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1.
Crit Care ; 26(1): 219, 2022 07 18.
Article in English | MEDLINE | ID: covidwho-2281130

ABSTRACT

BACKGROUND: Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position. METHODS: This was a prospective study conducted in a 25-bed intensive care unit at a university hospital. We included patients with ARDS under prone position, ventilated with 6 mL/kg tidal volume and monitored by a transpulmonary thermodilution device. We measured PPV and its changes during a TVC (ΔPPV TVC6-8) after increasing the tidal volume from 6 to 8 mL/kg for one minute. Changes in cardiac index (CI) during a Trendelenburg maneuver (ΔCITREND) and during end-expiratory occlusion (EEO) at 8 mL/kg tidal volume (ΔCI EEO8) were recorded. Preload responsiveness was defined by both ΔCITREND ≥ 8% and ΔCI EEO8 ≥ 5%. Preload unresponsiveness was defined by both ΔCITREND < 8% and ΔCI EEO8 < 5%. RESULTS: Eighty-four sets of measurements were analyzed in 58 patients. Before prone positioning, the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen was 104 ± 27 mmHg. At the inclusion time, patients were under prone position for 11 (2-14) hours. Norepinephrine was administered in 83% of cases with a dose of 0.25 (0.15-0.42) µg/kg/min. The positive end-expiratory pressure was 14 (11-16) cmH2O. The driving pressure was 12 (10-17) cmH2O, and the respiratory system compliance was 32 (22-40) mL/cmH2O. Preload responsiveness was detected in 42 cases. An absolute change in PPV ≥ 3.5% during a TVC assessed preload responsiveness with an area under the receiver operating characteristics (AUROC) curve of 0.94 ± 0.03 (sensitivity: 98%, specificity: 86%) better than that of baseline PPV (0.85 ± 0.05; p = 0.047). In the 56 cases where baseline PPV was inconclusive (≥ 4% and < 11%), ΔPPV TVC6-8 ≥ 3.5% still enabled to reliably assess preload responsiveness (AUROC: 0.91 ± 0.05, sensitivity: 97%, specificity: 81%; p < 0.01 vs. baseline PPV). CONCLUSION: In patients with ARDS under low tidal volume ventilation during prone position, the changes in PPV during a TVC can reliably assess preload responsiveness without the need for cardiac output measurements. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04457739). Registered 30 June 2020 -Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04457739.


Subject(s)
Prone Position , Respiration, Artificial , Respiratory Distress Syndrome , Tidal Volume , COVID-19/epidemiology , Humans , Pandemics , Prone Position/physiology , Prospective Studies , Respiration, Artificial/methods , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Tidal Volume/physiology , Treatment Outcome
2.
Antibiotics (Basel) ; 12(1)2023 Jan 09.
Article in English | MEDLINE | ID: covidwho-2199677

ABSTRACT

(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.

3.
Crit Care ; 26(1): 338, 2022 11 04.
Article in English | MEDLINE | ID: covidwho-2108872

ABSTRACT

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.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Respiratory Distress Syndrome , Humans , Intensive Care Units , Pepsin A , Pronation , Equipment Design , Pneumonia, Ventilator-Associated/etiology , Intubation, Intratracheal/adverse effects , alpha-Amylases
4.
PLoS One ; 17(4): e0267038, 2022.
Article in English | MEDLINE | ID: covidwho-1817490

ABSTRACT

INTRODUCTION: Remdesivir and Dexamethasone represent the cornerstone of therapy for critically ill patients with acute hypoxemic respiratory failure caused by Coronavirus Disease 2019 (COVID-19). However, clinical efficacy and safety of concomitant administration of Remdesivir and Dexamethasone (Rem-Dexa) in severe COVID-19 patients on high flow oxygen therapy (HFOT) or non-invasive ventilation (NIV) remains unknown. MATERIALS AND METHODS: Prospective cohort study that was performed in two medical Intensive Care Units (ICUs) of a tertiary university hospital. The clinical impact of Rem-Dexa administration in hypoxemic patients with COVID-19, who required NIV or HFOT and selected on the simplified acute physiology score II, the sequential organ failure assessment score and the Charlson Comorbidity Index score, was investigated. The primary outcome was 28-day intubation rate; secondary outcomes were end-of-treatment clinical improvement and PaO2/FiO2 ratio, laboratory abnormalities and clinical complications, ICU and hospital length of stay, 28-day and 90-day mortality. RESULTS: We included 132 patients and found that 28-day intubation rate was significantly lower among Rem-Dexa group (19.7% vs 48.5%, p<0.01). Although the end-of-treatment clinical improvement was larger among Rem-Dexa group (69.7% vs 51.5%, p = 0.05), the 28-day and 90-day mortalities were similar (4.5% and 10.6% vs. 15.2% and 16.7%; p = 0.08 and p = 0.45, respectively). The logistic regression and Cox-regression models showed that concomitant Rem-Dexa therapy was associated with a reduction of 28-day intubation rate (OR 0.22, CI95% 0.05-0.94, p = 0.04), in absence of laboratory abnormalities and clinical complications (p = ns). CONCLUSIONS: In COVID-19 critically ill patients receiving HFO or NIV, 28-day intubation rate was lower in patients who received Rem-Dexa and this finding corresponded to lower end-of-treatment clinical improvement. The individual contribution of either Remdesevir or Dexamethasone to the observed clinical effect should be further investigated.


Subject(s)
COVID-19 Drug Treatment , Noninvasive Ventilation , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Cohort Studies , Critical Illness , Dexamethasone/therapeutic use , Humans , Oxygen , Prospective Studies
5.
Respir Physiol Neurobiol ; 298: 103844, 2022 04.
Article in English | MEDLINE | ID: covidwho-1620996

ABSTRACT

BACKGROUND: Use of high positive end-expiratory pressure (PEEP) and prone positioning is common in patients with COVID-19-induced acute respiratory failure. Few data clarify the hemodynamic effects of these interventions in this specific condition. We performed a physiologic study to assess the hemodynamic effects of PEEP and prone position during COVID-19 respiratory failure. METHODS: Nine adult patients mechanically ventilated due to COVID-19 infection and fulfilling moderate-to-severe ARDS criteria were studied. Respiratory mechanics, gas exchange, cardiac output, oxygen consumption, systemic and pulmonary pressures were recorded through pulmonary arterial catheterization at PEEP of 15 and 5 cmH2O, and after prone positioning. Recruitability was assessed through the recruitment-to-inflation ratio. RESULTS: High PEEP improved PaO2/FiO2 ratio in all patients (p = 0.004), and significantly decreased pulmonary shunt fraction (p = 0.012), regardless of lung recruitability. PEEP-induced increases in PaO2/FiO2 changes were strictly correlated with shunt fraction reduction (rho=-0.82, p = 0.01). From low to high PEEP, cardiac output decreased by 18 % (p = 0.05) and central venous pressure increased by 17 % (p = 0.015). As compared to supine position with low PEEP, prone positioning significantly decreased pulmonary shunt fraction (p = 0.03), increased PaO2/FiO2 (p = 0.03) and mixed venous oxygen saturation (p = 0.016), without affecting cardiac output. PaO2/FiO2 was improved by prone position also when compared to high PEEP (p = 0.03). CONCLUSIONS: In patients with moderate-to-severe ARDS due to COVID-19, PEEP and prone position improve arterial oxygenation. Changes in cardiac output contribute to the effects of PEEP but not of prone position, which appears the most effective intervention to improve oxygenation with no hemodynamic side effects.


Subject(s)
Blood Pressure/physiology , COVID-19/physiopathology , COVID-19/therapy , Heart Rate/physiology , Outcome and Process Assessment, Health Care , Oxygen Consumption/physiology , Positive-Pressure Respiration , Prone Position , Vascular Resistance/physiology , Aged , Aged, 80 and over , Female , Hemodynamic Monitoring , Humans , Intensive Care Units , Italy , Male , Middle Aged , Prone Position/physiology
6.
Crit Care ; 25(1): 197, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1261277

ABSTRACT

BACKGROUND: Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19. METHODS: We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed. RESULTS: We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R2 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non-COVID-19 group of SA-VAP patients. CONCLUSIONS: In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.


Subject(s)
COVID-19/complications , Pneumonia, Ventilator-Associated/microbiology , Staphylococcal Infections/etiology , Staphylococcus aureus/isolation & purification , Aged , Anti-Bacterial Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Italy , Logistic Models , Lung/microbiology , Male , Middle Aged , Organ Dysfunction Scores , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/etiology , Prospective Studies , Respiration, Artificial , Staphylococcal Infections/drug therapy
7.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1241490

ABSTRACT

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 Participants: Multicenter 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 ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) 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 Measures: The 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, 13-28] vs 25 [IQR 4-28]; 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 effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
10.
Crit Care ; 24(1): 529, 2020 08 28.
Article in English | MEDLINE | ID: covidwho-733031

ABSTRACT

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.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Respiratory Distress Syndrome/physiopathology , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/therapy , Female , Humans , Intensive Care Units , Italy , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Respiratory Function Tests , Respiratory Mechanics/physiology , SARS-CoV-2
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