Intravenous immunoglobulin in the management of neonatal sepsis: A randomised controlled trial
Tropical doctor. 2023;:494755221138689
Sepsis is a leading cause of neonatal mortality and morbidity in low and middle-income countries. We designed a double-blinded randomised controlled trial in a neonatal intensive care unit (NICU) of a tertiary care teaching hospital to determine the role of intravenous immunoglobulin (IVIG) in decreasing hospital stay. Eighty neonates with clinical features of sepsis were enrolled in the study and placebo groups to receive 500 mg/kg of IVIG for three consecutive days or a placebo. The primary outcome measure was duration of hospital stay in days. The babies in both groups were comparable in terms of birth weight, gestation and sex distribution. There was no significant difference in duration of hospital stay (days) in the study and placebo groups. We found that treatment with IVIG did not shorten the duration of hospital stay in our setting.
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.
A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]
Journal of hepatology. 2022
BACKGROUND AND AIM The choice of resuscitation fluid in cirrhosis patients with sepsis-induced hypotension (SIH) is unclear. 5% albumin has been superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties with plasmalyte in reversing SIH. METHODS Critically-ill cirrhosis(CIC) patients underwent open-label randomization to receive either 20% albumin [0.5-1.0gm/kg over 3 hours; n=50] or plasmalyte (30ml/kg over 3 hours, n=50). The primary end-point of the study was the attainment of mean arterial pressure (MAP) above 65 mmHg at three hours. RESULTS Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate(mmol/L) [6.16±3.18 vs. 6.38±4.77; p=0.78), MAP (mmHg) [51.4±6.52 vs. 49.9±4.45; p=0.17] and SOFA score [10.8±2.96 vs. 11.1±4.2; p=0.68] respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat (ITT) analysis, albumin was superior to plasmalyte in achieving the primary end-point (62% vs. 22%; p<0.001). A rapid decline in arterial lactate (P=0.03), a lesser proportion of dialysis [48% vs. 62%; p=0.16], and a higher time to initiation of dialysis (in hours) [68.13±47.79 vs. 99.7± 63.4; p=0.06] was seen with albumin. However, the 28-day mortality was not different (58% vs. 62%, p=0.57). Patients in the albumin group required discontinuation of therapy in 11 (22%) patients due to adverse effects compared to none in plasmalyte group. CONCLUSION In patients with cirrhosis and SIH, 20% albumin transiently improves the hemodynamics with early lactate clearance than plasmalyte but needs monitoring as it is more often attended with pulmonary complications. Both fluids provide comparable 28 days survival. NCT02721238 LAY SUMMARY The current randomized controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores hemodynamics but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in deaths at 28-days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.
Pentaglobin (immunoglobulin M-enriched immunoglobulin) as adjuvant therapy for premature and very low-birth-weight neonates with sepsis
Indian journal of pharmacology. 2021;53(5):364-370
OBJECTIVES The purpose of this research was to determine the effectiveness of Pentaglobin® as adjuvant therapy in the treatment of sepsis in preterm newborns. MATERIALS AND METHODS It was a prospective, observational, randomized study for 272 premature neonates and very low birth weight (VLBW) that were diagnosed with sepsis carried at neonatal intensive care units. The patients randomized into control group who received standard sepsis antibiotic treatments, and an intervention group who received Pentaglobin® 5 ml/kg daily for 3 consecutive days as an adjunct therapy to a standard sepsis antibiotic treatment. RESULTS Multiple organisms that isolated from culture specimens were Gram-negative bacteria, Gram-positive, and candida (56.25%, 42.28%, and 1.47%, respectively). The disease duration was distinctively longer in patients who were treated by the standard antibiotic protocol (mean ± standard deviation [SD]: 30.76 ± 3.97, odds ratio [OR]: 30.76, 95% confidence interval [CI]: 30.051, 31.473) comparing to the patients who received Pentaglobin adjuvant therapy (mean ± SD: 26.48 ± 5.55, OR: 26.48, 95% CI: 25.489, 27.477) (P < 0.000). Patients treated by standard antibiotic protocol were associated to a substantially increased risk of death (11.76%, hazard ratio 4.400, 95% CI: 1.432, 13.529, P = 0.009). CONCLUSION Neonatal sepsis is more common in premature and VLBW newborns, and Pentaglobin® management of newborn nosocomial sepsis might be used in addition to other therapies.
Albumin replacement therapy in immunocompromised patients with sepsis - Secondary analysis of the ALBIOS trial
Journal of critical care. 2021;63:83-91
BACKGROUND The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear. METHODS We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay. RESULTS Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69-1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709-1.352) as compared to crystalloid. CONCLUSION Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis.
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.
Lactated Ringer's Versus 4% Albumin on Lactated Ringer's in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial
Critical care medicine. 2019
OBJECTIVE To investigate the effects of the administration of 4% albumin on lactated Ringer's, when compared with lactated Ringer's alone, in the early phase of sepsis in cancer patients. DESIGN Single-center, randomized, double-blind, controlled-parallel trial. SETTING A tertiary care university cancer hospital. PATIENTS Cancer patients with severe sepsis or septic shock. INTERVENTIONS Between October 2014 and December 2016, patients were randomly assigned to receive either bolus of albumin in a lactated Ringer's solution or lactated Ringer's solution alone during the first 6 hours of fluid resuscitation after intensive care medicine (ICU) admission. Primary outcome was defined as death from any cause at 7 days. Secondary outcomes were defined as death from any cause within 28 days, change in Sequence Organ Failure Assessment scores from baseline to day 7, days alive and free of mechanical ventilation, days alive and free of vasopressor, renal replacement therapy during ICU stay, and length of ICU and hospital stay. MEASUREMENTS AND MAIN RESULTS A total of 360 patients were enrolled in the trial. At 7 days, 46 of 180 patients (26%) died in the albumin group and 40 of 180 (22%) died in the lactated Ringer's group (p = 0.5). At 28 days, 96 of 180 patients (53%) died in the albumin group and 83 of 180 (46%) died in the lactated Ringer's group (p = 0.2). No significant differences in secondary outcomes were observed. CONCLUSIONS Adding albumin to early standard resuscitation with lactated Ringer's in cancer patients with sepsis did not improve 7-day survival.