Point-of-Care Hemostatic Testing in Cardiac Surgery: A Stepped-Wedge Clustered Randomized Controlled Trial.
Cardiac surgery is frequently complicated by coagulopathic bleeding that is difficult to optimally manage using standard hemostatic testing. We hypothesized that point-of-care hemostatic testing within the context of an integrated transfusion algorithm would improve the management of coagulopathy in cardiac surgery and thereby reduce blood transfusions.
We conducted a pragmatic multicenter stepped-wedge cluster randomized controlled trial of a point-of-care-based transfusion algorithm in consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at 12 hospitals from October 6, 2014, to May 1, 2015. Following a 1-month data collection at all participating hospitals, a transfusion algorithm incorporating point-of-care hemostatic testing was sequentially implemented at 2 hospitals at a time in 1-month intervals, with the implementation order randomly assigned. No other aspects of care were modified. The primary outcome was red blood cell transfusion from surgery to postoperative day 7. Other outcomes included transfusion of other blood products, major bleeding, and major complications. The analysis adjusted for secular time trends, within-hospital clustering, and patient-level risk factors. All outcomes and analyses were prespecified before study initiation.
Among the 7402 patients studied, 3555 underwent surgery during the control phase and 3847 during the intervention phase. Overall, 3329 (45.0%) received red blood cells, 1863 (25.2%) received platelets, 1645 (22.2%) received plasma, and 394 (5.3%) received cryoprecipitate. Major bleeding occurred in 1773 (24.1%) patients, and major complications occurred in 740 (10.2%) patients. The trial intervention reduced rates of red blood cell transfusion (adjusted relative risk, 0.91; 95% confidence interval, 0.85-0.98; P=0.02; number needed to treat, 24.7), platelet transfusion (relative risk, 0.77; 95% confidence interval, 0.68-0.87; P<0.001; number needed to treat, 16.7), and major bleeding (relative risk, 0.83; 95% confidence interval, 0.72-0.94; P=0.004; number needed to treat, 22.6), but had no effect on other blood product transfusions or major complications.
Implementation of point-of-care hemostatic testing within the context of an integrated transfusion algorithm reduces red blood cell transfusions, platelet transfusions, and major bleeding following cardiac surgery. Our findings support the broader adoption of point-of-care hemostatic testing into clinical practice.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02200419.
Karkouti K
，Callum J
，Wijeysundera DN
，Rao V
，Crowther M
，Grocott HP
，Pinto R
，Scales DC
，TACS Investigators
... -
《-》
Blood transfusion strategies for major bleeding in trauma.
Trauma is a leading cause of morbidity and mortality worldwide. Research shows that haemorrhage and trauma-induced coagulopathy are reversible components of traumatic injury, if identified and treated early. Lack of consensus on definitions and transfusion strategies hinders the translation of this evidence into clinical practice.
To assess the beneficial and harmful effects of transfusion strategies started within 24 hours of traumatic injury in adults (aged 16 years and over) with major bleeding.
CENTRAL, MEDLINE, Embase, five other databases, and three trial registers were searched on 20 November 2023. We also checked reference lists of included studies to identify any additional studies.
We included randomised controlled trials (RCTs) of adults (aged 16 years and over) receiving blood products for the management of bleeding within 24 hours of traumatic injury.
We used standard Cochrane methodology to perform the review and assessed the certainty of the evidence using GRADE.
We included 18 RCTs with 5041 participants. Comparison 1: Prehospital transfusion strategies Five studies compared use of plasma (fresh frozen plasma (FFP) or lyophilised plasma) versus 'standard of care'. We are uncertain of the effect of plasma on all-cause mortality at 24 hours (risk ratio (RR) 1.05, 95% confidence interval (CI), 0.48 to 2.30; 3 studies, 279 participants; very low certainty evidence). There is probably no difference between plasma and standard of care in all-cause mortality at 30 days (RR 0.95, 95% CI 0.78 to 1.17; 3 studies, 664 participants; moderate-certainty evidence). However, the results of one cluster-RCT that could not be included in our meta-analysis suggested that plasma may be associated with a lower risk of death at 30 days (RR 0.54, 95% CI 0.42 to 0.70; 1 study, 481 participants; low-certainty evidence). There may be no difference between plasma and standard of care in the total number of thromboembolic events in 30 days (RR 1.23, 95% CI 0.67 to.2.27; 4 studies, 586 participants; low-certainty evidence). Comparison 2: In-hospital transfusion strategies Ten studies evaluated this comparison, seven providing usable data. The studies evaluated cryoprecitate (three studies); fixed-ratio blood component transfusion (three studies); fresh frozen plasma (FFP) (one study); lyophilised plasma (one study); leucoreduced red blood cells (one study); and a restrictive transfusion strategy (one study). All-cause mortality at 24 hours For all-cause mortality at 24 hours, there is probably no difference between: • cryoprecipitate plus a major haemorrhage protocol (MHP) versus MHP alone (RR 0.92, 95% CI 0.70 to 1.21; 1 study, 1577 participants; moderate-certainty evidence); and • blood products (plasma:platelets:red blood cells (RBCs)) transfused in 1:1:1 ratio versus 1:1:2 ratio (RR 0.75, 95% CI 0.52 to 1.08; 1 study, 680 participants; moderate-certainty evidence). We are uncertain of the effect on all-cause mortality at 24 hours for: • blood products (RBCs:FFP) transfused in 1:1 ratio versus transfusion according to coagulation and full blood count results (Peto odds ratio (POR) 0.45, 0.17 to 1.22; 1 study, 434 participants; very low certainty evidence); and • lyophilised (FlyP) plasma versus FFP (POR 1.04, 95% CI 0.06 to 17.23; 1 study, 47 participants; very low certainty evidence); All-cause mortality at 30 days For all-cause mortality at 30 days, there is probably no difference between blood products (plasma:platelets:RBCs) transfused in a 1:1:1 ratio versus a 1:1:2 ratio (RR 0.85, 95% CI 0.65 to 1.11; 1 study, 680 participants; moderate-certainty evidence). There may be little to no difference between the following interventions in all-cause mortality at 30 days: • cryoprecipitate plus MHP versus MHP alone (RR 0.77, 95% CI 0.33 to 1.78; 2 studies, 1572 participants; low-certainty evidence); and •leucoreduced RBCs versus standard RBCs (RR 1.20, 95% CI 0.74 to 1.95; 1 study,55 participants; low certainty evidence). We are uncertain of the effect on all-cause mortality at 30 days for: •lyophilised plasma versus FFP (RR 0.75, 95% CI 0.28 to 2.02; 1 study, 47 participants; very low certainty evidence); and • blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus standard MHP (RR 2.25, 95% CI 0.90 to 5.62; 1 study, 69 participants; very low certainty evidence). Total number of thromboembolic events at 30 days There may be little to no difference between the following interventions for total thromboembolic events at 30 days: • cryoprecipitate plus MHP versus MHP alone (RR 0.55, 95% CI 0.08 to 3.72; 2 studies, 1645 participants; low-certainty evidence); and • blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus 1:1:2 ratio (RR 1.03, 95% CI 0.75 to 1.42; 1 study, 680 participants; low-certainty evidence). We are uncertain of the effect on the total number of thromboembolic events at 30 days for: •blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus standard MHP (POR 6.83, 95% CI 0.68 to 68.35; 1 study, 69 participants; very low certainty evidence). Comparison 3: Whole blood versus individual blood products We are uncertain of the effect of modified (leucoreduced) whole blood versus blood products (RBCs:plasma) transfused in a 1:1 ratio on all-cause mortality at 24 hours (RR 1.13, 95% CI 0.37 to 3.49) or 30 days (RR 1.62, 95% CI 0.69 to 3.80) (1 study, 107 participants; very low certainty evidence). Comparison 4: Goal-directed blood transfusion strategy of viscoelastic haemostatic assay (VHA) versus conventional laboratory coagulation tests (CCT) to guide haemostatic therapy There may be little or no difference in all-cause mortality at 24 hours between VHA and CCT (RR 0.85, 95% CI 0.54 to 1.35; 1 study, 396 participants; low-certainty evidence). We are uncertain of the effects on all-cause mortality at 30 days (RR 0.75, 95% CI 0.48 to 1.17; 2 studies, 506 participants; very low certainty evidence). There is probably no difference between VHA and CCT in total thromboembolic events at 30 days (RR 0.65, 95% CI 0.35 to 1.18; 1 study 396 participants; moderate-certainty evidence).
Overall, there was little to no evidence of a difference between blood transfusion strategies for mortality or thromboembolic events. The studies covered a wide range of interventions, and the comparators and standard of care practice varied between trials, thereby limiting the pooling of data. Further research is needed.
Brunskill SJ
，Disegna A
，Wong H
，Fabes J
，Desborough MJ
，Dorée C
，Davenport R
，Curry N
，Stanworth SJ
... -
《-》
Implementation strategies for WHO guidelines to prevent, detect, and treat postpartum hemorrhage.
Despite World Health Organization (WHO) guidelines for preventing, detecting, and treating postpartum hemorrhage (PPH), effective implementation has lagged.
To evaluate the clinical benefits and harms of implementation strategies used to promote adherence to WHO clinical guidelines for the prevention, detection, and treatment of PPH.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and two trial registries, along with reference checking, citation searching, and contact with study authors. The latest search date was 25 April 2024.
We included randomized controlled trials (RCTs), including cluster, pragmatic, and stepped-wedge designs, and non-randomized studies of interventions (NRSIs), including interrupted time series (ITS) studies, controlled before-after (CBA) studies, and follow-up (cohort) studies containing concurrent controls that focused on or described implementation strategies of WHO guidelines for the prevention, detection, and treatment of PPH. Participants were birth attendants and people giving birth in a hospital or healthcare facility. We excluded studies that did not implement a WHO PPH recommendation, had no comparator group, or did not report clinical/implementation outcomes.
Our critical outcomes were: adherence to WHO-recommended guidelines for PPH prevention, detection, and treatment; PPH ≥ 500 mL; PPH ≥ 1000 mL; additional uterotonics within 24 hours after birth; blood transfusions; maternal death; severe morbidities (major surgery; admission to intensive care unit [ICU]); and adverse effects (variable and related to the clinical intervention) during hospitalization for birth. Our important outcomes were: breastfeeding at discharge; implementation outcomes such as acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability of the implementation strategy; and health professional outcomes such as knowledge and skill.
We used the RoB 2 and ROBINS-I tools to assess risk of bias in RCTs and NRSIs, respectively.
Two review authors independently selected studies, performed data extraction, and assessed risk of bias and trustworthiness. Due to the nature of the data, we reported relevant results for each comparison and outcome but did not attempt quantitative synthesis. We used GRADE to assess the certainty of evidence.
We included 13 studies (9 cluster-RCTs and 4 NRSIs) with a total of 1,027,273 births and more than 4373 birth attendants. The included studies were conducted in 17 different countries. Most trials were conducted in resource-limited settings. None of the included studies reported data on the use of additional uterotonics within 24 hours after birth or adverse effects.
Single-component implementation strategies versus usual care for PPH prevention, detection, and treatment We do not know if single-component implementation strategies have any effect on adherence to WHO PPH prevention recommendations, PPH ≥ 500 mL, PPH ≥ 1000 mL, or blood transfusion (very low-certainty evidence). Low-certainty evidence suggests that single-component implementation strategies may have little to no effect on maternal death (86,788 births, 3 trials); may increase severe morbidity related to ICU admission (26,985 births, 1 trial); and may reduce severe morbidity related to surgical outcomes (26,985 births, 1 trial). No trials in this comparison measured the effect on adherence to WHO treatment guidelines. Multicomponent implementation strategies versus usual care for PPH prevention, detection, and treatment We do not know if multicomponent implementation strategies have any effect on adherence to WHO PPH treatment recommendations, PPH ≥ 500 mL, blood transfusion, or severe morbidity relating to surgical outcomes (very low-certainty evidence). Multicomponent implementation strategies may have little to no effect on maternal death (274,008 births, 2 trials; low-certainty evidence) compared to usual care. No trials in this comparison measured the effect on adherence to WHO PPH prevention recommendations, PPH ≥ 1000 mL, or severe morbidity (outcomes related to ICU admission). Multicomponent implementation strategies versus enhanced usual care for PPH prevention, detection, and treatment Low-certainty evidence suggests that multicomponent implementation strategies may improve adherence to WHO PPH prevention recommendations (14,718 births, 2 trials) and adherence to WHO PPH treatment recommendations (356,913 births, 2 trials) compared to enhanced usual care. Multicomponent implementation strategies probably have little to no effect on maternal death (224,850 births, 2 trials; moderate-certainty evidence), severe morbidity related to ICU admission (224,850 births, 2 trials; moderate-certainty evidence), and surgical morbidity (210,132 births, 1 trial; moderate-certainty evidence) compared to enhanced usual care. We do not know if multicomponent implementation strategies affect PPH ≥ 500 mL, PPH ≥ 1000 mL, or blood transfusion (very low-certainty evidence).
Multicomponent implementation strategies may improve adherence to WHO PPH prevention and treatment recommendations, but they probably result in little to no difference in ICU admissions, surgical morbidity, or maternal death. The majority of available evidence is of low to very low certainty, thus we cannot draw any robust conclusions on the effects of implementation strategies for WHO guidelines to prevent, detect, and treat PPH. While all included studies used the implementation strategy of 'train and educate,' the effects seem to be limited when used as a single strategy. Additional research using pragmatic, hybrid effectiveness-implementation study designs that measure implementation outcomes simultaneously alongside clinical outcomes would be beneficial to understand contextual factors, barriers, and facilitators that affect implementation.
This Cochrane review had no dedicated external funding. Dr Rose Molina, who is employed by Beth Israel Deaconess Medical Center, received funding from Ariadne Labs (Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital) for her time. As a funder, Ariadne Labs had no involvement in the development of the protocol or conduct of the review. The views and opinions expressed therein are those of the review authors and do not necessarily reflect those of Ariadne Labs.
Registration: PROSPERO (CRD42024563802) available via https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024563802.
Semrau K
，Litman E
，Molina RL
，Marx Delaney M
，Choi L
，Robertson L
，Noel-Storr AH
，Guise JM
... -
《Cochrane Database of Systematic Reviews》
ResearchGate
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