Abstract

BACKGROUND To assess the efficacy and safety of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants. METHODS We searched MEDLINE, EMBASE, and Cochrane database without any language restrictions. The last search was conducted in August 15, 2020. All randomized controlled trials comparing the use of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight (VLBW) infants were selected. Pooled risk ratio (RR) for dichotomous variable with 95% confidence intervals were assessed by a random-effects model. The primary outcome was all-cause mortality. RESULTS Overall, this meta-analysis included 6 randomized controlled trials comprising 3,483 participants. Restrictive transfusion does not increase the risk of all-cause mortality (RR, 0.99; 95% CI, 0.84 to 1.17; I2 = 0%; high-quality evidence), and does not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01, 95% CI, 0.93-1.09; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume. CONCLUSIONS In very low birth weight infants, a restrictive threshold for red blood cell transfusion was not associated with increased risk of all-cause mortality, in either short term or long term.

Abstract

Contemporary packed red blood cell transfusion practices in anaemic preterm infants are primarily based on measurement of hemoglobin or haematocrit. In neonatal intensive care units, most preterm infants receive at least 1 packed red cell transfusion as standard treatment for anaemia of prematurity. Clinicians are faced with a common question "at what threshold should anaemic preterm infants receive packed red blood cell transfusion?". While evidence from interventional trials offers a range of haemoglobin levels to clinicians on thresholds to initiate red cell transfusion, it does not offer identification of exact haemoglobin level at which regional oxygenation and perfusion gets compromised. Assessment of regional oxygenation using near infrared spectroscopy and perfusion using ultrasound could offer a personalized transfusion medicine approach to optimize transfusion practices. We conducted a systematic review of the literature to identify the role of both regional oxygenation and/or ultrasound-based perfusion monitoring as a potential trigger to initiate packed red blood cell transfusion in anaemic preterm infants. MEDLINE, Embase, Maternity and Infant Care database were searched up to March 2021. Publications identified were screened and relevant data was extracted. Changes to regional oxygenation and/or perfusion monitoring before and after packed red blood cell transfusion were the primary outcomes. 44 out of 755 studies met the inclusion criteria and were included in the final analysis. Most were prospective, observational studies in stable preterm infants. Overall, studies reported an improvement in regional oxygenation and/or ultrasound-based perfusion after packed red blood cell transfusion. These changes were more consistently observed when hemoglobin <9.6g/dL or hematocrit was <0.30. Significant variation was found for patient characteristics, postnatal age at the time of monitoring, criteria for diagnosis of anaemia, and period of monitoring as well as regional oxygenation monitoring methodology. Regional oxygenation and/or perfusion monitoring can identify at-risk anaemic preterm infants and are promising tools to individualize packed red blood cell transfusion practices. However, there is lack of evidence for incorporating this monitoring, in their present form, into standard clinical practice. Additionally, consistency in reporting of study methodology should be improved.

Abstract

OBJECTIVE We aimed to determine whether the restrictive red-cell transfusion strategy was superior to the liberal one in reducing all-cause mortality in critically ill adults. METHODS The MEDLINE, EMBASE, PubMed, Web of Science, and Cochrane Library Central Register of Controlled Trials databases were searched from inception to January 2019 to identify meta-analyses or systematic reviews and published randomized controlled trials which were restrictive versus liberal blood transfusion with mortality as the endpoint in critically ill adults. We used two search routes whereby one search was restricted to systematic reviews, reviews, or meta-analysis, and the other was not restricted. There were no date restrictions, but language was limited to English and the population was restricted to critically ill adults. The data of study methods, participant characteristics, and outcomes were extracted and analyzed independently by 2 reviewers. The main outcome was all-cause mortality. RESULTS Through screening the obtained records, we enrolled 7 randomized clinical trials that included information on restrictive versus liberal red-cell transfusion and mortality of intensive care unit (ICU) patients. Involving a total of 7,363 ICU adult patients, ICU mortality (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.08, p = 0.15), 28/30-day mortality (RR 0.98, 95% CI 0.84, 1.13, p = 0.74), 60-day mortality (RR 1.01, 95% CI 0.87, 1.16, p = 0.91), 90-day mortality (RR 1.02, 95% CI 0.92, 1.14, p = 0.69), 120-day mortality (RR 1.29, 95% CI 0.67, 2.47, p = 0.44), and 180-day mortality (RR 0.91, 95% CI 0.75, 1.12, p = 0.38) were not statistically significantly different when the restrictive transfusion strategy was compared with the liberal transfusion strategy. However, we surprisingly discovered that 112 out of 469 (24%) patients who received a unit RBC transfusion when hemoglobin was less than 7 g/dL, and 142 out of 469 (30.3%) who received a unit of RBC transfused with hemoglobin less than 9 g/dL, had died during hospitalization (RR 0.79, 95% CI 0.64, 0.97, p = 0.03). The results showed that the restrictive transfusion strategy could decrease in-hospital mortality compared with the liberal transfusion strategy. It was safe to utilize a restrictive transfusion threshold of less than 7 g/dL in stable critically ill adults. CONCLUSIONS In this study, we found that the restrictive red-cell transfusion strategy potentially reduced in-hospital mortality in critically ill adults with anemia compared with the liberal strategy.

Abstract

Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO). Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants. Data Sources: PubMed, Embase, reference lists. Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO. Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively. Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes. Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants.

Abstract

OBJECTIVE To review studies that have evaluated the effects of liberal or restrictive red cell transfusion thresholds on clinical outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) support for cardiac or respiratory failure. DESIGN A systematic review and meta-analysis. SETTING AND PARTICIPANTS The study comprised 1,070 patients from observational studies and randomized controlled trials analyzing transfusion policies in venoarterial (VA) and venovenous (VV) ECMO adult populations. MEASUREMENTS AND MAIN RESULTS Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials, Medline, and EMBASE until March 4, 2020, using a combination of subject headings and text words. Risk of bias assessment was performed to assess study quality according to the ROBINS-I tool and the case series studies appraisal checklist. There was high risk of bias in the studies analyzed, and none had methodologic adequacy. Three studies analyzed VA ECMO and VV ECMO patients separately. Five datasets were related exclusively or mostly to VA ECMO. Four were retrospective analyses, and one was conducted as a prospective observational study; the median transfusion threshold reported was 8 g/dL, with a mean mortality of 52%. Eight datasets were related either exclusively or mostly to VV ECMO. Six were retrospective and two were prospective observational studies; the median transfusion threshold was 8 g/dL, and the mean mortality rate was 33%. CONCLUSIONS The present study did not resolve uncertainty as to transfusion management in ECMO, although several studies (most of them in VV ECMO) demonstrated that a restrictive threshold has acceptable outcomes in single-center cohorts.

Abstract

PURPOSE To investigate the effects of red blood cell (RBC) transfusion on sublingual microcirculation in critically ill patients. METHODS Systematic strategy was conducted to search studies that measured sublingual microcirculation before and after transfusion in critically ill patients. This review was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Scoping Review Extension. RESULTS The literature search yielded 114 articles. 11 studies met the inclusion criteria. Observational evidence showed diffusive capacity of the microcirculation significantly improved in intraoperative and anemic hematological patients after transfusion, while the convective parameters significantly improved in traumatic patients. RBC transfusion improved both diffusive and convective microcirculatory parameters in hypovolemic hemorrhagic shock patients. Most of the studies enrolled septic patients showed no microcirculatory improvements after transfusion. The positive effects of the leukoreduction was insufficiently supported. The effects of the storage time of the RBCs was not conclusive. The majority of the evidence supported a negative correlation between baseline proportion of perfused vessels (PPV) and changes in PPV. CONCLUSIONS This scoping review has catalogued evidence that RBC transfusion differently improves sublingual microcirculation in different populations. The existing evidence is not sufficient to conclude the effects of the leukoreduction and storage time of RBCs.

Abstract

PURPOSE Patients in the intensive care unit (ICU) are often transfused with red blood cells (RBC). During storage, the RBCs and storage medium undergo changes, which may have clinical consequences. Several trials now have assessed these consequences, and we reviewed the present evidence on the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients. METHODS We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials including adult ICU patients transfused with fresher versus older or standard issue blood. RESULTS We included seven trials with a total of 18,283 randomised ICU patients; two trials of 7504 patients were judged to have low risk of bias. We observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97-1.11; 7349 patients; TSA-adjusted CI 0.93-1.15), adverse events (1.26, 0.76-2.09; 7332 patients; TSA-adjusted CI 0.16-9.87) or post-transfusion infections (1.07, 0.96-1.20; 7332 patients; TSA-adjusted CI 0.90-1.27). The results were unchanged by including trials with high risk of bias. TSA confirmed the results and the required information size was reached for mortality for a relative risk change of 20%. CONCLUSIONS We may be able to reject a clinically meaningful effect of RBC storage time on mortality in transfused adult ICU patients as our trial sequential analyses reject a 10% relative risk change in death when comparing fresher versus older blood for transfusion.

Abstract

The prevention and treatment of anaemia in newborn patients made tremendous progress in the last decades. However, red-blood-cell (RBC) transfusions remain unavoidable in many neonates candidate to surgery and especially in preterm infants. In particular, anaemia occurring in neonates born at extremely low gestational age is actually severe and frequently requires transfusions. Several approaches have been explored to prevent or even to reduce the threshold and the frequency of RBC transfusions. Among these, umbilical cord blood (UCB) collection and processing to obtain RBC components for autologous or allogeneic transfusion have been extensively investigated. In this systematic review, we revised the literature concerning the use of UCB for either autologous or allogeneic transfusion purposes and we illustrated the rationale for a transfusion therapy tailored to extremely preterm neonates, based on RBC concentrates from allogeneic UCB donations.

Abstract

BACKGROUND The number of observational studies that report an association between packed red blood cell (PRBC) transfusions and necrotizing enterocolitis (NEC) has increased. The primary objective of this study was to evaluate the association between PRBC transfusions and NEC in observational studies. METHODS Medline, Embase and Cochrane Library databases as well as the Pediatrics Academic Societies abstract archives were systematically searched to identify observational studies that investigated the association between PRBC transfusions and NEC. Key search terms included premature infant, blood transfusion and necrotizing enterocolitis. The generic inverse variance method with a random-effects model was used to meta-analyze selected studies. Odds ratios (ORs) and confidence intervals (CIs) were calculated. RESULTS A meta-analysis of 17 observational studies that reported the association between PRBC transfusions and NEC was performed. The meta-analysis revealed no evidence of an association between PRBC transfusions and a higher risk of NEC (OR: 0.96; 95% CI: 0.53-1.71; P=0.88). The effect estimates that suggested an association between PRBC transfusion and NEC in matched case-control studies (OR: 1.20; 95% CI: 0.58-2.47; P=0.63) differed from those reported in cohort studies (OR: 0.51; 95% CI: 0.34-0.75; P=<0.01). CONCLUSIONS This updated meta-analysis of predominantly low-to-moderate quality observational studies suggests that there is no significant association between PRBC transfusions and NEC. A higher quality of evidence on this topic is needed.

Abstract

CONTEXT Significant controversy exists surrounding the possible association between recent packed red blood cell (PRBC) transfusion and the subsequent development of necrotizing enterocolitis (NEC) in infants. Previous studies and meta-analyses reporting a statistically significant association led to a practice change to withhold enteral feeds in the peri-transfusion period in many centers in an effort to prevent NEC; however, results from more recent studies do not support the existence of an association and, thus, question the validity of this practice change. OBJECTIVE This study aimed to perform a systematic review and meta-analysis to determine whether exposure to recent PRBC transfusion (defined as within 48 h) is associated with the subsequent development of NEC stage ≥II (Bell's criteria) in infants. METHODS Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to October 7, 2015. A gray literature search was also performed. Studies comparing the risk of NEC in infants exposed and unexposed to recent PRBC transfusion were included. Thirteen studies met eligibility criteria, and 10 (n=15,675 infants) were included in the meta-analysis. Three authors independently extracted data, and meta-analysis was performed using a random effects model. RESULTS We found a statistically significant 45% reduction in the unadjusted odds of NEC in infants exposed to a recent PRBC transfusion (odds ratio=0.55, 95% confidence interval=0.31-0.98). CONCLUSION Our results show a protective effect of recent PRBC transfusion on the subsequent development of NEC. The practice of withholding enteral feeds during the peri-transfusion period should be re-evaluated in light of these results.