Table 1 The conventional meta-analysis and trial sequential analysis using random-effects and fixed-effects for all outcomes

  All trials (11 trials)

0.58 (0.42–0.81)

0.001

0.56 (0.41–0.76)

< 0.001

0%

0.23–1.51

0.22–1.39

0%

4.6%

22,114

  Low risk of bias (4 trials)

0.64 (0.45–0.92)

0.017

0.64 (0.45–0.92)

0.016

0%

0.15–2.80

0.15–2.77

0%

4.1%

24,928

  High risk of bias (7 trials)

0.38 (0.17–0.84)

0.017

0.35 (0.18–0.67)

0.002

11.8%

0.01–9.93

0.03–4.93

19%

6.7%

13,827

  Received PPI (6 trials)

0.61 (0.43–0.88)

0.008

0.61 (0.43–0.88)

0.008

0%

0.14–2.70

0.14–2.68

0%

3.8%

26,970

  Received H2RA (6 trials)

0.45 (0.17–1.22)

0.116

0.42 (0.23–0.78)

0.006

42.6%

–

–

50%

10.4%

–

  Received EN (8 trials)

0.61 (0.44–0.85)

0.004

0.61 (0.44–0.84)

0.003

0%

0.16–2.38

0.16–2.33

0%

4.2%

24,310

  Did not receive EN (3 trials)

0.27 (0.04–2.09)

0.211

0.27 (0.10–0.73)

0.010

62.3%

–

–

65%

13.0%

–

  All trials (27 trials)

0.48 (0.36–0.63)

< 0.001

0.50 (0.42–0.59)

< 0.001

34.6%

0.31–0.75

0.38–0.65

62%

12.1%

15,468

  Low risk of bias (4 trials)

0.62 (0.48–0.79)

< 0.001

0.62 (0.49–0.79)

< 0.001

0%

0.37–1.04

0.37–1.04

0%

8.6%

11,384

  High risk of bias (23 trials)

0.42 (0.30–0.60)

< 0.001

0.40 (0.32–0.51)

< 0.001

37.4%

0.25–0.72

0.28–0.57

52%

18.1%

7595

  Received PPI (8 trials)

0.57 (0.45–0.71)

< 0.001

0.57 (0.45–0.71)

< 0.001

0%

0.36–0.88

0.36–0.88

0%

8.9%

10,969

  Received H2RA (22 trials)

0.45 (0.30–0.67)

< 0.001

0.43 (0.33–0.54)

< 0.001

45.7%

0.26–0.79

0.30–0.60

59%

19.3%

8258

  Received EN (13 trials)

0.64 (0.42–0.96)

0.029

0.60 (0.48–0.74)

< 0.001

25.7%

0.12–3.35

0.25–1.42

71%

9.2%

27,681

  Did not receive EN (14 trials)

0.37 (0.25–0.55)

< 0.001

0.36 (0.27–0.48)

< 0.001

38.4%

0.22–0.63

0.25–0.52

52%

21.9%

6029

  All trials (24 trials)

1.01 (0.93–1.09)

0.842

1.02 (0.93–1.11)

0.692

0%

0.90–1.13

0.91–1.14

0%

26.8%

3230

  Low risk of bias (4 trials)

1.01 (0.92–1.12)

0.813

1.01 (0.91–1.12)

0.858

0%

0.67–1.52

0.67–1.52

0%

29.8%

2801

  High risk of bias (20 trials)

1.00 (0.87–1.16)

0.994

1.04 (0.89–1.22)

0.643

0%

0.80–1.24

0.82–1.32

0%

21.1%

4380

  Received PPI (9 trials)

1.02 (0.93–1.13)

0.647

1.02 (0.93–1.13)

0.619

0%

0.82–1.28

0.82–1.28

0%

28.5%

2976

  Received H2RA (18 trials)

0.97 (0.83–1.14)

0.711

0.99 (0.83–1.18)

0.921

0%

0.74–1.28

0.73–1.35

0%

22.3%

4089

Received EN (12 trials)

1.05 (0.96–1.16)

0.264

1.05 (0.96–1.16)

0.254

0%

0.88–1.27

0.88–1.27

0%

28%

3048

  Did not receive EN (12 trials)

0.85 (0.71–1.02)

0.077

0.82 (0.66–1.02)

0.075

0%

0.63–1.15

0.58–1.17

0%

21.7%

4230

  All trials (12 trials)

1.09 (0.95–1.24)

0.221

1.07 (0.94–1.22)

0.321

0%

0.90–1.31

0.89–1.29

0%

14.8%

6681

  Low risk of bias (3 trials)

1.00 (0.86–1.17)

0.959

1.00 (0.86–1.17)

0.954

0%

0.79–1.27

0.79–1.27

0%

16.3%

5972

  High risk of bias (9 trials)

1.47 (1.10–1.97)

0.010

1.40 (1.03–1.89)

0.032

0%

0.44–4.87

0.40–4.83

0%

9.9%

10,496

  Received PPI (6 trials)

1.03 (0.89–1.20)

0.668

1.04 (0.89–1.20)

0.642

0%

0.82–1.29

0.83–1.30

0%

15.2%

6478

  Received H2RA (8 trials)

1.39 (1.01–1.91)

0.046

1.29 (0.93–1.80)

0.130

0%

0.37–5.13

0.33–5.03

0%

12.3%

8246

  Received EN (8 trials)

1.09 (0.95–1.25)

0.236

1.07 (0.93–1.24)

0.312

0%

0.88–1.34

0.87–1.32

0%

15.1%

6528

  Did not receive EN (4 trials)

1.08 (0.65–1.80)

0.757

1.02 (0.63–1.67)

0.935

0%

0.14–8.58

0.14–7.53

0%

11.8%

8640

All trials (4 trials)

0.78 (0.45–1.35)

0.377

0.78 (0.46–1.34)

0.370

0%

0.08–7.32

0.09–7.01

0%

1.6%

70,261

Low risk of bias (3 trials)

0.75 (0.43–1.31)

0.309

0.74 (0.43–1.29)

0.290

0%

0.08–7.26

0.08–7.01

0%

1.7%

66,068

High risk of bias (1 trial)

3.06 (0.13–74.19)

0.492

3.06 (0.1–74.19)

0.492

–

–

–

0%

–

Received PPI (4 trials)

0.78 (0.45–1.35)

0.377

0.78 (0.46–1.34)

0.370

0%

0.08–7.32

0.09–7.01

0%

1.6%

70,261

Received EN (4 trials)

0.78 (0.45–1.35)

0.377

0.78 (0.46–1.34)

0.370

0%

0.08–7.32

0.09–7.01

%

1.6%

70,261

  All trials (11 trials)

−0.23 (−1.19–0.73)

0.635

−0.13 (−0.90–0.65)

0.751

18.4%

  Low risk of bias (3 trials)

0.11 (−3.20–3.43)

0.947

−0.42 (−2.02–1.18)

0.607

54.3%

  High risk of bias (8 trials)

−0.16 (−1.18–0.86)

0.757

−0.03 (− 0.92–0.85)

0.938

10.5%

  Received PPI (5 trials)

− 0.54 (− 1.66–0.59)

0.349

− 0.57 (− 1.63–0.49)

0.294

7.0%

  Received H2RA (7 trials)

−0.20 (−1.94–1.54)

0.820

0.38 (−0.76–1.52)

0.510

22.6%

  Received EN (7 trials)

−0.00 (−1.15–1.15)

0.998

0.05 (−0.79–0.88)

0.915

30.5%

  Did not receive EN (4 trials)

−1.18 (−3.26–0.90)

0.266

−1.18 (− 3.26–0.90)

0.266

0%

  All trials (7 trials)

−0.41 (−1.42–0.61)

0.434

−0.41 (−1.42–0.61)

0.434

0%

  Low risk of bias (3 trials)

−0.01 (−2.56–2.53)

0.991

−0.52 (−1.80–0.76)

0.423

46.6%

  High risk of bias (4 trials)

−0.21 (−1.87–1.46)

0.809

−0.21 (−1.87–1.46)

0.809

0%

  Received PPI (4 trials)

−0.04 (−1.63–1.55)

0.965

−0.35 (−1.55–0.85)

0.567

20.8%

  Received H2RA (4 trials)

−0.57 (−2.57–1.43)

0.574

−0.55 (− 2.47–1.37)

0.576

5.6%

  Received EN (6 trials)

−0.25 (−1.43–0.93)

0.676

−0.37(−1.40–0.66)

0.481

11.5%

  Did not receive EN (1 trial)

−2.00 (−8.83–4.83)

0.566

−2.00 (−8.83–4.83)

0.566

–