Table 1 Characteristics of the included studies

Reusser et al., 1990 [11]

40

57/97 (59 %)

Single center/Switzerland

26

TBI, ICH

No

Severe acute traumatic or spontaneous hemorrhage intracranial lesion and neurosurgery and MV >48 h

Age <15 yr, GI surgery, PUD, SUP, UGI bleeding

Ranitidine 50 mg IV every 8/6 h titrated to maintain gastric pH ≥4

No prophylaxis

Overt UGI bleeding, mortality

Bright red bleeding via NG tube, melena, or decrease of blood hemoglobin level >2 g/dl within 24 h associated with a positive stool guaiac test or with gastric drainage of >100 ml of coffee-ground material

Burgess et al., 1995 [12]

34

0 (0 %)

Single center/United States

9

TBI

No

Severe head injury and GCS ≤10

PUD, GI injury, SUP, oral intake

Ranitidine 6.25 mg/h continuous IV for up to 72 h

Placebo

Overt UGI bleeding, mortality

Hematemesis, hematochezia, bright red blood per NG tube or coffee-ground NG tube aspirates, and a 5 % decrease from baseline in hematocrit occurring at least 8 h after study drug initiation

Chan et al., 1995 [22]

101

0 (0 %)

Single center/China

17

CVD, brain tumor, CNS infection, hydrocephalus

Yes

Nontraumatic cerebral disease and at least two risk factors for UGI bleeding^b

UGI bleeding; chronic GI disease; PUD; concurrent heart, lung, kidney, hematological, and liver diseases

Ranitidine 50 mg IV every 6 h or 150 mg PO every 12 h when starting EN

Placebo

Clinically important UGI bleeding, nosocomial pneumonia

Gastroduodenal bleeding requiring blood transfusions and/or surgery for acute perforated ulcers, lesions confirmed either endoscopically or during abdominal surgery

Halloran et al., 1980 [13]

50

0 (0 %)

Single center/United States

20

TBI

Yes

Severe head injury and neurological deficits

Apnea and fixed dilated pupils and no motor response, PUD, pregnancy, GI injury, severe hepatic or renal disease

Cimetidine 300 mg IV every 4 h for up to 3 wk

Placebo

Overt UGI bleeding, mortality

Bright red blood or a 4+ positive stool guaiac test in the gastric aspirate for three consecutive 8-h periods (exclusive of first day after injury), excluding oropharyngeal source of bleeding

Liu et al., 2013 [16]

165

19/184 (10 %)

Single center/China

32

ICH

No

CT-proven ICH within 72 h of ictus and neurosurgery, NG tube in place, baseline gastric pH <4, negative GOBT, age >18 yr

AVM, PUD, facial trauma, anticoagulants, AKI, thrombocytopenia, died within 72 h after ictus

Omeprazole 40 mg IV every 12 h for up to 7 days, cimetidine 300 mg IV every 6 h for up to 7 days

Placebo

Overt UGI bleeding, mortality, nosocomial pneumonia

Hematemesis, aspiration of coffee-ground material from NG tube, or melena, proven by positive GOBT or FOBT, with or without hemodynamic instability resulting from gross bleeding that needed transfusion

Metz et al., 1993 [14]

167

0 (0 %)

Multicenter/United States

20

TBI

No

Severe head injury with 24 h of injury and GCS ≤10, NG tube in place, age >18 yr, expected ICU stay ≥72 h

GI bleeding, severe burns >20 %, AKI, PUD, thrombocytopenia, SUP

Ranitidine 6.25 mg/h continuous IV for up to 5 days

Placebo

Overt UGI bleeding, nosocomial pneumonia

• Gastroccult positive NG tube drainage and coffee-ground material for the previous 8 h

• Minimum of 50 ml bright red blood per NG tube

• Hematemesis in the last 8 h

• Hemoccult positive stool

• Melena

• Hematochezia;

with or without endoscopic or surgical confirmation of UGI source of bleeding

Misra et al., 2005 [15]

141

35/176 (20 %)

Single center/India

24

ICH

Yes

CT-proven ICH within 7 days of ictus

AVM, coagulopathy, hepatic or renal disease, PUD, anticoagulants

Ranitidine 50 mg IV every 8 h

Placebo

Overt UGI bleeding, mortality, nosocomial pneumonia

Gross blood, coffee-ground aspirate from NG tube, hematemesis or melena

Zhang et al., 2014 [28]

180

0 (0 %)

Single center/China

NA

ICH

Yes

CT-proven ICH within 72 h of ictus, age 30–75 yr

Traumatic or brain tumor-related hemorrhage, coagulopathy, PUD, mental disorder or dementia, concurrently included in other clinical trials

Esomeprazole 40 mg/day (n = 36) or lansoprazole 40 mg/day (n = 36) PO, ranitidine 150 mg/day (n = 36) or famotidine 40 mg/day (n = 36) PO

Placebo

Overt UGI bleeding

Clinical evidence of GI bleeding reported, but definition not specified (endoscopy used in all patients at approximately day 21 since SUP)