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Reverse triggering dyssynchrony is a frequent phenomenon recently recognized in sedated critically ill patients under controlled ventilation. It occurs in at least 30 to 55% of these patients and often occurs in the transition from fully passive to assisted mechanical ventilation. During reverse triggering, patient´s inspiratory efforts start after the passive insufflation by mechanical breaths. The most often referred mechanism is the entrainment of the patient´s intrinsic respiratory rhythm from the brainstem respiratory centers to periodic mechanical insufflations from the ventilator. However, reverse triggering might also occur because of local reflexes without involving the respiratory rhythm generator in the brainstem. Reverse triggering is observed during the acute phase of the disease, when patients may be susceptible to potential deleterious consequences of injurious or asynchronous efforts. Diagnosing reverse triggering might be challenging and can easily be missed. Inspection of ventilator waveforms or more sophisticated methods such as electrical activity of the diaphragm or esophageal pressure can be used for diagnosis. The occurrence of reverse triggering might have clinical consequences. Based on physiological data, reverse triggering might be beneficial or injurious for the diaphragm and the lung depending on the magnitude of the inspiratory effort. Reverse triggering can cause breath-stacking and loss of protective lung ventilation when triggering a second cycle. Little is known about how to manage patients with reverse triggering; however, available evidence can guide management based on physiological principles.

Rationale: The physiological basis of lung protection and the impact of positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. Obj...

Rationale: Asymmetrical lung injury is a frequent clinical presentation. Regional distribution of Vt and positive end-expiratory pressure (PEEP) could result in hyperinflation of the less-injured l...

Rationale: Diaphragm function is a key determinant of dyspnea in chronic obstructive pulmonary disease (COPD); however, it is rarely assessed in clinical practice. Lung hyperinflation can also impa...

Rationale: Monitoring and controlling respiratory drive and effort may help to minimize lung and diaphragm injury. Airway occlusion pressure (P0.1) is a noninvasive measure of respiratory drive.Obj...

Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of the acute respiratory distress syndrome. Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a post-hoc analysis of that trial, a meta-analysis, and a large, international, multicenter observational study, all suggest that extracorporeal life support, when combined with lower tidal volumes and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of the acute respiratory distress syndrome. These findings raise important questions not only about the optimal ventilator strategies for patients receiving extracorporeal support, but how various mechanisms of lung injury in the acute respiratory distress syndrome may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.

Rationale: Abnormal patterns of sleep and wakefulness exist in mechanically ventilated patients.Objectives: In this study (SLEEWE [Effect of Sleep Disruption on the Outcome of Weaning from Mechanic...

Rationale: End-tidal CO2 (EtCO2) is used to monitor cardiopulmonary resuscitation (CPR), but it can be affected by intrathoracic airway closure. Chest compressions induce oscillations in expired CO...

Rationale: Respiratory muscle weakness is common in critically ill patients; the role of targeted inspiratory muscle training (IMT) in intensive care unit rehabilitation strategies remains poorly defined. Objectives: The primary objective of the present study was to describe the range and tolerability of published methods for IMT. The secondary objectives were to determine whether IMT improves respiratory muscle strength and clinical outcomes in critically ill patients. Methods: We conducted a systematic review to identify randomized and nonrandomized studies of physical rehabilitation interventions intended to strengthen the respiratory muscles in critically ill adults. We searched the MEDLINE, Embase, HealthSTAR, CINAHL, and CENTRAL databases (inception to September Week 3, 2017) and conference proceedings (2012 to 2017). Data were independently extracted by two authors and collected on a standardized report form. Results: A total of 28 studies (N = 1,185 patients) were included. IMT was initiated during early mechanical ventilation (8 studies), after patients proved difficult to wean (14 studies), or after extubation (3 studies), and 3 other studies did not report exact timing. Threshold loading was the most common technique; 13 studies employed strength training regimens, 11 studies employed endurance training regimens, and 4 could not be classified. IMT was feasible, and there were few adverse events during IMT sessions (nine studies; median, 0%; interquartile range, 0–0%). In randomized trials (n = 20), IMT improved maximal inspiratory pressure compared with control (15 trials; mean increase, 6 cm H(2)O; 95% confidence interval [CI], 5–8 cm H(2)O; pooled relative ratio of means, 1.19; 95% CI, 1.14–1.25) and maximal expiratory pressure (4 trials; mean increase, 9 cm H(2)O; 95% CI, 5–14 cm H(2)O). IMT was associated with a shorter duration of ventilation (nine trials; mean difference, 4.1 d; 95% CI, 0.8–7.4 d) and a shorter duration of weaning (eight trials; mean difference, 2.3 d; 95% CI, 0.7–4.0 d), but confidence in these pooled estimates was low owing to methodological limitations, including substantial statistical and methodological heterogeneity. Conclusions: Most studies of IMT in critically ill patients have employed inspiratory threshold loading. IMT is feasible and well tolerated in critically ill patients and improves both inspiratory and expiratory muscle strength. The impact of IMT on clinical outcomes requires future confirmation.

Rationale: Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ventilation is unknown.Objectives: To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation.Methods: Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity.Measurements and Main Results: Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median Day 4 (interquartile range, 3–5). Developme...

Acute respiratory distress syndrome is a multifactorial lung injury that continues to be associated with high levels of morbidity and mortality. Mechanical ventilation, although lifesaving, is associated with new iatrogenic injury. Current best practice involves the use of small Vt, low plateau and driving pressures, and high levels of positive end-expiratory pressure. Collectively, these interventions are termed "lung-protective ventilation." Recent investigations suggest that individualized measurements of pulmonary mechanical variables rather than population-based ventilation prescriptions may be used to set the ventilator with the potential to improve outcomes beyond those achieved with standard lung protective ventilation. This review outlines the measurement and application of clinically applicable pulmonary mechanical concepts, such as plateau pressures, driving pressure, transpulmonary pressures, stress index, and measurement of strain. In addition, the concept of the "baby lung" and the utility of dynamic in addition to static measures of pulmonary mechanical variables are discussed.

No methodical assessment of the lung, cardiac, and sleep function of patients surviving an acute hypercapnic respiratory failure episode requiring admission to the intensive care unit (ICU) has been reported in the literature.To prospectively investigate the prevalence and impact of comorbidities in patients treated by mechanical ventilator support (invasive or noninvasive) for acute hypercapnic respiratory failure in the ICU.Seventy-eight consecutive patients admitted for an episode of acute hypercapnic respiratory failure underwent an assessment of lung, cardiac, and sleep function by pulmonary function tests, transthoracic echocardiography, and polysomnography 3 months after ICU discharge.Sixty-seven percent (52 of 78) of patients exhibited chronic obstructive pulmonary disease (COPD), although only 19 had been previously diagnosed. Patients without COPD were primarily obese. Prevalence of severe obstructive sleep apnea was 51% (95% confidence interval, 34-69) in patients with COPD and 81% (95% confidence interval, 54-96) in patients without COPD. Previously undiagnosed cardiac dysfunction with preserved ejection fraction was highly prevalent (44%), as was hypertension (67%). More than half of the population demonstrated at least three major comorbidities known to precipitate acute hypercapnic respiratory failure. Multimorbidity was associated with longer time to hospital discharge. Hospital readmission or death occurred in 46% of patients over an average of 3.5 months after discharge.Severe hypercapnic respiratory failure requiring ICU admission resulted primarily from COPD or obesity. Major comorbidities are highly prevalent in both cases and most often ignored. Surviving acute hypercapnic respiratory failure should be an opportunity to systematically evaluate lung, heart, and sleep functions to improve poor outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 02111876).

Contains fulltext : 176006.pdf (Publisher’s version ) (Closed access) RATIONALE: Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes. OBJECTIVES: To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support. METHODS: In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured. MEASUREMENTS AND MAIN RESULTS: Rocuronium titration resulted in significant declines of Vt (mean +/- SEM, 9.3 +/- 0.6 to 5.6 +/- 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 +/- 2.5 to 10.7 +/- 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 +/- 2.3 to 4.5 +/- 0.7 muV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 +/- 0.02 to 7.35 +/- 0.02; P < 0.0001), and mean arterial blood pressure increased (84 +/- 6 to 99 +/- 6 mm Hg; P = 0.0004), as did heart rate (83 +/- 7 to 93 +/- 8 beats/min; P = 0.0004). CONCLUSIONS: Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.

During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O, but its impact on clinical outcomes remains unknown. To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations. This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with Pa ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, Pa ≤ 50 mm Hg, and oxygen saturation (arterial [Sa] or measured by pulse oximetry [Sp]) ≤ 90%. A 6-month follow-up was performed. The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, Pa, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality. Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).

Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design.To stratify patients for post-ICU disability and recovery to 1 year after critical illness.We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling.The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year.ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

Improved ventilation strategies have been the mainstay for reducing mortality in acute respiratory distress syndrome. Their unique clinical effectiveness is, however, unmatched by our understanding of the underlying mechanobiology, and their impact on alveolar dynamics and gas exchange remains largely speculative.To assess changes in alveolar dynamics and associated effects on local gas exchange in experimental models of acute lung injury (ALI) and their responsiveness to sighs.Alveolar dynamics and local gas exchange were studied in vivo by darkfield microscopy and multispectral oximetry in experimental murine models of ALI induced by hydrochloric acid, Tween instillation, or in antibody-mediated transfusion-related ALI.Independent of injury mode, ALI resulted in asynchronous alveolar ventilation characteristic of alveolar pendelluft, which either spontaneously resolved or progressed to a complete cessation or even inversion of alveolar ventilation. The functional relevance of the latter phenomena was evident as impaired blood oxygenation in juxtaposed lung capillaries. Individual sighs (2 × 10 s at inspiratory plateau pressure of 30 cm H2O) largely restored normal alveolar dynamics and gas exchange in acid-induced ALI, yet not in Tween-induced surfactant depletion.We describe for the first time in detail the different forms and temporal sequence of impaired alveolar dynamics in the acutely injured lung and report the first direct visualization of alveolar pendelluft. Moreover, we identify individual sighs as an effective strategy to restore intact alveolar ventilation by a mechanism independent of alveolar collapse and reopening.

Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown.To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon.In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound.Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison).Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and...

In mechanically ventilated patients, the effect of draining pleural effusion on oxygenation is controversial. We investigated the effect of large pleural effusion drainage on oxygenation, respiratory function (including lung volumes), and hemodynamics in mechanically ventilated patients after ultrasound-guided drainage. Arterial blood gases, respiratory mechanics (airway, pleural and transpulmonary pressures, end-expiratory lung volume, respiratory system compliance and resistance), and hemodynamics (blood pressure, heart rate, and cardiac output) were recorded before and at 3 and 24 hours (H24) after pleural drainage. The respiratory settings were kept identical during the study period.The mean volume of effusion drained was 1,579 ± 684 ml at H24. Uncomplicated pneumothorax occurred in two patients. Respiratory mechanics significantly improved after drainage, with a decrease in plateau pressure and a large increase in end-expiratory transpulmonary pressure. Respiratory system compliance, end-expiratory lung volume, and PaO2/FiO2 ratio all improved. Hemodynamics were not influenced by drainage. Improvement in the PaO2/FiO2 ratio from baseline to H24 was positively correlated with the increase in end-expiratory lung volume during the same time frame (r = 0.52, P = 0.033), but not with drained volume. A high value of pleural pressure or a highly negative transpulmonary pressure at baseline predicted limited lung expansion following effusion drainage. A lesser improvement in oxygenation occurred in patients with ARDS.Drainage of large (≥500 ml) pleural effusion in mechanically ventilated patients improves oxygenation and end-expiratory lung volume. Oxygenation improvement correlated with an increase in lung volume and a decrease in transpulmonary pressure, but was less so in patients with ARDS.

The day of extubation is a critical time during an intensive care unit (ICU) stay. Extubation is usually decided after a weaning readiness test involving spontaneous breathing on a T-piece or low levels of ventilatory assist. Extubation failure occurs in 10 to 20% of patients and is associated with extremely poor outcomes, including high mortality rates of 25 to 50%. There is some evidence that extubation failure can directly worsen patient outcomes independently of underlying illness severity. Understanding the pathophysiology of weaning tests is essential given their central role in extubation decisions, yet few studies have investigated this point. Because extubation failure is relatively uncommon, randomized controlled trials on weaning are underpowered to address this issue. Moreover, most studies evaluated patients at low risk for extubation failure, whose reintubation rates were about 10 to 15%, whereas several studies identified high-risk patients with extubation failure rates exceeding 25 or 30%. Strategies for identifying patients at high risk for extubation failure are essential to improve the management of weaning and extubation. Two preventive measures may prove beneficial, although their exact role needs confirmation: one is noninvasive ventilation after extubation in high-risk or hypercapnic patients, and the other is steroid administration several hours before extubation. These measures might help to prevent postextubation respiratory distress in selected patient subgroups.