Stress Ulcer Prophylaxis in the ICU:

If you can’t feed them, proton pump inhibit them

Karen LoUniversity of Colorado, PGY4

March 26, 2012

Stress Related Mucosal InjuryOverview

History Physiology Who is at risk? The medications:

Why PPIs are better

Stress Related Mucosal InjuryHistory

1800s: Curling described ulcers in burn patient

1969: Skillman reported stress ulcers in ICU patients

1970s: Lucas coined he term stress related mucosal damage

1980s incidence of stress ulcers decreasing by increasing gastric PH

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

Stress Related Mucosal Injury

Endoscopic studies have shown nearly all critically ill patients develop upper GI erosions 90% ICU patients have

gastric erosions by ICU day 3

Eddleston; Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients , CritCare Med, 1994; 22:1949-1954

Stress Related Mucosal injuryPathophysiology

Stress Related Mucosal InjuryWho is at risk?

Level 1 Mechanical ventilation

over 48 hours Coagulopathy

INR >1.5 or ptl<50

Traumatic brain injury Major burn

Level 2ICU pt with: Multi-trauma Sepsis Acute Renal failure

Guillamondegui, OG., et al. Eastern Trauma Association Practice Management Guidelines for Stress Ulcer Prophylaxis. 2008

Stress Related Mucosal InjuryProphylaxis:

What drug do I use? Antacid Carafate H2 blockers PPI

Stress Related Mucosal Injurythe other meds:

Antacids Neutralizes the acid of the

stomach Oral Re-dose every 1-2 hours Aspiration pneumonia Toxicity:

Hypermagnesium Hyperphosphotemia Hypercalemia

Stress Related Mucosal Injurythe other meds:

Antacids Neutralizes the acid of the

stomach Oral Re-dose every 1-2 hours Aspiration pneumonia Toxicity:

Hypermagnesium Hyperphosphotemia Hypercalemia

Stress Related Mucosal Injurythe other meds:

Sucralfate Oral Coats and adheres to

gastric mucosa Does not change gastric ph Decreases absorption of

some medications Aluminum toxicity

Stress Related Mucosal Injurythe other meds:

Sucralfate Oral Coats and adheres to

gastric mucosa Does not change gastric ph Decreases absorption of

some medications Aluminum toxicity

Stress Related Mucosal Injurythe other meds:

Histamine Receptor Antagonist Oral and IV Ranitidine superior to

sucralfate in preventing UGI bleed in ICU Pt *

Reversibly binds to H2 receptor of partietalcells

*Cook, Risk factors for clinically important UGI bleeding in pts requiring mechanical Ventilation. Critical Care Med 1999 Dec 27(12):28 12-7

Partietal cell

Stress Related Mucosal Injurythe other meds:

Histamine Receptor Antagonist Does not acid stop

stimulation from Acetycholine and Gastrin receptors

Partietal cell

H H

Stress Related Mucosal Injurythe other meds:

Histamine Receptor Antagonist Less gastric acid control Multiple daily dosing Unwanted side effects: 7% adverse reactions

Altered mental status, neutropenia, thrombocytopenia

Increased incidence of hospital acquired pneumonia

Drug Resistance: Tachyphylaxis

Stress Related Mucosal InjuryPPI

Irreversibly binds to Proton pump Inhibiting the final step

in acid production Rapid onset of action Longer duration of

action

Stress Related Mucosal InjuryPPI

Irreversibly binds to Proton pump Inhibiting the final step

in acid production Rapid onset of action Longer duration of

action

Stress Related Mucosal InjuryPPI

Safe

Do not increase the risk of hospital acquired pneumonia

Thomson, Safety of the long term use of PPR, World Journal of Gastroenterology, 2010, May 21;16 (19) 2323-2330

Stress Related Mucosal InjuryOral PPI versus IV H2B

Direct comparison omeprazole versus ranitidine in 77 trauma patients

Prospective RCT Single institution

Levy, Comparison of Omeprazole and Ranitidine for Stress Ulcer Prophylaxis, Digestive Diseases Science. 1997; 42;6.

Stress Related Mucosal InjuryPPI versus H2B

PPI less incidence of stress ulcer bleed: 6%

H2B increased incidence of stress ulcer bleeding: 31%

Levy, Comparison of Omeprazole and Ranitidine for Stress Ulcer Prophylaxis, Digestive Diseases Science. 1997; 42;6

Stress Related Mucosal InjuryPPI versus H2B

H2B do increased the risk of hospital acquired Pneumonia

PPIs do not increase the risk of hospital acquired Pneumonia

Levy. Digestive Diseases Science. 1997.Thomson, Safety of long term use of PPI, World Journal of Gastroenterology 2010 May 21;16(19) 2323-2330

Stress Related Mucosal InjuryOral PPI versus IV H2B

Conrad. Randomized, double blind comparison of immediate-release omeprazole oral suspension ve IC cimetidine for prevention of UGI bleed in Critically ill patients, Critical care med 2005;33 760-765

Stress Related Mucosal InjuryOral PPI versus IV H2B

Conrad. Randomized, double blind comparison of immediate-release omeprazole oral suspension ve IC cimetidine for prevention of UGI bleed in Critically ill patients, Critical care med 2005;33 760-765

Stress Related Mucosal InjuryOral PPI versus IV H2B

Conrad. Randomized, double blind comparison of immediate-release omeprazole oral suspension ve IC cimetidine for prevention of UGI bleed in Critically ill patients, Critical care med 2005;33 760-765

Stress Related Mucosal InjuryPPI versus H2B cost

Observational study of ICU patients

32 pts on Cimetidine 25 pts on Cimetidine

who were changed lansoprazole

31 pts on Lansoprazole

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

Stress Related Mucosal InjuryPPI versus H2B cost

Of 32 patients on Cimetidine 5 failed

All 31 patients on Lansoprazole had successful treatment

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

Stress Related Mucosal InjuryPPI versus H2B

H2 Blockers Proton Pump InhibitorsFDA approved medications for stress-ulcer prophylaxis

Cimetidine Omeprazole

Potency to reduce gastric acid secretion

++ ++++

Common side effects +++ ++Drug interactions +++ +Tachyplaxis + NoneCost-effectiveness ++++ ++Therapeutic effectiveness ++ ++++

Ali, Stress -Induced Ulcer Bleeding in critically Ill patients, Gastroenterology 2009 245-265

References Ali, Stress -Induced Ulcer Bleeding in critically Ill patients, Gastroenterology 2009 245-265 Cook, DJ, Reeve, BK, Guyatt, GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant

meta-analyses. JAMA 1996; 275:308. Cook, DJ, Witt, LA, Cook, RJ, Guyatt, GH. Stress ulcer prophylaxis in the critically ill: A meta-analysis. Am J

Med 1991; 91:519. Conrad, SA, Gabrielli, A, Margolis, B, et al. Randomized, double-blind comparison of immediate-release

omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med 2005; 33:760

Eddleston; Prospective endoscopic study of stresserosions and ulcers in critically ill adult patients , Crit Care Med, 1994; 22:1949-1954

Lasky, MR, Metzler, MH, Phillips, JO. A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients. J Trauma 1998; 44:527.

Levine, Meta-Anaylsis : the efficacy of intravenous H2-receptor antagonist in bleeding peptic ulcer. Aliment Pharmacol Ther 2002 16: 1147-1142

McCarthy, Management of bleeding peptic ulcers: Current status of intravenous proton pump inhibitors, Best Practice and Research Clinical Gastroenterology 2004: 18: 7-12

Mohebbi, L et al. Stress Ulcer Prophylasix in the ICU, Pharmacology Notes 2009; 22(4):373-376 Shuman, RB, Schuster, DP, Zuckerman, GR. Prophylactic therapy for stress ulcer bleeding: A reappraisal.

Ann Intern Med 1987; 106:562 Phillips JO, Metzler MH, Palmieri MT, et al. A prospective study of simplified omeprazole suspension for the

prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24:1793. Phillips JO, Metzler MH, Palmieri MT, et al. A multicenter, prospective, randomized clinical trial of continuous

infusion IV ranitidine vs omeprazole suspension in prophylaxis of stress ulcers. Crit Care Med 1998; 26:A101. Tryba, M. Prophylaxis of stress ulcer bleeding. A meta-analysis. J Clin Gastroenterol 1991; 13 Suppl 2:S44 Walt, Continuous intravenous famotidine for haemorrhage from peptic ulcer. Lancet 1992 340:1058-1062