Abstract

BACKGROUND Despite appropriate antibiotic therapy, the risk of mortality in neonatal sepsis still remains high. We conducted a systematic review to comprehensively evaluate different adjuvant therapies in neonatal sepsis in a network meta-analysis. METHODS We included randomized controlled trials (RCTs) and quasi-RCTs that evaluated adjuvant therapies in neonatal sepsis. Neonates of all gestational and postnatal ages, who were diagnosed with sepsis based on blood culture or sepsis screen were included. We searched MEDLINE, CENTRAL, EMBASE and CINAHL until 12th April 2021 and reference lists. Data extraction and risk of bias assessment were performed in duplicate. A network meta-analysis with bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. RESULTS We included 45 studies involving 6,566 neonates. Moderate CoE showed IVIG [Relative Risk (RR); 95% Credible Interval (CrI): 1.00; (0.67-1.53)] as an adjunctive therapy probably does not reduce all-cause mortality before discharge, compared to standard care. Melatonin [0.12 (0-0.08)] and granulocyte transfusion [0.39 (0.19-0.76)] may reduce mortality before discharge, but CoE is very low. The evidence is also very uncertain regarding other adjunctive therapies to reduce mortality before discharge. Pentoxifylline may decrease the duration of hospital stay [Mean difference; 95% CrI: -7.48 days (-14.50-0.37)], but CoE is very low. CONCLUSION Given the biological plausibility for possible efficacy of these adjuvant therapies and that the CoE from the available trials is very low to low except for IVIG, we need large adequately powered RCTs to evaluate these therapies in sepsis in neonates.

Abstract

OBJECTIVES Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. METHODS PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period and including one or more RCTs reporting LOS. Two authors independently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. RESULTS A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC, chlorhexidine for skin or cord care, and kangaroo care for low birth weight babies. Similarly, moderate-quality evidence showed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. CONCLUSIONS The overview summarizes the evidence from the Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.

Abstract

OBJECTIVE To explore the clinical effects of albumin supplements on the basis of crystalloid solution in patients with sepsis or septic shock. METHODS The online databases including PubMed, Web of Science, Cochrane Library, and EMBASE were comprehensively searched from inception to June 28, 2021, with the keywords including "albumin," "sepsis," or "septic shock." Retrospective cohort (RC) and randomized controlled trials (RCT) were included for analysis. Two authors independently searched and analyzed the literature. The in-hospital mortality at 7 days and 28 days, duration of mechanical ventilation, renal replacement therapy, length of ICU stay, and length of hospital stay were compared between patients with albumin supplements and crystalloid solution and those with crystalloid alone. RESULTS A total of 10 studies with 6463 patients were eventually included for meta-analysis. The in-hospital mortality of patients at 7 days (OR = 1.00, 95% CI: 0.81-1.23) and 28 days (OR = 1.02, 95% CI: 0.91-1.13) did not show a significant difference between the two groups of patients. Also, the pooled results demonstrated no significant differences in duration of mechanical ventilation (OR = 0.29, 95% CI: -0.05-0.63), renal replacement therapy (WMD = 1.15, 95% CI: 0.98-1.35), length of ICU stay (WMD = -0.07, 95% CI: -0.62-0.48), and length of hospital stay (WMD = -0.09, 95% CI: -0.70-0.52) between patients receiving albumin plus crystalloid solution and those with crystalloid solution alone. CONCLUSION Albumin supplements on the basis of crystalloid solution did not improve the 7-day and 28-dayin-hospital mortality in patients with sepsis or septic shock compared with those with crystalloid solution alone.

Abstract

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

Abstract

BACKGROUND Whether to use limited fluid resuscitation (LFR) in patients with hemorrhagic shock or septic shock remains controversial. This research was aimed to assess the pros and cons of utilizing LFR in hemorrhagic shock or septic shock patients. METHODS PubMed, Cochrane Library, Embase, Web of science, CNKI, VIP, and Wan Fang database searches included for articles published before December 15, 2020. Randomized controlled trials of LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients were selected. RESULT This meta-analysis including 28 randomized controlled trials (RCTs) and registered 3288 patients. The 7 of 27 RCTs were the patients with septic shock. Others were traumatic hemorrhagic shock patients. Comparing LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients, the summary odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.42-0.60, P < .00001) for mortality, 0.46 (95% CI 0.31-0.70, P = .0002) for multiple organ dysfunction syndrome (MODS), 0.35 (95% CI 0.25-0.47) for acute respiratory distress syndrome (ARDS), and 0.33 (95% CI 0.20-0.56) for disseminated intravascular coagulation (DIC). CONCLUSION Limited fluid resuscitation is the benefit of both traumatic hemorrhagic shock patients and septic shock patients.

Abstract

BACKGROUND Based on the 2018 update of the Surviving Sepsis Campaign, the Committee for Quality Improvement of the NHSs of England recommended the instigation of the elements of the 'Sepsis-6 bundle' within 1 hour to adult patients screened positive for sepsis. This bundle includes a bolus infusion of 30 mL/kg crystalloids in the ED. Besides the UK, both in the USA and Australia, compliance with similar 1-hour targets became an important quality indicator. However, the supporting evidence may neither be contemporaneous nor necessarily valid for emergency medicine settings. METHOD A systematic review was designed and registered at PROSPERO to assess available emergency medicine/prehospital evidence published between 2012 and 2020, investigating the clinical benefits associated with a bolus infusion of a minimum 30 mL/kg crystalloids within 1 hour to adult patients screened positive for sepsis. Due to the small number of papers that addressed this volume of fluids in 1 hour, we expanded the search to include studies looking at 1-6 hours. RESULTS Seven full-text articles were identified, which investigated various aspects of the fluid resuscitation in adult sepsis. However, none answered completely to the original research question aimed to determine either the effect of time-to-crystalloids or the optimal fluid volume of resuscitation. Our findings demonstrated that in the USA/UK/Australia/Canada, adult ED septic patients receive 23-43 mL/kg of crystalloids during the first 6 hours of resuscitation without significant differences either in mortality or in adverse effects. CONCLUSION This systematic review did not find high-quality evidence supporting the administration of 30 mL/kg crystalloid bolus to adult septic patients within 1 hour of presentation in the ED. Future research must investigate both the benefits and the potential harms of the recommended intervention.

Abstract

BACKGROUND Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. METHODS This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. RESULTS We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. CONCLUSION Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.

Abstract

BACKGROUND After being used for more than a decade the use of hydroxyethyl starch (HES) 130/0.38-0.45 in clinical practice was discouraged because of serious adverse events including bleeding, acute kidney injury and death. But could these adverse effects have been discovered sooner? By comparing the summary effect estimates of the adverse effects of HES 130/0.38-0.45 in different study designs we aimed to disclose any signal of this. METHODS We systematically searched MEDLINE, EMBASE and Cochrane Library and hand-searched the reference lists of relevant studies to identify studies for inclusion. Eligible trials were randomised clinical trials (RCTs) and observational studies in patients with sepsis and randomised trials in animals with induced sepsis comparing HES 130/0.38-0.45 to any type of crystalloid. Relevant outcomes were all-cause mortality at longest follow-up, renal replacement therapy (RRT), acute kidney injury (AKI) and bleeding. We extracted data, conducted conventional meta-analyses and assessed risk of bias and the quality of evidence. RESULTS We included 8 RCTs including 3,273 patients, 1 observational study including 379 patients and 5 randomised animal trials including 94 test animals. There was no suggestion of interaction in subgroup analyses comparing the different study designs for any outcomes (all-cause mortality at longest follow-up P=0.33; RRT P=0.70; AKI P=0.63; bleeding P=0.20). CONCLUSIONS We observed no interaction between the summary effect estimates of RCTs, observational studies in patients and randomised animal trials for any of the outcomes. Accordingly, we found no evidence indicating that the adverse effects of HES 130/0.38-0.45 could have been discovered sooner.

Abstract

BACKGROUND The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups. CONCLUSIONS Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock.

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.