Haemodilution shows promise in decreasing blood loss and blood transfusion requirements during liver resection

Blood loss during liver resection (partial removal of liver) is one of the important factors affecting the post-operative complications experienced by patients. Allogeneic blood transfusion (using blood donated by a different individual) is associated with increased morbidity and lower survival in patients with liver cancer. This systematic review was aimed at determining whether any cardiopulmonary intervention (interventions that change the circulation or breathing during surgery) decreased blood loss or decreased allogeneic blood transfusion requirements in patients undergoing liver resections. This review included 10 trials with 617 patients. All trials had high risk of bias (with the possibility of overestimating the benefits and underestimating the harms of the treatment) and play of chance ('random error'). The interventions included low central venous pressure (CVP; lowering the pressure in the major veins), autologous blood donation (using the patient's own blood obtained prior to liver resection), haemodilution (replacing blood with other fluids), haemodilution with controlled hypotension (lowering the blood pressure in addition to diluting the blood), and hypoventilation (decreasing the rate of artificial breathing). They were compared with controls not receiving the interventions. There were no differences in the number of deaths or complications due to surgery in any of the comparisons. Long-term survival was not reported in any of the trials. Fewer patients required transfusion of blood donated by others when haemodilution or haemodilution with controlled hypotension were compared with a control group. The other comparisons did not decrease the transfusion requirements. However, there is a high risk of type I errors (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included and the small sample size in each trial, as well as the inherent risk of bias (systematic errors which can result in overestimation of the benefits and underestimation of the harms of the intervention). Haemodilution showed promise in the reduction of blood transfusion requirements in patients undergoing liver resections. Further randomised clinical trials with low risk of bias (systematic errors) and low risk of play of chance (random errors) which assess clinically important outcomes (such as death and complications due to the operation) are necessary to assess cardiopulmonary interventions aimed at decreasing blood loss in liver resections. Trials need to be designed to assess the effect of a combination of different interventions during liver resections.

Authors' conclusions: 

None of the interventions seemed to decrease peri-operative morbidity or offer any long-term survival benefit. Haemodilution shows promise in the reduction of blood transfusion requirements in liver resection surgery. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the high risk of bias in the trials. Further randomised clinical trials with low risk of bias and random errors that assess clinically important outcomes such as peri-operative mortality are necessary to assess any cardiopulmonary interventions aimed at decreasing blood loss and blood transfusion requirements in patients undergoing liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.

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Background: 

Blood loss during liver resection is considered one of the most important factors affecting the peri-operative outcomes of patients undergoing liver resection.

Objectives: 

To determine the benefits and harms of cardiopulmonary interventions to decrease blood loss and to decrease allogeneic blood transfusion requirements in patients undergoing liver resections.

Search strategy: 

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until January 2012 to identify randomised trials.

Selection criteria: 

We included all randomised clinical trials comparing various cardiopulmonary interventions aimed at decreasing blood loss and allogeneic blood transfusion requirements in patients undergoing liver resection. Trials were included irrespective of whether they included major or minor liver resections of normal or cirrhotic livers, vascular occlusion was used or not, and irrespective of the reason for liver resection.

Data collection and analysis: 

Two authors independently identified trials for inclusion and independently extracted data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. For each outcome we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat analysis or available case analysis. For dichotomous outcomes with only one trial included under the outcome, we performed the Fisher's exact test.

Main results: 

Ten trials involving 617 patients satisfied the inclusion criteria. The interventions included low central venous pressure (CVP), autologous blood donation, haemodilution, haemodilution with controlled hypotension, and hypoventilation. Only one or two trials were included under most comparisons. All trials had a high risk of bias. There was no significant difference in the peri-operative mortality in any of the comparisons: low CVP versus no intervention (3 trials, 0/88 (0%) patients in the low CVP group versus 1/89 (1.1%) patients in the no intervention group); autologous blood donation versus no intervention (1 trial, 0/40 (0%) versus 0/39 (0%)); haemodilution versus no intervention (2 trials, 1/73 (1.4%) versus 3/77 (3.9%) in one of these trials); haemodilution with controlled hypotension versus no intervention (1 trial, 0/10 (0%) versus 0/10 (0%)); haemodilution with bovine haemoglobin (HBOC-201) versus haemodilution with hydroxy ethyl starch (HES) (1 trial, 1/6 (16.7%) versus 0/6 (0%)); hypoventilation versus no intervention (1 trial, 0/40 (0%) versus 0/39 (0%)). None of the trials reported long-term survival or quality of life. The risk ratio of requiring allogeneic blood transfusion was significantly lower in the haemodilution versus no intervention groups (3 trials, 16/115 (weighted proportion = 14.2%) versus 41/118 (34.7%), RR 0.41 (95% CI 0.25 to 0.66), P = 0.0003); and for haemodilution with controlled hypotension versus no intervention (1 trial, 0/10 (0%) versus 10/10 (100%), P < 0.0001). There were no significant differences in the allogeneic transfusion requirements in the other comparisons which reported this outcome, such as low CVP versus no intervention, autologous blood donation versus control, and hypoventilation versus no intervention.

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