A randomised controlled trial and economic evaluation of intraoperative cell salvage during caesarean section in women at risk of haemorrhage: the SALVO (cell SALVage in Obstetrics) trial
Health Technology Assessment (Winchester, England). 2018;22((2)):1-88.
BACKGROUND Caesarean section is associated with blood loss and maternal morbidity. Excessive blood loss requires transfusion of donor (allogeneic) blood, which is a finite resource. Cell salvage returns blood lost during surgery to the mother. It may avoid the need for donor blood transfusion, but reliable evidence of its effects is lacking. OBJECTIVES To determine if routine use of cell salvage during caesarean section in mothers at risk of haemorrhage reduces the rates of blood transfusion and postpartum maternal morbidity, and is cost-effective, in comparison with standard practice without routine salvage use. DESIGN Individually randomised controlled, multicentre trial with cost-effectiveness analysis. Treatment was not blinded. SETTING A total of 26 UK obstetric units. PARTICIPANTS Out of 3054 women recruited between June 2013 and April 2016, we randomly assigned 3028 women at risk of haemorrhage to cell salvage or routine care. Randomisation was stratified using random permuted blocks of variable sizes. Of these, 1672 had emergency and 1356 had elective caesareans. We excluded women for whom cell salvage or donor blood transfusion was contraindicated. INTERVENTIONS Cell salvage (intervention) versus routine care without salvage (control). In the intervention group, salvage was set up in 95.6% of the women and, of these, 50.8% had salvaged blood returned. In the control group, 3.9% had salvage deployed. MAIN OUTCOME MEASURES Primary - donor blood transfusion. Secondary - units of donor blood transfused, time to mobilisation, length of hospitalisation, mean fall in haemoglobin, fetomaternal haemorrhage (FMH) measured by Kleihauer-Betke test, and maternal fatigue. Analyses were adjusted for stratification factors and other factors that were believed to be prognostic a priori. Cost-effectiveness outcomes - costs of resources and service provision taking the UK NHS perspective. RESULTS We analysed 1498 and 1492 participants in the intervention and control groups, respectively. Overall, the transfusion rate was 2.5% in the intervention group and 3.5% in the control group [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42 to 1.01; p = 0.056]. In a planned subgroup analysis, the transfusion rate was 3.0% in the intervention group and 4.6% in the control group among emergency caesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 1.8% in the intervention group and 2.2% in the control group among elective caesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46, suggesting that the difference in effect between subgroups was not statistically significant). Secondary outcomes did not differ between groups, except for FMH, which was higher under salvage in rhesus D (RhD)-negative women with RhD-positive babies (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14; p = 0.013). No case of amniotic fluid embolism was observed. The additional cost of routine cell salvage during caesarean was estimated, on average, at pound8110 per donor blood transfusion avoided. CONCLUSIONS The modest evidence for an effect of routine use of cell salvage during caesarean section on rates of donor blood transfusion was associated with increased FMH, which emphasises the need for adherence to guidance on anti-D prophylaxis. We are unable to comment on long-term antibody sensitisation effects. Based on the findings of this trial, cell salvage is unlikely to be considered cost-effective. FUTURE WORK Research into risk of alloimmunisation among women exposed to cell salvage is needed. TRIAL REGISTRATION Current Controlled Trials ISRCTN66118656. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 2. See the NIHR Journals Library website for further project information.
Cell salvage and donor blood transfusion during cesarean section: a pragmatic, multicentre randomised controlled trial (SALVO)
Plos Medicine. 2017;14((12)):e1002471.
BACKGROUND Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. METHODS AND FINDINGS We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. CONCLUSIONS The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. TRIAL REGISTRATION This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656.
Acid-base changes caused by 5% albumin versus 6% hydroxyethyl starch solution in patients undergoing acute normovolemic hemodilution: a randomized prospective study
BACKGROUND Preoperative acute normovolemic hemodilution (ANH) is an excellent model for evaluating the effects of different colloid solutions that are free of bicarbonate but have large chloride concentrations on acid-base equilibrium. METHODS In 20 patients undergoing gynecologic surgery, ANH to a hematocrit of 22% was performed. Two groups of 10 patients each were randomly assigned to receive either 5% albumin or 6% hydroxyethyl starch solutions containing chloride concentrations of 150 and 154 mm, respectively, during ANH. Blood volume (double label measurement of plasma and red cell volumes), pH, Paco2, and serum concentrations of sodium, potassium, chloride, lactate, ionized calcium, phosphate, albumin, and total protein were measured before and 20 min after completion of ANH. Strong ion difference was calculated as serum sodium plus serum potassium minus serum chloride minus serum lactate. The amount of weak plasma acid was calculated using a computer program. RESULTS After ANH, blood volume was well maintained in both groups. ANH caused slight metabolic acidosis with hyperchloremia and a concomitant decrease in strong ion difference. Plasma albumin concentration decreased after hemodilution with 6% hydroxyethyl starch solution and increased after hemodilution with 5% albumin solution. Despite a three-times larger decrease in strong ion difference after ANH with 6% hydroxyethyl starch solution, the decrease in pH was nearly the same in both groups. CONCLUSIONS ANH with 5% albumin or 6% hydroxyethyl starch solutions led to metabolic acidosis. A dilution of extracellular bicarbonate or changes in strong ion difference and albumin concentration offer explanations for this type of acidosis.
Blood salvage during caesarean section
British Journal of Anaesthesia. 1998;80((2):):195-8.
The aim of this study was to assess blood salvage during Caesarean section. In 15 Caesarean sections, red cells lost were collected and washed with a Dideco machine and tested for the presence of fetoplacental material, bacterial contamination, free haemoglobin and fetal blood cells. Successive patients were allocated randomly to one of two groups. In group 1 (n = 34), intraoperative blood was salvaged, while group 2 served as a control. The mean amount of blood salvaged in group 1 was 363 (SD 153) ml. Blood was salvaged following these guidelines: identification of blood group of the mother and fetus; avoidance of aspirating blood from the umbilical cord; commencement of salvage after removing the fetoplacental unit; completely filling the centrifugation bowl with red cells; washing the cells using at least 1000 ml of physiological solution per bowl; and mixing the contents of the bowl, completely eliminating the buffy coat where fetal cells are located. In group 1, the use of homologous blood transfusions was significantly lower (one of 34 (2.9%) patients compared with eight of 34 (23.5%); P = 0.01), haemoglobin concentrations during the first 4 days after operation were significantly higher and postoperative hospital stay was significantly shorter. Duration of hospital stay was significantly shorter in group 1 (5.3 (1.9) vs 7.3 (4) days; P = 0.003). Mean base haemoglobin concentrations were significantly lower in group 1 (10.7 (1.4) vs 11.7 (1.5) g dl-1; P > 0.0001), while after surgery mean haemoglobin concentrations were significantly higher approximately 3 h after operation compared with the control group (10.2 (1.5) vs 8.6 (1.2) g dl-1; P < 0.0001). On the first day, haemoglobin concentrations were 9.8 (1.5) vs 8 (1.4) g dl-1 (P < 0.0001), on the second day 9.8 (1.4) vs 7.7 (1.4) g dl-1 (P < 0.0001), on the third day 10.1 (1.5) vs 7.5 (1.3) g dl-1 (P < 0.0001) and on the fourth day 10.4 (1.5) vs 8.1 (1.4) g dl-1 (P < 0.0001).