Methods to decrease blood loss during liver resection: a network meta‐analysis: blood transfusion requirements
Patient or population: people undergoing liver resection Settings: secondary or tertiary setting Intervention and control: various treatments Follow‐up: perioperative period
Outcomes	Anterior approach versus conventional approach	Autologous blood donation versus control	Cardiopulmonary interventions	Methods of parenchymal transection	Methods of dealing with raw surface	Methods of vascular occlusion	Pharmacological interventions
Treatments The first treatment listed is the control. The remaining are interventions.	Conventional approach Anterior approach	Control Autologous blood donation	Control Acute normovolemic haemodilution plus low central venous pressure Hypoventilation Low central venous pressure	Clamp‐crush method Cavitron ultrasonic surgical aspirator Hydrojet Radiofrequency dissecting sealer Sharp transection method Stapler	Control Argon beam Collagen Cyanoacrylate Fibrin sealant Fibrin sealant plus collagen Oxidised cellulose Plasmajet	Control Continuous hepatic vascular exclusion Continuous portal triad clamping Continuous selective hepatic vascular exclusion Continuous selective portal triad clamping Intermittent portal triad clamping Intermittent selective portal triad clamping	Control Anti‐thrombin III Recombinant factor VIIa Tranexamic acid
Blood transfusion (proportion)	There was no evidence of differences in blood transfusion (proportion) between the 2 groups (quality of evidence = very low)1,2,3,4.	The blood transfusion (proportion) was lower in autologous blood donation than control. Proportion requiring blood transfusion in control group: 619 per 1000 Proportion requiring blood transfusion in autologous blood donation group: 111 per 1000 (25 to 409) Relative effect: OR 0.18, 95% CrI 0.04 to 0.66 42 participants; 1. Quality of evidence = low1,2.	The blood transfusion (proportion) was higher in low central venous pressure than acute normovolemic haemodilution plus low central venous pressure. Proportion requiring blood transfusion in acute normovolemic haemodilution plus low central venous pressure: 118 per 1000 Proportion requiring blood transfusion in low central venous pressure group: 376 per 1000 (184 to 820) Relative effect: OR 3.19, 95% CrI 1.56 to 6.95 208 participants; 2. Quality of evidence = low1,2. There was no evidence of differences in other comparisons (quality of evidence = very low)1,2,3.	*There was no evidence of differences in blood transfusion (proportion) for any of the comparisons (quality of evidence = very low)1,2,3,4.	There was no evidence of differences in blood transfusion (proportion) for any of the comparisons (quality of evidence = very low)1,2,3,4.	* The blood transfusion (proportion) was lower in continuous portal triad clamping than control. Proportion requiring blood transfusion in control group: 300 per 1000 Proportion requiring blood transfusion in continuous portal triad clamping: 18 per 1000 (0 to 148) Relative effect: OR 0.06, 95% CrI 0.00 to 0.49 34 participants; 1. Quality of evidence = low1,2. The blood transfusion (proportion) was higher in continuous portal triad clamping than continuous hepatic vascular exclusion Proportion requiring blood transfusion in continuous hepatic vascular exclusion: 133 per 1000 Proportion requiring blood transfusion in continuous portal triad clamping group: 785 per 1000 (326 to 2072) Relative effect: OR 5.90, 95% CrI 2.45 to 15.58 118 participants; 1. Quality of evidence = low1,2. There was no evidence of differences in other comparisons (quality of evidence = very low)1,2,3,4.	The blood transfusion (proportion) was lower in aprotinin than control. Proportion requiring blood transfusion in control group: 291 per 1000 Proportion requiring blood transfusion in aprotinin group: 90 per 1000 (32 to 227) Relative effect: OR 0.31, 95% CrI 0.11 to 0.78. 97 participants; 1. Quality of evidence = low1,2. The blood transfusion (proportion) was lower in tranexamic acid than control. Proportion requiring blood transfusion in tranexamic acid group: 3 per 1000 (0 to 38) Relative effect: OR 0.01, 95% CrI 0.00 to 0.13. 214 participants; 1. Quality of evidence = low1,2. There was no evidence of differences in other comparisons (quality of evidence = very low)1,2,3.
Blood transfusion (red blood cells)	None of the trials reported this outcome.	There was no evidence of differences in blood transfusion quantity (red blood cells) between the groups (quality of evidence = very low)1,2,3.	* The blood transfusion quantity (red blood cells) was lower in acute normovolemic haemodilution. The mean blood transfusion quantity (red blood cells) in the control group was 1.38 units. The mean blood transfusion quantity (red blood cells) in the acute normovolemic haemodilution was 1.25 lower (1.74 to 0.75 lower). 20 participants; 1. Quality of evidence: very low)1,2,3. The mean blood transfusion quantity (red blood cells) in the acute normovolemic haemodilution plus hypotension was 1.66 lower (2.06 to 1.32 lower). 20 participants; 1. Quality of evidence: low1,2. The mean blood transfusion quantity (red blood cells) in the acute normovolemic haemodilution plus low central venous pressure was 0.27 higher (0.01 to 0.52 higher). 30 participants; 1. Quality of evidence: very low1,2,3. There was no evidence of differences in other comparisons (quality of evidence = very low)1,2,3.	The blood transfusion quantity (red blood cells) was lower in hydrojet than cavitron ultrasonic surgical aspirator. The mean blood transfusion quantity (red blood cell) in the cavitron ultrasonic surgical aspirator group was 2.48 units. The mean blood transfusion quantity (red blood cells) in the hydrojet group was 0.98 lower (1.90 to 0.06 lower). 61 participants; 1. Quality of evidence = very low1,2,3. There was no evidence of difference in blood transfusion quantity (red blood cells) in the remaining comparisons (quality of evidence = very low)1,2,3.	The blood transfusion quantity (red blood cells) was lower in fibrin sealant than control. The mean blood transfusion quantity (red blood cells) in the control group was 3.5 units. The mean blood transfusion quantity (red blood cells) in the fibrin sealant group was 0.53 lower (1.00 to 0.07 lower). 122 participants; 2. Quality of evidence = very low1,2,3. The blood transfusion quantity (red blood cells) was higher in fibrin sealant than cyanoacrylate. The mean blood transfusion quantity (red blood cells) in the cyanoacrylate group was 2.13 units. The mean blood transfusion quantity (red blood cells) in the fibrin sealant group was 2.20 higher (1.59 to 2.81 higher). 30 participants; 1. Quality of evidence = low1,2. There was no evidence of difference in blood transfusion quantity (red blood cells) in the remaining comparisons (quality of evidence =very low)1,2,3,4.	* The blood transfusion quantity (red blood cells) was lower in continuous portal triad clamping than control. The mean blood transfusion quantity (red blood cells) in the control group was 1.7 units. The mean blood transfusion quantity (red blood cells) in the intermittent portal triad clamping was 1.25 lower (2.39 to 0.10 lower). (network meta‐analysis) 786 participants; 10. Quality of evidence = very low1,2,3. The blood transfusion quantity (red blood cells) was lower in intermittent portal triad clamping than control. The mean blood transfusion quantity (red blood cells) in the intermittent portal triad clamping was 1.50 lower (2.75 to 0.26 lower). 100 participants; 1. Quality of evidence = very low1,2,3. The blood transfusion quantity (red blood cells) was lower in continuous selective hepatic vascular exclusion than continuous portal triad clamping. The mean blood transfusion quantity (red blood cells) in the continuous portal triad clamping group was 1.125 units. The mean blood transfusion quantity (red blood cells) in the continuous selective hepatic vascular exclusion was 1.20 lower (2.37 to 0.04 lower). 160 participants; 1. Quality of evidence = very low1,2,3. The blood transfusion quantity (red blood cells) was lower in continuous selective portal triad clamping than continuous portal triad clamping. The mean blood transfusion quantity (red blood cells) in the continuous selective portal triad clamping was 0.20 lower (0.31 to 0.09 lower). 120 participants; 1. Quality of evidence = very low1,2,3. There was no evidence of difference in blood transfusion quantity (red blood cells) in the remaining comparisons (quality of evidence = very low)1,2,3,4.	The blood transfusion quantity (red blood cells) was lower in aprotinin than control. The mean blood transfusion quantity (red blood cells) in the control group was 2.10 units. The mean blood transfusion quantity (red blood cells) in the aprotinin group was 0.94 lower (no information to calculate confidence intervals; P = 0.015). 97 participants; 1. Quality of evidence = very lowa,b,c. There was no evidence of difference in blood transfusion quantity (red blood cells) in the remaining comparisons (quality of evidence = very low)1,2,3.
Blood transfusion (platelets)	None of the trials reported this outcome.	None of the trials reported this outcome.	None of the trials reported this outcome.	None of the trials reported this outcome.	None of the trials reported this outcome.	None of the trials reported this outcome.	There was no evidence of differences in blood transfusion quantity (platelets) between the groups (quality of evidence = very low)1,2,3.
Blood transfusion (fresh frozen plasma)	None of the trials reported this outcome.	None of the trials reported this outcome.	The blood transfusion quantity (fresh frozen plasma) was lower in low central venous pressure than control The mean blood transfusion quantity (fresh frozen plasma) in the control group was 4.23 units. The mean blood transfusion quantity (red blood cells) in the low central venous pressure was 2.48 lower (3.58 to 1.37 lower). 50 participants; 1. Quality of evidence = low1,2. There was no evidence of differences in the other comparison (quality of evidence = very low)1,2,3.	There was no evidence of differences in blood transfusion quantity (fresh frozen plasma) between the groups (quality of evidence = very low)1,2,3.	The blood transfusion quantity (fresh frozen plasma) was lower in fibrin sealant than cyanoacrylate. The mean blood transfusion quantity (fresh frozen plasma) in the cyanoacrylate group was 0.8 units. The mean blood transfusion quantity (fresh frozen plasma) in the fibrin sealant group was 0.81 lower (1.04 to 0.62 lower). 30 participants; 1. Quality of evidence = very low1,2,3. The blood transfusion quantity (fresh frozen plasma) was higher in oxidised cellulose than fibrin sealant. The mean blood transfusion quantity (fresh frozen plasma) in the fibrin sealant group was 8.8 units. The mean blood transfusion quantity (fresh frozen plasma) in the oxidised cellulose group was 0.53 higher (0.36 to 0.71 higher). 80 participants; 2. Quality of evidence = very low1,2,3. There was no evidence of difference in blood transfusion quantity (fresh frozen plasma) in the remaining comparisons (quality of evidence = very low)1,2,3.	None of the trials reported this outcome.	There was no evidence of differences in blood transfusion quantity (fresh frozen plasma) between the groups (quality of evidence = very low)1,2,3.
Blood transfusion (cryoprecipitate)	None of the trials reported this outcome.	None of the trials reported this outcome.	There was no evidence of differences in blood transfusion quantity (cryoprecipitate) between the groups (quality of evidence = very low)1,2,3.	None of the trials reported this outcome.	None of the trials reported this outcome.	None of the trials reported this outcome.	None of the trials reported this outcome.
Blood loss	There was no evidence of differences in blood loss between the groups (quality of evidence = very low)1,2,3.	There was no evidence of differences in blood loss between the groups (quality of evidence = very low)1,2,3.	* The blood loss was lower in acute normovolemic haemodilution plus hypotension than control The mean blood loss in the control group was 0.71 litres. The mean blood loss in the acute normovolemic haemodilution plus hypotension was 0.25 lower (0.37 to 0.13 lower). 20 participants; 1. Quality of evidence = very low1,2,3. The mean blood loss in the low central venous pressure was 0.34 lower (0.46 to 0.22 lower). 237 participants; 4. Quality of evidence = very low1,2,3. The mean blood loss in the acute normovolemic haemodilution group was 0.65 litres. The blood loss in acute normovolemic haemodilution plus hypotension was 0.25 lower (0.40 to 0.10 lower) 20 participants; 1. Quality of evidence = very low1,2,3. There was no evidence of differences in other comparisons (quality of evidence = very low)1,2,3.	There was no evidence of differences in blood loss between the groups (quality of evidence = very low)1,2,3.	There was no evidence of differences in blood loss between the groups (quality of evidence = very low)1,2,3.	There was no evidence of differences in blood loss between the groups (quality of evidence = very low)1,2,3,4.	The blood loss was lower in tranexamic acid than control (difference in median: ‐0.30 litres, P < 0.001; 214 participants; 1 study). The mean blood loss in the control group was 0.45 litres. The mean blood loss in the tranexamic acid was 0.30 lower (no information to calculate confidence intervals; P < 0.001). 214 participants; 1. Quality of evidence = low1,2. There was no evidence of difference in blood transfusion quantity (red blood cells) in the remaining comparisons (quality of evidence = very low)1,2,3.
Major blood loss (proportion)	There was no evidence of differences in major blood loss (proportion) between the 2 groups (quality of evidence = very low)1,2,3,4.	There was no evidence of differences in major blood loss (proportion) between the 2 groups (quality of evidence = very low)1,2,3.	There was no evidence of differences in major blood loss (proportion) between the groups (quality of evidence = very low)1,2,3.	None of the trials reported this outcome.	None of the trials reported this outcome.	There was no evidence of differences in major blood loss (proportion) between the groups (quality of evidence = very low)1,2,3.	None of the trials reported this outcome.
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.
Footnotes 1 Risk of bias was unclear or high in the trial[s) (downgraded by 1 point). 2 Sample size was low (total number of participants fewer than 400 for continuous outcomes and fewer than 300 events in total in both groups for other outcomes) (downgraded by 1 point). 3 Credible intervals overlapped no effect and clinically significant effect (20% relative risk reduction for binary outcomes;1 unit of transfusion quantity; 500 ml blood loss) (downgraded by 1 point). 4 There was considerable or substantial heterogeneity in the pair‐wise comparison or at least 1 of the comparisons in the network (downgrade by 2 points). *Network meta‐analysis was performed for these outcome because of the availability of direct and indirect comparisons in the network. The remaining outcomes were analysed by direct comparisons. CrI: credible intervals; MD: mean difference; OR: odds ratio.