Introduction: Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT). Methods: This is a retrospective, case–control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment. Results: Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65). Conclusions: In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.

"Balanced" solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis. Recently, the term "balanced" solution has been also employed to indicate intravenous fluids with low chloride content, being the concentration of this electrolyte the most altered and supra-physiologic in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental effect on renal function associated with hyperchloremia. Despite efforts for its identification, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available. After the accumulation of pre-clinical and clinical physiologic data, in the last three years, several clinical trials, mostly observational and retrospective, have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival. Nonetheless, the first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solution on renal function in critically-ill patients (SPLIT trial, the 0.9% Saline vs Plasma-Lyte 148 for Intensive Cate Unit Fluid Therapy), just recently published, showed identical equipoise between the two treatments. In the present review, we offer a comprehensive and updated summary on this issue, firstly, by providing a full physiological background of balanced solutions, secondly, by summarizing their potential pathophysiologic effects, and lastly, by presenting the clinical evidence available to support, at the moment, their use.

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028–1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572–18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.

Although the loop-diuretic furosemide is widely employed in critically ill patients with known long-term effects on plasma electrolytes, accurate data describing its acute effects on renal electrolyte handling and the generation of plasma electrolyte alterations are lacking. We hypothesized that the long-term effects of furosemide on plasma electrolytes and acid–base depend on its immediate effects on electrolyte excretion rate and patient clinical baseline characteristics. By monitoring urinary electrolytes quasi-continuously, we aimed to verify this hypothesis in a cohort of surgical ICU patients with normal renal function. We retrospectively enrolled 39 consecutive patients admitted to a postoperative ICU after major surgery, and receiving single low-dose intravenous administration of furosemide. Urinary output, pH, sodium [Na+], potassium [K+], chloride [Cl−] and ammonium [NH4 +] concentrations were measured every 10 min for three to 8 h. Urinary anion gap (AG), electrolyte excretion rate, fractional excretion (Fe) and time constant of urinary [Na+] variation (τNa+) were calculated. Ten minutes after furosemide administration (12 ± 5 mg), urinary [Na+] and [Cl−], and their excretion rates, increased to similar levels (P < 0.001). After the first hour, urinary [Cl−] decreased less rapidly than [Na+], leading to a reduction in urinary AG and pH and an increment in urinary [NH4 +] (P < 0.001). Median urinary [Cl−] over the first 3-h period was higher than baseline urinary and plasmatic [Cl−] (P < 0.001). During the first 2 h, difference between FeCl− and FeNa+ increased (P < 0.05). Baseline higher values of central venous pressure and FeNa+ were associated with greater increases in FeNa+ after furosemide (P = 0.03 and P = 0.007), whereas higher values of mean arterial and central venous pressures were associated with a longer τNa+ (P < 0.05). In patients receiving multiple administrations (n = 11), arterial pH, base excess and strong ion difference increased, due to a decrease in plasmatic [Cl−]. Low-dose furosemide administration immediately modifies urinary electrolyte excretion rates, likely in relation to the ongoing proximal tubular activity, unveiled by its inhibitory action on Henle’s loop. Such effects, when cumulative, found the bases for the long-term alterations observed. Real-time urinary electrolyte monitoring may help in tailoring patient diuretic and hemodynamic therapies.