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ENDOSCOPIC MANAGEMENT OF NON-VARICEAL UPPER GI BLEEDING
RAJNISH MONGA*, NIRMAL KUMAR**
*Senior Resident; **Professor, Department of Gastroenterology, GB Pant Hospital, New Delhi.
Upper gastrointestinal (UGI) bleed is defined as gastrointestinal haemorrhage from a source proximal to the ligament of Treitz. With the introduction of upper gastrointestinal endoscopy proximal to the ligament of Treitz. With the introduction of upper gastrointestinal endoscopy (UGIE), a source of bleeding can be detected in more than 90% of cases.[1] In addition, UGIE provides therapeutic and risk stratification opportunity.
Despite recent advances mortality due to UGI bleeding continues to be high because of an aging population and presence of multiple co-morbidity factors. This article aims to review the management of UGI bleed with special emphasis on comparative analysis of available endoscopic haemostasis techniques.
Peptic ulcer disease (50%) Varices (10%) Haemorrhagic gastritis Oesophagitis Mallory-Weiss tear (5-15%) Cameron ulcers within hiatus hernia Oesophageal, gastric, duodenal neoplasms Haemobilia Dieulafoy's lesion Aortoenteric fistula
RESUSCITATION
Assessment and resuscitation measures to protect the airway and maintain adequate tissue perfusion take priority over all endoscopic procedures. Ideally the patient should be haemodynamically stable with a heart rate of less than 100 beats/min and systolic blood pressure greater than 100 mm Hg. Initial evaluation should focus on determining whether the bleed is from the upper or the lower gastrointestinal source. A clear nasogastric aspirate may be seen in 14% of bleeding duodenal ulcers (DU).[1] Blood transfusions should be instituted in patients with postural symptoms and haemoglobin less than 10 g/dL or patients with haemoglobin of less than 7-8 g/dL even without postural symptoms.
Protect airway. Intubate for active bleeding or altered mentation. Medical resuscitation with fluids and blood products. Correct coagulopathies (goal: PT<15 sec, platelets>50,000/cumm) Lavage with an orogastric tube if blood obscures much stomach. Use therapeutic double-channel videoendoscope. Have therapeutic instrumentation ready before endoscopy. Have a trained nurse assistant available.
Nonvariceal Upper Gastrointestinal Bleeding (NVUGIB)
NVUGIB can broadly be sub-classified for convenience of discussion into peptic ulcer bleed and non-ulcer bleed.
Variable Age (years) Shock Systolic BP (mm Hg) Pulse rate Co-morbidity Diagnosis Stigma of recent bleed (SRH)
PREDICTORS OF RE-BLEED, MORBIDITY AND MORTALITY
The risk of in-hospital mortality is dependent on age, presence of shock, co-morbid condition, stigmata of recent bleed on endoscopy and the underlying diagnosis.
Multivariable Scoring Systems which have been validated for use in gastrointestinal bleed include the APACHE scoring system.[3] those proposed by Zimmerman et al[4] and Rockall et al.[5]
Endoscopy provides important risk assessment for rebleed. Rockall Risk Score (Table 3) stratifies the risk of death and re-bleed, with a risk of rebleeding of 5% if the score is 0 and 40% if score is more than or equals 8. Mortality rate is below 1% and as high as 41% if the score is 0-2 and 8 or more, respectively.
Modified Forrest Criteria[8]:
1. Actively bleeding ulcer.
1a. Spurting.
1b. Oozing.
2. Non-actively bleeding ulcer
2a. Non-bleeding visible vessel.
2b. Ulcer with surface clot.
2c. Ulcer with red or dark blue spots.
3. Ulcer with clean base.
Presence of shock and type 1 bleeding peptic ulcer carries a rebleed risk of 80% and presence of non-bleeding visible vessel predisposes the patient to a 50% risk of further bleed. Ulcer with a clean base (type 3) and ulcers with red or dark blue spots (type 2c) rarely re-bleed during hospitalization. Bleeding peptic ulcer in the posterior duodenal bulb and proximal gastric lesser curve are located near major vessels and are associated with higher re-bleed rates and are more likely to cause death.[5,6]
Predictors of Mortality
Patient characteristic that have been reported to be associated with increase in mortality are:
Age, onset of bleeding, co-morbidity, hypotension and shock at presentation, fresh bleed in Ryle's tube aspirate, haemoglobin level at presentation and on serial follow-up, number of packed cells transfusions, corticosteroids and combined use of aspirin and oral anticoagulants.
Patients who start bleeding during hospitalization (secondary bleeding) have a significantly higher mortality as compared to those who bleed prior to hospitalization (primary bleeding).[9] This is primarily because of presence of co-morbidity factors in hospitalized patients. Mortality is significantly higher in patients with co-morbid illnesses which include CNS diseases, hepatic insufficiency, pulmonary diseases, cardiac diseases, renal failure, physiological stress and cancer. The mortality increases with increase in number of co-morbid conditions.[5,9]
Use of low dose aspirin is associated with moderately reduced risk of severe bleeding and a decreased mortality from GI bleeding.[10,11] Possible explanation is the increased patient awareness and vigilance and propensity to bleed from minor lesions with aspirin therapy.
Predictors of Rebleeding
As many as 10% patients rebleed after endoscopic therapy. Failure of therapy and recurrent upper GI bleeding is associated with an increase in mortality.[12] Apart from the endoscopic stigmata of recent ulcer bleed, many independent factors predict the rebleeding risk. These include age more than 65 yr., tachycardia and shock at admission, obesity, haematemesis, specific ulcer location and diameter more than 2 cm.[12-14,15]
Helicobacter pylori and recurrence of ulcer bleed
H. pylori eradication in patients with bleeding ulcers is known to reduce the recurrence of bleeding. In various small studies with a follow up period ranging from 4 to 48 months, the rate of duodenal ulcer relapse and rebleeding was significantly reduced in patients with successful eradication of H. pylori.[16-18] In patients with bleeding peptic ulcer associated with H pylori, eradication should be confirmed by urea breath test or the biopsy urease test at endoscopy.
ENDOSCOPIC THERAPY
Peptic ulcer disease accounts for about two third of all cases of upper gastrointestinal haemorrhage as diagnosed on upper GI endoscopy.[19]Forrest type 3 (clean base) ulcers on endoscopy are seen in approximately 30-50% of peptic ulcer bleeds. These along with type 2c ulcers don't require any further endoscopic therapy.
For ulcers with active bleed or evidence of stigmata of recent bleed, the endoscopic modalities available are listed in Table 4.[21]
Endoscopy has beyond doubt reduced morbidity, hospital stay, risk of recurrent bleeding and need for surgery in patients with non-variceal upper GI bleed. Early endoscopy (within 24 hours) in an intensive care setting in patients of NVUGIB significantly effects the transfusion requirement, duration of ICU stay and rebleed rate.[22]
Endoscopic stigmata of ulcer haemorrhage, their prevalence, risk of rebleeding and effect of endoscopic therapy on rebleed rates is listed out in Table 5.
RANDOMIZED CONTROL TRIALS (RCT) COMPRISING ENDOSCOPIC THERAPEUTIC MODALITIES
Haemoclips versus hypertonic saline-epinephrine injection
Injection therapy with Epinephrine at concentration of 1:10,000 or 1:20,000 using 23 to 25-guage sclerotherapy needle is widely used. It causes local tamponade, vasoconstriction and enhances platelet aggregation to achieve local haemostasis. Epinephrine is injected into the submucosa in 0.5-1.0 ml increments in all four quadrants around the bleeding site. Endoscopic metallic clips were compared in an RCT to hypertonic saline-epinephrine injection versus the combination of both by Chung et al.[23] The authors achieved initial haemostasis in 95% of patients with active bleeding or visible vessel with a tendency to produce less rebleed rates and surgeries with the use of haemoclips. Haemoclips have their technical and practical limitations that include need for special training, special devices, possibility of clip tearing the vessel wall and inability to stop bleed in arteries greater than 1-2 mm size.
Endoscopic Appearance Active arterial bleeding Visible Vessel Adherent clot Oozong without stigmata Flat spot Clean base ulcer
Ethanol injection versus Haemoclips
Injection of alcohol carries a high risk of ulceration and perforation, thus only small volume (maximum of 2 ml) is recommended. A retrospective study reported similar haemostasis rates with haemoclip application and ethanol injection group.[24] Alcohol injection produces dehydration and fixation of tissue and subsequent necrosis and ulceration. Because of this risk of ulceration and perforation only small dose of alcohol is used.
Other sclerosants, such as sodium tetradecyl suphate, polidocanol and ethanolamine have been used alone or in combination with epinephrine for injection therapy of peptic ulcer bleed.
Heater probe versus Haemoclips
Thermocoagulation when compared to haemoclips for visible or bleeding vessel in the ulcer base revealed a similar death rate and surgery rates.[25] The same study reported the superiority of haemoclips in prevention of rebleed (2% rebleed rate with haemoclip and 21% rebleeding in the heater probe group) and lower transfusion requirement and hospital stay. Haemoclip application failure in six out of 56 patients was attributed to the ulcer site (proximal posterior gastric wall or posterior wall of duodenal bulb) or size of ulcer greater than 15 mm.
Butyl-2-cyanoacrylate versus hypertonic saline-epinephrine injection
Butyl-2-cyanoacrylate is a liquid glue that polymerizes on contact with blood. Lee et al[25] reported similar initial haemostasis rates with both butyl-2-cyanoacrylate and hypertonic saline-epinephrine injection therapy in actively bleeding peptic ulcers but the glue injection group had a significantly lower rebleeding rate (14% vs. 42%). The rebleeding rates were similar in non-bleeding visible vessel ulcers in both groups. Glue embolization and perforation are the two feared complications with glue injection.
Fibrin Glue and hypertonic saline-epinephrine injection
Theoretically the injection of fibrin glue to halt peptic ulcer bleeding may be safer than other sclerosing agents as it would not cause necrosis or degeneration. However, results from a prospective randomized control trial conduced by Song et al comparing fibrin glue and hypertonic saline-epinephrine injection suggested no statistically significant difference between the two modalities of therapy.[26]
Combined modalities
There is trend towards combined use of two endoscopic modalities using injection and mechanical or injection and thermal probe therapy in actively bleeding peptic ulcer.[23,28] Rebleed rates with combined therapy using adrenaline injection and thermocoagulation showed a trend towards decreased rebleeding compared to injection alone when dealing with spurting peptic ulcer haemorhage.[28]
DRUG THERAPY
Intravenous high dose omeprazole (80 mg bolus followed by 8 mg/hr), after endoscopic haemostasis has been achieved in a peptic ulcer bleed reduces the risk of rebleeding and need for endoscopic re-treatment and surgery.[29] Use of H2 receptor antagonists is not supported by clinical trials.
Oral omeprazole in the dose of 40 mg twice a day has been reported to decrease the risk of rebleeding in patients with stigmata of recent bleed without endoscopic therapy by Khuroo et al.[30]
RECURRENT HAEMORHAGE
Rebleeding after successful endoscopic therapy range from 10-20%. In a prospective, randomized study, Lau et al compared endoscopic retreatment with surgery after initial endoscopy for recurrent ulcer bleed.[15] In patients with peptic ulcer and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduced the rate of surgery and complications. Second endoscopic procedure avoided surgery in 73% of rebleed patients. Multivariate analysis showed two predictors of rebleed; ulcer diameter more than 2 cm and hypotension during rebleeding. Patients who rebleed after second endoscopy should be subjected to either surgery or embolization for haemostasis.
ALGORITHM
An algorithm for management of acute upper gastrointestinal haemorrhage due to peptic ulcer bleed.[21] (Fig. 1).
NON-ULCER NVUGIB
Dieulafoy's lesions
A Dieulafoy's lesion is marked by the presence of large, submucosal artery that protrudes through the mucosa, is not associated with peptic ulcer and cause massive GI bleeding. Endoscopic therapy with injection therapy, thermal probes, clipping devices and band ligation has been evaluated. Narayan et al reported a rebleeding rate of 50% with single modality therapy.[31] A combined used of epinephrine injection and heater probe, as recommended for active bleeding or adherent clots, achieves an initial haemostasis in 90% and a rebleed rate of less than 20% of patients.[2] Tattooing with India Ink around the arterial spurter assists the surgeon in identifying the bleeding site at laparotomy.
Endoscopic band ligation for Dieulafoy's lesion in a case series was successfully used in 3 out of 4 patients.[32] One out of three successfully banded patients had rebleeding from the post banding ulcer site, which was managed successfully with epinephrine injection.
Mallory-Weiss Tears
Mallory-Weiss mucosal lacerations are usually secondary to vomiting and result in self limiting, small volume bleed. Haemorrhage is usually mild and self-limiting. Jensel et al prospectively evaluated endoscopic therapy for actively bleeding Mallory-Weiss tears, without portal hypertension.[33] They achieved a 100% haemostasis rate compared with 40% for medical therapy. Twenty per cent of patients with visible non-bleeding vessel or adherent clot rebleed. They recommend the use of low power setting of light touch bipolar coagulation, or epinephrine injection only in actively bleeding tears. Patients with portal hypertension and actively bleeding Mallory-Weiss tears should be subjected to therapy for the adjacent varix and not bipolar coagulation.
Haemclipping has been successfully used in actively bleeding Mallory-Weiss tears or tears with a visible vessel or fresh adherent clot. In a series of 58 patients, of whom 26 had high-risk signs on endoscopy, 2.8± 1.6 clips were deployed with 100% technical success and haemostasis rates. No rebleeding was noticed in any of the patients on a 2 months follow-up.[34]
Upper Gastrointestinal Malignancy
Upper gastrointestinal malignancies account for 1-5 per cent of upper gastrointestinal bleeding. Most tumours that cause severe upper gastrointestinal bleeding are advanced malignancies. Most common cancer in the study by Savides et al was gastric adenocarcinoma. Bleeding was active in 17 to 42 patients and was successfully managed using either epinephrine injection or thermal probe or a combination of both.[35] Despite therapy patients with severe bleeding from upper gastrointestinal tumours have a high 1 year mortality of 90%.[35]
CONCLUSIONS
Endoscopy is the key diagnostic tool for management of upper gastrointestinal bleeding. In addition it provides a unique therapeutic opportunity which has over the years reduced the need for emergency surgery, but the impact on survival is less dramatic with the mortality from severe UGI bleeding remaining fairly constant. Optimal use of endoscopic therapeutic modalities shall continue to play a pivotal role in management of UGI bleed in the years to come.
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