Dataset Information

Driving-pressure-independent protective effects of open lung approach against experimental acute respiratory distress syndrome.

ABSTRACT:

Background

The open lung approach (OLA) reportedly has lung-protective effects against acute respiratory distress syndrome (ARDS). Recently, lowering of the driving pressure (?P), rather than improvement in lung aeration per se, has come to be considered as the primary lung-protective mechanism of OLA. However, the driving pressure-independent protective effects of OLA have never been evaluated in experimental studies. We here evaluated whether OLA shows protective effects against experimental ARDS even when the ?P is not lowered.

Methods

Lipopolysaccharide was intratracheally administered to rats to establish experimental ARDS. After 24 h, rats were mechanically ventilated and randomly allocated to the OLA or control group. In the OLA group, 5 cmH₂O positive end-expiratory pressure (PEEP) and recruitment maneuver (RM) were applied. Neither PEEP nor RM was applied to the rats in the control group. Dynamic ?P was kept at 15 cmH₂O in both groups. After 6 h of mechanical ventilation, rats in both groups received RM to inflate reversible atelectasis of the lungs. Arterial blood gas analysis, lung computed tomography, histological evaluation, and comprehensive biochemical analysis were performed.

Results

OLA significantly improved lung aeration, arterial oxygenation, and gas exchange. Even after RM in both groups, the differences in these parameters between the two groups persisted, indicating that the atelectasis-induced respiratory dysfunction observed in the control group is not an easily reversible functional problem. Lung histological damage was severe in the dorsal dependent area in both groups, but was attenuated by OLA. White blood cell counts, protein concentrations, and tissue injury markers in the broncho-alveolar lavage fluid (BALF) were higher in the control than in the OLA group. Furthermore, levels of CXCL-7, a platelet-derived chemokine, were higher in the BALF from the control group, indicating that OLA protects the lungs by suppressing platelet activation.

Conclusions

OLA shows protective effects against experimental ARDS, even when the ?P is not decreased. In addition to reducing ?P, maintaining lung aeration seems to be important for lung protection in ARDS.

SUBMITTER: Tojo K

PROVIDER: S-EPMC6151188 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Driving-pressure-independent protective effects of open lung approach against experimental acute respiratory distress syndrome.

Tojo Kentaro K Yoshida Tasuku T Yazawa Takuya T Goto Takahisa T

Critical care (London, England) 20180923 1

<h4>Background</h4>The open lung approach (OLA) reportedly has lung-protective effects against acute respiratory distress syndrome (ARDS). Recently, lowering of the driving pressure (ΔP), rather than improvement in lung aeration per se, has come to be considered as the primary lung-protective mechanism of OLA. However, the driving pressure-independent protective effects of OLA have never been evaluated in experimental studies. We here evaluated whether OLA shows protective effects against experi ...[more]

PMID: 30243301

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Project description:ImportanceMechanical power and driving pressure have known associations with survival for patients with acute respiratory distress syndrome.ObjectivesTo further understand the relative importance of mechanical power and driving pressure as clinical targets for ventilator management.DesignSecondary observational analysis of randomized clinical trial data.Setting and participantsPatients with the acute respiratory distress syndrome from three Acute Respiratory Distress Syndrome Network trials.Main outcomes and measuresAfter adjusting for patient severity in a multivariate Cox proportional hazards model, we examined the relative association of driving pressure and mechanical power with hospital mortality. Among 2,410 patients, the relationship between driving pressure and mechanical power with mortality was modified by respiratory rate, positive end-expiratory pressure, and flow.ResultsAmong patients with low respiratory rate (< 26), only power was significantly associated with mortality (power [hazard ratio, 1.82; 95% CI, 1.41-2.35; p < 0.001] vs driving pressure [hazard ratio, 1.01; 95% CI, 0.84-1.21; p = 0.95]), while among patients with high respiratory rate, neither was associated with mortality. Both power and driving pressure were associated with mortality at high airway flow (power [hazard ratio, 1.28; 95% CI, 1.15-1.43; p < 0.001] vs driving pressure [hazard ratio, 1.15; 95% CI, 1.01-1.30; p = 0.041]) and neither at low flow. At low positive end-expiratory pressure, neither was associated with mortality, whereas at high positive end-expiratory pressure (≥ 10 cm H2O), only power was significantly associated with mortality (power [hazard ratio, 1.22; 95% CI, 1.09-1.37; p < 0.001] vs driving pressure [hazard ratio, 1.16; 95% CI, 0.99-1.35; p = 0.059]).Conclusions and relevanceThe relationship between mechanical power and driving pressure with mortality differed within severity subgroups defined by positive end-expiratory pressure, respiratory rate, and airway flow.

Project description:BACKGROUND:We dissected total power into its primary components to resolve its relative contributions to tissue damage (VILI). We hypothesized that driving power or elastic (dynamic) power offers more precise VILI risk indicators than raw total power. The relative correlations of these three measures of power with VILI-induced histologic changes and injury biomarkers were determined using a rodent model of acute respiratory distress syndrome (ARDS). Herein, we have significantly extended the scope of our previous research. METHODS:Data analyses were performed in male Wistar rats that received endotoxin intratracheally to induce ARDS. After 24?h, they were randomized to 1?h of volume-controlled ventilation with low VT?=?6?ml/kg and different PEEP levels (3, 5.5, 7.5, 9.5, and 11 cmH2O). Applied levels of driving power, dynamic power inclusive of PEEP, and total power were correlated with VILI indicators [lung histology and biological markers associated with inflammation (interleukin-6), alveolar stretch (amphiregulin), and epithelial (club cell protein (CC)-16) and endothelial (intercellular adhesion molecule-1) cell damage in lung tissue]. RESULTS:Driving power was higher at PEEP-11 than other PEEP levels. Dynamic power and total power increased progressively from PEEP-5.5 and PEEP-7.5, respectively, to PEEP-11. Driving power, dynamic power, and total power each correlated with the majority of VILI indicators. However, when correlations were performed from PEEP-3 to PEEP-9.5, no relationships were observed between driving power and VILI indicators, whereas dynamic power and total power remained well correlated with CC-16 expression, alveolar collapse, and lung hyperinflation. CONCLUSIONS:In this mild-moderate ARDS model, dynamic power, not driving power alone, emerged as the key promoter of VILI. Moreover, hazards from driving power were conditioned by the requirement to pass a tidal stress threshold. When estimating VILI hazard from repeated mechanical strains, PEEP must not be disregarded as a major target for modification.

Dataset Information

Driving-pressure-independent protective effects of open lung approach against experimental acute respiratory distress syndrome.

Background

Methods

Results

Conclusions

Publications

Driving-pressure-independent protective effects of open lung approach against experimental acute respiratory distress syndrome.

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