ICU Stress Ulcer Prophylaxis: Non-PPI Methods. Nicole Nadlonek, PGY-3 University of Colorado Surgical Grand Rounds 3/26/11

Transcription

1 ICU Stress Ulcer Prophylaxis: Non-PPI Methods Nicole Nadlonek, PGY-3 University of Colorado Surgical Grand Rounds 3/26/11

2 Outline History Therapeutic Options Current Usage Efficacy Data Adverse Drug Effects Cost Recommendations

3 History: Why do we care? Sentinel paper from Dr. Eiseman and our institution Incidence: 11% Medical therapy: Iced saline lavage Antacid NG suction and blood replacement Surgical therapy: Vagotomy and pyoloroplasty Gastric resection (generous) Treatment of underlying factor causing stress (undrained pus) Eiseman and Hayman NEJM 1970

4 History: Why do we care? Critically ill patients in 2009: Stress-related mucosal damage % Occult bleeding 15-50% Clinically overt bleeding if no prophylaxis 5-25% Clinically significant bleeding 0.6-4% Confers a mortality of almost 50% Ali et al, GI Clin N Am 2009

5 Therapeutic Options H2-receptor antagonists (Cimetidine, Ranitidine, Famotidine) Blocks histamine receptor on parietal cells PPI (Omeprazole, lansoprazole, pantoprazole) Irreversible H/K ATPase pump inhibitor

6 Therapeutic Options Misoprostol Synthetic PGE 1 analog Sucralfate Sucrose/aluminum hydroxide salts Coats the gastric mucosa Antacids (aluminum and magnesium hydroxide) Neutralize gastric acid and inactivate pepsin s proteolytic activity Enteral feeding

7 Current Usage Survey of 188 Level 1 trauma centers in the US 119 surveys returned (63%) 86% said they use stress ulcer prophylaxis in the majority of trauma patients Of those, 71% said that H2 blockers were most popular Barletta et al, Critical Care 2002

8 H2 Blockers vs: PPI Meta-analysis of 7 RCTs 936 patients Combine efficacy and safety information for randomized trials: PPIs vs H2 blockers UGI Bleeding Pneumonia Mortality IV and oral formulations Lin, Crit Care Med 2010

9 H2 Blockers vs: PPI No statistically significant difference in upper GI bleed Lin, Crit Care Med 2010

10 H2 Blockers vs: PPI No statistically significant difference in rates of pneumonia Lin, Crit Care Med 2010

11 H2 Blockers vs: PPI No statistically significant difference in rates of mortality Lin, Crit Care Med 2010

12 Antacids vs. H2 Blockers Meta-analysis 42 randomized trials, 4409 patients Examined antacids, H2 blockers, sucralfate and prostaglandins Antacids vs H2 blockers: included 14 studies Looking for: overt bleeding, clinically important bleeding and mortality Cook et al, Am J Med 1991

13 Antacids vs. H2 Blockers Antacids vs placebo : Overt bleeding - OR 0.40 (95% CI ) H2 blocker vs placebo overt bleeding: OR 0.29 (95% CI ) H2 blocker vs Antacids overt bleeding: OR 0.56 (95% CI ) Cook et al, Am J Med 1991

14 Sucralfate vs H2 Blockers Multicenter, randomized, blinded, placebo controlled 1200 pts on mechanical ventilation Assigned to either: Ranitidine + sucralfate placebo Ranitidine placebo + sucralfate Cook et al, NEJM 1998

15 Sucralfate vs. H2 Blockers Rates of bleeding: Ranitidine 1.7% Sucralfate 3.8% Relative risk: 0.44 (95% CI ) No significant difference in rates of VAP (19 vs 16% p = 0.19) or mortality (23.5 vs 22.8% p = 0.79) Cook et al, NEJM 1998

16 Enteral Nutrition Animal models: enteral nutrition increases GI blood flow, decreases macroscopic lesions Continuous administration of intragastric enteral nutrition to critically ill pts increases gastric ph More likely to raise gastric ph to >3.5 Compared to no nutrition (OR 4.5) Compared to antacids, H2 blockers or PPIs (OR 2.04) MacLaren et al, Ann Pharm 2001

17 Adverse Effects: Pneumonia Retrospective review 887 CT patients receiving stress ulcer prophylaxis (pantoprazole vs ranitidine) Examine rates of nosocomial pneumonia Rates of upper GI bleeding: 0.8% in pantoprazole group 0.2% in ranitidine group Miano et al, Chest 2009

18 Adverse Effects: Pneumonia Increased rates of nosocomial pneumonia in PPI group OR 6.6 (95% CI ) Miano et al, Chest 2009

19 Adverse Effects: C difficile Systematic literature review Included observational studies 12 studies included, 2948 pts with C difficile Examined association between acid suppression therapy and enteric infections Leonard et al, Am J GI 2007

20 Adverse Effects: C difficile H2 Blockers PPIs Increased risk of C difficile infection with PPIs. OR 1.94 (95% CI 1.37 to 2.75) Leonard et al, Am J GI 2007

21 Cost Protonix IV requires refrigeration, has limited stability, is twenty times more expensive per day ($20 per 40 mg IV versus $0.49 per 20 mg famotidine IV) and is more complex to administer, requiring filtration with the filter placed below the site Bon Secours Richmond Pharmacy & Therapeutics Committees Proton Pump Inhibitors 7/2002

22 Conclusions H2 blockers are as effective or more effective than other non-ppi alternatives. H2 blockers are as clinically as effective as PPIs H2 blockers confer a lower risk of pneumonia and C difficile infection H2 blockers are at WORST 25% of the cost of PPIs. Bon Secours Richmond

23 Recommendations: In coagulopathic, intubated patients with either TBI or major burns H2 Blocker until extubated or for 7 days Consider use of prophylaxis in critically ill patients with: Acute hepatic failure Prolonged NG tube Alcoholism Renal failure Appropriate monitoring of critically ill patients Feed em if possible DO NOT send the patients to the floor with stress ulcer prophylaxis

24 References: 1. Bon Secors Richmond Pharmacy and Therapeutics Committees: Proton Pump Inhibitors 7/ Cook RJ, Cook RJ, Guyatt GH. Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am J Med. 1991; 91: Lin PC et al. The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med. 2010; 38: Miano et al. Nosocomial pneumonia risk and stress ulcer prophylaxis. Chest 2009; 136: Fohl AL and Randolph ER. Proton pump inhibitor-associated pneumonia: not a breath of fresh air after all? World J GI Pharm Ther 2011; 2(3): Humphries TJ and Meritt GJ. Review article: drug interactions with agents used to treat acid related diseases. Aliment Pharm Ther 1999; 3: Leonard J et al. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J GI 2007; 102: Allen ME et al. Stress ulcer prophylaxis in the postoperative period. Am J Health-Syst Pharm 2004; 61: Perwaiz MK et al. Inappropriate use of intravenous PPI for stress ulcer prophylaxis in an inner city community hospital. J Clin Med Res 2010; 2(5): Cook D et al. A comparison of sucralfate and ranititidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. N Engl J Med 1998; 338: Heidelbaugh JJ et al. Overutilization of PPIs: a review of cost-effectiveness and risk in PPI. Am J GI 2009;104:S Eiseman B and Heyman RL. Stress Ulcers a Continuing Challenge. NEJM 1971; 282: Ali T and Harty RF. Stress-induced Ulcer bleeding in Critically Ill patients. GI Clinic N Am 2009; 38: Guillamondegui OD et al. Practice management guidelines for stress ulcer prophylaxis Eastern Assoc for Surgery of Trauma 15. Somberg L et al. Intermittent intravenous pantoprazole and continuous cimetidine infusion: effect on gastric ph control in Critically ill patients at risk of developing stress-related mucosal disease. J Trauma 2008; 64: MacLaren R et al. Use of enteral nutrition for stress ulcer prophylaxis. Ann Pharm 2001; 35: Barletta JF et al. Stress ulcer prophylaxis in trauma patients. Crit Care 2002; 6:

25 Enteral Nutrition Burn patients: 181 burn pts total Prospective randomized studies Antacid therapy, continuous elemental enteral nutrition, or combination No difference in bleeding rates MacLaren et al, Ann Pharm 2001

26 Cost Perwaiz et al, J Clin Med Res 2010

27 Cost Retrospective study Primary outcome: appropriateness of use of PPI Per American GI Association guidelines 1472 pts received IV PPI Randomly selected 75% chart reviewed 713 pts received IV PPI for stress ulcer prophylaxis In 68.5% of those, PPI were not indicated Perwaiz et al, J Clin Med Res 2010