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Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis
Wang, T., Wang, J., Zhang, M., Zhang, H., Zhang, Q., Liu, G., Dong, W., Wang, Y., Ji, B.
BMC anesthesiology. 2024;24(1):26
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Editor's Choice
Abstract
BACKGROUND In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. METHODS The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. RESULTS The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. CONCLUSION Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.
PICO Summary
Population
Adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (10 randomised controlled trials).
Intervention
Network meta-analysis (NMA) to perform direct comparisons, including albumin vs. artificial colloid and artificial colloid vs. crystalloid, and to obtain indirect evidence for the comparisons between albumin and crystalloid priming strategies.
Comparison
Outcome
Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative red blood cell (RBC) transfusions (MD -0.68U; 95% CI [-1.26, -0.09U]) and intraoperative RBC transfusions (MD -0.20U; 95% CI [-0.39, -0.01U]) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant (MD -0.16U; 95% CI: [-0.45, 0.14U]). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance.
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Perioperative transfusion and long-term mortality after cardiac surgery: a meta-analysis
Woldendorp K, Manuel L, Srivastava A, Doane M, Bassin L, Marshman D
General thoracic and cardiovascular surgery. 2023
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Editor's Choice
Abstract
OBJECTIVES Cardiac surgical procedures are associated with a high incidence of periprocedural blood loss and blood transfusion. Although both may be associated with a range of postoperative complications there is disagreement on the impact of blood transfusion on long-term mortality. This study aims to provide a comprehensive review of the published outcomes of perioperative blood transfusion, examined as a whole and by index procedure. METHODS A systematic review of perioperative blood transfusion cardiac surgical patients was conducted. Outcomes related to blood transfusion were analysed in a meta-analysis and aggregate survival data were derived to examine long-term survival. RESULTS Thirty-nine studies with 180,074 patients were identified, the majority (61.2%) undergoing coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR 3.87, p < 0.001). After a median of 6.4 years (range 1-15), mortality remained significantly higher for those who received a perioperative transfusion (OR 2.01, p < 0.001). Pooled hazard ratio for long-term mortality similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies. CONCLUSIONS Perioperative red blood transfusion appears to be associated with a significant reduction in long-term survival for patients after cardiac surgery. Strategies such as preoperative optimisation, intraoperative blood conservation, judicious use of postoperative transfusions, and professional development into minimally invasive techniques should be utilised where appropriate to minimise the need for perioperative transfusions.
PICO Summary
Population
Patients undergoing cardiac surgery (39 studies, n= 180,074).
Intervention
Red blood cell (RBC) transfusion.
Comparison
No RBC transfusion.
Outcome
The meta-analysis identified 180,074 patients with follow-up data ranging from 1 to 15 years. The majority (61.2%) of patients underwent coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR= 3.87). After a median of 6.4 years (range 1, 15), mortality remained significantly higher for those who received a perioperative transfusion (OR= 2.01). Pooled hazard ratio for long-term mortality was similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies.
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Prothrombin Complex Concentrate versus Fresh Frozen Plasma in Adult Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis
Viana, P., Relvas, J. H., Persson, M., Cabral, T. D. D., Persson, J. E., de Oliveira, J. S., Bonow, P., Freire, C. V. S., Amaral, S.
Journal of chest surgery. 2023
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Editor's Choice
Abstract
BACKGROUND Prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) are commonly used to manage bleeding in patients during cardiac surgery. However, the relative efficacy and safety of these 2 strategies remain uncertain. METHODS MEDLINE, Embase, and Cochrane were searched for studies comparing PCC and FFP in patients who underwent cardiac surgery complicated by bleeding. Review Manager (RevMan) ver. 5.4 (Nordic Cochrane Centre, The Cochrane Collaboration) was used for statistical analysis. Binary and continuous outcomes were compared using pooled risk ratios and mean differences, respectively. The meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews under protocol number CRD42022379144. RESULTS We included 8 studies with 1,500 patients, of whom 613 (40.9%) received PCC. The mean follow-up period ranged from 28 to 90 days. The PCC group had significantly lower chest tube drainage at 24 hours (mean difference [MD], -148.50 mL; 95% CI, -253.02 to -43.99 mL; p=0.005; I(2)=42%). Fewer units of red blood cells (RBCs) were transfused within the first 24 hours (MD, -1.02 units; 95% CI, -1.81 to -0.24 units; p=0.01; I(2)=56%), and fewer patients required RBC transfusion within the first 24 hours (risk ratio, 0.85; 95% CI, 0.78-0.93; p<0.007; I(2)=45%) in the PCC group. There were no statistically significant differences in secondary outcomes. Nonetheless, a subgroup analysis of randomized controlled trials failed to corroborate the results obtained from the main analysis. CONCLUSION Our findings suggest that PCC can be effective, without increased adverse events, when compared with FFP in patients undergoing cardiac surgery complicated by bleeding.
PICO Summary
Population
Adult patients undergoing cardiac surgery (8 studies, n= 1,500).
Intervention
Prothrombin complex concentrate (PCC).
Comparison
Fresh frozen plasma.
Outcome
The PCC group had significantly lower chest tube drainage at 24 hours (mean difference (MD), -148.50 mL; 95% CI [-253.02, -43.99 mL]; I(2)= 42%). Fewer units of red blood cells (RBCs) were transfused within the first 24 hours (MD -1.02 units; 95% CI [-1.81, -0.24 units]; I(2)= 56%), and fewer patients required RBC transfusion within the first 24 hours (risk ratio, 0.85; 95% CI [0.78, 0.93; I(2)= 45%) in the PCC group. There were no statistically significant differences in secondary outcomes. Nonetheless, a subgroup analysis of randomized controlled trials failed to corroborate the results obtained from the main analysis.
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Intravenous iron administration before cardiac surgery reduces red blood cell transfusion in patients without anaemia
Friedman, T., Dann, E. J., Bitton-Worms, K., Makhoul, M., Glam, R., Weis, A., Tam, D. Y., Bolotin, G.
British journal of anaesthesia. 2023
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Editor's Choice
Abstract
BACKGROUND Reducing the need for blood transfusion among patients undergoing cardiac surgery FLA reduce postoperative complications and mortality. Our study aimed to assess the effects of administering preoperative i.v. ferric carboxymaltose on postoperative red cell transfusion requirements in patients without anaemia undergoing on-pump cardiac surgery. METHODS This double-blind, randomised, placebo-controlled trial was conducted between October 2016 and November 2019, with a follow-up period of up to 6 weeks after surgery. Patients without anaemia who underwent on-pump cardiac surgery were included as participants and administered i.v. iron in the form of ferric carboxymaltose or placebo once, 24-72 h before surgery. The primary outcome was the number of red cell units transfused during the first four postoperative days, and the secondary outcome measures were blood haemoglobin concentrations at 4 days and 6 weeks after surgery. RESULTS The 200 patients included were randomly assigned to the ferric carboxymaltose (n=102) and placebo (n=98) groups. By postoperative Day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs 1.6 (4.4), respectively; P=0.007. The mean haemoglobin concentrations on postoperative Day 4 were 9.7 (1) g dl(-1) and 9.3 (1) g dl(-1), respectively (P=0.03). Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl(-1) and 11.8 (1.5) g dl(-1), respectively (P=0.012). CONCLUSIONS In patients without anaemia undergoing on-pump cardiac surgery, treatment with a single dose of 1000 mg ferric carboxymaltose i.v. 1-3 days before surgery significantly reduced the need for red cell transfusions and increased the postoperative haemoglobin concentration. CLINICAL TRIAL REGISTRATION NCT02939794.
PICO Summary
Population
Patients without anaemia who underwent on-pump cardiac surgery (n= 200).
Intervention
Ferric carboxymaltose (n= 102).
Comparison
Placebo (n= 98).
Outcome
By postoperative day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs. 1.6 (4.4), respectively. The mean haemoglobin concentrations on postoperative day 4 were 9.7 (1) g dl(-1) and 9.3 (1) g dl(-1), respectively. Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl(-1) and 11.8 (1.5) g dl(-1), respectively.
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Drugs to reduce bleeding and transfusion in major open vascular or endovascular surgery: a systematic review and network meta-analysis
Beverly A, Ong G, Kimber C, Sandercock J, Dorée C, Welton NJ, Wicks P, Estcourt LJ
The Cochrane database of systematic reviews. 2023;2(2):Cd013649
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Editor's Choice
Abstract
BACKGROUND Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion. OBJECTIVES To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss. SEARCH METHODS We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status. SELECTION CRITERIA We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence. MAIN RESULTS We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes. AUTHORS' CONCLUSIONS Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.
PICO Summary
Population
Adults undergoing major vascular surgery or vascular procedures with a risk of moderate or severe blood loss (22 randomised controlled trials, n= 3,393).
Intervention
Drug treatments to reduce bleeding: anti-fibrinolytic and haemostatic drugs and agents.
Comparison
Placebo, usual care or another drug regimen.
Outcome
The primary outcomes were units of red blood cells transfused, all-cause mortality and thromboembolic events. There was too little data for a network meta-analysis. The reporting of outcomes was sparse. There was no evidence of increased risk of thromboembolic events with tranexamic acid [low certainty evidence]. The authors reported a need for larger trials with better reporting of post-surgical outcomes.
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Effect of red blood cell storage time in pediatric cardiac surgery patients: A subgroup analysis of a randomized controlled trial
Martin, S. M., Tucci, M., Spinella, P. C., Ducruet, T., Fergusson, D. A., Freed, D. H., Lacroix, J., Poirier, N., Sivarajan, V. B., Steiner, M. E., et al
JTCVS open. 2023;15:454-467
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Editor's Choice
Abstract
OBJECTIVE This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery. METHODS Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death. RESULTS One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P = .49). CONCLUSIONS In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results.
PICO Summary
Population
Children admitted to a paediatric intensive care unit after cardiac surgery with cardiopulmonary bypass, enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial (ABC-PICU), (n= 178).
Intervention
Fresh (stored ≤7 days) red blood cells (RBCs), (n= 89).
Comparison
Standard-issue RBCs (n= 89).
Outcome
The authors performed a preplanned subgroup analysis of the ABC-PICU trial. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days post-randomization or at paediatric intensive care unit discharge, or death. There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12; 95% CI [0.81, 1.54] and an unadjusted absolute risk difference of 5.1%; 95% CI [-9.5%, 19.8%].
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Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients
Abrahamyan L, Tomlinson G, Callum J, Carcone S, Grewal D, Bartoszko J, Krahn M, Karkouti K
JAMA surgery. 2023
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Editor's Choice
Abstract
IMPORTANCE Excessive bleeding requiring fibrinogen replacement is a serious complication of cardiac surgery. However, the relative cost-effectiveness of the 2 available therapies-fibrinogen concentrate and cryoprecipitate-is unknown. OBJECTIVE To determine cost-effectiveness of fibrinogen concentrate vs cryoprecipitate for managing active bleeding in adult patients who underwent cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS A within-trial economic evaluation of the Fibrinogen Replenishment in Surgery (FIBERS) randomized clinical trial (February 2017 to November 2018) that took place at 4 hospitals based in Ontario, Canada, hospitals examined all in-hospital resource utilization costs and allogeneic blood product (ABP) transfusion costs incurred within 28 days of surgery. Participants included a subset of 495 adult patients from the FIBERS trial who underwent cardiac surgery and developed active bleeding and acquired hypofibrinogenemia requiring fibrinogen replacement. INTERVENTIONS Fibrinogen concentrate (4 g per dose) or cryoprecipitate (10 units per dose) randomized (1:1) up to 24 hours postcardiopulmonary bypass. MAIN OUTCOMES AND MEASURES Effectiveness outcomes included number of ABPs administered within 24 hours and 7 days of cardiopulmonary bypass. ABP transfusion (7-day) and in-hospital resource utilization (28-day) costs were evaluated and a multivariable net benefit regression model built for the full sample and predefined subgroups. RESULTS Patient level costs for 495 patients were evaluated (mean [SD] age 59.2 [15.4] years and 69.3% male.) Consistent with FIBERS, ABP transfusions and adverse events were similar in both treatment groups. Median (IQR) total 7-day ABP cost was CAD $2280 (US dollars [USD] $1697) (CAD $930 [USD $692]-CAD $4970 [USD $3701]) in the fibrinogen concentrate group and CAD $2770 (USD $1690) (IQR, CAD $1140 [USD $849]-CAD $5000 [USD $3723]) in the cryoprecipitate group. Median (interquartile range) total 28-day cost was CAD $38 180 (USD $28 431) $(IQR, CAD $26 350 [USD $19 622]-CAD $65 080 [USD $48 463]) in the fibrinogen concentrate group and CAD $38 790 (USD $28 886) (IQR, CAD $26 180 [USD $19 495]-CAD $70 380 [USD $52 409]) in the cryoprecipitate group. After exclusion of patients who were critically ill before surgery (11%) due to substantial variability in costs, the incremental net benefit of fibrinogen concentrate vs cryoprecipitate was positive (probability of being cost-effective 86% and 97% at $0 and CAD $2000 (USD $1489) willingness-to-pay, respectively). Net benefit was highly uncertain for nonelective and patients with critical illness. CONCLUSIONS AND RELEVANCE Fibrinogen concentrate is cost-effective when compared with cryoprecipitate in most bleeding adult patients who underwent cardiac surgery with acquired hypofibrinogenemia requiring fibrinogen replacement. The generalizability of these findings outside the Canadian health system needs to be verified.
PICO Summary
Population
A subset of patients enrolled in the FIBERS trial who underwent cardiac surgery and experienced bleeding resulting in acquired hyperfibrinogenemia (n= 495).
Intervention
Fibrinogen concentrate (n= 251).
Comparison
Cryoprecipitate (n= 244).
Outcome
Patient level costs were evaluated. Median (interquartile range (IQR)) total 7-day allogeneic blood product (ABP) cost was CAD $2,280 (US dollars [USD] $1,697) (CAD $930 [USD $692]-CAD $4,970 [USD $3,701]) in the fibrinogen concentrate group and CAD $2,770 (USD $1,690) (IQR, CAD $1,140 [USD $849]-CAD $5,000 [USD $3,723]) in the cryoprecipitate group. Median (IQR) total 28-day cost was CAD $38,180 (USD $28 431) (IQR, CAD $26,350 [USD $19,622]-CAD $65,080 [USD $48,463]) in the fibrinogen concentrate group and CAD $38,790 (USD $28,886) (IQR, CAD $26,180 [USD $19,495]-CAD $70,380 [USD $52,409]) in the cryoprecipitate group. After exclusion of patients who were critically ill before surgery (11%) due to substantial variability in costs, the incremental net benefit of fibrinogen concentrate vs. cryoprecipitate was positive (probability of being cost-effective 86% and 97% at $0 and CAD $2,000 (USD $1,489) willingness-to-pay, respectively). Net benefit was highly uncertain for nonelective and patients with critical illness.
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Prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis of non-pharmacological interventions
Hariri, G., Collet, L., Duarte, L., Martin, G. L., Resche-Rigon, M., Lebreton, G., Bouglé, A., Dechartres, A.
Critical care (London, England). 2023;27(1):354
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Editor's Choice
Abstract
BACKGROUND Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. METHODS We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I(2) = 0%; P(het) = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I(2) = 23%; P(het) = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I(2) = 53%; P(het) < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; P(het) = 0.67; I(2) = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; P(het) = 0.25; I(2) = 26%). CONCLUSIONS Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.
PICO Summary
Population
Adult patients undergoing cardiac surgery such as coronary artery bypass grafting and/or valve surgery (86 randomised controlled trials (RCTs) n= 25,855).
Intervention
Non-pharmacological interventions to reduce the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI): Goal directed perfusion (GDP), pulsatile flow during cardiopulmonary bypass (CPB), minimally invasive extracorporeal circulation (MECC), epidural analgesia, remote ischemic preconditioning (RIPc), tight glycemic control, kidney disease improving global outcomes care bundle, hyperoxia during CPB, restrictive transfusion strategy, high target arterial pressure.
Comparison
Usual care.
Outcome
No intervention had high-quality evidence to reduce CSA-AKI. From the included studies, the most frequent intervention was RIPc (31 RCTs, n= 7,738), MECC, (14 RCTs, n= 1,617) and pulsatile blood flow during CPB (10 RCTs, n= 1,993). Three interventions were associated with a significantly reduced risk of CSA-AKI: GDP, RIPc and pulsatile flow during CPB.
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9.
Intravenous albumin in cardiac and vascular surgery: a systematic review and meta-analysis
Skubas, N. J., Callum, J., Bathla, A., Keshavarz, H., Fergusson, D., Wu, B., Stanworth, S., Shehata, N.
British journal of anaesthesia. 2023
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Editor's Choice
Abstract
BACKGROUND Intravenous albumin is commonly utilised in cardiovascular surgery for priming of the cardiopulmonary bypass circuit, volume replacement, or both, although the evidence to support this practice is uncertain. The aim was to compare i.v. albumin with synthetic colloids and crystalloids for paediatric and adult patients undergoing cardiovascular surgery for all-cause mortality and other perioperative outcomes. METHODS A systematic review and meta-analysis of randomised controlled trials (RCTs) of i.v. albumin compared with synthetic colloids and crystalloids on the primary outcome of all-cause mortality was conducted. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use; subgroups were analysed by age, comparator fluid, and intended use (priming, volume, or both). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CCRT) from 1946 to November 23, 2022. RESULTS Of 42 RCTs, mortality was assessed in 15 trials (2711 cardiac surgery patients) and the risk difference was 0.00, 95% confidence interval (CI) -0.01 to 0.01, I(2)=0%. Among secondary outcomes, i.v. albumin resulted in smaller fluid balance, mean difference -0.55 L, 95% CI -1.06 to -0.4, I(2)=90% (nine studies, 1975 patients) and higher albumin concentrations, mean difference 7.77 g L(-1), 95% CI 3.73-11.8, I(2)=95% (six studies, 325 patients). CONCLUSIONS Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids. The lack of improvement in patient-important outcomes with albumin and its higher cost suggests it should be used restrictively. SYSTEMATIC REVIEW PROTOCOL PROSPERO; CRD42020171876.
PICO Summary
Population
Paediatric and adult patients undergoing cardiovascular surgery (42 randomised controlled trials).
Intervention
Intravenous albumin.
Comparison
Synthetic colloids and crystalloids.
Outcome
Primary outcome of all-cause mortality. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use. Mortality was assessed in 15 trials (n= 2,711) and the risk difference was 0.00; 95% confidence interval (CI) [-0.01, 0.01] I(2)= 0%. Among secondary outcomes, intravenous albumin resulted in smaller fluid balance, mean difference -0.55 L; 95% CI [-1.06, -0.4], I(2)= 90% (nine studies, n= 1,975) and higher albumin concentrations, mean difference 7.77 gL(-1); 95% CI [3.73, 11.8], I(2)= 95% (six studies, n= 325). Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids.
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10.
Prothrombin Complex Concentrate vs Plasma for Post-Cardiopulmonary Bypass Coagulopathy and Bleeding: A Randomized Clinical Trial
Smith MM, Schroeder DR, Nelson JA, Mauermann WJ, Welsby IJ, Pochettino A, Montonye BL, Assawakawintip C, Nuttall GA
JAMA surgery. 2022
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Editor's Choice
Abstract
IMPORTANCE Post-cardiopulmonary bypass (CPB) coagulopathy and bleeding are among the most common reasons for blood product transfusion in surgical practices. Current retrospective data suggest lower transfusion rates and blood loss in patients receiving prothrombin complex concentrate (PCC) compared with plasma after cardiac surgery. OBJECTIVE To analyze perioperative bleeding and transfusion outcomes in patients undergoing cardiac surgery who develop microvascular bleeding and receive treatment with either PCC or plasma. DESIGN, SETTING, AND PARTICIPANTS A single-institution, prospective, randomized clinical trial performed at a high-volume cardiac surgical center. Patients were aged 18 years or older and undergoing cardiac surgery with CPB. Patients undergoing complex cardiac surgical procedures (eg, aortic replacement surgery, multiple procedures, or repeated sternotomy) were preferentially targeted for enrollment. During the study period, 756 patients were approached for enrollment, and 553 patients were randomized. Of the 553 randomized patients, 100 patients met criteria for study intervention. INTERVENTIONS Patients with excessive microvascular bleeding, a prothombin time (PT) greater than 16.6 seconds, and an international normalized ratio (INR) greater than 1.6 were randomized to receive treatment with either PCC or plasma. The PCC dose was 15 IU/kg or closest standardized dose; the plasma dose was a suggested volume of 10 to 15 mL/kg rounded to the nearest unit. MAIN OUTCOMES AND MEASURES The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. Secondary outcomes were PT/INR, rates of intraoperative red blood cell (RBC) transfusion after treatment, avoidance of allogeneic transfusion from the intraoperative period to the end of postoperative day 1, postoperative bleeding, and adverse events. RESULTS One hundred patients (mean [SD] age, 66.8 [13.7] years; 61 [61.0%] male; and 1 [1.0%] Black, 1 [1.0%] Hispanic, and 98 [98.0%] White) received the study intervention (49 plasma and 51 PCC). There was no significant difference in chest tube output between the plasma and PCC groups (median [IQR], 1022 [799-1575] mL vs 937 [708-1443] mL). After treatment, patients in the PCC arm had a greater improvement in PT (effect estimate, -1.37 seconds [95% CI, -1.91 to -0.84]; P < .001) and INR (effect estimate, -0.12 [95% CI, -0.16 to -0.07]; P < .001). Fewer patients in the PCC group required intraoperative RBC transfusion after treatment (7 of 51 patients [13.7%] vs 15 of 49 patients [30.6%]; P = .04); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events. CONCLUSIONS AND RELEVANCE The results of this study suggest a similar overall safety and efficacy profile for PCCs compared with plasma in this clinical context, with fewer posttreatment intraoperative RBC transfusions, improved PT/INR correction, and higher likelihood of allogeneic transfusion avoidance in patients receiving PCCs. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02557672.
PICO Summary
Population
Patients undergoing cardiac surgery who developed microvascular bleeding (n= 100).
Intervention
Prothrombin complex concentrate (PCC), (n= 51).
Comparison
Plasma (n= 49).
Outcome
The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. There was no significant difference in chest tube output between the plasma and PCC groups (median [IQR], 1022 [799, 1575] mL vs. 937 [708, 1443] mL). After treatment, patients in the PCC group had a greater improvement in prothombin time, (effect estimate, -1.37 seconds, 95% CI [-1.91, -0.84]) and international normalized ratio (effect estimate, -0.12, 95% CI [-0.16, -0.07]). Fewer patients in the PCC group required intraoperative red blood cell transfusion after treatment (7 of 51 patients [13.7%] vs. 15 of 49 patients [30.6%]); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs. none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events.