The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis
European journal of pediatrics. 2021
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.
Prophylactic intravenous calcium therapy for exchange blood transfusion in the newborn
The Cochrane Database of Systematic Reviews. 2017;((10)):CD011048.
BACKGROUND Exchange blood transfusion (EBT) is a form of whole blood transfusion in which the total blood volume is replaced within a few hours. In perinatal and neonatal medicine, EBT is most often used in the management of severe anaemia or severe hyperbilirubinaemia in the first week of life. Hypocalcaemia, one of the common morbidities associated with EBT, is thought to arise from the chelating effects of the citrate commonly used as an anticoagulant in the donor's blood. This disorder manifests with muscular and nervous irritability and cardiac arrhythmias. OBJECTIVES To determine whether the use of prophylactic calcium reduces the risk of hypocalcaemia-related morbidities and death among newborn infants receiving EBT. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to 29 June 2016), Embase (1980 to 29 June 2016), and CINAHL (1982 to 29 June 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA All randomised and quasi-randomised trials of prophylactic intravenous calcium in EBT for newborns. DATA COLLECTION AND ANALYSIS Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes (mean total and ionised serum calcium before and after EBT and the presence of adverse events such as hypoglycaemia, apnoea, cardiac arrest, and death immediately after EBT). We reported results as means difference (MD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) and risk differences (RD) and 95% CIs for dichotomous outcomes. We assessed quality using the Cochrane 'Risk of bias' assessment tool and the GRADE system. MAIN RESULTS We found only one quasi-randomised trial with 30 participants that met our inclusion criteria. In the small trial, total and ionised serum calcium levels were measured immediately before and immediately after EBT. All the participants were included in the final analysis and all the important outcomes were reported. Primary outcomesThere was one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1). The study did not report the presence of cardiac arrhythmias within one week of EBT and the number of infants with serum calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL (1.1 mmol/L)).Pair-wise comparison of EBT with intravenous 10% calcium gluconate versus EBT without intravenous calcium (change from baseline) showed mean total serum calcium was raised in the intervention group compared to the control group (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low-quality evidence also indicated an increase in the levels of mean ionised serum calcium in the intervention group compared to the control group (MD -0.22, 95% CI -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomesAdverse reactions to intravenous calcium therapy included cardiac arrest in one neonate in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to 0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1) in the two neonates who died. Data were not available for other major secondary outcomes such as the number of infants with reduced serum magnesium, reduced parathormone, increased calcitonin, presence of seizures, carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography within one week of EBT. AUTHORS' CONCLUSIONS Very low-quality data from one quasi-randomised controlled trial suggested that the mean serum total and ionised calcium increased in the study group but decreased in the control group immediately after EBT. However, the mean values of total and ionised cal
The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Critical Care (London, England). 2014;18((6):):699.
INTRODUCTION Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n=128) and the mean age of children ranged from 0.9 to 18 years (n=66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.