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The role of preoperative transfusion in sickle cell disease, a systematic review and meta-analysis
Abdu, Y., Rahhal, A., Ahmed, K., Adli, N., Abdou, M., Ali, E. A. H., Al-Kindi, S., Al Rasheed, M., Altooq, J., Bougmiza, I., et al
Blood reviews. 2024;:101183
Abstract
This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022. Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75-10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.
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Evidence-based interventions for reducing sickle cell disease-associated morbidity and mortality in sub-Saharan Africa: A scoping review
Arji, E. E., Eze, U. J., Ezenwaka, G. O., Kennedy, N.
SAGE open medicine. 2023;11:20503121231197866
Abstract
OBJECTIVE Sickle cell disease is a lifelong illness affecting millions of people globally, but predominantly burdensome in sub-Saharan Africa, where most affected children do not live to adulthood, despite available evidence-based interventions that reduce the disease burden in high-income countries. METHOD We reviewed studies evaluating evidence-based interventions that decrease sickle cell disease-related morbidity and mortality among children living in sub-Saharan Africa. We used the Joanna Briggs scoping review methodological framework and grouped identified evidence-based interventions into preventative pharmacotherapeutic agents, newborn screening and comprehensive healthcare, disease-modifying agents, nutritional supplementation, systemic treatment, supportive agents and patient/carer/population education. RESULTS We included 36 studies: 18 randomized controlled trials, 11 observational studies, 5 before-and-after studies and 2 economic evaluation studies, with most of the studies performed in West African countries. Included studies suggest evidence-based interventions effectively to reduce the common morbidities associated with sickle cell disease such as stroke, vaso-occlusive crisis, acute chest syndrome, severe anaemia and malaria infection. Evidence-based interventions also improve survival among study participants. Specifically, our review shows hydroxyurea increases haemoglobin and foetal haemoglobin levels, a finding with practical implications given the challenges with blood transfusion in this setting. The feasibility of implementing individual interventions is hampered by challenges such as affordability, accessibility and the availability of financial and human resources. CONCLUSION Our review suggests that regular use of low-dose hydroxyurea therapy, sulphadoxine-pyrimethamine chemoprophylaxis, L-arginine and Omega-3 fatty acid supplementation and establishment of specialist stand-alone sickle cell clinics could reduce the sickle cell disease-associated morbidity and mortality in sub-Saharan Africa countries.
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Preoperative hemoglobin and perioperative blood transfusion in major head and neck surgery: a systematic review and meta-analysis
Ali, M., Dort, J. C., Sauro, K. M.
Journal of Otolaryngology - Head & Neck Surgery = Le Journal D'oto-Rhino-Laryngologie Et De Chirurgie Cervico-Faciale. 2023;52(1):3
Abstract
BACKGROUND There is a growing concern with inappropriate, excessive perioperative blood transfusions. Understanding the influence of low preoperative hemoglobin (Hgb) on perioperative blood transfusion (PBT) in head and neck cancer (HNC) surgery with free flap reconstruction may help guide clinical practice to reduce inappropriate treatment among these patients. The objective is to synthesize evidence regarding the association between preoperative Hgb and PBT among major HNC free flap surgeries. METHODS Terms and synonyms for HNC surgical procedures, Hgb and PBT were used to search MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Reviews from inception to February 2020. Reference lists of included full texts and studies reporting the preoperative Hgb, anemia or hematocrit (exposure) and the PBT (outcome) in major HNC surgery with free flap reconstruction were eligible. Studies examining esophageal, thyroid and parathyroid neoplasms were excluded; as were case reports, case series (n < 20), editorials, reviews, perspectives, viewpoints and responses. Two independent, blinded reviewers screened titles, abstracts and full texts in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. A random-effects model was used to pool reported data. The primary outcome was the proportion of patients who had a PBT. Subgroup analysis examined sources of heterogeneity for perioperative predictors of PBT (age, sex, flap type, flap site and preoperative Hgb). We also examined mean preoperative Hgb in the PBT and no PBT groups. RESULTS Patients with low preoperative Hgb were transfused more than those with normal Hgb (47.62%, 95% CI = 41.19-54.06, I(2) = 0.00% and 13.92%, 95% CI = 10.19-17.65, I(2) = 20.69%, respectively). None of the predictor variables explained PBT. The overall pooled mean preoperative Hgb was 12.96 g/dL (95% CI = 11.33-14.59, I(2) = 0.00%) and was 13.58 g/dL (95% CI = 11.95-15.21, I(2) = 0.00%) in the no PBT group and 12.05 g/dL (95% CI = 10.01 to 14.09, I(2) = 0.00%) in the PBT group. CONCLUSIONS The heterogeneity between studies, especially around the trigger for PBT, highlights the need for additional research to guide clinical practice of preoperative Hgb related to PBT to enhance patient outcomes and improve healthcare stewardship.
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Shock index as predictor of massive transfusion and mortality in patients with trauma: a systematic review and meta-analysis
Carsetti, A., Antolini, R., Casarotta, E., Damiani, E., Gasparri, F., Marini, B., Adrario, E., Donati, A.
Critical Care (London, England). 2023;27(1):85
Abstract
BACKGROUND Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. METHODS This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. RESULTS Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR-) were 4.24 [3.18-5.65] and 0.39 [0.29-0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR- were 1.39 [1.36-1.42] and 0.87 [0.85-0.89], respectively. CONCLUSIONS Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality.
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Red Blood Cell Transfusion Guided by Hemoglobin Only or Integrating Perfusion Markers in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis
Putaggio, A., Tigano, S., Caruso, A., La Via, L., Sanfilippo, F.
Journal of cardiothoracic and vascular anesthesia. 2023
Abstract
OBJECTIVE Strategies for red blood cell (RBC) transfusion in patients undergoing cardiac surgery have been traditionally anchored to hemoglobin (Hb) targets. A more physiologic approach would consider markers of organ hypoperfusion. DESIGN The authors conducted a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials (RCTs). SETTING Cardiac surgery. PARTICIPANTS Adult patients. INTERVENTION RBC transfusion targeting only Hb levels compared with strategies combining Hb values with markers of organ hypoperfusion. MEASUREMENTS AND MAIN RESULTS Primary outcomes were the number of RBC units transfused, the number of patients transfused at least once, and the average number of transfusions. Secondary outcomes were postoperative complications, intensive care (ICU) and hospital lengths of stay, and mortality. Only 2 RCTs were included (n = 257 patients), and both used central venous oxygen saturation (ScvO(2)) as a marker of organ hypoperfusion (cut-off: <70% or ≤65%). A transfusion protocol combining Hb and ScvO(2) reduced the overall number of RBC units transfused (risk ratio [RR]: 1.57 [1.33-1.85]; p < 0.0001, I(2) = 0%), and the number of patients transfused at least once (RR: 1.33 [1.16-1.53]; p < 0.0001, I(2) = 41%), but not the average number of transfusions (mean difference [MD]: 0.18 [-0.11 to 0.47]; p = 0.24, I(2) = 66%), with moderate certainty of evidence. Mortality (RR: 1.29, [0.29-5.77]; p = 0.73, I(2) = 0%), ICU length-of-stay (MD: -0.06 [-0.58 to 0.46]; p = 0.81, I(2) = 0%), hospital length-of-stay (MD: -0.05 [-1.49 to 1.39];p = 0.95, I(2) = 0%), and all postoperative complications were not affected. CONCLUSIONS In adult patients undergoing cardiac surgery, a restrictive protocol integrating Hb values with a marker of organ hypoperfusion (ScvO(2)) reduces the number of RBC units transfused and the number of patients transfused at least once without apparent signals of harm. These findings were preliminary and warrant further multicentric research.
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Prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis of non-pharmacological interventions
Hariri, G., Collet, L., Duarte, L., Martin, G. L., Resche-Rigon, M., Lebreton, G., Bouglé, A., Dechartres, A.
Critical care (London, England). 2023;27(1):354
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Editor's Choice
Abstract
BACKGROUND Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. METHODS We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. RESULTS We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I(2) = 0%; P(het) = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I(2) = 23%; P(het) = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I(2) = 53%; P(het) < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; P(het) = 0.67; I(2) = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; P(het) = 0.25; I(2) = 26%). CONCLUSIONS Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.
PICO Summary
Population
Adult patients undergoing cardiac surgery such as coronary artery bypass grafting and/or valve surgery (86 randomised controlled trials (RCTs) n= 25,855).
Intervention
Non-pharmacological interventions to reduce the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI): Goal directed perfusion (GDP), pulsatile flow during cardiopulmonary bypass (CPB), minimally invasive extracorporeal circulation (MECC), epidural analgesia, remote ischemic preconditioning (RIPc), tight glycemic control, kidney disease improving global outcomes care bundle, hyperoxia during CPB, restrictive transfusion strategy, high target arterial pressure.
Comparison
Usual care.
Outcome
No intervention had high-quality evidence to reduce CSA-AKI. From the included studies, the most frequent intervention was RIPc (31 RCTs, n= 7,738), MECC, (14 RCTs, n= 1,617) and pulsatile blood flow during CPB (10 RCTs, n= 1,993). Three interventions were associated with a significantly reduced risk of CSA-AKI: GDP, RIPc and pulsatile flow during CPB.
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Potential benefits of restrictive transfusion in upper gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials
Teutsch, B., Veres, D. S., Pálinkás, D., Simon, O. A., Hegyi, P., Erőss, B.
Scientific reports. 2023;13(1):17301
Abstract
The optimal red blood cell (RBC) transfusion strategy in acute gastrointestinal bleeding (GIB) is debated. We aimed to assess the efficacy and safety of restrictive compared to liberal transfusion strategies in the GIB population. We searched PubMed, CENTRAL, Embase, and Web of Science for randomised controlled trials on 15.01.2022 without restrictions. Studies comparing lower to higher RBC transfusion thresholds after GIB were eligible. We used the random effect model and calculated pooled mean differences (MD), risk ratios (RR) and proportions with 95% confidence intervals (CI) to calculate the overall effect size. The search yielded 3955 hits. All seven eligible studies reported on the upper GIB population. Restrictive transfusion did not increase the in-hospital- (RR: 0.94; CI 0.46, 1.94) and 30-day mortality (RR: 0.71; CI 0.35, 1.45). In-hospital- and 28 to 45-day rebleeding rate was also not higher with the restrictive modality (RR: 0.67; CI 0.30, 1.50; RR:0.75; CI 0.49, 1.16, respectively). Results of individual studies showed a lower rate of transfusion reactions and post-transfusion intervention if the transfusion was started at a lower threshold. A haemoglobin threshold > 80 g/L may result in a higher untoward outcome rate. In summary, restrictive transfusion does not appear to lead to a higher rate of significant clinical endpoints. The optimal restrictive transfusion threshold should be further investigated.
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Definitions of massive transfusion in adults with critical bleeding: a systematic review
Lin, V. S., Sun, E., Yau, S., Abeyakoon, C., Seamer, G., Bhopal, S., Tucker, H., Doree, C., Brunskill, S. J., McQuilten, Z. K., et al
Critical care (London, England). 2023;27(1):265
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Editor's Choice
Abstract
BACKGROUND Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT. METHODS We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure. RESULTS Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5). CONCLUSIONS Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
PICO Summary
Population
Adult patients with major bleeding who had received, or were anticipated to receive, a massive transfusion (MT) in any clinical setting (30 randomised controlled trials (RCTs)).
Intervention
Systematic review identifying all MT definitions used in RCTs to date to inform the development of consensus definitions for MT.
Comparison
Outcome
Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n= 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n= 5).
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Effective management of foetal anaemia in Rh(D) alloimmunised pregnant women with intrauterine transfusion: a Systematic Review
Prescott, B., Jackson, D. E.
Hematology, transfusion and cell therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops. STUDY DESIGN AND METHOD A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method. RESULTS Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present. CONCLUSION The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.
PICO Summary
Population
Rh(D) alloimmunised pregnant women (15 studies).
Intervention
Systematic review and meta-analysis to determine the effectiveness and safety of intrauterine transfusions (IUTs).
Comparison
Outcome
The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present.
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The Role of Non-genetic Therapies to Reduce the Incidence of Sickle Cell Crisis: A Systematic Review
Pingili, S., Makkena, V. K., Jaramillo, A. P., Awosusi, B. L., Ayyub, J., Dabhi, K. N., Gohil, N. V., Tanveer, N., Hussein, S., Hamid, P.
Cureus. 2023;15(8):e42785
Abstract
Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts due to blood vessel occlusion, resulting in hypoxia, ischemia, and inflammation. Preventing these incidents improves the quality of life and lowers mortality rates in Sickle Cell Disease (SCD) patients. This systematic review aims to describe the drugs, their mechanisms of action, dosages, changes in hemoglobin parameters, decrease in VOCs, delay the time for the next VOC, decrease in the length of hospital stay, and side effects associated with these drugs. This review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. For this review, we searched the PubMed, Google Scholar, and Cochrane databases and screened them for full free texts published in English and studied in humans in the last five years beginning in 2018. Randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and traditional reviews were all included in the search. According to the type of study, quality assessment tools are used, and eight papers are chosen. Full-text articles from these papers are studied, analyzed, and tabulated. We discussed seven interventions that are used to treat sickle cell disease. Voxelotor, crizanlizumab, L-glutamate, long-term blood transfusions, Zinc (Zn), Niprisan®, and Ciklavit* were found to reduce the number and severity of VOC. We discovered that VOCs containing L -glutamate reduced the length of hospitalization. Magnesium (Mg) did not affect the number and severity of VOCs. This review includes a few articles for the study. Future papers on this subject should include a large sample size and many papers. More clinical trials are required to evaluate the dosages and outcomes of using these drugs in combination to prevent VOCs.