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Abstract Background Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP. Methods We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality. Results Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97). Conclusion In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes. Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476 .

Abstract Background Recent alerts have highlighted an increase in group A streptococcal (GAS) infections since 2022 in Europe and the United States. Streptococcus pyogenes can cause limited skin or mucosal disease, but can also present as severe invasive disease necessitating critical care. We performed a multicenter retrospective study of patients with GAS infections recently admitted to Belgian intensive care units (ICUs) since January 2022. We describe patient characteristics and investigate the molecular epidemiology of the S. pyogenes strains involved. Results Between January 2022 and May 2023, a total of 86 cases (56 adults, 30 children) with GAS disease were admitted to critical care in the university hospitals of Leuven, Antwerp and Liège. We noted a strikingly high incidence of severe community-acquired pneumonia (sCAP) (45% of adults, 77% of children) complicated with empyema in 45% and 83% of adult and pediatric cases, respectively. Two-thirds of patients with S. pyogenes pneumonia had viral co-infection, with influenza (13 adults, 5 children) predominating. Other disease presentations included necrotizing fasciitis (23% of adults), other severe skin/soft tissue infections (16% of adults, 13% of children) and ear/nose/throat infections (13% of adults, 13% of children). Cardiogenic shock was frequent (36% of adults, 20% of children). Fifty-six patients (65%) had toxic shock syndrome. Organ support requirements were high and included invasive mechanical ventilation (77% of adults, 50% of children), renal replacement therapy (29% of adults, 3% of children) and extracorporeal membrane oxygenation (20% of adults, 7% of children). Mortality was 21% in adults and 3% in children. Genomic analysis of S. pyogenes strains from 55 out of 86 patients showed a predominance of emm1 strains (73%), with a replacement of the M1global lineage by the toxigenic M1UK lineage (83% of emm1 strains were M1UK). Conclusions The recent rise of severe GAS infections (2022–23) is associated with introduction of the M1UK lineage in Belgium, but other factors may be at play—including intense circulation of respiratory viruses and potentially an immune debt after the COVID pandemic. Importantly, critical care physicians should include S. pyogenes as causative pathogen in the differential diagnosis of sCAP.

Abstract The use of citrate, through reversible binding of calcium, has become the preferred choice for anticoagulation in continuous renal replacement therapy in the critically ill patient. Though generally considered as very efficacious in acute kidney injury, this type of anticoagulation can cause acid–base disorders as well as citrate accumulation and overload, phenomena which have been well described. The purpose of this narrative review is to provide an overview of some other, non-anticoagulation effects of citrate chelation during its use as anticoagulant. We highlight the effects seen on the calcium balance and hormonal status, phosphate and magnesium balance, as well as oxidative stress resulting from these unapparent effects. As most of these data on these non-anticoagulation effects have been obtained in small observational studies, new and larger studies documenting both short- and long-term effects should be undertaken. Subsequent future guidelines for citrate-based continuous renal replacement therapy should take not only the metabolic but also these unapparent effects into account.

Abstract Purpose Iatrogenic fluid overload is a potential side effect of intravenous fluid therapy in the hospital. Little attention has been paid to sodium administration as a separate cause of harm. With this narrative review, we aim to substantiate the hypothesis that a considerable amount of fluid-induced harm is caused not only by fluid volume, but also by the sodium that is administered to hospitalized patients. Methods We show how a regular dietary sodium intake is easily surpassed by the substantial amounts of sodium that are administered during typical hospital stays. The most significant sodium burdens are caused by isotonic maintenance fluid therapy and by fluid creep, defined as the large volume unintentionally administered to patients in the form of dissolved medication. In a section on physiology, we elaborate on the limited renal handling of an acute sodium load. We demonstrate how the subsequent retention of water is an energy-demanding, catabolic process and how free water is needed to excrete large burdens of sodium. We quantify the effect size of sodium-induced fluid retention and discuss its potential clinical impact. Finally, we propose preventive measures, discuss the benefits and risks of low-sodium maintenance fluid therapy, and explore options for reducing the amount of sodium caused by fluid creep. Conclusion The sodium burdens caused by isotonic maintenance fluids and fluid creep are responsible for an additional and avoidable derailment of fluid balance, with presumed clinical consequences. Moreover, the handling of sodium overload is characterized by increased catabolism. Easy and effective measures for reducing sodium load and fluid retention include choosing a hypotonic rather than isotonic maintenance fluid strategy (or avoiding these fluids when enough free water is provided through other sources) and dissolving as many medications as possible in glucose 5%.

Abstract Background Antibiotics are frequently used in intensive care units (ICUs), and their use is associated with the emergence of bacterial resistance to antibiotics. The aim of this study was to investigate the association between the emergence of Pseudomonas aeruginosa resistance and the duration of antibiotic exposure or mode of administration in an ICU unit. Methods A 4-year cohort study of intensive care unit was performed in patients with P. aeruginosa isolates from clinical specimens, initially susceptible to the investigated antibiotics (piperacillin/tazobactam, ceftazidime, ciprofloxacin, meropenem and amikacin). Odds ratios (ORs) with 95% confidence interval (95% CI) of emergence of resistance were calculated using logistic regression analysis for various exposure periods to antibiotics (1–3, 4–7, 8–15 and >15 days) relative to no exposure with adjustment for age, sex, Simplified Acute Physiology Score 3 (SAPS 3) and length of stay. ORs on the emergence of P. aeruginosa resistance were also calculated for the various modes of administration. Results Included were 187 patients [mean age 61 years, 69% male, mean SAPS 3 score (SD): 59 (12.3)]. None of the antibiotics investigated showed the emergence of resistance within 1–3 days. Significant meropenem resistance emerged within 8–15 days [OR 79.1 (14.9–421.0)] after antibiotic exposure unlike other antibiotics (>15 days). No difference was observed between intermittent and extended administration of meropenem and between beta-lactam mono- or combined therapy. Conclusions Use of meropenem was associated with the emergence of resistance as soon as 8 days after exposure to the antibiotic.