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 and objective: The early detection of underlying hemorrhage of pelvic trauma has been a critical issue. The aim of this study was to systematically determine the diagnostic accuracy of computed tomography (CT) for detecting severe pelvic hemorrhage. Materials and Methods: Relevant articles were obtained by searching PubMed, EMBASE, and Cochrane databases through 28 November 2020. Diagnostic test accuracy results were reviewed to obtain the sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve of CT for the diagnosis in pelvic trauma patients. The positive finding on CT was defined as the contrast extravasation. As the reference standard, severe pelvic hemorrhage was defined as an identification of bleeding at angiography or by direct inspection using laparotomy that required hemostasis by angioembolization or surgery. A subgroup analysis was performed according to the CT modality that is divided by the number of detector rows. Result: Thirteen eligible studies (29 subsets) were included in the present meta-analysis. Pooled sensitivity of CT was 0.786 [95% confidence interval (CI), 0.574-0.909], and pooled specificity was 0.944 (95% CI, 0.900-0.970). Pooled sensitivity of the 1-4 detector row group and 16-64 detector row group was 0.487 (95% CI, 0.215-0.767) and 0.915 (95% CI, 0.848-0.953), respectively. Pooled specificity of the 1-4 and 16-64 detector row groups was 0.956 (95% CI, 0.876-0.985) and 0.906 (95% CI, 0.828-0.951), respectively. Conclusion: Multi-detector CT with 16 or more detector rows has acceptable high sensitivity and specificity. Extravasation on CT indicates severe hemorrhage in patients with pelvic trauma.

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

OBJECTIVES To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies. DATA SOURCES Embase, Pubmed, Web of Science, and the Cochrane Library. STUDY SELECTION Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage. DATA EXTRACTION Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event. DATA SYNTHESIS A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents. CONCLUSIONS Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.

Abstract

Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic process of blood coagulation, from activation of clotting factors to fibrinolysis, has emerged and a comprehensive review of hemostasis and fibrinolysis following aSAH may reveal targets of treatment. We conducted a systematic review of existing literature assessing coagulation and fibrinolysis following aSAH, but prior to treatment. PubMed, Embase, and Web of Science were searched on November 18, 2020, without time boundaries. In total, 45 original studies were eventually incorporated into this systematic review, divided into studies presenting data only from conventional or quantitative assays (n = 22) and studies employing dynamic assays (n = 23). Data from conventional or quantitative assays indicated increased platelet activation, whereas dynamic assays detected platelet dysfunction possibly related to an increased risk of rebleeding. Secondary hemostasis was activated in conventional, quantitative, and dynamic assays and this was related to poor neurological outcome and mortality. Studies systematically investigating fibrinolysis were sparse. Measurements from conventional or quantitative assays, as well as dynamic fibrinolysis assays, revealed conflicting results with normal or increased lysis and changes were not associated with outcome. In conclusion, dynamic assays were able to detect reduced platelet function, not revealed by conventional or quantitative assays. Activation of secondary hemostasis was found in both dynamic and nondynamic assays, while changes in fibrinolysis were not convincingly demonstrable in either dynamic or conventional or quantitative assays. Hence, from a mechanistic point of view, desmopressin to prevent rebleeding and heparin to prevent DCI may hold potential as therapeutic options. As changes in fibrinolysis were not convincingly demonstrated and not related to outcome, the use of tranexamic acid prior to aneurysm closure is not supported by this review.

Abstract

BACKGROUND AND PURPOSE Recovery after intracerebral haemorrhage (ICH) is often slower than ischemic stroke. Despite this, ICH research often quantifies recovery using the same outcome measures obtained at the same timepoints as ischemic stroke. The primary objective of this scoping review is to map the existing literature to determine when and how outcomes are being measured in prospective studies of recovery after ICH. METHODS We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception to November 2019, for prospective studies that included patients with ICH. Two investigators independently screened the studies and extracted data around timing and type of outcome assessment. RESULTS Among the 9761 manuscripts reviewed, 395 met inclusion criteria, of which 276 were observational studies and 129 were interventional studies that enrolled 66274 patients. Mortality was assessed in 93% of studies. Functional outcomes were assessed in 85% of studies. The most frequently used functional assessment tool was the modified Rankin Scale (mRS) (60%), followed by the National Institute of Health Stroke Severity Scale (22%) and Barthel Index (21%). The most frequent timepoint at which mortality was assessed was 90 days (41%), followed by 180 days (18%) and 365 days (12%), with 2% beyond 1 year. The most frequent timepoint used for assessing mRS was 90 days (62%), followed by 180 days (21%) and 365 days (17%). CONCLUSION While most prospective ICH studies report mortality and functional outcomes only at 90 days, a significant proportion do so at 1 year and beyond. Our results support the feasibility of collecting long-term outcome data to optimally assess recovery in ICH.

Abstract

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Abstract

INTRODUCTION Vasospasm and delayed ischemic neurological deficits (DIND) are the leading causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Several therapeutic agents have been assessed in randomized controlled trials (RCTs) for their efficacy in reducing the incidence of vasospasm and improving functional outcome. The aim of this network meta-analysis is to compare all these therapeutic agents for their effect on functional outcome and other parameters following aSAH. METHODS A comprehensive search of different databases was performed to retrieve RCTs describing the effect of various therapeutic approaches on functional outcome and other parameters following aSAH. RESULTS Ninety-two articles were selected for full text review and 57 articles were selected for the final analysis. Nicardipine prolonged released implants (NPRI) was found to be the best treatment in terms of favorable outcome (OR, 8.55; 95% CrI, 1.63 to 56.71), decreasing mortality (OR, 0.08; 95% CrI, 0 to 0.82), and preventing angiographic vasospasm (OR, 0.018; 95% CrI, 0.00057 to 0.16). Cilostazol was found to be the second-best treatment in improving favorable outcomes (OR, 3.58; 95% CrI, 1.97 to 6.57) and decreasing mortality (OR, 0.41; 95% CrI, 0.12 to 1.15). Fasudil (OR, 0.16; 95% CrI, 0.03 to 0.78) was found to be the best treatment in decreasing raised vessel velocity and enoxaparin (OR, 0.25; 95% CrI, 0.057 to 1.0) in preventing DIND. CONCLUSIONS Our analysis revealed that NPRI and Cilostazol were associated with the best chances to improve favorable outcome and mortality in patients with aSAH. However, larger multicentric studies from different parts of the world are required to confirm these findings.

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

BACKGROUND Tranexamic acid (TXA) is an antifibrinolytic drug associated with improved survival among trauma patients with haemorrhage. TXA is considered a primary haemostatic intervention in pre-hospital for treatment of bleeding alongside blood product transfusion. METHODS A Systematic Review and Meta-Analysis was conducted to investigate the impact of pre-hospital TXA on mortality among trauma patients with bleeding. A systematic search was conducted using the National Institute for Health and Care Excellence (NICE) Healthcare Databases Advanced Search (HDAS) library which contain the following of databases: EMBASE, Medline, PubMed, BNI, EMCARE, and HMIC. Other databases searched included SCOPUS and the Cochrane Central Register for Clinical Trials Library (CENTRAL). Quality assessment tools were applied among included studies; Cochrane Risk of Bias (ROB) for Randomised Control Trials RCTs and Newcastle-Ottawa Scale (NOS) for cohort observational studies. RESULTS A total of 797 publications were identified from the initial database search. After removing duplicates and applying inclusion/exclusion criteria, Four studies were included in the review and meta-analysis which identified a significant survival benefit in patients who received pre-hospital TXA vs no TXA. Three observational cohort and one RCT were included into the review with a total of 2347 patients (TXA: 1169 vs No TXA: 1178). There was a significant reduction in 24 hours mortality; Odds ratios (OR) 0.60 (95% CI: 0.37-0.99). No Statistical significant differences in 28 to 30 days mortality OR 0.69 (95% CI: 0.47-1.02), or VTE OR 1.49 (95% CI: 0.90 - 2.46) were found. CONCLUSION This review demonstrates that pre-hospital TXA is associated with significant reductions in the early (24 hour) mortality of trauma patients with suspected or confirmed haemorrhage but no increase in the incidence of VTE. LEVEL OF EVIDENCE (I) Systematic review and meta-analysis.