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Stress Ulcer Prophylaxis: Guideline Update April 2014
Rob Wills, Pharm.D., BCPS
Clinical Manager of Pharmacy
PGY1 Residency Program Director
St. Luke’s Boise-Meridian Medical Centers
Disclosure Statement
�No conflict of interest
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Objectives� Who should be receiving stress ulcer prophylaxis in your institution?
� Pathophysiology
� Risk Factors
� What medications are best to use to prevent stress ulcers?
� The great debate: PPI’s vs. H2RA’s vs. sucralfate
� What are the complications of providing stress ulcer prophylaxis?
� Strategies for gaining back the control
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Why is this important?� Unnecessary Costs
� Meds without an indication
� Inappropriate use
� Patients sent home on SUP agents
� Opportunistic Infections
� C. difficile
� Pneumonia
� Readmissions
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Question 1
�Who’s been anxiously awaiting the release of the new Stress Ulcer Prophylaxis guidelines?
A. Check ASHP website at least weekly
B. What Guidelines
C. I thought this was a Law Talk?
D. None of the above
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ASHP GuidelinesDocument Publishe
d
Next
Review Date
Estimated
Publication Date
Antimicrobial Prophylaxis in Surgery
2013 2016 --
Clinical Practice Guidelines for Sustained Use of Neuromuscular Blockade in the Adult Critically Ill Patient
2002 In process
--
Clinical Practice Guidelines for the Management of Pain Agitation and Delirium in Adult Patients in the ICU
2013 2016 --
Gastrointestinal Stress Ulcer Prophylaxis
New In process
Q1 2014
www.ASHP.org accessed 3/3/14
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The Guidelines
� Last updated 1999
�What’s missing?
�Are they still relevant?
ASHP Therapeutic Guidelines on SUP. AJHP.1999;56(4):347-379.
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History
1800’s
Erosions & Gastric Ulcers have been known to develop
1970’s
Gastric Acid linked as possible cause of stress ulcer development
1980’s
Incidence of stress-ulcer related bleeding was found to be decreased by
increasing gastric pH
ASHP Therapeutic Guidelines on SUP. AJHP.1999;56(4):347-379.Schuster DP. Crit Care Med. 1993;21:4-6.Schuster DP, et al. Am J Med. 1984;76:623-630.Sesler JM. ACCN. 2007;18(2):119-128.
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Background� 1970
� Skillman and Silen reported a clinical syndrome of lethal “stress ulceration” in patients with� respiratory failure� hypotension� sepsis in the ICU
� 1971� Lucas et al labeled this as “stress-related erosive syndrome”
� Today� Stress Related Mucosal Disease
Skillman JJ, Silen W. Acute gastroduondenal “stress” ulceration: Barrier disruption of varied pathogenesis? Gastroenterology. 1970;59:478-482Lucas CE, SugawaC, Riddle J, et al. Natural history and surgical dilemma of “stress” gastric bleeding. Arch Surg. 1871;102:266-273.
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Terminology� Stress Ulcers
� Ulceration
� Stress erosions
� Stress gastritis
� Hemorrhagic gastritis
� Erosive gastritis
� Peptic Ulcers
� Gastric Ulcers
� Stress-Related Mucosal Disease
� SRMD
Sesler JM. ACCN. 2007;18(2):119-128.
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CHEST. 2001;119(4):1222-1241. doi:10.1378/chest.119.4.1222
Proposed mechanisms for development of stressulceration. SRMD results from the complex interaction of multiplesystems. The specific relationships depicted remain somewhatspeculative. Reprinted with permission from Bresalier.44
Figure Legend:
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GI Complications in Patients Receiving Mechanical Ventilation*
CHEST. 2001;119(4):1222-1241. doi:10.1378/chest.119.4.1222
Proposed mechanisms for the development of GI complications during MV. MV can contribute to the pathogenesis of GI problems in much the same way as critical illness by affectingsplanchnicblood flow and leading to increased release ofproinflammatorymediators. SIRS = systemic inflammatory response syndrome; TNF-α = tumor necrosis factor-α.
Figure Legend:
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Pathogenesis of stress ulcerationOccurs in 50 to 70% of ICU patients within 12 to 24 hours
GI Mucosal Ischemia
Impaired defense mechanisms:� H+ back-diffusion� Mucous/bicarbonate barrier� Prostaglandin production� Epithelial renewal
Stress Ulceration
Gastrointestinal bleed
Mortality rate is 50 to 70%
Acid Secretion
H. Pylori infection?
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP
Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference
Classification of GI Bleeding
Outcome Measure of GI Bleeding
DefinitionIncidence in ICU
patients
Endoscopic EvidenceEndoscopic evidence of gastroduodenal SRMD lesions
74 to 100%
Occult Guaiac-positive stools or nasogastric aspirate 15 to 50%
Overt ORClinicallyevident
Hematemesis, gross blood or coffee grounds material in nasogastric tube aspirate, hematochezia or melena
5 to 25%
Clinically Significant
Overt bleeding accompanied by- Hemodynamic compromise
- Decrease in BP by 20 mmHg- Need for blood transfusion
- Decrease in Hgb by 2 g/dL AND transfusion of 2 units of blood
- Need for surgeryShould be used as outcome measure for all trials
< 5%
Table 1
Naylor DF. Clinical Applications of Stress Ulcer Prophylaxis. Soc of Crit Care Med. 2012 conference.Cook et al. NEJM.1994;330:377-381.
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Appearance� Appearance
� Diffuse sub-epithelial hemorrhage with or without erosions
CHEST. 2001;119(4):1222-1241. doi:10.1378/chest.119.4.1222
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Where is this occurring?�Acid-producing areas of stomach
� Upper body
� Fundus
Accessed from www.webmd.com
8-2012
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Outcomes
�Morbidity
� Increases length of ICU stay from 4 to 8 days, or even 11 days longer stay
�Mortality
� 50% - 75% of patients with clinically significant bleed
� ~ 12% directly attributable to the bleed
�Cost of bleed
� $7000 in 1999
Cook et al. NEJM.1994;330:377-381.Sesler JM. ACCN. 2007;18(2):119-128.
AJHP. 1999:56;347-379.
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Question 2
�Which of the following is a risk factor for stress-related ulcer bleeding in a 73 year old critically ill patient?
A. An INR of 5
B. Acute renal failure
C. ARDS with ventilator support for 72 hours
D. All of the above
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP
Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference
Critical Illness
Splanchnic Hypoperfusion
Reduced HCO3 Secretion
Reduced Mucosal Blood Flow
Decreased GI Motility
Acid Back Diffusion
Decreased Cardiac Output
Increased Catecholamines
HypovolemiaProinflammatory Cytokine Release
Acute Stress Ulcer
Increased Vasoconstriction
Mutlu GM, Mutlu EA, Factor P. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222-1241.
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Risk factors for Stress Ulcer Bleeding in Critically Ill Patients
Study Design
� N=2252
� Primary Diagnosis� CV surgery (48.5%)
� Respiratory (12%)
� Head Injury (1.2%
� Sepsis (1.6%)
� Multiple trauma (0.8%)
� APACHE II score: 21± 9 (moderate-severe illness)
Risk Factor Multiple Regression: Odds Ratio for Developing GI Bleed
Respiratory failure 15.6*
Coagulopathy 4.3*
Hypotension 3.7
Sepsis 2.0
Hepatic Failure 1.6
Renal Failure 1.6
Cook et al. NEJM.1994;330:377-381.
.
*Identified as independent risk factors; P< 0.001
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Risk factors for SRMD� Respiratory failure requiring mechanical ventilation ≥ 48 hrs
� Coagulopathy (INR > 1.5, PTT > 2x control or Thrombocytopenia)
� Acute renal insufficiency
� Acute hepatic failure
� Sepsis, Shock requiring vasopressors
� Multi-organ Failure
� Extensive burn or thermal injury involving more than 35% of the BSA
� Severe head or spinal cord injury
� History of gastrointestinal bleeding
� Organ transplantation
� Ulcerogenic Drugs (NSAIDS, Aspirin, Corticosteroids)
� Fibrinolytics, Anticoagulants
Cook et al. NEJM.1994;330:377-381.Sesler JM. ACCN. 2007;18(2):119-128.
AJHP. 1999:56;347-379.Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Degree of Acid Suppression Required Varies Depending on Indication
Gastric pH Physiologic Activity
≥ 3.5 Decreased incidence of stress-induced bleeding
≥ 4.5 Pepsin inactivation
5 99.9% acid neutralization
< 5 to 7 Alterations in coagulation and platelet aggregation
≥ 7 Potential decrease in incidence of rebleeding
≥ 8 Pepsin destruction
Prevention of Stress-Related Mucosal Disease
Prevention of Stress-Related Mucosal Disease
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference
Question 3� 57 year old male admitted to the ICU with sepsis 2 days ago� Placed on Mechanical Vent at that time due to respiratory
failure
� Also experiencing some acute
renal failure, thrombocytopenia, and hypotension
� Which of the following can be used as first-line stress
ulcer bleeding prevention?
A. Famotidine IV
B. Esomeprazole IV
C. Omeprazole NGT
D. Sucralfate NGT
Accessed from heart-valve-surgery.com August 2012
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Therapeutic Options
�Antacids
� Sucralfate
� Histamine 2 Receptor Antagonists (H2RA)
� Proton Pump Inhibitors (PPI)
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AntacidsDose: 30 – 60 mL q 1 – 2 Hrs with pH monitoring
� Rarely used today
�Disadvantages� Labor intensive – frequent dosing and frequent monitoring
� Dosed to pH of 3.5 to 4
� Required frequent monitoring
� High volume may pre-dispose patients to aspiration pneumonia
� GI disturbances
� Electrolyte imbalances (magnesium and aluminum)
� Metabolic acidosis
� Numerous drug interactions (digoxin, quinolones, iron)
� Not cost effective
Blogs.cbn.comCohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally
here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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SucralfateDose: 1 to 2 grams Q 4 – 8 Hours
� Doesn’t change the pH of the stomach� Thought to have less risk of pneumonia� No pH monitoring required
� MOA:� In acidic environment forms a polymer that eventually binds with the protein cations in the exposed ulcer
� Disadvantages� Not available intravenously� Requires timing spaced from enteralfeeds
� Feeding tube occlusion� Aluminum toxicity� Hypophosphatemia� Constipation� Drug Interactions via chelation
� Quinolones, digoxin, warfarin, quinidine, levothyroxine, azoles
Drsfosterandsmith.comCohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally
here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Histamine-2 Receptor Antagonists (H2RA’s)Cimetidine, Ranitidine, Famotidine, Nizatidine
Started in the mid 90’s with cimetidine infusion = well studied
� IV and PO formulation
� Cimetidine IV = only H2RA FDA approved for SUP
� Intermittent vs Continuous infusions
� No advantage to pH monitoring vs no pH monitoring
� Tachyphylaxis with CI
� Renal dosing required
� Cost effective – generics available
www.medicineworld.orgCohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally
here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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IV PPI For Management of UGI Bleed: ToleranceOmeprazole 80 mg + 8 mg/hr vs Ranitidine 50 mg + 0.25 mg/hr x 72 hrs
DB crossover with gastric pH
Results (n=34 healthy
volunteers)Day One Day Three
Median pH Omeprazole*
6.1 6.3
Median pH Ranitidine 5.1 2.7
% pH > 4 Omeprazole* 95% >99%
% pH > 4 Ranitidine 70% 26%
% ph > 6 Omeprazole 59% 71%
% pH > 6 Ranitidine 30%# 7%*
* p ranitidine > nizatidine > famotidine
� Pneumonia – CAP
� Rapid IVP: hypotension and arrhythmias
� Pseudo-renal failure with cimetidine
� CYP-450 drug interactions: 3A4, 2D6, 2C19, 1A2
� Phenytoin, warfarin, amiodarone, colchicine, BZDs, CCBs
� Cimetidine >> ranitidine (low) > nizatidine: famotidine (none)
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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H2RA-Induced Thrombocytopenia
� Structure Related
�Onset is 4 – 7 days
�Can occur earlier with prior exposure
�Cross reactivity is 100%
http://oregonstate.edu/instruct/bb350/textmaterials/ch03.html
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Sucralfate vs. Ranitidine for Prevention of Upper GI Bleeding in Mechanically Ventilated Patients
0
20
40
60
80
100
120
GI Bleeding Ventilator Associated
Pneumonia
Occurrence Rate (%)
Events
Sucralfate (n=596)
Ranitidine (n=604)
N=1200
P=0.19
Cook D et al. N Engl J Med 1998;338:791-797.
Ranitidine 50 mg IV Q8H vs. Sucralfate 1 gm Q6H
RR = 0.44
P=0.02
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference
Question 4
�Which of the following is an adverse effect of PPIs?
A. Interstitial nephritis
B. Hypomagnesemia
C. C. difficile diarrhea
D. All of the Above
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Proton Pump Inhibitors (PPIs)Pantoprazole, Omeprazole, Lansoprazole, etc.� Activated by protination in parietal cells and then binds to H/K counter exchange ATPase to block acid production
� Most potent of gastric acid secretion agents
� Superior to H2RA’s in other settings
� Consistent pH control
� IV and PO forms
� Most trials studied enteral PPIs for SUP
� Lack of data for IV PPIs
� Becoming less expensive
� ADR’s
� Pneumonia
� C.diff
� Possible drug interactions
� P450’s and Clopidogrel
� Latest Sepsis Guidelines seem to favor PPIs
Cloudfront.net Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Medication Route DoseMetabolism by Hepatic CYP450enzymes
Excretion
EsomeprazolePONG & IV
40 mg daily 2C19 > 3A480% renal inactivemetabolites, < 1% parent drug in urine
LansoprazolePONG & IV
15 or 30 mg daily
15 mg = 81%30 mg = 91%
14 – 25% renalInactive metabolites, < 1%Parent drug in urine 67% bile
OmeprazolePONG
20 to 40 mg daily
2C19 > 3A477% renal inactive metabolites, “minimal” parent drug in urine 19% bile
PantoprazolePONG & IV
40 mg daily 2C19 > 3A4
71 – 82% renal inactive metabolites, no active drug in urine 18 – 20% fecal
RabeprazolePONG
20 mg daily 2C19 = 3A490% renal inactivemetabolites, no active drug in urine10% fecal
PPI Dosing
ASHP Therapeutic Guidelines on SUP. AJHP.1999;56(4):347-379.Lexi-comp Online. Accessed 8-2012Sesler JM. ACCN. 2007;18(2):119-128.
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference
PPI Adverse Effects� Gastrointestinal
� Diarrhea, nausea, vomiting, abdominal pain
� Headaches (3 to 5%)� Acute Interstitial Nephritis
� Rash, fever, arthralgias� Oliguric ARF, eosinophillia, eosinophilluria, pyuria, hematuria
� Pneumonia – CAP, HAP, VAP� C. difficileDiarrhea� Hip Fractures
� PPIs >> HrRAs
� Hypomagnesemia with chronic use (3 months)� Seizures reported� PPIs may change interstitial absorption of Mg� Pantoprazole plus Magnesium supplements have been used
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Clostridium difficile
� FDA Warning links PPIs to C. difficile-Associated Diarrhea
� Feb 8th, 2012� FDA Safety Alert warned that PPI’s may be associated with an increased risk for Clostridium difficile associated diarrhea
Pharmacy Practice News – March 2012
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PPIs and Risk of Community-Acquired CDAD- 317 cases of community-acquired C. difficile-associated disease treated with oral vancomycin and 3167 controls
Exposure within 90 days Odds ratio for C. difficile-
associated disease
95% CI
Antibiotic 8.2 6.1 – 11.0
PPI 3.5 2.3 – 5.2
Questions• Epidemiologic studies have limitations• C. difficile-associated disease involves a complex interaction between host, pathogen, and environment
Cunningham R. CMAJ. 2006;175:757-758.Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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Copyright © 2012 American Medical
Association. All rights reserved.
Use of Gastric Acid–Suppressive Agents and the Risk of Community-Acquired Clostridium difficile–Associated
Disease
JAMA. 2005;294(23):2989-2995. doi:10.1001/jama.294.23.2989
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Howell et al. Arch Intern Med. 2010;170(9):784-790.
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Howell et al. Arch Intern Med. 2010;170(9):784-790.
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Odds Ratios for Health Care–Associated Clostridium difficile Infection and Colonization According to Various Patient and Pathogen Characteristics.
Loo VG et al. N Engl J Med 2011;365:1693-1703
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Times to Health Care–Associated Clostridium difficile Infection and Colonization during Hospitalization.
Loo VG et al. N Engl J Med 2011;365:1693-1703
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Risk of Recurrent C. difficile
� 1166 patients� Metronidazole or Vancomycin treated CDI
� 527 (45.2%) received PPI’s
� Similar antibiotic exposure in both groups
� Results� 42% increased risk of recurrence
Linsky et al. Arch Intern Med. 2010;170(9):772-778.
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Proton Pump Inhibitors and Risk for Recurrent Clostridium difficile Infection
Arch Intern Med. 2010;170(9):772-778. doi:10.1001/archinternmed.2010.73
Recurrence-free survival in those exposed vs unexposed to proton pump inhibitors (PPIs) during treatment for incident Clostridium difficile infection. Time to recurrence started from the incident toxin finding or the start of antibiotic treatment (≤3 days after thediagnosis).
Figure Legend:
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Use of Proton Pump Inhibitors and the Risk of Community-Acquired Pneumonia: A Population-
Based Case-Control Study
Arch Intern Med. 2007;167(9):950-955. doi:10.1001/archinte.167.9.950
Association between current use of proton pump inhibitors (PPIs) and community-acquired pneumonia, according to the timing of first PPI prescription. ORs indicates odds ratios.
Figure Legend:
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Community-Acquired PneumoniaComparing the Literature
Current PPI Use
OR (CI)
Current H2RA Use
OR (CI)
Arch Intern Med 2007
1.5 (1.3 – 1.7) 1.10 (0.8 – 1.3)
Ann Intern Med 2008 1.02 (0.97 – 1.08) 0.99 (0.95 – 1.04)
JAMA 2004 1.89 (1.36 – 2.62) 1.63 (1.07 – 2.48)
JAMA. 2004;292(16):1955-1960. doi:10.1001/jama.292.16.1955
Arch Intern Med. 2007;167(9):950-955. doi:10.1001/archinte.167.9.950
Ann Intern Med. 2008;149(6):391-398.
Naylor DF. Clinical Applications of Stress Ulcer Prophylaxis. Soc of Crit Care Med. 2012 conference.
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Community-Acquired PneumoniaRecent PPI Initiation & Increased Risk
PPI Initiation & CAP Risk
OR (95% CI)
Ann Intern Med 2008 2.45 (2.04 – 2.95)
Arch Intern Med 2007 2.30 (1.22 – 4.35)
JAMA 2004 2.24 (1.42 – 3.54)
Epidemiol 2009 1.21 (0.9 – 1.63)
Am J Med 2010 1.83 (1.24 – 2.70)
Overall CAP Risk*: 1.92 (1.40 – 2.63)
JAMA. 2004;292(16):1955-1960. doi:10.1001/jama.292.16.1955
Eurich D, et al. Am J Med 2010:123
Arch Intern Med. 2007;167(9):950-955. doi:10.1001/archinte.167.9.950
Ann Intern Med. 2008;149(6):391-398.
Naylor DF. Clinical Applications of Stress Ulcer Prophylaxis. Soc of Crit Care Med. 2012 conference.
* Dose response relationship also noted with high dose PPI use
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Long-Term PI Use and Hip Fractures- Nested case-control study of patients aged > 50 years- 13,556 patients with hip fracture and 135,386 controls
� Association stronger in men than women� Possible mechanisms
� Calcium malabsorption secondary to acid suppression� Reduction in bone resorption through inhibition of osteoclasticvacuolar proton pumps
� Did not include information on OTC calcium and vitamin D use
Yang y-X, et al. JAMA. 2006;296:2947-53Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Exposure Group Adjusted Odds Ratio
for Hip Fracture
95% CI
> 1 year of PPI therapy
1.44 1.30 – 1.59
Long-term high-dose PPI therapy
2.65 1.80 – 3.90
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Stress
Impaired Proton Removal
Reperfusion Injury
Free Radical Formation &
Inflammation
Acid Injury
Impaired Proton Buffering
Pepsinogen Activation
Mucosal Ischemia
Impaired Blood Flow
Impaired Defense Mechanism
Acute Stress Ulcer
Mutlu GM, Mutlu EA, Factor P. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222-1241.
GI BleedMacLaren R. A Review of StressUlcer Prophylaxis. J Pharm Prac. 2002;15:147 -157
Idaho Society of Health System Pharmacists2014 Spring Conference
Stress
Impaired Proton Removal
Reperfusion Injury
Free Radical Formation &
Inflammation
Acid Injury
Impaired Proton Buffering
Pepsinogen Activation
Mucosal Ischemia
Impaired Blood Flow
Impaired Defense Mechanism
Acute Stress Ulcer
Mutlu GM, Mutlu EA, Factor P. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222-1241.
GI BleedMacLaren R. A Review of StressUlcer Prophylaxis. J Pharm Prac. 2002;15:147 -157
PPI’s& H2RA’s
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Stress
Impaired Proton Removal
Reperfusion Injury
Free Radical Formation &
Inflammation
Acid Injury
Impaired Proton Buffering
Pepsinogen Activation
Mucosal Ischemia
Impaired Blood Flow
Impaired Defense Mechanism
Acute Stress Ulcer
Mutlu GM, Mutlu EA, Factor P. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222-1241.
GI BleedMacLaren R. A Review of StressUlcer Prophylaxis. J Pharm Prac. 2002;15:147 -157
PPI’s
H2RA’s H2RA’s
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Does Enteral Nutrition Help?� Benefits in critically ill
� Improves splanchnic blood flow
� Reduces macroscopic ulceration
�Does it reduce the risk of developing SRMD?
� Lack of significant evidence
� Bottom line
� Don’t use Enteral nutrition as sole SRMD prophylaxis measure
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H2RA vs PPI - Clinically Important GI Bleeding- Meta-Analysis
AlhazzaniW. et al. Proton Pump Inhibitors Versus Histamine 2 Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Systematic review and Meta-Analysis. Crit Care Med.2013;41(3):693-705.
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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H2RA vs PPI - Clinically Important GI Bleeding- Bias Risk
AlhazzaniW. et al. Proton Pump Inhibitors Versus Histamine 2 Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Systematic review and Meta-Analysis. Crit Care Med.2013;41(3):693-705.
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference
H2RA vs PPI - Comparison of H2RA’s: Up-close
AlhazzaniW. et al. Proton Pump Inhibitors Versus Histamine 2 Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Systematic review and Meta-Analysis. Crit Care Med.2013;41(3):693-705.
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Trial N PPI H2RAUpper GI Bleeding
Cases
PPI H2RA
Conrad (2005) 350Omeprazole/Bicarb
NGTCimetidine IV 7 10
Kantorova (2004) 143 Omeprazole IV Famotidine IV 1 2
Solouki (2009) 129 Omeprazole NGTRanitidine IV 50
mg BID3 14
Levy (1997) 32OmeprazolePO/NGT
Ranitidine IV 2 11
Somberg (2008) 200 Pantoprazole IV Cimetidine IV 0 0
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Is Stress Ulcer Prophylaxis Needed?(Prophylaxis is recommended for ICU patients with one or more risk factors)
No Risk Factors Present
Continue daily assessment for stress ulcer risk factors
Discontinue when risk factors are no longer present. If patient was on pre-existing H2RA or PPI, evaluate indications for continued treatement.
AntisecretoryIV H2RA (first line)
PPI (if H2RA not tolerated)
GastroprotectiveSucralfate
(only via gastric access)Can be used when H2RAs
or PPIs are contraindicated or not
tolerated
Functional GI tract?
Consider oral therapy
IV therapy
YES NO
NO
NO
YES
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
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When Do We Stop?
� Patients should be reassessed daily
�Once the indication is removed the med should be discontinued
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652 ICU Admissions
248 patients initiated on Stress Ulcer Prophylaxis in
ICU
215/248 (84%) transferred from ICU on SUP
24% Discharged from hospital on SUP without appropriate indication
523 ICU Admissions
357 patients received SUP in
ICU
316/357 (89%) were transferred out of ICU on SUP
24% Discharged from hospital on SUP with no indication
Transitions of Care
Wohlt et al. Ann of Pharmacotherapy. 2007;41:1611-1616.
Murphy et al. Pharmacotherapy. 2008;28:968-766.
Idaho Society of Health System Pharmacists2014 Spring Conference
What can we do?
� Start with education
� Hatch et al. 2010
� Looked at educational intervention to reduce non-indicated prescribing of gastric acid suppressants for SUP
Hatch JB, et al. Ann of Pharmacotherapy. 2010;44:1565-71.
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Pharmacist Intervention
1. Dosing card with indications
2. Pharmacist interaction during multidisciplinary rounds
3. Medication reconciliation by RPh at discharge
Hatch JB, et al. Ann of Pharmacotherapy. 2010;44:1565-71.
Idaho Society of Health System Pharmacists2014 Spring Conference
Results356 patients included in study
158 (44%) were using acid-
suppressing meds prior to admission
Compared to 25.6% in Wohlt’s
study
308 received SUP while in
ICU
11% had no identifiable indication
259 continued upon transfer out of the ICU
84 (24%) had no clear indication
Improvement of 50.7% from previous study
After discharge
197 continued acid-suppression
therapy
31 (8.7%) not having a clear indication
64.3% reduction
Hatch JB, et al. Ann of Pharmacotherapy. 2010;44:1565-71.
Wohlt et al. Ann of Pharmacotherapy. 2007;41:1611-1616.
Idaho Society of Health System Pharmacists2014 Spring Conference
Pharmacy Protocol
� Worked with the intensivists to create a Stress Ulcer Prophylaxis per Pharmacy Protocol
� When ‘SUP Per Pharmacy’ ordered the pharmacist would
� Identify risk factors
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Applying this to your practiceH2RA’s are the preferred agent for initial prevention of GI hemorrhage resulting from Stress Related Mucosal Disease in patients that are at risk
PPI’s should be reserved for patients unable to tolerate H2RA’s
Antacids are not recommended for prevention of SRMD
Sucralfatemay be used for SUP when H2RA’s and PPI’s cannot be used
The need for SUP should be evaluated daily, and pharmacotherapy should be discontinued when the patient no longer has risk factors for SRMD
Naylor DF, Rebuck JA, Maclaren R, et al. Clinical Applications of Stress Ulcer Prophylaxis. 2012. SCCM Annual Conference.
Cohen H. Stop Stressing Out: The new stress ulcer prophylaxis guidelines are finally here. 2013 ASHP Clinical Midyear Meeting. Orlando, FL
Idaho Society of Health System Pharmacists2014 Spring Conference