Liberal Transfusion versus Restrictive Transfusion and Outcomes in Critically Ill Adults: A Meta-Analysis
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2021;48(1):60-68
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.
Intrapartum Resuscitation Interventions for Category II Fetal Heart Rate Tracings and Improvement to Category I
Obstetrics and gynecology. 2021
OBJECTIVE To evaluate intrapartum resuscitation interventions and improvement in category II fetal heart rate (FHR) tracings. METHODS This secondary analysis of a randomized trial of intrapartum fetal electrocardiographic ST-segment analysis included all participants with category II FHR tracings undergoing intrauterine resuscitation: maternal oxygen, intravenous fluid bolus, amnioinfusion, or tocolytic administration. Fetal heart rate pattern-recognition software was used to confirm category II FHR tracings 30 minutes before intervention and to analyze the subsequent 60 minutes. The primary outcome was improvement to category I within 60 minutes. Secondary outcomes included FHR tracing improvement to category I 30-60 minutes after the intervention and composite neonatal outcome. RESULTS Of 11,108 randomized participants, 2,251 (20.3%) had at least one qualifying intervention for category II FHR tracings: 63.7% improved to category I within 60 minutes and 50.5% improved at 30-60 minutes. Only 3.4% underwent cesarean delivery and 4.1% an operative vaginal delivery for nonreassuring fetal status within 60 minutes after the intervention. Oxygen administration was the most common intervention (75.4%). Among American College of Obstetricians and Gynecologists-defined subgroups that received oxygen, the absent FHR accelerations and absent-minimal FHR variability subgroup (n=332) was more likely to convert to category I within 60 minutes than the FHR accelerations or "moderate FHR variability" subgroup (n=1,919) (77.0% vs 63.0%, odds ratio [OR] 2.0, 95% CI 1.4-2.7). The incidence of composite neonatal adverse outcome for category II tracings was 2.9% (95% CI 2.2-3.7%) overall; 2.8% (95% CI 2.0-3.8%) for improvement to category I within 60 minutes (n=1,433); and 3.2% (95% CI 2.1-4.6%) for no improvement within 60 minutes (n=818). However, the group with improvement had 29% lower odds for higher level neonatal care (11.8% vs 15.9%, OR 0.71, 95% CI 0.55-0.91). CONCLUSION Nearly two thirds of category II FHR tracings improved to category I within 60 minutes of intervention with a relatively low overall rate of the composite neonatal adverse outcome. FUNDING SOURCE Funded in part by Neoventa Medical.
Risk factors for transfusion-related acute lung injury
Respiratory care. 2021
Background: Until now, transfusion-related acute lung injury (TRALI) has been considered to be the leading cause of blood transfusion-related diseases and death. And there is no clinically effective treatment plan for TRALI. The aim of this study was to systematically summarize the literature on risk factors for TRALI in critical patients.Methods: Electronic searches (up to March 2020) were performed in the Cochrane Library, Web of Knowledge, Embase, and PubMed databases. We included studies reporting on the risk factors of TRALI for critical patients and extracted the risk factors. Finally, thirteen studies met the inclusion criteria.Results: We summarized and analyzed the potential risk factors of TRALI for critical patients in 13 existing studies. The host-related factors were age (odds ratio (OR) [95% confidence interval] = 1.16 [1.08-1.24]), female sex (OR = 1.26 [1.16-1.38]), tobacco use status (OR = 3.82 [1.91-7.65]), chronic alcohol abuse (OR = 3.82 [2.97-26.83]), positive fluid balance (OR = 1.24 [1.08-1.42]), shock before transfusion (OR = 4.41 [2.38-8.20]), and ASA score of the recipients (OR = 2.72 [1.43-5.16]). The transfusion-related factors were the number of transfusions (OR = 1.40 [1.14-1.72]) and fresh frozen plasma (FFP) units (OR = 1.21 [1.01-1.46]). The device-related factor was mechanical ventilation (OR = 4.13 [2.20-7.76]).Conclusions: The risk factors for TRALI in this study included Number of transfusions and FFP units were positively correlated with TRALI. Age, female sex, tobacco use, chronic alcohol abuse, positive fluid balance, shock before transfusion, ASA score and mechanical ventilation may be potential risk factors for TRALI. Our study suggests that host-related risk factors may play a more important role in the occurrence and development of TRALI than blood transfusion-related risk factors.
Critical care patients (13 studies).
Systematic review on the risk factors for transfusion-related acute lung injury (TRALI).
The host-related factors were age, female sex, tobacco use status, chronic alcohol abuse, positive fluid balance, shock before transfusion, and ASA score of the recipients. The transfusion-related factors were the number of transfusions and fresh frozen plasma units. The device-related factor was mechanical ventilation.
Enteral Iron Supplementation in Extremely Preterm Infants and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the PENUT Randomized Controlled Trial
The Journal of pediatrics. 2021
OBJECTIVES To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN This is a post hoc analysis of a randomized trial which enrolled infants born at 24 to 28 completed weeks of gestation. All PENUT infants who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged 0-14.7 mg/kg/day (IQR 2.1-5.8 mg/kg/day) at day 60, with a mean of 3.6 mg/kg/day in placebo-treated infants and 4.8 mg/kg/day in Epo-treated infants. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Higher iron doses were associated with higher motor and language scores, but did not reach statistical significance. Results at 90 days were not significant. The effect size in the Epo-treated infants compared with placebo was consistently higher. CONCLUSION A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in preterm infants, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo.
Infants enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT), (n= 692).
Erythropoietin (Epo), (n= 337).
Placebo (n= 355).
Enteral iron supplementation ranged 0-14.7 mg/kg/day (IQR 2.1-5.8 mg/kg/day) at day 60, with a mean of 3.6 mg/kg/day in placebo-treated infants and 4.8 mg/kg/day in Epo-treated infants. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose. Higher iron doses were associated with higher motor and language scores, but did not reach statistical significance. Results at 90 days were not significant. The effect size in the Epo-treated infants compared with placebo was consistently higher.
Comparison of Hematocrit Change in Preterm Neonates with Birth Weight Based Versus Formula Based Packed Red Blood Cell Transfusion: A Randomized Control Trial
Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2021;:1-7
Conventionally the packed red blood cell (PRBC) transfusion volume given to neonates is 10 ml/kg to 20 ml/kg. The weight-based formulae underestimate the volume of PRBC required to achieve a target hematocrit (Hct) in preterm neonates. The study was done to compare the rise in Hct after transfusing PRBC volume calculated either based on body weight or using formula considering Hct of blood bag and Hct of preterm neonates. This prospective study included a total of 68 preterm neonates requiring transfusion for the first time having ≤ 34 weeks of gestational age. Neonates were randomized using block randomization, to receive 15 ml/kg of PRBC transfusion (group A) or transfusion based on the formula (group B). The primary outcome of interest was post-transfusion rise in hematocrit. The secondary outcome was the effect of transfusion on neonatal morbidities in terms of retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and death. Baseline variables (birth weight, gestation age, APGAR score and score of neonatal acute physiology) pre-transfusion hemodynamics and hematocrit of the bag were comparable in both groups. The mean volume of PRBC in group A was 18.8 ± 4.9 ml, whereas in group B it was 29.6 ± 7.3 ml, p = 0.0001. Group B transfusions had a statistically significant change in 24 h post-transfusion hematocrit. Secondary outcomes were comparable in two groups. Post transfusion rise in Hct of the patient in group B was significant as compared to group A. The study needed huge sample size to establish a difference in the number of re-transfusions required across two groups. The trial was registered under the clinical trial registry of India (CTRI/2018/01/011,063). SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s12288-021-01420-1.
Transfusions and neurodevelopmental outcomes in extremely low gestation neonates enrolled in the PENUT Trial: a randomized clinical trial
Pediatric research. 2021;:1-8
BACKGROUND Outcomes of extremely low gestational age neonates (ELGANs) may be adversely impacted by packed red blood cell (pRBC) transfusions. We investigated the impact of transfusions on neurodevelopmental outcome in the Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial population. METHODS This is a post hoc analysis of 936 infants 24-0/6 to 27-6/7 weeks' gestation enrolled in the PENUT Trial. Epo 1000 U/kg or placebo was given every 48 h × 6 doses, followed by 400 U/kg or sham injections 3 times a week through 32 weeks postmenstrual age. Six hundred and twenty-eight (315 placebo, 313 Epo) survived and were assessed at 2 years of age. We evaluated associations between BSID-III scores and the number and volume of pRBC transfusions. RESULTS Each transfusion was associated with a decrease in mean cognitive score of 0.96 (95% CI of [-1.34, -0.57]), a decrease in mean motor score of 1.51 (-1.91, -1.12), and a decrease in mean language score of 1.10 (-1.54, -0.66). Significant negative associations between BSID-III score and transfusion volume and donor exposure were observed in the placebo group but not in the Epo group. CONCLUSIONS Transfusions in ELGANs were associated with worse outcomes. We speculate that strategies to minimize the need for transfusions may improve outcomes. IMPACT Transfusion number, volume, and donor exposure in the neonatal period are associated with worse neurodevelopmental (ND) outcome at 2 years of age, as assessed by the Bayley Infant Scales of Development, Third Edition (BSID-III). The impact of neonatal packed red blood cell transfusions on the neurodevelopmental outcome of preterm infants is unknown. We speculate that strategies to minimize the need for transfusions may improve neurodevelopmental outcomes.
Effect of blood transfusions on cognitive development in very low birth weight infants
Journal of perinatology : official journal of the California Perinatal Association. 2021
OBJECTIVE Preterm infants frequently receive red cell transfusions; however, the effect of transfusions on cognition is unclear. We evaluated the relationship between transfusions and cognitive outcomes in preterm infants enrolled in a randomized trial of erythropoiesis stimulating agents (ESAs). STUDY DESIGN Preterm infants were randomized to ESAs or placebo during initial hospitalization, and transfusions recorded. Children were evaluated using standard developmental tests of cognition at 18-22 months (56 ESA, 24 placebo) and 3.5-4 years (39 ESA, 14 placebo). RESULTS Cognitive scores at 18-22 months were inversely correlated with transfusion volume (p = 0.02). Among those receiving ≥1 transfusion, cognitive scores were significantly higher in the ESA-treated group (p = 0.003). At 3.5-4 years, transfusions were not correlated with cognitive scores. CONCLUSIONS In the placebo group, transfused children had lower cognitive scores than did non-transfused children at 18-22 months. In the ESA group, cognitive scores did not differ by transfusion status, suggesting ESAs might provide neuroprotection.
Restrictive Transfusion Strategy after Cardiac Surgery
BACKGROUND Recent guidelines on transfusion in cardiac surgery suggest that hemoglobin might not be the only criterion to trigger transfusion. Central venous oxygen saturation (Svo2), which is related to the balance between tissue oxygen delivery and consumption, may help the decision process of transfusion. We designed a randomized study to test whether central Svo2-guided transfusion could reduce transfusion incidence after cardiac surgery. METHODS This single center, single-blinded, randomized controlled trial was conducted on adult patients after cardiac surgery in the intensive care unit (ICU) of a tertiary university hospital. Patients were screened preoperatively and were assigned randomly to two study groups (control or Svo2) if they developed anemia (hemoglobin less than 9 g/dl), without active bleeding, during their ICU stay. Patients were transfused at each anemia episode during their ICU stay except the Svo2 patients who were transfused only if the pretransfusion central Svo2 was less than or equal to 65%. The primary outcome was the proportion of patients transfused in the ICU. The main secondary endpoints were (1) number of erythrocyte units transfused in the ICU and at study discharge, and (2) the proportion of patients transfused at study discharge. RESULTS Among 484 screened patients, 100 were randomized, with 50 in each group. All control patients were transfused in the ICU with a total of 94 transfused erythrocyte units. In the Svo2 group, 34 (68%) patients were transfused (odds ratio, 0.031 [95% CI, 0 to 0.153]; P < 0.001 vs. controls), with a total of 65 erythrocyte units. At study discharge, eight patients of the Svo2 group remained nontransfused and the cumulative count of erythrocyte units was 96 in the Svo2 group and 126 in the control group. CONCLUSIONS A restrictive transfusion strategy adjusted with central Svo2 may allow a significant reduction in the incidence of transfusion.
Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage
CNS drugs. 2021
BACKGROUND Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury. OBJECTIVE The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH. METHODS This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age. RESULTS A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality (p = 0.176) or incidence of neurological disability (p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199-0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122-0.875; p = 0.026. CONCLUSIONS Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH. TRIAL REGISTRATION The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).
Comparison of Balanced Crystalloid Solutions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Critical care explorations. 2021;3(5):e0398
OBJECTIVE To summarize the evidence comparing various balanced crystalloid solutions. DATA SOURCES We searched MEDLINE, EMBASE, PUBMED, and CENTRAL databases. STUDY SELECTION We included randomized controlled trials that directly compared the IV administration of one balanced crystalloid solution with another. DATA EXTRACTION AND ANALYSIS We examined metabolic and patient-important outcomes and conducted meta-analysis using random effects model. For comparisons or outcomes with insufficient data to allow for pooling, we describe results narratively. We assessed risk of bias for individual trials using the Cochrane risk of bias tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. DATA SYNTHESIS We included 24 randomized controlled trials comparing Plasmalyte, Ringer's Lactate, Ringerfundin, Hartmann's solution, Ringer's Bicarbonate, Sterofundin, Kabilyte, Normosol, and novel balanced solutions. Of the included studies, 16 were performed in the perioperative setting, six in the ICU, one in the emergency department, and one in healthy volunteers. Administration of Plasmalyte resulted in a lower postinfusion serum chloride concentration (mean difference, 0.83 mmol/L lower; 95% CI, 0.03-1.64 mmol/L lower, low certainty), higher postinfusion base excess (mean difference, 0.65 mmol/L higher, 95% CI, 0.25-1.05 mmol/L higher, low certainty), and lower postinfusion serum lactate levels (mean difference, 0.46 mmol/L lower; 95% CI, 0.05-0.87 mmol/L lower, low certainty) compared with administration of any other balanced crystalloid. There were no important differences in postinfusion serum pH or potassium when comparing Plasmalyte with other balanced crystalloids. Data addressing other comparisons or examining the impact of different balanced crystalloids on patient-important outcomes were sparsely reported and too heterogeneous to allow for pooling. CONCLUSIONS Administration of Plasmalyte results in lower serum concentrations of chloride and lactate, and higher base excess than other balanced crystalloids. The certainty of evidence is low and requires further study in large randomized controlled trials to inform the choice of balanced crystalloid in patients requiring volume replacement.