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.

Challenges in Diagnosing COVID-19-Associated Pulmonary Aspergillosis in Critically Ill Patients: The Relationship between Case Definitions and Autoptic Data.

Critically ill COVID-19 patients can develop invasive pulmonary aspergillosis (CAPA). Considering the weaknesses of diagnostic tests/case definitions, as well as the results from autoptic studies, there is a debate on the real burden of aspergillosis in COVID-19 patients. We performed a retrospective observational study on mechanically ventilated critically ill COVID-19 patients in an intensive care unit (ICU). The primary objective was to determine the burden of CAPA by comparing clinical diagnosis (through case definitions/diagnostic algorithms) with autopsy results. Twenty patients out of 168 (11.9%) developed probable CAPA. Seven (35%) were females, and the median age was 66 [IQR 59-72] years. Thirteen CAPA patients (65%) died and, for six, an autopsy was performed providing a proven diagnosis in four cases. Histopathology findings suggest a focal pattern, rather than invasive and diffuse fungal disease, in the context of prominent viral pneumonia. In a cohort of mechanically ventilated patients with probable CAPA, by performing a high rate of complete autopsies, invasive aspergillosis was not always proven. It is still not clear whether aspergillosis is the major driver of mortality in patients with CAPA.

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.

Case Report: A Fatal Case of West Nile Virus Meningoencephalomyelitis in a Woman with Systemic Lupus Erythematosus Initially Misdiagnosed as SARS-CoV-2 Infection.

We present a fatal case of West Nile virus meningoencephalomyelitis initially misdiagnosed as COVID-19 in a 63-year-old Egyptian woman with a previous diagnosis of systemic lupus erythematosus. The patient's medical history and immunosuppressive therapy, as well as the COVID-19 pandemic, substantially broadened the differential diagnosis of her encephalitis.

Role of serum albumin and proteinuria in patients with SARS-CoV-2 pneumonia.

BACKGROUND: Hypoalbuminemia is frequently observed in patients with SARS-CoV-2 infection although its underlying mechanism and relationship with the clinical outcome still need to be clarified. METHODS: We retrospectively evaluated in patients with COVID-19 hospitalised at the Fatebenefratelli-Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID-19, with the levels of C-reactive protein, d-dimer and interleukin-6 and with clinical outcome over a follow-up period of 30 days. Urinalysis was evaluated in a subgroup of patients. RESULTS: Serum albumin levels <30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25-32.8). A negative association was found between albumin levels and severity of COVID-19 (P < .0001) and death (P = .003). An inverse correlation was observed between albumin and both C-reactive protein and D-dimer at hospital admission (r = -.487 and r = -.479, respectively; P < .0001). Finally, a positive correlation was found between albumin levels and eGFR (r = .137; P = .049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin ≥30 g/L (81% and 67%, respectively; P = .09). CONCLUSION: In patients with COVID-19, hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID-19.

Unexpectedly High Frequency of Enterococcal Bloodstream Infections in Coronavirus Disease 2019 Patients Admitted to an Italian ICU: An Observational Study.

OBJECTIVES: We aimed to assess the frequency of ICU-acquired bloodstream infections in coronavirus disease 2019 patients. DESIGN: Retrospective observational study. SETTING: The emergency expansion of an ICU from eight general beds to 30 coronavirus disease 2019 beds. PARTICIPANTS: Patients with coronavirus disease 2019 admitted to the ICU of Luigi Sacco Hospital (Milan, Italy) for greater than or equal to 48 hours between February 21, 2020, and April 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency of bloodstream infections per 1,000 days of ICU stay was calculated in 89 coronavirus disease 2019 patients, and the cumulative probability of bloodstream infection was estimated using death and ICU discharge as competing events. Sixty patients (67.4%) experienced at least one of the 93 recorded episodes of bloodstream infection, a frequency of 87 per 1,000 days of ICU stay (95% CI, 67-112).The patients who experienced a bloodstream infection had a higher Sequential Organ Failure Assessment score upon ICU admission (9.5; interquartile range, 8-12 vs 8, interquartile range, 5-10; p = 0.042), a longer median ICU stay (15 d; interquartile range, 11-23 vs 8, interquartile range, 5-12; p < 0.001), and more frequently required invasive mechanical ventilation (98.3% vs 82.8%; p = 0.013) than those who did not. The median time from ICU admission to the first bloodstream infection episode was 10 days. Gram-positive bacteria accounted for 74 episodes (79.6%), with Enterococcus species being the most prevalent (53 episodes, 55.8%). Thirty-two isolates (27.3%) showed multidrug resistance. CONCLUSIONS: Coronavirus disease 2019 seemed to increase the frequency of bloodstream infections (particularly Enterococcus-related bloodstream infection) after ICU admission. This may have been due to enteric involvement in patients with severe coronavirus disease 2019 and/or limitations in controlling the patient-to-patient transmission of infectious agents in extremely challenging circumstances.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.

BACKGROUND: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. METHODS: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. RESULTS: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). CONCLUSION: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

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.

Severe Plasmodium falciparum malaria in the intensive care unit: A 6-year experience in Milano, Italy.

BACKGROUND: Severe imported Plasmodium falciparum malaria is a potentially life-threatening disease with a reported mortality rate of 5-10% when patients are admitted to the Intensive Care Unit. METHODS: To retrospectively review the clinical aspects, the value of severity predictive scores and the management of patients with severe P. falciparum malaria admitted to an ICU in Milano, Italy between January 2010 and December 2015. RESULTS: Twelve patients were included: seven were male and five female with a median age of 43 years. All were initially treated with intravenous quinine. Median parasitaemia upon admission was 14,5% (range 1-20%). At the time of ICU admission, 3 patients (25%) had 5 or more World Health Organization criteria for severe malaria while another 6 of them developed one or more of the latter during their stay in ICU. Five required mechanical ventilation because of respiratory failure due to ARDS. Four patients required renal replacement therapy. Three patients underwent blood exchange transfusion. All patients survived. CONCLUSIONS: Our retrospective evaluation of adults patients admitted to the ICU with severe imported P. falciparum malaria demonstrated a favourable outcome. Severity predictive scores currently in use probably overestimate the risk of malaria mortality in patients treated in health care systems of high income countries.