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Table 1 Characteristics of trials included

From: Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials

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
  1. Description of populations, settings, interventions, outcomes and funding sources. APACHE Acute Physiology and Chronic Health Evaluation, MV mechanically ventilated, NR not reported, GI gastrointestinal, IV intravenous, PO oral, hb hemoglobin, USFDA US Food and Drug Agency, SBP systolic blood pressure, HR heart rate, ETT endotracheal tube, WBC white blood cells, BAL, bronchiolar lavage, CFU colony-forming units, DBP diastolic blood pressure, Hct hematocrit, PPI proton pump inhibitor, H2RA histamine-2-receptor antagonist, MAP mean arterial pressure, CDC Center of disease control, NG nasogastric, NA not applicable