Is there a renoprotective value to leukodepletion during heart valve surgery? A randomized controlled trial (ROLO)
Journal of cardiothoracic surgery. 2021;16(1):58
BACKGROUND Acute Kidney Injury (AKI) adversely affects outcomes after cardiac surgery. A major mediator of AKI is the activation of leukocytes through exposure to the cardiopulmonary bypass circuit. We evaluate the use of leukodepletion filters throughout bypass to protect against post-operative AKI by removing activated leukocytes during cardiac surgery. METHODS This is a single-centre, double-blind, randomized controlled trial comparing the use of leukodepletion versus a standard arterial filter throughout bypass. Elective adult patients undergoing heart valve surgery with or without concomitant procedures were investigated. The primary clinical outcome measured was the development of AKI according to the KDIGO criteria. Secondary measures included biomarkers of renal tubular damage (urinary Retinol Binding Protein and Kidney Injury Molecule-1), glomerular kidney injury (urinary Micro Albumin and serum Cystatin C) and urinary Neutrophil Gelatinase Associated Lipocalin, as well as the length of hospital stay and quality of life measures through EQ-5D-5L questionnaires. RESULTS The ROLO trial randomized 64 participants with a rate of recruitment higher than anticipated (57% achieved, 40% anticipated). The incidence of AKI was greater in the leukodepletion filter group (44% versus 23%, risk difference 21, 95% CI - 2 to 44%). This clinical finding was supported by biomarker levels especially by a tendency toward glomerular insult at 48 h, demonstrated by a raised serum Cystatin C (mean difference 0.11, 95% CI 0.00 to 0.23, p = 0.068) in the leukodepleted group. There was however no clear association between the incidence or severity of AKI and length of hospital stay. On average, health related quality of life returned to pre-operative levels in both groups within 3 months of surgery. CONCLUSIONS Leukocyte depletion during cardiopulmonary bypass does not significantly reduce the incidence of AKI after valvular heart surgery. Other methods to ameliorate renal dysfunction after cardiac surgery need to be investigated. TRIAL REGISTRATION The trial was registered by the International Standard Randomized Controlled Trial Number Registry ISRCTN42121335 . Registered on the 18 February 2014. The trial was run by the Bristol Clinical Trials and Evaluation Unit. This trial was financially supported by the National Institute of Health Research (Research for Patient Benefit), award ID: PB-PG-0711-25,090.
Transfusion Strategies for Pediatric Cardiac Surgery: A Meta-Analysis and Trial Sequential Analysis
Pediatric cardiology. 2021
This study aimed to compare the effects of restrictive and liberal red blood cell (RBC) transfusion strategies on pediatric patients undergoing cardiac surgery, including cyanotic and non-cyanotic children. A literature search of the MEDLINE, EMBASE, PubMed, and the Cochrane Library database was conducted. Meta-analyses were carried out comparing restrictive and liberal transfusion strategies. Subgroup analyses were performed based on the basis of cyanotic status. Five randomized controlled trials with a total of 497 children were included. There was no significant difference in the risk of in-hospital mortality between the two transfusion strategies (risk ratio 1.21; 95% confidence interval 0.49 to 2.99; P = 0.68). The trial sequential analysis suggested that the current meta-analysis had an absence of evidence for in-hospital mortality, and the data were insufficient. Moreover, no significant differences existed between groups in terms of risk of infection, blood loss, duration of mechanical ventilation, pediatric intensive care unit (PICU) stay duration, or hospital stay duration. Cyanotic children treated with a liberal transfusion strategy had a shorter ventilator duration, but the transfusion strategy did not affect in-hospital mortality, infection, hospital stay, or PICU stay duration. On the basis of the available data, our analysis indicates that a liberal transfusion strategy did not lead to a better outcomes, but the data are extremely sparse, which highlights the need for clearer transfusion guidelines specific to this specific population.Trial registration number CRD42018102283.
Cerebral Revascularization for Moyamoya syndrome associated with Sickle Cell Disease: A systematic review of literature on the role of EC-IC bypass in treating neurological manifestations of pediatric patients with Sickle Cell Disease
World neurosurgery. 2020
Moyamoya syndrome (MMS) in patients with sickle cell disease (SCD) accentuates the risk of recurrent strokes. Chronic transfusion therapy (CTT) is an excellent option for preventing recurrent strokes in most SCD patients. In SCD with MMS, CTT may fail as a long-term solution. Cerebral revascularization, in the form of EC-IC bypass, has been shown to prevent recurrent strokes in this cohort. We review the evolution of this paradigm shift in the management of SCD-associated MMS. A systematic review, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol, was conducted. Our primary objectives were: 1.) to study the evolution of cerebral revascularization techniques in management of MMS in SCD; and 2.) to analyze the impact of neurosurgical intervention in this high-risk population. Four patients with SCD-associated MMS, who underwent indirect cerebral revascularization at our institute were retrospectively reviewed. A summary of 13 articles chronicling the advent and subsequent evolution of cerebral revascularization as a viable treatment strategy for stroke prevention in SCD-associated MMS, is presented. Literature review suggests early detection and surgical intervention (in addition to CTT) could significantly reduce stroke recurrence and improve neuro-cognitive outcome. Our short series of 4 patients also had a good outcome and no recurrence of strokes post-operatively. Current literature emphasizes the use of a traditional standardized protocol for early identification (TCDs, selective MRA, and CTT). Early treatment and screening that involves early MR angiography and referral to neurosurgery for revascularization may be considered for this high-risk population.
The effect of restrictive versus liberal transfusion strategies on longer-term outcomes after cardiac surgery: a systematic review and meta-analysis with trial sequential analysis
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2020
PURPOSE Blood transfusions are frequently administered in cardiac surgery. Despite a large number of published studies comparing a "restrictive" strategy with a "liberal" strategy, no clear consensus has emerged to guide blood transfusion practice in cardiac surgery patients. The purpose of this study was to identify, critically appraise, and summarize the evidence on the overall effect of restrictive transfusion strategies compared with liberal transfusion strategies on mortality, other clinical outcomes, and transfusion-related outcomes in adult patients undergoing cardiac surgery. SOURCE We searched MEDLINE (OvidSP), EMBASE (OvidSP) and Cochrane CENTRAL (Wiley) from inception to 1 December 2017 and queried clinical trial registries and conference proceedings for randomized-controlled trials of liberal vs restrictive transfusion strategies in cardiac surgery. PRINCIPAL FINDINGS From 7,908 citations, we included ten trials (9,101 patients) and eight companion publications. Overall, we found no significant difference in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; 95% confidence interval [CI], 0.76 to 1.54; I(2) = 33%; seven trials; 8,661 patients). The use of a restrictive transfusion strategy did not appear to adversely impact any of the secondary clinical outcomes. As expected, the proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; 95% CI, 0.64 to 0.73; I(2) = 56%; 5 trials; 8,534 patients). Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy. CONCLUSIONS In adult patients undergoing cardiac surgery, a restrictive transfusion strategy reduces RBC transfusion without impacting mortality rate or the incidence of other perioperative complications. Nevertheless, further large trials in subgroups of patients, potentially of differing age, are needed to establish firm evidence to guide transfusion in cardiac surgery. TRIAL REGISTRATION PROSPERO (CRD42017071440); registered 20 April, 2018.
Adult patients undergoing cardiac surgery (10 studies, n= 9101).
Restrictive transfusion strategies.
Liberal transfusion strategies.
No significant difference was found in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; I2 (2) = 33%. The proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; I2 (2) = 56%. Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy.
Does Blood Transfusion Have an Effect on Outcomes After Aortic Valve Replacement Surgery?
Heart, lung & circulation. 2020
OBJECTIVE Long-term outcomes following surgical aortic valve replacement (AVR) are excellent. However, there is a significant early morbidity burden. Red cell transfusion is common in the perioperative period and deleterious effects of receiving a transfusion on early postoperative morbidity are well described in observational studies. This study aimed to assess the effect of transfusion on ischaemic or infective outcomes after aortic valve replacement. METHODS Data from 270 patients enrolled in the Manubrium-limited ministernotomy versus conventional sternotomy for aortic valve replacement (MAVRIC) randomised controlled trial was used to create two cohorts, patients that received red cell transfusions following AVR and those that did not. Propensity score matching was performed to limit the effect of confounding variables. Strict transfusion thresholds were maintained, with patients receiving a transfusion if haemoglobin concentration fell below 80 g/L, or if significant bleeding or haemodynamic instability occurred. The primary outcome was a composite of ischaemic event (myocardial infarction, permanent stroke, gut ischaemia or acute kidney injury) or serious infection (sepsis, endocarditis, respiratory tract or wound infection). Patients were followed for 12 weeks following surgery. RESULTS Sixty-three (63) of 270 patients received a red cell transfusion (23.3%). Transfused patients had significantly lower body mass index (BMI), a higher proportion of females, a lower preoperative haemoglobin and haematocrit, a higher EuroSCORE II score, worse renal function and were more likely to have undergone urgent surgery compared to the unadjusted control cohort. Once matched, there was no difference in the primary outcome between cohorts. There was a significantly increased length of hospital stay in the transfused group (median 7 days transfused, median 5 days not-transfused, p=0.001). CONCLUSIONS Red cell transfusion, using a transfusion threshold of 80 g/L, does not appear to be associated with adverse ischaemic or infective outcomes after aortic valve replacement.
Effect of low vs. high haemoglobin transfusion trigger on cardiac output in patients undergoing elective vascular surgery: post-hoc analysis of a randomised trial
Acta anaesthesiologica Scandinavica. 2020
BACKGROUND During vascular surgery, restricted red-cell transfusion reduces frontal lobe oxygen (ScO(2) ) saturation as determined by near-infrared spectroscopy. We evaluated whether inadequate increase in cardiac output (CO) following haemodilution explains reduction in ScO(2) . METHODS This is a post-hoc analysis of data from the Transfusion in Vascular surgery (TV) Trial where patients were randomised on haemoglobin drop below 9.7 g/dL to red-cell transfusion at haemoglobin below 8.0 (low-trigger) vs. 9.7 g/dL (high-trigger). Fluid administration was guided by optimising stroke volume. We compared mean intraoperative levels of CO, haemoglobin, oxygen delivery, and CO at nadir ScO(2) with linear regression adjusted for age, operation type and baseline. Data for forty-six patients randomised before end of surgery were included for analysis. RESULTS The low-trigger resulted in a 7.1% lower mean intraoperative haemoglobin level (mean difference, -0.74 g/dl; P<0.001) and reduced volume of red-cell transfused (median [inter-quartile range], 0 [0-300] vs. 450 ml [300-675]; P<0.001) compared with the high-trigger group. Mean CO during surgery was numerically 7.3% higher in the low-trigger compared with the high-trigger group (mean difference, 0.36 L/min; 95% confidence interval (CI.95), -0.05 to 0.78; P=0.092; n=42). At the nadir ScO(2) -level, CO was 11.9% higher in the low-trigger group (mean difference, 0.58 L/min; CI.95, 0.10 to 1.07; P=0.024). No change in oxygen delivery was detected between trial groups (MD, 1.39 dL(O2) /min; CI.95, -6.16 to 8.93; P=0.721). CONCLUSION Vascular surgical patients exposed to restrictive RBC transfusion elicit the expected increase in CO making it unlikely that their potentially limited cardiac capacity explains the associated ScO(2) decrease.
Association Between Adverse Clinical Outcomes After Coronary Artery Bypass Grafting and Perioperative Blood Transfusions
Critical care nurse. 2019;39(1):26-35
BACKGROUND Bleeding is a serious complication of coronary artery bypass grafting that often leads to blood transfusion. Approximately 50% of patients who have the surgery receive blood products, and blood transfusions play a role in adverse outcomes after the surgery. OBJECTIVE To examine the association between perioperative blood transfusion and postoperative adverse outcomes in patients undergoing coronary artery bypass grafting. METHODS A systematic review of the literature, via the matrix method of quality evaluation, was conducted. PubMed, CINAHL, and Science Direct databases for 2000 through 2016 were searched. Inclusion criteria were articles published in English and original research related to clinical outcomes of blood transfusion after coronary artery bypass grafting. Seventeen articles were included in the review. RESULTS Mortality, both short- and long-term, was significantly higher in transfusion patients than in nontransfusion patients. Patients with transfusion of red blood cells had higher resource utilization and more complications, including infection, pneumonia, renal failure, graft occlusion, and atrial fibrillation, than did nontransfusion patients. CONCLUSION An association exists between red blood cell transfusions and adverse clinical outcomes for patients undergoing coronary artery bypass grafting. Transfusion of red blood cells is sometimes unnecessary, may be injurious, and should be used cautiously. Even a single-unit increase in perioperative red blood cell transfusions can have a significant adverse impact on outcomes. Individual benefits and risks should be weighed before transfusion to avoid adverse outcomes. Transfusion guidelines should be reviewed to include the latest evidence to guarantee the most appropriate use of blood products.
Thromboelastography or rotational thromboelastometry for bleeding management in adults undergoing cardiac surgery: a systematic review with meta-analysis and trial sequential analysis
Journal of thoracic disease. 2019;11(4):1170-1181
Background: Severe bleeding and massive transfusion of blood products may be associated with increased morbidity and mortality of cardiac surgery. A transfusion algorithm incorporating thromboelastography (TEG) or rotational thromboelastometry (ROTEM) can help to determine the appropriate time and target for the use of hemostatic blood products, which may thus reduce the quantity of blood loss as well as blood products transfused. Methods: We conducted meta-analysis and trial sequential analysis to evaluate the effects of TEG or ROTEM-guided transfusion algorithms vs. standard treatments for patients undergoing cardiac surgery with cardiac pulmonary bypass. Results: Nineteen studies with a total of 15,320 participants, including 13 randomized controlled trials (RCTs), were included. All-cause mortality was not reduced either in overall studies or in RCTs. Blood loss volume was reduced by 132 mL in overall studies [mean difference (MD): -132.46, 95% CI: -207.49, -57.43; I(2) =53%, P<0.01], and by 103 mL in RCTs (MD: -103.50, 95% CI: -156.52, -50.48; I(2) =0%, P<0.01). The relative risks (RRs) in RCTs were 0.89 (95% CI: 0.80-0.98; I(2) =0%, P=0.02) for red blood cells transfusion, 0.59 (95% CI: 0.42-0.82; I(2) =55%, P<0.01) for fresh frozen plasma transfusion, and 0.81 (95% CI: 0.74-0.90; I(2) =0%, P<0.01) for platelet transfusion, respectively. Trial sequential analysis of continuous data on blood loss and dichotomous outcomes on transfusion of blood products suggested the benefits of a TEG/ROTEM-guided algorithm. Conclusions: TEG or ROTEM-guided transfusion strategies may reduce blood loss volume and the transfusion rates in adult patients undergoing cardiac surgery.
Safety of a Restrictive versus Liberal Approach to Red Blood Cell Transfusion on the Outcome of AKI in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial
Journal of the American Society of Nephrology : JASN. 2019
BACKGROUND Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk. METHODS In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin<7.5 g/dl, intraoperatively and postoperatively) with a liberal threshold (transfuse if hemoglobin<9.5 g/dl in the operating room or intensive care unit, or if hemoglobin<8.5 g/dl on the nonintensive care ward). We studied 4531 patients undergoing cardiac surgery with cardiopulmonary bypass who had a moderate-to-high risk of perioperative death. The substudy's primary outcome was AKI, defined as a postoperative increase in serum creatinine of ≥0.3 mg/dl within 48 hours of surgery, or ≥50% within 7 days of surgery. RESULTS Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted-threshold group compared with the liberal-threshold group; P<0.001). AKI occurred in 27.7% of patients in the restrictive-threshold group (624 of 2251) and in 27.9% of patients in the liberal-threshold group (636 of 2280). Similarly, among patients with preoperative CKD, AKI occurred in 33.6% of patients in the restrictive-threshold group (258 of 767) and in 32.5% of patients in the liberal-threshold group (252 of 775). CONCLUSIONS Among patients undergoing cardiac surgery, a restrictive transfusion approach resulted in fewer red blood cell transfusions without increasing the risk of AKI.
Why does a point of care guided transfusion algorithm not improve blood loss and transfusion practice in patients undergoing high-risk cardiac surgery? A prospective randomized controlled pilot study
BMC anesthesiology. 2019;19(1):24
BACKGROUND Adult cardiac surgery is often complicated by elevated blood losses that account for elevated transfusion requirements. Perioperative bleeding and transfusion of blood products are major risk factors for morbidity and mortality. Timely diagnostic and goal-directed therapies aim at the reduction of bleeding and need for allogeneic transfusions. METHODS Single-centre, prospective, randomized trial assessing blood loss and transfusion requirements of 26 adult patients undergoing elective cardiac surgery at high risk for perioperative bleeding. Primary endpoint was blood loss at 24 h postoperatively. Random assignment to intra- and postoperative haemostatic management following either an algorithm based on conventional coagulation assays (conventional group: platelet count, aPTT, PT, fibrinogen) or based on point-of-care (PoC-group) monitoring, i.e. activated rotational thromboelastometry (ROTEM(R)) combined with multiple aggregometry (Multiplate(R)). Differences between groups were analysed using nonparametric tests for independent samples. RESULTS The study was terminated after interim analysis (n = 26). Chest tube drainage volume was 360 ml (IQR 229-599 ml) in the conventional group, and 380 ml (IQR 310-590 ml) in the PoC-group (p = 0.767) after 24 h. Basic patient characteristics, results of PoC coagulation assays, and transfusion requirements of red blood cells and fresh frozen plasma did not differ between groups. Coagulation results were comparable. Platelets were transfused in the PoC group only. CONCLUSION Blood loss via chest tube drainage and transfusion amounts were not different comparing PoC- and central lab-driven transfusion algorithms in subjects that underwent high-risk cardiac surgery. Routine PoC coagulation diagnostics do not seem to be beneficial when actual blood loss is low. High risk procedures might not suffice as a sole risk factor for increased blood loss. TRIAL REGISTRATION NCT01402739 , Date of registration July 26, 2011.