Respiratory rate is one of the key variables that is set and monitored during mechanical ventilation. As part of increasing efforts to optimize mechanical ventilation, it is prudent to expand understanding of the potential harmful effects of not only volume and pressures but also respiratory rate. The mechanisms by which respiratory rate may become injurious during mechanical ventilation can be distinguished in two broad categories. In the first, well-recognized category, concerning both controlled and assisted ventilation, the respiratory rate per se may promote ventilator-induced lung injury, dynamic hyperinflation, ineffective efforts, and respiratory alkalosis. It may also be misinterpreted as distress delaying the weaning process. In the second category, which concerns only assisted ventilation, the respiratory rate may induce injury in a less apparent way by remaining relatively quiescent while being challenged by chemical feedback. By responding minimally to chemical feedback, respiratory rate leaves the control of V̇e almost exclusively to inspiratory effort. In such cases, when assist is high, weak inspiratory efforts promote ineffective triggering, periodic breathing, and diaphragmatic atrophy. Conversely, when assist is low, diaphragmatic efforts are intense and increase the risk for respiratory distress, asynchronies, ventilator-induced lung injury, diaphragmatic injury, and cardiovascular complications. This review thoroughly presents the multiple mechanisms by which respiratory rate may induce injury during mechanical ventilation, drawing the attention of critical care physicians to the potential injurious effects of respiratory rate insensitivity to chemical feedback during assisted ventilation.

In mechanically ventilated patients, assisted mechanical ventilation (MV) is employed early, following the acute phase of critical illness, in order to eliminate the detrimental effects of controlled MV, most notably the development of ventilator-induced diaphragmatic dysfunction. Nevertheless, the benefits of assisted MV are often counteracted by the development of patient-ventilator dyssynchrony. Patient-ventilator dyssynchrony occurs when either the initiation and/or termination of mechanical breath is not in time agreement with the initiation and termination of neural inspiration, respectively, or if the magnitude of mechanical assist does not respond to the patient's respiratory demand. As patient-ventilator dyssynchrony has been associated with several adverse effects and can adversely influence patient outcome, every effort should be made to recognize and correct this occurrence at bedside. To detect patient-ventilator dyssynchronies, the physician should assess patient comfort and carefully inspect the pressure- and flow-time waveforms, available on the ventilator screen of all modern ventilators. Modern ventilators offer several modifiable settings to improve patient-ventilator interaction. New proportional modes of ventilation are also very helpful in improving patient-ventilator interaction.

During passive mechanical ventilation, the driving pressure of the respiratory system is an important mediator of ventilator-induced lung injury. Monitoring of driving pressure during assisted ventilation, similar to controlled ventilation, could be a tool to identify patients at risk of ventilator-induced lung injury. The aim of this study was to describe driving pressure over time and to identify whether and when high driving pressure occurs in critically ill patients during assisted ventilation. Sixty-two patients fulfilling criteria for assisted ventilation were prospectively studied. Patients were included when the treating physician selected proportional assist ventilation (PAV+), a mode that estimates respiratory system compliance. In these patients, continuous recordings of all ventilator parameters were obtained for up to 72 h. Driving pressure was calculated as tidal volume-to-respiratory system compliance ratio. The distribution of driving pressure and tidal volume values over time was examined, and periods of sustained high driving pressure (≥ 15 cmH2O) and of stable compliance were identified and analyzed. The analysis included 3200 h of ventilation, consisting of 8.8 million samples. For most (95%) of the time, driving pressure was < 15 cmH2O and tidal volume < 11 mL/kg (of ideal body weight). In most patients, high driving pressure was observed for short periods of time (median 2.5 min). Prolonged periods of high driving pressure were observed in five patients (8%). During the 661 periods of stable compliance, high driving pressure combined with a tidal volume ≥ 8 mL/kg was observed only in 11 cases (1.6%) pertaining to four patients. High driving pressure occurred almost exclusively when respiratory system compliance was low, and compliance above 30 mL/cmH2O excluded the presence of high driving pressure with 90% sensitivity and specificity. In critically ill patients fulfilling criteria for assisted ventilation, and ventilated in PAV+ mode, sustained high driving pressure occurred in a small, yet not negligible number of patients. The presence of sustained high driving pressure was not associated with high tidal volume, but occurred almost exclusively when compliance was below 30 mL/cmH2O.

Proportional assist ventilation+ (PAV+) delivers airway pressure (P aw) in proportion to patient effort (P mus) by using the equation of motion of the respiratory system. PAV+ calculates automatically respiratory mechanics (elastance and resistance); the work of breathing (WOB) is estimated by the ventilator. The accuracy of P mus estimation and hence accuracy of the delivered P aw and WOB calculation have not been assessed. This study aimed at assessing the accuracy of delivered P aw and calculated WOB by PAV+ and examining the factors influencing this accuracy. Using an active lung model with different respiratory mechanics, we compared (1) the actual delivered P aw by the ventilator to the theoretical P aw as defined by the equation of motion and (2) the WOB value displayed by the ventilator to the WOB measured from a Campbell diagram. Irrespective of respiratory mechanics and gain, the ventilator provided a P aw approximately 25 % lower than expected. This underassistance was greatest at the beginning of the inspiration. Intrinsic PEEP (PEEPi), associated with an increase in trigger delay, was a major factor affecting PAV+ accuracy. The absolute value of total WOB displayed by the ventilator was underestimated, but the changes in WOB were accurately detected by the ventilator. The assistance provided by PAV+ well follows P mus but with a constant underassistance. This is associated with an underestimation by the ventilator of the WOB. PEEPi can be a major factor contributing to PAV+ inaccuracy. Clinical recommendations should include using a high trigger sensitivity and a careful PEEP titration.

Early exercise of critically ill patients may have beneficial effects on muscle strength, mass and systemic inflammation. During pressure support ventilation (PSV), a mismatch between demand and assist could increase work of breathing and limit exercise. A better exercise tolerance is possible with a proportional mode of ventilation (Proportional Assist Ventilation, PAV+ and Neurally Adjusted Ventilatory Assist, NAVA). We examined whether, in critically ill patients, PSV and proportional ventilation have different effects on respiratory muscles unloading and work efficiency during exercise. Prospective pilot randomized cross-over study performed in a medico-surgical ICU. Patients requiring mechanical ventilation >48 h were enrolled. At initiation, the patients underwent an incremental workload test on a cycloergometer to determine the maximum level capacity. The next day, 2 15-min exercise, at 60% of the maximum capacity, were performed while patients were randomly ventilated with PSV and PAV+ or NAVA. The change in oxygen consumption (ΔVO2, indirect calorimetry) and the work efficiency (ratio of ΔVO2 per mean power) were computed. Ten patients were examined, 6 ventilated with PSV/PAV+ and 4 with PSV/NAVA. Despite the same mean inspiratory pressure at baseline between the modes, baseline VO2 (median, IQR) was higher during proportional ventilation (301 ml/min, 270–342) compared to PSV (249 ml/min, 206–353). Exercise with PSV was associated with a significant increase in VO2 (ΔVO2, median, IQR) (77.6 ml/min, 59.9–96.5), while VO2 did not significantly change during exercise with proportional modes (46.3 ml/min, 5.7–63.7, p < 0.05). As a result, exercise with proportional modes was associated with a better work efficiency than with PSV. The ventilator modes did not affect patient’s dyspnea, limb fatigue, distance, hemodynamics and breathing pattern. Proportional ventilation during exercise results in higher work efficiency and less increase in VO2 compared to ventilation with PSV. These preliminary findings suggest that proportional ventilation could enhance the training effect and facilitate rehabilitation.