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.
Highlights
The administration of endovenous immunoglobulins in patients with septic shock could be beneficial and preparations enriched with IgA and IgM seem to be more effective than those containing only IgG
By the Sepsis Campaign (SSC), the intravenous IgM- and IgA-enriched immunoglobulins (ivIgGAM) are widely used but a new preparation containing almost double concentrations of IgM (⁓23%) and IgA (⁓21%) has been developed whose use has been associated with an improved survival in patients with community-acquired pneumonia enrolled in a recent randomized clinical trials (RCT) (CIGMA) [12]; noteworthy, this effect was more marked in patients with baseline elevated levels of C-reactive protein, low levels of IgM or a combination of these abnormalities, possibly indicating a subset of patients who could take the maximal advantage from this approach
The other variables significantly related to a higher risk of dying in intensive care unit (ICU) were higher SAPS Simplified Acute Physiology Score (II), sequential organ failure assessment (SOFA) D1 and Lung Injury Score (LIS) and cultures positive for MDR bacteria or fungi
Summary
The 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. Despite a better knowledge of their mechanisms of action and some meta-analyses demonstrating that (a) the administration of polyclonal intravenous Ig (ivIg) was associated with an improved outcome in septic patients; and (b) this effect was more marked when the preparation used in the trial contained increased amount of IgA and IgM (12% each one) (ivIgGAM) [7,8,9,10], the previous as well as the current guidelines of the Surviving Sepsis Campaign (SSC) recommend against their use; this statement is based on either the lack of randomized clinical trials (RCT) satisfying the evidence-based medicine (EBM) standards and to the different composition of the ivIg used [11]. The beneficial effect of IgM could be ascribed to its pentameric structure, including the neutralization of exo- and endotoxins, the enhancement of opsonization and phagocytosis and the increased bacterial lysis obtained via the activation of the alternative pathway of the complement system [12,13,14,15,16,17,18,19,20,21]; besides these anti-infective actions, IgM molecules have some immunomodulatory effects such as the scavenging of excessive complement factors and the blunting of the production of some sepsis mediators [22]
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