Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Forced vital capacity (FVC) less than 50% of predicted is one of the main parameters used for Non-Invasive Ventilation (NIV) initiation in Amyotrophic Lateral Sclerosis (ALS). Recent studies suggest that higher values of FVC could be considered as a threshold. The aim of this study is to evaluate whether early use of NIV improves the prognosis of ALS patients compared with standard initiation. METHODS: This is a randomized, parallel, multicenter, open-label, controlled clinical trial, with recruitment at the ALS outpatient multidisciplinary units of six Spanish hospitals. Patients were included when their FVC reached the 75% threshold and were randomized by computer, stratifying by center in an allocation ratio of 1:1 to Early NIV (FVC below 75%) or Standard NIV (FVC below 50%) initiation. The primary outcome was time to death or tracheostomy.Trial registration number ClinicalTrials.gov: NCT01641965. RESULTS: Between May 2012 and June 2014, 42 patients were randomized to two groups, 20 to Early NIV and 22 to Standard NIV initiation. We found differences in survival in favor of the intervention group: an incidence of mortality (2.68 [1.87-5.50] vs. 3.33 [1.34-4.80] person-months) and a median survival (25.2 vs. 19.4 months), although without reaching statistical significance (p = 0.267). CONCLUSIONS: This trial did not reach the primary endpoint of survival; nevertheless, it is the first Randomized Controlled Trial (RCT) to demonstrate the benefits of early NIV in slowing the decline of respiratory muscle strength and reducing adverse events. Although not all the results reached statistical significance, all the analyzed data favor early NIV. In addition, this study demonstrates good tolerance and compliance with early NIV without quality of sleep impairment. These data reinforce the early respiratory evaluation of ALS patients and NIV initiation with an FVC of around 75%.

Outcomes of COVID-19 Patients Admitted to the Intermediate Respiratory Care Unit: Non-Invasive Respiratory Therapy in a Sequential Protocol.

The intermediate respiratory care units (IRCUs) have a pivotal role managing escalation and de-escalation between the general wards and the intensive care units (ICUs). Since the COVID-19 pandemic began, the early detection of patients that could improve on non-invasive respiratory therapies (NRTs) in IRCUs without invasive approaches is crucial to ensure proper medical management and optimize limiting ICU resources. The aim of this study was to assess factors associated with survival, ICU admission and intubation likelihood in COVID-19 patients admitted to IRCUs. Observational retrospective study in consecutive patients admitted to the IRCU of a tertiary hospital from March 2020 to April 2021. Inclusion criteria: hypoxemic respiratory failure (SpO2 ≤ 94% and/or respiratory rate ≥ 25 rpm with FiO2 > 50% supplementary oxygen) due to acute COVID-19 infection. Demographic, comorbidities, clinical and analytical data, and medical and NRT data were collected at IRCU admission. Multivariate logistic regression models assessed factors associated with survival, ICU admission, and intubation. From 679 patients, 79 patients (12%) had an order to not do intubation. From the remaining 600 (88%), 81% survived, 41% needed ICU admission and 37% required intubation. In the IRCU, 51% required non-invasive ventilation (NIV group) and 49% did not (non-NIV group). Older age and lack of corticosteroid treatment were associated with higher mortality and intubation risk in the scheme, which could be more beneficial in severe forms. Initial NIV does not always mean worse outcomes.

Higher mortality and intubation rate in COVID-19 patients treated with noninvasive ventilation compared with high-flow oxygen or CPAP.

The effectiveness of noninvasive respiratory support in severe COVID-19 patients is still controversial. We aimed to compare the outcome of patients with COVID-19 pneumonia and hypoxemic respiratory failure treated with high-flow oxygen administered via nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV), initiated outside the intensive care unit (ICU) in 10 university hospitals in Catalonia, Spain. We recruited 367 consecutive patients aged ≥ 18 years who were treated with HFNC (155, 42.2%), CPAP (133, 36.2%) or NIV (79, 21.5%). The main outcome was intubation or death at 28 days after respiratory support initiation. After adjusting for relevant covariates and taking patients treated with HFNC as reference, treatment with NIV showed a higher risk of intubation or death (hazard ratio 2.01; 95% confidence interval 1.32-3.08), while treatment with CPAP did not show differences (0.97; 0.63-1.50). In the context of the pandemic and outside the intensive care unit setting, noninvasive ventilation for the treatment of moderate to severe hypoxemic acute respiratory failure secondary to COVID-19 resulted in higher mortality or intubation rate at 28 days than high-flow oxygen or CPAP. This finding may help physicians to choose the best noninvasive respiratory support treatment in these patients.Clinicaltrials.gov identifier: NCT04668196.

Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

OBJECTIVE: Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. METHODS: Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. RESULTS: 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. CONCLUSIONS: In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

Comparison Between Neurally Adjusted Ventilatory Assist and Pressure Support Ventilation Levels in Terms of Respiratory Effort.

OBJECTIVES: To understand the potential equivalence between neurally adjusted ventilatory assist and pressure support ventilation levels in terms of respiratory muscle unloading. To compare the respiratory pattern, variability, synchronization, and neuromuscular coupling within comparable ranges of assistance. DESIGN: Prospective single-center physiologic study. SETTING: A 13-bed university medical ICU. PATIENTS: Eleven patients recovering from respiratory failure. INTERVENTIONS: The following levels of assistance were consecutively applied in a random order: neurally adjusted ventilatory assist levels: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, and 7 cm H2O/µvolt; pressure support levels: 7, 10, 15, 20, and 25 cm H2O. MEASUREMENTS AND MAIN RESULTS: Flow, airway pressure, esophageal pressures, and peak electrical activity of the diaphragm were continuously recorded. Breathing effort was calculated. To express the percentage of assist assumed by the ventilator, the total pressure including muscular and ventilator pressure was calculated. The median percentage of assist ranged from 33% (24-47%) to 82% (72-90%) between pressure support 7 and 25 cm H2O. Similar levels of unloading were observed for neurally adjusted ventilatory assist levels from 0.5 cm H2O/µvolt (46% [40-51%]) to 2.5 cm H2O/µvolt (80% [74-84%]). Tidal variability was higher during neurally adjusted ventilatory assist and ineffective efforts appeared only in pressure support. In neurally adjusted ventilatory assist, double triggering occurred sometimes when electrical activity of the diaphragm signal depicted a biphasic aspect, and an abnormal oscillatory pattern was frequently observed from 4 cm H2O/µvolt. For both modes, the relationship between peak electrical activity of the diaphragm and muscle pressure depicted a curvilinear profile. CONCLUSIONS: In patients recovering from acute respiratory failure, levels of neurally adjusted ventilatory assist between 0.5 and 2.5 cm H2O/µvolt are comparable to pressure support levels ranging from 7 to 25 cm H2O in terms of respiratory muscle unloading. Neurally adjusted ventilatory assist provides better patient-ventilator interactions but can be sometimes excessively sensitive to electrical activity of the diaphragm in terms of triggering.

Severe but not mild hypercapnia affects the outcome in patients with severe cardiogenic pulmonary edema treated by non-invasive ventilation.

BACKGROUND: Patients with severe cardiogenic pulmonary edema (CPE) are frequently hypercapnic, possibly because of associated underlying chronic lung disease (CLD). Since hypercapnia has been associated with outcome, we aimed to identify factors associated to hypercapnia and its role on outcome of patients with CPE and no underlying CLD. METHODS: Observational cohort study using data prospectively collected over a 3-year period. After excluding patients with any CLD or obstructive sleep apneas, all patients treated by non-invasive ventilation (NIV) for severe CPE were included. Hypercapnia was defined as PaCO2 >45 mmHg and non-rapid favorable outcome was defined as the need for intubation or continuation of NIV for more than 48 h. RESULTS: After excluding 60 patients with underlying CLD or sleep apneas, 112 patients were studied. The rates of intubation and of prolonged NIV were 6.3 % (n = 7) and 21.4 % (n = 24), respectively. Half of the patients (n = 56) had hypercapnia upon admission. Hypercapnic patients were older, more frequently obese, and were more likely to have a respiratory tract infection than non-hypercapnic patients. Hypercapnia had no influence on intubation rate or the need for prolonged NIV. However, patients with severe hypercapnia (PaCO2 >60 mmHg) needed longer durations of NIV and intensive care unit (ICU) stay than the others. CONCLUSIONS: Among the patients admitted for severe CPE without CLD, half of them had hypercapnia at admission. Hypercapnic patients were older and more frequently obese but their outcome was similar compared to non-hypercapnic patients. Patients with severe hypercapnia needed longer durations of NIV than the others without increase in intubation rate.

Sleep continuity: a new metric to quantify disrupted hypnograms in non-sedated intensive care unit patients.

INTRODUCTION: Sleep in intensive care unit (ICU) patients is severely altered. In a large proportion of critically ill patients, conventional sleep electroencephalogram (EEG) patterns are replaced by atypical sleep. On the other hand, some non-sedated patients can display usual sleep EEG patterns. In the latter, sleep is highly fragmented and disrupted and conventional rules may not be optimal. We sought to determine whether sleep continuity could be a useful metric to quantify the amount of sleep with recuperative function in critically ill patients with usual sleep EEG features. METHODS: We retrospectively reanalyzed polysomnographies recorded in non-sedated critically ill patients requiring non-invasive ventilation (NIV) for acute hypercapnic respiratory failure. Using conventional rules, we built two-state hypnograms (sleep and wake) and identified all sleep episodes. The percentage of time spent in sleep bouts (<10 minutes), short naps (>10 and <30 minutes) and long naps (>30 minutes) was used to describe sleep continuity. In a first study, we compared these measures regarding good (NIV success) or poor outcome (NIV failure). In a second study performed on a different patient group, we compared these measurements during NIV and during spontaneous breathing. RESULTS: While fragmentation indices were similar in the two groups, the percentage of total sleep time spent in short naps was higher and the percentage of sleep time spent in sleep bouts was lower in patients with successful NIV. The percentage of total sleep time spent in long naps was higher and the percentage of sleep time spent in sleep bouts was lower during NIV than during spontaneous breathing; the level of reproducibility of sleep continuity measures between scorers was high. CONCLUSIONS: Sleep continuity measurements could constitute a clinically relevant and reproducible assessment of sleep disruption in non-sedated ICU patients with usual sleep EEG.

Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors.

INTRODUCTION: We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF). METHODS: This is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital. RESULTS: Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO2/FiO2 >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation. CONCLUSIONS: With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO2/FiO2 > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.

Noninvasive ventilation for acute hypercapnic respiratory failure: intubation rate in an experienced unit.

BACKGROUND: Failure of noninvasive ventilation (NIV) is common in patients with COPD admitted to the ICU for acute hypercapnic respiratory failure (AHRF). We aimed to assess the rate of NIV failure and to identify early predictors of intubation under NIV in patients admitted for AHRF of all origins in an experienced unit. METHODS: This was an observational cohort study using data prospectively collected over a 3-year period after the implementation of a nurse-driven NIV protocol in a 24-bed medical ICU of a French university hospital. RESULTS: Among 242 subjects receiving NIV for AHRF (P(aCO2) > 45 mm Hg), 67 had cardiogenic pulmonary edema (CPE), 146 had acute-on-chronic respiratory failure (AOCRF) (including 99 subjects with COPD and 47 with other chronic respiratory diseases), and 29 had non-AOCRF (mostly pneumonia). Overall, the rates of intubation and ICU mortality were respectively 15% and 5%. The intubation rates were 4% in CPE, 15% in AOCRF, and 38% in non-AOCRF (P < .001). After adjustment, non-AOCRF was independently associated with NIV failure, as well as acidosis (pH < 7.30) and severe hypoxemia (P(aO2)/F(IO2) ≤ 200 mm Hg) after 1 hour of NIV initiation, whereas altered consciousness on admission and ventilatory settings had no influence on outcome. CONCLUSIONS: With a nurse-driven NIV protocol, the intubation rate was reduced to 15% in patients receiving NIV for AHRF, with a mortality rate of only 5%. Whereas the risk of NIV failure is associated with hypoxemia and acidosis after initiation of NIV, it is also markedly influenced by the presence or absence of an underlying chronic respiratory disease.

Comparison of sleep quality with mechanical versus spontaneous ventilation during weaning of critically III tracheostomized patients.

BACKGROUND: In mechanically ventilated patients under mechanical ventilation in the ICU, ventilatory mode or settings may influence sleep quality. The aim of this study was to evaluate the direct impact of mechanical ventilation per se on sleep quantity and quality in patients who were able to tolerate separation from mechanical ventilation over prolonged periods. DESIGN AND SETTING: Randomized crossover clinical trial in a medical ICU. PATIENTS: Sixteen conscious patients, free of sedation and tracheostomized because of prolonged weaning from mechanical ventilation, were included in the study when able to tolerate at least 5 hours of spontaneous ventilation. INTERVENTIONS: Patients were randomized to receive either spontaneous ventilation or mechanical ventilation at low levels of pressure support for two crossover periods of 5-hour duration each, from 22:00 to 08:00. Polysomnography was performed throughout the study. MEASUREMENTS AND RESULTS: Total sleep time was higher during mechanical ventilation than during spontaneous ventilation (183 min vs 132 min, p = 0.04). No significant differences between mechanical ventilation and spontaneous ventilation were observed in slow wave sleep time (45 min vs 28 min), rapid eye movement sleep time (11 min vs 3 min), or the fragmentation index (25 vs 23 arousals and awakenings per hr). In four patients, however, our analysis of patient-ventilator interaction suggested that the ventilatory settings were suboptimal and could have been improved to potentially improve sleep. CONCLUSIONS: In difficult-to-wean tracheostomized patients, sleep quality was similar with or without the ventilator. Sleep quantity was higher during mechanical ventilation. Reconnection to the ventilator during the night period may favor sleep efficiency in tracheostomized patients in prolonged weaning.

Sleep in hypercapnic critical care patients under noninvasive ventilation: conventional versus dedicated ventilators.

OBJECTIVE: To compare sleep quality between two types of ventilators commonly used for noninvasive ventilation: conventional ICU ventilators and dedicated noninvasive ventilators; and to evaluate sleep during and between noninvasive ventilation sessions in critically ill patients. DESIGN: Physiological sleep study with a randomized assessment of the ventilator type. SETTING: Medical ICU in a university hospital. PATIENTS: Twenty-four patients admitted for acute hypercapnic respiratory failure requiring noninvasive ventilation. INTERVENTIONS: Patients were randomly assigned to receive noninvasive ventilation with either an ICU ventilators (n = 12) or a dedicated noninvasive ventilators (n = 12), and their sleep and respiratory parameters were recorded by polysomnography from 4 PM to 9 AM on the second, third, or fourth day after noninvasive ventilation initiation. MEASUREMENTS AND MAIN RESULTS: Sleep architecture was similar between ventilator groups, including sleep fragmentation (number of arousals and awakenings/hr), but the dedicated noninvasive ventilators group showed a higher patient-ventilator asynchrony-related fragmentation (28% [17-44] vs. 14% [7.0-22]; p = 0.02), whereas the ICU ventilators group exhibited a higher noise-related fragmentation. Ineffective efforts were more frequent in the dedicated noninvasive ventilators group than in the ICU ventilators group (34 ineffective efforts/hr of sleep [15-125] vs. two [0-13]; p < 0.01), possibly as a result of a higher tidal volume (7.2 mL/kg [6.7-8.8] vs. 5.8 [5.1-6.8]; p = 0.04). More sleep time occurred and sleep quality was better during noninvasive ventilation sessions than during spontaneous breathing periods (p < 0.05) as a result of greater slow wave and rapid eye movement sleep and lower fragmentation. CONCLUSIONS: There were no observed differences in sleep quality corresponding to the type of ventilator used despite slight differences in patient-ventilator asynchrony. Noninvasive ventilation sessions did not prevent patients from sleeping; on the contrary, they seem to aid sleep when compared with unassisted breathing.

Patient-ventilator asynchrony during noninvasive ventilation: a bench and clinical study.

BACKGROUND: Different kinds of ventilators are available to perform noninvasive ventilation (NIV) in ICUs. Which type allows the best patient-ventilator synchrony is unknown. The objective was to compare patient-ventilator synchrony during NIV between ICU, transport­both with and without the NIV algorithm engaged­and dedicated NIV ventilators. METHODS: First, a bench model simulating spontaneous breathing efforts was used to assess the respective impact of inspiratory and expiratory leaks on cycling and triggering functions in 19 ventilators. Second, a clinical study evaluated the incidence of patient-ventilator asynchronies in 15 patients during three randomized, consecutive, 20-min periods of NIV using an ICU ventilator with and without its NIV algorithm engaged and a dedicated NIV ventilator. Patient-ventilator asynchrony was assessed using flow, airway pressure, and respiratory muscles surface electromyogram recordings. RESULTS: On the bench, frequent auto-triggering and delayed cycling occurred in the presence of leaks using ICU and transport ventilators. NIV algorithms unevenly minimized these asynchronies, whereas no asynchrony was observed with the dedicated NIV ventilators in all except one. These results were reproduced during the clinical study: The asynchrony index was significantly lower with a dedicated NIV ventilator than with ICU ventilators without or with their NIV algorithm engaged (0.5% [0.4%-1.2%] vs 3.7% [1.4%-10.3%] and 2.0% [1.5%-6.6%], P < .01), especially because of less auto-triggering. CONCLUSIONS: Dedicated NIV ventilators allow better patient-ventilator synchrony than ICU and transport ventilators, even with their NIV algorithm. However, the NIV algorithm improves, at least slightly and with a wide variation among ventilators, triggering and/or cycling off synchronization.