Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

Reverse triggering neural network and rules-based automated detection in acute respiratory distress syndrome.

PURPOSE: Dyssynchrony may cause lung injury and is associated with worse outcomes in mechanically ventilated patients. Reverse triggering (RT) is a common type of dyssynchrony presenting with several phenotypes which may directly cause lung injury and be difficult to identify. Due to these challenges, automated software to assist in identification is needed. MATERIALS AND METHODS: This was a prospective observational study using a training set of 15 patients and a validation dataset of 13 patients. RT events were manually identified and compared with "rules-based" programs (with and without esophageal manometry and reverse triggering with breath stacking), and were used to train a neural network artificial intelligence (AI) program. RT phenotypes were identified using previously defined rules. Performance of the programs was compared via sensitivity, specificity, positive predictive value (PPV) and F1 score. RESULTS: 33,244 breaths were manually analyzed, with 8718 manually identified as reverse-triggers. The rules-based and AI programs yielded excellent specificity (>95% in all programs) and F1 score (>75% in all programs). RT with breath stacking (24.4%) and mid-cycle RT (37.8%) were the most common phenotypes. CONCLUSIONS: Automated detection of RT demonstrated good performance, with the potential application of these programs for research and clinical care.

Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: To investigate if sevoflurane based anesthesia is superior to propofol in preventing lung inflammation and preventing postoperative pulmonary complications. DESIGN: Randomized controlled trial. SETTING: Single tertiary care university hospital. PARTICIPANTS: Forty adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 ratio to anesthetic maintenance with sevoflurane or propofol. MEASUREMENTS AND MAIN RESULTS: Blood and bronchoalveolar lavage fluid was sampled before and after bypass to measure pulmonary inflammation using a biomarker panel. The change in bronchoalveolar lavage concentration of tumor necrosis factor alpha (TNFα) was the primary outcome. Secondary outcomes included lung inflammation defined as changes in other biomarkers and postoperative pulmonary complications. There were no significant differences between groups in the change in bronchoalveolar lavage TNFα concentration (median [IQR] change, 17.24 [1.11-536.77] v 101.51 [1.47-402.84] pg/mL, sevoflurane v propofol, p = 0.31). There was a significantly lower postbypass concentration of plasma interleukin 8 (median [IQR], 53.92 [34.5-55.91] v 66.92 [53.03-94.44] pg/mL, p = 0.04) and a significantly smaller postbypass increase in the plasma receptor for advanced glycosylation end products (median [IQR], 174.59 [73.59-446.06] v 548.22 [193.15-852.39] pg/mL, p = 0.03) in the sevoflurane group compared with propofol. The incidence of postoperative pulmonary complications was 100% in both groups, with high rates of pleural effusion (17/18 [94.44%] v 19/22 [86.36%], p = 0.39) and hypoxemia (16/18 [88.88%] v 22/22 [100%], p = 0.11). CONCLUSIONS: Sevoflurane anesthesia during cardiac surgery did not consistently prevent lung inflammation or prevent postoperative pulmonary complications compared to propofol. There were significantly lower levels of 2 plasma biomarkers specific for lung injury and inflammation in the sevoflurane group.

Association between intraoperative tidal volume and postoperative respiratory complications is dependent on respiratory elastance: a retrospective, multicentre cohort study.

BACKGROUND: The impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative respiratory complications is dependent on respiratory system elastance. METHODS: We retrospectively recorded tidal volume (Vt; ml kg-1 ideal body weight [IBW]) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/[ml kg-1]). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low [Vt ≤8 ml kg-1] or high [Vt >8 ml kg-1]), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling. RESULTS: Overall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg-1; 95% confidence interval [CI], 1.35-1.50]; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O-1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% [95% CI, 0.0-0.5] at 41.2 ml cm H2O-1 compliance, compared with 5.8% [95% CI, 3.8-7.8] at 14 ml cm H2O-1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O-1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001). CONCLUSIONS: The association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.

Transpulmonary pressure measurements and lung mechanics in patients with early ARDS and SARS-CoV-2.

PURPOSE: Acute Respiratory Distress Syndrome (ARDS) secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has demonstrated variable oxygenation and respiratory-system mechanics without investigation of transpulmonary and chest-wall mechanics. This study describes lung, chest wall and respiratory-system mechanics in patients with SARS-CoV-2 and ARDS. METHODS: Data was collected from forty patients with confirmed SARS-CoV-2 and ARDS at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Esophageal balloons were placed to estimate pleural and transpulmonary pressures. Clinical characteristics, respiratory-system, transpulmonary, and chest-wall mechanics were measured over the first week. RESULTS: Patients had moderate-severe ARDS (PaO2/FiO2 123[98-149]) and were critically ill (APACHE IV 108 [94-128] and SOFA 12 [11-13]). PaO2/FiO2 improved over the first week (150 mmHg [122.9-182] to 185 mmHg [138-228] (p = 0.035)). Respiratory system (30-35 ml/cm H2O), lung (40-50 ml/cm H2O) and chest wall (120-150 ml/cm H2O) compliance remained similar over the first week. Elevated basal pleural pressures correlated with BMI. Patients required prolonged mechanical ventilation (14.5 days [9.5-19.0]), with a mortality of 32.5%. CONCLUSIONS: Patients displayed normal chest-wall mechanics, with increased basal pleural pressure. Respiratory system and lung mechanics were similar to known existing ARDS cohorts. The wide range of respiratory system mechanics illustrates the inherent heterogeneity that is consistent with typical ARDS.

Rescue therapy for severe COVID-19-associated acute respiratory distress syndrome with tissue plasminogen activator: A case series.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings. Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation. Here, we report a case series of five patients suffering from profound, medically refractory COVID-19-associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA; alteplase). All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration. LEVEL OF EVIDENCE: Therapeutic, Level V.