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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Tooth Aspiration in a Patient with Traumatic Brain Injury.

Tooth aspiration is a rare issue in the course of patients with trauma and may remain undiagnosed for a long period, resulting in delayed complications, such as atelectasis and recurrent infections. Flexible bronchoscopy is considered the preferred primary procedure for the management of airway foreign bodies in adults. However, it may cause intracranial hypertension in trauma patients with concomitant head injuries. We herein report a case of a patient with traumatic brain injury who underwent tooth aspiration using flexible bronchoscopy, with continuous monitoring of intracranial pressure (ICP). The importance of a thorough review of radiographs and chest computed tomography for foreign body aspiration in trauma patients was highlighted, particularly in a maxillofacial trauma, as tooth aspiration may remain undiagnosed for extended periods. Moreover, the difficulty in maintaining the ICP within normal limits during bronchoscopy in patients with traumatic brain injury was reinstated, and the need for continuous monitoring of the cerebral hemodynamics and harmonization was emphasized, with recommendations for bronchoscopy via an endotracheal tube.

Contribution of Levosimendan in Weaning from Mechanical Ventilation in Patients with Left Ventricular Dysfunction: A Pilot Study.

PURPOSE: Mechanically ventilated patients with left ventricular (LV) dysfunction are at risk of weaning failure. We hypothesized that optimization of cardiovascular function might facilitate the weaning process. Therefore, we investigated the efficacy of levosimendan in difficult-to-wean patients with impaired LV performance. MATERIALS AND METHODS: Nineteen mechanically ventilated patients, with LV ejection fraction (LVEF) 34 ± 8%, difficult-to-wean from the ventilator, were assessed by transthoracic echocardiography before the start and at the end of a spontaneous breathing trial (SBT) (first SBT). Eight patients successfully weaned. The remaining 11 failed-to-wean patients received a 24-hour infusion of levosimendan, and they were reassessed during a second SBT. RESULTS: After levosimendan administration, LVEF increased from 30 ± 10 to 36 ± 3% (p=0.01). End-SBT peak e' velocity increased from 7 to 9 cm/s (p=0.02). E/e' increased from 10.5 to 12.9 during the first SBT, whereas it remained constant at 10 throughout the second SBT (p=0.01). During the second SBT, partial pressure of arterial oxygen and central venous oxygen saturation improved, compared to the first one (93 ± 34 vs. 67 ± 28 mmHg, p=0.03, and 66 ± 11% vs. 57 ± 9%, p=0.02, respectively). Nine of the 11 patients were successfully weaned from the ventilator. CONCLUSIONS: In difficult-to-wean from mechanical ventilation patients with LV dysfunction, levosimendan might contribute to successful weaning by improving both systolic and diastolic LV function.

Weaning failure of cardiovascular origin: how to suspect, detect and treat-a review of the literature.

Among the multiple causes of weaning failure from mechanical ventilation, cardiovascular dysfunction is increasingly recognized as a quite frequent cause that can be treated successfully. In this review, we summarize the contemporary evidence of the most important clinical and diagnostic aspects of weaning failure of cardiovascular origin with special focus on treatment. Pathophysiological mechanisms are complex and mainly include increase in right and left ventricular preload and afterload and potentially induce myocardial ischemia. Patients at risk include those with preexisting cardiopulmonary disease either known or suspected. Clinically, cardiovascular etiology as a predominant cause or a contributor to weaning failure, though critical for early diagnosis and intervention, may be difficult to be recognized and distinguished from noncardiac causes suggesting the need of high suspicion. A cardiovascular diagnostic workup including bedside echocardiography, lung ultrasound, electrocardiogram and biomarkers of cardiovascular dysfunction or other adjunct techniques and, in selected cases, right heart catheterization and/or coronary angiography, should be obtained to confirm the diagnosis. Official clinical practice guidelines that address treatment of a confirmed weaning-induced cardiovascular dysfunction do not exist. As the etiologies of weaning-induced cardiovascular dysfunction are diverse, principles of management depend on the individual pathophysiological mechanisms, including preload optimization by fluid removal, guided by B-type natriuretic peptide measurement, nitrates administration in excessive afterload and/or myocardial ischemia, contractility improvement in severe systolic dysfunction as well as other rational treatment in specific indications in order to lead to successful weaning from mechanical ventilation.

Route of nutrition and risk of blood stream infections in critically ill patients; a comparative study.

BACKGROUND AND AIMS: The association of nutritional support practices with intensive care unit (ICU) - acquired infections is a current field of interest. The objective of this study was to determine whether different routes of delivery of nutritional support are associated with a different risk of bloodstream infection (BSI) in critically ill patients. METHODS: An observational study in a multidisciplinary ICU. Adult ICU patients, with ICU stay ≥96 h who were fed artificially were included. Patients were grouped into three categories of nutrition support routes: those on enteral nutrition alone (EN group), on parenteral nutrition alone (PN group) or on both EN and PN (EN+PN group). Illness severity, co-morbidities and routine laboratory values were recorded on ICU admission. Route of feeding, caloric, protein and immunonutrient intake was recorded daily for each patient. Nosocomial BSIs were identified by infection control surveillance methods. The incidence of BSI among the three groups was compared with Kaplan-Meier plots and Cox proportional-hazards models. RESULTS: A total of 249 patients were included in the analysis. There were no significant differences between groups in illness severity scores and in the time to nutritional support initiation (median time 48 [24-48] hours). The median daily caloric intake was significantly lower for the EN group than for patients of PN and EN+PN group (415 [157-687] kcal vs. 1077 [297-2087] kcal and 1292 [890-1819] kcal respectively, p < 0.001). BSI occurred in 69 (27.7%) patients. Bivariate Cox analysis revealed that APACHE II score and admission category were significantly associated to BSI development [hazard ratio (HR), 1.05; 95% confidence interval (CI), 1.01-1.09 and HR 0.45; 95% CI 0.18-1.15, respectively]. Presence of co-morbidities, SOFA score, hospital length of stay (LOS) before ICU admission, late initial feeding, serum albumin at admission, average daily maximum concentration of serum glucose, caloric, protein and immunonutrient intake did not affect the hazard of BSI development. After adjustment for the confounding variables, in a multivariate analysis, patients of the EN + PN group had lower incidence of BSI than the other two groups (HR 0.30; 95% CI 0.17-0.53), irrespective of the number of days of PN intake and the percentage of calories received from PN. There was no difference in the hazard for BSI development between the EN and PN group. Patients with EN + PN had a significantly longer ICU-LOS whereas mortality was not different among the three groups. CONCLUSIONS: In this retrospective analysis of 249 consecutively enrolled ICU patients, we found that in critically ill patients EN + PN feeding strategy was associated with a significantly reduced hazard of BSI development, compared to EN or PN route of nutritional support.

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.