for the COVID-ICU Gemelli Study Group IMPORTANCE High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.OBJECTIVE To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. DESIGN, SETTING, AND PARTICIPANTSMulticenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen Յ200).INTERVENTIONS Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H 2 O; pressure support, 10-12 cm H 2 O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). MAIN OUTCOMES AND MEASURESThe primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. RESULTS Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, −2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, −21% [95% CI, −38% to −3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] vs 25 ; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, −1% [95% CI, −17% to 15%]; P > .99).CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine...

In expert centers, NPPV applied as first-line intervention in ARDS avoided intubation in 54% of treated patients. A SAPS II >34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure.

Passive leg raising-induced changes in cardiac output can reliably predict fluid responsiveness regardless of ventilation mode and cardiac rhythm. PLR-cCO has a significantly higher predictive value than PLR-cPP.

Background Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. Methods Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH 2 O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO 2 /FiO 2 , FiO 2 , PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. Results Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th–75th percentiles] PaO 2 /FiO 2 in the two groups was 119 mmHg [101–142] and 116 mmHg [87–154]. Average compliance (41 ml/cmH 2 O [32–52] vs. 36 ml/cmH 2 O [27–42], p = 0.045) and ventilatory ratio (2.1 [1.7–2.3] vs. 1.6 [1.4–2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO 2 /FiO 2 was linearly correlated with respiratory system compliance ( r = 0.52 p = 0.003). High PEEP improved PaO 2 /FiO 2 in both cohorts, but more remarkably in COVID-19 patients ( p = 0.005). Recruitability was not different between cohorts ( p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. Conclusions Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.

IntroductionThe high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses.MethodsWe conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated.ResultsOver the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure.ConclusionsTGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria.

IntroductionThe culture-independent serum (1→3)-β-D-glucan (BG) detection test may allow early diagnosis of invasive fungal disease, but its clinical usefulness needs to be firmly established. A prospective single-center observational study was conducted to compare the diagnostic value of BG assay, Candida score (CS), and colonization index in intensive care unit (ICU) patients at risk for Candida sepsis.MethodsOf 377 patients, consecutively admitted to ICU for sepsis, 95 patients having an ICU stay of more than five days were studied. Blood specimens for fungal culture and BG measurement were obtained at the onset of clinical sepsis. For CS and colonization index calculations, surveillance cultures for Candida growth, and/or clinical data were recorded.ResultsSixteen (16.8%) patients were diagnosed with proven invasive fungal infection, 14 with candidiasis (13 candidemia and 1 mediastinitis) and 2 with pulmonary aspergillosis or fusariosis. Of 14 invasive Candida-infection patients, 13 had a serum sample positive for BG, 10 had a CS value ≥3, and 7 a colonization index ≥0.5. In the 12 candidemic patients, a positive BG result was obtained 24 to 72 hrs before a culture-documented diagnosis of invasive candidiasis. The positive and negative predictive values for the BG assay were higher than those of CS and colonization index (72.2% versus 57.1% and 27.3%; and 98.7% versus 97.2% and 91.7%, respectively).ConclusionsA single-point BG assay based on a blood sample drawn at the sepsis onset, alone or in combination withCS, may guide the decision to start antifungal therapy early in patients at risk for Candida infection.

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Our findings highlight the importance of IIAT as a risk factor for mortality in ICU patients with PA pneumonia. MDR in the PA isolate, like IIAT, can significantly increase the need for MV.