Table 1 Characteristics of trials included
Author | Population | Interventions | Definition of GI bleeding | Definition of pneumonia | Funding |
|---|---|---|---|---|---|
Conrad [35] USA (n = 359) | MV patients with risk factors Age (mean) 55.6 years Male 59 % APACHE II (mean) 23.7 | Omeprazole 40 mg IV twice daily loading, then 40 mg daily (n = 178) Cimetidine 300 mg IV bolus, then infusion at 50 mg/h (n = 181) | (1) Bright red blood not clearing after tube adjustment and lavage (2) 8 h of persistent coffee grounds material with aspirates every 2 h not clearing with lavage or (3) Persistent coffee grounds material over 2–4 h on day 3–14 in 3 consecutive aspirates not clearing with lavage | USFDA | Pharmaceutical |
Azevedo [36] Brazil (n = 108) | Critically ill patients with risk factors Age (mean) 56.7 years Male 52 % APAHE (mean) 55.3 | Omeprazole 40 mg IV twice daily (n = 38) Ranitidine 150 mg/day IV (n = 38) Sucralfate 1 g PO four times daily (n = 32) | Overt bleeding | CDC criteria | NR |
Hata [37] Japan (n = 210) | Cardiac surgery patients Age (mean) 64.5 years Male 73 % APACHE II NR | Rabeprazole 10 mg PO daily (n = 70) Ranitidine 300 mg PO daily (n = 70) Teprenone 150 mg NG daily (n = 70) | Overt bleeding with endoscopic lesions | NA | NR |
Kantorova [38] Czech Republic (n = 287) | Surgical ICU with risk factors Age (mean) 47 years Male 67 % APACHE II (mean) 18.4 | Omeprazole 40 mg IV daily (n = 72) Famotidine 40 mg IV twice daily (n = 71) Sucralfate 1 g PO four times daily (n = 69) Placebo (n = 75) | Overt bleeding with one of the following: (1) Drop in SBP >20 mmHg or rise in HR >20 beats/min within 24 h not explained by other causes or (2) Drop in hemoglobin >2 g/dL not explained by other causes | New or progressive infiltrate and 3 of the following: (1) Purulent ETT aspirate with >25 WBC/LPF (2) Peripheral leukocytosis >11 × 109/or >10 % bands (3) Temperature >38.5 °C (4) Pathogen from aspirate, BAL (≥104 CFU/mL) or protected brush sampling (≥103 CFU/mL) (5) Positive blood or pleural cultures | Pharmaceutical |
Kotlyanskaya [31] Abstract USA (n = 66) | MV patients. Age 71.2 years Male NR APACHE II 27.6 | Lansoprazole (suspension) NG (n = 22) Lansoprazole (tablet) NG (n = 23) Ranitidine (n = 21) (dose and frequency not reported) | Overt bleeding associated with hemodynamic changes or Hb drop | NR | NR |
Levy [39] USA (n = 67) | Medical and surgical ICU patients with risk factors. Age 57.1 years Male 55 % APACHE II 18.9 | Omeprazole 40 mg NG daily (n = 32) Ranitidine 50 mg IV bolus, then 150 mg IV daily (n = 35) | Overt bleeding with hemodynamic instability, or a decrease Hb >2 g/dL requiring transfusion or associated with hemodynamic instability | NR | NR |
Pan [40] China (n = 30) | Severe pancreatitis Age 48 years Male 45 % APACHE II 12.2 | Rabeprazole 20 mg PO daily (n = 20) Famotidine 40 mg IV twice daily (n = 10) | Overt bleeding | NA | NR |
Phillips [32] Abstract USA (n = 58) | MV patients with risk factors Age NR Male NR APACHE II NR | Omeprazole 40 mg PO, then 20 mg PO daily (n = 33) Ranitidine 50 mg IV loading, then 150–200 mg/day infusion (n = 25) | No clear definition | NR | NR |
Powell [41] UK (n = 41) | Cardiac surgery Age 56.5 years Male 86 % APACHE II NR | Omeprazole 80 mg IV bolus, then 40 mg IV bolus three times daily (n = 10) Omeprazole 80 mg IV bolus then 40 mg IV infusion three times daily (n = 10) Ranitidine 50 mg IV three times daily (n = 11) Placebo (n = 10) | Overt bleeding | NA | Academic |
Risaliti [42] Italy (n = 28) | Surgical ICU Age 61.5 years Male 64 % APACHE II NR | Omeprazole 40 mg IV daily, then 20 mg PO daily (n = 14) Ranitidine 150 mg IV daily, then 300 mg PO daily (n = 14) | No clear definition | NA | NR |
Solouki [43] Iran (n = 129) | MV patients with other risk factors. Age 50.8 years Male 52 % APACHE II NR | Omeprazole 20 mg PO twice daily (n = 61) Ranitidine 50 mg IV twice daily (n = 68) | Overt bleeding associated with one of the following: (1) 20 mmHg decrease in SBP or DBP within 24 h or 20 beat/min increase in HR or postural drop by 10 mmHg in SBP (2) 2 g/dL decrease in Hb or 6 % decrease in Hct within 24 h (3) Lack of increase in Hb after two units of packed cells | New infiltrate and two of the following: (1) Fever ≥38.3 °C (2) WBC >10 × 109/L (3) Pus in ETT aspirate | NR |
Somberg [34] USA (n = 202) | Medical and surgical ICU patients with risk factors Age 42 years Male 74 % APACHE II 15.2 | Pantoprazole 40 mg IV daily (n = 32) Pantoprazole 40 mg IV twice daily (n = 38) Pantoprazole 80 mg IV daily (n = 23) Pantoprazole 80 mg IV twice daily (n = 39) Pantoprazole 80 mg IV three times daily (n = 35) Cimetidine 300 mg IV bolus, then 50 mg/h infusion (n = 35) | (1) Hematemesis or bright red blood in gastric aspirate that did not clear after tube adjustment and 10-min lavage (2) Persistent coffee ground material for 8 h that did not clear with lavage, or accompanied by 5 % decrease in Hct (3) Decrease in Hct requiring ≥1 transfusions in the absence of obvious source or (4) Melena or hematochizia | Radiological changes | Pharmaceutical |
Fink [33] Abstract USA (n = 189) | Adult critically ill patients Age NR Male NR APACHE II 15 | Pantoprazole 40 mg IV daily, 40 mg IV twice daily, 80 mg IV daily, or 80 mg IV twice daily (n = 158); Cimetidine IV 300 mg bolus, then 50 mg/h infusion (n = 31) | No clear definition | NA | NR |
Bashar [21] Iran (n = 120) | MV trauma patients, APACHE II < 25 Age 40.15 Male 7 % APACHE II 15.2 | Pantoprazole 40 mg IV daily then 40 mg PO daily when enteral feeds started (n = 60) Ranitidine 50 mg IV three times daily while NPO then 150 mg PO daily when enteral feeds started (n = 60) | No clear definition | Clinical Pulmonary Infection Score (CPIS) | NR |
Lee [23] Taiwan (n = 60) | Neurosurgical ICU Age 57.7 years Male 60 % APACHE II 17.1 | Esomeprazole 40 mg PO daily for 7 days (n = 30) Famotidine 20 mg IV twice daily for 7 days (n = 30) | Overt bleeding, or decreased hemoglobin level >2 g/dL and lesions on endoscopy | >48 h of ventilation and 3 or more of: (1) Persistent (>48 h) or new infiltrate (2) Positive sputum smear (3) Fever >38.3 °C (4) WBC >12 × 109/L | Academic |
Liu [24] China (n = 165) | Neurosurgical ICU with ICH Age NA Male 65 (58 %) APACHE II NR | Omeprazole 40 mg IV twice daily (n = 58) Cimetidine 300 mg IV four times daily (n = 54) Placebo (n = 53) | Overt bleeding that requires transfusion, with or without hemodynamic instability | NR | Academic |
Fogas [22] Abstract Hungary (n = 79) | MV patients Age 69.5 Male 61 % APACHE II 27 | PPI (n = 38) H2RA (n = 41) No molecule, route, dose or frequency described | No clear definition | Leukocytosis, elevated procalcitonin, fever, purulent ETT secretion, positive ETT microbiology, new/increased infiltrate | NR |
Wee [20] Abstract USA (n =129) | Critically ill patients with risk factors Age median 72 Male NR APACHE II 22 | Pantoprazole 40 mg IV daily (n = 68) Famotidine 20 mg IV twice daily (n = 61) | Overt bleeding with any of the following: (1) Decrease in SBP by >20 mmHg (2) Decrease in MAP to <65 mmHg 3. Decrease in Hb >2 g/dL and need for >1 unit of blood | NA | NR |
Bhanot [38] Abstract India (n = 150) | Mechanically ventilated, critically ill. | Omeprazole 40 mg PO daily (n = 50) Ranitidine 50 mg IV four times daily (n = 50) Sucralfate 1 gm PO four times daily (n = 50) | NR | NR | NR |