Pharmacological interventions to decrease blood loss and blood transfusion requirements for liver resection

Kurinchi Selvan Gurusamy; Jun Li; Dinesh Sharma; Brian R Davidson

doi:10.1002/14651858.CD008085

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Figure 1

Reference flow chart

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Analysis 1.1

Comparison 1 Intervention versus control, Outcome 1 Mortality.

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Study
Aprotinin versus control
Lentschener 1999	In this trial, survival was reported for patients undergoing liver resection for colorectal liver metastases. The exact number of patients in each group was not stated and survival outcomes could not be included for meta‐analysis. The one‐year survival in patients with colorectal liver metastases was statistically greater in the aprotinin group than the control group. However, the survival advantage was lost at 28 months.

Analysis 1.2

Comparison 1 Intervention versus control, Outcome 2 Survival.

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Study	Antithrombin	Control	P value
Antithrombin III versus control
Shimada 1994	1/13 (7.7%)	1/11 (9.1%)	P > 0.9999

Analysis 1.3

Comparison 1 Intervention versus control, Outcome 3 Liver failure.

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Analysis 1.5

Comparison 1 Intervention versus control, Outcome 5 Number requiring allogeneic blood transfusion.

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Analysis 1.6

Comparison 1 Intervention versus control, Outcome 6 Red cell transfusion.

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Analysis 1.7

Comparison 1 Intervention versus control, Outcome 7 Operating time (minutes).

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Study	Tranexamic acid Mean (standard deviation)	ControlMean (standard deviation)	P value
Tranexamic acid versus control
Wu 2006	8 (7.66)	9 (7.66)	0.34

Analysis 1.8

Comparison 1 Intervention versus control, Outcome 8 Hospital stay (days).

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Analysis 1.9

Comparison 1 Intervention versus control, Outcome 9 Transection blood loss (ml).

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Analysis 1.10

Comparison 1 Intervention versus control, Outcome 10 Operative blood loss (ml).

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Study	Antithrombin III Mean (standard deviation)	Control Mean (standard deviation)	Mean difference (95% confidence intervals)	Statistical signficance
Antithrombin III versus control
Shimada 1994	2.1(1.1)	2.5(1.3)	‐0.40 (‐1.37 to 0.57)	P = 0.42

Analysis 1.11

Comparison 1 Intervention versus control, Outcome 11 Bilirubin (micromol/litre).

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Study	Aprotinin Mean (standard deviation)	Control Mean (standard deviation)	Mean difference(95% confidence intervals)	Statistical significance
Aprotinin versus control
Lentschener 1999	63(12)	63(15)	0 (‐5.4 to 5.4)	P = 1.00

Analysis 1.12

Comparison 1 Intervention versus control, Outcome 12 Prothrombin activity (percentage of normal activity).

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Study	Antithrombin III Mean (standard deviation)	Control Mean (standard deviation)	Mean difference (95% confidence intervals)	Statistical significance
Antithrombin III versus control
Shimada 1994	170 (86.5)	177(63)	‐7.00 (‐66.98 to 52.98)	P = 0.82

Analysis 1.13

Comparison 1 Intervention versus control, Outcome 13 Aspartate transaminase (international units per litre) (peak).

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Study	Antithrombin III Mean (standard deviation)	Control Mean (standard deviation)	Mean difference (95% confidence intervals)	Statistical significance
Antithrombin III versus control
Shimada 1994	95 (39.7)	86 (39.8)	9.00 (‐22.92 to 40.92)	P = 0.58

Analysis 1.14

Comparison 1 Intervention versus control, Outcome 14 Alanine transminase (international units per litre) (peak).

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Analysis 2.1

Comparison 2 Peri‐operative morbidity, Outcome 1 Tranexamic acid versus control.

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Analysis 2.2

Comparison 2 Peri‐operative morbidity, Outcome 2 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control.

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Analysis 2.3

Comparison 2 Peri‐operative morbidity, Outcome 3 Recombinant VIIa (rFVIIa) low dose (20 to 50 mcg/kg) versus control.

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Analysis 2.4

Comparison 2 Peri‐operative morbidity, Outcome 4 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg).

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Study	Antithrombin	Control	P value
Infected intra‐abdominal collection
Shimada 1994	1/13 (7.7%)	1/11 (9.1%)	P > 0.9999

Analysis 2.5

Comparison 2 Peri‐operative morbidity, Outcome 5 Anitithrombin III versus control.

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Comparison 1. Intervention versus control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Aprotinin versus control	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.18, 7.48]
1.2 Tranexamic acid versus control	1	217	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control	2	272	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.18, 3.51]
1.4 Recombinant VIIa (rFVIIa) low dose (20 to 50 mcg/kg) versus control	2	273	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.43, 5.89]
1.5 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg)	2	267	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.10, 2.08]
2 Survival Show forest plot			Other data	No numeric data

2.1 Aprotinin versus control			Other data	No numeric data
3 Liver failure Show forest plot			Other data	No numeric data

3.1 Antithrombin III versus control			Other data	No numeric data
4 Peri‐operative morbidity			Other data	No numeric data
4.1 See analysis 2			Other data	No numeric data
5 Number requiring allogeneic blood transfusion Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Aprotinin versus control	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.21, 0.89]
5.2 Tranexamic acid versus control	1	214	Risk Ratio (M‐H, Fixed, 95% CI)	0.03 [0.00, 0.46]
5.3 Desmopressin versus control	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.15, 2.21]
5.4 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control	2	272	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.62, 1.20]
5.5 Recombinant VIIa (rFVIIa) low dose (20 to 50 mcg/kg) versus control	2	273	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.94, 1.64]
5.6 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg)	2	267	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.51, 0.94]
6 Red cell transfusion Show forest plot	4		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6.1 Desmopressin versus control	1	59	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.31 [‐0.82, 0.21]
6.2 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control	2	272	Std. Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.23, 0.24]
6.3 Recombinant VIIa (rFVIIa) high dose (20 to 50 mcg/kg) versus control	2	269	Std. Mean Difference (IV, Fixed, 95% CI)	0.19 [‐0.05, 0.43]
6.4 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg)	2	267	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐0.43, 0.05]
6.5 Antithrombin versus control	1	24	Std. Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.73, 0.88]
7 Operating time (minutes) Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Aprotinin versus control	1	97	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐30.08, 28.08]
7.2 Tranexamic acid versus control	1	214	Mean Difference (IV, Fixed, 95% CI)	‐52.20 [‐86.15, ‐18.25]
7.3 Desmopressin versus control	1	59	Mean Difference (IV, Fixed, 95% CI)	‐30.0 [‐112.69, 52.69]
7.4 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control	2	272	Mean Difference (IV, Fixed, 95% CI)	‐16.80 [‐40.42, 6.81]
7.5 Recombinant VIIa (rFVIIa) high dose (20 to 50 mcg/kg) versus control	2	269	Mean Difference (IV, Fixed, 95% CI)	7.38 [‐18.41, 33.16]
7.6 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg)	2	267	Mean Difference (IV, Fixed, 95% CI)	‐24.29 [‐48.84, 0.27]
7.7 Antithrombin versus control	1	24	Mean Difference (IV, Fixed, 95% CI)	‐28.0 [‐79.80, 23.80]
8 Hospital stay (days) Show forest plot			Other data	No numeric data

8.1 Tranexamic acid versus control			Other data	No numeric data
9 Transection blood loss (ml) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 Tranexamic acid versus control	1	214	Mean Difference (IV, Fixed, 95% CI)	‐260.0 [‐434.99, ‐85.01]
9.2 Desmopressin versus control	1	59	Mean Difference (IV, Fixed, 95% CI)	‐45.0 [‐626.86, 536.86]
10 Operative blood loss (ml) Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

10.1 Aprotinin versus control	1	97	Mean Difference (IV, Fixed, 95% CI)	‐434.00 [‐873.67, 1.67]
10.2 Tranexamic acid versus control	1	214	Mean Difference (IV, Fixed, 95% CI)	‐300.0 [‐502.05, ‐97.95]
10.3 Desmopressin versus control	1	59	Mean Difference (IV, Fixed, 95% CI)	32.5 [‐695.69, 760.69]
10.4 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control	2	272	Mean Difference (IV, Fixed, 95% CI)	‐156.86 [‐427.71, 113.99]
10.5 Recombinant VIIa (rFVIIa) low dose (20 to 50 mcg/kg) versus control	2	273	Mean Difference (IV, Fixed, 95% CI)	138.29 [‐166.99, 443.57]
10.6 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg)	2	267	Mean Difference (IV, Fixed, 95% CI)	‐299.54 [‐577.54, ‐21.54]
10.7 Antithrombin versus control	1	24	Mean Difference (IV, Fixed, 95% CI)	463.00 [‐326.67, 1252.67]
11 Bilirubin (micromol/litre) Show forest plot			Other data	No numeric data

11.1 Antithrombin III versus control			Other data	No numeric data
12 Prothrombin activity (percentage of normal activity) Show forest plot			Other data	No numeric data

12.1 Aprotinin versus control			Other data	No numeric data
13 Aspartate transaminase (international units per litre) (peak) Show forest plot			Other data	No numeric data

13.1 Antithrombin III versus control			Other data	No numeric data
14 Alanine transminase (international units per litre) (peak) Show forest plot			Other data	No numeric data

14.2 Antithrombin III versus control			Other data	No numeric data

Comparison 1. Intervention versus control

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Comparison 2. Peri‐operative morbidity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tranexamic acid versus control Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ascites	1	214	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.29, 3.29]
1.2 Intra‐abdominal abscess	1	214	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.26, 2.05]
1.3 Bile leak	1	214	Risk Ratio (M‐H, Fixed, 95% CI)	1.96 [0.37, 10.49]
1.4 Wound infection	1	214	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.11, 3.84]
1.5 Pleural effusion	1	214	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.05, 5.33]
2 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus control Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Bile leak	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.01, 8.27]
2.2 Hyperamylasemia	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	3.08 [0.13, 74.42]
2.3 Pleural effusion	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	3.08 [0.13, 74.42]
2.4 Myocardial infarction	2	272	Risk Ratio (M‐H, Fixed, 95% CI)	3.08 [0.13, 74.42]
2.5 Pulmonary embolism	2	272	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.15, 7.28]
2.6 Deep vein thrombosis	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.16, 7.34]
2.7 Portal vein thrombosis	2	272	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.01, 8.56]
2.8 Mesenteric vein thrombosis	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	3.08 [0.13, 74.42]
3 Recombinant VIIa (rFVIIa) low dose (20 to 50 mcg/kg) versus control Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Bile leak	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.07, 16.79]
3.2 Hyperamylasemia	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Pleural effusion	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.4 Myocardial infarction	2	273	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.24, 102.10]
3.5 Pulmonary embolism	2	273	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.14, 7.38]
3.6 Deep vein thrombosis	1	126	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.08]
3.7 Portal vein thrombosis	2	273	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.15, 7.14]
3.8 Mesenteric vein thrombosis	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Recombinant VIIa (rFVIIa) high dose (80 to 100 mcg/kg) versus low dose (20 to 50 mcg/kg) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Bile leak	1	145	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.73]
4.2 Hyperamylasemia	1	145	Risk Ratio (M‐H, Fixed, 95% CI)	2.88 [0.12, 69.55]
4.3 Pleural effusion	1	145	Risk Ratio (M‐H, Fixed, 95% CI)	2.88 [0.12, 69.55]
4.4 Myocardial infarction	2	267	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.11, 4.12]
4.5 Pulmonary embolism	2	267	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.07, 16.69]
4.6 Deep vein thrombosis	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	5.33 [0.26, 108.84]
4.7 Portal vein thrombosis	2	267	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.73]
4.8 Mesenteric vein thrombosis	1	145	Risk Ratio (M‐H, Fixed, 95% CI)	2.88 [0.12, 69.55]
5 Anitithrombin III versus control Show forest plot			Other data	No numeric data

5.1 Infected intra‐abdominal collection			Other data	No numeric data

Comparison 2. Peri‐operative morbidity

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