On this page you can view articles from previous editions of the Transfusion Evidence Alert and Round-Up; use the button on the left to sign up to receive future editions direct to your inbox. The Transfusion Evidence Alert is a monthly overview of 10 selected evidence-based publications in the field of transfusion medicine, including relevant COVID-19 articles. The articles are selected by experts in the field from the Systematic Review Initiative, funded by the four UK blood services. The Transfusion Evidence Round-Up is a quarterly overview of the top 10 high quality studies about an internationally relevant subject in the field of transfusion medicine. The articles are selected by members from the International Society of Blood Transfusion and drawn from the Transfusion Evidence Library and where relevant Stem Cell Evidence.
Vanderbruggen, W., Brits, T., Tilborghs, S., Derickx, K., De Wachter, S.
The Prostate. 2023
Editor's Choice
Abstract
BACKGROUND Bleeding and bleeding-related complications remain common after bipolar transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. This may possibly lead to prolonged postoperative irrigation, catheterization, and hospital stay. The objective of this trial was to evaluate the effect of high-dose tranexamic acid (TXA) on perioperative blood loss in patients treated with bipolar TURP for prostate sizes between 30 and 80 g. METHODS We conducted a single-center, prospective, double-blind, randomized controlled trial. Eighty patients were screened for inclusion between March 2020 and January 2023. After exclusion, 65 patients were randomized in two comparable groups. The TXA group (31 patients) received a TXA intravenous loading dose of 10 mg/kg over 30 min before induction, followed by a maintenance dose of 5 mg/kg/h over 12 h. The placebo group (34 patients) received an equal dose of saline infusion. We measured age, weight, preoperative prostate size, anticoagulant use, 5-alpha reductase inhibitor use, preoperative urinary tract infection, American Society of Anesthesiologists score, difference in pre- and 24 h postoperative hemoglobin and hematocrit levels, operative time, resected adenoma weight, duration of postoperative irrigation, total amount of postoperative irrigation fluid, indwelling catheter time, duration of hospital stay, blood transfusion rate, and 4-week complication rate. RESULTS Baseline characteristics in both groups were comparable. Postoperative hemoglobin decrease in TXA versus placebo group was 1 versus 1.6 mg/dL, respectively (p = 0.04). In addition, the amount of postoperative irrigation fluid (10.7 vs. 18.5 L), irrigation time (24.3 vs. 37.9 h), catheterization time (40.8 vs. 53.7 h), and hospital stay (46.9 vs. 59.2 h) were statistically significant in favor of TXA use. No blood transfusions were carried out. Four-week complication rate was comparable between the two groups. CONCLUSIONS Perioperative high-dose TXA seems beneficial in reducing hemoglobin loss, postoperative irrigation, catheterization time, and hospital stay in bipolar TURP for prostate sizes between 30 and 80 g, without increased risk of TXA-related thromboembolic events.
PICO Summary
Population
Patients treated with bipolar transurethral resection of the prostate (n= 65).
Intervention
Tranexamic acid (TXA), (n= 31).
Comparison
Placebo (saline infusion), (n= 34).
Outcome
Postoperative haemoglobin decrease in TXA compared to placebo was 1 versus 1.6 mg/dL, respectively. The amount of postoperative irrigation fluid (10.7 vs. 18.5 L), irrigation time (24.3 vs. 37.9 h), catheterization time (40.8 vs. 53.7 h), and hospital stay (46.9 vs. 59.2 h) were statistically significant in favor of TXA use. No blood transfusions were carried out. Four-week complication rate was comparable between the two groups.
Walker, B. S., Schmidt, R. L., White, S. K., Metcalf, R. A.
Transfusion. 2023
Editor's Choice
Abstract
BACKGROUND The relative safety of bacterial risk control strategies for platelets that include culture with or without rapid testing has been compared using simulation analysis. A wide range of bacterial lag and doubling times were included. However, published data on growth rates are available and these data have not been synthesized. We conducted a systematic review and meta-analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance STUDY DESIGN AND METHODS Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. RESULTS In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1-5 h. The revised comparative safety simulation using the narrower 1-5-h range showed similar rankings to the prior simulation, with 48-h large-volume delayed sampling with 7-day expiration (48C-7) demonstrating the lowest-ranking relative performance at the 10(3) and 10(5) colony forming unit (CFU)/mL exposure thresholds. DISCUSSION This was a two-step study. First, meta-analysis of published data on aerobic bacterial growth rates in stored platelets showed the vast majority of doubling times were 1-5 h. Next, an updated comparative safety simulation yielded similar results to a prior study, with 48C-7 showing the least favorable relative safety performance.
PICO Summary
Population
Recipients of platelet transfusions (12 studies).
Intervention
Systematic review and meta-analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance.
Comparison
Outcome
Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1-5 h. The revised comparative safety simulation using the narrower 1-5-h range showed similar rankings to the prior simulation, with 48-h large-volume delayed sampling with 7-day expiration (48C-7) demonstrating the lowest-ranking relative performance at the 10(3) and 10(5) colony forming unit (CFU)/mL exposure thresholds.
PURPOSE The efficacy and safety of tourniquets use during total knee arthroplasty (TKA) in patients with osteoarthritis remain debated. This updated systematic review and meta-analysis aimed to further evaluate the role of tourniquets use in patients undergoing TKA for knee osteoarthritis by introducing trial sequential analysis. METHODS PubMed, Embase, and the Cochrane Library were searched. We used the Cochrane risk of bias tool for quality assessment. Statistical heterogeneity across studies was evaluated using Cochran's Q and I(2) statistic. Meta-analysis was performed using Stata/SE 14.0, and trail sequential analysis was performed using TSA software version 0.9.5.10 Beta. In addition, qualitative summary was also used to describe results. RESULTS 15 randomized controlled trials (RCTs) involving 1202 patients were included in the meta-analysis. The pooled results showed that tourniquet use during TKA significantly reduced intraoperative blood loss (mean difference (MD)= -123.84, 95% confidence interval (CI): -163.37 to -84.32, p < .001)and shortened operation time (MD = -4.71, 95% CI: -7.6 to -1.82, p = .001), but there were no significant differences in postoperative blood loss, calculated blood loss, total blood loss, transfusion rate (p = .939), and deep venous thrombosis (DVT) rate between the tourniquet and no-tourniquet groups. TSA confirmed that the result of operation time was false positive, but the results of other outcomes were conclusive. The results of qualitative summary showed conflicting findings in terms of pain, range of motion (RoM) and swelling ratio between the two groups. CONCLUSIONS Tourniquet use in patients receiving TKA for osteoarthritis benefits to reduce intraoperative blood loss but has no effect on postoperative blood loss, calculated blood loss, total blood loss, operation time, transfusion rate, and DVT rate. In addition, it remains unclear the difference between the tourniquet and non-tourniquet groups in terms of pain, RoM and swelling ratio.
PICO Summary
Population
Patients undergoing total knee arthroplasty (TKA) for osteoarthritis (15 randomised controlled trials, n= 1,202).
Intervention
Tourniquet.
Comparison
Non-use of tourniquet.
Outcome
The pooled results showed that tourniquet use during TKA significantly reduced intraoperative blood loss (mean difference (MD)= -123.84; 95% confidence interval (CI) [-163.37, -84.32]) and shortened operation time (MD= -4.71; 95% CI [-7.6 to, -1.82]), but there were no significant differences in postoperative blood loss, calculated blood loss, total blood loss, transfusion rate, and deep venous thrombosis rate between the tourniquet and no-tourniquet groups. Trial sequential analyses confirmed that the result of operation time was false positive, but the results of other outcomes were conclusive. The results of qualitative summary showed conflicting findings in terms of pain, range of motion and swelling ratio between the two groups.
Ponikowski, P., Mentz, R. J., Hernandez, A. F., Butler, J., Khan, M. S., van Veldhuisen, D. J., Roubert, B., Blackman, N., Friede, T., Jankowska, E. A., et al
BACKGROUND AND AIMS Whereas a beneficial effect of intravenous ferric carboxymaltose (FCM) on symptoms and exercise capacity among patients with iron deficiency (ID) and heart failure (HF) has been consistently demonstrated, the effects of treatment on clinical events remain the subject of research. This meta-analysis aimed to characterize the effects of FCM therapy on hospitalizations and mortality. METHODS Patient-level data from randomized, placebo-controlled FCM trials including adults with HF and ID with ≥52 weeks follow-up were analysed. The co-primary efficacy endpoints were (1) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death, and (2) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. Key secondary endpoints included individual composite endpoint components. Event rates were analysed using a negative binomial model. Treatment-emergent adverse events were also examined. RESULTS Three FCM trials with a total of 4501 patients were included. FCM was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio [RR] 0.86; 95% confidence interval [CI] 0.75-0.98; P=0.029; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (RR 0.87; 95% CI 0.75-1.01; P=0.076; Cochran Q: 0.024). Treatment effects appeared to result from reduced hospitalization rates, not improved survival. Treatment appeared to have a good safety profile and was well-tolerated. CONCLUSIONS In iron-deficient patients with HF with reduced left ventricular ejection fraction, intravenous FCM was associated with significantly reduced risk of hospital admissions for HF and cardiovascular causes, with no apparent effect on mortality.
PICO Summary
Population
Adults with heart failure (HF) and iron deficiency enrolled in the ferric carboxymaltose (FCM) trials: CONFIRM-HF, AFFIRM-AHF, and HEART-FID (3 randomised controlled trials, n= 4,501).
Intervention
FCM (n= 2,251).
Comparison
Placebo (n= 2,250).
Outcome
The co-primary efficacy endpoints were (1) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death, and (2) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. FCM was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio [RR] 0.86; 95% confidence interval (CI) [0.75, 0.98]; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (RR 0.87; 95% CI [0.75, 1.01]; Cochran Q: 0.024).
OBJECTIVES The sterile exsanguination tourniquet (SET) could be an alternative for providing bloodless surgeries in orthopedic femoral-related surgeries in pediatric patients where the standard pneumatic tourniquet would not be feasible. This randomized-controlled study aimed to evaluate the efficacy of SET in decreasing total perioperative blood loss and blood transfusion. METHODS We conducted an unplanned interim analysis of data from a randomized-controlled trial. At the time of the analysis, 31 pediatric patients had been randomly assigned to undergo surgery with the SET application (the SET group, 15 patients) and without the SET application (the control group, 16 patients). An intention-to-treat analysis was performed to evaluate the total perioperative blood loss, postoperative blood transfusion, estimated intraoperative blood loss, total drainage volume, postoperative hemoglobin level, and operative time according to the significance level adjusted for multiplicity (p < 0.029). RESULTS There was a borderline statistically significant lower body weight-adjusted TBL in the SET group (SET = 14.1 (7.7, 16.9) ml/kg vs. control 18.3 (14.8, 37.2) ml/kg, p-value = 0.027). The body weight-adjusted transfusion volume was statistically significantly greater in the control group (SET = 0.0 (0.0, 0.0) ml/kg vs. control = 2.1 (0.0, 9.7) ml/kg, p = 0.017). Body weight-adjusted estimated intraoperative blood loss was significantly lower in the SET group (SET = 0.8 (0.2, 3.5) ml/kg vs. control = 5.6 (3.4, 21.5) ml/kg, p < 0.001). In addition, the operative time was lower in the SET group with borderline statistical significance (SET = 105 (85.0, 125.0) vs. control = 130 (101.3, 167.5), p = 0.039). CONCLUSION Utilization of a sterile exsanguination tourniquet (SET) significantly reduced an estimated intraoperative blood loss while preventing the need for blood transfusion after pediatric orthopedic femoral-related surgeries. Trial registration TCTR20220412003.
PICO Summary
Population
Paediatric patients aged 3 to 18 undergoing elective femoral-related surgery (n= 31).
The primary outcomes were perioperative total blood loss (TBL) and transfusion rate at 72 hours after surgery. There was a borderline statistically significant lower body weight-adjusted TBL in the SET group (SET= 14.1 (7.7, 16.9) ml/kg vs. control 18.3 (14.8, 37.2) ml/kg). The body weight-adjusted transfusion volume was statistically significantly greater in the control group (SET= 0.0 (0.0, 0.0) ml/kg vs. control= 2.1 (0.0, 9.7) ml/kg). Body weight-adjusted estimated intraoperative blood loss was significantly lower in the SET group (SET= 0.8 (0.2, 3.5) ml/kg vs. control= 5.6 (3.4, 21.5) ml/kg). The operative time was lower in the SET group with borderline statistical significance (SET= 105 (85.0, 125.0) vs. control= 130 (101.3, 167.5)).
BACKGROUND Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017. OBJECTIVES To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination. SEARCH METHODS We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE). MAIN RESULTS We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m(2), 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life. AUTHORS' CONCLUSIONS We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
PICO Summary
Population
Children and adults with sickle cell disease (3 randomised controlled trials, n= 385).
Intervention
Interventions to prevent or reduce kidney complications or chronic kidney disease, including: hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.
Comparison
Placebo.
Outcome
This systematic review is an update of a review first published in 2017. The authors rated the certainty of the evidence as low to very low across different outcomes. The authors are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. The authors are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. The authors are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria.
BACKGROUND Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.
FBHAs vs. no intervention (6 RCTs, 1,001 participants): It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58; 95% CI [0.89, 7.44] 4 trials), serious adverse events (RR 0.96; 95% CI [0.88, 1.05] 4 trials), postoperative transfusion (RR 1.04; 95% CI [0.77, 1.40] 5 trials), reoperation (RR 2.92, 95% CI [0.58, 14.61] 2 trials), or postoperative bile leak (RR 1.00; 95% CI [0.67, 1.48] 4 trials), as the certainty of evidence was very low for all these outcomes. FBHAs vs. non-FBHAs (16 RCTs, 1,944 participants): It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03; 95% CI [0.62, 1.72] 11 trials), postoperative transfusion (RR 0.92; 95% CI [0.68, 1.25] 7 trials), reoperation (RR 0.48; 95% CI [0.25, 0.90] 3 trials), or postoperative bile leak (RR 1.15; 95% CI [0.60, 2.21] 9 trials), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99; 95% CI [0.95, 1.03] 9 trials, low-certainty evidence).
BACKGROUND Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. METHODS STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. DISCUSSION The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. TRIAL REGISTRATION ISRCTN 10412338. Registration date: October 24, 2019.
PICO Summary
Population
Whole blood donors enrolled in the Strategies to Improve Donor Experiences (STRIDES) trial from all 73 blood donation sites of National Health Service Blood and Transplant (NHSBT) in England (n= 1.4 million).
Intervention
(i) 500ml isotonic drink before donation; (ii) 3-min rest on donation chair after donation; (iii) New modified applied muscle tension (AMT); (iv) Psychosocial intervention using preparatory materials upon arrival and registration.
Comparison
NHSBT’s current practices: (i) 500ml plain water before donation. (ii) 2-min rest on donation chair after donation; (iii) Current practice of AMT; (iv) No psychosocial intervention.
Outcome
The primary outcome is the number of in-session vasovagal reactions (VVRs) with loss of consciousness. Secondary outcomes include all in-session VVRs, all delayed VVRs and any in-session non-VVR adverse events or reactions. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Researchers will test the hypothesis that that the implementation of one or more interventions, singly or in combination, will reduce VVRs when compared to current practice in NHSBT.
Mentz, R. J., Garg, J., Rockhold, F. W., Butler, J., De Pasquale, C. G., Ezekowitz, J. A., Lewis, G. D., O'Meara, E., Ponikowski, P., Troughton, R. W., et al
The New England journal of medicine. 2023
Editor's Choice
Abstract
BACKGROUND Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed. METHODS In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01. RESULTS We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group). CONCLUSIONS Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).
PICO Summary
Population
Patients with heart failure and iron deficiency (n= 3,065).
Intervention
Intravenous ferric carboxymaltose group (n= 1,532).
Comparison
Placebo (n= 1,533).
Outcome
Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (unmatched win ratio, 1.10; 99% confidence interval [0.99, 1.23]). The number of patients with serious adverse events occurring during the treatment period was similar in the two groups: 413 patients (27.0%) in the ferric carboxymaltose group, and 401 (26.2%) in the placebo group.
Lasocki, S., Capdevila, X., Vielle, B., Bijok, B., Lahlou-Casulli, M., Collange, V., Grillot, N., Danguy des Deserts, M., Duchalais, A., Delannoy, B., et al
The Lancet. Haematology. 2023
Editor's Choice
Abstract
BACKGROUND Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery. METHODS In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants. FINDINGS Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups. INTERPRETATION In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it. FUNDING French Ministry of Health, HiFIT trial.
PICO Summary
Population
Adults hospitalised for hip fractures in 12 medical centres in France, enrolled in the Hip Fracture Iron and Tranexamic acid (HiFIT) trial (n= 413).
Intervention
Iron plus tranexamic acid (n= 104).
Comparison
Iron plus placebo (n= 103). Tranexamic acid plus placebo (n= 103). Double placebo (n= 103).
Outcome
Among patients on double placebo, 31 (30%) were transfused vs. 16 (15%) on both drugs (relative risk 0.51; 98.3% CI [0.27, 0.97]); 27 (26%) participants on iron (relative risk 0.81; 98.3% CI [0.50, 1.29]) and 28 (27%) on tranexamic acid (relative risk 0.85; 98.3% CI [0.54, 1.33]) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse events were sepsis, pneumonia, and urinary infection, with similar rates among all groups.
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.
Hu RT, Royse AG, Royse C, Scott DA, Bowyer A, Boggett S, Summers P, Mazer CD
Transfusion. 2022
Editor's Choice
Abstract
BACKGROUND Transfusion Requirements in Cardiac Surgery III (TRICS III), a multi-center randomized controlled trial, demonstrated clinical non-inferiority for restrictive versus liberal RBC transfusion for patients undergoing cardiac surgery. However, it is uncertain if transfusion strategy affects long-term health-related quality of life (HRQOL). STUDY DESIGN AND METHODS In this planned sub-study of Australian patients in TRICS III, we sought to determine the non-inferiority of restrictive versus liberal transfusion strategy on long-term HRQOL and to describe clinical outcomes 24 months postoperatively. The restrictive strategy involved transfusing RBCs when hemoglobin was <7.5 g/dl; the transfusion triggers in the liberal group were: <9.5 g/L intraoperatively, <9.5 g/L in intensive care, or <8.5 g/dl on the ward. HRQOL assessments were performed using the 36-item short form survey version 2 (SF-36v2). Primary outcome was non-inferiority of summary measures of SF-36v2 at 12 months, (non-inferiority margin: -0.25 effect size; restrictive minus liberal scores). Secondary outcomes included non-inferiority of HRQOL at 18 and 24 months. RESULTS Six hundred seventeen Australian patients received allocated randomization; HRQOL data were available for 208/311 in restrictive and 217/306 in liberal group. After multiple imputation, non-inferiority of restrictive transfusion at 12 months was not demonstrated for HRQOL, and the estimates were directionally in favor of liberal transfusion. Non-inferiority also could not be concluded at 18 and 24 months. Sensitivity analyses supported these results. There were no differences in quality-adjusted life years or composite clinical outcomes up to 24 months after surgery. DISCUSSION The non-inferiority of a restrictive compared to a liberal transfusion strategy was not established for long-term HRQOL in this dataset.
PICO Summary
Population
Patients undergoing cardiac surgery, enrolled in the Australian cohort of the randomised controlled trial: Transfusion Requirements in Cardiac Surgery III (TRICS III), (n= 617).
Intervention
Restrictive transfusion strategy (n= 311).
Comparison
Liberal transfusion strategy (n= 306).
Outcome
Health-related quality of life (HRQOL) data were available for 208 (67%) patients in the restrictive and 217 (71%) patients in the liberal group. After multiple imputation, non-inferiority of restrictive transfusion at 12 months was not demonstrated for HRQOL, and the estimates were directionally in favor of liberal transfusion. Non-inferiority also could not be concluded at 18 and 24 months. Sensitivity analyses supported these results. There were no differences in quality-adjusted life years or composite clinical outcomes up to 24 months after surgery.
BACKGROUND Coagulopathy following cardiac surgery is associated with considerable blood product transfusion and high morbidity and mortality. The treatment of coagulopathy following cardiac surgery is challenging, with the replacement of clotting factors being based on transfusion of fresh frozen plasma (FFP). Prothrombin complex concentrate (PCCs) is an alternative method to replace clotting factors and warrants evaluation. PCCs are also an alternative method to treat refractory ongoing bleeding post-cardiac surgery compared to recombinant factor VIIa (rFVIIa) and also warrants evaluation. OBJECTIVES Assess the benefits and harms of PCCs in people undergoing cardiac surgery who have coagulopathic non-surgical bleeding. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase and Conference Proceedings Citation Index-Science (CPCI-S) on the Web of Science on 20 April 2021. We searched Clinicaltrials.gov (www. CLINICALTRIALS gov), and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/), for ongoing or unpublished trials. We checked the reference lists for additional references. We did not limit the searches by language or publication status. SELECTION CRITERIA We included randomised controlled trials (RCTs) and non-randomised trials (NRSs). DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS Eighteen studies were included (4993 participants). Two were RCTs (151 participants) and 16 were NRSs. Both RCTs had low risk of bias (RoB) in almost all domains. Of the 16 NRSs, 14 were retrospective cohort analyses with one prospective study and one case report. The nine studies used in quantitative analysis were judged to have critical RoB, three serious and three moderate. 1. PCC versus standard treatment Evidence from RCTs showed PCCs are likely to reduce the number of units transfused compared to standard care (MD -0.89, 95% CI -1.78 to 0.00; participants = 151; studies = 2; moderate-quality evidence). Evidence from NRSs agreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (MD -1.87 units, 95% CI -2.53 to -1.20; participants = 551; studies = 2; very low-quality evidence). There was no evidence from RCTs showing a difference in the incidence of red blood cell (RBC) transfusion compared to standard care (OR 0.53, 95% CI 0.20 to 1.40; participants = 101; studies = 1; low-quality evidence). Evidence from NRSs disagreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (OR 0.54, 95% CI 0.30 to 0.98; participants = 1046; studies = 4; low-quality evidence). There was no evidence from RCTs showing a difference in the number of thrombotic events with PCC compared to standard care (OR 0.68 95% CI 0.20 to 2.31; participants = 152; studies = 2; moderate-quality evidence). This is supported by NRSs, showing that PCCs may have no effect on the number of thrombotic events compared to standard care but the evidence is very uncertain (OR 1.32, 95% CI 0.87 to 1.99; participants = 1359; studies = 7; very low-quality evidence). There was no evidence from RCTs showing a difference in mortality with PCC compared to standard care (OR 0.53, 95% CI 0.12 to 2.35; participants = 149; studies = 2; moderate-quality evidence). This is supported by evidence from NRSs, showing that PCCs may have little to no effect on mortality compared to standard care but the evidence is very uncertain (OR 1.02, 95% CI 0.69 to 1.51; participants = 1334; studies = 6; very low-quality evidence). Evidence from RCTs indicated that there was little to no difference in postoperative bleeding (MD -107.05 mLs, 95% CI -278.92 to 64.83; participants = 151, studies = 2; low-quality evidence). PCCs may have little to no effect on intensive care length of stay (RCT evidence: MD -0.35 hours, 95% CI -19.26 to 18.57; participants = 151; studies = 2; moderate-quality evidence) (NRS evidence: MD -18.00, 95% CI -43.14 to 7.14; participants = 225; studies = 1; very low-quality evidence) or incidence of renal replacement therapy (RCT evidence: OR 0.72, 95% CI 0.14 to 3.59; participants = 50; studies = 1; low-quality evidence) (NRS evidence: OR 1.46, 95% CI 0.71 to 2.98; participants = 684; studies = 2; very low-quality evidence). No studies reported on additional adverse outcomes. 2. PCC versus rFVIIa For this comparison, all evidence was provided from NRSs. PCC likely results in a large reduction of RBCs transfused intra-operatively in comparison to rFVIIa (MD-4.98 units, 95% CI -6.37 to -3.59; participants = 256; studies = 2; moderate-quality evidence). PCC may have little to no effect on the incidence of RBC units transfused comparative to rFVIIa; evidence is very uncertain (OR 0.16, 95% CI 0.02 to 1.56; participants = 150; studies = 1; very low-quality evidence). PCC may have little to no effect on the number of thrombotic events comparative to rFVIIa; evidence is very uncertain (OR 0.51, 95% CI 0.23 to 1.16; participants = 407; studies = 4; very low-quality evidence). PCC may have little to no effect on the incidence of mortality (OR 1.07, 95% CI 0.38 to 3.03; participants = 278; studies = 3; very low-quality evidence) or intensive care length of stay comparative to rFVIIa (MD -40 hours, 95% CI -110.41 to 30.41; participants = 106; studies = 1; very low-quality evidence); evidence is very uncertain . PCC may reduce bleeding (MD -674.34 mLs, 95% CI -906.04 to -442.64; participants = 150; studies = 1; very low-quality evidence) and incidence of renal replacement therapy (OR 0.29, 95% CI 0.12 to 0.71; participants = 106; studies = 1; very low-quality evidence) comparative to rFVIIa; evidence is very uncertain. No studies reported on other adverse events. AUTHORS' CONCLUSIONS PCCs could potentially be used as an alternative to standard therapy for coagulopathic bleeding post-cardiac surgery compared to FFP as shown by moderate-quality evidence and it may be an alternative to rFVIIa in refractory non-surgical bleeding but this is based on moderate to very low quality of evidence.
PICO Summary
Population
Patients of all age groups undergoing cardiac surgery who had coagulopathic bleeding (18 studies, n= 4,993).
Intervention
Prothrombin complex concentrates (PCCs).
Comparison
Standard therapy (current institutional protocol for bleeding diathesis), fresh frozen plasma (FFP) and recombinant factor VIIa (rFVIIa).
Outcome
Of the 18 studies included, two were randomised controlled trials (RCTs), and 16 were non‐randomised trials (NRSs). PCCs compared to standard therapy: PCCs had an overall reduction in red blood cell (RBC) transfusion (both units of RBC transfusion and incidence of RBC transfusion) when compared to FFP. There was potentially no reduction in chest drain output (bleeding) in the RCTs. There was no difference in the reported outcomes of blood clots, death, intensive care stay and the requirement of dialysis in both RCTs and NRSs. The RCTs had moderate to low quality of evidence and the NRS had very low to low quality of evidence. PCCs compared to rFVIIa: PCCs had a large reduction in red blood cell transfusion when compared to rFVIIa. The quality of this evidence was moderate. For the remaining outcomes, two studies found that there was no difference in blood clots, death, bleeding into drains, intensive care stay and the requirement for dialysis. The quality of the evidence for these outcomes was very low.
BACKGROUND Coagulopathy in cardiac surgery is frequently associated with acquired hypofibrinogenaemia, which can be treated with either purified fibrinogen concentrate (FC) or cryoprecipitate. Because the latter is not purified and therefore contains additional coagulation factors, it is thought to be more effective for treatment of coagulopathy that occurs after prolonged cardiopulmonary bypass (CPB). We examined the impact of CPB duration on the efficacy of the two therapies in cardiac surgery. METHODS This was a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) RCT comparing FC (4 g) to cryoprecipitate (10 U) in adult patients undergoing cardiac surgery and experiencing bleeding with acquired hypofibrinogenaemia (n=735). The primary outcome was allogeneic blood products transfused within 24 h after CPB. Subjects were stratified by CPB duration (≤120, 121-180, and >180 min). The interaction of treatment assignment with CPB duration was tested. RESULTS Subjects with longer CPB duration experienced more bleeding and transfusion. With CPB time ≤120 min (FC, n=134; cryoprecipitate, n=146), the ratio of least-squares means between the FC and cryoprecipitate groups for total allogeneic blood products at 24 h was 0.90 (one-sided 97.5% confidence interval [CI]: 0.00-1.12); P=0.004. For subjects with CPB time 121-180 min, it was 1.00 ([one-sided 97.5% CI: 0.00-1.22]; P=0.03], and for CPB time >180 min it was 0.91 ([one-sided 97.5% CI: 0.00-1.12]; P=0.005). Results were similar for all secondary outcomes, with no interaction between treatment and CPB duration for all outcomes. CONCLUSIONS The haemostatic efficacy of FC was non-inferior to cryoprecipitate irrespective of CPB duration in cardiac surgery. CLINICAL TRIAL REGISTRATION NCT03037424.
PICO Summary
Population
Adult patients undergoing cardiac surgery and experiencing bleeding with acquired hypofibrinogenaemia, enrolled in the FIBRES trial, across 11 centres in Canada (n= 735).
Intervention
Fibrinogen concentrate (FC), (n= 372).
Comparison
Cryoprecipitate (n= 363).
Outcome
The primary outcome was allogeneic blood products transfused within 24 hours after cardiopulmonary bypass (CPB). Patients with longer CPB duration experienced more bleeding and transfusion. With CPB time ≤120 min (FC, n= 134; cryoprecipitate, n= 146), the ratio of least-squares means between the FC and cryoprecipitate groups for total allogeneic blood products at 24 hours was 0.90 (one-sided 97.5% confidence interval (CI), [0.00, 1.12]). For patients with CPB time 121-180 min, it was 1.00 ([one-sided 97.5% CI [0.00, 1.22]), and for CPB time >180 min it was 0.91 ([one-sided 97.5% CI [0.00, 1.12]). Results were similar for all secondary outcomes, with no interaction between treatment and CPB duration for all outcomes.
BACKGROUND AND OBJECTIVES Transfusion-associated circulatory overload (TACO) is a major cause of severe transfusion-related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product-specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change. MATERIALS AND METHODS In a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post-operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). RESULTS Change in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline. CONCLUSION Transfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO.
PICO Summary
Population
Patients undergoing coronary bypass surgery (n= 16).
Intervention
Autologous red blood cells (RBCs) transfusion, with a subsequent infusion of saline (RBCs: Saline, n= 8).
Comparison
Saline infusion with a subsequent transfusion of RBCs (Saline: RBCs, n= 8).
Outcome
The primary outcome was the difference in pulmonary capillary wedge pressure (PCWP) before and after transfusion (ΔPCWP). Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). Change in PCWP was not higher after autologous RBCs transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBCs transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBCs transfusion versus saline.
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.
OBJECTIVES Cardiopulmonary bypass in cardiac surgery has been associated with several deleterious effects including haemodilution and systemic inflammation. Modified ultrafiltration (MUF) has been well established in paediatric cardiac surgery in counteracting postperfusion syndrome. However, MUF is less commonly used in adult cardiac surgery. In this meta-analysis, we compared clinical outcomes in adult patients who underwent cardiopulmonary bypass with and without MUF. METHODS Electronic searches were performed using Pubmed, Ovid Medline, EMBASE and the Cochrane Library until April 2020. Selection criteria were randomized studies of adult cardiac surgery patients comparing MUF versus no MUF. Primary outcomes were postoperative mortality, haematocrit, blood transfusion, chest tube drainage, duration of intensive care unit (ICU) stay and duration of mechanical ventilation. RESULTS Thirteen randomized controlled trials were included, comprising 626 patients in the MUF group, and 610 patients in the control (no-MUF) group. There was a significantly improved postoperative haematocrit [mean difference 2.70, 95% confidence interval (CI) 0.68-4.73, P = 0.009], lower chest tube drainage (mean difference -105 ml, 95% CI -202 to -7 ml, P = 0.032), lower postoperative blood transfusion rate (mean difference -0.73 units, 95% CI -0.98 to -0.47 units, P < 0.0001) and shorter duration of ICU stay (mean difference -0.13 days, 95% CI -0.27 to -0.00 days, P = 0.048) in the MUF group. There was no difference in ventilation time (mean difference -0.47 h, 95% CI -2.05 to 1.12 h, P = 0.56) or mortality rates (odds ratio 0.62, 95% CI 0.28-1.33, P = 0.22). There were no reported complications associated with MUF. CONCLUSIONS MUF is a safe and feasible option in adult cardiac patients, with significant benefits including improved postoperative haematocrit, as well as reduced postoperative chest tube bleeding, transfusion requirements and duration of ICU stay.
There was a significantly improved postoperative haematocrit (mean difference 2.70; 95% CI [0.68, 4.73]), lower chest tube drainage (mean difference -105 ml; 95% CI [-202, -7 ml]), lower postoperative blood transfusion rate (mean difference -0.73 units; 95% CI [-0.98, -0.47 units]) and shorter duration of intensive care unit stay (mean difference -0.13 days; 95% CI [-0.27, -0.00 days]) in the MUF group. There was no difference in ventilation time (mean difference -0.47 h; 95% CI [-2.05, 1.12 h]) or mortality rates (odds ratio 0.62; 95% CI [0.28, 1.33]). There were no reported complications associated with MUF.
BACKGROUND Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding. OBJECTIVES The aim of this study was to investigate clinical outcomes associated with the use of 4-factor prothrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding. METHODS The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model. RESULTS The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used. CONCLUSIONS The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed.
PICO Summary
Population
Patients with severe direct oral anticoagulant-related bleeding (60 studies, n= 4,735).
Mortality rates, thromboembolic events, and haemostatic efficacy were meta-analyzed using a random effects model. The mortality rate was 17.7%; 95% CI [15.1%, 20.4%], and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial haemorrhages (15.4%). The thromboembolism rate was 4.6%; 95% CI [3.3%, 6.0%], being particularly high with andexanet (10.7%; 95% CI [6.5%, 15.7%]). The effective haemostasis rate was 78.5%; 95% CI [75.1%, 81.8%] and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2%; 95% CI [5.5%, 23.1%] and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective haemostasis (relative risk: 3.63; 95% CI [2.56, 5.16]). The results were robust regardless of the type of study or the haemostatic scale used.
Objective: Anemia is frequent in patients with acute myocardial infarction (AMI), and the optimal red blood cell transfusion strategy for AMI patients with anemia is still controversial. We aimed to compare the efficacy of restrictive and liberal red cell transfusion strategies in AMI patients with anemia. Methods: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, and Clinicaltrials.gov, from their inception until March 2021. Studies designed to compare the efficacy between restrictive and liberal red blood cell transfusion strategies in patients with AMI were included. The primary outcome was all-cause mortality, including overall mortality, in-hospital or follow-up mortality. Risk ratios (RR) with 95% confidence intervals (CI) were presented and pooled by random-effects models. Results: The search yielded a total of 6,630 participants in six studies. A total of 2,008 patients received restrictive red blood cell transfusion while 4,622 patients were given liberal red blood cell transfusion. No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups (RR = 1.07, 95% CI = 0.82-1.40, P = 0.62; RR = 0.89, 95% CI = 0.56-1.42, P = 0.62). However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion (RR = 1.22, 95% CI = 1.00-1.50, P = 0.05). No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. In addition, subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design. Conclusion: Restrictive and liberal red blood cell transfusion have a similar effect on overall mortality and follow-up mortality in AMI patients with anemia. However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion. The findings suggest that transfusion strategy should be further evaluated in future studies.
PICO Summary
Population
Patients with acute myocardial infarction and anaemia (6 studies, n= 6,630).
Intervention
Restrictive red blood cell transfusion strategy (n= 2,008).
Comparison
Liberal red blood cell transfusion strategy (n= 4,622).
Outcome
No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups (RR= 1.07; 95% CI [0.82, 1.40]; RR= 0.89; 95% CI [0.56, 1.42]). However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion (RR= 1.22; 95% CI [1.00, 1.50]). No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. In addition, subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design.
McGuinness S, Charlewood R, Gilder E, Parke R, Hayes K, Morley S, Al-Ibousi A, Deans R, Howe B, Johnson L, et al
Vox sanguinis. 2021
Editor's Choice
Abstract
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.
PICO Summary
Population
Adult cardiac surgery patients who were at high risk of platelet transfusion, enrolled in the CLIP-NZ Pilot study (n= 89).
Intervention
Cryopreserved platelet transfusion (n= 49).
Comparison
Liquid-stored platelet transfusion (n= 40).
Outcome
The primary outcome was protocol safety and feasibility. 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 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.
Editor's Choice