Inflammatory biomarkers and pendelluft magnitude in ards patients transitioning from controlled to partial support ventilation

Abstract

The transition from controlled to partial support ventilation is a challenge in acute respiratory distress syndrome (ARDS) patients due to the risks of patient-self-inflicted lung injury. The magnitude of tidal volume (V_T) and intrapulmonary dyssynchrony (pendelluft) are suggested mechanisms of lung injury. We conducted a prospective, observational, physiological study in a tertiary academic intensive care unit. ARDS patients transitioning from controlled to partial support ventilation were included. On these, we evaluated the association between changes in inflammatory biomarkers and esophageal pressure swing (ΔP_es), transpulmonary driving pressure (ΔP_L), V_T, and pendelluft. Pendelluft was defined as the percentage of the tidal volume that moves from the non-dependent to the dependent lung region during inspiration, and its frequency at different thresholds (- 15, - 20 and - 25%) was also registered. Blood concentrations of inflammatory biomarkers (IL-6, IL-8, TNF-α, ANGPT2, RAGE, IL-18, Caspase-1) were measured before (T₀) and after 4-h (T₄) of partial support ventilation. Pendelluft, ΔP_es, ΔP_L and V_T were recorded. Nine out of twenty-four patients (37.5%) showed a pendelluft mean ≥ 10%. The mean values of ΔP_es, ΔP_L, and V_T were - 8.4 [- 6.7; - 10.2] cmH₂O, 15.2 [12.3-16.5] cmH₂O and 8.1 [7.3-8.9] m/kg PBW, respectively. Significant associations were observed between the frequency of high-magnitude pendelluft and IL-8, IL-18, and Caspase-1 changes (T₀/T₄ ratio). These results suggest that the frequency of high magnitude pendelluft may be a potential determinant of inflammatory response related to inspiratory efforts in ARDS patients transitioning to partial support ventilation. Future studies are needed to confirm these results.

Figure 1

Histograms of inspiratory dyssynchrony (pendelluft) at different magnitudes. X axis corresponds to the magnitude of pendelluft and Y axis, to the percentage of ventilatory cycles with certain magnitude of pendelluft. The negative value of pendelluft represents the lost volume in non-dependent region during inspiration, expressed as fraction. The vertical red dotted line delimits the pendelluft with high magnitude cut-off − 0.2 (i.e. 20% of lost volume in non-dependent region during inspiration). (A) corresponds to Subject #2, a patient with a pendelluft mean of − 0.2 (− 20%), who presented high frequency of high-magnitude pendelluft. (B) corresponds to Subject #23, a patient with pendelluft mean of − 0.02 (− 0.2%), who presented low frequency of high-magnitude pendelluft.

Figure 2

Scatter plots and regression analysis between (A) IL-8, (B) IL-18, (C) Caspase-1 ratios and frequencies of pendelluft magnitude − 15, − 20 and − 25%. Biomarker ratio [(biomarker at T₄)/(biomarker at T₀)] and the mean of pendelluft frequencies at different cut-off points of pendelluft magnitude (− 15, − 20 and − 25%), through the 4 h period of observation, were obtained for each patient. Pendelluft_-15: mean of pendelluft frequency at magnitude of − 15%; Pendelluft_-20: mean of pendelluft frequency at magnitude of − 20%; Pendelluft_-25: mean pendelluft frequency at magnitude of − 25%. ΔP_es: mean of negative deflection of esophageal pressure from the onset of inspiratory effort during the ventilatory cycle; ΔP_L: mean of tidal change in transpulmonary pressure. V_T: tidal volume.

Figure 3

Scatter plots and regression analysis between (A) IL-8, (B) IL-18, (C) Caspase-1 ratios, and respiratory variables. Biomarker ratio [(biomarker at T₄)/(biomarker at T₀)] and the mean values by patient of ΔP_es , ΔP_L and V_T, through the 4 h period of observation, were obtained for each patient ΔP_es: mean of negative deflection of esophageal pressure (P_es) from the onset of inspiratory effort during the ventilatory cycle; ΔP_L: mean of tidal change in transpulmonary pressure. Only the association between ΔP_es and ΔP_L and the pendelluft ₂₅ frequency was significant (R² 0.202 and p-value = 0.047). Several patients presented pendelluft of higher magnitude at lower than − 15 and 20 cmH₂O of ΔP_es and ΔP_L, respectively.