Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation.

We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.

High Failure Rate of Noninvasive Oxygenation Strategies in Critically Ill Subjects With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19. METHODS: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, [Formula: see text] and [Formula: see text] at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes. RESULTS: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score (P = .009) and serum lactate dehydrogenase at enrollment (P = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, P = .01). CONCLUSIONS: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.

Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies.

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 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2/FiO2, FiO2, 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] PaO2/FiO2 in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmH2O [32-52] vs. 36 ml/cmH2O [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, PaO2/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2/FiO2 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.