Efficacy of IVIG therapy for patients with sepsis: a systematic review and meta-analysis
Journal of translational medicine. 2023;21(1):765
BACKGROUND Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality. It requires urgent interventions in order to improve outcomes. Intravenous immunoglobulins (IVIG) are considered as potential therapy in sepsis patients. Results of trials on IVIG as adjunctive therapy for sepsis have been conflicting due to the variability in population characteristics, country geography and drug dosage form in different studies. METHODS A systematic article search was performed for eligible studies published up to January, 31, 2023, through the PubMed, Embase, Cochrane Library and Chinese National Knowledge Infrastructure database. The included articles were screened by using rigorous inclusion and exclusion criteria. Subgroup analyses were conducted according to different IVIG types, ages and economic regions. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. RESULTS In total, 31 randomized controlled trials were included with a sample size of 6,276 participants. IVIG could reduce the mortality (RR 0.86, 95% CI: 0.77-0.95, p = 0.005), the hospital stay (MD - 4.46, 95% CI: - 6.35 to - 2.57, p = 0.00001), and the APACHE II scores (MD - 1.65, 95% CI: - 2.89 to - 0.63, p = 0.001). Additionally, the results showed that IgM-enriched IVIG was effective in treating sepsis (RR 0.55, 95% CI: 0.40 - 0.76; p = 0.0003), while standard IVIG failed to be effective (RR 0.91, 95% CI: 0.81-1.02, p = 0.10). And the effect of IVIG in reducing neonatal mortality was inconclusive (RR 0.93, 95% CI: 0.81-1.05, p = 0.24), but it played a large role in reducing sepsis mortality in adults (RR 0.70, 95% CI: 0.57-0.86, p = 0.0006). Besides, from the subgroup of different economic regions, it indicated that IVIG was effective for sepsis in high-income (RR 0.89, 95% CI: 0.79-0.99, p = 0.03) and middle-income countries (RR 0.49, 95% CI: 0.28-0.84, p = 0.01), while no benefit was demonstrated in low-income countries (RR 0.56, 95% CI: 0.27-1.14, p = 0.11). CONCLUSIONS There is sufficient evidence to support that IVIG reduces sepsis mortality. IgM-enriched IVIG is effective in both adult and neonatal sepsis, while standard IVIG is only effective in adult sepsis. IVIG for sepsis has shown efficacy in high- and middle-income countries, but is still debatable in low-income countries. More RCTs are needed in the future to confirm the true clinical potential of IVIG for sepsis in low-income countries.
Different Concentrations of Albumin Versus Crystalloid in Patients with Sepsis and Septic Shock: A Meta-Analysis of Randomized Clinical Trials
Journal of intensive care medicine. 2023;:8850666231170778
OBJECTIVE The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis. MATERIALS AND METHODS PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals. RESULTS Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; P = .11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; P = .04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; P = .03), which was better than 4% to 5% albumin and crystalloid. CONCLUSIONS Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation.
Interventions for reducing late-onset sepsis in neonates: an umbrella review
Journal of perinatal medicine. 2022
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.
Effects of Albumin Supplements on In-Hospital Mortality in Patients with Sepsis or Septic Shock: A Systemic Review and Meta-Analysis
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:2384730
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.
Resuscitation Fluids in Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials
Shock (Augusta, Ga.). 2019
The aim of this study was to assess the efficacy and safety of various resuscitation fluids in septic shock by adopting a network meta-analysis (NMA). Randomized controlled trials (RCTs) comparing resuscitation fluids in septic shock were carried out by retrieving electronic databases. NMAs of 28-day mortality, 90-day mortality, incidence of acute kidney injury (AKI), and the need for renal replacement therapy (RRT) were conducted using the STATA 15.0 software. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the optimal resuscitation fluid. Inconsistencies were evaluated by node-splitting analysis and a loop-specific approach. Furthermore, publication bias was analyzed by funnel plots. A total of 13 RCTs were enrolled in the analysis. The NMA results revealed that no significant differences were detected in the outcomes of 28-day mortality and 90-day mortality among various resuscitation fluids. The SUCRAs (the first indicates the best) of 28-day mortality showed that the hypertonic sodium chloride/hydroxyethyl starch 40 solution ranked the highest (93.8%), followed by the balanced solution (BS) (69.6%), and albumin (61.9%). On the other hand, the SUCRAs of 90-day mortality revealed that gelatin (GEL) ranked the highest (75.1%), followed by BS (55.1%), and NS (52.4%). The NMA results of AKI demonstrated that high-molecular-weight hydroxyethyl starch (H-HES) was associated with increased risk of AKI in comparison with GEL, BS, and L-HES. The SUCRAs of AKI showed that GEL ranked the highest (74.4%), followed by NS (64.9%), and BS (58.3%). In addition, the NMA results of RRT revealed that H-HES was associated with an increased need for RRT in comparison with BS and NS, and L-HES was associated with increased need of RRT in comparison with BS. The SUCRAs of RRT revealed that NS ranked the highest (91.6%), followed by BS (74.4%) and L-HES (36.1%). No significant inconsistencies were shown by the node-splitting analysis and no publication bias was demonstrated in the funnel plots. In conclusion, BS was determined as the preferred resuscitation fluid for septic shock. Moreover, the use of GEL requires further evaluation. H-HES was associated with a significant risk of AKI and RRT, whereas L-HES with an increased need for RRT compared with BS. Thus, both resuscitation fluids should be avoided for septic shock.
Evaluation of the Effect of Intravenous Immunoglobulin Dosing on Mortality in Patients with Sepsis: A Network Meta-analysis
Clinical therapeutics. 2019
PURPOSE Intravenous immunoglobulin (IVIG) has been proposed as an adjunctive therapy for sepsis. Related systematic reviews and meta-analyses of IVIG in sepsis indicate that IVIG can reduce the mortality of sepsis in adults. However, the effective dose of IVIG has not been clearly determined to date. We aimed to conduct an updated meta-analysis and use a network meta-analysis to elucidate the efficacy of IVIG dosing regimens in sepsis treatment. METHODS We searched PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE for articles published on or before February 14, 2019. We performed a direct meta-analysis to update a previous meta-analysis of the effects of IVIG therapy on mortality in adult patients with septic shock and a network meta-analysis to evaluate the efficacy of IVIG dosing regimens in sepsis treatment. FINDINGS Compared with the control treatment, the IVIG treatment reduced the all-cause mortality of patients with sepsis (odds ratio = 0.61; 95% CI, 0.41-0.92; P = 0.018), but significant heterogeneity was found across the studies (I(2) = 45.0%; P = 0.04). Regarding the IVIG dosage regimens, the highest total dose range (1.5-2 g/kg) was the optimal dose of administration (surface under the cumulative ranking curve = 84.7%). IMPLICATIONS On the basis of the available data, IVIG treatment is likely to reduce the all-cause mortality of patients with sepsis, and the highest total dose range (1.5-2 g/kg) is likely the optimal dose of administration.
Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis
Sao Paulo medical journal = Revista paulista de medicina. 2018;136((5):):421-432.
BACKGROUND This study aimed to compare the effects on mortality of albumin and crystalloid, used for fluid resuscitation among adult patients with septic shock, through conducting a meta-analysis and trial sequential analysis (TSA). DESIGN AND SETTING Meta-analysis and TSA conducted at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. METHODS Data were collected from several major databases including MEDLINE, EMBASE, Clinical Trials.gov and Cochrane Central Register of Controlled Trials. Studies that compared the effects of albumin therapy versus crystalloid therapy on mortality among adult septic shock patients were eligible for inclusion in the analyses. The study name, year of publication, country of the trial, albumin concentration, type of crystalloid and all reported mortalities at different follow-up endpoints were extracted. RESULTS Compared with crystalloid, albumin did not decrease all-cause mortality at the final follow-up. However, in TSA, the required information size was not achieved in all groups, which means that the effect size was not definitive and further RCTs are needed to confirm or deny these findings. CONCLUSIONS Compared with crystalloid solutions, albumin was unable to decrease all-cause mortality. However, TSA indicated that these results could be false-negative. Additional randomized controlled trials are needed to clarify this discrepancy.
Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness
Minerva Anestesiologica. 2016;82((5)):559-72.
INTRODUCTION Sepsis is characterized by a complex immune response. In this study we aimed to provide a review of the mechanisms of action of immunoglobulin (Ig) related to sepsis and an updated meta-analysis of the clinical effectiveness of the Ig use in septic patients. EVIDENCE ACQUISITION We performed two separate searches of Medline and other databases with the keywords Ig, sepsis, septic shock, septicemia, septicemia with no language restrictions in order to review the mechanisms of action of Igs in sepsis and to update the previous meta-analysis on the effects of the Ig therapy on the mortality of adult patients with septic shock. EVIDENCE SYNTHESIS Pathogens and toxin clearance, anti-inflammatory effects and anti-apoptotic effects on immune cells seems to be the main mechanisms of action of Ig therapy in sepsis. The meta-analysis of 18 RCTs indicated that the use of intravenous Ig reduces the mortality risk of septic patients (odds ratio=0.50 [95% CI 0.34-0.71], I2=44.68%). Low study quality, heterogeneous dosing regimens and type of Ig preparations, and different control interventions (placebo or albumin) may have influenced our results. CONCLUSIONS Our study showed that the use of intravenous Ig therapy in adult septic patients may have a rationale and seems to be associated with a reduced mortality. Anyway, the treatment effect generally tended to be smaller or less consistent if considering only those studies that were deemed adequate on each indicator. So, the available evidence is not clearly sufficient to support the widespread use of Ig in the treatment of sepsis.
Meta-analysis of mortality in adults, newborns and older children with bacterial infections and sepsis when treated by Igm-enriched intravenous immunoglobulins and standard schemes
Value in Health. 2015;18((7)):A578.
The efficacy of activated protein C for the treatment of sepsis: incorporating observational evidence with a Bayesian approach
BMJ Open. 2015;5((1):):e006524.
OBJECTIVE The present study aimed to combine observational evidence with randomised controlled trials (RCTs) by using the Bayesian approach. DATA SOURCES Electronic databases, including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EMBASE and EBSCO were searched from inception to January 2014. STUDY ELIGIBILITY RCTs and observational studies (OS) investigating the effectiveness of activated protein C (aPC) on mortality reduction were included for analysis. PARTICIPANTS Patients with sepsis. INTERVENTION aPC. SYNTHESIS METHODS Observational evidence was incorporated into the analysis by using power transformed priors in a Bayesian. Trial sequential analysis was performed to examine changes over time and whether further studies need to be conducted. MAIN RESULTS a total of 7 RCTs and 12 OS were included for the analysis. There was moderate heterogeneity among included RCTs (I(2)=48.6%, p=0.07). The pooled OR for mortality from RCTs was 1.00 (95% CI 0.84 to 1.19). In OS, there was potential publication bias as indicated by the funnel plot and the pooled OR for mortality with the use of aPC was 0.67 (95% CI 0.62 to 0.72). The pooled effect sizes of RCTs were changed by using different power transform priors derived from observational evidence. When observational evidence was used at its 'face value', the treatment effect of aPC was statistically significant in reducing mortality. CONCLUSIONS while RCT evidence showed no beneficial effect of aPC on sepsis, observational evidence showed a significant treatment effect of aPC. By using power transform priors in Bayesian model, we explicitly demonstrated how RCT evidence could be changed by observational evidence. TRIAL REGISTRATION NUMBER The protocol for the current study was registered in PROSPERO (registration number: CRD42014009562).Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.