Abstract

BACKGROUND The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

Abstract

INTRODUCTION In critically ill patients, Transfusion Related Acute Lung Injury (TRALI) remains the leading cause of transfusion-related fatalities in critical care setting and associated with inflammation and oxidative stress state. Recent research raised the potential efficacy of high dose intravenous ascorbic acid in critically ill patients. OBJECTIVE The aim of this trial was to investigate the effect of high dose intravenous ascorbic acid (VC) as a targeted therapy for TRALI in terms of serum proinflammatory (interleukin-8, interleukin-1β, C-reactive protein), anti-inflammatory (interleukin-10), oxidative stress (superoxide dismutase, malondialdehyde) markers, and plasma VC levels. Secondary outcomes were oxygenation (PaO(2) /FiO(2) ratio), vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality. METHODS Eighty critically ill patients with TRALI (n=80) were randomized to receive 2.5gm/6hr intravenous vitamin C for 96 hours (ASTRALI group) or placebo. Patients were followed-up to measure the outcomes initially (T0) and at the end of treatment (T96). RESULTS When compared to control group, ASTRALI group at T96, showed significantly higher median of interleukin-10 (31.6 ± 25.8 Vs. 17.7 ± 12.0 pg/mL, p<0.0001) levels and superoxide dismutase (12876 ± 4627 U/L Vs. 5895 ± 6632 U/L, p<0.0001) activities, lower median C-reactive protein (76 ± 50 Vs. 89 ± 56 mg/L, p=0.033), interleukin-8 (11.8 ± 7.3, 35.5 ± 19.8 pg/mL, p<0.0001), and malondialdehyde (0.197 ± 0.034 Vs. 0.234 ± 0.074 μM/L, p=0.002) levels. CONCLUSION High dose ascorbic acid was associated with significantly reduced oxidative stress, reduced pro-inflammatory markers except IL-1β, elevated anti-inflammatory marker, and elevated plasma VC levels.

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

INTRODUCTION Trauma resuscitation at dedicated trauma centers typically consist of ad-hoc teams performing critical tasks in a time-limited manner. This creates a high stakes environment apt or avoidable errors. Reporting of errors in trauma resuscitation is generally center-dependent and lacks common terminology. METHODS We conducted a systematic review by searching Ovid Medline, Scopus and Embase from inception to February 24, 2021 for errors in adult trauma resuscitation. English studies published after 2001 were included. Studies were assessed by two independent reviewers for meeting inclusion/exclusion criteria. Errors were characterized from the included studies and a summary table was developed. Our review was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020152875). RESULTS The literature search retrieved 4658 articles with 26 meeting eligibility criteria. Errors were identified by morbidity and mortality rounds or other committee in 62%, missed injuries on tertiary assessment or radiology review in 12%, deviations from algorithmic guidelines in 12% or predefined for chest tube complications, critical incident reporting, aspiration or delays in care. In total there were 39 unique error types identified and divided into 9 categories including Emergency Medical Services handover, airway, assessment of injuries, patient monitoring and access, transfusion/blood related, management of injuries, team communication/dynamics, procedure error and disposition. CONCLUSIONS Overall, our systematic review identified 39 unique error types in trauma resuscitation. Identifying these errors is imperative in developing systems for improvement of trauma care.

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

INTRODUCTION Transfusion therapy in hemorrhaging trauma patients is associated with the development of thromboembolic events. It is unknown whether current resuscitation strategies, including large volumes of plasma and early administration of procoagulant therapy, increases this risk. METHODS A systematic search was conducted in MEDLINE, PubMed, and Embase. Studies were screened by two independent reviewers and included if they reported on thromboembolic events in patients with severe trauma (injury severity score ≥16) who received transfusion of at least 1 unit of red blood cells. The ratio by which blood products were transfused, as well as use of procoagulant or antifibrinolytic medication, was recorded. RESULTS A total of 40 studies with 11.074 bleeding trauma patients were included, in which 1.145 thromboembolic events were reported, yielding an incidence of 10% thromboembolic events. In studies performing routine screening for thromboembolic complications, the incidence ranged from 12% to 23%. The risk of thromboembolic events was increased after administration of tranexamic acid (TXA; odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7-4.1; p < 0.001) and fibrinogen concentrate (OR, 2.1; 95% CI, 1.0-4.2; p = 0.04). Blood product ratio, the use of prothrombin complex concentrate or recombinant factor VIIa were not associated with thromboembolic events. CONCLUSION This systematic review identified an incidence of thromboembolic events of 10% in severely injured bleeding trauma patients. The use of TXA and fibrinogen concentrate was associated with the development of thromboembolic complications.

Abstract

OBJECTIVES RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding. DATA SOURCES PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019. STUDY SELECTION All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion. DATA EXTRACTION Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients. DATA SYNTHESIS We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were -0.0 L/min/m (-0.1 to 0.1 L/min/m) (p = 0.86) for cardiac index; -1.8 beats/min (-3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m (71.1-122.5 mL/min/m) (p < 0.01) for oxygen delivery index; 2.9% (2.2-3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; -3.7% (-4.4% to -3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m (0.9-9.0 mL/min/m) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m (2.3-14.5 mL/min/m; p = 0.01). CONCLUSIONS Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis.

Abstract

BACKGROUND Stroke is the second leading cause of death and a major cause of morbidity worldwide. Retrospective clinical and animal studies have demonstrated neuroprotective effects of iron chelators in people with haemorrhagic or ischaemic stroke. This is the first update of the original Cochrane Review published in 2012. OBJECTIVES To evaluate the effectiveness and safety of iron-chelating drugs in people with acute stroke. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (2 September 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2019, Issue 9; 2 September 2019), MEDLINE Ovid (2 September 2019), Embase Ovid (2 September 2019), and Science Citation Index (2 September 2019). We also searched ongoing trials registers. SELECTION CRITERIA We included randomised controlled trials (RCTs) of iron chelators versus no iron chelators or placebo for the treatment of acute stroke, including subarachnoid haemorrhage. DATA COLLECTION AND ANALYSIS Two review authors independently screened the search results. We obtained the full texts of potentially relevant studies and evaluated them for eligibility. We assessed risk of bias using the Cochrane 'Risk of bias' tool, and the certainty of evidence using the GRADE approach. MAIN RESULTS Two RCTs (333 participants) were eligible for inclusion; both compared the iron-chelating agent deferoxamine against placebo. Both studies evaluated participants with spontaneous intracerebral haemorrhage. We assessed one study to have a low risk of bias; the other study had potential sources of bias. The limited and heterogeneous data did not allow for meta-analysis of the outcome parameters. The evidence suggests that administration of deferoxamine may result in little to no difference in deaths (8% in placebo vs 8% in deferoxamine at 180 days; 1 RCT, 291 participants; low-certainty evidence). These RCTs suggest that there may be little to no difference in good functional outcome (modified Rankin Scale score 0 to 2) between groups at 30, 90 and 180 days (placebo vs deferoxamine: 67% vs 57% at 30 days and 36% vs 45% at 180 days; 2 RCTs, 333 participants; low-certainty evidence). One RCT suggests that administration of deferoxamine may not increase the number of serious adverse events or deaths (placebo vs deferoxamine: 33% vs 27% at 180 days; risk ratio 0.81, 95 % confidence interval 0.57 to 1.16; 1 RCT, 291 participants; low-certainty evidence). No data were available on any deaths within the treatment period. Deferoxamine may result in little to no difference in the evolution of National Institute of Health Stroke Scale scores from baseline to 90 days (placebo vs deferoxamine: 13 to 4 vs 13 to 3; P = 0.37; 2 RCTs, 333 participants; low-certainty evidence). Deferoxamine may slightly reduce relative oedema surrounding intracerebral haemorrhage at 15 days (placebo vs deferoxamine: 1.91 vs 10.26; P = 0.042; 2 RCTs, 333 participants; low-certainty evidence). Neither study reported quality of life. AUTHORS' CONCLUSIONS We identified two eligible RCTs for assessment. We could not demonstrate any benefit for the use of iron chelators in spontaneous intracerebral haemorrhage. The added value of iron-chelating therapy in people with ischaemic stroke or subarachnoid haemorrhage remains unknown.

Abstract

Transfusion-associated circulatory overload is the most frequent serious adverse transfusion reaction, with an incidence close to 1% of transfused patients in the general adult population. Patients in ICUs are probably more at risk of transfusion-associated circulatory overload as they are more frequently transfused and associated with more comorbidities. However, the epidemiology of transfusion-associated circulatory overload in ICU is not well characterized, leading to a risk of underdiagnosis. OBJECTIVES We conducted a scoping review to describe the incidence, risk factors, and outcomes of transfusion-associated circulatory overload in PICU and adult ICU. DATA SOURCES PubMed, Ovid Medline, Ovid All EBM Reviews, Ovid Embase, and EBSCO CINAHL COMPLETE. STUDY SELECTION Two reviewers independently screened each article for inclusion criteria. Studies were eligible if they reported data on incidence, risk factors, or outcomes of transfusion-associated circulatory overload in at least 10 ICU patients. DATA SYNTHESIS Among 5,926 studies identified, nine were included. Five studies were prospective, and four were retrospective. The definition of transfusion-associated circulatory overload varied among studies. The pooled incidence of transfusion-associated circulatory overload was of 5.5% (95% CI, 2.6-9.4%) in adult ICUs (four studies, 2,252 patients, high heterogeneity). In PICUs, two studies (345 patients) reported 0 cases, and a third study (136 patients) reported variable incidences between 1.5% and 76%, depending on diagnostic criteria. Risk factors for transfusion-associated circulatory overload included positive fluid balance, the number and type of products transfused, rate of transfusion, and cardiovascular and renal comorbidities. Transfusion-associated circulatory overload was associated with increased ICU and hospital lengths of stay, whereas the association with mortality was not consistent. CONCLUSIONS Transfusion-associated circulatory overload is frequent in ICU patients and is associated with adverse outcomes. The lack of a pediatric-adjusted definition of transfusion-associated circulatory overload may lead to a risk of underdiagnosis of this condition in PICUs. Further research is warranted to improve the knowledge of transfusion-associated circulatory overload and the safety of transfusion in ICU patients.