Lung ultrasound predicts non-invasive ventilation outcome in COVID-19 acute respiratory failure: a pilot study.

BACKGROUND: The aim of this study is to determine relationships between lung aeration assessed by lung ultrasound (LUS) with non-invasive ventilation (NIMV) outcome, intensive care unit (ICU) admission and mechanical ventilation (MV) needs in COVID-19 respiratory failure. METHODS: A cohort of adult patients with COVID-19 respiratory failure underwent LUS during initial assessment. A simplified LUS protocol consisting in scanning six areas, three for each side, was adopted. A score from 0 to 3 was assigned to each area. Comprehensive LUS score (LUSsc) was calculated as the sum of the score in all areas. LUSsc, the amount of involved sonographic lung areas (LUSq), the number of lung quadrants radiographically infiltrated and the degree of oxygenation impairment at admission (SpO2/FiO2 ratio) were compared to NIMV Outcome, MV needs and ICU admission. RESULTS: Among 85 patients prospectively included in the analysis, 49 of 61 needed MV. LUSsc and LUSq were higher in patients who required MV (median 12 [IQR 8-14] and median 6 [IQR 4-6], respectively) than in those who did not (6 [IQR 2-9] and 3 [IQR 1-5], respectively), both P<0.001. NIMV trial failed in 26 patients out 36. LUSsc and LUSq were significantly higher in patients who failed NIMV than in those who did not. From ROC analysis, LUSsc ≥12 and LUSq ≥5 gave the best cut-off values for NIMV failure prediction (AUC=0.95, 95%CI 0.83-0.99 and AUC=0.81, 95% CI 0.65-0.91, respectively). CONCLUSIONS: Our data suggest LUS as a possible tool for identifying patients who are likely to require MV and ICU admission or to fail a NIMV trial.

Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study.

BACKGROUND: A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients. METHODS: Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed. RESULTS: Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72-0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001). CONCLUSION: DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF. Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.

Tidal Volume Lowering by Instrumental Dead Space Reduction in Brain-Injured ARDS Patients: Effects on Respiratory Mechanics, Gas Exchange, and Cerebral Hemodynamics.

BACKGROUND: Limiting tidal volume (VT), plateau pressure, and driving pressure is essential during the acute respiratory distress syndrome (ARDS), but may be challenging when brain injury coexists due to the risk of hypercapnia. Because lowering dead space enhances CO2 clearance, we conducted a study to determine whether and to what extent replacing heat and moisture exchangers (HME) with heated humidifiers (HH) facilitate safe VT lowering in brain-injured patients with ARDS. METHODS: Brain-injured patients (head trauma or spontaneous cerebral hemorrhage with Glasgow Coma Scale at admission < 9) with mild and moderate ARDS received three ventilatory strategies in a sequential order during continuous paralysis: (1) HME with VT to obtain a PaCO2 within 30-35 mmHg (HME1); (2) HH with VT titrated to obtain the same PaCO2 (HH); and (3) HME1 settings resumed (HME2). Arterial blood gases, static and quasi-static respiratory mechanics, alveolar recruitment by multiple pressure-volume curves, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and mean flow velocity in the middle cerebral artery by transcranial Doppler were recorded. Dead space was measured and partitioned by volumetric capnography. RESULTS: Eighteen brain-injured patients were studied: 7 (39%) had mild and 11 (61%) had moderate ARDS. At inclusion, median [interquartile range] PaO2/FiO2 was 173 [146-213] and median PEEP was 8 cmH2O [5-9]. HH allowed to reduce VT by 120 ml [95% CI: 98-144], VT/kg predicted body weight by 1.8 ml/kg [95% CI: 1.5-2.1], plateau pressure and driving pressure by 3.7 cmH2O [2.9-4.3], without affecting PaCO2, alveolar recruitment, and oxygenation. This was permitted by lower airway (- 84 ml [95% CI: - 79 to - 89]) and total dead space (- 86 ml [95% CI: - 73 to - 98]). Sixteen patients (89%) showed driving pressure equal or lower than 14 cmH2O while on HH, as compared to 7 (39%) and 8 (44%) during HME1 and HME2 (p < 0.001). No changes in mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and middle cerebral artery mean flow velocity were documented during HH. CONCLUSION: The dead space reduction provided by HH allows to safely reduce VT without modifying PaCO2 nor cerebral perfusion. This permits to provide a wider proportion of brain-injured ARDS patients with less injurious ventilation.

Microbiologic surveillance through subglottic secretion cultures during invasive mechanical ventilation: a prospective observational study.

PURPOSE: Whether subglottic secretions (SS) culture during invasive mechanical ventilation may aid microbiological surveillance is unknown. We conducted a prospective study to assess SS cultures predictivity of endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) isolates. MATERIALS AND METHODS: 109 patients receiving mechanical ventilation for ≥48 hours underwent SS and ETA surveillance cultures twice weekly; blind BAL was performed in case of clinically suspected pneumonia. RESULTS: SS and ETA cultures were fully concordant in 170 (81%-overall accuracy) of 211 sample pairs. As compared to ETA, SS culture global sensitivity and specificity were 84% [95%CI: 77 to 91] and 74% [95%CI: 66 to 82]; negative and positive predictive values were 82% and 77%. Forty-four episodes of clinically suspected pneumonia were observed. Compared to BAL, SS culture global sensitivity and specificity were 68% [95%CI: 45 to 81] and 63% [95%CI: 44 to 82]; negative and positive predictive values were both 65%. SS sensitivity, specificity, positive and negative predictive values in anticipating BAL isolates were comparable to ETA (all p > 0.20). CONCLUSIONS: SS cultures show worthy accuracy in identifying ETA isolates, with excellent sensitivity and good negative predictivity. SS cultures may be not inferior to ETA in predicting BAL results in case of ventilator-associated pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03153241. Registered on 15 May 2017, https://clinicaltrials.gov/ct2/show/NCT03153241.

Physiological Comparison of High-Flow Nasal Cannula and Helmet Noninvasive Ventilation in Acute Hypoxemic Respiratory Failure.

Rationale: High-flow nasal cannula (HFNC) and helmet noninvasive ventilation (NIV) are used for the management of acute hypoxemic respiratory failure.Objectives: Physiological comparison of HFNC and helmet NIV in patients with hypoxemia.Methods: Fifteen patients with hypoxemia with PaO2/FiO2 < 200 mm Hg received helmet NIV (positive end-expiratory pressure ≥ 10 cm H2O, pressure support = 10-15 cm H2O) and HFNC (50 L/min) in randomized crossover order. Arterial blood gases, dyspnea, and comfort were recorded. Inspiratory effort was estimated by esophageal pressure (Pes) swings. Pes-simplified pressure-time product and transpulmonary pressure swings were measured.Measurements and Main Results: As compared with HFNC, helmet NIV increased PaO2/FiO2 (median [interquartile range]: 255 mm Hg [140-299] vs. 138 [101-172]; P = 0.001) and lowered inspiratory effort (7 cm H2O [4-11] vs. 15 [8-19]; P = 0.001) in all patients. Inspiratory effort reduction by NIV was linearly related to inspiratory effort during HFNC (r = 0.84; P < 0.001). Helmet NIV reduced respiratory rate (24 breaths/min [23-31] vs. 29 [26-32]; P = 0.027), Pes-simplified pressure-time product (93 cm H2O ⋅ s ⋅ min-1 [43-138] vs. 200 [168-335]; P = 0.001), and dyspnea (visual analog scale 3 [2-5] vs. 8 [6-9]; P = 0.002), without affecting PaCO2 (P = 0.80) and comfort (P = 0.50). In the overall cohort, transpulmonary pressure swings were not different between treatments (NIV = 18 cm H2O [14-21] vs. HFNC = 15 [8-19]; P = 0.11), but patients exhibiting lower inspiratory effort on HFNC experienced increases in transpulmonary pressure swings with helmet NIV. Higher transpulmonary pressure swings during NIV were associated with subsequent need for intubation.Conclusions: As compared with HFNC in hypoxemic respiratory failure, helmet NIV improves oxygenation, reduces dyspnea, inspiratory effort, and simplified pressure-time product, with similar transpulmonary pressure swings, PaCO2, and comfort.

Physiological effects of high-flow oxygen in tracheostomized patients.

BACKGROUND: High-flow oxygen therapy via nasal cannula (HFOTNASAL) increases airway pressure, ameliorates oxygenation and reduces work of breathing. High-flow oxygen can be delivered through tracheostomy (HFOTTRACHEAL), but its physiological effects have not been systematically described. We conducted a cross-over study to elucidate the effects of increasing flow rates of HFOTTRACHEAL on gas exchange, respiratory rate and endotracheal pressure and to compare lower airway pressure produced by HFOTNASAL and HFOTTRACHEAL. METHODS: Twenty-six tracheostomized patients underwent standard oxygen therapy through a conventional heat and moisture exchanger, and then HFOTTRACHEAL through a heated humidifier, with gas flow set at 10, 30 and 50 L/min. Each step lasted 30 min; gas flow sequence during HFOTTRACHEAL was randomized. In five patients, measurements were repeated during HFOTTRACHEAL before tracheostomy decannulation and immediately after during HFOTNASAL. In each step, arterial blood gases, respiratory rate, and tracheal pressure were measured. RESULTS: During HFOTTRACHEAL, PaO2/FiO2 ratio and tracheal expiratory pressure slightly increased proportionally to gas flow. The mean [95% confidence interval] expiratory pressure raise induced by 10-L/min increase in flow was 0.2 [0.1-0.2] cmH2O (ρ = 0.77, p < 0.001). Compared to standard oxygen, HFOTTRACHEAL limited the negative inspiratory swing in tracheal pressure; at 50 L/min, but not with other settings, HFOTTRACHEAL increased mean tracheal expiratory pressure by (mean difference [95% CI]) 0.4 [0.3-0.6] cmH2O, peak tracheal expiratory pressure by 0.4 [0.2-0.6] cmH2O, improved PaO2/FiO2 ratio by 40 [8-71] mmHg, and reduced respiratory rate by 1.9 [0.3-3.6] breaths/min without PaCO2 changes. As compared to HFOTTRACHEAL, HFOTNASAL produced higher tracheal mean and peak expiratory pressure (at 50 L/min, mean difference [95% CI]: 3 [1-5] cmH2O and 4 [1-7] cmH2O, respectively). CONCLUSIONS: As compared to standard oxygen, 50 L/min of HFOTTRACHEAL are needed to improve oxygenation, reduce respiratory rate and provide small degree of positive airway expiratory pressure, which, however, is significantly lower than the one produced by HFOTNASAL.

Patient self-inflicted lung injury: implications for acute hypoxemic respiratory failure and ARDS patients on non-invasive support.

The role of spontaneous breathing among patients with acute hypoxemic respiratory failure and ARDS is debated: while avoidance of intubation with noninvasive ventilation (NIV) or high-flow nasal cannula improves clinical outcome, treatment failure worsens mortality. Recent data suggest patient self-inflicted lung injury (P-SILI) as a possible mechanism aggravating lung damage in these patients. P-SILI is generated by intense inspiratory effort yielding: (A) swings in transpulmonary pressure (i.e. lung stress) causing the inflation of big volumes in an aerated compartment markedly reduced by the disease-induced aeration loss; (B) abnormal increases in transvascular pressure, favouring negative-pressure pulmonary edema; (C) an intra-tidal shift of gas between different lung zones, generated by different transmission of muscular force (i.e. pendelluft); (D) diaphragm injury. Experimental data suggest that not all subjects are exposed to the development of P-SILI: patients with a PaO2/FiO2 ratio below 200 mmHg may represent the most at risk population. For them, current evidence indicates that high-flow nasal cannula alone may be superior to intermittent sessions of low-PEEP NIV delivered through face mask, while continuous high-PEEP helmet NIV likely promotes treatment success and may mitigate lung injury. The optimal initial noninvasive treatment of hypoxemic respiratory failure/ARDS remains however uncertain; high-flow nasal cannula and high-PEEP helmet NIV are promising tools to enhance success of the approach, but the best balance between these techniques has yet to be identified. During noninvasive support, careful clinical monitoring remains mandatory for prompt detection of treatment failure, in order not to delay intubation and protective ventilation.

Patient-ventilator interaction with conventional and automated management of pressure support during difficult weaning from mechanical ventilation.

PURPOSE: Optimizing pressure support ventilation (PSV) can improve patient-ventilator interaction. We conducted a two-center, randomized cross-over study to determine whether automated PSV lowers asynchrony rate during difficult weaning from mechanical ventilation. METHODS: Thirty patients failing the first weaning attempt were randomly ventilated for 2 three-hour consecutive periods with: 1)PSV managed by physicians (convPSV); 2)PSV managed by Smartcare® (autoPSV). These 2 periods were applied in the afternoon and overnight, for a 12-h total study time. Two independent clinicians offline analyzed ventilator waveforms to compute asynchrony index(AI). RESULTS: AI was lower during autoPSV than during convPSV (medians[interquartile ranges] 5.1[2.6-9.5]% vs. 7.3[2.3-13.4]%, p = 0.02), without changes in the proportion of patients with AI>10%(p = 0.31). Pressure support (PS) variability was higher during autoPSV (p < 0.001), but average PS did not vary. In patients with baseline PS > 12 cmH2O (n = 15), PS and tidal volume were lower with autoPSV (12 [10-15]cmH2O vs. 15 [14-18]cmH2O,p = 0.003; 7.2[6.2-8.3]ml/Kg vs. 8.2[7.1-9.1]ml/Kg, p = 0.02) and AI reduction was driven by lower tidal volume (p = 0.03). In patients with baseline PS ≤ 12 cmH2O, AI reduction during autoPSV was mediated by increased PS variability (p = 0.04). CONCLUSION: During difficult weaning, autoPSV improves patient-ventilator interaction by lowering tidal volume and enhancing PS variability. In expert centres, however, the size effect of the intervention appears clinically small, likely because physicians themselves adequately limit PS and tidal volume.