Abstract

OBJECTIVES Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion-related pro-inflammatory cytokine production. This may be because of alterations in recipient immune responses. METHODS This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro-inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks' gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. RESULTS By the third transfusion, infants receiving unwashed blood had an increase in IL-17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL-17A (P = 0.013), TNF (P = 0.048), IL-6 (P = 0.001), IL-8 (P = 0.037), IL-12 (P = 0.001) and IFN-γ (P = 0.001). The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12 (P = 0.001), IL-17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine). CONCLUSION The pro-inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.

Abstract

BACKGROUND The effect of resuscitative endovascular balloon occlusion of aorta (REBOA) in lowering mortality rate compared to resuscitative thoracotomy (RT) is inconclusive. In this updated systematic review and meta-analysis, we determined the effectiveness of the two techniques in patients with noncompressible torso hemorrhage (NCTH). MATERIALS AND METHODS Online databases (PubMed, Embase, and MEDLINE) were searched until April 23, 2021, for original articles investigating the effect of REBOA on relevant outcomes (e.g., mortality in ED, mortality before discharge, in-hospital mortality, length of hospital stay and length of ICU stay) among NCTH patients in contrast to open aortic occlusion by RT. Data on baseline characteristics and endpoints were extracted. Review Manager version 5.4.1 and OpenMetaAnalyst were used for analyses. Risk ratios (RR) and the weighted mean differences (WMD) with corresponding 95% confidence intervals were calculated. RESULTS Eight studies were included having 3241 patients in total (REBOA 1179 and RT: 2062). The pooled analysis demonstrated that compared to RT, mortality was significantly lower in the REBOA group in all settings: In emergency department (ED) (RR 0.63 [0.45, 0.87], P = 0.006, I(2) = 81%), before discharge (RR= 0.86 [0.75, 0.98], P = 0.03, I(2 =) 93%), and in-hospital mortality (RR 0.80 [0.68, 0.95], P = 0.009, I(2 =) 85%). Similarly, the length of ICU stay was significantly lower in REBOA group (WMD = 0.50 [-0.48, 1.48], P = 0.32, I(2 =)97%). However, no significant differences were observed in the length of hospital stay (WMD = 0.0 [-0.26, 0.26] P = 1). CONCLUSIONS Our pooled analysis shows REBOA to be effective in reducing mortality among NCTH patients. However, due to limited studies, the positive findings should be viewed discreetly and call for further investigation.

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 Dynamic arterial elastance (Ea(dyn)) has been extensively considered as a functional parameter of arterial load. However, conflicting evidence has been obtained on the ability of Ea(dyn) to predict mean arterial pressure (MAP) changes after fluid expansion. This meta-analysis sought to assess the predictive performance of Ea(dyn) for the MAP response to fluid expansion in mechanically ventilated hypotensive patients. METHODS We systematically searched electronic databases through November 28, 2020, to retrieve studies that evaluated the association between Ea(dyn) and fluid expansion-induced MAP increases in mechanically ventilated hypotensive adults. Given the diverse threshold value of Ea(dyn) among the studies, we only reported the area under the hierarchical summary receiver operating characteristic curve (AUHSROC) as the primary measure of diagnostic accuracy. RESULTS Eight observational studies that included 323 patients with 361 fluid expansions met the eligibility criteria. The results showed that Ea(dyn) was a good predictor of MAP increases in response to fluid expansion, with an AUHSROC of 0.92 [95% confidence interval (CI) 0.89 to 0.94]. Six studies reported the cut-off value of Ea(dyn), which ranged from 0.65 to 0.89. The cut-off value of Ea(dyn) was nearly conically symmetrical, most data were centred between 0.7 and 0.8, and the mean and median values were 0.77 and 0.75, respectively. The subgroup analyses indicated that the AUHSROC was slightly higher in the intensive care unit (ICU) patients (0.96; 95% CI 0.94 to 0.98) but lower in the surgical patients in the operating room (0.72; 95% CI 0.67 to 0.75). The results indicated that the fluid type and measurement technique might not affect the diagnostic accuracy of Ea(dyn). Moreover, the AUHSROC for the sensitivity analysis of prospective studies was comparable to that in the primary analysis. CONCLUSIONS Ea(dyn) exhibits good performance for predicting MAP increases in response to fluid expansion in mechanically ventilated hypotensive adults, especially in the ICU setting.

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

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

The present study aimed to explore the efficacy of intravenous immunoglobulin (IVIG) injection in neonates with acute lung injury (ALI) and assess its effects on serum inflammatory cytokine levels. The research subjects were 140 neonates with ALI who were evenly distributed into a control group (COG) and a study group (STG). The COG patients were treated routinely, whereas patients in the STG were administered IVIG in addition to the standard treatment received by the COG. The arterial partial pressure of oxygen (PaO(2)), PaO(2)/fraction of inspired oxygen (FIO(2)), mechanical ventilation time and hospitalization time were compared between the two groups. ELISA was used to determine the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the patients before treatment and at 12, 24 and 36 h after treatment. The Kaplan-Meier method was used to analyze the survival of the patients, including their survival for 30 days after treatment. The patients were divided into high and low cytokine expression groups based on their mean expression levels of serum IL-6 and TNF-α before treatment. After treatment, PaO(2) and PaO(2)/FiO2 were significantly higher and mechanical ventilation and hospitalization time were reduced in the STG in comparison with the COG (all P<0.001). At 12, 24 and 36 h after treatment, serum IL-6 and TNF-α levels in the STG were lower than those in the COG (both P<0.05). The 30-day survival rate after treatment was not significantly different between the two groups (P>0.05). The 30-day survival rate in the high IL-6 and high TNF-α expression COG was lower than that in the low IL-6 and low TNF-α expression COG (both P<0.05). The results of the present study indicate that IVIG may improve pulmonary gas exchange, shorten the course of disease and reduce the inflammatory response in neonates with ALI.

Abstract

OBJECTIVE To analyze the efficacy of hydroxyethyl starch (HES) combined with Ulinastatin (Uti) in the treatment of newborns with capillary leak syndrome (CLS). METHODS A total of 60 newborns with CLS admitted to four hospitals were selected as the study subjects, and were randomly divided into the control group (n = 30) and the observation group (n = 30) in accordance with the random number table. The control group was treated with HES alone, while the observation group was treated with Uti combined with HES. RESULTS At 5 d after treatment, the incidence rates of systemic edema and pulmonary edema, the levels of CRP, NE, and BUN, and the duration for the improvement of systemic edema, pulmonary edema and NICU hospital stay in the control group were superior to those in the observation group, while the 24-h urine output, PaO(2) and MAP levels, the levels of A, SCr, ALT, and IL-10 in the observation group were superior to those in the control group (P < 0.05). After 3 months of follow-up after treatment, the mortality rate of newborns in the observation group (13.33%) was lower than that in the control group (36.67%) (P < 0.05). CONCLUSION HES combined with Uti can effectively alleviate edema, control inflammatory levels, and improve hepatic and renal functions and neonatal survival rate of newborns with CLS.