The following summarises the management recommendations for control of active variceal bleeding in patients with cirrhosis:
● Treatment should ideally be undertaken by a dedicated appropriately equipped and staffed unit.
● Resuscitate in a setting appropriate to the severity of bleeding. Maintain mean arterial pressure at 80 mmHg and Hb at around 8 g/dL. Use gelatine-based colloids and packed red blood cells for volume replacement. Avoid dextrans (may increase bleeding times), hydroxyethyl starch (can worsen liver function) and Ringer’s lactate solution.
● Electively intubate patients with severe uncontrolled variceal bleeding, severe encephalopathy, oxygen saturation below 90 per cent and aspiration pneumonia.
● Place a nasogastric tube for repeated gastric lavage or administer intravenous low-dose erythro- mycin in order to clear the stomach for endoscopy.
● Start vasoactive therapy as soon as possible. Intravenous octreotide, a synthetic analogue of somatostatin, is often begun as soon as the diagnosis is certain. This newer agent has mostly replaced vasopressin, due to its ease of use. Vasopressin’s mechanism of action is thought to be splanchnic arteriolar vasoconstriction, resulting in decreased portal pressure, although it remains controversial whether this effect is maintained in the face of severe haemorrhage. The usual dose for vasopressin is 0.2–0.4 units/min, although high-dose therapy (1.0–1.5 units/min) has been advocated. The potential side effects of vasopressin are primarily cardiovascular and increase with higher doses. Sublingual nitroglycerine administered simultaneously with vasopressin sig- nificantly decreases the complication rate of vasopressin. The control of bleeding with this com- bination therapy is superior to that achieved with vasopressin alone. An alternative to vasopressin for control of variceal haemorrhage is the synthetic analogue terlipressin (1–2 mg, depending on body weight, given by bolus every 4 h for 2–5 days); this is more effective than vasopressin. The most commonly used drug for treating variceal bleeding is somatostatin (an ini- tial bolus of 250 μg followed by intravenous infusion at a rate of 250 μg/h for 2–5 days). This has been shown to be equally efficacious with terlipressin and vasopressin. Although concerns over potential effects on renal function have been raised, octreotide (continuous intravenous infusion of 25 μg/h for 2–5 days) is a widely used alternative to vasopressin and nitroglycerine because of the simplicity of single-agent use.
● Start ciprofloxacin (1 g/day for 7 days) in order to prevent bacterial infections such as sponta- neous peritonitis and bacteraemia.
● Upper gastrointestinal endoscopy should be performed by an experienced endoscopist as soon as the patient is haemodynamically stable.
● Variceal band ligation is the method of first choice for endoscopic therapy. Failing that, endo- scopic intravariceal or paravariceal injection sclerotherapy should be performed. Its risks include oesophageal perforation, ulceration and stricture. Alternatively, a tissue adhesive (e.g. cyano- acrylate) can be injected into bleeding varices to plug the lumen; this is 90 per cent successful in achieving haemostasis. Its risks include pulmonary embolisation, portal vein embolisation, splenic infarction, and permanent damage to the lens of the endoscope.
● Combined endoscopic and vasoactive therapy is superior to either treatment in the control of bleeding.
Management of patients with variceal upper gastrointestinal bleeding In clinical practice, the choice of sclerosant has largely remained a matter of personal pref- erence and has depended on the availability of the particular sclerosants in various countries. In the USA, sodium morrhuate and sodium tetradecyl have been those used most widely. Ethanolamine, which is also available in the USA, has been used exclusively in the UK and South Africa. Polidocanol is the sclerosant of choice in Austria and Germany. Sodium mor- rhuate, sodium tetradecyl sulphate, ethanolamine or ethanol is usually injected directly into the varix. Depending on the size of the varix, 0.5–2 mL of the selected sclerosant is used in each injection. The total volume used per sclerotherapy session is usually around 10–20 mL. Polidocanol, on the other hand, is injected into the submucosa around the varix. At each injection, 0.5–1.5 mL may be delivered, and 40–60 mL of polidoconal may be used per scle- rotherapy session. Isobutyl 2-cyanoacrylate, a liquid tissue adhesive, has been used for intravariceal injections into bleeding oesophageal and gastric varices. This liquid polymer solidifies instantly in blood and obliterates the varix immediately. This adhesive plug sloughs off in a few weeks, leaving a fibrotic scar at the injection site. Cyanoacrylate is diluted with lip- iodol (0.5 : 0.8 mL) before injection in order to prevent the adhesive from hardening too fast and to allow fluoroscopic monitoring. The biopsy channel and tip of the endoscope should be treated with silicone oil to prevent sticking of cyanoacrylate to the instrument. A single 0.5-mL dose of this solution may be injected intravascularly into each oesophageal variceal channel through a regular sclerotherapy needle. Two to three injections of 0.5 mL each are often required for large varices in the gastric fundus. After each injection of 0.5 mL of the cyanoacrylate solution, the sclerotherapy needle must be rinsed thoroughly with distilled water. There are differences in opinion regarding the correct injection site. Intravariceal injection was the first method described and is still used by most endoscopists around the world, espe- cially in the USA and the UK. Injection is performed initially at the bleeding site. All the variceal channels are then injected at the bottom of the varix, which is usually located at or just below the gastro-oesophageal junction. Finally, the variceal channels are injected 3–5 cm proximally. Cyanoacrylate must be injected directly into the varix. Inadvertent injection of this chemical into surrounding tissue causes severe ulceration.
Some endoscopists inject the sclerosant alongside the varix or paravariceally. The aim of paravariceal injection is to create a layer of fibrosis covering the variceal channels. Injections are performed starting at the cardia and repeated 30–50 times, producing a helical arrangement of wheals as the endoscope is withdrawn. The injections are limited to the distal oesophagus unless there is a more proximal bleeding site. This technique is currently the method of choice in Germany, Austria and some other European countries.
Sclerotherapy as a long-term treatment requires repeated injection sessions in order to achieve obliteration of varices. Despite the popularity of the procedure since the 1970s, no uniform follow-up sclerotherapy schedule has emerged. After the initial treatment, subsequent sclerother- apy sessions have been scheduled at various intervals, ranging from a few days to a few weeks.
In summary, although the concept of endoscopic sclerotherapy for varices appears to be straightforward, the clinical practice of the technique has not been standardised. The overall importance of the multiple technical variables outlined above is not well understood. Many investigators believe that these factors are of secondary importance when compared with the patient’s overall clinical status at the time of sclerotherapy. The sclerotherapy patient should usually anticipate a long-term treatment programme. In the USA, the patient will probably undergo two to three sclerotherapy sessions during the index hospitalisation for an acute episode of variceal haemorrhage. Two to three subsequent sessions will be performed in the fol- lowing 4–8 weeks before the variceal channels are obliterated. The patient will return for follow-up endoscopies every 3–6 months, presumably for the rest of their life, because oesophageal varices recur in up to 60 per cent of patients.
UPPER GASTROINTESTINAL BLEEDING 162
If endoscopic therapy is unavailable, vasoconstrictors such as octreotide (unlicensed) or ter- lipressin are administered, or a Sengstaken–Blackmore or Minnesota tube (with both gastric and oesophageal balloons) or a Linton–Nachlas tube (with gastric balloon only) with adequate provision for airways protection can be placed until definitive therapy is arranged. The tube is inserted into the stomach and the gastric balloon partially inflated with 40–50 mL of air. The balloon position within the stomach and below the diaphragm is confirmed with abdominal radiography before its further inflation with 300 mL of air. Upward traction is then applied to the tube. If bleeding continues, the oesophageal balloon is inflated to a pressure of 35– 40 mmHg. The oesophageal balloon should be deflated every 4 h for 15 min in order to avoid oesophageal necrosis, and the entire tube should not be left in place for more than 24–48 h. Unlike the Sengstaken tube, which has three lumens, the Minnesota tube has a fourth lumen that enables oesophageal drainage above the inflated oesophageal balloon. These tubes are suc- cessful in 85 per cent of cases, but recurrent bleeding after balloon deflation is common. Tube- related complications, such as airway obstruction, aspiration and oesophageal necrosis with rupture, occur in 20 per cent of patients.
If endoscopic control of bleeding cannot be achieved, then a Sengstaken or Minnesota tube can be inserted until further endoscopic treatment, transjugular intrahepatic portosystemic shunt (TIPS) or surgical treatment is possible. The TIPS procedure involves the transjugular insertion of a self-expanding nitinol stent in the liver to connect the portal and hepatic veins, thus creating a portosystemic shunt (Figure 12.2). Specialist help should be sought at this time, and transfer to a specialist centre should be considered, where the choice of definitive inter- vention is determined by the preference of that centre.
Transjugular intrahepatic portosystemic shunt with or without transvenous variceal emboli- sation is the standard therapy for patients with bleeding oesophagogastric varices that are un - responsive to, or who rebleed severely soon after, endoscopic and pharmacological first-line therapy. Patients with marginal liver function (Child class B or C cirrhosis) may also receive TIPS as a bridge to liver transplantation. Transjugular intrahepatic portosystemic shunt con- trols variceal bleeding in more than 90 per cent of patients but risks hepatic encephalopathy in 25–35 per cent of patients and a mortality of 15 per cent (due mainly to multisystem organ fail- ure in Child class C patients).
Hepatic vein
Portal vein
Figure 12.2 ● Transjugular intrahepatic portosystemic shunt (TIPS) is an expandable stent placed angiographically between a branch of the hepatic vein and a branch of the portal vein to create a non-surgical shunt.
Management of patients with variceal upper gastrointestinal bleeding 163 Liver transplantation should be considered in patients with Child class C cirrhosis, although this is often an unavailable option due to organ shortages. Transjugular intrahepatic porto - systemic shunt can be used as a bridge to transplantation. Portal decompression (e.g. TIPS) is preferable to transplantation in patients with Child class A or B cirrhosis.
Surgical decompression of the portal system is reserved for patients with failed initial non- surgical treatment who still have preserved liver function and in patients who are bleeding from colonic and stomal varices. Surgical shunts carry a success rate greater than 90 per cent and a rebleeding rate of less than 10 per cent, but they risk encephalopathy in 25 per cent of patients. In the presence of actively bleeding varices, non-selective shunts such as portocaval or mesocaval shunt or interposition graft are favoured over selective distal splenorenal (Warren) shunt (DSRS). Gastro-oesophageal decongestion and splenectomy (GEDS; Hassab operation), when done properly, is as effective in controlling bleeding as DSRS with higher survival and minimal or no encephalopathy. Combined with sclerotherapy, GEDS could be an ideal therapy for bleeding varices. Oesophagogastric devascularisation with oesophageal tran- section and re-anastomosis with (the ‘modified Sugiura procedure’) or without splenectomy
Box 12.1 Prophylaxis of variceal bleeding in cirrhosis Primary prophylaxis
■ Pharmacological therapy with propranolol is the best available modality to prevent variceal bleeding.
■ In case of contraindication or intolerance to propranolol, variceal band ligation is the treatment of choice.
■ Where neither propranolol nor variceal band ligation can be used, isosorbide mononitrate is the treatment of first choice.
■ All patients with cirrhosis should undergo regular endoscopy at the time of diagnosis (yearly if varices are detected, or every 3 years if no varices are found).
■ KEY POINT
All patients with cirrhosis should undergo regular endoscopy at the time of diagnosis.
Secondary prophylaxis
■ Following control of active variceal bleeding, the varices should be eradicated using endoscopic methods. The method of first choice is variceal band ligation. If banding is not available, sclerotherapy should be used.
■ It is recommended that endoscopic variceal therapy is delivered at weekly intervals until variceal eradication, and that endoscopy is repeated at 3 months and every 6 months thereafter.
■ Either combination treatment of sclerotherapy and non-selective beta-blocker or either of these alone may be used. If the latter strategy is used, then it is recommended that the hepatic venous pressure gradient is measured in order to confirm that this has been successfully reduced to less than 12 mmHg.
■ Transjugular intrahepatic portosystemic shunt (TIPS) is more effective than endoscopic treatment in reducing variceal rebleeding but does not improve survival and is associated with more encephalopathy. It is a treatment option that may be used in certain centres with particular expertise.
UPPER GASTROINTESTINAL BLEEDING
may have a role in patients with Child class A or B cirrhosis with well-preserved liver function and contraindications for Warren shunt, TIPS and liver transplantation.
In order to prevent encephalopathy, the use of intravenous flumazenil, a benzodiazepine receptor antagonist, appears beneficial; the use of lactulose remains controversial.