The value of a dynamic echocardiographic approach to diastolic dysfunction in intensive care medicine.

Diastolic dysfunction is an underestimated feature in the context of the critically ill setting and perioperative medicine. Advances in echocardiography, its noninvasive, safe and easy use, have allowed Doppler echocardiography to become a cornerstone for diagnosing diastolic dysfunction in clinical practice. The diagnosis of diastolic dysfunction and increased filling pressures is nevertheless complex. Using an echocardiographic assessment and the routine application of preload stress maneuvers during echocardiographic examination can help identify early stages of diastolic dysfunction leading to better management of patients at risk of acute heart decompensation in the perioperative period or during ICU stay.

Risk factors associated with bacteremia in COVID-19 patients admitted to intensive care unit: a retrospective multicenter cohort study.

PURPOSE: This multicenter observational study was done to evaluate risk factors related to the development of BSI in patients admitted to ICU for COVID-19. METHODS: All patients with COVID-19 admitted in two COVID-19 dedicated ICUs in two different hospital between 02-2020 and 02-2021 were recruited. RESULT: 537 patients were included of whom 265 (49.3%) experienced at least one BSI. Patients who developed bacteremia had a higher SOFA score [10 (8-12) vs 9 (7-10), p < 0.001], had been intubated more frequently [95.8% vs 75%, p < 0.001] and for a median longer time [16 days (9-25) vs 8 days (5-14), p < 0.001]. Patients with BSI had a median longer ICU stay [18 days (12-31.5) vs 9 days (5-15), p < 0.001] and higher mortality [54% vs 42.3%, p < 0.001] than those who did not develop it. Development of BSI resulted in a higher SOFA score [aHR 1.08 (95% CI 1.03-1.12)] and a higher Charlson score [csAHR 1.15 (95% CI 1.05-1.25)]. CONCLUSION: A high SOFA score and a high Charlson score resulted associated with BSI's development. Conversely, immunosuppressive therapy like steroids and tocilizumab, has no role in increasing the risk of bacteremia.

Effects of Prone Position on Lung Recruitment and Ventilation-Perfusion Matching in Patients With COVID-19 Acute Respiratory Distress Syndrome: A Combined CT Scan/Electrical Impedance Tomography Study.

OBJECTIVES: Prone positioning allows to improve oxygenation and decrease mortality rate in COVID-19-associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT). DESIGN: Experimental, physiologic study. SETTING: Patients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU. PATIENTS: Twenty-one intubated patients with moderate or severe C-ARDS. INTERVENTIONS: First, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position). MEASUREMENTS AND MAIN RESULTS: Prone position induced recruitment in the dorsal part of the lungs (12.5% ± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (-6.9% ± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ± 15 vs 45 ± 18 mL/cm H2O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ± 0.16 vs 1.30 ± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3-23.4] vs 4.3 [0.7-6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching. CONCLUSIONS: Several changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.

Lung histopathologic clusters in severe COVID-19: a link between clinical picture and tissue damage.

BACKGROUND: Autoptic pulmonary findings have been described in severe COVID-19 patients, but evidence regarding the correlation between clinical picture and lung histopathologic patterns is still weak. METHODS: This was a retrospective cohort observational study conducted at the referral center for infectious diseases in northern Italy. Full lung autoptic findings and clinical data of patients who died from COVID-19 were analyzed. Lung histopathologic patterns were scored according to the extent of tissue damage. To consider coexisting histopathologic patterns, hierarchical clustering of histopathologic findings was applied. RESULTS: Whole pulmonary examination was available in 75 out of 92 full autopsies. Forty-eight hospitalized patients (64%), 44 from ICU and four from the medical ward, had complete clinical data. The histopathologic patterns had a time-dependent distribution with considerable overlap among patterns. Duration of positive-pressure ventilation (p < 0.0001), mean positive end-expiratory pressure (PEEP) (p = 0.007), worst serum albumin (p = 0.017), interleukin 6 (p = 0.047), and kidney SOFA (p = 0.001) differed among histopathologic clusters. The amount of PEEP for long-lasting ventilatory treatment was associated with the cluster showing the largest areas of early and late proliferative diffuse alveolar damage. No pharmacologic interventions or comorbidities affected the lung histopathology. CONCLUSIONS: Our study draws a comprehensive link between the clinical and pulmonary histopathologic findings in a large cohort of COVID-19 patients. These results highlight that the positive end-expiratory pressures and the duration of the ventilatory treatment correlate with lung histopathologic patterns, providing new clues to the knowledge of the pathophysiology of severe SARS-CoV-2 pneumonia.

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. METHODS: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels. RESULTS: ICU patients showed a marked increase in neutrophils (1.24 × 105 ml- 1, 0.85-2.07), lower lymphocyte (0.97 × 105 ml- 1, 0.024-0.34) and macrophages fractions (0.43 × 105 ml- 1, 0.34-1.62) compared to IMW patients (0.095 × 105 ml- 1, 0.05-0.73; 0.47 × 105 ml- 1, 0.28-1.01 and 2.14 × 105 ml- 1, 1.17-3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05). CONCLUSIONS: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

The effect of prolonged steep head-down laparoscopy on the optical nerve sheath diameter.

Both the steep head-down position and pneumoperitoneum increase the intracranial pressure (ICP), and their combination for a prolonged period during laparoscopic radical prostatectomy (LRP) might influence the central nervous system homeostasis. Changes in optic nerve sheath diameter (ONSD) may reflect those in ICP. This study aims to quantify the change in ONSD in response to peritoneal CO2 insufflation and steep Trendelenburg position during LRP. ONSD was measured by ultrasound in 20 patients undergoing LRP and ten awake healthy volunteers. In patients, ONSD was assessed at baseline immediately after induction of general anesthesia in supine position, 10 and 60 min from baseline in a 25° head-down position during pneumoperitoneum, and after deflation of pneumoperitoneum with the patient supine at 0° angle. ONSD in controls was assessed at baseline with the patient lying supine, after 10 and 60 min of 25° head-down position, and 10 min after repositioning at 0° angle. ONSD increased significantly in both patients and controls (p < 0.0001) without between-group differences. The mean increase was 10.3% (95% CI 7.7-12.9%) in patients versus 7.5% (95% CI 2.5-12.6%) in controls (p = 0.28), and didn't affect the time to recovery from anesthesia. In the studied patients, with a limited increase of end-tidal CO2 and airway pressure, and low volume fluid infusion, the maximal ONSD was always below the cut-off value suspect for increased ICP. ONSD reflects the changes in hydrostatic pressure in response to steep Trendelenburg position, and its increase might be minimized by careful handling of general anesthesia.

Echocardiographic clues of the "atrial pump mechanism" during cardiopulmonary resuscitation.

Instead of the ventricles, atria may be the cardiac structures mainly compressed during cardiopulmonary resuscitation (CPR). This study aimed to assess the prevalence and the mechanical characteristics of atrial compression, named the "atrial pump mechanism", in patients undergoing CPR. A retrospective cohort study was conducted on patients with witnessed refractory out-of-hospital cardiac arrest who were admitted to a tertiary referral center for extracorporeal CPR. The area of maximal compression (AMC) by chest compressions was assessed by transesophageal echocardiography. Right atrial wall excursion (RAWE), left atrial fractional shortening (LAFS), right ventricular fractional area change (RVFAC), and left ventricular fractional shortening (LVFS) were measured. Common carotid and middle cerebral artery peak velocities were assessed using color-Doppler imaging as markers of cardiac outflow and cerebral perfusion. Forty patients were included in the study. Five (12.5%) had AMC over the atria. The atrial pump pattern was characterized by marked atrial compression with higher RAWE and LAFS values compared to the other patients (p < 0.001). Common carotid Doppler and transcranial Doppler-velocity patterns were detectable in all patients with open left ventricular outflow tract, without differences between patients. CPR was successful in four patients (80%) with atrial pump compared to 14 (40%) with no atrial pump mechanism (p = 0.155). In this series of selected patients with witnessed cardiac arrest, the prevalence of the atrial pump mechanism was not negligible. It may contribute to forward blood flow and the maintenance of cerebral perfusion during prolonged cardiopulmonary resuscitation.

Awake pronation with helmet CPAP in early COVID-19 ARDS patients: effects on respiratory effort and distribution of ventilation assessed by EIT.

Prone positioning with continuous positive airway pressure (CPAP) is widely used for respiratory support in awake patients with COVID-19-associated acute respiratory failure. We aimed to assess the respiratory mechanics and distribution of ventilation in COVID-19-associated ARDS treated by CPAP in awake prone position. We studied 16 awake COVID-19 patients with moderate-to-severe ARDS. The study protocol consisted of a randomized sequence of supine and prone position with imposed positive end-expiratory pressure (PEEP) of 5 and 10 cmH2O delivered by helmet CPAP. Respiratory mechanics and distribution of ventilation were assessed through esophageal pressure (PES) and electrical impedance tomography (EIT). At the end of each 20-min phase, arterial blood gas analysis was performed, and PES swing and EIT tracings were recorded for the calculation of the respiratory mechanics and regional ventilation. The patient's position had no significant effects on respiratory mechanics. EIT analysis did not detect differences among global indices of ventilation. A significant proportion of pixels in the sternal region of interest showed an increase in compliance from the supine to prone position and PaO2/FIO2 increased accordingly. The best improvement of both PaO2/FIO2 and sternal compliance was obtained in the prone position with PEEP 10 cmH2O. In the studied subjects, prone positioning during CPAP treatment raised oxygenation without improvement of "protective" ventilation or global ventilatory inhomogeneity indices. Prone positioning with higher PEEP significantly increased the compliance of sternal regions.

The efficacy of venous-arterial membrane oxygenation for emergency extracorporeal life support: results from a single-center large series over 6 years.

The efficacy of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in supporting cardio-pulmonary resuscitation for cardiac arrest is still debated. This study aimed to evaluate the outcome of patients treated with VA-ECMO positioned according to different clinical indications. The method is retrospective data analysis from patients admitted to a tertiary referral center for VA-ECMO in 6 years. The study population was divided into three groups based on the VA-ECMO indication: patients with refractory cardiac arrest (CA group), cardiogenic shock after return of spontaneous circulation (CS-ROSC group), and cardiogenic shock without cardiac arrest (CS group). Seventy-nine patients underwent emergency VA-ECMO, 49 patients (62.0%) were in the CA group, 14 (17.7%) in the CS-ROSC group, and 16 patients (20.3%) in the CS group. The overall survival at 28 days was different between the three groups (6.1% in the CA group, 64.2% in the CS-ROSC group, and 50.0% in the CS group, p < 0.001) and remained significant at 12 months (p < 0.001). Furthermore, the Cerebral Performance Category at 12 months differed between groups with good outcomes in 4.1% of patients in CA, 50.0% in CS-ROSC, and 31.2% in CS groups (p < 0.001). In the studied population, emergency VA-ECMO had negligible efficacy in refractory cardiac arrest, while it was correlated with a good outcome in cardiogenic shock after cardiac arrest, such as in cardiogenic shock alone. Patients with ROSC appear to benefit from VA-ECMO in the setting of persistent shock at rates comparable to cardiogenic shock patients who never sustained cardiac arrest.

Cardiorespiratory coupling in mechanically ventilated patients studied via synchrogram analysis.

Respiration and cardiac activity are strictly interconnected with reciprocal influences. They act as weakly coupled oscillators showing varying degrees of phase synchronization and their interactions are affected by mechanical ventilation. The study aims at differentiating the impact of three ventilatory modes on the cardiorespiratory phase coupling in critically ill patients. The coupling between respiration and heartbeat was studied through cardiorespiratory phase synchronization analysis carried out via synchrogram during pressure control ventilation (PCV), pressure support ventilation (PSV), and neurally adjusted ventilatory assist (NAVA) in critically ill patients. Twenty patients were studied under all the three ventilatory modes. Cardiorespiratory phase synchronization changed significantly across ventilatory modes. The highest synchronization degree was found during PCV session, while the lowest one with NAVA. The percentage of all epochs featuring synchronization regardless of the phase locking ratio was higher with PCV (median: 33.9%, first-third quartile: 21.3-39.3) than PSV (median: 15.7%; first-third quartile: 10.9-27.8) and NAVA (median: 3.7%; first-third quartile: 3.3-19.2). PCV induces a significant amount of cardiorespiratory phase synchronization in critically ill mechanically ventilated patients. Synchronization induced by patient-driven ventilatory modes was weaker, reaching the minimum with NAVA. Findings can be explained as a result of the more regular and powerful solicitation of the cardiorespiratory system induced by PCV. The degree of phase synchronization between cardiac and respiratory activities in mechanically ventilated humans depends on the ventilatory mode.

Failing categorization of severe COVID-19 ARDS into ventilatory subphenotypes studied via the clinical-histopathologic relationship.

BACKGROUND: Categorization of severe COVID-19 related acute respiratory distress syndrome (CARDS) into subphenotypes does not consider the trajectories of respiratory mechanoelastic features and histopathologic patterns. This study aimed to assess the correlation between mechanoelastic ventilatory features and lung histopathologic findings in critically ill patients who died because of CARDS. METHODS: Mechanically ventilated patients with severe CARDS who had daily ventilatory data were considered. The histopathologic assessment was performed through full autopsy of deceased patients. Patients were categorized into two groups according to the median worst respiratory system compliance during ICU stay (CrsICU). RESULTS: Eighty-seven patients admitted to ICU had daily ventilatory data. Fifty-one (58.6%) died in ICU, 41 (80.4%) underwent full autopsy and were considered for the clinical-histopathological correlation analysis. Respiratory system compliance at ICU admission and its trajectory were not different in survivors and non-survivors. Median CrsICU in the deceased patients was 22.9 ml/cmH2O. An inverse correlation was found between the CrsICU and late-proliferative diffuse alveolar damage (DAD) (r = -0.381, p = 0.026). Late proliferative DAD was more extensive (p = 0.042), and the probability of stay in ICU was higher (p = 0.004) in the "low" compared to the "high" CrsICU group. Cluster analysis further endorsed these findings. CONCLUSIONS: In critically ill mechanically ventilated patients, worsening of the respiratory system compliance correlated pathologically with the transition from early damage to late fibroproliferative patterns in non-survivors of CARDS. Categorization of CARDS into ventilatory subphenotypes by mechanoelastic properties at ICU admission does not account for the complexity of the histopathologic features.

Mechanical chest compression and extracorporeal life support for out-of-hospital cardiac arrest. A 30-month observational study in the metropolitan area of Milan, Italy.

BACKGROUND: Return of spontaneous circulation (ROSC) is achieved in 25% of out-of-hospital cardiac arrest (OHCA) patients. Mechanical chest compression (mechCPR) may maintain better perfusion during transport, allowing hospital treatments like extracorporeal circulation life support (ECLS). We aim to assess the effectiveness of a pre-hospital protocol introduction. METHODS: Observational, retrospective study assessing all OHCA patients aged 12-75, with no-flow time <20 min in a metropolitan area (Milan, Italy, 2013-2016). PRIMARY OUTCOMES: ROSC and Cerebral Performance Category score (CPC) ≤2 at hospital discharge. Logistic regressions with multiple comparison adjustments balanced with propensity scores calculated with inverse probability of treatment weighting were performed. RESULTS: 1366 OHCA were analysed; 305 received mechCPR, 1061 manual chest compressions (manCPR), and 108 ECLS. ROSC and CPC ≤2 were associated with low-flow minutes (odds ratio [95% confidence interval] 0.90 [0.88-0.91] and 0.90 [0.87-0.93]), shockable rhythm (2.52 [1.71-3.72] and 10.68 [5.63-20.28]), defibrillations number (1.15 [1.07-1.23] and 1.15 [1.04-1.26]), and mechCPR (1.86 [1.17-2.96] and 2.06 [1.11-3.81]). With resuscitation times >13 min, mechCPR achieved more frequently ROSC compared to manCPR. Among ECLS patients, 70% had time exceeding protocol: 8 (7.5%) had CPC ≤2 (half of them with low-flow times between 45 and 90 min), 2 (1.9%) survived with severe neurological disabilities, and 13 brain-dead (12.0%) became organ donors. CONCLUSIONS: MechCPR patients achieved ROSC more frequently than manual CPR patients; mechCPR was a crucial factor in an ECLS protocol for refractory OHCA. ECLS offered a chance of survival to patients who would otherwise die.

Acute kidney injury (AKI) in patients with Covid-19 infection is associated with ventilatory management with elevated positive end-expiratory pressure (PEEP).

BACKGROUND: Acute kidney injury (AKI) in Covid-19 patients admitted to the intensive care unit (ICU) is common, and its severity may be associated with unfavorable outcomes. Severe Covid-19 fulfills the diagnostic criteria for acute respiratory distress syndrome (ARDS); however, it is unclear whether there is any relationship between ventilatory management and AKI development in Covid-19 ICU patients. PURPOSE: To describe the clinical course and outcomes of Covid-19 ICU patients, focusing on ventilatory management and factors associated with AKI development. METHODS: Single-center, retrospective observational study, which assessed AKI incidence in Covid-19 ICU patients divided by positive end expiratory pressure (PEEP) tertiles, with median levels of 9.6 (low), 12.0 (medium), and 14.7 cmH2O (high-PEEP). RESULTS: Overall mortality was 51.5%. AKI (KDIGO stage 2 or 3) occurred in 38% of 101 patients. Among the AKI patients, 19 (53%) required continuous renal replacement therapy (CRRT). In AKI patients, mortality was significantly higher versus non-AKI (81% vs. 33%, p < 0.0001). The incidence of AKI in low-, medium-, or high-PEEP patients were 16%, 38%, and 59%, respectively (p = 0.002). In a multivariate analysis, high-PEEP patients showed a higher risk of developing AKI than low-PEEP patients (OR = 4.96 [1.1-21.9] 95% CI p < 0.05). ICU mortality rate was higher in high-PEEP patients, compared to medium-PEEP or low-PEEP patients (69% vs. 44% and 42%, respectively; p = 0.057). CONCLUSION: The use of high PEEP in Covid-19 ICU patients is associated with a fivefold higher risk of AKI, leading to higher mortality. The cause and effect relationship needs further analysis.

Autonomic biomarkers of shock in idiopathic systemic capillary leak syndrome.

OBJECTIVE: The term Idiopathic Systemic Capillary Leak Syndrome (ISCLS) refers to an uncommon condition of severe distributive shock, resulting from an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesise that the autonomic nervous system (ANS) fails in regulating the response to hypovolemia in acute ISCLS and that ANS variables characterise the progression to the recovery. DESIGN: Prospective cohort study of patients admitted to ICU for severe ISCLS flares. SETTING: Single, referral center in Italy for ISCLS. PATIENTS: Analysis of cardiovascular signals recorded during seven severe ISCLS attacks and one prodromal period in five patients. INTERVENTIONS: ANS was studied non-invasively by means of heart rate variability (HRV) and blood pressure variability analysis, as an estimation of vagal and sympathetic modulation directed to the heart and vessels. Heart rate and systolic arterial pressure (SAP) variability were also used to assess baroreflex sensitivity. ANS variables were measured during the subsequent phases which characterise ISCLS flares, namely the acute phase, the post-acute phase, and the recovery phase. MEASUREMENTS AND MAIN RESULTS: HRV was severely depressed during the acute phase accounting for the loss of ANS modulation during massive capillary extravasation. This phase was characterised by shock and impaired baroreflex control, which allowed SAP to oscillate driven by respiratory activity. Impending shock and transition from shock to a post-acute phase were marked by change of baroreflex spectral variables. The baroreflex control was fully restored during recovery. CONCLUSIONS: ANS modulation and baroreflex control are severely impaired during the acute haemodynamic instability which characterises ISCLS crises and their progressive restoration may be a clue of improvement. ANS indices during ISCLS flares might serve as useful biomarkers, able to timely announce the transition from one phase to the subsequent one, thus helping to adapt therapy accordingly.

Transesophageal echocardiography in patients with cardiac arrest: from high-quality chest compression to effective resuscitation.

BACKGROUND: Survival after cardiac arrest depends on prompt and effective cardiopulmonary resuscitation (CPR). Transesophageal echocardiography (TEE) can be applied to evaluate the effectiveness of chest compression-decompression maneuvers in the setting of cardiac arrest undergoing CPR. The efficacy of chest compression can be continuously assessed by TEE that can improve the effectiveness of CPR guiding the rescuer to optimize or correct chest compression and decompression by directly examining the movements of the cardiac walls and valve leaflets. PURPOSE: The review describes how to perform TEE in the emergency setting of cardiopulmonary arrest, its advantages, and limitations, and ultimately propose an echo-guided approach to CPR.

Full-Length Recombinant hSP-D Binds and Inhibits SARS-CoV-2.

SARS-CoV-2 infection of host cells is driven by binding of the SARS-CoV-2 spike-(S)-protein to lung type II pneumocytes, followed by virus replication. Surfactant protein SP-D, member of the front-line immune defense of the lungs, binds glycosylated structures on invading pathogens such as viruses to induce their clearance from the lungs. The objective of this study is to measure the pulmonary SP-D levels in COVID-19 patients and demonstrate the activity of SP-D against SARS-CoV-2, opening the possibility of using SP-D as potential therapy for COVID-19 patients. Pulmonary SP-D concentrations were measured in bronchoalveolar lavage samples from patients with corona virus disease 2019 (COVID-19) by anti-SP-D ELISA. Binding assays were performed by ELISAs. Protein bridge and aggregation assays were performed by gel electrophoresis followed by silver staining and band densitometry. Viral replication was evaluated in vitro using epithelial Caco-2 cells. Results indicate that COVID-19 patients (n = 12) show decreased pulmonary levels of SP-D (median = 68.9 ng/mL) when compared to levels reported for healthy controls in literature. Binding assays demonstrate that SP-D binds the SARS-CoV-2 glycosylated spike-(S)-protein of different emerging clinical variants. Binding induces the formation of protein bridges, the critical step of viral aggregation to facilitate its clearance. SP-D inhibits SARS-CoV-2 replication in Caco-2 cells (EC90 = 3.7 µg/mL). Therefore, SP-D recognizes and binds to the spike-(S)-protein of SARS-CoV-2 in vitro, initiates the aggregation, and inhibits viral replication in cells. Combined with the low levels of SP-D observed in COVID-19 patients, these results suggest that SP-D is important in the immune response to SARS-CoV-2 and that rhSP-D supplementation has the potential to be a novel class of anti-viral that will target SARS-CoV-2 infection.

The effects of severe hemoconcentration on acid-base equilibrium in critically ill patients: the forgotten role of buffers in whole blood.

PURPOSE: Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a paroxysmal permeability disorder characterized by abrupt onset of shock and hemoconcentration due to massive shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesize that increased hemoglobin concentration has a pivotal role in the acid-base imbalance during life-threatening crises. MATERIALS AND METHODS: Analysis of the acid-base balance fluctuations during six severe ISCLS flares admitted to ICU of a referral center for ISCLS. RESULTS: Acid-base equilibrium was assessed for plasma and the whole blood by single and multicompartmental models. The acute phase of ISCLS was characterized by shock, hypoalbuminemia, severe hemoconcentration, and acidosis. The physical-chemical approach for plasma found a remarkable component of unmeasured anions (SIG) during the acute phase. After correction of the physical-chemical model for the whole blood, the SIG variations disappeared because the buffer role of hemoglobin was relevant. CONCLUSION: Hemoglobin has a remarkable role in buffering metabolic acidosis during the shock phase of ISCLS. In these circumstances, the assessment of acid-base equilibrium in plasma alone may overestimate unmeasured anions. On the contrary, the physical-chemical model corrected for whole blood better explains the metabolic component of acid-base imbalance when marked shift of hemoglobin concentration occurs.

Myocardial edema in paroxysmal permeability disorders: The paradigm of Clarkson's disease.

PURPOSE: Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. MATERIALS AND METHODS: Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. RESULTS: Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1-21 mm) vs. 9.9 mm (9-11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. CONCLUSIONS: During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

Tethering role of the autonomic nervous system on cardioventilatory coupling.

Hypovolemia and intermittent positive pressure ventilation are conditions that frequently characterize the state of critical illness, but their interaction and resulting cardioventilatory coupling is poorly understood even in healthy humans. We explored heart rate variability, baroreflex activity, and their interaction in an experimental protocol involving twelve mildly hypovolemic healthy subjects during spontaneous breathing and noninvasive positive-pressure ventilation. In seven subjects, an echocardiographic assessment was also performed. Correction of hypovolemia, raising cardiac preload, produced an increase in high-frequency spectral power density of heart rate, left low-frequency spectral power density unchanged but enhanced baroreflex sensitivity. Cardioventilatory coupling was affected by both central blood volume and ventilatory mode and was mainly entrained by the respiratory oscillation. In conclusion, the autonomic nervous system and baroreflex have a significant role in compensating the hemodynamic perturbation due to changes of volemia and ventilatory-induced fluctuations of venous return. They exert an integrative function on the adaptive pattern of cardioventilatory coupling.

Kinetics of manual and automated mechanical chest compressions.

AIM: Early onset of adequate chest compression is mandatory for cardiopulmonary resuscitation (CPR) following cardiac arrest. Transmission of forces from chest strain to the heart may be variable between manual and mechanical chest compressions. Furthermore, automated mechanical chest devices can deliver an active decompression, thus improving the venous return to the heart. This pilot study investigated the kinetics of cardiac deformation during these two CPR methods. METHODS: Transesophageal echocardiographic analysis of the right ventricular wall behind the sternum during CPR was assessed during manual and mechanical chest compression in adult patients admitted to the emergency department for out-of-hospital cardiac arrest. RESULTS: 9 patients had manual and 11 mechanical chest compression. Mechanical chest compression was characterized by greater right ventricular lateral wall displacement [with a median (IQR) of 3.7 (3.12-4.27) vs. 2.53 (2.27-2.6) cm, p < 0.0001], and lower rising time [123 (102-169) vs. 187 (164-215) ms, p = 0.002], relaxing time [109 (102-127) vs. 211 (133-252) ms, p = 0.0003], compression rate [100.6 (99.6-102.2) vs. 131.9 (125.4-151.4) bpm, p < 0.0001], with compression-decompression time ratio of [1.04 (0.86-1.1) vs. 0.86 (0.78-0.96), p = 0.046]. CONCLUSION: Mechanical compared to manual chest compression delivered a more rapid compression and decompression of the cardiac structures at an adequate rate, with broader inward-outward movement of the ventricular walls suggesting greater emptying and filling of the ventricles. Transesophageal echocardiography may be a useful tool to assess the adequacy of chest compression without CPR interruption.