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.

Early and late effects of volatile sedation with sevoflurane on respiratory mechanics of critically ill COPD patients.

BACKGROUND: The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation. METHODS: Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint. RESULTS: Sixteen patients were enrolled and were sedated for 126 h(61-228) in the propofol group and 207 h(171-216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8-21.6) in the propofol group and 20.4cmH2O/l/s(18.6-26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176-290) in the propofol group and 73 ml(35-126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1-3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups. CONCLUSIONS: In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.

Understanding the variability of the electrophysiologic laryngeal adductor reflex.

OBJECTIVE: The laryngeal adductor reflex (LAR) is vital for airway protection and can be electrophysiologically obtained under intravenous general anesthesia (IGA). This makes the electrophysiologic LAR (eLAR) an important tool for monitoring of the vagus nerves and relevant brainstem circuitry during high-risk surgeries. We investigated the intra-class variability of normal and expected abnormal eLAR. METHODS: Repeated measures of contralateral R1 (cR1) were performed under IGA in 58 patients. Data on presence/absence of cR2 and potential confounders were also collected. Review of neuroimaging, pathology and clinical exam, allowed classification into normal and expected abnormal eLAR groups. Using univariate and multivariate analysis we studied the variability of cR1 parameters and their differences between the two groups. RESULTS: In both groups, cR1 latencies had coefficients of variation of <2%. In the abnormal group, cR1 had longer latencies, required higher activation currents and was more frequently desynchronized and unsustained; cR2 was more frequently absent. CONCLUSIONS: cR1 latencies show high analytical precision for measurements. Delayed onset, difficult to elicit, desynchronized and unsustained cR1, and absence of cR2 signal an abnormal eLAR. SIGNIFICANCE: Understanding the variability and behavior of normal and abnormal eLAR under IGA can aid in the interpretation of its changes during monitoring.