Abstract

BACKGROUND Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. PURPOSE To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. METHODS/SEARCH STRATEGY Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. FINDINGS Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. IMPLICATIONS FOR PRACTICE To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. IMPLICATIONS FOR RESEARCH It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.

Abstract

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.

Abstract

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).

Abstract

OBJECTIVES Patients with severe spontaneous intracranial haemorrhages, managed in intensive care units, face ethical issues regarding the difficulty of anticipating their recovery. Prognostic tools help clinicians in counselling patients and relatives and guide therapeutic decisions. We aimed to methodologically assess prognostic tools for functional outcomes in severe spontaneous intracranial haemorrhages. DATA SOURCES Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, we conducted a systematic review querying Medline, Embase, Web of Science, and the Cochrane in January 2020. STUDY SELECTION We included development or validation of multivariate prognostic models for severe intracerebral or subarachnoid haemorrhage. DATA EXTRACTION We evaluated the articles following the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies and Transparent Reporting of multivariable prediction model for Individual Prognosis Or Diagnosis statements to assess the tools' methodological reporting. RESULTS Of the 6149 references retrieved, we identified 85 articles eligible. We discarded 43 articles due to the absence of prognostic performance or predictor selection. Among the 42 articles included, 22 did not validate models, 6 developed and validated models and 14 only externally validated models. When adding 11 articles comparing developed models to existing ones, 25 articles externally validated models. We identified methodological pitfalls, notably the lack of adequate validations or insufficient performance levels. We finally retained three scores predicting mortality and unfavourable outcomes: the IntraCerebral Haemorrhages (ICH) score and the max-ICH score for intracerebral haemorrhages, the SubArachnoid Haemorrhage International Trialists score for subarachnoid haemorrhages. CONCLUSIONS Although prognostic studies on intracranial haemorrhages abound in the literature, they lack methodological robustness or show incomplete reporting. Rather than developing new scores, future authors should focus on externally validating and updating existing scores with large and recent cohorts.

Abstract

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.

Abstract

BACKGROUND Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. METHODS In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was < 20 μg/l and with intravenous iron and erythropoietin for 20 ≤ hepcidin < 41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue, day 90 mortality and 1-year survival. RESULTS Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). A total of 220 patients (55%) had ID at discharge (i.e., a hepcidin < 41 μg/l). Primary endpoint was not different (medians (IQR) post-ICU LOS 33(13;90) vs. 33(11;90) days for intervention and control, respectively, median difference - 1(- 3;1) days, p = 0.78). D90 mortality was significantly lower in intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference - 8.7 (- 15.1 to - 2.3)%, p = 0.008, OR 95% IC, 0.46, 0.22-0.94, p = 0.035), and one-year survival was improved (p = 0.04). CONCLUSION Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but was associated with a significant reduction in D90 mortality and with improved 1-year survival in critically ill patients about to be discharged after a prolonged stay. TRIAL REGISTRATION www.clinicaltrial.gov NCT02276690 (October 28, 2014; retrospectively registered).

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

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.

Abstract

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.

Abstract

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.