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IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial

BACKGROUND: Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis. METHODS: Single-centre, randomized, double-blind, plac...

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Autores principales: Domizi, Roberta, Adrario, Erica, Damiani, Elisa, Scorcella, Claudia, Carsetti, Andrea, Giaccaglia, Paolo, Casarotta, Erika, Gabbanelli, Vincenzo, Pantanetti, Simona, Lamura, Elena, Ciucani, Silvia, Donati, Abele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890901/
https://www.ncbi.nlm.nih.gov/pubmed/31797105
http://dx.doi.org/10.1186/s13613-019-0609-5
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author Domizi, Roberta
Adrario, Erica
Damiani, Elisa
Scorcella, Claudia
Carsetti, Andrea
Giaccaglia, Paolo
Casarotta, Erika
Gabbanelli, Vincenzo
Pantanetti, Simona
Lamura, Elena
Ciucani, Silvia
Donati, Abele
author_facet Domizi, Roberta
Adrario, Erica
Damiani, Elisa
Scorcella, Claudia
Carsetti, Andrea
Giaccaglia, Paolo
Casarotta, Erika
Gabbanelli, Vincenzo
Pantanetti, Simona
Lamura, Elena
Ciucani, Silvia
Donati, Abele
author_sort Domizi, Roberta
collection PubMed
description BACKGROUND: Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis. METHODS: Single-centre, randomized, double-blind, placebo-controlled phase II trial including adult patients with a diagnosis of sepsis or septic shock for less than 24 h. Patients received an intravenous infusion of 250 mg/kg (5 mL/kg) per day of IgM-enriched immunoglobulins (Pentaglobin, n = 10) for 72 h or placebo (NaCl 0.9%, n = 9). At baseline and after 24 and 72 h of infusion, the sublingual microcirculation was assessed with Incident Dark Field videomicroscopy. Thenar near-infrared spectroscopy (NIRS) was applied with a vascular occlusion test to assess tissue oxygenation and microvascular reactivity. Levels of interleukin (IL) 1-beta, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were measured in the serum. RESULTS: The perfused vessel density (PVD) for small vessels (diameter < 20 micron) increased in the Pentaglobin group (from 21.7 ± 4.7 to 25.5 ± 5.1 mm/mm(2)) and decreased in the placebo group (from 25 ± 5.8 to 20.7 ± 4.1 mm/mm(2), p for interaction < 0.001, two-way analysis of variance). The absolute between-group difference at 72 h was 4.77 (standard error 2.34), p = 0.140. The microvascular flow index for small vessels increased at 24 h in the Pentaglobin group (from 2.68 [2.38–2.78] to 2.93 [2.82–3], p < 0.01) and decreased at 72 h in the placebo group (from 2.83 [2.60–2.97] to 2.67 [2.48–2.73], p < 0.05). Changes in general parameters, cytokines and NIRS-derived parameters were similar between the two groups, except for IL-6 and IL-10 that significantly decreased at 72 h only in the Pentaglobin group. CONCLUSIONS: A 72-h infusion of IgM-enriched immunoglobulins (Pentaglobin) in patients with sepsis or septic shock may be associated with an increase in sublingual microvascular perfusion. Further studies are needed to confirm our findings. Trial registration NCT02655133, www.ClinicalTrials.gov, date of registration 7th January 2016, https://www.clinicaltrials.gov/ct2/show/NCT02655133.
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spelling pubmed-68909012019-12-17 IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial Domizi, Roberta Adrario, Erica Damiani, Elisa Scorcella, Claudia Carsetti, Andrea Giaccaglia, Paolo Casarotta, Erika Gabbanelli, Vincenzo Pantanetti, Simona Lamura, Elena Ciucani, Silvia Donati, Abele Ann Intensive Care Research BACKGROUND: Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis. METHODS: Single-centre, randomized, double-blind, placebo-controlled phase II trial including adult patients with a diagnosis of sepsis or septic shock for less than 24 h. Patients received an intravenous infusion of 250 mg/kg (5 mL/kg) per day of IgM-enriched immunoglobulins (Pentaglobin, n = 10) for 72 h or placebo (NaCl 0.9%, n = 9). At baseline and after 24 and 72 h of infusion, the sublingual microcirculation was assessed with Incident Dark Field videomicroscopy. Thenar near-infrared spectroscopy (NIRS) was applied with a vascular occlusion test to assess tissue oxygenation and microvascular reactivity. Levels of interleukin (IL) 1-beta, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were measured in the serum. RESULTS: The perfused vessel density (PVD) for small vessels (diameter < 20 micron) increased in the Pentaglobin group (from 21.7 ± 4.7 to 25.5 ± 5.1 mm/mm(2)) and decreased in the placebo group (from 25 ± 5.8 to 20.7 ± 4.1 mm/mm(2), p for interaction < 0.001, two-way analysis of variance). The absolute between-group difference at 72 h was 4.77 (standard error 2.34), p = 0.140. The microvascular flow index for small vessels increased at 24 h in the Pentaglobin group (from 2.68 [2.38–2.78] to 2.93 [2.82–3], p < 0.01) and decreased at 72 h in the placebo group (from 2.83 [2.60–2.97] to 2.67 [2.48–2.73], p < 0.05). Changes in general parameters, cytokines and NIRS-derived parameters were similar between the two groups, except for IL-6 and IL-10 that significantly decreased at 72 h only in the Pentaglobin group. CONCLUSIONS: A 72-h infusion of IgM-enriched immunoglobulins (Pentaglobin) in patients with sepsis or septic shock may be associated with an increase in sublingual microvascular perfusion. Further studies are needed to confirm our findings. Trial registration NCT02655133, www.ClinicalTrials.gov, date of registration 7th January 2016, https://www.clinicaltrials.gov/ct2/show/NCT02655133. Springer International Publishing 2019-12-03 /pmc/articles/PMC6890901/ /pubmed/31797105 http://dx.doi.org/10.1186/s13613-019-0609-5 Text en © The Author(s) 2019 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.
spellingShingle Research
Domizi, Roberta
Adrario, Erica
Damiani, Elisa
Scorcella, Claudia
Carsetti, Andrea
Giaccaglia, Paolo
Casarotta, Erika
Gabbanelli, Vincenzo
Pantanetti, Simona
Lamura, Elena
Ciucani, Silvia
Donati, Abele
IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
title IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
title_full IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
title_fullStr IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
title_full_unstemmed IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
title_short IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
title_sort igm-enriched immunoglobulins (pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890901/
https://www.ncbi.nlm.nih.gov/pubmed/31797105
http://dx.doi.org/10.1186/s13613-019-0609-5
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