Background
Many cancerous and non-cancerous growths that develop in the liver are treated by removing part of the liver (liver resection), which is major surgery with high risk of complications, including blood loss during division of the liver tissue. Specialists have tested several methods to decrease blood loss during liver resection. These include lowering the pressure in the liver veins (low central venous pressure) or decreasing the amount of air that enters and leaves the lungs (hypoventilation), again aimed at decreasing central venous pressure; different ways of cutting the liver, for example, without any special equipment or using ultrasound waves or high-frequency (radiofrequency); applying glue to decrease bleeding from the cut surface; blocking the blood supply to the liver during the operation, a process known as vascular occlusion, which could be performed continuously or intermittently. In addition, medical treatments that improve clotting of blood can be given to decrease blood loss. A surgeon typically uses one or more methods to decrease blood loss during liver surgery. The optimal method is unknown. We sought to identify the best methods of decreasing blood loss during liver surgery by performing a literature search that included all studies reported until September 2015. We used special statistical methods, so-called network meta-analyses. to compare the different treatments simultaneously as compared to the traditional Cochrane method of comparing two treatments at a time as there are multiple treatment strategies.
Study characteristics
We identified 67 randomised clinical trials involving a total of 6197 participants that met our inclusion criteria. However, we were only able to include 5771 participants from 64 trials since investigators either did not include the remaining participants in the analysis or did not report any outcomes of interest.
Source of funding: 24 trials (35.8%) were funded by parties with no financial interest in obtaining positive results for the treatment being evaluated. The remaining trials received funding from either parties who would gain financially from the results of the study or did not report the funding.
Quality of evidence
All the trials were at high risk of bias, that is, investigators may have overestimated the benefits or underestimated the harms of one method or the other because of the way that the studies were conducted. Many trials included few participants, and there was a good chance of arriving at the wrong conclusions because of this. The overall quality of evidence was low or very low.
Key results
There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. Such evidence is unreliable. So, we mention only the evidence that was available in more than one trial. Of the primary outcomes, the only one where there was evidence of difference was in the number of adverse events, which was higher with radiofrequency dissecting sealer than with clamp-crush method. Among the secondary outcomes, the only evidence of difference was in the following:
Blood transfusion (percentage): higher in the low central venous pressure group than in the acute normovolemic haemodilution (diluting the blood by giving fluids during operation) plus low central venous pressure group.
Blood transfusion amount: lower in the fibrin sealant group (a type of glue applied to the cut surface of the liver) than in the control.
Blood transfusion (fresh frozen plasma − a component of blood): higher in the oxidised cellulose (another type of glue applied to the cut surface of the liver) group than in the fibrin sealant group.
Blood loss, total hospital stay, and operating time: lower with the low central venous pressure group than control.
For other comparisons, the evidence for difference was based on single small trials, or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work. There is no evidence to suggest that using special equipment for liver resection is of any benefit.
Paucity of data meant that we could not assess transitivity assumptions and inconsistency for most analyses. When direct and indirect comparisons were available, network meta-analysis provided additional effect estimates for comparisons where there were no direct comparisons. However, the paucity of data decreases the confidence in the results of the network meta-analysis. Low-quality evidence suggests that liver resection using a radiofrequency dissecting sealer may be associated with more adverse events than with the clamp-crush method. Low-quality evidence also suggests that the proportion of people requiring a blood transfusion is higher with low central venous pressure than with acute normovolemic haemodilution plus low central venous pressure; very low-quality evidence suggests that blood transfusion quantity (red blood cells) was lower with fibrin sealant than control; blood transfusion quantity (fresh frozen plasma) was higher with oxidised cellulose than with fibrin sealant; and blood loss, total hospital stay, and operating time were lower with low central venous pressure than with control. There is no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality, morbidity, or blood transfusion requirements (very low-quality evidence). Radiofrequency dissecting sealer should not be used outside the clinical trial setting since there is low-quality evidence for increased harm without any evidence of benefits. In addition, it should be noted that the sample size was small and the credible intervals were wide, and we cannot rule out considerable benefit or harm with a specific method of liver resection.
Liver resection is a major surgery with significant mortality and morbidity. Specialists have tested various methods in attempts to limit blood loss, transfusion requirements, and morbidity during elective liver resection. These methods include different approaches (anterior versus conventional approach), use of autologous blood donation, cardiopulmonary interventions such as hypoventilation, low central venous pressure, different methods of parenchymal transection, different methods of management of the raw surface of the liver, different methods of vascular occlusion, and different pharmacological interventions. A surgeon typically uses only one of the methods from each of these seven categories. The optimal method to decrease blood loss and transfusion requirements in people undergoing liver resection is unknown.
To assess the effects of different interventions for decreasing blood loss and blood transfusion requirements during elective liver resection.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Science Citation Index Expanded to September 2015 to identify randomised clinical trials. We also searched trial registers and handsearched the references lists of identified trials.
We included only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different methods of decreasing blood loss and blood transfusion requirements in people undergoing liver resection.
Two review authors independently identified trials and collected data. We assessed the risk of bias using Cochrane domains. We conducted a Bayesian network meta-analysis using the Markov chain Monte Carlo method in WinBUGS 1.4, following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit guidance documents. We calculated the odds ratios (OR) with 95% credible intervals (CrI) for the binary outcomes, mean differences (MD) with 95% CrI for continuous outcomes, and rate ratios with 95% CrI for count outcomes, using a fixed-effect model or random-effects model according to model-fit. We assessed the evidence with GRADE.
We identified 67 randomised clinical trials involving a total of 6197 participants. All the trials were at high risk of bias. A total of 5771 participants from 64 trials provided data for one or more outcomes included in this review. There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. We summarise only the evidence that was available in more than one trial below. Of the primary outcomes, the only one with evidence of a difference from more than one trial under the pair-wise comparison was in the number of adverse events (complications), which was higher with radiofrequency dissecting sealer than with the clamp-crush method (rate ratio 1.85, 95% CrI 1.07 to 3.26; 250 participants; 3 studies; very low-quality evidence). Among the secondary outcomes, the only differences we found from more than one trial under the pair-wise comparison were the following: blood transfusion (proportion) was higher in the low central venous pressure group than in the acute normovolemic haemodilution plus low central venous pressure group (OR 3.19, 95% CrI 1.56 to 6.95; 208 participants; 2 studies; low-quality evidence); blood transfusion quantity (red blood cells) was lower in the fibrin sealant group than in the control (MD −0.53 units, 95% CrI −1.00 to −0.07; 122 participants; 2; very low-quality evidence); blood transfusion quantity (fresh frozen plasma) was higher in the oxidised cellulose group than in the fibrin sealant group (MD 0.53 units, 95% CrI 0.36 to 0.71; 80 participants; 2 studies; very low-quality evidence); blood loss (MD −0.34 L, 95% CrI −0.46 to −0.22; 237 participants; 4 studies; very low-quality evidence), total hospital stay (MD −2.42 days, 95% CrI −3.91 to −0.94; 197 participants; 3 studies; very low-quality evidence), and operating time (MD −15.32 minutes, 95% CrI −29.03 to −1.69; 192 participants; 4 studies; very low-quality evidence) were lower with low central venous pressure than with control. For the other comparisons, the evidence for difference was either based on single small trials or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work.