Introduction: Effective resuscitation with human albumin solutions is achieved with less fluid than with crystalloid solutions. However, the role of albumin in today’s critical care unit is also linked to its multiple pharmacological effects. Areas covered: The potential clinical benefits of albumin in select populations of critically ill patients like sepsis seem related to immunomodulatory and anti-inflammatory effects, antibiotic transportation and endothelial stabilization. Albumin transports many drugs used in critically ill patients. Such binding to albumin is frequently lessened in critically ill patients with hypoalbuminemia. These changes could result in sub-optimal treatment. Albumin has immunomodulatory capacity by binding several bacterial products. Albumin also influences vascular integrity, contributing to the maintenance of the normal capillary permeability. Moreover, the albumin molecule encompasses several antioxidant properties, thereby significantly reducing re-oxygenation injury, which is especially important in sepsis. In fact, most studies of albumin administration are a combination of a degree of resuscitation with a degree of maintenance or supplementation of albumin. Expert commentary: The potential clinical benefits of the use of albumin in selected critically ill patients such as sepsis seem related to its immunomodulatory and anti-inflammatory effects, antioxidant properties, antibiotic transportation and endothelial stabilization. Additional studies are warranted to further elucidate the underlying physiologic and molecular rationale.

Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation.Methods: Bead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming.Results: Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance.Conclusion: We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.

Vitamin C is an antioxidant with anti-inflammatory and immune-supportive properties. Its levels are decreased in patients with sepsis-related acute respiratory distress syndrome (ARDS). Moreover, a significant number of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease developed ARDS [1]. Therefore, we hypothesized that ARDS coronavirus disease 2019 (COVID-19) patients may present vitamin C deficiency. Plasma vitamin C levels in a population of adult ICU patients COVID-19 who met ARDS criteria according to the Berlin definition [2] were prospectively measured. The study was approved by the local Clinical Research Ethics Committee (PR (AG)270/ 2020). Main characteristics of the population included are presented in Table 1. None of the patients included presented shock or sepsis on admission. Equally, no bacterial co-infection during their ICU course was documented. All patients survived. Vitamin C was determined by high-performance liquid chromatography with photodiode detector (detection limit 1.5 mg/L). Vitamin C reference values in general

Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, which is time-dependent and associated with unacceptably high mortality. Thus, when treating suspicious or confirmed cases of sepsis, clinicians must initiate broad-spectrum antimicrobials within the first hour of diagnosis. Optimizing antibiotic use is essential to ensure successful outcomes and to reduce adverse antibiotic effects, as well as preventing drug resistance. All likely pathogens involved should be considered to provide an appropriate antibiotic coverage. Clinicians must investigate on the previous risk of multidrug-resistant (MDR) pathogens, and the principle of individualized dosing should replace the principle of standard dosing. The loading dose is an initial higher dose of an antibiotic for all patients, yet an individualized treatment approach for further doses should be implemented according to pharmacokinetics (PK)/pharmacodynamics (PD) and the presence of renal/liver dysfunction. Extended or continuous infusion of beta-lactams and therapeutic drug monitoring (TDM) can help to achieve therapeutic levels of antimicrobials. Reevaluation of duration and appropriateness of treatment at regular intervals are also necessary. De-escalation and shortened courses of antimicrobials must be considered for most patients, except in some justified circumstances. Leadership, teamwork, antimicrobial stewardship (AS) frameworks, guideline’s recommendations on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches will help us to improve patients’ quality of care.