Prefrontal cortex activation during incremental inspiratory loading in healthy participants.

We aimed to investigate whether changes in prefrontal cortex (PFC) oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) associates with inspiratory muscle effort during inspiratory threshold loading (ITL) in healthy participants. Participants performed an incremental ITL. Breathing pattern, partial pressure of end-tidal CO2 (PETCO2), mouth pressure and O2Hb and HHb over the right dorsolateral PFC, sternocleidomastoid (SCM), and diaphragm/intercostals (Dia/IC) were monitored. Fourteen healthy participants (8 men; 29 ± 5 years) completed testing. Dyspnea was higher post- than pre-ITL (5 ± 1 vs. 0 ± 1, respectively; P<0.05). PFC O2Hb increased (P < 0.001) and HHb decreased (P = 0.001) at low loads but remained stable with increasing ITL intensities. PFC total hemoglobin increased at task failure compared to rest. SCM HHb increased throughout increasing intensities. SCM and Dia/IC total hemoglobin increased in the at task failure compared to rest. PETCO2 did not change (P = 0.528). PFC is activated early during the ITL but does not show central fatigue at task failure despite greater dyspnea and an imbalance of SCM oxygen demand and delivery.

Comorbidities and Readmissions in Survivors of Acute Hypercapnic Respiratory Failure.

Chronic obstructive pulmonary disease (COPD) is defined by chronic airflow obstruction, but is presently considered as a complex, heterogeneous, and multicomponent disease in which comorbidities and extrapulmonary manifestations make important contributions to disease expression. COPD-related hospital readmission. In particular frequent intensive care unit (ICU) readmissions for exacerbations represent a major challenge and place a high burden on patient outcomes and health-related quality of life, as well as on the healthcare system.In this narrative review, we first address major and often undiagnosed comorbidities associated with COPD that could have an impact on hospital readmission after an index ICU admission for acute hypercapnic respiratory failure. Some guidance for treatment is discussed. Second, we present predictors of hospital and ICU readmission and discuss various strategies to reduce such events.There is a strong rationale to detect and treat major comorbidities early after index ICU admission for acute hypercapnic respiratory failure. It still remains unclear, however, if a comprehensive and holistic approach to comorbidities in frail patients surviving hypercapnic respiratory failure can efficiently reduce the readmission rate.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study.

BACKGROUND: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). RESULTS: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). CONCLUSIONS: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073.

Beyond the guidelines for non-invasive ventilation in acute respiratory failure: implications for practice.

Non-invasive ventilation is standard therapy in the management of both hypoxaemic and hypercapnic respiratory failure of various causes. The evidence base for its use and when and how it should be used has been reviewed in two recent guidelines. In this Series paper, we look beyond the guidelines to what is happening in everyday clinical practice in the real world, how patient selection can be refined to maximise the chances of a successful outcome, and emerging alternative therapies. Real-world application of non-invasive ventilation diverges from guideline recommendations, particularly with regard to patient selection and timing of initiation. To improve patient outcomes education programmes need to stress these issues and the effectiveness of non-invasive ventilation that is delivered needs to be monitored by regular audit.

Bench testing of a new hyperbaric chamber ventilator at different atmospheric pressures.

PURPOSE: Providing mechanical ventilation is challenging at supra-atmospheric pressure. The higher gas density increases resistance, reducing the flow delivered by the ventilator. A new hyperbaric ventilator (Siaretron IPER 1000) is said to compensate for these effects automatically. The aim of this bench test study was to validate the compensation, define its limits and provide details on the ventilator's output at varied atmospheric pressures. METHODS: Experiments were conducted inside a multiplace hyperbaric chamber at 1, 2.2, 2.8 and 4 atmospheres absolute (ATA), with the ventilator connected to a test lung. Transducers were recalibrated at each ATA level. Various ventilator settings were tested in volume and pressure control modes. Measured tidal volumes were compared with theoretical predictions based on gas laws. RESULTS: Results confirmed the ventilator's ability to provide compensation, but also identified its limits. The compensation range could be predicted and depended on the maximal flow attainable, decreasing linearly with increasing atmospheric pressure. With settings inside the range, tidal volumes approximated set values (mean error 10 ± 5 %). With settings outside the range, the volume was limited to the predicted maximal value calculated from maximal flow. A practical guide for clinicians is provided. CONCLUSION: The IPER 1000 ventilator attempted to deliver stable tidal volume by adjusting the opening of the inspiratory valve in proportion to atmospheric pressure. Adequate compensation was observed, albeit only within a predictable range, which can be reliably predicted for each setting and ATA level combination. Setting a tidal volume outside this range can result in an unwanted decrease in minute ventilation.

Effect of granulocyte colony-stimulating factor on bleomycin-induced acute lung injury and pulmonary fibrosis.

OBJECTIVE: Potentially fatal pulmonary toxicity is a dreaded complication of bleomycin. Increased use of granulocyte colony-stimulating factor in patients receiving chemotherapy has been paralleled by an increased incidence of bleomycin-induced pulmonary toxicity. We investigated whether granulocyte colony-stimulating factor (25 microg x kg(-1) x day(-1), 4 days) enhanced endotracheal bleomycin-induced (5 mg/kg) acute lung injury and fibrosis in rats. SETTING: University laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: We compared the effects of alveolar instillation of bleomycin in rats treated with either granulocyte colony-stimulating factor or saline. MEASUREMENTS AND MAIN RESULTS: Mortality was 25% with bleomycin only and 50% with bleomycin + granulocyte colony-stimulating factor. Granulocyte colony-stimulating factor increased alveolar neutrophil recruitment, pulmonary edema, and lung myeloperoxidase activity on day 4. Lung static compliance on day 15 was severely decreased with bleomycin alone and showed a further significant decrease when granulocyte colony-stimulating factor was added (controls, 3.85 +/- 0.14 mL/kPa; bleomycin, 1.44 +/- 0.06 mL/kPa; and bleomycin + granulocyte colony-stimulating factor, 0.65 +/- 0.09 mL/kPa; control vs. bleomycin, p <.0001; and bleomycin vs. bleomycin + granulocyte colony-stimulating factor, p =.0003). Lung morphology with bleomycin + granulocyte colony-stimulating factor showed, in addition to the changes observed with bleomycin alone, four patterns indicating more severe disease: honeycomb foci, pleural thickening with hyaline fibrosis, interstitial granuloma with increased number of macrophages but not neutrophils, and established interstitial fibrosis. Lidocaine, which prevents neutrophil adhesion to endothelial cells, inhibited granulocyte colony-stimulating factor-related exacerbation of acute lung injury (bronchoalveolar lavage fluid cells and pulmonary edema) and pulmonary fibrosis (lung static compliance and morphologic changes). CONCLUSIONS: Granulocyte colony-stimulating factor enhances bleomycin-induced lung toxicity by a mechanism that probably involves neutrophils.