Lara Pisani

Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.

Objectives:To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. Design:Matched cohort study with historical control. Setting:Two academic Italian ICUs. Patients:Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). Interventions:Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ⩽ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. Measurements and Main Results:Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07–0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5–31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6–57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. Conclusions:These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

Physiological changes during low and high “intensity “ noninvasive ventilation

In a physiological randomised cross-over study performed in stable hypercapnic chronic obstructive disease patients, we assessed the short-term effects of two settings of noninvasive ventilation. One setting was aimed at maximally reducing arterial carbon dioxide tension (Pa,CO2) (high-intensity (Hi) noninvasive positive pressure ventilation (NPPV)): mean±sd 27.6±2.1 cmH2O of inspiratory positive airway pressure, 4±0 cmH2O of expiratory positive airway pressure and respiratory rate of 22 breaths·min−1. The other was performed according to the usual parameters used in earlier studies (low-intensity (Li)-NPPV): 17.7±1.6 cmH2O of inspiratory positive airway pressure, 4±0 cmH2O of expiratory positive airway pressure and respiratory rate of 12 breaths·min−1. Both modes of ventilation significantly improved gas exchange compared with spontaneous breathing (SB), but to a greater extent using Hi-NPPV (Pa,CO2 59.3±7.5, 55.2±6.9 and 49.4±7.8 mmHg for SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater reduction in the pressure–time product of the diaphragm per minute from 323±149 cmH2O·s·min−1 during SB to 132±139 cmH2O·s·min−1 during Li-NPPV and 40±69 cmH2O·s·min−1 during Hi-NPPV, while in nine out of 15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked reduction in cardiac output (CO) measured noninvasively with a Finometer PRO (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV. We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in CO, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.

Spheres Derived from Lung Adenocarcinoma Pleural Effusions: Molecular Characterization and Tumor Engraftment

Malignant pleural effusions (MPEs) could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells.

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.

Oronasal mask versus helmet in acute hypercapnic respiratory failure

The choice of the interface for noninvasive ventilation (NIV) is a key factor in NIV success. We hypothesised that a new helmet specifically design to improve performance in hypercapnic patients would be clinically equivalent to a standard oronasal mask. In a multicentre, short-term, physiological, randomised trial in chronic obstructive pulmonary disease patients facing an acute hypercapnic respiratory failure episode, we compared the changes in arterial blood gases (ABGs) and tolerance score obtained using the helmet or mask, and, as secondary end-points, dyspnoea, vital signs, early NIV discontinuation and rate of intubation. 80 patients were randomly assigned to receive NIV either with the helmet (n=39) or mask (n=41), using an intensive care unit ventilator. Compared with baseline, in the first 6 h, NIV improved ABGs, dyspnoea and respiratory rate (p<0.05) in both groups. Changes in ABGs and discomfort were similar with the two groups, while dyspnoea decreased more (p<0.005) using the mask. The rate of intubation and the need for interface change during the whole period of NIV were very low and not different between groups. The new helmet may be a valid alternative to a mask in improving ABGs and achieving a good tolerance during an episode of acute hypercapnic respiratory failure. In COPD patients undergoing NIV, an oronasal mask and a helmet equally improved ABGs and tolerance score http://ow.ly/DMVIg

Noninvasive Ventilation in Critically Ill Patients

Since its first application in the late 1980s, noninvasive ventilation (NIV) has been the first-line intervention for certain forms of acute respiratory failure. NIV may be delivered through the patients mouth, nose, or both using noninvasive intermittent positive pressure ventilation or continuous positive airway pressure. When applied appropriately, NIV may reduce morbidity and mortality and may avert iatrogenic complications and infections associated with invasive mechanical ventilation. This article provides physicians and respiratory therapists with a comprehensive, practical guideline for using NIV in critical care.

Effects of Extracorporeal CO2 Removal on Inspiratory Effort and Respiratory Pattern in Patients Who Fail Weaning from Mechanical Ventilation.

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Efficacy of non-invasive mechanical ventilation in the general ward in patients with chronic obstructive pulmonary disease admitted for hypercapnic acute respiratory failure and pH < 7.35: a feasibility pilot study.

To date non‐invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a ‘protected environment’. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in‐hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward.

Neurotrophin system activation in pleural effusions

Neurotrophins (NTs) expression was assessed in malignant and non-malignant pleural effusions (inflammatory exudates and transudates). Enzyme-linked immunosorbent assay, in malignant exudates from small and non-small cell lung cancer (SCLC and NSCLC), detected nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their levels are higher as compared with inflammatory and transudative effusions. By immunoblots, in cultured cancer cells coming from malignant pleural effusions, NTs and low- and high-affinity NT receptors were detected in a percentage of SCLC and NSCLC. Proliferation assay demonstrated that BDNF significantly increased cancer cell proliferation in vitro, on the contrary, NT-3 reduced cancer cell growth rate and NGF did not modify cell growth. Moreover, NGF protects cells from death during starvation. These effects are reverted by the addition of NT receptor antagonists. Cultured cancer cells injected into the lung of immunodeficient mice generate lung tumors expressing NTs and NT receptors. These findings suggest that NTs may be able to modulate cancer cell behavior and their growth.

Different tracheotomy tube diameters influence diaphragmatic effort and indices of weanability in difficult to wean patients.

OBJECTIVE: To determine the effects of different tracheotomy tube sizes on diaphragm effort and weanability indices. METHODS: Ten tracheotomized and difficult to wean subjects were randomized to 2 T-piece trials, with different tracheotomy tube diameters: inner diameters 8 mm and 6.5 mm. Diaphragm pressure-time product per min. (PTPdi/min), lung compliance and resistance (CL and RL), breathing pattern, tension-time index of the diaphragm (TTdi), and the ratio of breathing frequency to tidal volume (f/VT) were recorded. In an in vitro model, the flow-pressure relationship was measured using the 2 tracheotomy tubes and 2 endotracheal tubes of the same diameter. RESULTS: The use of a smaller diameter resulted in an increase of PTPdi (337.63 ± 194.35 cm H2O · s/min vs 263.28 ± 156.23 cm H2O · s/min for 6.5 mm and 8 mm, respectively, P = .004) and RL (16.74 ± 8.10 cm H2O · s/min vs 11.72 ± 7.88 cm H2O · s/min, respectively, P = .008). Both weanability indices were also significantly higher using the smaller tube: f/VT 93.32 ± 20.91 vs 77.06 ± 19.26 for 6.5 mm and 8 mm, respectively, P < .02; TTdi 0.09 ± 0.052 vs 0.08 ± 0.04, respectively, P < .02. In vitro measurements confirmed that the resistances were higher with the smaller diameter and similar between the tracheotomy tubes and the endotracheal tubes of the same diameters. CONCLUSIONS: In tracheotomized difficult to wean subjects the decrease of the tracheotomy tube size was associated with an increased PTPdi, f/VT, and TTdi, that were otherwise normal, using a higher diameter. The in vitro study showed that the resistances increased similarly for tracheotomy tube and endotracheal tube, decreasing the diameter and increasing the flows.