The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis

BACKGROUND: Sepsis is characterized by a complex immune response. This meta-analysis evaluated the clinical effectiveness of intravenous IgM-enriched immunoglobulin (IVIgGM) in patients with sepsis and septic shock. METHODS: Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 to update the 2013 edition of the Cochrane review by two investigators, who independently selected studies, extracted relevant data, and evaluated study quality. Data were subjected to a meta-analysis and trial sequential analysis (TSA) for the primary and secondary outcomes. Level of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. RESULTS: Nineteen studies comprising 1530 patients were included in this meta-analysis. Pooled analyses showed that the use of IVIgGM reduced the mortality risk of septic patients (relative risk 0.60; 95% confidence interval [CI] 0.52–0.69, I(2) = 0%). TSA showed that IVIgGM had a significant effect on mortality. Additionally, the meta-analysis suggested that use of IVIgGM shortened length of mechanical ventilation (mean difference − 3.16 days; 95% CI − 5.71 to − 0.61 days) and did not shorten length of stay in the intensive care unit (mean difference − 0.38 days; 95% CI − 3.55 to 2.80 days). The GRADE scale showed that the certainty of the body of evidence was low for both benefits and IVIgGM. CONCLUSION: Administration of IVIgGM to adult septic patients may be associated with reduced mortality. Treatment effects tended to be smaller or less consistent when including only those studies deemed adequate for each indicator. The available evidence is not clearly sufficient to support the widespread use of IVIgGM in the treatment of sepsis. Trial registration PROSPERO registration number: CRD42018084120. Registered on 11 February 2018. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-019-0501-3) contains supplementary material, which is available to authorized users.