Delirium incidence and risk factors in patients undergoing non-invasive ventilation for acute respiratory failure: a multicenter observational trial.

BACKGROUND: Noninvasive ventilation (NIV) still has high failure rate when used for de novo acute respiratory failure (ARF). Delirium may impact the outcome, however data regarding its incidence, timing of occurrence and clinical predictors in this subset of patients are scarce. METHODS: Consecutive patients with de novo ARF subjected to NIV were recruited in 10 Italian Respiratory Intensive Care Units (RICUs) and Intensive Care Units (ICUs). Demographics and clinical features, including tolerance to interface and NIV setting were recorded on admission and during stay, whereas delirium onset and type was assessed by the Confusion Assessment Method for ICU (CAM-ICU)-7 scale and Richmond Agitation Sedation Scale (RASS) twice/per day up to a week. The association between clinical variables and the occurrence of delirium and its influence on NIV failure and other clinical outcomes were analyzed. RESULTS: Thirty-two out of 90 enrolled patients (36%) developed delirium over seven days upon admission; median time to onset was 48 hours (24-60). Older age (OR=2.7 [1.9-9], P=0.01), the presence of cancer OR=3.7 [2-5.4], P=0.002), sepsis (OR=1.7 [1.1-3.4], P=0.01), SOFA Score (OR=1.8 [1.1-3.1], P=0.01), low tolerance to interface (OR=3.2 [2.1-5], P=0.002), use of helmet (OR=1.9 [1.2-4.3] P=0.04), and higher PRE-DELIRIC (OR=3.5 [1.3-15], P=0.03) and BORG (OR=1.7 [1.1-4.6], P=0.02] scores were significantly associated with delirium. Delirium had high risk for NIV failure (HR=3.5 95% CI: [1.4-8.6], P=0.0002) and it significantly associated with longer RICU/ICU stay and higher mortality. CONCLUSIONS: Delirium onset in acute hypoxic patients undergoing NIV is frequent and negatively affects the outcome. Multiple related clinical factors should be addressed early on admission to prevent the delirium-related risk of NIV failure in these patients.

Effects of non-invasive respiratory supports on inspiratory effort in moderate-severe COVID-19 patients. A randomized physiological study.

RATIONALE AND OBJECTIVE: Various forms of Non-invasive respiratory support (NRS) have been used during COVID-19, to treat Hypoxemic Acute Respiratory Failure (HARF), but it has been suggested that the occurrence of strenuous inspiratory efforts may cause Self Induced Lung Injury(P-SILI). The aim of this investigation was to record esophageal pressure, when starting NRS application, so as to better understand the potential risk of the patients in terms of P-SILI and ventilator induced lung injury (VILI). METHODS AND MEASUREMENTS: 21 patients with early de-novo respiratory failure due to COVID-19, underwent three 30 min trials applied in random order: high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and non-invasive ventilation (NIV). After each trial, standard oxygen therapy was reinstituted using a Venturi mask (VM). 15 patients accepted a nasogastric tube placement. Esophageal Pressure (ΔPes) and dynamic transpulmonary driving pressure (ΔPLDyn), together with the breathing pattern using a bioelectrical impedance monitor were recorded. Arterial blood gases were collected in all patients. MAIN RESULTS: No statistically significant differences in breathing pattern and PaCO2 were found. PaO2/FiO2 ratio improved significantly during NIV and CPAP vs VM. NIV was the only NRS to reduce significantly ΔPes vs. VM (-10,2 ±5 cmH20 vs -3,9 ±3,4). No differences were found in ΔPLDyn between NRS (10,2±5; 9,9±3,8; 7,6±4,3; 8,8±3,6 during VM, HFNC, CPAP and NIV respectively). Minute ventilation (Ve) was directly dependent on the patient's inspiratory effort, irrespective of the NRS applied. 14% of patients were intubated, none of them showing a reduction in ΔPes during NRS. CONCLUSIONS: In the early phase of HARF due to COVID-19, the inspiratory effort may not be markedly elevated and the application of NIV and CPAP ameliorates oxygenation vs VM. NIV was superior in reducing ΔPes, maintaining ΔPLDyn within a range of potential safety.

Early awake proning in critical and severe COVID-19 patients undergoing noninvasive respiratory support: A retrospective multicenter cohort study.

BACKGROUND/MATERIALS AND METHODS: This retrospective cohort study was conducted in two teaching hospitals over a 3-month period (March 2010-June 2020) comparing severe and critical COVID-19 patients admitted to Respiratory Intensive Care Unit for non-invasive respiratory support (NRS) and subjected to awake prone position (PP) with those receiving standard care (SC). Primary outcome was endotracheal intubation (ETI) rate. In-hospital mortality, time to ETI, tracheostomy, length of RICU and hospital stay served as secondary outcomes. Risk factors associated to ETI among PP patients were also investigated. RESULTS: A total of 114 patients were included, 76 in the SC and 38 in the PP group. Unadjusted Kaplan-Meier estimates showed greater effect of PP compared to SC on ETI rate (HR = 0.45 95% CI [0.2-0.9], p = 0.02) even after adjustment for baseline confounders (HR = 0.59 95% CI [0.3-0.94], p = 0.03). After stratification according to non-invasive respiratory support, PP showed greater significant benefit for those on High Flow Nasal Cannulae (HR = 0.34 95% CI [0.12-0.84], p = 0.04). Compared to SC, PP patients also showed a favorable difference in terms of days free from respiratory support, length of RICU and hospital stay while mortality and tracheostomy rate were not significantly different. CONCLUSIONS: Prone positioning in awake and spontaneously breathing Covid-19 patients is feasible and associated with a reduction of intubation rate, especially in those patients undergoing HFNC. Although our results are intriguing, further randomized controlled trials are needed to answer all the open questions remaining pending about the real efficacy of PP in this setting.

High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial.

BACKGROUND: The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. METHODS: We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. RESULTS: Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. CONCLUSIONS: HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. TRIAL REGISTRATION: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study.

BACKGROUND: Persistent hypercapnia after COPD exacerbation is associated with excess mortality and early rehospitalization. High Flow Nasal cannula (HFNC), may be theoretically an alternative to long-term noninvasive ventilation (NIV), since physiological studies have shown a reduction in PaCO2 level after few hours of treatment. In this clinical study we assessed the acceptability of HFNC and its effectiveness in reducing the level of PaCO2 in patients recovering from an Acute Hypercapnic Respiratory Failure (AHRF) episode. We also hypothesized that the response in CO2 clearance is dependent on baseline level of hypercapnia. METHODS: Fifty COPD patients recovering from an acute exacerbation and with persistent hypercapnia, despite having attained a stable pH (i.e. pH > 7,35 and PaCO2 > 45 mmHg on 3 consecutive measurements), were enrolled and treated with HFNC for at least 8 h/day and during the nighttime RESULTS: HFNC was well tolerated with a global tolerance score of 4.0 ± 0.9. When patients were separated into groups with or without COPD/OSA overlap syndrome, the "pure" COPD patients showed a statistically significant response in terms of PaCO2 decrease (p = 0.044). In addition, the subset of patients with a lower pH at enrolment were those who responded best in terms of CO2 clearance (score test for trend of odds, p = 0.0038). CONCLUSIONS: HFNC is able to significantly decrease the level of PaCO2 after 72 h only in "pure" COPD patients, recovering from AHRF. No effects in terms of CO2 reduction were found in those with overlap syndrome. The present findings will help guide selection of the best target population and allow a sample size calculation for future long-term randomized control trials of HFNC vs NIV. TRIAL REGISTRATION: This study is registered with www. clinicaltrials.gov with identifier number NCT03759457.

High-flow nasal therapy versus noninvasive ventilation in COPD patients with mild-to-moderate hypercapnic acute respiratory failure: study protocol for a noninferiority randomized clinical trial.

BACKGROUND: Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis. METHODS: We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3-5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a ß error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group). DISCUSSION: HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03370666 . Registered on December 12, 2017.

High-Flow Oxygen Therapy After Noninvasive Ventilation Interruption in Patients Recovering From Hypercapnic Acute Respiratory Failure: A Physiological Crossover Trial.

OBJECTIVES: Assessing gas exchange, diaphragm function, respiratory rate, and patient comfort during high-flow oxygen therapy and standard oxygen at the time of noninvasive ventilation discontinuation. DESIGN: Randomized crossover physiologic study. SETTING: Two ICUs. PATIENTS: Thirty chronic obstructive pulmonary disease patients with hypercapnic acute respiratory failure receiving noninvasive ventilation greater than 24 hours. INTERVENTIONS: All patients underwent five 30-minute trials, the first, third, and fifth trial in noninvasive ventilation, whereas the second and fourth were randomly conducted with either standard oxygen and high-flow oxygen therapy. MEASUREMENTS AND MAIN RESULTS: Diaphragm displacement and thickening fraction were determined by sonographic evaluation at the end of each trial. Arterial blood gases, respiratory rate, and patient comfort were also assessed. PaCO2 (p = 0.153) and pH (p = 0.114) were not different among trials, while PaO2 was greater in noninvasive ventilation than with both standard oxygen (p ≤ 0.005) and high-flow oxygen therapy (p ≤ 0.001). The diaphragm displacement was no different among trials (p = 0.875), while its thickening fraction was greater with standard oxygen, compared with high-flow oxygen therapy and all noninvasive ventilation trials (p < 0.001 for all comparisons), without differences between high-flow oxygen therapy and noninvasive ventilation. Respiratory rate also increased with standard oxygen, compared with both high-flow oxygen therapy (p < 0.001) and noninvasive ventilation (p < 0.01). High-flow oxygen therapy improved comfort, compared with standard oxygen (p = 0.004) and noninvasive ventilation (p < 0.001). CONCLUSIONS: At the time of noninvasive ventilation interruption, PaCO2 and diaphragm displacement remained unchanged regardless of the modality of oxygen administration. However, although standard oxygen resulted in a remarkable increase in diaphragm thickening fraction, high-flow oxygen therapy allowed maintaining it unchanged, while improving patient comfort.

Benefits of non-invasive ventilation in acute hypercapnic respiratory failure.

Non-invasive ventilation (NIV) with bilevel positive airway pressure is a non-invasive technique, which refers to the provision of ventilatory support through the patient's upper airway using a mask or similar device. This technique is successful in correcting hypoventilation. It has become widely accepted as the standard treatment for patients with hypercapnic respiratory failure (HRF). Since the 1980s, NIV has been used in intensive care units and, after initial anecdotal reports and larger series, a number of randomized trials have been conducted. Data from these trials have shown that NIV is a valuable treatment for HRF. This review aims to explore the principal areas in which NIV can be useful, focusing particularly on patients with acute HRF (AHRF). We will update the evidence base with the goal of supporting clinical practice. We provide a practical description of the main indications for NIV in AHRF and identify the group of patients with hypercapnic failure who will benefit most from the application of NIV.

Magnetic Stimulation Therapy in Patients with COPD: A Systematic Review.

Magnetotherapy (MT) is a therapeutic treatment based on the use of magnetic fields (MF) that can have an anti-inflammatory and analgesic effect. MT represents a possible treatment or an ancillary therapeutic intervention for a wide range of diseases and it is often used in the field of physiotherapeutic practices. A crucial point in the treatment of chronic obstructive pulmonary disease (COPD) patients, to counteract muscular depletion and respiratory symptoms, is represented by physiotherapy. Nevertheless, the knowledge about the application of MF as a therapeutic option in COPD patients is very limited. The purpose of the present study was to define what is currently known about the use of MF in patients with COPD. A systematic review of the literature was conducted during the month of October 2017, searching three main databases. Only those citations providing detailed informations about the use of MF to treat COPD symptoms either during an acute or a chronic phase of the disease, were selected. Following the selection process three articles were included in the final analysis. The present review focused on a total of thirty-six patients with COPD, and on the effects of the application of MF. In the majority of cases, the treatment sessions with MF were carried-out in an outpatient setting, and they differed with regard to the duration; frequency of application; dosage; intensity of the applied MF. Basing on the available informations, it seems that MF is a feasible, well tolerated, safe therapeutic option, for the treatment of motor-related COPD symptoms.

Intensive care unit patients with lower respiratory tract nosocomial infections: the ENIRRIs project.

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.

Change in pulmonary mechanics and the effect on breathing pattern of high flow oxygen therapy in stable hypercapnic COPD.

: We studied the effects of high flow oxygen therapy (HFOT) versus non-invasive ventilation (NIV) on inspiratory effort, as assessed by measuring transdiaphragmatic pressure, breathing pattern and gas exchange. Fourteen patients with hypercapnic COPD underwent five 30-min trials: HFOT at two flow rates, both with open and closed mouth, and NIV, applied in random order. After each trial standard oxygen therapy was reinstituted for 10 min. Compared with baseline, HFOT and NIV significantly improved breathing pattern, although to different extents, and reduced inspiratory effort; however, arterial carbon dioxide oxygen tension decreased but not significantly. These results indicate a possible role for HFOT in the long-term management of patients with stable hypercapnic COPD. TRIAL REGISTRATION NUMBER: NCT02363920.

Noninvasive ventilation versus oxygen therapy for the treatment of acute respiratory failure.

INTRODUCTION: There is an ongoing discussion on whether oxygen therapy or noninvasive ventilation (NIV) should be used in patient with acute respiratory failure. While respiratory acidosis, especially in case of COPD exacerbation, is a clear indication for NIV, data available in patients with acute hypoxemic respiratory failure (AHRF) are ambiguous. In addition, recently the use of nasal high flow (NHF) has been increased. Despite that NHF has been studied as an alternative to NIV, the clinical advantages of NHF need to be confirmed. AREAS COVERED: The purpose of this review is to enhance our understanding about the management of AHRF in specific settings, focusing on recent papers in which NIV and standard oxygen or NHF have been compared. Expert commentary: The choice of the most appropriate strategy for AHRF treatment should be made based upon patient's clinical status, underlying diseases, level of required respiratory support and patient's tolerance and comfort.