Abstract

BACKGROUND Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING National Institute for Health Research Efficacy and Mechanism Evaluation.

Abstract

IMPORTANCE Auditing and feedback are frequently used to improve patient care. However, it remains unclear how to optimize feedback effectiveness for the appropriate use of treatments such as blood transfusion, a common but costly procedure that is more often overused than underused. OBJECTIVE To evaluate 2 theoretically informed feedback interventions to improve the appropriate use of blood transfusions. DESIGN, SETTING, AND PARTICIPANTS Two sequential, linked 2 × 2 cluster randomized trials were performed in hospitals in the UK participating in national audits of transfusion for perioperative anemia and management of hematological disorders. Data were collected for a surgical trial from October 1, 2014, to October 31, 2016, with follow-up completed on October 31, 2016. Data were collected for a hematological trial through follow-up from July 1, 2015, to June 30, 2017. Trial data were analyzed from November 1, 2016, to June 1, 2019. INTERVENTIONS Hospitals were randomized to standard content or enhanced content to improve feedback clarity and usability and to standard support or enhanced support for staff to act on feedback. MAIN OUTCOMES AND MEASURES The primary end point was appropriateness of transfusions audited at 12 months. Secondary end points included volume of transfusions (aiming for reductions at patient and cluster levels) and transfusion-related adverse events and reactions. RESULTS One hundred thirty-five of 152 eligible clusters participated in the surgical audit (2714 patients; mean [SD] age, 74.9 [14.0] years; 1809 women [66.7%]), and 134 of 141 participated in the hematological audit (4439 patients; median age, 72.0 [IQR, 64.0-80.0] years; 2641 men [59.5%]). Fifty-seven of 69 clusters (82.6%) in the surgical audit randomized to enhanced content downloaded reports compared with 52 of 66 clusters (78.8%) randomized to standard reports. Fifty-nine of 68 clusters (86.8%) randomized to enhanced support logged onto the toolkit. The proportion of patients with appropriate transfusions was 0.184 for standard content and 0.176 for enhanced content (adjusted odds ratio [OR], 0.91 [97.5% CI, 0.61-1.36]) and 0.181 for standard support and 0.180 for enhanced support (adjusted OR, 1.05 [97.5% CI, 0.68-1.61]). For the hematological audit, 53 of 66 clusters (80.3%) randomized to enhanced content downloaded the reports compared with 53 of 68 clusters (77.9%) randomized to standard content. Forty-nine of 67 clusters sites (73.1%) assigned to enhanced support logged into the toolkit at least once. The proportion of patients with appropriate transfusions was 0.744 for standard content and 0.714 for enhanced content (adjusted OR, 0.81 [97.5% CI, 0.56-1.12]), and 0.739 for standard support and 0.721 for enhanced support (adjusted OR, 0.96 [97.5% CI, 0.67-1.38]). CONCLUSIONS AND RELEVANCE This comparison of cluster randomized trials found that interventions to improve feedback usability and guide local action were no more effective than standard feedback in increasing the appropriate use of blood transfusions. Auditing and feedback delivered at scale is a complex and costly program; therefore, effective responses may depend on developing robust local quality improvement arrangements, which can be evaluated using rigorous experimental designs embedded within national programs. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN15490813.

Abstract

BACKGROUND Protocols for transfusion therapy in transfusion-dependent thalassemia (TDT) children differ among various medical centers. In India, most centers consider only the patient's weight while calculating the volume of packed red blood cells (PRBCs) to be transfused. This study aimed to compare the efficacy of PRBC transfusions of different volumes calculated either by weight or by a formula using weight and pretransfusion hemoglobin of patient and hematocrit of PRBC. STUDY DESIGN AND METHODS Sixty TDT patients in the age group of 3-9 years were enrolled and randomly allocated to two groups. Group A received PRBC transfusion volume based on the patient's weight, and Group B received PRBC volume calculated using a formula for 6 months. RESULTS Average pretransfusion hemoglobin in Group A and Group B (9 ± 0.4 vs. 8.9 ± 0.4 g/dl) was not significantly different (p = .353). Although the average number of visits in 6 months was less for Group A compared to Group B (7 ± 1 vs. 8 ± 1; p = .001); the average volume transfused per visit was more (351 ± 78 vs. 287 ± 68 ml; p = .003). The calculated average annual pure red cell requirement of the patients was 178 ml/kg/year for Group A and 154 ml/kg/year for Group B (p = .000). Total donor exposures were significantly lower in Group B than Group A (11 ± 3 vs. 14 ± 3; p = .006). CONCLUSION The number of donor exposures and annual pure red cell requirement was significantly lower in the formula-based group. Transfusions based on formula are recommended in TDT patients.

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.

Abstract

BACKGROUND The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4-6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint). Because data on the safety of blood components are scarce, we conducted a secondary analysis to examine the safety and efficacy of different pack types (whole blood vs red cell concentrates) on clinical outcomes. METHODS This study is a secondary analysis of the TRACT trial data restricted to those who received an immediate transfusion (using whole blood or red cell concentrates). TRACT was an open-label, multicentre, factorial, randomised trial conducted in three hospitals in Uganda (Soroti, Mbale, and Mulago) and one hospital in Malawi (Blantyre). The trial enrolled children aged between 2 months and 12 years admitted to hospital with severe anaemia (haemoglobin <6 g/dL). The pack type used (supplied by blood banks) was based only on availability at the time. The outcomes were haemoglobin recovery at 8 h and 180 days, requirement for retransfusion, length of hospital stay, changes in heart and respiratory rates until day 180, and the main clinical endpoints (mortality until day 28 and day 180, and readmission until day 180), measured using multivariate regression models. FINDINGS Between Sept 17, 2014, and May 15, 2017, 3199 children with severe anaemia were enrolled into the TRACT trial. 3188 children were considered in our secondary analysis. The median age was 37 months (IQR 18-64). Whole blood was the first pack provided for 1632 (41%) of 3992 transfusions. Haemoglobin recovery at 8 h was significantly lower in those who received packed cells or settled cells than those who received whole blood, with a mean of 1·4 g/dL (95% CI -1·6 to -1·1) in children who received 30 mL/kg and -1·3 g/dL (-1·5 to -1·0) in those who received 20 mL/kg packed cells versus whole blood, and -1·5 g/dL (-1·7 to -1·3) in those who received 30 mL/kg and -1·0 g/dL (-1·2 to -0·9) in those who received 20 mL/kg settled cells versus whole blood (overall p<0·0001). Compared to whole blood, children who received blood as packed or settled cells in their first transfusion had higher odds of receiving a second transfusion (odds ratio 2·32 [95% CI 1·30 to 4·12] for packed cells and 2·97 [2·18 to 4·05] for settled cells; p<0·001) and longer hospital stays (hazard ratio 0·94 [95% CI 0·81 to 1·10] for packed cells and 0·86 [0·79 to 0·94] for settled cells; p=0·0024). There was no association between the type of blood supplied for the first transfusion and mortality at 28 days or 180 days, or readmission to hospital for any cause. 823 (26%) of 3188 children presented with severe tachycardia and 2077 (65%) with tachypnoea, but these complications resolved over time. No child developed features of confirmed cardiopulmonary overload. INTERPRETATION Our study suggests that the use of packed or settled cells rather than whole blood leads to additional transfusions, increasing the use of a scarce resource in most of sub-Saharan Africa. These findings have substantial cost implications for blood transfusion and health services. Nevertheless, a clinical trial comparing whole blood transfusion with red cell concentrates might be needed to inform policy makers. FUNDING UK Medical Research Council (MRC) and the Department for International Development. TRANSLATION For the French translation of the abstract see Supplementary Materials section.

Abstract

OBJECTIVES Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma. DESIGN This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma. SETTING Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial. PATIENTS Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission. INTERVENTIONS Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days. MEASUREMENTS AND MAIN RESULTS Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001). CONCLUSIONS RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

Abstract

BACKGROUND Autologous blood injection (ABI) for patients with chronic plantar fasciitis has been promoted as an approach to improve outcomes over standard dry-needling approaches. The purpose of this trial was to investigate if there are improved outcomes following an ultrasonography-guided ABI compared to dry needling alone for patients with chronic plantar fasciitis. METHODS A double-blinded (participant-blinded and observer-blinded) RCT within a single clinic enrolled 90 patients with symptoms of plantar fasciitis that had failed to improve with a minimum of 3 months of rehabilitation. The mean age was 49.5±8.9 years, 67% were female, and the mean symptom duration was 40.0±28.2 months (range: 8 months-10 years). Participants were randomized to receive ABI or an identical dry-needle fenestration-procedure without coadministration of autologous blood. All participants received identical structured rehabilitation and were followed up at 2, 6, 12, and 26 weeks. Outcome measures included local foot pain, validated foot patient-reported outcome measures (Foot Function Index-revised, Manchester-Oxford Foot Questionnaire, Foot and Ankle Ability Measure), measures of general function and "ability" (EuroQol [EQ]-5D-5L, Oswestry Disability Index), specific measures of activity (International Physical Activity Questionnaire), sleep (Pittsburgh Sleep Quality Index), and mood (Hospital Anxiety and Depression Scale). RESULTS There were no significant between-group differences seen at any time-point studied. There were a number of statistically significant within-group improvements for local foot pain and function in both groups comparing baseline/follow-up data. Overall, levels of pain improved by 25% by 6 weeks and by 50% at 6 months. There were improvements in some generalized function markers. Activity rates did not change, demonstrating that improvements in pain did not necessarily influence physical activity. CONCLUSION Coadministration of 3 mL of autologous blood had no additional effect compared to a dry-needling procedure alone for patients with chronic plantar fasciitis. LEVEL OF EVIDENCE Level I, double-blinded randomized controlled trial.

Abstract

INTRODUCTION Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients. METHODS This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO CRD42021242943. RESULTS Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature (N = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection. CONCLUSION EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM.KEY MESSAGESExtramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before.There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities.More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines.

Abstract

INTRODUCTION Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remains limited. METHODS We performed a single center, prospective, cluster randomized, prehospital thru in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (SBP ≤ 90 mmHg and HR ≥ 108 bpm) or (SBP ≤ 70 mmHg) for patients at risk of hemorrhage. Primary outcome was feasibility. Secondary outcomes included 28-day and 24 hour mortality, multiple organ failure, nosocomial infection, 24 hr transfusion requirements and arrival coagulation parameters. RESULTS Between November 2018 thru October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent to treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p < 0.01) and a lower incidence of abnormal thromboelastographic measurements. No transfusion reactions during the prehospital or in-hospital phase of care were documented. CONCLUSION Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with protocol adjustment and would allow the effects of prehospital LTOWB on survival and other pertinent clinical outcomes to be appropriately characterized. LEVEL OF EVIDENCE II, Cluster randomized pilot trial.

Abstract

BACKGROUND Anemia is a known risk factor for ischemic heart disease and serves as an independent predictor of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This meta-analysis pools data from randomized controlled trials (RCTs) to better define hemoglobin (Hb) thresholds for transfusion in this setting. RESULTS MEDLINE, EMBASE, and Cochrane databases were searched using the terms "Acute Coronary Syndrome" AND "Blood Transfusion" including their synonyms. A total of three randomized controlled trials were included. Restrictive transfusion strategy (RTS) was defined as transfusing for Hb ≤ 8 g/dl with a post-transfusion goal of 8 to 10 g/dl. Liberal transfusion strategy (LTS) was defined as Hb ≤ 10 g/dl and post-transfusion goal of at least 11 g/dl. The primary end point was 30-day mortality. Secondary outcomes included recurrent ACS events, new or worsening CHF within 30 days, and major adverse cardiac events (MACE). The primary analytic method used was random effects model. Out of 821 patients, 400 were randomized to LTS, and 421 to RTS. Mean age was 70.3 years in RTS versus 76.4 in LTS. There was no statistically significant difference for 30-day mortality in LTS compared to RTS [odds ratio (OR) 1.69; 95% CI 0.35 to 8.05]. Similarly, there was no difference in MACE (OR 0.74; 95% CI 0.21 to 2.63), CHF (OR 0.82; 95% CI 0.18 to 3.76), or the incidence of recurrent ACS (OR 1.21; 95% CI 0.49 to 2.95). CONCLUSIONS In the setting of ACS, there is no difference between LTS and RTS for the outcomes of mortality, MACE, recurrent ACS, or CHF at 30 days. Further evidence in the form of high-quality RCTs are needed to compare RTS and LTS.