Megan Anderson PGY2August 15, 2011

OverviewBackground & PhysiologyWho needs treatmentWhat kind of treatmentWhy PPIs are superiorFuture Trends

Lucas, Charles E. "Natural History and Surgical Dilemma of "Stress" Gastric Bleeding." Arch Surg 102 (1970): 266-73.

Background

Significant Complications Developing prior to Hemorrhage

(deaths)Severe Respiratory Failure

17 (10)

Massive Wound Sepsis 9 (7)

Large intra-abdominal abscess

9 (3)

“Septic” Jaundice 12 (6)

Renal Failure 11 (9)

Prolonged Ileus 13 (8)

SEMmembrane disruption and apical cell loss

Hastings, Paul R. "Antacid Titration in the Prevention of Acute Gastrointestinal Bleeding. A controlled randomized trial in 100 critically ill patients." NEJM 298.19 (1978): 1041-045

Antacid titrationHastings – NEJM 1978Randomized Controlled Trial 100 patients

Epidemiology and Incidence Incidence of 1.5% - 4% in critically ill patients Pathogenesis: gastric mucosal injury

Ischemia & Reperfusion Oxidative stress Decrease mucosal circulation

Location: Multiple, superficial, non-ulcerating erosions that begin in the proximal (acid secreting) portion of stomach and progress distally

Sabiston, David C., and Courtney M. Townsend. "Ch 47." Sabiston Textbook of Surgery: the Biological Basis of Modern Surgical Practice. Philadelphia: Saunders/Elsevier, 2008

Presentation and Treatment Presents as…

Painless upper GI bleeding, flecks of blood in NGT, drop in Hb/Hct, FOB +, profound hemorrhage, melena/hematochezia rare

Treatment Treat underlying cause Saline lavage (prevents distension, removes bile &

pancreatic juice) Maintain pH > 5 Correct coagulopathy

Ali, Tauseef, and Richard F. Harty. "Stress-Induced Ulcer Bleeding in Critically Ill Patients." Gastroenterology Clinics of North America 38.2 (2009): 245-65

GastricMucosal DefenseMechanisms

Ali, Tauseef, and Richard F. Harty. "Stress-Induced Ulcer Bleeding in Critically Ill Patients." Gastroenterology Clinics of North America 38.2 (2009): 245-65

Ali, Tauseef, and Richard F. Harty. "Stress-Induced Ulcer Bleeding in Critically Ill Patients." Gastroenterology Clinics of North America 38.2 (2009): 245-65

Reduced Blood Flow

Mucosal Ischemia

Reperfusion Injury & Damage to Mucosal Defenses

Risk Factor IdentificationCOOK ET AL NEJM 1994 – PROSPECTIVE MULTICENTER COHORT STUDY

Cook, Deborah J. ”Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients." NEJM 330.6 (1994): 377-381.

Overall risk: 1.5%

With Mech Ventilation ±Coagulopathy: 3.7%

Without risk factors: 0.2%

Would need to offer ppx to 900 low-risk pts to prevent one episode of bleeding

Who is at Risk?

≥ 2 of the followingSepsis Burns > 35% TBSA

ICU stay > 1 week Partial Hepatectomy

Occult bleeding > 6 days ISS > 16

High dose Steroids (>250 mg/day of hyrocort or equiv)

Transplant Patients in ICU

GCS < 10 Hepatic Failure

Spinal Cord Injuries

Schupp, Kelly. "A Cost-Effectiveness Analysis of Stress Ulcer Prophylaxis." Annals of Pharmacotherapy 37 (2003): 631-35

ICU + 1 of the followingCoagulopathy Ventilator > 48h

GI bleed within last year or h/o ulceration

Antacids:NaHCO3CaCO3Mg(OH)2Al(OH3)2

Guillamondegui OD, Gunter OL Jr, Bonadies JA, Coates JE, Kurek SJ, De Moya MA, Sing RF, Sori AJ. Practice management guidelines for stress ulcer prophylaxis. Chicago (IL): Eastern Association for the Surgery of Trauma (EAST); 2008. 24 p

RecommendationsGuillamondegui: Eastern Trauma - 2008Practice management guidelines for stress ulcer prophylaxis

Guillamondegui OD, Gunter OL Jr, Bonadies JA, Coates JE, Kurek SJ, De Moya MA, Sing RF, Sori AJ. Practice management guidelines for stress ulcer prophylaxis. Chicago (IL): Eastern Association for the Surgery of Trauma (EAST); 2008. 24 p

RecommendationsGuillamondegui: Eastern Trauma - 2008Practice management guidelines for stress ulcer prophylaxis

Which to Use? Enteral Feedings?

Antacid? Cheap, oral, neutralized acid directly,

need to dose q1-2, hypermag, hyperphos, hypercalcemia

Sucralfate? Oral, does not alter pH, coats and

adheres to the mucosa, forms a physical barrier, rare aluminum tox

Which to Use? H2RA?

Oral or IV, binds to H2 receptor on parietal cell to block its activation and cAMP release

Development of tolerance PPI?

Oral or IV, Irreversibly binds to the H+

K+ ATPase pump of the parietal cell, preventing acid secretion.

Only binds to actively secreting pumps. Parietal cell must make new pumps in order to function

What are the Risks? Increased risk of infection?

Altered vitamin/electrolytes/minerals?

Drug-drug interaction?

Side effects?

Levy, Michael J. "Comparison of Omeprazole and Ranitidine for Stress Ulcer Prophylaxis." Digestive Diseases and Sciences 42.6 (1997): 1255-259

Omeprazole vs. RanitidineLevy – Comparison of Omeprazole and Ranitidine for SUPProspective, RCT of 67 Patients

Conrad, Steven A.. "Randomized, Double-blind Comparison of Immediate-release Omeprazole Oral Suspension versus Intravenous Cimetidine for the Prevention of Upper Gastrointestinal Bleeding in Critically Ill Patients." Critical Care Medicine 33.4 (2005): 760-65

Omeprazole vs. CimetidineConrad et al – Crit Care Med 2005Prospective, Double Blind359 patients

Pantoprazole vs. CimetidineSomberg – TRAUMA 2008Randomized Controlled 202 patients

Somberg, Lewis. "Intermittent Intravenous Pantoprazole and Continuous Cimetidine Infusion: Effect on Gastric PH Control in Critically Ill Patients at Risk of Developing Stress-related Mucosal Disease." TRAUMA 64 (2008): 1202-210

Pantoprazole vs. CimetidineSomberg – TRAUMA 2008Randomized Controlled 202 patients

Somberg, Lewis. "Intermittent Intravenous Pantoprazole and Continuous Cimetidine Infusion: Effect on Gastric PH Control in Critically Ill Patients at Risk of Developing Stress-related Mucosal Disease." TRAUMA 64 (2008): 1202-210

Somberg, Lewis. "Intermittent Intravenous Pantoprazole and Continuous Cimetidine Infusion: Effect on Gastric PH Control in Critically Ill Patients at Risk of Developing Stress-related Mucosal Disease." TRAUMA 64 (2008): 1202-210

Pantoprazole vs. CimetidineSomberg – TRAUMA 2008Randomized Controlled 202 patients

Somberg, Lewis. "Intermittent Intravenous Pantoprazole and Continuous Cimetidine Infusion: Effect on Gastric PH Control in Critically Ill Patients at Risk of Developing Stress-related Mucosal Disease." TRAUMA 64 (2008): 1202-210

Pantoprazole vs. CimetidineSomberg – TRAUMA 2008Randomized Controlled 202 patients

What about Cost?Schupp – Pharmacotherapy 2003Observational study 88 patients

Schupp, Kelly. "A Cost-Effectiveness Analysis of Stress Ulcer Prophylaxis." Annals of Pharmacotherapy 37 (2003): 631-35.

Benefits & Safety Don’t develop tolerance

vs. H2RAs More consistent pH control

vs. H2RAs, Sucralfate More palatable

vs. Sucralfate, Antacids More cost effective

Lansoprazole po vs. IV Cimetidine Does not accelerate progression of chronic gastritis, gastric

atrophy, intestinal metaplasia Iron/B12 deficiency. No increased risk except B12 def in elderly Short term PPI use – increase CAP, but not in long term

Do not increase risk of HAP

Thomson, Alan. "Safety of the Long-term Use of Proton Pump Inhibitors." World Journal of Gastroenterology 16.19 (2010): 2323-330.

The future? Systematic review of randomized controlled studies

that evaluated association between SUP and GI bleeding 17 studies (1836 patients)

H2 Receptor Blockers reduced GI bleeding only in subgroup who did not receive enteral nutrition.

Increased pneumonia in patients with H2 Blockers AND enteral feeding

Higher mortality in patients with H2 Blockers AND enteral feeding

1. Lucas, Charles E. "Natural History and Surgical Dilemma of "Stress" Gastric Bleeding." Arch Surg 102 (1970): 266-73.

2. Hastings, Paul R. "Antacid Titration in the Prevention of Acute Gastrointestinal Bleeding." NEJM 298.19 (1978): 1041-045.

3. Cook, Deborah J. ”Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients." NEJM 330.6 (1994): 377-381.

4. Ali, Tauseef, and Richard F. Harty. "Stress-Induced Ulcer Bleeding in Critically Ill Patients." Gastroenterology Clinics of North America 38.2 (2009): 245-65.

5. Sabiston, David C., and Courtney M. Townsend. "Ch 47." Sabiston Textbook of Surgery: the Biological Basis of Modern Surgical Practice. Philadelphia: Saunders/Elsevier, 2008. Print.

6. Guillamondegui OD, Gunter OL Jr, Bonadies JA, Coates JE, Kurek SJ, De Moya MA, Sing RF, Sori AJ. Practice management guidelines for stress ulcer prophylaxis. Chicago (IL): Eastern Association for the Surgery of Trauma (EAST); 2008. 24

7. Levy, Michael J. "Comparison of Omeprazole and Ranitidine for Stress Ulcer Prophylaxis." Digestive Diseases and Sciences 42.6 (1997): 1255-259

8. Conrad, Steven A.. "Randomized, Double-blind Comparison of Immediate-release Omeprazole Oral Suspension versus Intravenous Cimetidine for the Prevention of Upper Gastrointestinal Bleeding in Critically Ill Patients." Critical Care Medicine 33.4 (2005): 760-65.

9. Somberg, Lewis. "Intermittent Intravenous Pantoprazole and Continuous Cimetidine Infusion: Effect on Gastric PH Control in Critically Ill Patients at Risk of Developing Stress-related Mucosal Disease." TRAUMA 64 (2008): 1202-210.

10. Thomson, Alan. "Safety of the Long-term Use of Proton Pump Inhibitors." World Journal of Gastroenterology 16.19 (2010): 2323-330.

11. Schupp, Kelly. "A Cost-Effectiveness Analysis of Stress Ulcer Prophylaxis." Annals of Pharmacotherapy 37 (2003): 631-35.

12. Marik, Paul E. "Stress Ulcer Prophylaxis in the New Millennium: A Systematic Review and Meta-Analysis." Crit Care Med 38.11 (2010): 2222-2228