Patient blood management interventions do not lead to important clinical benefits or cost-effectiveness for major surgery: a network meta-analysis

Abstract

Background: Patient blood management (PBM) interventions aim to improve clinical outcomes by reducing bleeding and transfusion. We assessed whether existing evidence supports the routine use of combinations of these interventions during and after major surgery.

Methods: Five systematic reviews and a National Institute of Health and Care Excellence health economic review of trials of common PBM interventions enrolling participants of any age undergoing surgery were updated. The last search was on June 1, 2019. Studies in trauma, burns, gastrointestinal haemorrhage, gynaecology, dentistry, or critical care were excluded. The co-primary outcomes were: risk of receiving red cell transfusion and 30-day or hospital all-cause mortality. Treatment effects were estimated using random-effects models and risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity assessments used I². Network meta-analyses used a frequentist approach. The protocol was registered prospectively (PROSPERO CRD42018085730).

Results: Searches identified 393 eligible randomised controlled trials enrolling 54 917 participants. PBM interventions resulted in a reduction in exposure to red cell transfusion (RR=0.60; 95% CI 0.57, 0.63; I²=77%), but had no statistically significant treatment effect on 30-day or hospital mortality (RR=0.93; 95% CI 0.81, 1.07; I²=0%). Treatment effects were consistent across multiple secondary outcomes, sub-groups and sensitivity analyses that considered clinical setting, type of intervention, and trial quality. Network meta-analysis did not demonstrate additive benefits from the use of multiple interventions. No trial demonstrated that PBM was cost-effective.

Conclusions: In randomised trials, PBM interventions do not have important clinical benefits beyond reducing bleeding and transfusion in people undergoing major surgery.

Keywords: bleeding; cost; effectiveness; haematology; network; patient blood management; surgery; transfusion.

Fig 1

Forest plots of transfusion and bleeding, effectiveness and resource use outcomes. Interventions were compared with controls, showing a significant reduction of the effect on transfusion and bleeding outcomes, but no significant difference in the effectiveness outcomes. There was moderate heterogeneity for the risk of red blood cell transfusion (I²=77%) and no heterogeneity for mortality (I²=0%). The results are expressed as risk ratio (RR), mean difference (MD), or standard mean difference (SMD), along with 95% confidence intervals (CIs). The heterogeneity for each outcome is expressed as I². AKI, acute kidney injury.

Fig 2

A network meta-analysis of eligible comparisons for the rate of red blood cells transfusions. (a) Width of the lines is proportional to the number of trials comparing every pair of treatments. (b) The network model comparing different combinations of interventions show that a combination of restrictive threshold (Restr), tranexamic acid (TXA), point of care (POC) testing and cell salvage ranked highest in reducing the rate of red blood cells transfusions (risk ratio [RR]=0.22; 95% confidence interval [CI] 0.14, 0.34; P score=0.88), followed by a combination of restrictive threshold, tranexamic acid, and iron treatment (RR=0.2; 95% CI 0.08, 0.49) when compared with the control group. There were no inconsistencies between direct and indirect comparisons. There is a moderate global heterogeneity (I²=71%, P<0.001). The effects are reported as P score, which is the probability of an intervention having a higher effect when compared with other treatments, with P=1 showing the maximum probability. The results are expressed as RR along with 95% CIs and P scores. The global heterogeneity is expressed as I², with P<0.05 considered statistically significant.

Fig 3

A network meta-analysis of eligible comparisons for mortality. (a) Width of the lines is proportional to the number of trials comparing every pair of treatments. (b) The network model comparing different combinations of interventions show that a combination of tranexamic acid (TXA), point of care (POC), and cell salvage ranked highest in reducing mortality (risk ratio [RR]=0.26; 95% confidence interval [CI] 0.01, 5.56; P=0.76), followed by a combination of cell salvage and iron treatment (RR=0.32; 95% CI 0.03, 3.25) when compared with the control group. There were no inconsistencies between direct and indirect comparisons. There is no significant global heterogeneity (I²=0%, P=0.99). The effects reported as p-score, which is the probability of an intervention having a higher effect when compared with other treatments, with P=1 showing the maximum probability. The results are expressed as RR along with 95% CIs and P scores. The global heterogeneity is expressed as I², with P<0.05 considered statistically significant. Restr, restrictive threshold.