Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory ...Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema,
hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
High-flow nasal cannula (HFNC) and helmet noninvasive ventilation (NIV) are used for the management of acute hypoxemic respiratory failure.
Physiological comparison of HFNC and helmet NIV in patients ...with hypoxemia.
Fifteen patients with hypoxemia with Pa
/Fi
< 200 mm Hg received helmet NIV (positive end-expiratory pressure ≥ 10 cm H
O, pressure support = 10-15 cm H
O) 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.
As compared with HFNC, helmet NIV increased Pa
/Fi
(median interquartile range: 255 mm Hg 140-299 vs. 138 101-172;
= 0.001) and lowered inspiratory effort (7 cm H
O 4-11 vs. 15 8-19;
= 0.001) in all patients. Inspiratory effort reduction by NIV was linearly related to inspiratory effort during HFNC (
= 0.84;
< 0.001). Helmet NIV reduced respiratory rate (24 breaths/min 23-31 vs. 29 26-32;
= 0.027), Pes-simplified pressure-time product (93 cm H
O ⋅ s ⋅ min
43-138 vs. 200 168-335;
= 0.001), and dyspnea (visual analog scale 3 2-5 vs. 8 6-9;
= 0.002), without affecting Pa
(
= 0.80) and comfort (
= 0.50). In the overall cohort, transpulmonary pressure swings were not different between treatments (NIV = 18 cm H
O 14-21 vs. HFNC = 15 8-19;
= 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.
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, Pa
, and comfort.
Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect ...of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain.
Airway closure causes lack of communication between proximal airways and alveoli, making tidal inflation start only after a critical airway opening pressure is overcome. The authors conducted a ...matched cohort study to report the existence of this phenomenon among obese patients undergoing general anesthesia.
Within the procedures of a clinical trial during gynecological surgery, obese patients underwent respiratory/lung mechanics and lung volume assessment both before and after pneumoperitoneum, in the supine and Trendelenburg positions, respectively. Among patients included in this study, those exhibiting airway closure were compared to a control group of subjects enrolled in the same trial and matched in 1:1 ratio according to body mass index.
Eleven of 50 patients (22%) showed airway closure after intubation, with a median (interquartile range) airway opening pressure of 9 cm H2O (6 to 12). With pneumoperitoneum, airway opening pressure increased up to 21 cm H2O (19 to 28) and end-expiratory lung volume remained unchanged (1,294 ml 1,154 to 1,363 vs. 1,160 ml 1,118 to 1,256, P = 0.155), because end-expiratory alveolar pressure increased consistently with airway opening pressure and counterbalanced pneumoperitoneum-induced increases in end-expiratory esophageal pressure (16 cm H2O 15 to 19 vs. 27 cm H2O 23 to 30, P = 0.005). Conversely, matched control subjects experienced a statistically significant greater reduction in end-expiratory lung volume due to pneumoperitoneum (1,113 ml 1,040 to 1,577 vs. 1,000 ml 821 to 1,061, P = 0.006). With airway closure, static/dynamic mechanics failed to measure actual lung/respiratory mechanics. When patients with airway closure underwent pressure-controlled ventilation, no tidal volume was inflated until inspiratory pressure overcame airway opening pressure.
In obese patients, complete airway closure is frequent during anesthesia and is worsened by Trendelenburg pneumoperitoneum, which increases airway opening pressure and alveolar pressure: besides preventing alveolar derecruitment, this yields misinterpretation of respiratory mechanics and generates a pressure threshold to inflate the lung that can reach high values, spreading concerns on the safety of pressure-controlled modes in this setting.
Pediatric (PARDS) and neonatal (NARDS) acute respiratory distress syndrome have different age-specific characteristics and definitions. Trials on surfactant for ARDS in children and neonates have ...been performed well before the PARDS and NARDS definitions and yielded conflicting results. This is mainly due to heterogeneity in study design reflecting historic lack of pathobiology knowledge. We reviewed the available clinical and preclinical data to create an expert consensus aiming to inform future research steps and advance the knowledge in this area. Eight trials investigated the use of surfactant for ARDS in children and ten in neonates, respectively. There were improvements in oxygenation (7/8 trials in children, 7/10 in neonates) and mortality (3/8 trials in children, 1/10 in neonates) improved. Trials were heterogeneous for patients' characteristics, surfactant type and administration strategy. Key pathobiological concepts were missed in study design. Consensus with strong agreement was reached on four statements: 1. There are sufficient preclinical and clinical data to support targeted research on surfactant therapies for PARDS and NARDS. Studies should be performed according to the currently available definitions and considering recent pathobiology knowledge. 2. PARDS and NARDS should be considered as syndromes and should be pre-clinically studied according to key characteristics, such as direct or indirect (primary or secondary) nature, clinical severity, infectious or non-infectious origin or patients' age. 3. Explanatory should be preferred over pragmatic design for future trials on PARDS and NARDS. 4. Different clinical outcomes need to be chosen for PARDS and NARDS, according to the trial phase and design, trigger type, severity class and/or surfactant treatment policy. We advocate for further well-designed preclinical and clinical studies to investigate the use of surfactant for PARDS and NARDS following these principles.
Traumatic brain injury is one of the main causes of mortality and disability worldwide. Traumatic brain injury is characterized by a primary injury directly induced by the impact, which progresses ...into a secondary injury that leads to cellular and metabolic damages, starting in the first few hours and days after primary mechanical injury. To date, traumatic brain injury is not targetable by therapies aimed at preventing and/or limiting the outcomes of secondary damage but only by palliative therapies. Nerve growth factor is a neurotrophin targeting neuronal and non-neuronal cells, potentially useful in preventing/limiting the outcomes of secondary damage in traumatic brain injury. This potential has further increased in the last two decades since the possibility of reaching neurotrophin targets in the brain through its intranasal delivery has been exploited. Indeed, molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrier and reach their therapeutic targets in the brain, with favorable kinetics, dynamics, and safety profile. In the first part of this review, we aimed to report the traumatic brain injury-induced dysfunctional mechanisms that may benefit from nerve growth factor treatment. In the second part, we then exposed the experimental evidence relating to the action of nerve growth factor (both in vitro and in vivo, after administration routes other than intranasal) on some of these mechanisms. In the last part of the work, we, therefore, discussed the few manuscripts that analyze the effects of treatment with nerve growth factor, intranasally delivered to the brain parenchyma, on the outcomes of traumatic brain injury.
The current global outbreak of COVID-19 represents a major challenge in terms of epidemiology, contagiousness, treatment, as well as clinical and radiological behavior of this disease. Radiological ...imaging plays a key role in the diagnostic process and during the monitoring of the clinical conditions especially of patients with severe symptoms. According to the preliminary data collected in our tertiary center, we have documented a peculiar behavior in patients requiring endotracheal intubation who underwent seriate chest X-rays. In fact, the radiological pattern of COVID-19 patients may worsen despite a prompt amelioration after the onset of mechanical ventilation. Thus, according to our initial evidence, we recommend to perform seriate chest X-rays in the days following the onset of mechanical ventilation even if the immediate monitoring suggests an improvement. Studies on a larger scale are necessary to fully assess the findings at chest radiographs of critical, mechanically ventilated patients and their correlation with the long-term outcome.
Abstract
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.
Lung ultrasound allows lung aeration to be assessed through dedicated lung ultrasound scores (LUS). Despite LUS have been validated using several techniques, scanty data exist about the relationships ...between LUS and compliance of the respiratory system (Crs) in restrictive respiratory failure. Aim of this study was to investigate the relationship between LUS and Crs in neonates and adults affected by acute hypoxemic restrictive respiratory failure, as well as the effect of patients' age on this relationship.
Observational, cross-sectional, international, patho-physiology, bi-center study recruiting invasively ventilated, adults and neonates with acute respiratory distress syndrome (ARDS), neonatal ARDS (NARDS) or respiratory distress syndrome (RDS) due to primary surfactant deficiency. Subjects without lung disease (NLD) and ventilated for extra-pulmonary conditions were recruited as controls. LUS, Crs and resistances (Rrs) of the respiratory system were measured within 1 h from each other.
Forty adults and fifty-six neonates were recruited. LUS was higher in ARDS, NARDS and RDS and lower in control subjects (overall p < 0.001), while Crs was lower in ARDS, NARDS and RDS and higher in control subjects (overall p < 0.001), without differences between adults and neonates. LUS and Crs were correlated in adults r = - 0.86 (95% CI - 0.93; - 0.76), p < 0.001 and neonates r = - 0.76 (95% CI - 0.85; - 0.62), p < 0.001. Correlations remained significant among subgroups with different causes of respiratory failure; LUS and Rrs were not correlated. Multivariate analyses confirmed the association between LUS and Crs both in adults B = - 2.8 (95% CI - 4.9; - 0.6), p = 0.012 and neonates B = - 0.045 (95% CI - 0.07; - 0.02), p = 0.001.
Lung aeration and compliance of the respiratory system are significantly and inversely correlated irrespective of patients' age. A restrictive respiratory failure has the same ultrasound appearance and mechanical characteristics in adults and neonates.
In randomized studies of heterogeneous patients with hypoxemic acute respiratory failure, noninvasive positive pressure ventilation (NPPV) was associated with a significant reduction in endotracheal ...intubation. The role of NPPV in patients with acute respiratory distress syndrome (ARDS) is still unclear. The objective was to investigate the application of NPPV as a first-line intervention in patients with early ARDS, describing what happens in everyday clinical practice in centers having expertise with NPPV.
Prospective, multiple-center cohort study.
Three European intensive care units having expertise with NPPV.
Between March 2002 and April 2004, 479 patients with ARDS were admitted to the intensive care units. Three hundred and thirty-two ARDS patients were already intubated, so 147 were eligible for the study.
Application of NPPV.
NPPV improved gas exchange and avoided intubation in 79 patients (54%). Avoidance of intubation was associated with less ventilator-associated pneumonia (2% vs. 20%; p < .001) and a lower intensive care unit mortality rate (6% vs. 53%; p < .001). Intubation was more likely in patients who were older (p = .02), had a higher Simplified Acute Physiology Score (SAPS) II (p < .001), or needed a higher level of positive end-expiratory pressure (p = .03) and pressure support ventilation (p = .02). Only SAPS II >34 and a Pao2/Fio2 < or =175 after 1 hr of NPPV were independently associated with NPPV failure and need for endotracheal intubation.
In expert centers, NPPV applied as first-line intervention in ARDS avoided intubation in 54% of treated patients. A SAPS II >34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure.
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