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.