Background
Concern exists that noninvasive ventilation (NIV) may promote ventilation-induced lung injury(VILI) and worsen outcome in acute hypoxemic respiratory failure (AHRF). Different individual ...ventilatory variables have been proposed to predict clinical outcomes, with inconsistent results.
Mechanical power (MP), a measure of the energy transfer rate from the ventilator to the respiratory system during mechanical ventilation, might provide solutions for this issue in the framework of predictive, preventive and personalized medicine (PPPM). We explored (1) the impact of ventilator-delivered MP normalized to well-aerated lung (MP
WAL
) on physio-anatomical and clinical responses to NIV in COVID-19-related AHRF and (2) the effect of prone position(PP) on MP
WAL
.
Methods
We analyzed 216 noninvasively ventilated COVID-19 patients (108 patients receiving PP + NIV and 108 propensity score-matched patients receiving supine NIV) with moderate-to-severe(paO2/FiO2 ratio < 200) AHRF enrolled in the PRO-NIV controlled non-randomized study (ISRCTN23016116).
Quantification of differentially aerated lung volumes by lung ultrasonography (LUS) was validated against CT scans. Respiratory parameters were hourly recorded, ABG were performed 1 h after each postural change. Time-weighed average values of ventilatory variables, including MP
WAL
, and gas exchange parameters (paO2/FiO2 ratio, dead space indices) were calculated for each ventilatory session. LUS and circulating biomarkers were assessed daily.
Results
Compared with supine position, PP was associated with a 34% MP
WAL
reduction, attributable largely to an absolute MP reduction and secondly to an enhanced lung reaeration.
Patients receiving a high MP
WAL
during the 1
st
24 h of NIV MP
WAL
(day 1) had higher 28-d NIV failure (HR = 4.33,95%CI:3.09 − 5.98) and death (HR = 5.17,95%CI: 3.01 − 7.35) risks than those receiving a low MP
WAL
(day 1).
In Cox multivariate analyses, MP
WAL
(day 1) remained independently associated with 28-d NIV failure (HR = 1.68,95%CI:1.15–2.41) and death (HR = 1.69,95%CI:1.22–2.32).
MP
WAL
(day 1) outperformed other power measures and ventilatory variables as predictor of 28-d NIV failure (AUROC = 0.89;95%CI:0.85–0.93) and death (AUROC = 0.89;95%CI:0.85–0.94).
MP
WAL
(day 1) predicted also gas exchange, ultrasonographic and inflammatory biomarker responses, as markers of VILI, on linear multivariate analysis.
Conclusions
In the framework of PPPM, early bedside MP
WAL
calculation may provide added value to predict response to NIV and guide subsequent therapeutic choices i.e. prone position adoption during NIV or upgrading to invasive ventilation, to reduce hazardous MP
WAL
delivery, prevent VILI progression and improve clinical outcomes in COVID-19-related AHRF.
The gene coding for Pseudomonas aeruginosa cytochrome c-551 was expressed in Pseudomonas putida under aerobic conditions, using two different expression vectors; the more efficient proved to be ...pNM185, induced by m-toluate. Mature holo-(cytochrome c-551) was produced in high yield by this expression system, and was purified to homogeneity. Comparison of the recombinant wild-type protein with that purified from Ps. aeruginosa showed no differences in structural and functional properties. Trp56, an internal residue in cytochrome c-551, is located at hydrogen-bonding distance from haem propionate-17, together with Arg47. Ionization of propionate-17 was related to the observed pH-dependence of redox potential. The role of Trp56 in determining the redox properties of Ps. aeruginosa cytochrome c-551 was assessed by site-directed mutagenesis, by substitution with Tyr (W56Y) and Phe (W56F). The W56Y mutant is similar to the wild-type cytochrome. On the other hand, the W56F mutant, although similar to the wild-type protein in spectral properties and electron donation to azurin, is characterized by a weakening of the Fe-Met61 bond, as shown in the oxidized protein by the loss of the 695 nm band approx. 2 pH units below the wild-type. Moreover, in W56F, the midpoint potential and its pH-dependence are both different from the wild-type. These results are consistent with the hypothesis that hydrogen-bonding to haem propionate-17 is important in modulation of the redox properties of Ps. aeruginosa cytochrome c-551.
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