Should Cell Salvage be Used in Liver Resection and Transplantation? A Systematic Review and Meta-analysis
Rajendran L, Lenet T, Shorr R, Abou Khalil J, Bertens KA, Balaa FK, Martel G
Annals of surgery. 2022
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OBJECTIVE To evaluate the effect of intraoperative blood salvage and autotransfusion (IBSA) use on red blood cell (RBC) transfusion and postoperative outcomes in liver surgery. BACKGROUND Intraoperative RBC transfusions are common in liver surgery and associated with increased morbidity. IBSA can be utilized to minimize allogeneic transfusion. A theoretical risk of cancer dissemination has limited IBSA adoption in oncologic surgery. METHODS Electronic databases were searched from inception until May 2021. All studies comparing IBSA use to control in liver surgery were included. Screening, data extraction, and risk of bias assessment were conducted independently, in duplicate. The primary outcome was intraoperative allogeneic RBC transfusion (proportion of patients and volume of blood transfused). Core secondary outcomes included: overall survival (OS) and disease-free survival (DFS), transfusion-related complications, length of hospital stay, and hospitalization costs. Data from transplant and resection studies were analyzed separately. Random effects models were used for meta-analysis. RESULTS Twenty-one observational studies were included (16 transplant, 5 resection, n=3,433 patients). Seventeen studies incorporated oncologic indications. In transplant, IBSA was associated with decreased allogeneic RBC transfusion (MD -1.81, 95% CI[-3.22, -0.40], P=0.01, I2=86%, very-low certainty). Few resection studies reported on transfusion for meta-analysis. No significant difference existed in OS or DFS in liver transplant (HR=1.12[0.75, 1.68], P=0.59, I2=0%; HR=0.93[0.57, 1.48], P=0.75, I2=0%) and liver resection (HR=0.69[0.45, 1.05], P=0.08, I2=0%; HR=0.93[0.59, 1.45], P=0.74, I2=0%). CONCLUSION IBSA may reduce intraoperative allogeneic RBC transfusion without compromising oncologic outcomes. The current evidence base is limited in size and quality, and high-quality randomized controlled trials are needed.
Patients undergoing oncologic and non-oncologic liver surgery (either resection or transplantation), (21 studies, n= 3,433).
Any intraoperative blood salvage and autotransfusion (IBSA) device.
No IBSA use.
Data from transplant and resection studies were analyzed separately. Despite significant heterogeneity, most studies reported lower rates and volumes of intraoperative allogeneic red blood cell transfusion in patients undergoing IBSA. In transplant, IBSA was associated with decreased allogeneic red blood cell transfusion (mean difference: -1.81, very-low certainty). Few resection studies reported on transfusion for meta-analysis. There was no significant difference in overall survival or disease-free survival in liver transplant and liver resection.
Clinical prognosis of intraoperative blood salvage autotransfusion in liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis
Wang Z, Li S, Jia Y, Liu M, Yang K, Sui M, Liu D, Liang K
Frontiers in oncology. 2022;12:985281
BACKGROUND Intraoperative blood salvage autotransfusion(IBSA) has been widely used in a variety of surgeries, but the use of IBSA in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) is controversial. Numerous studies have reported that IBSA used during LT for HCC is not associated with adverse oncologic outcomes. This systematic review and meta-analysis aims to estimate the clinical prognosis of IBSA for patients with H+CC undergoing LT. METHODS MEDLINE, Embase, Web of Science, and Cochrane Library were searched for articles describing IBSA in HCC patients undergoing LT from the date of inception until May 1, 2022, and a meta-analysis was performed. Study heterogeneity was assessed by I(2) test. Publication bias was evaluated by funnel plots, Egger's and Begg's test. RESULTS 12 studies enrolling a total of 2253 cases (1374 IBSA and 879 non-IBSA cases) are included in this meta-analysis. The recurrence rate(RR) at 5-year(OR=0.75; 95%CI, 0.59-0.95; P=0.02) and 7-year(OR=0.65; 95%CI, 0.55-0.97; P=0.03) in the IBSA group is slightly lower than non-IBSA group. There are no significant differences in the 1-year RR(OR=0.77; 95% CI, 0.56-1.06; P=0.10), 3-years RR (OR=0.79; 95% CI, 0.62-1.01; P=0.06),1-year overall survival outcome(OS) (OR=0.90; 95% CI, 0.63-1.28; P=0.57), 3-year OS(OR=1.16; 95% CI, 0.83-1.62; P=0.38), 5-year OS(OR=1.04; 95% CI, 0.76-1.40; P=0.82),1-year disease-free survival rate(DFS) (OR=0.80; 95%CI, 0.49-1.30; P=0.36), 3-year DFS(OR=0.99; 95%CI, 0.64-1.55; P=0.98), and 5-year DFS(OR=0.88; 95%CI, 0.60-1.28; P=0.50). Subgroup analysis shows a difference in the use of leukocyte depletion filters group of 5-year RR(OR=0.73; 95%CI, 0.55-0.96; P=0.03). No significant differences are found in other subgroups. CONCLUSIONS IBSA provides comparable survival outcomes relative to allogeneic blood transfusion and does not increase the tumor recurrence for HCC patients after LT. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier CRD42022295479.
Effect of acute normovolemic hemodilution combined with controlled low central venous pressure on blood coagulation function and blood loss in patients undergoing resection of liver cancer operation
Guo JR, Shen HC, Liu Y, Xu F, Zhang YW, Shao Y, Su YJ
BACKGROUND/AIMS: This paper aims to investigate the effect of acute normovolemic hemodilution (ANH) used with controlled low central venous pressure (LCVP) technology on perioperative bleeding and coagulation in hepatocellular carcinoma operation patients. METHODOLOGY A total of 60 cases undergoing hepatic resection operation were randomly divided into the control group, LCVP group (Group II), and ANH + LCVP group (Group III). The changes of hemodynamic indexes at different time points in each group were observed and recorded, along with the volume of allogenous blood transfusion and the number of patients undergoing allogenous blood transfusion. RESULTS Compared with Group I (control), there was evident reduction of the bleeding volume, allogenic blood transfusion volume, and number of patients undergoing allogenic blood transfusion in Groups II and III. CONCLUSION The application of ANH combined with LCVP in hepatic resection can evidently reduce intraoperative hemorrhages and homologous blood transfusions; moreover, it has no significant adverse effect on the coagulation function.
Effect of acute normovolemic hemodilution combined with controlled low central venous pressure on cerebral oxygen metabolism of patients with hepalobectomy
Guo JR, Shen HC, Liu Y, Xu F, Zhang YW, Zhang JP, Yang DW
BACKGROUND/AIMS: The effect of acute normovolemic hemodilution (ANH) combined with controlled low central venous pressure (LCVP) on the cerebral oxygen metabolism of patients with hepalobectomy. METHODOLOGY Undergoing hepatic resection operation in 60 cases, were randomly divided into control group, LCVP group (Group II) and ANH + LCVP group (Group IIl). Before hemodilution (T1), decrease of CVP (T2) and increase of CVP (T3) and at the end of surgery (T4), the blood was sampled via the jugular vein bulb and radial artery for blood gas analysis. RESULTS Compared with group I, the CaO2 of group II at T3 and T4 was increased; in group III, CaO2 and Da-jvO2 at T2 and T3 were decreased, CjvO2 at T2 decreased, and CaO2 and CjvO2 at T4 increased. Compared with group II, CaO2, CjvO2 and Da-jvO2 of group III at T2 and T3 were decreased. CERO2 of the three groups at T3 and T4 were all decreased (P<0.05 or 0.01). The jugular venous oxygen saturation (SjvO2) and VADL of the three groups at each time point were all within the normal range. CONCLUSION The moderate ANH combined with LCVP had no adverse effect on the cerebral oxygen metabolism of the patients with the hepalobectomy.
Cardiopulmonary interventions to decrease blood loss and blood transfusion requirements for liver resection
Gurusamy KS, Li J, Vaughan J, Sharma D, Davidson BR
Cochrane Database of Systematic Reviews. 2012;5:CD007338
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 METHODS 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. 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 o
The role of cell salvage autotransfusion in abdominal aortic aneurysm surgery
Shantikumar S, Patel S, Handa A
European Journal of Vascular and Endovascular Surgery. 2011;42((5):):577-84.
OBJECTIVE Abdominal aortic aneurysm (AAA) repairs, both elective and rupture, are associated with significant blood loss often requiring transfusion. Cell-salvage autotransfusion has been developed to reduce the need for allogeneic blood. We review the literature to delineate the role of cell salvage in reducing allogeneic blood use in open AAA repairs. METHODS A systematic search of the English-language literature was performed using the PubMed, Embase and Cochrane databases up to August 2010. RESULTS Twenty-three studies were identified. Whilst some data are conflicting, cell salvage appears to reduce overall use and exposure to allogeneic blood, and reduces length of intensive care unit and hospital stay after elective AAA repairs. There may be additional benefit by combining cell salvage with other blood-conservation techniques. Use of cell salvage in ruptured AAA repairs consistently reduced blood-product requirements. CONCLUSIONS Cell salvage appears to reduce blood-product use in both elective and rupture AAA repairs. Owing to the heterogeneity in methodology of published data, further study may be required before cell salvage becomes standard practice in open AAA repairs. Copyright 2011. Published by Elsevier Ltd.
A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection
Jarnagin WR, Gonen M, Maithel SK, Fong Y, D'Angelica MI, Dematteo RP, Grant F, Wuest D, Kundu K, Blumgart LH, et al
Annals of Surgery. 2008;248((3):):360-9.
BACKGROUND Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection. METHODS One hundred thirty patients undergoing major hepatic resection (> or =3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8. 0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay. RESULTS From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12. 7% (n = 8) vs. 25. 4% (n = 17), respectively; P = 0. 067. ANH patients were less often transfused intraoperatively (n = 1, 1. 6%) compared with the STD group (n = 7, 10. 4%) (P = 0. 036), had higher postoperative hemoglobin levels (P = 0. 01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss > or =800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18. 2% vs. 42. 4%, P = 0. 045) but also the proportion of patients requiring fresh frozen plasma (21. 1% vs. 48. 3%, P = 0. 025). CONCLUSION For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit.
Acute normovolemic hemodilution combined with controlled hypotension in patients undergoing liver tumorectomy
Yao XH, Wang B, Xiao ZK, Zhou P, Chen CY, Qing ZH
Nan Fang Yi Ke Da Xue Xue Bao [Journal of Southern Medical University]. 2006;26((6):):828-30.
OBJECTIVE To evaluate the effects of acute normovolemic hemodilution (ANH) combined with controlled hypotension on reducing heterogeneous transfusion and safety during liver tumorectomy. METHODS Thirty patients undergoing elective liver tumorectomy were randomly divided into 3 groups (10 each), namely ANH group (group A), ANH combined with controlled hypotension group (group B) and control group (group C). All the patients were anesthetized via endotracheal intubation. Before the operation, ANH was performed in groups A and B after anesthesia induction, and controlled hypotension was initiated in group B during tumorectomy. Blood transfusion and fluid infusion were carried out routinely in group C. Hb and Hct were measured before operation, after ANH, and immediately, 1 day and 7 days after the operation. The difference in intraoperative blood loss and heterogeneous blood transfusion volume in the 3 groups was observed. RESULTS In group A, heterogeneous blood transfusion was avoided in 6 cases and but given in the other cases for an average of 400 ml. In group C, every patient received heterogeneous blood transfusion (664. 8-/+248. 1 ml), but none of the patients received heterogeneous blood in group B. The difference in transfusion volume between the 3 groups was significant (P<0. 01). Hemodynamics was basically stable during operation in the 3 groups. CONCLUSION ANH combined with controlled hypotension is safe and effective for decreasing and even avoiding homologous blood transfusion in liver tumorectomy.
Prospective randomized controlled trial of acute normovolaemic haemodilution in major gastrointestinal surgery
Sanders G, Mellor N, Rickards K, Rushton A, Christie I, Nicholl J, Copplestone A, Hosie K
British Journal of Anaesthesia. 2004;93((6):):775-81.
BACKGROUND The efficacy of acute normovolaemic haemodilution (ANH) remains uncertain because of a lack of well-designed prospective randomized controlled trials. The aim of this study was to assess the effects of ANH on allogeneic transfusion, postoperative complications, and duration of stay. METHODS Consecutive patients undergoing major gastrointestinal surgery were randomized to a planned 3-unit ANH, or no ANH. Both groups underwent identical management including adherence to a transfusion protocol after surgery. Outcome measures included the number of patients receiving allogeneic blood, complications, and duration of stay. RESULTS 380 patients were screened of which 160 were included in the study, median age was 62 yr (range 23-90), 'ANH' n=78, 'no ANH' n=82. There was no significant difference between groups in the number of patients receiving allogeneic blood 22/78 (28%) vs 25/82 (30%), the total number of allogeneic units transfused (90 vs 93), complication rate, or duration of stay. Haemodilution significantly increased anaesthetic time, median 55 (range 15-90) vs 40 min (range 17-80) (P<0. 001). Significantly fewer patients in the ANH group experienced oliguria in the immediate postoperative period 37/78 (47%) vs 55/82 (67%) (P=0. 012). The most significant factors affecting transfusion were blood loss, starting haemoglobin, and age. When compared with ASA-matched historical controls, the introduction of a transfusion protocol reduced the transfusion rate in colorectal patients from 136/333 (41%) to 37/138 (27%), P=0. 004. CONCLUSIONS In this large pragmatic study, ANH did not affect allogeneic transfusion rate in major gastrointestinal surgery. Preoperative haemoglobin, blood loss, and transfusion protocol are the key factors influencing allogeneic transfusion.
Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections
Matot I, Scheinin O, Jurim O, Eid A
BACKGROUND Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH). METHODS The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population. RESULTS During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups. CONCLUSIONS Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood.