High-risk patients — Based upon randomized trials that demonstrate reduced bleeding rates, we and other guideline groups agree that SUP should be administered to critically ill patients who are assessed as high risk for gastrointestinal (GI) bleeding [33]. Although it is unclear what constitutes "high risk", we and others believe this includes patients with any one of the following characteristics:
●Bleeding diathesis / Coagulopathy (platelet count <50,000, international normalized ratio [INR] >1.5, or a partial thromboplastin time [PTT] >2 times the control value)
●Mechanical ventilation for >48 hours especially those who are not being enterally fed
●Chronic liver disease
●History of GI ulceration or GI bleeding within the past year
●Traumatic brain injury, traumatic spinal cord injury, or burn injury
Minor Criteria
●Two or more of the following minor criteria: sepsis, an ICU stay more than one week, occult GI bleeding for six or more days, or glucocorticoid therapy (more than 250 mg hydrocortisone or the equivalent)
●On nonsteroidal antiinflammatory or antiplatelet agents
Indications for SUP
1+
- Coagulopathy
- Pltlts < 50,000
- INR > 1.5
- PTT > 2x normal
- Mechanical ventilation > 48hr
- GI bleeding or ulceration in last 12 months
- Head trauma, spinal cord injury, major burn
- Glucocorticoid therapy
- >1 week ICU stay
- occult GI bleeding > 6 days
- sepsis
Proton Pump Inhibitors
Differences between omeprazole and pantoprazole
proton pump inhibitors interact with plavix
pantoprazole or lansoprazole
PPIs can cause AIN, hypomagnesemia,
osteoporosis and osteopenia
c diff
Doses
BID bleeding
Teaching Points for Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation (REVISE Trial)
1. What was the primary clinical question in the REVISE trial?
- Question: In critically ill, mechanically ventilated adults, does stress ulcer prophylaxis with IV pantoprazole (40 mg daily) compared to placebo reduce the risk of clinically important upper GI bleeding over 90 days?
- Answer: Yes, IV pantoprazole significantly reduced the incidence of clinically important upper GI bleeding in the ICU compared to placebo.
2. Why is stress ulcer prophylaxis relevant in critically ill patients?
- Question: Why is there concern about GI stress ulcers and prophylaxis in critically ill patients?
- Answer: Critical illness increases the risk of GI stress ulceration and upper GI bleeding. PPIs can reduce bleeding risk, although prior trials (SUP-ICU, PEPTIC) raised concerns about PPIs potentially increasing mortality and infection risk.
3. What were the design and key characteristics of the REVISE trial?
- Question: How was the REVISE trial designed?
- Answer: REVISE was a multi-center, double-blind, randomized controlled trial comparing IV pantoprazole to placebo in mechanically ventilated ICU patients. It enrolled 4900 patients with a 1:1 randomization to either pantoprazole or placebo, stratified by center and prior acid suppression.
4. Who was eligible to participate in the REVISE trial?
- Question: What were the inclusion and exclusion criteria for the REVISE trial?
- Answer: Eligible patients were adults in the ICU on mechanical ventilation expected to continue past the day after randomization. Exclusions included those on acid suppression for active or high-risk GI bleeding, recent anti-platelet/anticoagulation therapy, or contraindications to pantoprazole.
5. What were the main outcomes measured in the REVISE trial?
- Question: What was the primary outcome, and how was "clinically important GI bleeding" defined?
- Answer: The primary outcome was clinically important upper GI bleeding, defined as overt GI bleeding with significant hemodynamic change, a >20 g/L drop in hemoglobin, need for transfusion, or therapeutic intervention within 24 hours.
6. What was the result for the primary outcome?
- Question: Did pantoprazole reduce the risk of clinically important upper GI bleeding compared to placebo?
- Answer: Yes, pantoprazole significantly reduced clinically important upper GI bleeding (1% in the pantoprazole group vs. 3.5% in placebo). The number needed to treat (NNT) was 40.
7. Was there any effect on mortality?
- Question: Did pantoprazole impact all-cause mortality at 90 days?
- Answer: No, there was no significant difference in 90-day mortality between the pantoprazole (29.1%) and placebo (30.9%) groups.
8. What were the findings for secondary outcomes?
- Question: Were there any differences in secondary outcomes between pantoprazole and placebo?
- Answer: Pantoprazole reduced patient-important upper GI bleeding but showed no significant difference in ventilator-associated pneumonia, C. difficile infection, new renal-replacement therapy, ICU or hospital mortality, or ICU/hospital stay duration.
9. Did any subgroups show different responses to pantoprazole?
- Question: Was there any subgroup with different responses to stress ulcer prophylaxis?
- Answer: No significant effect modification was seen in subgroups (e.g., pre-hospital acid suppression, APACHE II score, type of ICU admission, COVID-19 status, or gender).
10. What are the main strengths and limitations of the REVISE trial?
- Question: What were the key strengths and limitations of this trial?
- Answer: Strengths: Large, multi-center RCT with blinding, minimal follow-up loss, and robust protocol adherence. Limitations: Did not address PPI use in non-ventilated patients, potential influence of concurrent corticosteroid use, and unknown screening exclusions.
11. How should stress ulcer prophylaxis be applied in clinical practice based on REVISE findings?
- Question: What is the practical takeaway from REVISE for prescribing pantoprazole in ventilated patients?
- Answer: Pantoprazole reduces the risk of clinically important GI bleeding in mechanically ventilated ICU patients without increasing mortality or infections. It can be prescribed for stress ulcer prophylaxis in these patients, even when enterally fed, unless contraindicated.
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