Effects of the timing of administration of IgM- and IgA-enriched intravenous polyclonal immunoglobulins on the outcome of septic shock patients

Abstract

BackgroundThe administration of endovenous immunoglobulins in patients with septic shock could be beneficial and preparations enriched with IgA and IgM (ivIgGAM) seem to be more effective than those containing only IgG. In a previous study Berlot et al. demonstrated that early administration of ivIgGAM was associated with lower mortality rate. We studied a larger population of similar patients aiming either to confirm or not this finding considering also the subgroup of patients with septic shock by multidrug-resistant (MDR) pathogens.MethodsAdult patients with septic shock in intensive care unit (ICU) treated with ivIgGAM from August 1999 to December 2016 were retrospectively examined. Collected data included the demographic characteristics of the patients, the diagnosis at admission, SOFA, SAPS II and Murray Lung Injury Score (LIS), characteristics of the primary infection, the adequacy of antimicrobial therapy, the delay of administration of ivIgGAM from the ICU admission and the outcome at the ICU discharge. Parametric and nonparametric tests and logistic regression were used for statistic analysis.ResultsDuring the study period 107 (30%) of the 355 patients died in ICU. Survivors received the ivIgGAM earlier than nonsurvivors (median delay 12 vs 14 h), had significantly lower SAPS II, SOFA and LIS at admission and a lower rate of MDR- and fungal-related septic shock. The appropriateness of the administration of antibiotics was similar in survivors and nonsurvivors (84 vs 79%, respectively, p: n.s). The delay in the administration of ivIgGAM from the admission was associated with in-ICU mortality (odds ratio per 1-h increase = 1.0055, 95% CI 1.003–1.009, p < 0.001), independently of SAPS II, LIS, cultures positive for MDR pathogens or fungi and onset of septic shock. Only 46 patients (14%) had septic shock due to MDR pathogens; 21 of them (46%) died in ICU. Survivors had significantly lower SAPS II, SOFA at admission and delay in administration of ivIgGAM than nonsurvivors (median delay 18 vs 66 h). Even in this subgroup the delay in the administration of ivIgGAM from the admission was associated with an increased risk of in-ICU mortality (odds ratio 1.007, 95% CI 1.0006–1.014, p = 0.048), independently of SAPS II.ConclusionsEarlier administration of ivIgGAM was associated with decreased risk of in-ICU mortality both in patients with septic shock caused by any pathogens and in patients with MDR-related septic shock.Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0466-7) contains supplementary material, which is available to authorized users.

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

“…Other studies have been carried out with specific monoclonal antibodies (e.g., monoclonal antibody against endotoxin in children with meningococcal septic shock), but there are no definitive data to support general benefit of polyclonal immunoglobulin in neonates or children with septic shock at this time. Data from adult patients with septic shock also do not support a routine benefit of IVIG [492], although administration of immunoglobulin M-and immunoglobulin A-enriched polyclonal IVIG has shown possible efficacy [493] (Supplemental Table 35, Supplemental Digital Content 1, http://links .lww.com/PCC/B139).…”

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

“…Among ICU patients with septic shock caused by any pathogens [including those that are multidrug-resistant (MDR)], those who received IgM- or IgA-enriched immunoglobulins earlier (median delay 12 h versus 14 h) were more likely to survive than those who received them later [ 71 , 72 ]. This suggests that the timing of treatment may play a critical role in treatment efficacy and patients with hyperinflammation should be treated with IgM- and IgA-enriched immunoglobulins as soon as possible.…”

How Clinical Flow Cytometry Rebooted Sepsis Immunology

“…Thus flow cytometry may be useful clinical tool for the management of sepsis emergency medicine. In addition, it reopens the door for potential use of various immunomodulatory agents that have been initially found ineffective due to lack of stratification whereas they retrospectively demonstrated significant protective effect in the most inflammatory patients .…”