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 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

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

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.

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

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

OBJECTIVE Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay. METHODS A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE(®) methodology. RESULTS The SFAR-SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus. CONCLUSIONS The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy).

Abstract

BACKGROUND AND STUDY AIMS To evaluate the effects of enteral administration of recombinant human erythropoietin (rhEPO) on feeding-related complications in preterm infants. PATIENTS AND METHODS This double-blind, randomized controlled pilot study enrolled 120 preterm infants born ≤ 32 weeks' gestation who were admitted to the neonatal intensive care unit in a tertiary hospital; 60 patients randomly received recombinant human erythropoietin while the other 60 received placebo. Newborns who underwent cardiopulmonary resuscitation, infants with genetic syndromes, infants with inborn errors of metabolism, infants with major congenital or acquired gastrointestinal tract malformations, infants with previous use of parenteral growth factors such as recombinant human erythropoietin and granulocyte-macrophage colony-stimuating factor (GM-CSF) and infants previously treated with intravenous immunoglobulin were excluded. Overall, 48 patients withdrew from the study because of intravenous haematopoietic growth factor intake or death before treatment was completed. A total of 72 preterm infants remained in the study: 36 preterm infants in the erythropoietin (EPO) group, and 36 preterm infants in the placebo group. The day that enteral feeding was successfully started, the time to establishing one-half, two-thirds, and full enteral feedings (reaching at least 150 mL/kg/day), the number of episodes of feeding intolerance, the time to regain birth weight and the incidence of necrotizing enterocolitis (NEC) were recorded. RESULTS Both groups showed no significant difference in the time to achieve one-half, two-thirds, or full enteral feeding, no signs of feeding intolerance, and no cases of NEC were recorded. CONCLUSION Enteral erythropoietin does not appear to affect feeding intolerance or NEC incidence.

Abstract

BACKGROUND Necrotising Enterocolitis (NEC) is a devastating neonatal disease. A temporal association between red cell transfusion and NEC has been recognized and there have been concerns about the effects of feeding during transfusion. We aimed to assess the effect of different enteral feeding regimens on splanchnic oxygenation in preterm infants receiving red cell transfusions. METHODS This was an open, multi-arm, parallel-group, randomised controlled trial conducted in a single centre in Australia. We compared three different enteral feeding regimes during a single red cell transfusion in preterm infants < 35 weeks gestational age at birth. Infants were randomised to either: (1) Withholding enteral feeds for 12 h from the start of transfusion or; (2) Continuing enteral feeds or; (3) Restriction of enteral feed volume to 120 ml/kg/day (maximum 20 kcal/30 ml) for 12 h. The primary outcome was mean splanchnic-cerebral oxygenation ratio (SCOR) and mean splanchnic fractional oxygen extraction (FOE) before (1 h prior), during (1 h into transfusion) and after (end of transfusion; 12 and 24 h post) transfusion. RESULTS There were 60 transfusion episodes (20 transfusion episodes in each group) included in the analysis. 41 infants with a median gestational age at birth of 27 weeks (range 23-32 weeks) were enrolled. The median postnatal age was 43 days (range 19-94 days) and the median pre-transfusion haematocrit was 0.27 (range 0.22-0.32). All three groups were similar at baseline. There were no differences in mean SCOR and mean splanchnic FOE at any of the pre-specified time points. There were also no differences in clinical outcomes. There were no episodes of NEC in any infant. Across all groups the mean SCOR increased from the start to the end of each transfusion (0.97 [CI95% 0.96-0.98] vs 1.00 [CI95% 0.99-1.01]; p = 0.04) and the mean FOE decreased from the start to the end of each transfusion (0.22 [CI95% 0.21-0.23] vs 0.17 [CI95% 0.16-0.18]; p < 0.001). CONCLUSIONS There were no differences in splanchnic oxygenation when enteral feeds were either withheld, continued or restricted during a transfusion. However, the successful conduct of this study supports the feasibility of a large trial powered to assess clinical outcomes. TRIAL REGISTRATION ANZCTR, ACTRN12616000160437. Registered 10 February 2016, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370069.

Abstract

BACKGROUND Transfusion of red blood cells (RBC) is common, can have adverse effects, and is a costly and limited resource. Interventions that reduce iatrogenic blood losses could reduce transfusions. The objectives of this pilot trial were to assess the feasibility (acceptability of the intervention and suitability of eligibility criteria) and potential effectiveness of pediatric size phlebotomy tubes in adult critically ill patients. METHODS We conducted a pilot, randomized controlled trial in the medical intensive care unit (ICU) of a university-affiliated, tertiary care referral hospital from November 2017 to September 2018. A total of 200 patients with hemoglobin of at least 7 g/dL and without bleeding were randomized to pediatric or adult size phlebotomy tubes. Stratification was according to baseline hemoglobin (7-9.49 g/dL, 9.5-11.99 g/dL, and 12 g/dL or greater). Acceptability was measured via the number of blood test recollections and the number of patients that discontinued the use of pediatric tubes. The suitability of patient eligibility criteria was determined by identifying baseline characteristics associated with RBC transfusions. Potential effectiveness was estimated from the time to RBC transfusion or to hemoglobin level below 7 g/dL. RESULTS The use of pediatric tubes was acceptable as patients experienced a low number of tests recollections (on average 1 every 57 days), and none of the participants discontinued their use. The baseline hemoglobin category was the only factor that appeared to be independently associated with RBC transfusions. A total of 6 patients (6%) in the pediatric tube group and 11 patients (11%) in the adult tube group (hazard ratio, 0.69; 95% CI, 0.25 to 1.9) received an RBC transfusion or reached hemoglobin below 7 g/dL. Almost all of these patients (16 of 17 participants) had baseline hemoglobin of 7-9.49 g/dL. CONCLUSIONS This pilot study suggests that pediatric phlebotomy tubes are acceptable to patients and can therefore be used in adult ICU patients. A future study should focus on patients with hemoglobin levels below 9.5 g/dL, as these patients have a high risk of transfusions. This intervention has the potential of being successful in selected patients. A definitive trial is warranted. TRIAL REGISTRATION ClinicalTrials.gov, NCT03286465. Retrospectively registered on September 18, 2017.