood flow in cirrhotic or noncirrhotic rats. Infusion of vasopressin at a rate of 0.08 μU/g body wt/min in non-cirrhotic rats and 0.04 and 0.08 μU/g body wt/min in cirrhotic rats decreased portal venous flow and increased liver blood flow. At higher rates of infusion (0.2 μU/g body wt/min in non-cirrhotic rats and 0.16 μU/g body wt/min in cirrhotic rats) these effects were reversed. Furthermore, an infusion of 0.08 μU/g body wt/min vasopressin significantly reduced portal pressure in the cirrhotic rat. However, portal pressure was not significantly altered following an infusion of 0.16 μU/g body wt vasopressin. The implications of these findings in relation to the possible deleterious effects of high rates of vasopressin infusion in the management of portal hypertension and bleeding oesophageal varices is discussed.