Introduction

Varicose veins that develop in the esophagous as a result of elevated pressure in the venous system of the abdomen.

Upper G.I. Bleeding is a Medical Emergency associated with high mortality.

80-90% bleed from esophageal varices & not from other sources.

Overall mortality of first bleed is 50% mainly due to patients dying before they reach hospital.
50-70% patients experience a re-bleeding episode during hospitalisation. At least, a third will re-bleed within 6 weeks of discharge from hospital. No more than third will survive beyond one year.

Esophageal Varices

Esophageal Varices
Varices in the distal esophagus as viewed through an endoscope

Facts & Figures

About 30% cirrhotic patients with demonstrable varices manifest bleed. Almost all bleeding episodes occur within 2 years of initial observation.

Once bleeding occurs 40-50% cirrhotic patients die within 6 months.

There is an 80% incidence of re-bleeding once patient bleeds from varices. Mortality seen with every re-bleeding is about 60%. Every re-bleeding even if treated successfully requires a lot of hospital resources, especially blood.

Causes of Portal Hypertension

Liver Cirrhosis (alcoholic, biliary, posthepatitis)

Non-cirrhotic portal fibrosis/ Portal hypertension Schistosomiasis

Budd-Chiari Syndrome

1st Degree Varices 2nd Degree Varices 3rd Degree Varices Predictors of Bleeding in EV - Size - Red Spots - Child Pugh Score

EMERGENCY MANAGEMENT OF UPPER G.I. BLEEDING AT FAMILY PHYSICIANS CLINIC

MINOR BLEEDING
(BP Stable, Pulse < 100/min)

MAJOR BLEEDING
Hypotensive Shock, Patient Collapse

History of past bleeding attacks, jaundice/NSAIDs, other medications Inject Octreotide 50 mcg* i.v. stat at the site of visit

Maintain i.v. line with Normal Saline & Plasma Expanders

No further bleeding Patient remains stable

Inject Octreotide 50 mcg stat i.v. AND START I.V. infusion of Sandostatin 25 mcg/hour HOW? (Add 3 ampoules of 100 mcg Sandostatin in 500 c.c. dextrose/water 5% in 12 hours) URGENTLY SHIFT PATIENT TO HOSPITAL

Consult G.I. Specialist/Hospital for further evaluation & Endoscopy

Note: Upper G.I. Bleeding may present with Vomiting of fresh blood Black color loose stools

* Sandostatin (Octreotide) is available as (a) 0.05 mg injection (50 mcg ampoule) (b) 0.1 mg injection (100 mcg ampoules)

For further Specialized Management please refer a Gastroenterologist

Prevention - Beta blockers and nitrates Acute variceal bleeding - Vasopressin - Vasopressin Analogue - Somatostatin - Somatostatin Analogue

Acts by decreasing portal pressure by constricting splanchnic blood vessels

LIMITATIONS - Short half life - Systemic vasoconstriction - MI and mesenteric Ischaemia

Same mode of action as vasopressin Longer half life Fewer side effects LIMITATIONS - Less effective in controlling active bleeding and preventing re-bleeding - No reduction in transfusion requirements - Should be use with trans-dermal Nitroglycerine to counter cardiac side effects
(Hepatology 1993, vol.18, p 61-65)

Contrindicated in IHD
(Management of Portal Hypertension and Budd Chiari Syndrome, Andrew K Burroughs)

ECG and BP must be monitored Can only be used when ICU facilities are available
(Terlipressin package insert)

Acts by selectively reducing hepatic blood flow and wedge hepatic venous pressure

LIMITATIONS - Shorter half life - Necessitates continuous IV infusion - Rebound bleeding

Same pharmacologic effects as Somatostatin Much longer half life Significantly reduces intra-variceal pressure Decreases the inflow of blood to the portal system Increased selectivity Potency greater than that of Somatostatin

Advantages of Sandostatin (Octreotide)

Longer plasma half-life (about 1-2 hours)

Longer duration of action

S.C. injection which can be self-administered by the patient

More potent

More selective

USES AND BENEFITS

Sandostatin is effective in control of acute variceal bleeding at 24 hours and stops variceal haemorrhage in 80% of patients. Sandostatin is equally effective as endoscopic therapy in mild, moderate and severe disease. Sclerotherapy is not available at all centres and depends upon the technical expertise. Sandostatin when used prior to sclerotherapy produces an effective Holding & prevents re-bleeding during the first 4 hours especially when used with sclerotherapy.

USES AND BENEFITS

Sandostatin is more effective than other modalities in the emergent control of active variceal bleeding. Sandostatin reduces the transfusion requirements as compared to other pharmacological treatment modalities i.e 1 unit versus 3 units within 48 hours. Sandostatin has an excellent safety profile than other treatments. It is well tolerated & has fewer side effects. Due to absence of systemic circulatory effects Sandostatin can be used without special monitoring.

A recent meta-analysis evaluated 13 randomized trials of octreotide v/s several alternative interventions for variceal hemorrhage[21] These 13 trials included a total of 1077 patients (numbers ranged from 40 to 199 total patients per trial). The endpoints analyzed involved assessments made at the end of the recorded follow-up, rather than at arbitrary times during the first few hours of hospitalization. The primary endpoints were:

Total rebleeding Mortality Complications

This study defined lack of control of bleeding as any episode of rebleeding during the follow-up period It defined major complications as hypertension or hypotension, cardiac or intestinal ischemia, arrhythmias, pneumonia, pulmonary edema, or any side effect that required termination of treatment
Corley DA, Cello JP, Adkisson W, et al. Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology. 2001;120:946-954.

Meta-analysis demonstrated that most studies favor octreotide vs alternative therapy (vasopressin/terlipressin, placebo/no therapy, and sclerotherapy) for the control of bleeding in acute variceal hemorrhage

100 90 80 70 60 50 40 30 20 10 0

Major Any

Oc tre

Va Sc Pl ac so le ro eb /T ot /B o er id an li e d

Ba llo on

Octreotide was associated with fewer Major Complication than vasopressin/ Terlipressin A trend towards Morality benefit especially against Balloon or Vasopressin Comparable in efficacy to Emergency Sclerotherapy and comparable or better than other modalities. Most common dosage regime in studies was 25 50 g IV for 48- 120 hours Addition of Octreotide to Sclerotherapy produced significant better initial bleeding control and Rebleeding rates and small survival advantage compared with vasopressin/Terlipressin
(Gastroenterology 2001, 120, p 946-954)

Emergency therapy required at Family Physicians Clinic for a patient with projectile bloody vomiting reports

50 mcg intravenous as bolus in case of acute bleeding

Maintain i.v. line and start 50 mcg per hour for 5 days by continous i.v. infusion

Based on the number of studies showing a clinical benefit for octreotide in the control of acute bleeds Octreotide infusion is included in the current American College of Gastroenterology guidelines for variceal bleeding in patients with cirrhosis

Conclusion
At present, available clinical evidence suggests that, because of its efficacy & lack of major side effects Sandostatin most closely

fulfil the requirements of the ideal vasoactive drug for the

control of acute variceal bleeding.