-Mortality related to haemorrhage, liver decompensation, aspiration, hepatic encephalopathy, HRS, septicaemia and alcohol withdrawal.
-Varices are present in 50% of patients with cirrhosis and 85% of Child-Pugh C patients.
-Portal Hypertension -----> Collateral circulation to decompress pressure, junctions of squamous and columnar mucosae (gastroesophageal, anal, peristomal) -----> Development of varices. Risks factors for rupture: 1. portosystemic pressure gradient > 10-12 mmHg ii. variceal size > 5mm iii. progressive hepatic dysfunction.
Treatment goal:
1. Resuscitation
-airway control in massive haemorhage and obtunded patients
-NG aspiration may be necessary
-hemodynamic with blood and blood products aim for stability (initial lab results)
-watch for hypocalcemia and thrombocytopenia in massive transfusion
-thiamine and monitor alcohol withdrawal
2. Diagnosis-upper endoscopy
Findings-fresh fibrin clot from varix, nipple like protrusion, red signs, varices with no other potential bleeding source.
3. Therapy
A. Pharmacology:
1. Octreotide (somatostatin analog) is the drug of choice. Started immediately with suspicion of variceal bleeding. Minimal side effects
IV 50mcg bolus, infusion 50mcg/hr
2. vasopressin -potent vasoconstrictor, reduces splanchnic BF and portal pressure. Adverse cardiac events (MI, hypertension) in ~ 30% of patients. Concurrent IV nitroglycerin for SBP ~100mmhg has been shown to reduce the systemic SE's.
3. Non selective B blockers, not in acute setting. For primary and secondary prevention of variceal bleeding.
4. Antibiotic prophylaxis- to prevent infection and rebleeding in all cirrhotic patients with variceal bleeding.
Norfloxacin 400mg bd
or Ceftriaxone 1g daily
B. Endoscopy
1. Band ligation- is the technique of choice to control bleeding. Active bleeding is controlled in 80%-90% of patients after one or two treatments.
-lower incidence of esophageal ulceration, stricture formation, perforation, bacrteraemia and respiratory failure compared to sclerotherapy.
2. Sclerotherapy - for gastric variceal bleeding and massive variceal bleeding
C. TIPS
Transjugular Intrahepatic Pportosystemic Stent (TIPS) shunt- Iatrogenic fistula between radicals of the hepatic and portal veins, created by interventional radiologists using ultrasonographic and fluoroscopic guidance
- An expandable metal stent is left in place and portosystemic pressue gradient is reduced to less than 12 mmHg
Indications:
i. Bleeding continues despite combinations of pharmacologic and endoscopic therapies
ii. Bleeding recurs after two endoscopic attempts at prevention
iii. Bleeding has occurred from gastric varices or portal hypertensive gastropathy
- The technical success rate is > 90%, with near universal success rate in bleeding control. Overall mortality is similar to endoscopic therapy.
-S hunt insufficiency is 15-60% within 6 months.
- Postprocedure bleeding recurrence---> dopler US examination for determining shunt patency. Revision of shunt usually results in low mortality
Complications:
- 20-30% develop transient deterioration of LFTs
- Up to 25% may experience new or worsened hepatic encephalopathy
D. Baloon tamponade
-gastric and oesophageal balloon devices for direct tamponade of the bleeding varices
-Sengstaken-Blakemore, Minnesota and Linton-Nachlas balloons--> for severe and persistent bleeding.
E. Other measures:
- surgical shunts
-non shunting operations
-embolisation of the short gastric veins in gastric variceal bleeding and splenectomy in splenic vein thrombosis
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SOMATOSTATIN AND ITS ANALOGS
Somatostatin inhibits the release of vasodilator hormones, such as glucagon, indirectly causing splanchnic vasoconstriction and decreased portal inflow.
It has a short half-life and disappears within minutes of a bolus infusion; octreotide is a long-acting analog of Somatostatin.
Pharmacodynamics — Following a bolus injection of either somatostatin or octreotide, portal venous inflow, portal pressures, azygos flow, and intravariceal pressures decrease within seconds. Of these effects, the changes in portal pressures, as measured by wedged hepatic pressures, are most variable and the decrease in collateral flow (azygos flow) are most consistently observed.
One of the most detailed studies to evaluate the pharmacodynamics of octreotide included 68 patients with cirrhosis who were given octreotide by four different methods (gastroenterology 2001):
-An intravenous injection of (50 or 500 microg) or placebo
-A 50 microg bolus followed by continuous infusion of 50 or 250 microg per hour or placebo infusion
-Repeated 50 microg injections or placebo after an initial 50 microg bolus
-After a placebo bolus and continuous infusion of 50 microg per hour.
Octreotide caused a marked but transient decrease in portal pressure and azygos blood flow and an increase in mean arterial pressure. These effects lasted only five minutes even with the addition of continuous infusions. Repeated bolus injections had shorter, less marked effects while continuous infusion did not decrease portal pressure, suggesting that there was rapid desensitization.
These findings make it unclear why octreotide should be of any benefit in portal hypertension since its effect on portal pressure is short-lived. However, the potential benefits of octreotide (and somatostatin) in portal hypertension may extend beyond the measures noted above. Both inhibit the release of glucagon and other hormones that have an important role in mediating the normal increase in mesenteric blood flow that occurs postprandially.
Variceal hemorrhage is associated with an increase in intestinal blood flow, presumably mediated by pathways that are activated by the presence of blood, a high protein substance, in the gut. Octreotide can blunt this response for at least 48 hours . In addition, activation of somatostatin receptors may decrease the rebound increase in portal venous pressure that occurs when blood enters the gastrointestinal tract and during correction of hypovolemia.
A number of clinical trials have compared somatostatin or octreotide to either vasopressin or placebo in the management of active bleeding. An initial placebo-controlled trial failed to demonstrate a benefit for somatostatin; however, over 80 percent of those treated with placebo spontaneously stopped bleeding which may have obscured a treatment benefit . Several subsequent studies have shown somatostatin to be significantly superior to placebo with respect to achievement of hemostasis and to prevention of early rebleeding .
Somatostatin versus vasopressin — Somatostatin is also superior to vasopressin and balloon tamponade due in part to the virtual absence of side effects. A meta-analysis of trials comparing somatostatin to vasopressin found two benefits with somatostatin [gastroenterology 1995]:
1. A higher relative risk (1.62, 95 percent CI 1.37 to 1.93) of achieving initial control of the bleeding; the absolute benefit was such that only three or four patients had to be treated with somatostatin for one to derive benefit over therapy with vasopressin.
2. A lower risk of adverse effects (0 versus 10 percent with vasopressin).
However, these beneficial effects on bleeding have not been shown to improve survival.
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