The coupling between ventilator delivered inspiratory flow and patient's demands both in terms of timing and drive is a challenging task that has become largely feasible in recent years. This review addresses the new advances to modulate and treat patient-ventilator dyssynchrony. Patient-ventilator dyssynchrony is a common phenomenon with conventional modes of mechanical ventilation which influence the duration of mechanical ventilation. Inspection of pressure, volume and flow waveforms represents a valuable tool for the physician to recognize and take the appropriate action to improve patient-ventilator synchrony. New developments have been introduced aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off. Patient-ventilator dyssynchrony may affect patients' outcome. New modes of assisted mechanical ventilation have been introduced and represent a major step forward in modulating patient-ventilator dyssynchrony.

Background: Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis. Methods: Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured. Results: With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters differ significantly between modes. Conclusions: In patients with ALI/ARDS due to sepsis, PAV and pressure-support ventilation both have clinically comparable short-term effects on gas exchange and hemodynamics.

Patient-ventilator asynchrony refers to the uncoupling between the mechanically delivered breath and the patient's respiratory effort. It is common during assisted mechanical ventilation and may affect the morbidity of critically ill patients. Close inspection of pressure, volume and flow waveforms - displayed by modern ventilators - may help the physician to recognize and act appropriately to minimize patient-ventilator asynchrony. During the last two decades new modes of assisted mechanical ventilation have been introduced, aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off.

Mechanical stress induced by injurious ventilation leads to pro-inflammatory cytokine production and lung injury. The extracellular-signal-regulated-kinase, ERK1/2, participates in the signaling pathways activated upon mechanical stress in the lungs to promote the inflammatory response. Tumor progression locus 2 (Tpl2) is a MAP3kinase that activates ERK1/2 upon cytokine or TLR signaling, to induce pro-inflammatory cytokine production. The role of Tpl2 in lung inflammation, and specifically in the one caused by mechanical stress has not been investigated. The aim of the study was to examine if genetic or pharmacologic inhibition of Tpl2 could ameliorate ventilator-induced lung injury. Adult male wild-type and Tpl2-deficient mice were ventilated with normal or high tidal volume for 4 h. Additional wild-type mice were treated with a Tpl2 inhibitor either before or 30 min after initiation of high tidal ventilation. Non-ventilated mice of both genotypes served as controls. The development of lung injury was evaluated by measuring lung mechanics, arterial blood gases, concentrations of proteins, IL-6, and MIP-2 in bronchoalveolar lavage fluid (BALF) and by lung histology. Data were compared by Kruskal-Wallis non-parametric test and significance was defined as p < 0.05. Mechanical ventilation with normal tidal volume induced a mild increase of IL-6 in BALF in both strains. High tidal volume ventilation induced lung injury in wild-type mice, characterized by decreased lung compliance, increased concentrations of proteins, IL-6 and MIP-2 in BALF, and inflammatory cell infiltration on histology. All indices of lung injury were ameliorated in Tpl2-deficient mice. Wild-type mice treated with the Tpl2 inhibitor, either prior of after the initiation of high tidal volume ventilation were protected from the development of lung injury, as indicated by preserved lung compliance and lower BALF concentrations of proteins and IL-6, than similarly ventilated, untreated wild-type mice. Genetic and pharmacologic inhibition of Tpl2 is protective in a mouse model of ventilator-induced lung injury, ameliorating both high-permeability pulmonary edema and lung inflammation.

BACKGROUND: In mechanically ventilated patients with COPD, the response of the expiratory resistance of the respiratory system (expiratory R _RS ) to bronchodilators is virtually unknown. OBJECTIVE: To examine the effect of inhaled albuterol on expiratory R _RS , and the correlation of albuterol-induced changes in expiratory R _RS with end-inspiratory resistance and the expiratory flow-volume relationship. METHODS: We studied 10 mechanically ventilated patients with COPD exacerbation, before and 30 min after administration of albuterol. We obtained flow-volume curves during passive expiration, divided the expired volume into 5 equal volume slices, and then calculated the time constant and dynamic effective deflation compliance of the respiratory system (effective deflation C _RS ) of each slice via regression analysis of the volume-flow and post-occlusion volume-tracheal pressure relationships, respectively. For each slice we calculated expiratory R _RS as the time constant divided by the effective deflation C _RS . RESULTS: Albuterol significantly decreased the expiratory R _RS (mean expiratory R _RS 42.68 ± 17.8 cm H ₂ O/L/s vs 38.08 ± 16.1 cm H ₂ O/L/s) and increased the rate of lung emptying toward the end of expiration (mean time constant 2.51 ± 1.2 s vs 2.21 ± 1.2 s). No correlation was found between the albuterol-induced changes in expiratory R _RS and that of end-inspiratory resistance. Only at the end of expiration did albuterol-induced changes in the expiratory flow-volume relationship correlate with changes in expiratory R _RS in all patients. CONCLUSIONS: In patients with COPD, albuterol significantly decreases expiratory resistance at the end of expiration. In mechanically ventilated patients, neither inspiratory resistance nor the whole expiratory flow-volume curve may be used to evaluate the bronchodilator response of expiratory resistance.