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.
Restrictive versus Liberal Transfusion in Patients with Diabetes Undergoing Cardiac Surgery: An Open-Label Randomized, Blinded Outcome Evaluation Trial
Diabetes, obesity & metabolism. 2021
AIM: To characterize the association between diabetes and transfusion and clinical outcomes in cardiac surgery, and to evaluate whether restrictive transfusion thresholds are harmful in these patients. MATERIALS AND METHODS The multinational, open-label, randomized controlled TRICS-III trial assessed a restrictive transfusion strategy (hemoglobin [Hb] transfusion threshold <75 g/L) compared to a liberal strategy (Hb <95 g/L for operating room or ICU; or < 85 g/L for ward) in patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate-to-high risk of death (EuroSCORE ≥6). Diabetes status was collected preoperatively. The primary composite outcome was all-cause death, stroke, myocardial infarction, and new-onset renal failure requiring dialysis at 6 months. Secondary outcomes included components of the composite outcome at 6 months, and transfusion and clinical outcomes at 28 days. RESULTS Of the 5092 patients analyzed, 1396 (27.4%) had diabetes (Restrictive: n = 679, Liberal n = 717). Patients with diabetes had more cardiovascular disease than patients without diabetes. Neither the presence of diabetes (OR [95%CI]1.10[0.93-1.31]) or the restrictive strategy increased the risk for the primary composite outcome (diabetes OR [95%CI]1.04[0.68-1.59] vs. no diabetes OR 1.02[0.85-1.22],p(interaction) = 0.92). In patients with versus without diabetes, a restrictive transfusion strategy was more effective at reducing red blood cell transfusion (diabetes OR [95%CI] 0.28[0.21-0.36]; no diabetes OR [95%CI] 0.40[0.35-0.47];p(interaction) = 0.04). CONCLUSIONS The presence of diabetes did not modify the effect of a restrictive transfusion strategy on the primary composite outcome, but improved its efficacy on red cell transfusion. Restrictive transfusion triggers are safe and effective in patients with diabetes undergoing cardiac surgery. This article is protected by copyright. All rights reserved.
Patients with diabetes undergoing cardiac surgery enrolled in the multinational TRICS-III trial (n= 1,396).
Restrictive transfusion threshold strategy (n= 679).
Liberal transfusion threshold strategy (n= 717).
Of the 5,092 patients analysed, 1396 (27.4%) had diabetes. Patients with diabetes had more cardiovascular disease than patients without diabetes. Neither the presence of diabetes nor the restrictive strategy increased the risk for the primary composite outcome vs. no diabetes. In patients with vs. without diabetes, a restrictive transfusion strategy was more effective at reducing red blood cell transfusion.
A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial
Vox sanguinis. 2021
BACKGROUND AND OBJECTIVES Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. MATERIALS AND METHODS This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. RESULTS Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 10(3) /μl vs. 157 × 10(3) /μl, median difference 39.5 ×10(3) /μl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. CONCLUSION This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.
Adult cardiac surgery patients (n= 89).
Cryopreserved platelet transfusions (n= 49).
Liquid-stored platelet transfusion (n= 40).
There were no differences in median blood loss up to 48 hours between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 10(3) /μl vs. 157 × 10(3) /μl, median difference 39.5 × 10(3) /μl). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24 hours blood loss, red cell transfusion or a composite bleeding outcome.
Comparison of fibrin sealants in peripheral vascular surgery: A systematic review and network meta-analysis
Annals of medicine and surgery (2012). 2021;61:161-168
BACKGROUND Evidence comparing fibrin sealants (FSs) in surgery are limited. This study evaluated the efficacy and safety of FSs, and manual compression in peripheral vascular surgery. METHODS A systematic review of randomized trials was conducted in Medline, Embase, and Cochrane databases within the last 15 years. Data were available to conduct a network meta-analysis (NMA) in peripheral vascular surgery. Fibrin sealant treatment arms were further broken-down and assessed by clotting time (i.e., 2-min [2C] or 1-min [1C]). The primary efficacy outcome was the proportion of patients achieving hemostasis by 4 min (T4). Treatment-related serious and non-serious adverse events (AEs) were qualitatively assessed. RESULTS Five studies (n = 693), were included in the NMA. Results predicted VISTASEAL 2C, followed by EVICEL 1C, had the highest probability of achieving T4. Compared with manual compression, significant improvements in T4 were found with VISTASEAL 2C (relative risk [RR] = 2.67, 95% CrI: 2.13-3.34), EVICEL 1C (RR = 2.58, 95% CrI: 2.04-3.23), VISTASEAL 1C (RR = 2.00, 95% CrI: 1.45-2.65), and TISSEEL 2C (RR = 1.99, 95% CrI: 1.48-2.60). TISSEEL 1C was not significantly different than manual compression (RR = 1.40, 95% CrI: 0.70-2.33). Among FSs, VISTASEAL 2C was associated with a significant improvements in T4 compared with VISTASEAL 1C (RR = 1.33, 95% CrI: 1.02-1.82), TISSEEL 2C (RR = 1.34, 95% CrI: 1.05-1.77), and TISSEEL 1C (RR = 1.90, 95% CrI: 1.18-3.74). Treatment-related serious and non-serious AE rates were typically lower than 2%. CONCLUSIONS In peripheral vascular surgeries, VISTASEAL 2C and EVICEL 1C were shown to have the highest probabilities for achieving rapid hemostasis among the treatments compared. Future studies should expand networks across surgery types as data become available.
Effects of Isovolumic Hemodilution and Platelet-Rich Plasma Separation on Platelet Activation State and Function, Complications, and Inflammation in Patients Undergoing Cardiac Surgery
Clinical laboratory. 2021;67(1)
BACKGROUND To explore the effects of isovolumic hemodilution and platelet-rich plasma separation on platelet activation state and function, complications, and inflammation in patients undergoing cardiac surgery. METHODS A total of 80 patients who needed cardiac surgery under extracorporeal circulation from February 2018 to December 2019 in our hospital were selected as research subjects and divided into observation group (n = 40) and control group (n = 40) according to the random number table method. The patients in the observation group underwent platelet-rich plasma separation, while those in control group received acute isovolumic hemodilution. Then the platelet activation state and functional indexes, hemorheological indexes, and the coagulation functional indexes were compared between the two groups of patients before operation. Next, the changes in the levels of hemoglobin and high-sensitivity C-reactive protein (hs-CRP), an inflammatory factor, during blood protection (before and at 6 hours and 12 hours after intervention) were analyzed. Moreover, the dosage of blood products during operation was compared between the two groups, and postoperative complications and recovery in the two groups were statistically assessed. RESULTS Before operation, the platelet adherence rate and aggregation rate in the observation group were significantly higher than those in control group (p < 0.05), while R and K values in thromboelastograms in the former were notably smaller than those in the latter (p < 0.05). Meanwhile, the whole blood low-shear viscosity, whole blood high-shear viscosity, and plasma viscosity in observation group were remarkably lower than those in control group (p < 0.05). In addition, the observation group exhibited shorter prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT) (p < 0.05) and a higher fibrinogen (Fib) level (p < 0.05) than the control group. At 6 hours and 12 hours after intervention and before operation, the hemoglobin level in observation group was markedly higher than that in control group (p < 0.05). In addition, the dosages of red blood cells, fresh frozen plasma, and platelets among blood products during operation in the observation group were evidently lower than those in the control group (p < 0.05), and the number of cases of hemorrhage, pulmonary infection, coagulation dysfunction, and paraplegia after operation in the former was distinctly smaller than that in the latter (p < 0.05). Furthermore, the observation group had an obviously smaller postoperative 24 hours drainage volume (p < 0.05) as well as shorter postoperative mechanical ventilation time and ICU treatment time than control group (p < 0.05). CONCLUSIONS For patients undergoing cardiac surgery under extracorporeal circulation, platelet-rich plasma separation and reinfusion technology can effectively ensure platelet activation state and function, reduce blood viscosity, ensure stable coagulation function, elevate hemoglobin level and decrease inflammatory reaction, and perioperative allogeneic blood infusion, with fewer adverse reactions in treatment, thus efficaciously facilitating the post-operative recovery of patients.
A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery
BACKGROUND This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room temperature-stored platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials. METHODS A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality. RESULTS In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature-stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature- and cold-stored up to 7 days arm was 75 ml (95% CI, -220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, -1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature- and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature-stored platelets. CONCLUSIONS This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients.
[Application of autologous platelet-rich plasma separation in cardiac valve replacement: a random clinical trial]
Zhonghua wai ke za zhi [Chinese journal of surgery]. 2020;58(12):924-928
Objective: To examine the blood protective effect of autologous platelet-rich plasma separation for cardiac valve replacement under cardiopulmonary bypass. Methods: Sixty patients who underwent cardiac valve replacement under cardiopulmonary bypass from August 2018 to May 2019 in Shanghai Chest Hospital, Shanghai Jiao Tong University were randomly divided into control and treatment groups(each 30 cases). There were 33 males and 27 females, aged (52.0±8.4) years (range: 35 to 65 years). Autologous platelet separation was performed in the treatment group after anaesthesia administration and was completed before systemic heparinisation. Platelet separation was not performed in the control group. The thromboelastogram, blood routine, blood coagulation, perioperative fluid infusion, allogeneic blood transfusion, postoperative pleural fluid volume and postoperative fibrinogen were recorded before the operation, and 1 hour and 24 hours post operation. The two groups' data was compared by t test, Kruskal-Wallis test, Mann-Whitney U test or χ(2) test. Repeated measurement analysis of variance was used to compare platelet and coagulation indexes at different times. Results: The perioperative red blood cell transfusion of 0, 1~2, 3~4,>4 units with 6, 11, 1, 12 cases in treatment group and 14, 8, 6, 2 cases in control group (Z=-2.516, P=0.012). The postoperative fibrinogen of 0, 1, 2 units with 19, 2, 9 cases in treat group and 26, 2, 2 cases in control group (Z=-2.190, P=0.029). There was no significant difference in the cost of blood transfusion between the two groups during admission ((1 732±1 275) yuan vs. (1 176±941) yuan; t=-1.570, P=0.125). Conclusion: The use of autologous platelet-rich plasma separation can reduce the amount of allogeneic blood transfusion during valvular surgery under cardiopulmonary bypass.
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.
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.