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Temas

Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Trial sequential analysis (60‐day mortality) ‐ aprotinin versus control.The blue line indicates the cumulative Z‐curve.Current information size: 280 patients; required information size: 15,302. information fraction: 1.83%.
Figuras y tablas -
Figure 4

Trial sequential analysis (60‐day mortality) ‐ aprotinin versus control.

The blue line indicates the cumulative Z‐curve.

Current information size: 280 patients; required information size: 15,302. information fraction: 1.83%.

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Trial sequential analysis (60‐day mortality) ‐ tranexamic acid versus control.The blue line indicates the cumulative Z‐curve.Current information size: 139 patients; required information size: 18,706. information fraction: 0.74%.
Figuras y tablas -
Figure 5

Trial sequential analysis (60‐day mortality) ‐ tranexamic acid versus control.

The blue line indicates the cumulative Z‐curve.

Current information size: 139 patients; required information size: 18,706. information fraction: 0.74%.

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Trial sequential analysis (60‐day mortality) ‐ recombinant factor VIIa versus control.The blue line indicates the cumulative Z‐curve.Current information size: 286 patients; required information size: 15,302. information fraction: 1.87%.
Figuras y tablas -
Figure 6

Trial sequential analysis (60‐day mortality) ‐ recombinant factor VIIa versus control.

The blue line indicates the cumulative Z‐curve.

Current information size: 286 patients; required information size: 15,302. information fraction: 1.87%.

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Trial sequential analysis (60‐day mortality) ‐ tranexamic acid versus aprotinin.The blue line indicates the cumulative Z‐curve.Current information size: 178 patients; required information size: 15,302. information fraction: 1.16%.
Figuras y tablas -
Figure 7

Trial sequential analysis (60‐day mortality) ‐ tranexamic acid versus aprotinin.

The blue line indicates the cumulative Z‐curve.

Current information size: 178 patients; required information size: 15,302. information fraction: 1.16%.

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Comparison 1 Intervention versus control, Outcome 1 60‐day mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Intervention versus control, Outcome 1 60‐day mortality.

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Comparison 1 Intervention versus control, Outcome 2 Mortality at maximal follow‐up.
Figuras y tablas -
Analysis 1.2

Comparison 1 Intervention versus control, Outcome 2 Mortality at maximal follow‐up.

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Comparison 1 Intervention versus control, Outcome 3 Primary graft non‐function.
Figuras y tablas -
Analysis 1.3

Comparison 1 Intervention versus control, Outcome 3 Primary graft non‐function.

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Comparison 1 Intervention versus control, Outcome 4 Retransplantation.
Figuras y tablas -
Analysis 1.4

Comparison 1 Intervention versus control, Outcome 4 Retransplantation.

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Comparison 1 Intervention versus control, Outcome 5 Thromboembolic episodes.
Figuras y tablas -
Analysis 1.5

Comparison 1 Intervention versus control, Outcome 5 Thromboembolic episodes.

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Comparison 1 Intervention versus control, Outcome 6 Serious adverse events.
Figuras y tablas -
Analysis 1.6

Comparison 1 Intervention versus control, Outcome 6 Serious adverse events.

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Comparison 1 Intervention versus control, Outcome 7 Blood loss.
Figuras y tablas -
Analysis 1.7

Comparison 1 Intervention versus control, Outcome 7 Blood loss.

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Comparison 1 Intervention versus control, Outcome 8 Red‐cell or whole blood transfusion.
Figuras y tablas -
Analysis 1.8

Comparison 1 Intervention versus control, Outcome 8 Red‐cell or whole blood transfusion.

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Comparison 1 Intervention versus control, Outcome 9 Red cell or whole blood transfusion.
Figuras y tablas -
Analysis 1.9

Comparison 1 Intervention versus control, Outcome 9 Red cell or whole blood transfusion.

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Comparison 1 Intervention versus control, Outcome 10 Platelet transfusion.
Figuras y tablas -
Analysis 1.10

Comparison 1 Intervention versus control, Outcome 10 Platelet transfusion.

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Comparison 1 Intervention versus control, Outcome 11 Plasma transfusion.
Figuras y tablas -
Analysis 1.11

Comparison 1 Intervention versus control, Outcome 11 Plasma transfusion.

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Comparison 1 Intervention versus control, Outcome 12 Cryoprecipitate.
Figuras y tablas -
Analysis 1.12

Comparison 1 Intervention versus control, Outcome 12 Cryoprecipitate.

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Comparison 1 Intervention versus control, Outcome 13 Hospital stay.
Figuras y tablas -
Analysis 1.13

Comparison 1 Intervention versus control, Outcome 13 Hospital stay.

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Comparison 1 Intervention versus control, Outcome 14 Intensive therapy unit stay.
Figuras y tablas -
Analysis 1.14

Comparison 1 Intervention versus control, Outcome 14 Intensive therapy unit stay.

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Summary of findings for the main comparison. Intervention versus control for liver transplantation (mortality, primary graft non‐function, and retransplantation)

Intervention versus control for liver transplantation

Patient or population: Patients with liver transplantation.
Settings: Transplantation centre.
Intervention: Intervention versus control.

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Intervention versus control

60‐day mortality ‐ Aprotinin versus control

Study population

RR 0.52
(0.18 to 1.45)

280
(3 studies)

⊕⊝⊝⊝
very low1,2,3

67 per 1000

35 per 1000
(12 to 97)

Moderate

73 per 1000

38 per 1000
(13 to 106)

60‐day mortality ‐ Tranexamic acid versus control

Study population

RR 0.55
(0.17 to 1.76)

139
(3 studies)

⊕⊝⊝⊝
very low1,2,3

89 per 1000

49 per 1000
(15 to 157)

Moderate

100 per 1000

55 per 1000
(17 to 176)

60‐day mortality ‐ Recombinant factor VIIa (rFVIIa) versus control

Study population

RR 1.51
(0.33 to 6.95)

286
(3 studies)

⊕⊝⊝⊝
very low1,2,3

22 per 1000

33 per 1000
(7 to 153)

Moderate

16 per 1000

24 per 1000
(5 to 111)

60‐day mortality ‐ Tranexamic acid versus aprotinin

Study population

RR 4.12
(0.71 to 23.76)

178
(2 studies)

⊕⊝⊝⊝
very low1,2,3

11 per 1000

47 per 1000
(8 to 273)

Moderate

8 per 1000

33 per 1000
(6 to 190)

Primary graft non‐function ‐ Aprotinin versus control

Study population

RR 0.15
(0.02 to 1.25)

217
(2 studies)

⊕⊝⊝⊝
very low1,3,4

45 per 1000

7 per 1000
(1 to 56)

Moderate

45 per 1000

7 per 1000
(1 to 56)

Retransplantation ‐ Aprotinin versus control

Study population

RR 0.21
(0.02 to 1.79)

217
(2 studies)

⊕⊝⊝⊝
very low1,3,4

67 per 1000

14 per 1000
(1 to 121)

Moderate

66 per 1000

14 per 1000
(1 to 118)

Retransplantation ‐ Tranexamic acid versus control

Study population

RR 0.79
(0.18 to 3.48)

77
(2 studies)

⊕⊝⊝⊝
very low1,2,3

83 per 1000

66 per 1000
(15 to 290)

Moderate

75 per 1000

59 per 1000
(14 to 261)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 All trials were at high risk of bias,
2 The confidence intervals overlap 0.75 and 1.25.
3 Funnel plots could not be performed for any of the outcomes.
4 Although the confidence intervals do not overlap 0.75 and 1.25, the confidence intervals were wide.

Figuras y tablas -
Summary of findings for the main comparison. Intervention versus control for liver transplantation (mortality, primary graft non‐function, and retransplantation)
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Summary of findings 2. Intervention versus control for liver transplantation (thromboembolic episodes and other serious adverse events)

Intervention versus control for liver transplantation

Patient or population: Patients with liver transplantation.
Settings: Transplantation centre.
Intervention: Intervention versus control.

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Intervention versus control

Thromboembolic episodes ‐ Aprotinin versus control

Study population

RR 0.6
(0.18 to 1.96)

280
(3 studies)

⊕⊝⊝⊝
very low1,2,3

42 per 1000

25 per 1000
(8 to 82)

Moderate

63 per 1000

38 per 1000
(11 to 123)

Thromboembolic episodes ‐ Tranexamic acid versus control

Study population

RR 2.2
(0.38 to 12.64)

179
(5 studies)

⊕⊝⊝⊝
very low1,2,3

13 per 1000

29 per 1000
(5 to 166)

Thromboembolic episodes ‐ Recombinant factor VIIa (rFVIIa) versus control

Study population

RR 1.38
(0.65 to 2.91)

266
(2 studies)

⊕⊝⊝⊝
very low1,2,3

99 per 1000

136 per 1000
(64 to 287)

Moderate

101 per 1000

139 per 1000
(66 to 294)

Serious adverse events ‐ Recombinant factor VIIa (rFVIIa) versus control

Study population

RR 1.3
(0.94 to 1.78)

266
(2 studies)

⊕⊝⊝⊝
very low1,3,4

370 per 1000

481 per 1000
(348 to 659)

Moderate

406 per 1000

528 per 1000
(382 to 723)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 All trials were at high risk of bias,
2 The confidence intervals overlap 0.75 and 1.25.
3 Funnel plots could not be performed for any of the outcomes.
4 Although the confidence intervals do not overlap 0.75 and 1.25, the confidence intervals were wide.

Figuras y tablas -
Summary of findings 2. Intervention versus control for liver transplantation (thromboembolic episodes and other serious adverse events)
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Summary of findings 3. Intervention versus control for liver transplantation (blood loss)

Intervention versus control for liver transplantation

Patient or population: Patients with liver transplantation.
Settings: Transplantation centre.
Intervention: Intervention versus control.

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Intervention versus control

Blood loss ‐ Aprotinin versus control (litre)

The mean blood loss ‐ aprotinin versus control in the intervention groups was
1.36 lower
(3.39 lower to 0.66 higher)

195
(3 studies)

⊕⊝⊝⊝
very low1,2,3

Blood loss ‐ Tranexamic acid versus control (litre)

The mean blood loss ‐ tranexamic acid versus control in the intervention groups was
4.98 lower
(10.18 lower to 0.23 higher)

65
(2 studies)

⊕⊝⊝⊝
very low1,2,3

Blood loss ‐ Thromboelastography versus control (litre)

The mean blood loss ‐ thromboelastography versus control in the intervention groups was
1.13 lower
(1.85 to 0.41 lower)

62
(2 studies)

⊕⊝⊝⊝
very low1,2,3

Blood loss ‐ Tranexamic acid versus aprotinin

The mean blood loss ‐ tranexamic acid versus aprotinin in the intervention groups was
1.01 lower
(2.31 lower to 0.29 higher)

71
(2 studies)

⊕⊝⊝⊝
very low1,2,3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 All trials were at high risk of bias,
2 Sample size was less than 400 patients in both groups put together,
3 Funnel plots could not be performed for any of the outcomes.

Figuras y tablas -
Summary of findings 3. Intervention versus control for liver transplantation (blood loss)
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Summary of findings 4. Intervention versus control for liver transplantation (red cell or whole blood allogeneic transfusion)

Intervention versus control for liver transplantation

Patient or population: Patients with liver transplantation.
Settings: Transplantation centre.
Intervention: Intervention versus control.

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Intervention versus control

Red cell or whole blood transfusion ‐ Aprotinin versus control

The mean red cell or whole blood transfusion ‐ aprotinin versus control in the intervention groups was
0.61 standard deviations lower
(0.82 to 0.40 lower)

375
(8 studies)

⊕⊝⊝⊝
very low1,2,3

SMD ‐0.61 (‐0.82 to ‐0.40)

Red cell or whole blood transfusion ‐ Tranexamic acid versus control

The mean red cell or whole blood transfusion ‐ tranexamic acid versus control in the intervention groups was
0.27 standard deviations lower
(0.59 lower to 0.06 higher)

159
(4 studies)

⊕⊝⊝⊝
very low1,3,4

SMD ‐0.27 (‐0.59 to 0.06)

Red cell or whole blood transfusion ‐ Recombinant factor VIIa (rFVIIa) versus control

The mean red cell or whole blood transfusion ‐ recombinant factor VIIa (rFVIIa) versus control in the intervention groups was
0.05 standard deviations higher
(0.32 lower to 0.23 higher)

221
(2 studies)

⊕⊝⊝⊝
very low1,3,4

SMD 0.05 (‐0.32 to 0.23)

Red cell or whole blood transfusion ‐ Thromboelastography versus control

The mean red cell or whole blood transfusion ‐ thromboelastography versus control in the intervention groups was
0.73 standard deviations lower
(1.69 lower to 0.24 higher)

62
(2 studies)

⊕⊝⊝⊝
very low1,2,3,4

SMD ‐0.73 (‐1.69 to 0.24)

Red cell or whole blood transfusion ‐ Tranexamic acid versus aprotinin

The mean red cell or whole blood transfusion ‐ tranexamic acid versus aprotinin in the intervention groups was
0.09 standard deviations lower
(0.36 lower to 0.19 higher)

198
(3 studies)

⊕⊝⊝⊝
very low1,3,4

SMD ‐0.09 (‐0.36 to 0.19)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 All trials were at high risk of bias.
2 High heterogeneity.
3 Funnel plots could not be performed for any of the outcomes.
4 Sample size was less than 400 patients in both groups put together.

Figuras y tablas -
Summary of findings 4. Intervention versus control for liver transplantation (red cell or whole blood allogeneic transfusion)
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Table 1. Doses used in the trials

Bolus

Continuous/hour

Additional boluses

Start time

End time

Approximate total including bolus

Aprotinin (million KIU units)

Aprotinin versus control*

Cottam 1991

2

0.5

0.05 per unit transfused

induction

not stated

5

Findlay 2001

1

0.25

None

not stated

end of surgery

2.5

Dalmau 2004 (control: tranexamic acid)

2

0.5

None

Beginning of surgery

2 hours after reperfusion

5

Garcia‐Huete 1997

2

0.5

None

induction

end of surgery

5

Groh 1993

2

0.5

None

induction

end of surgery

5

Hei 2005

None

0.4

None

induction

not stated

2.4

Ickx 1993

None

0.2

None

Beginning of surgery

not stated

1.2

Ickx 1995

2

0.5

None

anhepatic phase

not stated

5

Ickx 2006 (control: tranexamic acid)

2

0.5

None

anhepatic phase

2 hours after reperfusion

3.5

Marcel 1996

None

0.2

None

induction

not stated

1.2

Merle 1997

2

0.5

None

Beginning of surgery

end of surgery

5

Milroy 1995

2

0.5

None

induction

transfer to ITU

5

Porte 2000 (high dose A)

2

1

1 million KIU half an hour before reperfusion

induction

2 hours after reperfusion

8

Porte 2000 (high dose B)

2

0.5

None

induction

2 hours after reperfusion

5.5

Different doses or methods of administration of aprotinin

Himmelreich 1992 (bolus method)

0.5

None

0.5 during anhepatic phase and then at reperfusion

induction

reperfusion

1

Himmelreich 1992 (continuous method)

None

0.2, increased to 0.4 during anhepatic phase and decreased to 0.1 from reperfusion

None

induction

end of surgery

1.2

Lassale 1996 (high dose)

2

0.5

None

induction

end of surgery

5

Lassale 1996 (low dose)

None

0.1

None

induction

end of surgery

0.6

Soilleux 1995 (high dose)

2

0.5

None

induction

transfer to ITU

5

Soilleux 1995 (medium dose)

0.5

0.15

None

induction

transfer to ITU

1.4

Tranexamic acid versus control*

Units: mg/kg/hr

Boylan 1996

None

40

None

induction

reperfusion

240

Dalmau 2000

None

10

None

induction

reperfusion

60

Dalmau 2004 (control: aprotinin)

None

10

None

Beginning of surgery

2 hours after reperfusion

60

Ickx 1995

80

40

None

anhepatic phase

not stated

320

Ickx 2006 (control: aprotinin)

40

40

None

anhepatic phase

2 hours after reperfusion

280

Kaspar 1997

None

2

None

Beginning of surgery

end of surgery

12

Yassen 1993

10

3

None

anhepatic phase

transfer to ITU

28

Epsilon amino caproic acid (EACA) versus control*

Units: mg/kg/hour

Dalmau 2000

None

16

None

induction

reperfusion

96

Antithrombin versus control*

Units: units per hour

Baudo 1992

(100‐plasma activity level) per kg body weight

1000

None

induction 

end of surgery

6000

Recombinant Factor VIIa versus control*

(mcg/kg)

Lodge 2005 (high dose A)

60

None

60 mcg/kg every 2 hours to approximately 30 minutes before reperfusion and a final dose on wound closure

within 10 minutes of skin incision

None

180

Lodge 2005 (high dose B)

120

None

120 mcg/kg every 2 hours to approximately 30 minutes before reperfusion and a final dose on wound closure

within 10 minutes of skin incision

None

360

Planinsic 2005 (low dose A)

20

None

None

within 10 minutes of skin incision (single bolus)

None

20

Planinsic 2005 (low dose B)

40

None

None

within 10 minutes of skin incision (single bolus)

None

40

Planinsic 2005 (low dose C)

80

None

None

within 10 minutes of skin incision (single bolus)

None

80

Pugliese 2007

40

Just before induction

None

Just before induction

None

40

Oestrogen versus control*

Units: mg

Frenette 1998

100

None

100 mg 30 min after reperfusion

Beginning of surgery

None

200

Prostaglandin E versus control*

Units: microgram (mcg)

Himmelreich 1993

None

10 mcg increased to 40 mcg

None

Beginning of surgery

three post‐operative days

2800

Norpeinephrine versus control*

Units: mcg/min

Ponnudurai 2005

None

0.5 mcg/min increased by 1 mcg increments up to a maximum of 6 mcg/min to maintain a systolic blood pressure and pulmonary capillary wedge pressure more than 80% of baseline values.

* Control was placebo or no intervention unless stated.
ITU = intensive therapy unit.

Figuras y tablas -
Table 1. Doses used in the trials
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Table 2. Network analysis results

P value

Effect estimate
Point estimate and 95% confidence intervals (CI)

60‐day mortality

Solvent detergent FFP

0.5483

RR 0; 95% CI 0 to 257517954.02

Aprotinin

0.0489

RR 0.09; 95% CI 0.01 to 0.99

Tranexamic acid

0.0237

RR 0.44; 95% CI 0.22 to 0.88

EACA

0.387

RR 0.45; 95% CI 0.06 to 3.16

Antithrombin III

0.546

RR 0; 95% CI 0 to 225447979.34

rFVIIa

0.4494

RR 0.31; 95% CI 0.01 to 8.19

Mortality at maximal follow‐up

Not performed

Primary graft non‐function

Convergence not obtained

Graft failure

Not performed

Retransplantation

Convergence not obtained

Thromboembolic episodes

rFVIIa

0.0842

RR 2.23; 95% CI 0.88 to 5.69

control

0.2142

RR 0.5; 95% CI 0.16 to 1.6

Aprotinin

0.9371

RR 1.04; 95% CI 0.36 to 2.99

Tranexamic acid

0.8742

RR 0.88; 95% CI 0.14 to 5.46

Serious adverse events

Low CVP

0.1552

RR 0.29; 95% CI 0.03 to 3.13

Aprotinin

0.8512

RR 0.91; 95% CI 0.13 to 6.24

rFVIIa

0.2517

RR 1.54; 95% CI 0.48 to 4.88

Blood loss

Aprotinin

0.4028

MD 0.3 litre; 95% CI ‐ 0.47 to 1.07

Tranexamic acid

0.6075

MD 0.20 litre; 95% CI ‐0.63 to 1.03

Antithrombin III

0.9966

MD 0.03 litre; 95% CI ‐14.17 to 14.22

Thromboelastometry

0.0003

MD ‐1.83 litre; 95% CI ‐2.55 to ‐1.12

Low CVP

0.004

MD ‐1.12 litre; 95% CI ‐1.19 to ‐0.49

Proportion of patients requiring red cell or whole blood transfusion

rFVIIa

0.2765

RR 0.18; 95% CI 0 to 25.84

Aprotinin

0.1301

RR 0.37; 95% CI 0.07 to 2.04

Tranexamic acid

0.0937

RR 0.27; 95% CI 0.04 to 1.72

EACA

0.5714

RR 0.67; 95% CI 0.05 to 8.95

Amount of blood transfused

Convergence not obtained

Platelet transfusion

Aprotinin

0.0633

SMD ‐0.25; 95% CI ‐0.51 to 0.02

Tranexamic acid

0.0129

SMD ‐0.33; 95% CI ‐0.58 to ‐0.08

EACA

0.0231

SMD ‐0.5; 95% CI ‐0.92 to ‐0.08

rFVIIa

0.7865

SMD ‐0.04; 95% CI ‐0.32 to 0.25

Oestrogen

0.438

SMD 0.28; 95% CI ‐0.46 to 1.02

Thromboelastometry

0.1046

SMD 0.62; 95% CI ‐0.14 to 1.38

Norepinephrine

0.1552

SMD 0.36; 95% CI ‐0.15 to 0.87

Solvent detergent FFP

0.3926

SMD 0.34; 95% CI ‐0.48 to 1.17

Fresh frozen plasma

Aprotinin

0.4663

SMD ‐0.12; 95% CI ‐0.46 to 0.22

Tranexamic acid

0.7514

SMD ‐0.06; 95% CI ‐0.47 to 0.35

EACA

0.9742

SMD 0.01; 95% CI ‐0.56 to 0.58

Antithrombin III

0.9217

SMD ‐0.05; 95% CI ‐1.17 to 1.07

rFVIIa

0.9748

SMD 0.01; 95% CI ‐0.64 to 0.66

Oestrogen

0.5834

SMD ‐0.3; 95% CI ‐1.4 to 0.81

Prostaglandin

0.8881

SMD ‐0.08; 95% CI ‐1.31 to 1.14

Thromboelastometry

0.7947

SMD 0.14; 95% CI ‐0.98 to 1.27

Norepinephrine

0.628

SMD ‐0.23; 95% CI ‐1.18 to 0.73

Cryoprecipate

Aprotinin

0.2675

SMD ‐0.32; 95% CI ‐0.94 to 0.3

Tranexamic acid

0.2572

SMD ‐0.35; 95% CI ‐1.01 to 0.31

EACA

0.5333

SMD ‐0.29; 95% CI ‐1.32 to 0.74

Oestrogen

0.3963

SMD 0.36; 95% CI ‐0.56 to 1.27

Thromboelastometry

0.8342

SMD 0.1; 95% CI ‐0.92 to 1.11

Solvent detergent FFP

0.4925

SMD 0.31; 95% CI ‐0.68 to 1.29

Hospital stay

Aprotinin

0.8137

MD 0.59 days; 95% CI ‐5.89 to 7.06

Tranexamic acid

0.1876

MD 6.45 days; 95% CI ‐4.83 to 17.74

rFVIIa

0.5458

MD 3.04 days; 95% CI ‐9.78 to 15.87

Low CVP

0.1629

MD 11.91 days; 95% CI ‐7.46 to 31.28

Norepinephrine

0.3781

MD ‐1.1 days; 95% CI ‐4.19 to 1.99

Intensive therapy unit stay

Aprotinin

0.723

MD ‐0.11 days; 95% CI ‐0.8 to 0.59

Tranexamic acid

0.9696

MD 0.04 days; 95% CI ‐2.35 to 2.43

rFVIIa

0.6915

MD ‐0.21 days; 95% CI ‐1.45 to 1.03

Low CVP

0.6431

MD 0.6 days; 95% CI ‐2.39 to 3.59

Norepinephrine

0.8102

MD 0.19 days; 95% CI ‐1.67 to 2.06

CVP = central venous pressure.
EACA = epsilon amino caproic acid.
FFP = fresh frozen plasma.
rFVIIa = recombinant factor VIIa.

Figuras y tablas -
Table 2. Network analysis results
Ir a la tabla de la revisión
Comparison 1. Intervention versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 60‐day mortality Show forest plot

14

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Aprotinin versus control

3

280

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.18, 1.45]

1.2 Tranexamic acid versus control

3

139

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.17, 1.76]

1.3 Epsilon amino caproic acid (EACA) versus control

1

62

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.13, 3.94]

1.4 Antithrombin III versus control

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.01, 4.65]

1.5 Recombinant factor VIIa (rFVIIa) versus control

3

286

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [0.33, 6.95]

1.6 Aprotinin: bolus versus continuous infusion

1

23

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.7 Solvent detergent plasma versus standard fresh frozen plasma

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.8 Tranexamic acid versus EACA

1

84

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.21, 4.67]

1.9 Tranexamic acid versus aprotinin

2

178

Risk Ratio (M‐H, Fixed, 95% CI)

4.12 [0.71, 23.76]

2 Mortality at maximal follow‐up Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Antithrombin III versus control

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.03, 1.85]

2.2 Thromboelastography versus control

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.13, 3.40]

3 Primary graft non‐function Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Aprotinin versus control

2

217

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.02, 1.25]

3.2 Tranexamic acid versus control

1

32

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 68.57]

3.3 Recombinant factor VIIa (rFVIIa) versus control

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Retransplantation Show forest plot

7

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Aprotinin versus control

2

217

Risk Ratio (M‐H, Random, 95% CI)

0.21 [0.02, 1.79]

4.2 Tranexamic acid versus control

2

77

Risk Ratio (M‐H, Random, 95% CI)

0.79 [0.18, 3.48]

4.3 Prostaglandin versus control

1

20

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.4 Aprotinin: bolus versus continuous infusion

1

23

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.05, 10.85]

4.5 Tranexamic acid versus aprotinin

1

127

Risk Ratio (M‐H, Random, 95% CI)

2.95 [0.12, 71.17]

5 Thromboembolic episodes Show forest plot

12

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Aprotinin versus control

3

280

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.18, 1.96]

5.2 Tranexamic acid versus control

5

179

Risk Ratio (M‐H, Fixed, 95% CI)

2.20 [0.38, 12.64]

5.3 Epsilon amino caproic acid (EACA) versus control

1

62

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.09, 9.89]

5.4 Recombinant factor VIIa (rFVIIa) versus control

2

266

Risk Ratio (M‐H, Fixed, 95% CI)

1.38 [0.65, 2.91]

5.5 Tranexamic acid versus EACA

1

84

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.39, 10.34]

5.6 Tranexamic acid versus aprotinin

2

178

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [0.37, 10.37]

6 Serious adverse events Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Aprotinin versus control

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.49, 2.11]

6.2 Recombinant factor VIIa (rFVIIa) versus control

2

266

Risk Ratio (M‐H, Fixed, 95% CI)

1.30 [0.94, 1.78]

6.3 Low central venous pressure versus control

1

86

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.55, 0.92]

7 Blood loss Show forest plot

11

Mean Difference (IV, Random, 95% CI)

Subtotals only

7.1 Aprotinin versus control

3

195

Mean Difference (IV, Random, 95% CI)

‐1.36 [‐3.39, 0.66]

7.2 Tranexamic acid versus control

2

65

Mean Difference (IV, Random, 95% CI)

‐4.98 [‐10.18, 0.23]

7.3 Antithrombin III versus control

1

29

Mean Difference (IV, Random, 95% CI)

1.9 [‐4.86, 8.66]

7.4 Thromboelastography versus control

2

62

Mean Difference (IV, Random, 95% CI)

‐1.13 [‐1.85, ‐0.41]

7.5 Low central venous pressure versus control

1

86

Mean Difference (IV, Random, 95% CI)

‐1.19 [‐1.88, ‐0.50]

7.6 Tranexamic acid versus aprotinin

2

71

Mean Difference (IV, Random, 95% CI)

‐1.01 [‐2.31, 0.29]

8 Red‐cell or whole blood transfusion Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Aprotinin versus control

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.40, 1.18]

8.2 Tranexamic acid versus control

1

62

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.60, 0.98]

8.3 Epsilon amino caproic acid (EACA) versus control

1

62

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.77, 1.06]

8.4 Recombinant factor VIIa (rFVIIa) versus control

1

182

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.86, 0.97]

8.5 Tranexamic acid versus EACA

1

84

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

8.6 Tranexamic acid versus aprotinin

1

127

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.23]

9 Red cell or whole blood transfusion Show forest plot

29

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

9.1 Aprotinin versus control

8

375

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.61 [‐0.82, ‐0.40]

9.2 Tranexamic acid versus control

4

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐0.59, 0.06]

9.3 Epsilon amino caproic acid (EACA) versus control

1

62

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.71, 0.36]

9.4 Antithrombin III versus control

1

29

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.77, 0.69]

9.5 Recombinant factor VIIa (rFVIIa) versus control

2

221

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.05 [‐0.32, 0.23]

9.6 Oestrogen versus control

1

30

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.58 [‐1.32, 0.15]

9.7 Prostaglandin versus control

1

20

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.92, 0.83]

9.8 Norepinephrine versus control

1

65

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.53, 0.44]

9.9 Thromboelastography versus control

2

62

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.73 [‐1.25, ‐0.20]

9.10 Low central venous pressure versus control

1

86

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.17 [‐1.62, ‐0.71]

9.11 Aprotinin: bolus versus continuous infusion

1

23

Std. Mean Difference (IV, Fixed, 95% CI)

0.86 [‐0.00, 1.73]

9.12 Aprotinin: high dose versus medium dose

1

189

Std. Mean Difference (IV, Fixed, 95% CI)

0.16 [‐0.12, 0.45]

9.13 Aprotinin: high dose versus low dose

1

20

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.46 [‐2.47, ‐0.45]

9.14 Whole blood versus blood components

1

33

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.72, 0.65]

9.15 Solvent detergent plasma versus standard fresh frozen plasma

1

25

Std. Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.60, 0.98]

9.16 Tranexamic acid versus EACA

1

84

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.23 [‐0.66, 0.20]

9.17 Tranexamic acid versus aprotinin

3

198

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.09 [‐0.36, 0.19]

10 Platelet transfusion Show forest plot

21

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

10.1 Aprotinin versus control

5

185

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.44 [‐0.73, ‐0.14]

10.2 Tranexamic acid versus control

4

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.49, 0.16]

10.3 Epsilon amino caproic acid (EACA) versus control

1

62

Std. Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.52, 0.55]

10.4 Antithrombin III versus control

1

29

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.73, 0.73]

10.5 Recombinant factor VIIa (rFVIIa) versus control

2

216

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.31, 0.25]

10.6 Oestrogen versus control

1

30

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.53 [‐1.26, 0.20]

10.7 Norepinephrine versus control

1

65

Std. Mean Difference (IV, Fixed, 95% CI)

0.34 [‐0.15, 0.83]

10.8 Thromboelastography versus control

1

28

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.91, 0.58]

10.9 Aprotinin: high dose versus medium dose

1

189

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.48 [‐0.77, ‐0.19]

10.10 Whole blood versus blood components

1

33

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.81, 0.56]

10.11 Solvent detergent plasma versus standard fresh frozen plasma

1

25

Std. Mean Difference (IV, Fixed, 95% CI)

0.07 [‐0.71, 0.86]

10.12 Tranexamic acid versus EACA

1

84

Std. Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.37, 0.48]

10.13 Tranexamic acid versus aprotinin

3

198

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.08 [‐0.36, 0.20]

11 Plasma transfusion Show forest plot

25

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 Aprotinin versus control

8

420

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.33 [‐0.53, ‐0.13]

11.2 Tranexamic acid versus control

4

159

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.53, 0.11]

11.3 Epsilon amino caproic acid (EACA) versus control

1

62

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.66, 0.41]

11.4 Antithrombin III versus control

1

29

Std. Mean Difference (IV, Fixed, 95% CI)

0.04 [‐0.69, 0.77]

11.5 Recombinant factor VIIa (rFVIIa) versus control

2

262

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.28, 0.25]

11.6 Oestrogen versus control

1

30

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.67 [‐1.41, 0.07]

11.7 Prostaglandin versus control

1

20

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.88, 0.88]

11.8 Norepinephrine versus control

1

65

Std. Mean Difference (IV, Fixed, 95% CI)

0.11 [‐0.38, 0.60]

11.9 Thromboelastography versus control

1

28

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.82 [‐1.60, ‐0.05]

11.10 Aprotinin: bolus versus continuous infusion

1

23

Std. Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.78, 0.87]

11.11 Aprotinin: high dose versus medium dose

1

189

Std. Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.22, 0.35]

11.12 Aprotinin: high dose versus low dose

1

20

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.31 [‐2.29, ‐0.32]

11.13 Whole blood versus blood components

1

33

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.53 [‐2.32, ‐0.74]

11.14 Tranexamic acid versus EACA

1

84

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.22 [‐0.65, 0.21]

11.15 Tranexamic acid versus aprotinin

2

71

Std. Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.45, 0.48]

12 Cryoprecipitate Show forest plot

12

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

12.1 Aprotinin versus control

3

147

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.49 [‐0.82, ‐0.16]

12.2 Tranexamic acid versus control

4

181

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐0.57, 0.02]

12.3 Epsilon amino caproic acid (EACA) versus control

1

62

Std. Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.53, 0.54]

12.4 Antithrombin III versus control

1

29

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.73, 0.73]

12.5 Oestrogen versus control

1

30

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.72, 0.72]

12.6 Thromboelastography versus control

1

28

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.25 [1.00, 0.49]

12.7 Whole blood versus blood components

1

33

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.28 [‐0.97, 0.41]

12.8 Solvent detergent plasma versus standard fresh frozen plasma

1

25

Std. Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.68, 0.89]

12.9 Tranexamic acid versus EACA

1

62

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐0.69, 0.38]

13 Hospital stay Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

13.1 Aprotinin versus control

1

63

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐4.94, 4.94]

13.2 Tranexamic acid versus control

1

45

Mean Difference (IV, Fixed, 95% CI)

4.0 [‐16.18, 24.18]

13.3 Recombinant factor VIIa (rFVIIa) versus control

1

180

Mean Difference (IV, Fixed, 95% CI)

3.40 [‐7.51, 14.31]

13.4 Norepinephrine versus control

1

65

Mean Difference (IV, Fixed, 95% CI)

‐1.00 [‐3.18, 1.18]

13.5 Low central venous pressure versus control

1

86

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐19.43, 19.43]

13.6 Tranexamic acid versus aprotinin

1

51

Mean Difference (IV, Fixed, 95% CI)

5.0 [‐2.69, 12.69]

14 Intensive therapy unit stay Show forest plot

9

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

14.1 Aprotinin versus control

2

199

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.78, 0.36]

14.2 Tranexamic acid versus control

1

45

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐4.75, 2.75]

14.3 Recombinant factor VIIa (rFVIIa) versus control

2

199

Mean Difference (IV, Fixed, 95% CI)

0.22 [‐0.14, 0.58]

14.4 Norepinephrine versus control

1

65

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐1.65, 1.39]

14.5 Low central venous pressure versus control

1

86

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐3.71, 1.71]

14.6 Aprotinin: bolus versus continuous infusion

1

23

Mean Difference (IV, Fixed, 95% CI)

2.0 [‐3.99, 7.99]

14.7 Tranexamic acid versus aprotinin

1

51

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐2.40, 2.40]
Figuras y tablas -
Comparison 1. Intervention versus control
Ir a la tabla de la revisión