IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial.
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ABSTRACT:
SUBMITTER: Domizi R
PROVIDER: S-EPMC6890901 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial.
Domizi Roberta R Adrario Erica E Damiani Elisa E Scorcella Claudia C Carsetti Andrea A Giaccaglia Paolo P Casarotta Erika E Gabbanelli Vincenzo V Pantanetti Simona S Lamura Elena E Ciucani Silvia S Donati Abele A
Annals of intensive care 20191203 1
<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]
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Project description:BACKGROUND:Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite treatment being in line with current guidelines, mortality remains high in those with septic shock. Intravenous immunoglobulins represent a promising therapy to modulate both the pro- and anti-inflammatory processes and can contribute to the elimination of pathogens. In this context, there is evidence of the benefits of immunoglobulin M (IgM)- and immunoglobulin A (IgA)-enriched immunoglobulin therapy for sepsis. This manuscript aims to summarize current relevant data to provide expert opinions on best practice for the use of an IgM- and IgA-enriched immunoglobulin (Pentaglobin) in adult patients with sepsis. MAIN TEXT:Sepsis patients with hyperinflammation and patients with immunosuppression may benefit most from treatment with IgM- and IgA-enriched immunoglobulin (Pentaglobin). Patients with hyperinflammation present with phenotypes that manifest throughout the body, whilst the clinical characteristics of immunosuppression are less clear. Potential biomarkers for hyperinflammation include elevated procalcitonin, interleukin-6, endotoxin activity and C-reactive protein, although thresholds for these are not well-defined. Convenient biomarkers for identifying patients in a stage of immune-paralysis are still matter of debate, though human leukocyte antigen-antigen D related expression on monocytes, lymphocyte count and viral reactivation have been proposed. The timing of treatment is potentially more critical for treatment efficacy in patients with hyperinflammation compared with patients who are in an immunosuppressed stage. Due to the lack of evidence, definitive dosage recommendations for either population cannot be made, though we suggest that patients with hyperinflammation should receive an initial bolus at a rate of up to 0.6 mL (30 mg)/kg/h for 6 h followed by a continuous maintenance rate of 0.2 mL (10 mg)/kg/hour for???72 h (total dose???0.9 g/kg). For immunosuppressed patients, dosage is more conservative (0.2 mL [10 mg]/kg/h) for???72 h, without an initial bolus (total dose???0.72 g/kg). CONCLUSIONS:Two distinct populations that may benefit most from Pentaglobin therapy are described in this review. However, further clinical evidence is required to strengthen support for the recommendations given here regarding timing, duration and dosage of treatment.
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Project description:RationaleThe feasibility and clinical outcomes of conservative fluid management after sepsis resuscitation remain unknown.ObjectivesTo evaluate the effect of a conservative fluid management protocol on fluid balance and intensive care unit (ICU)-free days among patients with sepsis.MethodsIn a single-center phase II/III randomized trial, we enrolled adults with suspected infection, ≥2 systemic inflammatory response syndrome criteria, and either shock (mean arterial pressure <60 mm Hg or vasopressors) or respiratory insufficiency (mechanical ventilation or oxygen saturation <97% and fraction of inspired oxygen ≥0.3). Patients were randomized 1:1 to usual care or a conservative fluid management protocol. The protocol restricted intravenous fluid administration during shock to treatment of oliguria or increasing vasopressor requirement. In the absence of shock, loop diuretic infusion targeted equal fluid input and output each study day. The primary outcomes were mean daily fluid balance (phase II) and ICU-free days (phase III).ResultsAt the completion of phase II (n = 30), the difference in mean daily fluid balance between groups (-398 mL) was less than the prespecified threshold (-500 mL) and the trial was stopped. Patients in the conservative fluid management (n = 15) and usual care (n = 15) groups experienced similar cumulative fluid input (8450 mL vs 7049 mL; P = .90) of which only 14% was intravenous crystalloid or colloid. Loop diuretic infusion occurred more frequently in the conservative fluid management group (40% vs 0%; P = .02), and cumulative fluid output was 10 645 mL in the conservative fluid management group compared to 6286 mL in the usual care group (P = .39). Hemodynamic, respiratory, and renal function did not differ between the groups.ConclusionsIn this phase II trial, a conservative fluid management protocol did not decrease mean daily fluid balance by more than 500 mL among patients with sepsis.RegistrationClinicaltrials.gov; NCT02159079.
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Project description:Sepsis patients suffer from severe metabolic and immunologic dysfunction that may be amplified by standard nutritional approaches relying primarily on carbohydrates. We here hypothesize that a ketogenic diet improves sepsis treatment. We conducted a monocentric open-labeled randomized controlled trial enrolling 40 adult sepsis patients. Patients were randomly assigned to either ketogenic diet (KD) or standard high-carbohydrate nutrition for 14 days and followed up until day 30. The primary outcome measure was β-hydroxybutyrate (BHB) serum concentration on day 14. We assessed feasibility and safety of KD, as well as diet-associated clinical and immunological changes. The respective nutrition protocols were successfully applied, dropouts did not occur. Regression analysis revealed a greater increase in BHB concentrations from baseline to day 14 in KD patients compared to controls. Metabolic side effects were not observed under ketogenic diet. Ventilation-free, vasopressor-free, dialysis-free and ICU-free days significantly increased in patients under ketogenic diet. Transcriptome profiling of both CD4+ and CD8+ T cells at day 14 revealed substantial differential regulation of gene expression in the KD vs. the control group indicating a reduced T-cell activation and a shift towards a more regulated immunity.
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Project description: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, I2 = 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.
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