A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Intraoperative Red Blood Cell Transfusion Strategies
Annals of surgery. 2021
OBJECTIVE The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. SUMMARY OF BACKGROUND DATA RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. METHODS The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. RESULTS Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. CONCLUSIONS Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.
Adult patients undergoing surgery (14 studies, n= 8,641).
Restrictive blood transfusion strategy.
Liberal blood transfusion strategy.
There was no difference in 30-day mortality relative risk (RR) 0.96, and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53) and perioperative (RR 0.70) blood transfusions were significantly lower in the restrictive group compared to the liberal group.
Passive Versus Active Intra-Abdominal Drainage Following Pancreatic Resection: Does A Superior Drainage System Exist? A Systematic Review and Meta-Analysis
World journal of surgery. 2021
Postoperative pancreatic fistula (POPF) is a major source of morbidity following pancreatic resection. Surgically placed drains under suction or gravity are routinely used to help mitigate the complications associated with POPF. Controversy exists as to whether one of these drain management strategies is superior. The objective was to identify and compare the incidence of POPF, adverse events, and resource utilization associated with passive gravity (PG) versus active suction (AS) drainage following pancreatic resection. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from inception to May 18, 2020. Outcomes of interest included POPF, post-pancreatectomy hemorrhage (PPH), surgical site infection (SSI), other major morbidity, and resource utilization. Descriptive qualitative and pooled quantitative meta-analyses were performed. One randomized control trial and five cohort studies involving 10 663 patients were included. Meta-analysis found no difference in the odds of developing POPF between AS and PG (p = 0.78). There were no differences in other endpoints including PPH (p = 0.58), SSI (wound p = 0.21, organ space p = 0.05), major morbidity (p = 0.71), or resource utilization (p = 0.72). The risk of POPF or other adverse outcomes is not impacted by drain management following pancreatic resection. Based on current evidence, a suggestion cannot be made to support the use of one drain over another at this time. There is a trend toward increased intra-abdominal wound infections with AS drains (p = 0.05) that merits further investigation.
Techniques for blood loss estimation in major non-cardiac surgery: a systematic review and meta-analysis
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2020
PURPOSE Estimated blood loss (EBL) is an important tool in clinical decision-making and surgical outcomes research. It guides perioperative transfusion practice and serves as a key predictor of short-term perioperative risks and long-term oncologic outcomes. Despite its widespread clinical and research use, there is no gold standard for blood loss estimation. We sought to systematically review and compare techniques for intraoperative blood loss estimation in major non-cardiac surgery with the objective of informing clinical estimation and research standards. SOURCE A structured search strategy was applied to Ovid Medline, Embase, and Cochrane Library databases from inception to March 2020, to identify studies comparing methods of intraoperative blood loss in adult patients undergoing major non-cardiac surgery. We summarized agreement between groups of pairwise comparisons as visual estimation vs formula estimation, visual estimation vs other, and formula estimation vs other. For each of these comparisons, we described tendencies for higher or lower EBL values, consistency of findings, pooled mean differences, standard deviations, and confidence intervals. PRINCIPLE FINDINGS We included 26 studies involving 3,297 patients in this review. We found that visual estimation is the most frequently studied technique. In addition, visual techniques tended to provide lower EBL values than formula-based estimation or other techniques, though this effect was not statistically significant in pooled analyses likely due to sample size limitations. When accounting for the contextual mean blood loss, similar case-to-case variation exists for all estimation techniques. CONCLUSIONS We found that significant case-by-case variation exists for all methods of blood loss evaluation and that there is significant disagreement between techniques. Given the importance placed on EBL, particularly for perioperative prognostication models, clinicians should consider the universal adoption of a practical and reproducible method for blood loss evaluation. TRIAL REGISTRATION PROSPERO (CRD42015029439); registered: 18 November 2015.PROSPERO (CRD42015029439); registered: 18 November 2015.
Adult patients undergoing major non-cardiac surgery (26 studies, n= 3,297).
Visual estimation of blood loss.
Formula estimation of blood loss, and other tecnniques for estimating blood loss.
Visual estimation was the most frequently studied technique. Visual techniques tended to provide lower estimated blood loss values than formula-based estimation or other techniques, though this effect was not statistically significant in pooled analyses. When accounting for the contextual mean blood loss, similar case-to-case variation existed for all estimation techniques.
Intraoperative Red Blood Cell Transfusion Decision-Making: A systematic Review of Guidelines
Annals of surgery. 2020
OBJECTIVES The objective of this work was to carry out a systematic review of clinical practice guidelines (CPGs) pertaining to intraoperative red blood cell (RBC) transfusions, in terms of indications, decision-making, and supporting evidence base. SUMMARY BACKGROUND DATA Red blood cell (RBC) transfusions are common during surgery and there is evidence of wide variability in practice. METHODS Major electronic databases (MEDLINE, EMBASE, and CINAHL), guideline clearinghouses and Google Scholar were systematically searched from inception to January 2019 for CPGs pertaining to indications for intraoperative RBC transfusion. Eligible guidelines were retrieved and their quality assessed using AGREE II. Relevant recommendations were abstracted and synthesized to allow for a comparison between guidelines. RESULTS Ten guidelines published between 1992 and 2018 provided indications for intraoperative transfusions. No guideline addressed intraoperative transfusion decision-making as its primary focus. Six guidelines provided criteria for transfusion based on hemoglobin (range 6.0-10.0 g/dL) or hematocrit (<30%) triggers. In the absence of objective transfusion rules, CPGs recommended considering other parameters such as blood loss (n = 7), signs of end organ ischemia (n = 5), and hemodynamics (n = 4). Evidence supporting intraoperative recommendations was extrapolated primarily from the non-operative setting. There was wide variability in the quality of included guidelines based on AGREE II scores. CONCLUSION This review has identified several clinical practice guidelines providing recommendations for intraoperative transfusion. The existing guidelines were noted to be highly variable in their recommendations and to lack a sufficient evidence base from the intraoperative setting. This represents a major knowledge gap in the literature.
Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility
The British journal of surgery. 2020
BACKGROUND Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3.1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0.456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0.069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7.6(1.9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0.326). CONCLUSION Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).
The safety and efficacy of hypovolemic phlebotomy on blood loss and transfusion in liver surgery: a systematic review and meta-analysis
HPB : the official journal of the International Hepato Pancreato Biliary Association. 2019
BACKGROUND Hypovolemic phlebotomy (HP) is a novel intervention that involves intraoperative removal of whole blood (7-10 mL/kg) without volume replacement. The subsequent central venous pressure (CVP) reduction is hypothesized to decrease blood loss and the need for blood transfusion. The objective was to conduct a systematic assessment of the safety and efficacy of HP on blood loss and transfusion in the liver surgery literature. METHODS MEDLINE, EMBASE, and Cochrane Library databases were searched. Outcomes of interest included blood loss, allogenic red blood cell transfusion, postoperative adverse events, and CVP change. A qualitative synthesis and meta-analysis were performed as appropriate. RESULTS Four cohort studies, one case series, and three randomized controlled trials involving 2255 patients were included. Meta-analysis of studies involving liver resections for any indication (n = 6) found no difference in transfusion (OR 0.38, p = 0.12) or incidence of adverse events with HP compared to non-use. Pooling of studies involving liver resections for an underlying pathology (n = 4) revealed HP was associated with significant reduction in transfusion (OR 0.25, p = 0.03) but no differences in blood loss (-173 mL, p = 0.17). CONCLUSION This review suggests HP is safe and associated with decreased transfusion in patients undergoing liver surgery. It supports further investigation.
The impact of perioperative red blood cell transfusions in patients undergoing liver resection: a systematic review
Hpb : the Official Journal of the International Hepato Pancreato Biliary Association. 2017;19((4):):321-330
BACKGROUND Liver resection is associated with a high proportion of red blood cell transfusions. There is a proposed association between perioperative transfusions and increased risk of complications and tumor recurrence. This study reviews the evidence of this association in the literature. METHODS The Medline, EMBASE, and Cochrane databases were searched for clinical trials or observational studies of patients undergoing liver resection that compared patients who did and did not receive a perioperative red blood cell transfusion. Outcomes were mortality, complications, and cancer survival. RESULTS Twenty-two studies involving 6832 patients were included. All studies were retrospective, with no clinical trials. No studies were scored as low risk of bias. The overall proportion of patients transfused was 38.3%. After multivariate analysis, 1 of 5 studies demonstrated an association between transfusion and increased mortality; 5 of 6 demonstrated an association between transfusion and increased complications; and 10 of 18 demonstrated an association between transfusion and decreased cancer survival. CONCLUSION This review supports the evidence linking perioperative blood transfusions to negative outcomes. The most convincing association was with post-operative complications, some association with long-term cancer outcomes, and no convincing association with mortality. These findings support the initiation, and further study, of restrictive transfusion protocols.
The efficacy of postoperative iron therapy in improving clinical and patient-centered outcomes following surgery: a systematic review and meta-analysis
Transfusion Medicine Reviews. 2017;32((2):):89-101
Postoperative anemia is a common occurrence in surgical patients and leads to an increased risk for allogeneic blood transfusions. The efficacy of iron therapy in treating postoperative anemia has not been firmly established. The objective of this systematic review was to evaluate the efficacy of postoperative oral and intravenous (IV) iron therapy in increasing hemoglobin levels and improving patient outcomes following elective surgery. The databases Medline, EMBASE, CENTRAL, the Transfusion Evidence Library, and ClinicalTrials.gov were searched. Eligible studies were randomized controlled trials or prospective cohorts having a control group, where postoperative oral or IV iron was administered to elective surgery patients. Primary outcomes were hemoglobin levels and patient-centered outcomes of quality of life and functioning. Secondary outcomes were the safety of postoperative iron and blood transfusion requirement. Meta-analysis using a random-effects model was performed. Seventeen relevant studies were identified, of which 7 investigated IV iron, 7 investigated oral iron, and 3 compared IV with oral iron. Postoperative oral and IV iron therapies were ineffective in improving quality of life and functioning (the Grading of Recommendations Assessment, Development and Evaluation [GRADE]: moderate-low quality). Compared with control, IV iron increased mean hemoglobin levels by 3.40 g/L (95% confidence interval [CI]: 1.18-5.62) (GRADE moderate quality); however, this increase is likely not clinically meaningful. Overall, oral iron was ineffective in increasing hemoglobin concentrations compared with control (mean difference=0.77, 95% CI: -1.48-3.01) (GRADE moderate quality). Postoperative iron therapy did not significantly reduce the risk of blood transfusion (relative risk=0.75; 95% CI: 0.53-1.07) (GRADE low quality). IV iron was not associated with a significantly increased risk of adverse events (relative risk=4.50, 95% CI: 0.64-31.56). There was insufficient information to determine the risk of adverse events for postoperative oral iron. This systematic review found no evidence to support the routine use of postoperative iron therapy in all elective surgery patient populations; however, results are based largely on studies with non-iron-deficient patients preoperatively. Further research on the role of postoperative IV iron is warranted for certain high-risk groups, including patients with iron deficiency or anemia prior to surgery. This systematic review is registered in PROSPERO (CRD42017057837).