Infection is often difficult to recognize in critically ill patients because of the marked coexisting inflammatory process. Lack of early recognition prevents timely resuscitation and effective antimicrobial therapy, resulting in increased morbidity and mortality. Measurement of a biomarker, such as C-reactive protein (CRP) concentration, in addition to history and physical signs, could facilitate diagnosis. Although frequently measured in clinical practice, few studies have reported on the pathophysiological role of this biomarker and its predictive value in critically ill patients. In this review, we discuss the pathophysiological role of CRP and its potential interpretation in the inflammatory processes observed in critically ill patients.

Therapeutic hypothermia (TH between 32 and 34 °C) was recommended until recently in unconscious successfully resuscitated cardiac arrest (CA) patients, especially after initial shockable rhythm. A randomized controlled trial published in 2013 observed similar outcome between a 36 °C-targeted temperature management (TTM) and a 33 °C-TTM. The main aim of our study was to assess the impact of this publication on physicians regarding their TTM practical changes. A declarative survey was performed using the webmail database of the French Intensive Care Society including 3229 physicians (from May 2014 to January 2015). Five hundred and eighteen respondents from 264 ICUs in 11 countries fulfilled the survey (16 %). A specific attention was generally paid by 94 % of respondents to TTM (hyperthermia avoidance, normothermia, or TH implementation) in CA patients, whereas 6 % did not. TH between 32 and 34 °C was declared as generally maintained during 12–24 h by 78 % of respondents or during 24–48 h by 19 %. Since the TTM trial publication, 56 % of respondents declared no modification of their TTM practice, whereas 37 % declared a practical target temperature change. The new temperature targets were 35–36 °C for 23 % of respondents, and 36 °C for 14 %. The duration of overall TTM (including TH and/or normothermia) was declared as applied between 12 and 24 h in 40 %, and between 24 and 48 h in 36 %. In univariate analysis, the physicians’ TTM modification seemed related to hospital category (university versus non-university hospitals, P = 0.045), to TTM-specific attention paid in CA patients (P = 0.008), to TH durations (<12 versus 24–48 h, P = 0.01), and to new targets temperature (32–34 versus 35–36 °C, P < 0.0001). The TTM trial publication has induced a modification of current practices in one-third of respondents, whereas the 32–34 °C target temperature remained unchanged for 56 %. Educational actions are needed to promote knowledge translations of trial results into clinical practice. New international guidelines may contribute to this effort.

Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood–brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.

Background: Acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) is associated with high mortality. Several studies have reported that the microcirculation responds adequately to hypoxia in COVID-19 patients by increasing oxygen availability, in contrast to the inadequate response observed in patients with bacterial sepsis. Red blood cells (RBCs), the key cells for oxygen transport, and notably their rheology, are altered during bacterial sepsis, but few data are available in patients with COVID-19.Methods: In this prospective, non-interventional study, shape was assessed on admission (or inclusion for the volunteers) using Pearson’s second coefficient of dissymmetry (PCD) on the histogram obtained with a flow cytometer technique. A null value represents a perfect spherical shape. RBC deformability was determined using ektacytometry by the elongation index in relation to the shear stress (0.3 to 50 Pa) applied to the RBC membrane. A higher elongation index indicates greater RBC deformability. Results were compared across groups. Scanning electronic microscopy was performed on RBCs from COVID-19 patients. RBC shape and deformability were also assessed on days 3 and 7 in COVID-19 patients.Results: Forty-nine ICU patients were included (30 with COVID-19 ARDS and 19 with bacterial sepsis). ARDS was more severe in patients with COVID-19 than in those with sepsis (PaO₂/FiO₂ 99 [73–154] vs. 270 [239–295] mmHg p < 0.001) and mechanical ventilation was more frequently required (87 vs. 21%; p < 0.001). Mortality was significantly higher in COVID-19 patients (15/30 [50%] vs. 4/19 [21%], p = 0.046). RBCs were significantly more spherical in septic patients (PCD −0.40 [−0.56; −0.18]) than in healthy volunteers (PCD −0.54 [−0.66; −0.49]) but not than in COVID-19 patients (−0.48 [−0.55; −0.43]). In COVID-19 non-survivors (n = 11), sphericity was more marked on day 7 (PCD −0.40 [−0.47; −0.28]) than on day 1 (PCD vs. −0.49 [−0.59; −0.44]); p = 0.045. At ICU admission, RBC deformability was altered for all shear stress values studied in septic patients compared to COVID-19 patients and healthy volunteers (maximum elongation index for septic patients: 0.600 [0.594–0.630] vs. 0.646 [0.637–0.653] for COVID-19 patients and 0.640 [0.635–0.650] for healthy volunteers; both p < 0.001). In the 18 COVID-19 patients studied for 7 days, RBC deformability did not change over time and was not related to outcome. At day 1, RBCs from COVID-19 patients showed a normal structure on scanning electronic microscopy.Conclusion: In contrast to the significantly altered shape and decreased deformability in patients with bacterial sepsis, RBCs from severely hypoxemic COVID-19 patients had normal deformability on admission, and this pattern did not change over the first week despite a more spherical shape in non-survivors. As RBCs are the key cell for oxygen transport, this maintenance of normal deformability may contribute to the adequate microcirculatory response to severe hypoxia of the microcirculation that has been observed in these patients.

Erythrocytes have been long considered as dead cells with transport of oxygen (O2) as their only function. However, the ability of red blood cells (RBCs) to modulate the microcirculation is now recognized as an important additional function. This capacity is regulated by a key element in the rheologic process: the RBC membrane. This membrane is a complex unit with multiple interactions between the extracellular and intracellular compartments: blood stream, endothelium, and other blood cells on the one hand, and the intracytoplasmic compartment with possible rapid adaptation of erythrocyte metabolism on the other. In this paper, we review the alterations in the erythrocyte membrane observed in critically ill patients and the influence of these alterations on the microcirculatory abnormalities observed in such patients. An understanding of the mechanisms of RBC rheologic alterations in sepsis and their effects on blood flow and on oxygen transport may be important to help reduce morbidity and mortality from severe sepsis.