The Association Between Ventilator Dyssynchrony, Delivered Tidal Volume, and Sedation Using a Novel Automated Ventilator Dyssynchrony Detection Algorithm.

OBJECTIVE: Ventilator dyssynchrony is potentially harmful to patients with or at risk for the acute respiratory distress syndrome. Automated detection of ventilator dyssynchrony from ventilator waveforms has been difficult. It is unclear if certain types of ventilator dyssynchrony deliver large tidal volumes and whether levels of sedation alter the frequency of ventilator dyssynchrony. DESIGN: A prospective observational study. SETTING: A university medical ICU. PATIENTS: Patients with or at risk for acute respiratory distress syndrome. INTERVENTIONS: Continuous pressure-time, flow-time, and volume-time data were directly obtained from the ventilator. The level of sedation and the use of neuromuscular blockade was extracted from the medical record. Machine learning algorithms that incorporate clinical insight were developed and trained to detect four previously described and clinically relevant forms of ventilator dyssynchrony. The association between normalized tidal volume and ventilator dyssynchrony and the association between sedation and the frequency of ventilator dyssynchrony were determined. MEASUREMENTS AND MAIN RESULTS: A total of 4.26 million breaths were recorded from 62 ventilated patients. Our algorithm detected three types of ventilator dyssynchrony with an area under the receiver operator curve of greater than 0.89. Ventilator dyssynchrony occurred in 34.4% (95% CI, 34.41-34.49%) of breaths. When compared with synchronous breaths, double-triggered and flow-limited breaths were more likely to deliver tidal volumes greater than 10 mL/kg (40% and 11% compared with 0.2%; p < 0.001 for both comparisons). Deep sedation reduced but did not eliminate the frequency of all ventilator dyssynchrony breaths (p < 0.05). Ventilator dyssynchrony was eliminated with neuromuscular blockade (p < 0.001). CONCLUSION: We developed a computerized algorithm that accurately detects three types of ventilator dyssynchrony. Double-triggered and flow-limited breaths are associated with the frequent delivery of tidal volumes of greater than 10 mL/kg. Although ventilator dyssynchrony is reduced by deep sedation, potentially deleterious tidal volumes may still be delivered. However, neuromuscular blockade effectively eliminates ventilator dyssynchrony.

Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome.

BACKGROUND: Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia. METHODS: We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study. Our primary predictor variable was the number of days receiving NMB between study enrollment and day 3. Our primary outcome variables were the change in concentration of biomarkers of epithelial injury (serum surfactant protein-D (SP-D)), endothelial injury (von Willebrand factor (VWF)), and systemic inflammation (interleukin (IL)-8). Multivariable regression analysis was used to compare the change in biomarker concentration controlling for multiple covariates. Patients were stratified by treatment arm (12 versus 6 cm3/kg) and by an initial arterial oxygen tension (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio of 120. RESULTS: A total of 446 (49%) patients had complete SP-D, VWF, and IL-8 measurements on study enrollment and day 3. After adjusting for baseline differences, each day of NMB was associated with a decrease in SP-D (-23.7 ng/ml/day, p = 0.029), VWF (-33.5% of control/day, p = 0.015), and IL-8 (-362.6 pg/ml/day, p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving low tidal volume ventilation. However, patients with a P/F ratio of greater than 120 or receiving high tidal volume ventilation had either no change or an increase in SP-D, WVF, or IL-8 concentrations. CONCLUSION: NBM is associated with decreased biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients receiving low tidal volume ventilation and those with a P/F ratio less than or equal to 120.

Ventilator dyssynchrony - Detection, pathophysiology, and clinical relevance: A Narrative review.

Mortality associated with the acute respiratory distress syndrome remains unacceptably high due in part to ventilator-induced lung injury (VILI). Ventilator dyssynchrony is defined as the inappropriate timing and delivery of a mechanical breath in response to patient effort and may cause VILI. Such deleterious patient-ventilator interactions have recently been termed patient self-inflicted lung injury. This narrative review outlines the detection and frequency of several different types of ventilator dyssynchrony, delineates the different mechanisms by which ventilator dyssynchrony may propagate VILI, and reviews the potential clinical impact of ventilator dyssynchrony. Until recently, identifying ventilator dyssynchrony required the manual interpretation of ventilator pressure and flow waveforms. However, computerized interpretation of ventilator waive forms can detect ventilator dyssynchrony with an area under the receiver operating curve of >0.80. Using such algorithms, ventilator dyssynchrony occurs in 3%-34% of all breaths, depending on the patient population. Moreover, two types of ventilator dyssynchrony, double-triggered and flow-limited breaths, are associated with the more frequent delivery of large tidal volumes >10 mL/kg when compared with synchronous breaths (54% [95% confidence interval (CI), 47%-61%] and 11% [95% CI, 7%-15%]) compared with 0.9% (95% CI, 0.0%-1.9%), suggesting a role in propagating VILI. Finally, a recent study associated frequent dyssynchrony-defined as >10% of all breaths-with an increase in hospital mortality (67 vs. 23%, P = 0.04). However, the clinical significance of ventilator dyssynchrony remains an area of active investigation and more research is needed to guide optimal ventilator dyssynchrony management.