The current study examines the incidence and consequences of PVA in medical, surgical, and medical-surgical patients managed across a number of general and subspecialty ICUs staffed by providers of varying background (internal medicine/Pulm CC, anesthesia, surgery). The main findings include: (1) Overall, PVA was common. Double triggering was most prevalent, followed by flow starvation; (2) Risk factors for the development of PVA – and double triggering specifically – include a history of smoking, sepsis, pneumonia, or ARDS as etiology of respiratory failure. PC ventilation was associated with a lower overall incidence of PVA, double triggering, and flow starvation compared to VC; (3) Double triggering, flow starvation, and the total number of PVA per patient were associated with worse outcome and fewer hospital-free days.
In our study, the overall prevalence of PVA in adult, critically ill patients over their entire course of mechanical ventilation was 24%. The most prevalent PVA was double triggering, followed by flow starvation. This finding is, to some extent, consistent with previous studies reporting that double triggering occurs in most mechanically ventilated patients (11, 13, 15, 33). However, others have shown that the incidence of PVA varies widely with the most common being ineffective effort (1, 2, 4, 5, 7). This may be explained by differences in study population (e.g., COPD, trauma, medical or surgical patients), observation time (e.g., 1-10min, 30 min, or one day), detection method (e.g., clinical assessment, waveform continuously monitored, detection of esophageal pressure and electrical activity of the diaphragm), and ventilator settings (1, 2, 4, 5, 7).
PVA can occur throughout the course of mechanical ventilation and varies widely over time (15, 33). In a recent proof of concept study, Marchuk et al (34) developed a Hidden Markov model to predict the time course of PVA and inferred the probability that the number of PVA events would be above a given threshold, based on discrete time-series data in 51 mechanically ventilated patients. Here we report the cumulative incidence of PVA, identifying the first 12 days after mechanical ventilation initiation as a critical period over which the risk for development of any PVA event increases. The first 5 days appear to be a critical time with a high likelihood of developing double triggering; Over the first 8 days, flow starvation. This finding may suggest that critically ill, mechanically ventilated patients could benefit from closer monitoring of those with a higher risk of PVA over this time period, to enable early identification and intervention upon PVA to improve patient-ventilator interaction.
Factors associated with overall PVA
Patient factors may predict PVA. A history of smoking, cirrhosis, and pneumonia/sepsis/ARDS as etiology of respiratory failure, as opposed to a post-surgery status, were positively associated with overall PVA events. Conversely, heart disease was negatively associated with overall PVA. Several studies reported that COPD, ARDS, and greater severity of illness favor the occurrence of PVA (3, 11, 33). In PC ventilation, higher inspiratory pressure (>12 cmH20 above PEEP), and in VC-SIMV mode, higher inspiratory flow were associated with a higher risk of PVA, while higher PEEP levels were associated with lower risk. During VC ventilation, no association was observed between ventilator settings and overall PVA event. Robinson et al (24) found ventilator asynchrony was more common in SIMV with set breathing frequencies of > 10 breaths/min in trauma patients. Similar to the previous studies (30, 35, 36), the use of PC ventilation was associated with better patient-ventilator interaction than VC ventilation, but requires careful monitoring to avoid delivery of larger than targeted volumes.
Factors associated with double triggering and flow starvation
Double triggering occurs when there is a mismatch between set tidal volume or inspiratory time and patient’s ventilatory demand (16, 29, 31 37). Risk factors include a history of smoking, chronic kidney disease, and pneumonia/sepsis/ARDS, while chronic heart disease and immunosuppression had a reduced risk of double triggering. We speculate that kidney disease may cause acidosis, resulting in increased central respiratory drive. Pulmonary function impairment might be more severe in patients with pneumonia/sepsis/ARDS than those patients intubated in the postoperative period, and this may lead to high ventilatory demand.
Flow starvation occurs when ventilator flow rate is less than patient demand. Our results demonstrate a positive correlation between cirrhosis and ideal body weight with flow starvation. We speculate that patients with greater ideal body weight may need higher flow and that cirrhosis might cause increased ventilatory demand or neural drive through liver-lung cross talk.
We confirm previous reports (12, 30, 35, 36) that VC ventilation is associated with more frequent double triggering and flow mismatch events, perhaps due to inadequate tidal volume or flow as a result of strict limitation by operators. However, de Haro et al found a higher percentage of double cycling occurred in PCV than in VCV with constant flow or decelerated flow (33). A plausible explanation for this discrepancy could be related to differences in study population and ventilator settings. We did not analyze the influence of the ventilator mode-specific settings on the occurrence of double triggering and flow mismatch due to the limited number of events.
Outcome
In accordance with previous studies (12, 15, 17, 38), patients in our cohort who developed PVA had worse outcomes. Patients with greater overall PVA were associated with fewer ventilator-free days (longer duration of mechanical ventilation), longer ICU and hospital stay, and higher ICU and hospital mortality than those without. Overall PVA independently predicted shorter hospital-free days at day 28. After adjusting for a history of smoking, heart disease, reasons for mechanical ventilation, and initial ventilation mode, no association was observed between overall PVA and hospital mortality at day 28.
However, examining PVA in trauma patients (24) or in the early phase of weaning (38), with a short observation showed that asynchrony index (number of PVA events/total respiratory rate ×100) > 10 % was not associated with adverse clinical outcome. Additionally, Colomb et al(18) found that only clusters of ineffective triggering were correlated with a worse outcome. These discrepancies may be attributed to differences in patient population, the timing and duration of observation, and/or the definition of asynchrony employed.
Our study examined the relationships of double triggering, flow starvation, and patient outcome. Both were associated with worse outcomes. As expected, the total delivered volume during double triggering events was much larger than the set/targeted tidal volume, often double or more a normal breath (30, 33), which could lead to overinflation. Stronger spontaneous inspiratory effort during flow starvation can cause harmful transpulmonary pressure swings, which might lead to occult pendelluft and consequent regional lung overdistension (39, 40). Those mechanisms might cause ventilator induced lung injury and worsen outcomes (40). Our study reinforced the association of PVA with a poorer prognosis, but whether the relationship between PVA and outcome is causative or associative requires further investigation.
Strength
To our knowledge, this is the first and largest study to systemically investigate the incidence of overall and specific types of PVA, their risks, and associated outcomes among a heterogeneous population of ICU patients in a large, academic institution, where well trained RTs routinely manage PVA per local standardized clinical practice guidelines. This study used a PWP-GT approach to estimate the correlation of time to PVA events with factors related to patient characteristics, ventilator settings – time-dependent covariates throughout the entire course of mechanical ventilation; and analyzed the prediction of time to PVA events on the subsequent outcomes after extubation or weaning success.