Abstract

IMPORTANCE Approximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative. OBJECTIVES To determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020. INTERVENTIONS Prothrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation. MAIN OUTCOMES AND MEASURES Hemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery. RESULTS Of 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar. CONCLUSIONS AND RELEVANCE This randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04114643.

Abstract

PURPOSE Albumin solution is a colloid used for resuscitation in cardiac surgical patients, but it is unclear if it offers advantages over crystalloids. We examined current clinical practice across 11 cardiac surgical centres and the association of albumin with outcomes in a cohort of bleeding cardiac surgical patients. METHODS This was a post hoc analysis of data from the Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery (FIBRES) trial. Multivariable regression models adjusted for demographic and surgical characteristics were used to examine predictors of early albumin administration (within the initial 24 perioperative hours), late albumin administration (from 24 hr to seven days after cardiopulmonary bypass), and the association of albumin use with 28-day acute kidney injury, mortality, and length of hospital and intensive care unit (ICU) stay. RESULTS Of the 735 patients included, 525 (71%) received albumin, ranging from 4.8% to 97.4% of patients across institutions, with 475 (64.6%) receiving albumin early (5% or 25% solution). In the adjusted models, female sex and preoperative hospital admission were associated with early use, while heart failure, female sex, bleeding severity, older age, and prior albumin use were predictors of later administration. Early albumin use was not associated with differences in acute kidney injury (adjusted odds ratio [aOR] 1.77; 95% confidence interval [CI], 0.96 to 3.27; P = 0.07), mortality (aOR 1.66; 95% CI, 0.99 to 2.78; P = 0.05), or length of ICU stay (P = 0.11) or hospital stay (P = 0.67). CONCLUSIONS Albumin use is common but highly variable within and across sites. Albumin use was not associated with improved outcomes. High quality randomized controlled trials should clarify its role in cardiac surgical patients.

Abstract

PURPOSE Intravascular fluids are a necessary and universal component of cardiac surgical patient care. Both crystalloids and colloids are used to maintain or restore circulating plasma volume and ensure adequate organ perfusion. In Canada, human albumin solution (5% or 25% concentration) is a colloid commonly used for this purpose. In this narrative review, we discuss albumin supply in Canada, explore the perceived advantages of albumin, and describe the clinical literature supporting and refuting albumin use over other fluids in the adult cardiac surgical population. SOURCE We conducted a targeted search of PubMed, Embase, Medline, Web of Science, ProQuest Dissertations and Theses Global, the Cochrane Central Register of Controlled trials, and the Cochrane Database of Systematic Reviews. Search terms included albumin, colloid, cardiac surgery, bleeding, hemorrhage, transfusion, and cardiopulmonary bypass. PRINCIPAL FINDINGS Albumin is produced from fractionated human plasma and imported into Canada from international suppliers at a cost of approximately $21 million CAD per annum. While it is widely used in cardiac surgical patients across the country, it is approximately 30-times more expensive than equivalent doses of balanced crystalloid solutions, with wide inter-institutional variability in use and no clear association with improved outcomes. There is a general lack of high-quality evidence for the superiority of albumin over crystalloids in this patient population, and conflicting evidence regarding safety. CONCLUSIONS In cardiac surgical patients, albumin is widely utilized despite a lack of high- quality evidence supporting its efficacy or safety. A well-designed randomized controlled trial is needed to clarify the role of albumin in cardiac surgical patients.

Abstract

OBJECTIVE To investigate the perioperative management of patients with hemophilia A (HA) who undergo cardiac surgery. DESIGN Retrospective analysis of the published literature. SETTING University hospital. PARTICIPANTS HA patients undergoing cardiac surgery. INTERVENTIONS The PubMed, Embase, Web of Science Core Collection, CNKI, VIP, and WANFANG databases were searched with the terms "hemophilia A," "cardiac surgery," "cardiopulmonary bypass," "coronary artery bypass graft," "valve disease," and "congenital heart disease" to identify relevant articles. Data regarding patient characteristics, perioperative management protocols, and clinical outcomes were extracted and analyzed. MEASUREMENTS AND MAIN RESULTS Fifty articles, with 72 patients aging from 12 days to 80 years, were included. The analyzed population consisted of 36 (50%) mild HA, 10 (14%) moderate HA, and 25 (35%) severe HA patients. Factor VIII inhibitors were detected in 7 cases. Surgical procedures included 27 coronary artery bypass grafting procedures, 15 valve surgeries, 8 combined coronary artery bypass grafting with valve surgery procedures (1 with left ventricular assist device), 1 ventricular aneurysm resection with valve surgery, 11 corrections of congenital heart disease, 7 adult aortic surgeries, 3 heart transplantations, and 1 repair of heart injury. Factor VIII concentrates were used as a substitution therapy to ensure normalization of perioperative coagulation function. Although an uneventful clinical outcome was achieved in the majority of cases, 20% of patients developed complications with different severities. CONCLUSIONS Execution of a perioperative management strategy with a multidisciplinary approach, a thorough factor replacement protocol, and careful monitoring of factor levels facilitate an optimal outcome for HA patients undergoing cardiac surgery.

Abstract

Pre-procedural serum albumin's impact on prognosis after transcatheter aortic valve replacement (TAVR) has been studied. Literature on the prognostic role of serum albumin in the survival of patients undergoing TAVR shows conflicting results. This meta-analysis was conducted to evaluate the impact of pre-procedural serum albumin on outcomes after TAVR. A comprehensive literature search of EMBASE, MEDLINE, and the Cochrane Library was undertaken through July 2019. The primary end points were 30-day and one-year all-cause mortality after TAVR. Risk ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effect model. Ten eligible studies with 8,236 patients were analyzed. Of the 8,236 patients undergoing TAVR, with a mean age of 83 years, 48.8% were men and were categorized into two groups according to low and normal serum albumin (cut-off value: 3.5 or 4 g/dL). Overall, low albumin was significantly associated with an approximately two-fold increase in 30-day all-cause mortality (HR, 2.09; 95% CI, 1.53-2.86) and a 61% increase risk for one-year mortality (HR, 1.61; 95% CI, 1.31-1.98) in patients after TAVR. Sensitivity analyses showed the results to be robust. The association of low albumin level with an increase in one-year mortality risk was not modified by study design, albumin cut-off value, Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM), and study quality. In conclusion, low albumin levels were associated with poor prognosis in patients after TAVR. Pre-procedural albumin can be used as a simple tool related to prognosis after TAVR.

Abstract

BACKGROUND Mediastinal bleeding is common following pediatric cardiopulmonary bypass surgery for congenital heart disease. Fibrinogen concentrate (FC) represents a potential therapy for preventing bleeding. METHODS We performed a single-center, phase 1b/2a, randomized controlled trial on infants 2.5 to 12 kg undergoing cardiopulmonary bypass surgery, aimed at (1) demonstrating the feasibility of an intraoperative point-of-care test, rotational thromboelastometry, to screen out patients at low risk of postoperative bleeding and then guide individualized FC dosing in high-risk patients and (2) determining the dose, safety, and efficacy of intraoperative FC supplementation. Screening occurred intraoperatively 1-hour before bypass separation using the rotational thromboelastometry variable fibrinogen thromboelastometry maximum clot firmness (FibTEM-MCF; fibrinogen contribution to clot firmness). If FibTEM-MCF ≥7 mm, patients entered the monitoring cohort. If FibTEM-MCF ≤6 mm, patients were randomized to receive FC/placebo (2:1 ratio). Individualized FC dose calculation included weight, bypass circuit volume, hematocrit, and intraoperative measured and desired FibTEM-MCF. The coprimary outcomes, measured 5 minutes post-FC administration were FibTEM-MCF (desired range, 8-13 mm) and fibrinogen levels (desired range, 1.5-2.5 g/L). Secondary outcomes were thrombosis and thrombosis-related major complications and postoperative 24-hour mediastinal blood loss. RESULTS We enrolled 111 patients (cohort, n=21; FC, n=60; placebo, n=30); mean (SD) age, 6.4 months (5.8); weight, 5.9 kg (2.0). Intraoperative rotational thromboelastometry screening effectively excluded low-risk patients, in that none in the cohort arm (FibTEM-MCF, ≥7 mm) demonstrated clinically significant early postoperative bleeding (>10 mL/kg per 4 hours). Among randomized patients, the median (range) FC administered dose was 114 mg/kg (51-218). Fibrinogen levels increased from a mean (SD) of 0.91 (0.22) to 1.7 g/L (0.41). The postdose fibrinogen range was 1.2 to 3.3 g/L (72% within the desired range). The corresponding FibTEM-MCF values were as follows: pre-dose, 5.3 mm (1.9); post-dose, 13 mm (3.2). Ten patients (8 FC and 2 placebo) exhibited 12 possible thromboses; none were clearly related to FC. There was an overall difference in mean (SD) 24-hour mediastinal drain loss: cohort, 12.6 mL/kg (6.4); FC, 11.6 mL/kg (5.2); placebo, 17.1 mL/kg (14.3; ANOVA P=0.02). CONCLUSIONS Intraoperative, individualized dosing of FC appears feasible. The need for individualized dosing is supported by the finding that a 4-fold variation in FC dose is required to achieve therapeutic fibrinogen levels. Registration: URL: https://eudract.ema.europa.eu/; Unique identifier: 2013-003532-68. URL: https://www.isrctn.com/; Unique identifier: 50553029.

Abstract

OBJECTIVE In vascular and cardiac surgery, the ability to maintain haemostasis and seal haemorrhagic tissues is key. Fibrin and thrombin based sealants were introduced as a means to prevent or halt bleeding during surgery. Whether fibrin and thrombin sealants affect surgical outcomes is poorly established. A systematic review and meta-analysis was performed to examine the impact of fibrin or thrombin sealants on patient outcomes in vascular and cardiac surgery. DATA SOURCES Cochrane CENTRAL, Embase, and MEDLINE, as well as trial registries, conference abstracts, and reference lists of included articles were searched from inception to December 2019. REVIEW METHODS Studies comparing the use of fibrin or thrombin sealant with either an active (other haemostatic methods) or standard surgical haemostatic control in vascular and cardiac surgery were searched for. The Cochrane risk of bias tool and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) were used to assess the risk of bias of the included randomised and non-randomised studies; quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two reviewers screened studies, assessed risk of bias, and extracted data independently and in duplicate. Data from included trials were pooled using a random effects model. RESULTS Twenty-one studies (n = 7 622 patients) were included: 13 randomised controlled trials (RCTs), five retrospective, and three prospective cohort studies. Meta-analysis of the RCTs showed a statistically significant decrease in the volume of blood lost (mean difference 120.7 mL, in favour of sealant use [95% confidence interval {CI} -150.6 - -90.7; p < .001], moderate quality). Time to haemostasis was also shown to be reduced in patients receiving sealant (mean difference -2.5 minutes [95% CI -4.0 - -1.1; p < .001], low quality). Post-operative blood transfusions, re-operation due to bleeding, and 30 day mortality were not significantly different for either RCTs or observational data. CONCLUSION The use of fibrin and thrombin sealants confers a statistically significant but clinically small reduction in blood loss and time to haemostasis; it does not reduce blood transfusion. These Results may support selective rather than routine use of fibrin and thrombin sealants in vascular and cardiac surgery.

Abstract

Background: Prevention and optimal treatment of postoperative bleeding are of great clinical importance in various types of surgeries including coronary artery bypass graft (CABG). Reducing the amount of bleeding will reduce the complications subsequent to blood transfusion. The positive effects of coagulation factors, especially fibrinogen, after cardiovascular bypass could have beneficial effects due to reduced bleeding and less need for blood transfusion. However, different studies have reported controversial findings. Objectives: The present study aimed to evaluate the effect of prophylactic administration of fibrinogen on blood loss in patients undergoing CABG surgery to achieve more accurate clinical outcomes. Methods: This was a double-blind randomized clinical trial conducted on 36 patients hospitalized in Ahvaz Imam Khomeini Hospital for coronary artery bypass graft. Patients were randomized to receive either fibrinogen concentrate (n = 18) or placebo (n = 18). Hemoglobin, hematocrit, international normalized ratio, prothrombin time, partial thromboplastin time, and fibrinogen were checked preoperatively. The transfusion of allogeneic blood components and the volume of blood loss were recorded and compared between the groups. Results: Prophylactic fibrinogen injection reduced the need for blood transfusion, blood products, and postoperative hypotension in the fibrinogen group when compared to the control group (P ≤ 0.005). There was a significant difference between the two groups in terms of the amount of bleeding during operation (P ≤ 0.005). Conclusions: Fibrinogen plays a key role in preventing and stopping the bleeding. Accordingly, fibrinogen decreases bleeding and the need for paced cell in patients in CABG. Given the adverse outcomes of bleeding and coagulopathy in patients undergoing surgery, we conclude that the use of fibrinogen could be beneficial as a prophylactic in hemorrhagic surgery.

Abstract

AIM: Comparing the effects of Albumin 5% versus Ringer's lactate on blood loss and coagulation after vascular surgery using. METHODS In this randomised study, 60 patients, aged (18-60 years) ASA physical status (I-III) undergoing vascular surgery were included in the study and randomly allocated into two groups using a random number generator, to receive either Human albumin or Ringer lactate after obtaining written informed consent. Group A received 1-2 ml per minute of human albumin 5% combined with normal saline (0.9%). Group B received Ringer's lactate only as of the main solution. Variables were measured after administration of fluids as postoperative measures. The amount of blood needed for testing was 4 ml drawn before the operation and at the end of surgery with a citrate tube (blue tube) from the venous line or using a regular needle. The standard time of 15 minutes was considered to begin processing. RESULTS There was no statistically significant difference observed between both groups regarding demographic data, surgical wound drainage, haemoglobin level, hematocrit level and coagulation profile. Regarding ROTEM thermoelectrometry variables showed that there was no statistically significant difference was found between the two groups In-TEM variables (Ex-TEM Clotting time, TEM Clot Formation Time) but In-TEM Alpha Angel measured in degrees showed a Statistically significant difference between the two groups. P < 0.001 and Ex-TEM Maximum Clotting Firmness MCF values measured in mm, there was a statistically significant difference between the two groups P = 0.045. CONCLUSION This study concluded that the use of human albumin (5%) in vascular surgeries before reaching the trigger point for blood transfusion didn't improve blood loss or coagulation profile compared to the use of ringer lactate only. Therefore, ringer lactate can be used as a good replacement for human albumin. Ringer lactate is readily available and inexpensive while human albumin may be costly.

Abstract

OBJECTIVES To explore the effect of two different priming strategies (artificial colloid only vs. artificial colloid combined with human serum albumin) on the prognosis of children weighing less than 5 kg undergoing on-pump congenital heart disease (CHD) surgery. METHODS A total of 65 children weighing less than 5 kg who underwent on-pump CHD surgery in our hospital from September 2016 to December 2017 were enrolled in this study. The children were randomly divided into two groups: artificial colloid priming group (AC group, n=33) and artificial colloid combined albumin priming group (ACA group, n=32). The primary clinical endpoint was the peri-CPB colloid osmotic pressure (COP). Secondary clinical endpoints included perioperative blood product & hemostatic drug consumption, postoperative renal function, coagulation function, postoperative renal function and postoperative recovery parameters. RESULTS COP values were not significant in the priming system as well as peri-CPB time points between the two groups (P>0.05). Platelet consumption in the AC group was significantly lower than that in the ACA group (P<0.05). There were no significant differences in the use of other blood products and hemostatic drugs as well as perioperative coagulation parameters between the two groups (P>0.05). Postoperative length of stay in the AC group was significantly lower than that in the ACA group (P<0.05). There were no significant differences in mortality, postoperative mechanical ventilation time, ICU time and perioperative adverse event (including postoperative AKI) occurrences between the two groups (P>0.05). CONCLUSIONS In the on-pump cardiac surgeries of patients weighting less than 5kg, total colloidal priming would not affect peri-CPB COP values, postoperative coagulation function and blood products consumption. Total artificial colloidal priming strategy is feasible in low-weight patients.