De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock.

BACKGROUND: De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. OBJECTIVES: To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. METHODS: Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. RESULTS: A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005). CONCLUSIONS: In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS: We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.

The effect of high-flow oxygen via tracheostomy on respiratory pattern and diaphragmatic function in patients with prolonged mechanical ventilation: A randomized, physiological, crossover study.

Background: Compared to conventional oxygen devices, high-flow oxygen treatment (HFOT) through the nasal cannulae has demonstrated clinical benefits. Limited data exist on whether such effects are also present in HFOT through tracheostomy. Hence, we aimed to examine the short-term effects of HFOT through tracheostomy on diaphragmatic function and respiratory parameters in tracheostomized patients on prolonged mechanical ventilation. Methods: A randomized, crossover, physiological study was conducted in our ICU between December 2020 and April 2021, in patients with tracheostomy and prolonged mechanical ventilation. The patients underwent a 30-min spontaneous breathing trial (SBT) and received oxygen either via T-piece or by HFOT through tracheostomy, followed by a washout period of 15-min breathing through the T-piece and receipt of 30-min oxygen with the other modality in a randomized crossover manner. At the start and end of each session, blood gasses, breathing frequency (f), and tidal volume (VT) via a Wright's spirometer were measured, along with diaphragm ultrasonography including diaphragm excursion and diaphragmatic thickening fraction, which expressed the inspiratory muscle effort. Results: Eleven patients were enrolled in whom 19 sessions were uneventfully completed; eight patients were studied twice on two different days with alternate sessions; and three patients were studied once. Patients were randomly assigned to start the SBT with a T-piece (n=10 sessions) or with HFOT (n=9 sessions). With HFOT, VT and minute ventilation (VE) significantly increased during SBT (from [465±119] mL to [549±134] mL, P <0.001 and from [12.4±4.3] L/min to [13.1±4.2] L/min, P <0.05, respectively), but they did not change significantly during SBT with T-piece (from [495±132] mL to [461±123] mL and from [12.8±4.4] mL to [12.0±4.4] mL, respectively); f/VT decreased during HFOT (from [64±31] breaths/(min∙L) to [49±24] breaths/(min∙L), P <0.001), but it did not change significantly during SBT with T-piece (from [59±28] breaths/(min∙L) to [64±33] breaths/(min∙L)); partial pressure of arterial oxygen increased during HFOT (from [99±39] mmHg to [132±48] mmHg, P <0.001), but it decreased during SBT with T-piece (from [124±50] mmHg to [83±22] mmHg, P <0.01). In addition, with HFOT, diaphragmatic excursion increased (from [12.9±3.3] mm to [15.7±4.4] mm, P <0.001), but it did not change significantly during SBT with T-piece (from [13.4±3.3] mm to [13.6±3.3] mm). The diaphragmatic thickening fraction did not change during SBT either with T-piece or with HFOT. Conclusion: In patients with prolonged mechanical ventilation, HFOT through tracheostomy compared with T-piece improves ventilation, pattern of breathing, and oxygenation without increasing the inspiratory muscle effort. Trial Registration: Clinicaltrials.gov ldentifer: NCT04758910.

EARLY TRAJECTORY OF VENOUS EXCESS ULTRASOUND SCORE IS ASSOCIATED WITH CLINICAL OUTCOMES OF GENERAL ICU PATIENTS.

ABSTRACT: Background: Systemic venous congestion, assessed by the venous excess ultrasound (VExUS) score, has been associated with adverse effects, including acute kidney injury (AKI), in patients with cardiac disease. In general intensive care unit (ICU) patients, the association between VExUS score and outcomes is understudied. We aimed to investigate the association between the trajectory of VExUS score within the first 3 days of ICU admission and the composite clinical outcome of major adverse kidney events within 30 days (MAKE30). Methods: In this prospective observational study, including patients consecutively admitted to the ICU, VExUS score was calculated within 24 h after ICU admission (day 1) and at 48 to 72 h (day 3). D-VExUS was calculated as the difference between the VExUS score on day 3 minus that on day 1. Development of AKI within 7 days and all-cause mortality within 30 days were recorded. Results: A total of 89 patients (62% men; median age, 62 years; median Acute Physiology and Chronic Health Evaluation II score, 24) were included. Sixty (67%) patients developed AKI within 7 days, and 17 (19%) patients died within 30 days after ICU admission. D-VExUS was associated with MAKE30, even after adjustment for confounders (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P = 0.01). VExUS scores on days 1 or 3 were not associated with MAKE30. Also, VExUS scores on day 1 or on day 3 and D-VExUS were not associated with development of AKI or mortality. Conclusions: In a general ICU cohort, early trajectory of VExUS score, but not individual VExUS scores at different time points, was associated with the patient-centered MAKE30 outcome. Dynamic changes rather than snapshot measurements may unmask the adverse effects of systemic venous congestion on important clinical outcomes.

The Diagnostic Accuracy of Procalcitonin and Its Combination with Other Biomarkers for Candidemia in Critically Ill Patients.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.

Temporal trends in laboratory parameters in survivors and non­survivors of critical COVID­19 illness and the effect of dexamethasone treatment.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P<0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment.

The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis. OBJECTIVE: To determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis. SOURCES OF DATA: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciFinder, and Clinicaltrials.gov. SELECTION CRITERIA: Randomized controlled parallel group trials comparing selenium supplementation in doses greater than daily requirement to placebo on the outcome of mortality in patients with sepsis syndrome. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome was mortality; secondary outcomes were ICU length of stay, nosocomial pneumonia, and adverse events. Trial authors were contacted for additional or clarifying information. RESULTS: Nine trials enrolling a total of 792 patients were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, -0.51, 4.56; p = 0.12; I = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I = 56%). Significant heterogeneity among trials in adverse event reporting precluded pooling of results. CONCLUSIONS: In patients with sepsis, selenium supplementation at doses higher than daily requirement may reduce mortality. We observed no impact of selenium on ICU length of stay or risk of nosocomial pneumonia.

Novel biomarkers of acute kidney injury in the general adult ICU: a review.

Acute kidney injury is one of the most frequent problems occurring in the critically ill patients of the intensive care units and it is well established that it increases both morbidity and mortality in these patients. Moreover, despite technological and pharmaceutical advances during the last decades, the incidence as well as the mortality associated with acute kidney injury in these patients remains unchanged. Creatinine, the most common renal dysfunction biomarker in use, has many disadvantages, such as time delay in its increase and the influence by other factors on its serum concentration, such as age, gender, muscle mass, etc. Hence, the need for better renal biomarkers in order to timely intervene for acute kidney injury prevention is imperative. The lack of an early biomarker is an obstacle for the development of new acute kidney injury prevention strategies. With the incidence of acute kidney injury reaching epidemic dimensions, the need for novel markers is urgent. During the last years, the research for finding such biomarkers has been intense. The purpose of the present article is to review the studies which have tested the predictive ability of those markers (in urine and/or plasma) for early detection of acute kidney injury in the mixed adult intensive care unit population and underline the potential limitations encountered in the various studies.

Temporal evolution of laboratory characteristics in patients critically ill with COVID­19 admitted to the intensive care unit (Review).

In the context of coronavirus disease 2019 (COVID-19), laboratory medicine has played a crucial role in both diagnosis and severity assessment. Although the importance of baseline laboratory findings has been extensively reported, data regarding their evolution over the clinical course are limited. The aim of the present narrative review was to provide the dynamic changes of the routine laboratory variables reported in patients with severe COVID-19 over the course of their critical illness. A search was made of the literature for articles providing data on the time-course of routine laboratory tests in patients with severe COVID-19 during their stay in the intensive care unit (ICU). White blood cell, neutrophil and lymphocyte counts, neutrophil to lymphocyte ratio, platelet counts, as well as D-dimer, fibrinogen, C-reactive protein, lactate dehydrogenase and serum albumin levels were selected as disease characteristics and routine laboratory parameters. A total of 25 research articles reporting dynamic trends in the aforementioned laboratory parameters over the clinical course of severe COVID-19 were identified. During the follow-up period provided by each study, the majority of the laboratory values remained persistently abnormal in both survivors and non-survivors. Furthermore, in the majority of studies, the temporal trends of laboratory values distinctly differentiated patients between survivors and non-survivors. In conclusion, there are distinct temporal trends in selected routine laboratory parameters between survivors and non-survivors with severe COVID-19 admitted to the ICU, indicating their importance in the prognosis of clinical outcome.

Combination of renal biomarkers predicts acute kidney injury in critically ill adults.

OBJECTIVE: Most studies so far have focused on the performance of individual biomarkers to detect early acute kidney injury (AKI) in the adult intensive care unit (ICU) patients; however, they have not determined the predictive ability of their combinations. The aim of this study was to compare the predictive abilities of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urine neutrophil gelatinase-associated lipocalin (uNGAL), plasma cystatin C (pCysC), serum creatinine (sCr), and their combinations in detecting AKI in an adult general ICU population. METHODS: A total of 100 consecutive ICU patients were included in the analysis. AKI was defined according to RIFLE criteria. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: AKI occurred in 36% of patients 7 days post-admission. All three novel biomarkers as well as sCr had moderate predictive abilities for AKI occurrence. The most efficient combinations (pNGAL + sCr and pNGAL + uNGAL + sCr) were selected to participate in the subsequent analyses. Both combinations, when added to a reference clinical model, increased its AUC significantly (0.858, p = 0.04). Their NRI (0.78, p = 0.0002) was equal to that of pNGAL, but higher than that of the other three biomarkers, whereas their IDI was higher than that of any individual biomarker (0.23, p = 0.0001). Both combinations had better specificities, positive likelihood ratios, and positive predictive values than those of any individual biomarker. CONCLUSION: The biomarker combinations had better predictive characteristics compared with those of each biomarker alone.

Combined administration of membrane-permeable and impermeable iron-chelating drugs attenuates ischemia/reperfusion-induced hepatic injury.

BACKGROUND: The underlying pathophysiological mechanisms of hepatic ischemia-reperfusion (I/R) injury have not been completely elucidated. However, it is well known that oxidative stress, caused by a burst of reactive oxygen species (ROS) production during the reperfusion phase, plays a crucial role. A growing body of evidence indicates that the intracellular availability of free iron represents a requirement for ROS-induced adverse effects, as iron catalyzes the generation of highly reactive free radicals. The aim of this study was to examine whether a combination of iron chelators with varying lipophilicity could offer enhanced protection against I/R by diminishing the conversion of weak oxidants, like H2O2, to extremely reactive ones such as hydroxyl radicals (HO.). METHODS: HepG2 cells (hepatocellular carcinoma cell line) were exposed to oxidative stress conditions after pre-treatment with the iron chelators desferrioxamine (DFO) and deferiprone (DFP) alone or in combination. Labile iron pool was estimated using the calcein-acetoxymethyl ester (calcein-AM) method and DNA damage with the comet assay. We subsequently used a rabbit model (male New Zealand white rabbits) of hepatic I/R-induced injury to investigate, by measuring biochemical (ALT, ALT, ALP, γGT) and histological parameters, whether this may be true for in vivo conditions. RESULTS: The combination of a membrane-permeable iron chelator (DFP) with a strong membrane-impermeable one (DFO) raises the level of protection in both hepatic cell lines exposed to oxidative stress conditions and hepatic I/R rabbit model. CONCLUSIONS: Our results show that combinations of iron chelators with selected lipophilicity and iron-binding properties may represent a valuable strategy to protect against tissue damage during reperfusion after a period of ischemia.

Renal Resistive Index on Intensive Care Unit Admission Correlates With Tissue Hypoperfusion Indices and Predicts Clinical Outcome.

BACKGROUND: Renal resistive index (RRI) has been used to evaluate renal blood flow. Our aim was to investigate the relation between RRI and global tissue hypoperfusion indices and their association with clinical outcome, in intensive care unit (ICU) patients. METHODS: RRI was measured within 24 h of ICU admission. Gas exchange and routine hemodynamic variables at the time of RRI assessment were recorded. An elevated RRI was defined as >0.7. The ratio of central venous-to-arterial carbon dioxide partial pressure difference by arterial-to-central venous oxygen content difference (P(cv-a)CO2/C(a-cv)O2) and lactate were used as global tissue hypoperfusion indices. RESULTS: A total of 126 patients were included [median age 61 (IQR 28) years, 74% males]. P(cv-a)CO2/C(a-cv)O2 ratio and arterial lactate were significantly higher in patients with RRI >0.7 compared with those with RRI ≤0.7 [2.88 (3.39) vs. 0.62 (0.57) mmol/L and 2.4 (2.2) vs. 1.2 (0.6)] respectively, both P < 0.001)]. RRI was significantly correlated with P(cv-a)CO2/C(a-cv)O2 ratio and arterial lactate for the whole patient population (rho = 0.64, both P < 0.0001) and for the subset of patients with shock (rho = 0.47, P = 0.001; and r = 0.64, P < 0.0001 respectively). Logistic regression models showed a significant association between RRI and P(cv-a)CO2/C(a-cv)O2 ratio with clinical outcome. The combination of RRI with P(cv-a)CO2)/(C(a-cv)O2 ratio and lactate better predicted mortality than RRI alone [AUC 84.8% (95% CI 5.1% -94.4%)] vs. [AUC 74.9% (95% CI 61%-88.8%)] respectively, P < 0.001. CONCLUSIONS: Renal blood flow assessed by RRI, on ICU admission, correlates with global tissue hypoperfusion indices. In addition, RRI in combination with tissue perfusion estimation better predicts clinical outcome than RRI alone.

Epidemiology of Candidemia and Fluconazole Resistance in an ICU before and during the COVID-19 Pandemic Era.

The objectives of this study were to investigate the incidence of candidemia, as well as the factors associated with Candida species distribution and fluconazole resistance, among patients admitted to the intensive care unit (ICU) during the COVID-19 pandemic, as compared to two pre-pandemic periods. All patients admitted to the ICU due to COVID-19 from March 2020 to October 2021, as well as during two pre-pandemic periods (2005-2008 and 2012-2015), who developed candidemia, were included. During the COVID-19 study period, the incidence of candidemia was 10.2%, significantly higher compared with 3.2% and 4.2% in the two pre-pandemic periods, respectively. The proportion of non-albicans Candida species increased (from 60.6% to 62.3% and 75.8%, respectively), with a predominance of C. parapsilosis. A marked increase in fluconazole resistance (from 31% to 37.7% and 48.4%, respectively) was also observed. Regarding the total patient population with candidemia (n = 205), fluconazole resistance was independently associated with ICU length of stay (LOS) before candidemia (OR 1.03; CI: 1.01-1.06, p = 0.003), whereas the presence of shock at candidemia onset was associated with C. albicans (OR 6.89; CI: 2.2-25, p = 0.001), and with fluconazole-susceptible species (OR 0.23; CI: 0.07-0.64, p = 0.006). In conclusion, substantial increases in the incidence of candidemia, in non-albicansCandida species, and in fluconazole resistance were found in patients admitted to the ICU due to COVID-19, compared to pre-pandemic periods. At candidemia onset, prolonged ICU LOS was associated with fluconazole-resistant and the presence of shock with fluconazole-susceptible species.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

Background: The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. Methods: In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. Results: We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] µg/L, respectively, (p = 0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Conclusion: Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.

Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality.

BACKGROUND: Although older adults are at high risk for severe coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission, age is often used as a selection criterion in case of ICU beds scarcity. We sought to compare the proportion, clinical features and mortality between patients ≥70 years old and younger ICU patients with COVID-19. METHODS: All patients, consecutively admitted to our COVID ICU, where age was not used as an admission criterion, from March 2020 through April 2021, were included. Demographics, clinical and laboratory characteristics were recorded. Illness severity and Charlson comorbidity Index (CCI) were calculated. Patients≥70 years old were compared to youngers. RESULTS: Of 458 patients (68 [59-76] years, 70% males), 206 (45%) were ≥70 years old. Compared to younger, older patients had higher illness severity scores (APACHE II 18 [14-23] versus 12 [9-16], P<0.001, SOFA 8 [6-10] versus 6 [2-8], P<0.001, CCI 5 [4-6] versus 2 [1-3], P<0.001), increased need for mechanical ventilation (92% vs. 72%, P<0.001) and ICU mortality (74% versus. 29%, P<0.001). Age (HR: 1.045, CI: 1.02-1.07, P=0.001), CCI (HR: 1.135, CI: 1.037-1.243, P=0.006) and APACHE II (HR: 1.070, CI: 1.013-1.130, P=0.015) were independently associated with mortality. Among comorbidities, obesity, chronic pulmonary disease and chronic kidney disease were independent risk factors for death. CONCLUSIONS: When age is not used as criterion for admission to COVID ICU, patients ≥70 years old represent a considerable proportion and, compared to younger ones, they have higher mortality. Age, severity of illness and CCI, and certain comorbidities are independent risk factors for mortality.

Fewer Intubations but Higher Mortality Among Intubated Coronavirus Disease 2019 Patients During the Second Than the First Wave.

Since changes in pharmacological treatments for severely ill patients with coronavirus disease 2019 have been incorporated into clinical practice, both by their use (corticosteroids and remdesivir) and by stopping them (e.g., hydroxychloroquine), we sought to compare the rate of intubation and mortality of intubated patients in our ICUs between the first and second waves of the pandemic. DESIGN: Single-center, observational. SETTING: Four coronavirus disease 2019 designated ICUs at an urban Greek teaching hospital. PATIENTS: All adult patients with coronavirus disease 2019 consecutively admitted to ICU during the first (n = 50) and second (n = 212) waves of the pandemic. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The percentage of intubated ICU patients dropped from 82% during the first wave to 66% during the second wave (p = 0.042). However, the absolute number of intubated ICU patients was lower during the first than the second wave (41 vs 140 patients). ICU or hospital mortality of intubated patients increased from 39% during the first wave to 60% during the second wave (p = 0.028). The binary logistic regression for hospital mortality as the dependent variable in intubated patients and covariates the age, Acute Physiology and Chronic Health Evaluation II score, cardiovascular comorbidity, lactate, positive end-expiratory pressure, Sequential Organ Failure Assessment score, and wave, distinguished only Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.40 with 95% CI, 1.14-1.72; p = 0.001) as the sole independent predictor of hospital mortality. CONCLUSIONS: Pharmacological adaptations and other measures may have led to fewer intubations over time. However, these changes do not seem to be translated into improved outcomes of intubated patients. Perhaps the same change in the use of drugs and protocols that could cause fewer intubations of ICU patients might be a reason of increased mortality in those patients who are eventually intubated. Furthermore, the relative staff inexperience and overall increase in patients' comorbidities during the second wave could have contributed to increased Acute Physiology and Chronic Health Evaluation II score and mortality of intubated patients.

Elderly adults with COVID-19 admitted to intensive care unit: A narrative review.

BACKGROUND: In the context of the Coronavirus disease 2019 (COVID-19) pandemic, it has been reported that elderly patients are particularly at risk of developing severe illness and exhibiting increased mortality. While many studies on hospitalized elderly patients with COVID-19 have been published, limited information is available on the characteristics and clinical outcomes of those elderly patients admitted to intensive care unit (ICU). AIM: To review the available evidence of the clinical data of elderly patients admitted to the ICU due to COVID-19. METHODS: We searched for published articles available in English literature to identify those studies conducted in critically ill patients admitted to the ICU due to COVID-19, either exclusively designed for the elderly or for the whole ICU population with COVID-19, provided that analyses according to the patients' age had been conducted. RESULTS: Only one study exclusively focusing on critically ill elderly patients admitted to the ICU due to COVID-19 was found. Eighteen additional studies involving 17011 ICU patients and providing information for elderly patients as a subset of the whole study population have also been included in the present review article. Among the whole patient population, included in these studies, 8310 patients were older than 65 years of age and 2630 patients were older than 70 years. Clinical manifestations were similar for all patients; however, compared to younger ones, they suffered from more comorbidities and showed a varied, albeit high mortality. CONCLUSION: In summary, at present, although elderly patients constitute a considerable proportion of critically ill patients admitted to the ICU due to severe COVID-19, studies providing specific information are limited. The evidence so far suggests that advanced age and comorbidities are associated with worse clinical outcome. Future studies exclusively designed for this vulnerable group are needed.

Hospital Resources May Be an Important Aspect of Mortality Rate among Critically Ill Patients with COVID-19: The Paradigm of Greece.

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID-designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86-171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources.