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

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          Abstract

          Background

          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. 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.

          Methods

          Adult 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.

          Results

          During 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.

          Conclusions

          Earlier 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 material

          The online version of this article (10.1186/s13613-018-0466-7) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome.

          To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research.
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            The changing immune system in sepsis

            Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity.
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              Delays From First Medical Contact to Antibiotic Administration for Sepsis.

              To evaluate the association between total medical contact, prehospital, and emergency department delays in antibiotic administration and in-hospital mortality among patient encounters with community-acquired sepsis.

                Author and article information

                Contributors
                +39 040-3994540 , berlot@inwind.it
                claudiovassallo@alice.it
                busettonicola@gmail.com
                marganyabar@yahoo.it
                crystyan266@gmail.com
                baroniosilvia92@gmail.com
                giadagg48@gmail.com
                mattia.bixio@gmail.com
                gbarbati@units.it
                robdattola@gmail.com
                irenelongo.lng@gmail.com
                nino.guiza@gmail.com
                alicescamperle@libero.it
                arvag@hotmail.it
                ariella.tomasini9@gmail.com
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                10 December 2018
                10 December 2018
                2018
                : 8
                : 122
                Affiliations
                [1 ]ISNI 0000 0001 1941 4308, GRID grid.5133.4, Department of Anesthesia, Resuscitation and Pain Therapy, Cattinara Hospital, , University of Trieste, ; Strada di Fiume 447, 34149 Trieste, Italy
                [2 ]ISNI 0000 0004 1756 7871, GRID grid.410345.7, Department of Anesthesia and Intensive Care, , San Martino Hospital, ; Largo Rosanna Benzi 10, 16132 Genoa, Italy
                [3 ]ISNI 0000 0001 1941 4308, GRID grid.5133.4, Biostatistics Unit, Department of Medicine, Surgery and Health Sciences, Cattinara Hospital, , University of Trieste, ; Strada di Fiume 447, 34149 Trieste, Italy
                Article
                466
                10.1186/s13613-018-0466-7
                6288102
                30535962
                8aed3f0e-4050-4051-b3fc-f41b90aa85f6
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 17 August 2018
                : 30 November 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Emergency medicine & Trauma
                severe sepsis,septic shock,immunoglobulins,igm,multiple drug resistance,intensive care unit

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