PurposeThe CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP).MethodsIn this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L).ResultsOverall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58–78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline.ConclusionsNo significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation.Trial registration: NCT01420744.Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5143-7) contains supplementary material, which is available to authorized users.

No abstract

Background A profound inflammation-mediated lung injury with long-term acute respiratory distress and high mortality is one of the major complications of critical COVID-19. Immunoglobulin M (IgM)-enriched immunoglobulins seem especially capable of mitigating the inflicted inflammatory harm. However, the efficacy of intravenous IgM-enriched preparations in critically ill patients with COVID-19 is largely unclear. Methods In this retrospective multicentric cohort study, 316 patients with laboratory-confirmed critical COVID-19 were treated in ten German and Austrian ICUs between May 2020 and April 2021. The primary outcome was 30-day mortality. Analysis was performed by Cox regression models. Covariate adjustment was performed by propensity score weighting using machine learning-based SuperLearner to overcome the selection bias due to missing randomization. In addition, a subgroup analysis focusing on different treatment regimens and patient characteristics was performed. Results Of the 316 ICU patients, 146 received IgM-enriched immunoglobulins and 170 cases did not, which served as controls. There was no survival difference between the two groups in terms of mortality at 30 days in the overall cohort (HRadj: 0.83; 95% CI: 0.55 to 1.25; p = 0.374). An improved 30-day survival in patients without mechanical ventilation at the time of the immunoglobulin treatment did not reach statistical significance (HRadj: 0.23; 95% CI: 0.05 to 1.08; p = 0.063). Also, no statistically significant difference was observed in the subgroup when a daily dose of ≥ 15 g and a duration of ≥ 3 days of IgM-enriched immunoglobulins were applied (HRadj: 0.65; 95% CI: 0.41 to 1.03; p = 0.068). Conclusions Although we cannot prove a statistically reliable effect of intravenous IgM-enriched immunoglobulins, the confidence intervals may suggest a clinically relevant effect in certain subgroups. Here, an early administration (i.e. in critically ill but not yet mechanically ventilated COVID-19 patients) and a dose of ≥ 15 g for at least 3 days may confer beneficial effects without concerning safety issues. However, these findings need to be validated in upcoming randomized clinical trials. Trial registrationDRKS00025794, German Clinical Trials Register, https://www.drks.de. Registered 6 July 2021.

No abstract

Background. We use an intubating laryngeal mask (ILM) in preference to an endotracheal tube (ETT) as the ventilatory device during percutaneous dilatational tracheostomy (PDT) to overcome potential problems such as difficult ventilation, accidental extubation, damage of the ETT or of the bronchoscope, and need for additional assistant to secure the airway. We report our experience with this method.Methods. In this prospective observational study, PDT was performed using the ILM in 86 patients. The insertion of the ILM, the quality of ventilation, and the view of the tracheal puncture site were rated as: 'very good', 'good', 'difficult', and 'not possible with ILM'.Results. The bronchoscope was not damaged during any case, and all PDTs were performed by two physicians, without the need for an additional assistant. PDTs with ILM were successful in 95% of the patients (n¼82). The ratings were 'very good' or 'good' in 80% of cases with regards to ventilation, in 90% for identification of relevant structures and tracheal puncture site, and in 85% for the view inside the trachea during PDT. Tracheal re-intubation was required for inadequate ventilation with ILM in four patients.Conclusions. The advantages of this procedure were lack of damage to the bronchoscope, the need for two instead of three persons to perform the PDT, and the excellent view inside the trachea. We recommend the ILM as a standard device for ventilation during bronchoscope-guided PDT.