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What blood conservation practices are effective at reducing blood sampling volumes and other clinical sequelae in intensive care? A systematic review
Keogh S, Mathew S, Ullman AJ, Rickard CM, Coyer F
Australian critical care : official journal of the Confederation of Australian Critical Care Nurses. 2023
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Editor's Choice
Abstract
OBJECTIVES The objective of this study was to critically appraise and synthesise evidence for blood conservation strategies in intensive care. Blood sampling is a critical aspect of intensive care to guide clinical decision-making. Repeated blood sampling can result in blood waste and contamination, leading to iatrogenic anaemia and systemic infection. REVIEW METHOD USED Cochrane systematic review methods were used including meta-analysis, and independent reviewers. DATA SOURCES A systematic search was conducted in Medline, CINAHL, PUBMED and EMBASE databases. The search was limited to randomised controlled trials (RCTs) and cluster RCTs, published in English between 2000 and 2021. REVIEW METHODS Paired authors independently assessed database search results and identified eligible studies. Trials comparing any blood conservation practice or product in intensive care were included. Primary outcomes were blood sample volumes and haemoglobin change. Secondary outcomes included proportion of patients receiving transfusions and infection outcomes. Quality appraisal employed the Cochrane Risk of Bias tool. Meta-analysis using random effects approach and narrative synthesis summarised findings. RESULTS Eight studies (n = 1027 patients), all RCTs were eligible. Six studies included adults, one studied paediatrics and one studied preterm infants. Seven studies evaluated a closed loop blood sampling system, and one studied a conservative phlebotomy protocol. Studies were of low to moderate quality. Meta-analysis was not possible for interventions targeting blood sample volumes or haemoglobin. Decreased blood sample volumes reported in four studies were attributable to a closed loop system or conservative phlebotomy. No study reported a significant change in haemoglobin. Meta-analysis demonstrated that use of a closed system (compared to open system) reduced the proportion of patients receiving transfusion [Risk Ratio (RR) 0.65, 95% CI 0.46-0.92; 287 patients] and reduced intraluminal fluid colonisation [RR 0.25, 95% CI 0.07-0.58; 500 patients]. CONCLUSIONS Limited evidence demonstrates closed loop blood sampling systems reduced transfusion use and fluid colonisation. Simultaneous effectiveness-implementation evaluation of these systems and blood conservation strategies is urgently required. PROSPERO PROTOCOL REGISTRATION REFERENCE CRD42019137227.
PICO Summary
Population
Patients (adults, neonates and paediatrics) admitted to an intensive care unit (8 randomised controlled trials, n= 1,027).
Intervention
Different blood sampling strategies and systems, including the standard open arterial blood sampling system.
Comparison
Various comparators, including the closed-loop arterial blood sampling system, and adding small-volume tubes to the closed-loop system.
Outcome
Seven studies evaluated a closed loop blood sampling system, and one studied a conservative phlebotomy protocol. Studies were of low to moderate quality. Meta-analysis was not possible for interventions targeting blood sample volumes or haemoglobin. Decreased blood sample volumes reported in four studies were attributable to a closed loop system or conservative phlebotomy. No study reported a significant change in haemoglobin. Meta-analysis demonstrated that use of a closed system (compared to open system) reduced the proportion of patients receiving transfusion (Risk Ratio (RR) 0.65, 95% CI: 0.46-0.92; 287 patients) and reduced intraluminal fluid colonisation (RR 0.25, 95% CI: 0.07-0.58; 500 patients).
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Red Blood Cell Transfusion in Patients With Placenta Accreta Spectrum: A Systematic Review and Meta-analysis
Miller SE, Leonard SA, Meza PK, Ku S, Ren LY, Lyell DJ, Sultan P, Butwick A
Obstetrics and gynecology. 2023;141(1):49-58
Abstract
OBJECTIVE To evaluate red blood cell use during delivery in patients with placenta accreta spectrum. DATA SOURCES We searched MEDLINE, EMBASE, CINAHL, Cochrane Central, ClinicalTrials.gov, and Scopus for clinical trials and observational studies published between 2000 and 2021 in countries with developed economies. METHODS OF STUDY SELECTION Abstracts (n=4,275) and full-text studies (n=599) were identified and reviewed by two independent reviewers. Data on transfused red blood cells were included from studies reporting means and SDs, medians with interquartile ranges, or individual patient data. The primary outcome was the weighted mean number of units of red blood cells transfused per patient. Between-study heterogeneity was assessed with an I2 statistic. Secondary analyses included red blood cell usage by placenta accreta subtype. TABULATION, INTEGRATION, AND RESULTS Of the 599 full-text studies identified, 20 met criteria for inclusion in the systematic review, comprising 1,091 cases of placenta accreta spectrum. The number of units of red blood cells transfused was inconsistently described across studies, with five studies (25.0%) reporting means, 11 (55.0%) reporting medians, and four (20.0%) reporting individual patient data. The weighted mean number of units transfused was 5.19 (95% CI 4.12-6.26) per patient. Heterogeneity was high across studies (I2=91%). In a sensitivity analysis of five studies reporting mean data, the mean number of units transfused was 6.61 (95% CI 4.73-8.48; n=220 patients). Further quantification of units transfused by placenta accreta subtype was limited due to methodologic inconsistencies between studies and small cohort sizes. CONCLUSION Based on the upper limit of the CI in our main analysis and the high study heterogeneity, we recommend that a minimum of 6 units of red blood cells be available before delivery for patients with placenta accreta spectrum. These findings may inform future guidelines for predelivery blood ordering and transfusion support. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42021240993.
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Prognostic of red blood cell transfusion during extracorporeal membrane oxygenation therapy on mortality: A meta-analysis
Li Y, Wang J, Li C, Wang L, Chen Y
Perfusion. 2023;:2676591231157234
Abstract
BACKGROUND This meta-analysis aimed to explore the impact of red blood cell (RBC) transfusion on mortality during extracorporeal membrane oxygenation (ECMO). Previous studies investigated the prognostic impact of RBC transfusion during ECMO on the risk of mortality, but no meta-analysis has been published before. METHODS The PubMed, Embase, and the Cochrane library were systematically searched for papers published up to 13 December 2021, using the MeSH terms "ECMO", "'Erythrocytes", and "Mortality" to identify meta-analyses. Total or daily RBC transfusion during ECMO and mortality were examined. RESULTS The random-effect model was used. Eight studies (794 patients, including 354 dead) were included. The total volume of RBC was associated with higher mortality standardized weighted difference (SWD = -0.62, 95% CI: -1.06,-0.18, p = .006; I2 = 79.7%, P(heterogeneity) = 0.001). The daily volume of RBC was associated with higher mortality (SWD = -0.77, 95% CI: -1.11,-0.42, p < .001; I2 = 65.7%, P(heterogeneity) = 0.020). The total volume of RBC was associated with mortality for venovenous (VV) (SWD = -0.72, 95% CI: -1.23, -0.20, p = .006) but not venoarterial ECMO (p = .126) or when reported together (p = .089). The daily volume of RBC was associated with mortality for VV (SWD = -0.72, 95% CI: -1.18, -0.26, p = 0.002; I2 = 0.0%, P(heterogeneity) = 0.642) and venoarterial (SWD = -0.95, 95% CI: -1.32, -0.57, p < .001) ECMO, but not when reported together (p = .067). The sensitivity analysis suggested the robustness of the results. CONCLUSION When considering the total and daily volumes of RBC transfusion during ECMO, the patients who survived received smaller total and daily volumes of RBC transfusion. This meta-analysis suggests that RBC transfusion might be associated with a higher risk of mortality during ECMO.
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Health related quality of life in children with sickle cell disease: A systematic review and meta-analysis
Stokoe M, Zwicker HM, Forbes C, Abu-Saris Nelh, Fay-McClymont TB, Désiré N, Guilcher GMT, Singh G, Leaker M, Yeates KO, et al
Blood reviews. 2022;:100982
Abstract
This review had three aims: 1) describe the measures used to assess health-related quality of life (HRQL) in pediatric patients diagnosed with sickle cell disease (SCD); 2) document the biopsychosocial factors related to HRQL in pediatric patients diagnosed with SCD; and 3) complete a meta-analysis comparing HRQL in pediatric patients diagnosed with SCD to healthy controls. Included studies were published in English, quantitatively assessed HRQL as a primary aim, in both SCD and controls, and included participants between 0 and 21 years of age. The final review included 66 articles, with a total of 8642 participants with SCD, 4 months-21 years of age, and 62,458 controls, 5-27 years of age. HRQL was predominately measured using the Pediatric Quality of Life Inventory Generic Core and Sickle Cell Disease Module. Meta-analyses revealed children with SCD had significantly worse HRQL compared to healthy controls (standardized mean difference = -0.93, 95% CI = -1.25, -0.61, p < 0.00001). Worse HRQL was associated with more severe SCD, female sex, and pain. The findings indicate that children with SCD are at risk for worse HRQL compared to their healthy peers and their HRQL may be impacted by several biopsychosocial factors. Future research is needed to examine how sociocultural factors uniquely impact this population and their overall quality of life.
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Race/Ethnicity as a Risk Factor in the Development of Postpartum Hemorrhage: A Thorough Systematic Review of Disparity in the Relationship Between Pregnancy and the Rate of Postpartum Hemorrhage
Okunlola O, Raza S, Osasan S, Sethia S, Batool T, Bambhroliya Z, Sandrugu J, Lowe M, Hamid P
Cureus. 2022;14(6):e26460
Abstract
Postpartum hemorrhage (PPH) is a major cause of maternal death and morbidity worldwide. Throughout the years, there have not been many studies looking into the association of race and ethnicity with the occurrence of PPH. The goal of this study was to assess race and ethnicity as risk factors in the development of PPH in pregnant women. Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) standards, we conducted the analysis and conducted a literature search using Google Scholar and PubMed. After applying our inclusion and exclusion criteria, the search technique yielded a total of eight articles. The analysis included seven observational studies and one randomized controlled trial. The incidence of PPH was chosen as the major outcome measure. An evaluation of eight studies revealed that although Hispanics, Asians, Native Hawaiians, and other Pacific Islanders (NHOPI) have a higher chance of developing PPH caused by uterine atony, Caucasians had a greater rate of transfusion than the other groups. In addition, compared to Caucasians, African Americans or African descendants had a lower risk of atonic PPH but increased odds of atonic PPH requiring interventions. On the other hand, compared to non-native groups, Native Americans had increased odds of uterine atony. The results showed that, in contrast to other races/ethnicities, Caucasians had the lowest risk of PPH. Additionally, it was shown that African Americans or those descended from Africans had a higher chance of PPH but a lower risk of atonic PPH.
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The impact of red blood cell transfusion on mortality and treatment efficacy in patients treated with radiation: A systematic review
Deschner M, Vasanthamohan L, Zayed S, Lazo-Langner A, Palma D, D'Souza D, Omar Gilani S, Gabriel Boldt R, Solh Z
Clinical and translational radiation oncology. 2022;33:23-29
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Free full text
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Editor's Choice
Abstract
INTRODUCTION Packed red blood cell (RBC) transfusion is frequently used in patients undergoing radiotherapy (RT) because retrospective data suggest that anemic patients may respond sub-optimally to RT. No high-quality evidence currently exists to guide transfusion practices and establish hemoglobin (Hb) transfusion thresholds for this patient population, and practice varies significantly across centers. This systematic review investigated whether maintaining higher Hb via transfusion in radiation oncology patients leads to improved outcomes. METHODS We performed a literature search of studies comparing RBC transfusion thresholds in radiation oncology patients. Included studies assessed patients receiving RT for malignancy of any diagnosis or stage. Excluded studies did not evaluate Hb or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional control, number of transfusions and adverse events. RESULTS One study met inclusion criteria. The study pooled results from two randomized controlled trials that stratified anemic patients with head and neck squamous cell carcinoma to RBC transfusion versus no transfusion. The study found no significant differences in overall survival or locoregional control after five years, despite increased Hb levels in the transfused group. We conducted a narrative review by extracting data from 10 non-comparative studies involving transfusion in patients receiving RT. Results demonstrated no consistent conclusions regarding whether transfusions improve or worsen outcomes. CONCLUSIONS There is a lack of data on the effects of RBC transfusion on outcomes in patients undergoing RT. Well-designed prospective studies are needed in this area.
PICO Summary
Population
Patients undergoing radiotherapy (11 studies).
Intervention
Red blood cell transfusion.
Comparison
No transfusion.
Outcome
Only one study met the inclusion criteria which pooled results from two randomized controlled trials (DAHANCA 5 and 7). The study found no significant differences in overall survival or locoregional control after five years, despite increased haemoglobin levels in the transfused group (n= 235) vs. no transfused group (n= 230). A narrative review was conducted by extracting data from 10 other non-comparative studies involving transfusion in patients receiving radiotherapy. There were no consistent conclusions from these 10 studies on whether transfusions improve or worsen outcomes.
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Effects of perioperative blood transfusion in gastric cancer patients undergoing gastrectomy: A systematic review and meta-analysis
Wang W, Zhao L, Niu P, Zhang X, Luan X, Zhao D, Chen Y
Frontiers in surgery. 2022;9:1011005
Abstract
BACKGROUND The short-term and long-term effects of perioperative blood transfusion (PBT) on patients with gastric cancer are still intriguing. This systematic review and meta-analysis aimed to investigate the effects of blood transfusion on clinical outcomes in patients with gastric cancer undergoing gastrectomy. METHODS We searched PubMed, Web of Science, Embase, and The Cochrane Library on December 31th 2021. The main outcomes were overall survival (OS), disease-free survival (DFS), disease-specific survival (DFS), and postoperative complications. A fixed or random-effects model was used to calculate the hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS Fifty-one studies with a total of 41,864 patients were included for this review and meta-analysis. Compared with patients who did not receive blood transfusions (NPBT), PBT was associated with worse 5-year OS (HR = 2.39 [95%CI: 2.00, 2.84]; p < 0.001; Multivariate HR = 1.43 [95%CI: 1.24, 1.63]; p < 0. 001), worse 5-year DFS (HR = 2.26 [95%CI: 1.68, 3.05]; p < 0.001; Multivariate HR = 1.45 [95%CI: 1.16, 1.82]; p < 0. 001), and worse 5-year DSS (HR = 2. 23 [95%CI: 1.35, 3.70]; p < 0.001; Multivariate HR = 1.24 [95%CI: 0.96, 1.60]; p < 0.001). Moreover, The PBT group showed a higher incidence of postoperative complications [OR = 2.30 (95%CI:1.78, 2. 97); p < 0.001] than that in the NPBT group, especially grade III-V complications, according to the Clavien-Dindo classification. [OR = 2.50 (95%CI:1.71, 3.63); p < 0.001]. CONCLUSION In patients who underwent gastrectomy, PBT was associated with negative survival effects (OS, DFS, DSS) and a higher incidence of perioperative complications. However, more research was expected to further explore the impact of PBT. Meanwhile, strict blood transfusion management should be implemented to minimize the use of PBT.
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Experimental and approved treatments for skin photosensitivity in individuals with erythropoietic protoporphyria or X-linked protoporphyria: A systematic review
Heerfordt IM, Lerche CM, Philipsen PA, Wulf HC
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;158:114132
Abstract
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to review the clinical evidence of efficacy and safety of skin photosensitivity treatments in individuals with EPP or XLP. We systematically searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov. A total of 40 studies with data on 18 treatment modalities were included. Comprehensive treatment safety data were obtained from the European Medicines Agency and the United States Food and Drug Administration. The studies used different outcome measures to evaluate the sensitivity without a generally accepted method to assess treatment effect on skin photosensitivity. Of the included studies, 13 were controlled trials. Gathered, the trials showed moderate positive effect of inorganic sunscreen application and subcutaneous implant of afamelanotide and no effect of organic sunscreen application, or oral treatment with beta-carotene, cysteine, N-acetylcysteine, vitamin C, or warfarin. Studies without control groups suggested treatment effect of foundation cream, dihydroxyacetone/lawsone cream, narrow-band ultraviolet B phototherapy, erythrocyte transfusion, extracorporeal erythrocyte photodynamic therapy, or oral treatment with zinc sulphate, terfenadine, cimetidine, or canthaxanthin, but the real effect is uncertain. Assessment of treatment effect on photosensitivity in patients with EPP or XLP carries a high risk of bias since experienced photosensitivity varies with both weather conditions, exposure pattern, and pigmentation. Controlled trials of promising treatment options are important although challenging in this small patient population.
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Impact of restrictive red blood cell transfusion strategy on thrombosis-related events: A meta-analysis and systematic review
Maimaitiming M, Zhang C, Xie J, Zheng Z, Luo H, Ooi OC
Vox sanguinis. 2022
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Editor's Choice
Abstract
BACKGROUND AND OBJECTIVES There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. MATERIALS AND METHODS We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. RESULTS Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p = 0.020; I(2) = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64-1.09; p = 0.180; I(2) = 0.0%, very low-quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87-1.26; p = 0.620; I(2) = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups). CONCLUSIONS A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.
PICO Summary
Population
Adult patients in any clinical setting (30 studies, n= 17,334).
Intervention
Restrictive red blood cell transfusion.
Comparison
Liberal red blood cell transfusion.
Outcome
The pooled risk ratio (RR) for thromboembolic events was 0.65 (very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR= 0.83, very low-quality evidence) or myocardial infarction (RR= 1.05, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced thromboembolic events in trials conducted in North America, and myocardial infarctions in the subgroup of trials where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups).
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Transfusion Guidelines in Brain Tumor Surgery: A Systematic Review and Critical Summary of Currently Available Evidence
Rail B, Hicks WH, Oduguwa E, Barrie U, Pernik MN, Montgomery E, Tao J, Kenfack YJ, Mofor P, Adeyemo E, et al
World neurosurgery. 2022
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Editor's Choice
Abstract
OBJECTIVE Red blood cell (RBC) transfusion is commonly indicated in brain tumor surgery due to risk of blood loss. Current transfusion guidelines are based on evidence derived from critically ill patients and may not be optimal for brain tumor surgeries. Our study is the first to synthesize available evidence to suggest RBC transfusion thresholds in brain tumor patients undergoing surgery. METHODS A systematic review was conducted using PubMed, EMBASE, and Google Scholar databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to critically assess RBC transfusion thresholds in adult patients with brain tumors and complications secondary to transfusion following blood loss in the operating room (OR) or the perioperative period. RESULTS Seven (7) articles meeting our search criteria were reviewed. Brain tumor patients who received blood transfusions were older, had greater rates of ASA class 3 or 4, and presented with increased number of comorbidities including diabetes, hypertension, and cardiovascular diseases. In addition, transfused patients had a prolonged surgical time. Transfusions were associated with multiple postoperative major and minor complications, including longer hospital length of stay (LOS), increased return to the OR, and elevated 30-day mortality. Analysis of transfusion thresholds showed that a restrictive hemoglobin (Hb) threshold of 8 g/dL is safe in patients, as evidenced by a reduction in LOS, mortality, and complications (Level C Class IIa). CONCLUSIONS A restrictive Hb threshold of 8 g/dL appears to be safe and minimizes potential complications of transfusion in brain tumor patients. LEVEL OF EVIDENCE Class C Level IIa.
PICO Summary
Population
Brain tumor patients undergoing surgery (7 studies).
Intervention
Systematic review assessing red blood cell transfusion thresholds.
Comparison
Outcome
Patients who received blood transfusions were older, had greater rates of American Society of Anesthesiologists class 3 or 4, and presented with increased number of comorbidities including diabetes, hypertension, and cardiovascular diseases. Transfused patients had a prolonged surgical time. Transfusions were associated with multiple postoperative major and minor complications, including longer hospital length of stay (LOS), increased return to the operating room, and elevated 30-day mortality. Analysis of transfusion thresholds showed that a restrictive haemoglobin (Hb) threshold of 8 g/dL was safe in patients, as evidenced by a reduction in LOS, mortality, and complications.
