Upper GI Bleeding

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Upper GI Bleeding
Klaus Gottlieb, MD, FACP, FACG
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A common medical condition

• 250,000 500,000 admissions/year US
• UGI bleeding incidence 100/100,000 adults
• Incidence increases 20-30 fold from third to
  ninth decade of life
• LGI bleeding incidence 20/100,000 adults
• Overwhelmingly disease of the elderly
• GI bleeding stops spontaneously in 80

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Morbidity Data

• Majority will receive blood transfusions
• 2 10 require urgent surgery to arrest
  bleeding
• Average LOS 4 7 days
• Mortality rates for UGI bleeding 2 15
• Mortality for patients who develop bleeding after
  admission to hospital for another reason is 20
  30

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Costs

• Average hospital costs exceed 5,000 per
  admission
• Most of this for hospital bed and ICU stays
  rather than physician fees, blood products,
  diagnostic tests, or medications
• Reduction of hospital admissions and LOS has
  greatest potential to reduce costs

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UGI bleedingNomenclature

• Hematemesis 25
• Melena alone 25 , 50 100 cc of blood will
  render stool melenic
• Hematochezia 15 , seen in massive UGI hemorrhage
• Red blood hematemesis
• Coffee ground emesis

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Indications for Hospitalization and Intensive Care

• Traditional Endoscopy on the day of admission or
  on the day after
• Recent studies Complete endoscopic risk
  stratification PRIOR to admission
• Between 25- 30 of patients with UGI bleeding
  could be discharged from the Emergency Department

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Predictors of Outcome in UGI bleeding
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Ulcer Appearance and Prognosis
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Scoring System for Predicting Rebleeding and
Mortality

• A simplified scoring system based on endoscopic
  and clinical variables has been developed
• Rockhall TA et al. Selection of patients for
  early discharge or outpatient care after acute
  upper gastrointestinal haemorrhage. Lancet
  1996347 1138-1140

None or spot in ulcer base

0

Blood in the GI tract, clot, visible vessel

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in ulcer base


 
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Scoring is not Boring
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LOS Guidelines for UGI bleeding at UCSF
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Endoscopic Therapy in UGI bleeding

• Effectively reduces
• Rebleeding
• Need for Surgery
• Mortality (by meta-analysis)
• However, 10 20 percent of patients have
  rebleeding after (initially successful)
  endoscopic therapy

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The Role of Adjunctive Pharmacological Therapy

• Clot stabilization at a pH of above 6.0 pepsin
  is inactivated and cannot lyse clots
• Effective clotting may not occur at a pH of 5.9
  or lower
• Antacids, iced saline gastric lavage and
  H2-blockers and other interventions are
  ineffective in reducing rebleeding rates

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Proton Pump Inhibitors

• NEJM 1997 high dose oral omeprazole effective in
  reducing rebleeding rates. No endoscopic therapy
  performed in this study from India
• Two multicenter trials from Scandinavia showed
  benefit of high dose I.V. omeprazole (1997)
• Taiwanese study of 100 patients randomized
  between IV omeprazole and cimetidine.
  Intragastric pH was around 6.0 for first 24 hours
  in omeprazole group but only between 4.5 to 5.5
  for cimetidine group. 12 pts in the cimetidine
  group and 2 pts in the omeprazole group rebled.
  No change in LOS, number of procedures, or
  mortality (1998)

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Effect of Intravenous Omeprazole on Recurrent
Bleeding After Endoscopic Treatment of Bleeding
Peptic UlcersLau JYW, Sung JJY, Lee KKC, et
al.N Eng J Med. 2000 343 310-316

• Randomized, controlled, double-blind trial of 250
  pts to evaluate whether intravenous infusion of
  omeprazole (80 mg bolus, followed by 8 mg/hr) is
  more effective than placebo in reducing
  rebleeding risk over 30 days following endoscopic
  therapy
• Well conceived, designed, executed and analyzed
  study
• Patients included those with an actively bleeding
  ulcer or ulcers with a non-bleeding visible
  vessel in whom endoscopic therapy was successful
  in controlling bleeding
• Endoscopic therapy consisted of a combination of
  epinephrine injection plus thermocoagulation to
  the point of vessel obliteration

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Results

• Rebleeding 6.7 in omeprazole vs. 22.5 in
  placebo group (p lt .001, Relative Risk 3.38, 95
  C.I. 1.60 7.13)
• LOS median 4 days omeprazole, 5 days placebo
  (significant)
• Transfusions omeprazole mean 1.7, placebo 2.4
  (significant)
• Mortality 5 omeprazole, 9 placebo (mortality
  rate 5.8 ) (not significant)
• Surgery 3 omeprazole, 9 placebo (not
  significant)

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PROTONIX (Pantoprazole Sodium) Formulations

• 40-mg Delayed-Release Tablet
• 40-mg Lyophilized Powder for Injection

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PROTONIX (Pantoprazole Sodium)Specific Cysteine
Binding Sites
Binds two cysteine residues critical for the
inhibition of gastric acid secretion (Cys 813
and 822)
Modlin IM, Sachs G. Acid Related Diseases,
Biology and Treatment. Schnetztor-Verlag.
1998126-145.
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PPI Pharmacology (Day 1 Data)
Prescribing Information for Aciphex (rabeprazole
sodium), Nexium (esomeprazole magnesium),Prevaci
d (lansoprazole), Prilosec (omeprazole), and
PROTONIX (pantoprazole sodium).
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PROTONIX (Pantoprazole Sodium) 40 mg vs.
Prilosec (omeprazole) 40 mg
Intragastric pH
n 7 normal volunteers
Koop et al. 1994. Prilosec is a registered
trademark of AstraZeneca LP.
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PROTONIX I.V. (Pantoprazole Sodium) for
Injection is indicated for the short-term
treatment (7 to 10 days) of gastroesophageal
reflux disease (GERD), as an alternative for
patients who are unable to continue taking
PROTONIX Delayed-Release Tablets. Safety and
efficacy of PROTONIX I.V. for Injection as an
initial treatment for GERD have not been
demonstrated. The most frequently reported
adverse events with PROTONIX I.V. for Injection
were abdominal pain, chest pain, rash, and
pruritus. PROTONIX is contraindicated in
patients with known hypersensitivity to any
component of the formulation. Treatment with
PROTONIX I.V. for Injection should be
discontinued as soon as the patient is able to be
treated with PROTONIX Delayed-Release
Tablets. Data on safety and effective dosing for
conditions other than GERD (including concomitant
life-threatening upper gastrointestinal bleeds)
are not available. PROTONIX I.V. 40-mg once
daily dosing does not raise gastric pH to levels
sufficient to contribute to the treatment of such
life-threatening conditions. Please see full
Prescribing Information.
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PROTONIX I.V. (Pantoprazole Sodium) for
Injection in Inhibition of Acid Output40 mg I.V.
vs. Placebo
Data on file, Wyeth-Ayerst Laboratories. Study
100-US. Pisegna JR et al. Am J Gastroenterol.
1999942874-2880.
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PROTONIX I.V. (Pantoprazole Sodium) for
InjectionDosage and Administration

• DosageThe recommended dose is one vial (the
  equivalent of 40 mg pantoprazole) given once
  daily by intravenous infusion for 7 to 10 days.

• AdministrationPROTONIX I.V. for Injection should
  be administered intravenously over a period of
  approximately 15 minutes at a rate not greater
  than 3 mg/min (7 mL/min). PROTONIX I.V. for
  Injection should be administered using the
  in-line filter provided. The filter must be used
  to remove the precipitates that may form when the
  reconstituted drug product is mixed with I.V.
  solutions

PROTONIX I.V. for Injection Prescribing
Information. Wyeth-Ayerst Laboratories,
Philadelphia, Pa
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Proton Pump Inhibitor Activation in the NPO
Patient

• Acid is always secreted, but at varying levels
• Multiple pathways for stimulation of acid
  secretion not involving food including
• Basal
• Cephalic
• Canalicular pH is always sufficient to activate
  PPIs
• Blood contains protein and stimulates gastric
  acid secretion when present in the stomach

Modlin IM, Sachs G, Acid Related Diseases,
Biology and Treatment. 1998126-145. Feldman M.
In Feldman M, Scharschmidt BF, Sleisenger MH, et
al. eds. Sleisenger Fordtrans Gastrointestinal
and Liver Disease. 1998587-603.
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PROTONIX I.V. (Pantoprazole Sodium) for
Injection Summary

• Impressive acid suppression
• No evidence of tolerance in a clinical study
  (oral 10 days I.V. 7days)
• Fast onset (within 15-30 minutes) and long acting
• Generally well tolerated
• No known clinically relevant drug interactions

Data on file, Wyeth-Ayerst Laboratories.