Materials and methods

Statistical analysis

Quantitative variable are expressed as mean±sd. In order to overule pseudoreplication due to repeated measurement to the same animal, mixed effect regression models were use built with nlme package. In these cases, each animal was included as a random variable. Model conditional coefficients of determination for mixed-effect models were calculated using MuMIn package. A similar approach was used when fitting analysis of variance models.
Statistical analysis was performed with R version 3.3.3 (2017-03-06).

Results

Baseline respiratory parameters were as follows: Vt=295±83.95 ml, PaFiO2=125.68±70.16 mmHg, pH=7.2±0.06, PaCO2=62.09±13.63 mmHg, inspiratory static PAW=31.43±4.15 cmH2O and compliance=14.51±5.48 ml/cmH2O.

Measurements by PEEP

Table 1: TIE data by PEEP

0 5 10 15 20 25 30 P
Silent Spaces Non-Dependent [%] 2.26±2.05 2.45±1.99 5.98±2.98 7.25±3.19 7.56±3.35 7.22±2.67 6.57±2.85 3.8e-08
Silent Spaces Dependent [%] 9.98±7.91 8.51±6.37 5.05±4.4 1.01±1.55 0.48±0.9 0.61±1.14 0.91±1.52 3.7e-07
Stretch quartile - 0.19±0.05 0.19±0.06 0.21±0.07 0.26±0.05 0.27±0.05 0.27±0.03 0.29±0.05 6.1e-09
Stretch median 0.34±0.06 0.34±0.06 0.38±0.07 0.44±0.08 0.51±0.05 0.52±0.05 0.53±0.06 6.3e-13
Stretch quartile + 0.55±0.06 0.55±0.06 0.59±0.06 0.63±0.06 0.7±0.04 0.72±0.04 0.74±0.05 4.7e-10

Table 2: Mechanics by PEEP

0 5 10 15 20 25 30 P
Ptp-inspElas 29.63±5.73 28.93±5.57 28.2±4.75 29.03±4.74 32.28±5.74 36.53±5.36 45.76±5.77 1e-08
Pplat 33.32±5.94 34.02±5.58 33.62±4.32 35.49±5.07 40.46±4.68 48.1±7.19 57.59±8.31 <2e-16
CStatic 9.97±2.9 10.74±3.55 13.42±4.03 15.82±5.01 15.75±5.25 14.67±6.25 12.16±6.75 2.7e-09
Cdyn 6.44±1.47 6.98±1.62 9.14±1.95 10.74±2.76 10.53±2.91 10.01±3.04 8.98±3.66 8.7e-13
StressIndex 1.05±0.13 1.08±0.09 1.04±0.06 1.05±0.08 1.05±0.1 1.09±0.08 1.06±0.05 0.95
Ptp-insp 19.33±4.31 19.87±4.38 17.9±3.88 19.2±3.13 21.76±4.48 25.66±5.54 33.31±4.5 1.1e-10
Ptp-esp -8.11±7.03 -3.82±6.5 -1.06±5.91 3.18±4.95 6.23±5.27 9.29±5.24 12.54±5.79 <2e-16
Ep/Etot 0.85±0.05 0.82±0.04 0.82±0.06 0.8±0.05 0.79±0.11 0.77±0.1 0.8±0.09 0.33
Ptp-inspElas 29.63±5.73 28.93±5.57 28.2±4.75 29.03±4.74 32.28±5.74 36.53±5.36 45.76±5.77 1e-08

Table 3: VD/VT data by PEEP

0 5 10 15 20 25 30 P
VCO2br 4.32±2.13 5.07±3.11 5.37±2.89 5.71±2.95 5.02±2.74 4.59±2.5 4.18±2.7 5.3e-05
Bohr 0.51±0.08 0.52±0.09 0.53±0.06 0.55±0.05 0.61±0.07 0.65±0.08 0.69±0.1 <2e-16
VTalV 202.79±64.6 192.65±67.85 190.31±61.41 183.44±53.01 167.5±58.1 158.08±56.54 142.77±63.18 2.7e-14
VdalV/VTalV 0.27±0.05 0.26±0.05 0.25±0.02 0.27±0.03 0.3±0.03 0.33±0.03 0.35±0.06 6.7e-10

Table 4: Gas exchange data by PEEP

0 5 10 15 20 25 30 P
PH 7.16±0.06 7.16±0.08 7.2±0.06 7.21±0.07 7.2±0.08 7.23±0.09 7.2±0.06 0.00011
PaCO2 72.59±15.88 70.55±12.32 64.7±13.91 60.74±10.74 60.62±12.77 57.55±15.7 59.37±14.34 4.1e-07
Pa/FiO2 50.95±22.01 54.74±19.54 105.72±58.81 215.75±124.33 332.49±169.2 548.55±140.55 571.19±56.03 <2e-16

Table 5: Hemodynamics by PEEP

0 5 10 15 20 25 30 P
TAS 123.55±31.71 126.27±28.92 124.73±18.43 125±16.73 114.55±14.31 104.18±20.4 100.3±16.71 0.0035
TAM 94±30.1 96.45±29.04 94.82±17.57 94.27±18.3 90.73±14.17 81.09±17.41 78.9±14.25 0.058
IC 4.84±1.1 3.68±1.13 4.22±0.32 3.58±0.9 3.42±1.28 3.76±1.5 2.98±1.1 0.11
VVS 6.5±2.56 6.5±1.77 7.25±1.49 9.62±3.89 15.38±6.16 19±9.77 29.57±14.36 5.3e-09

PTP and PAW

As expected, PTP shows a linear relationship with PAW (conditional mixed model R2 =0.98, P= \(2.693\times 10^{-47}\))

VD/VT and PEEP

VD/VT and PTP

Silent spaces and PEEP

Silent spaces and PTP

Comparison among physiological data according to different optimized parameters

Optimized parameter where defined as follows:

  • VdalV/VTalV: lowest value
  • VCO2br: greatest value
  • Ptp-esp: nearest to 0 cmH2O
  • CStatic: greatest value
  • Pplat: nearest to 30 cmH2O
  • Ptp-inspElas (elastance derived inspiratory PTP): nearest to 27 cmH2O

Table 7 shows physiological values recorded with each optimized parameter in the rows.

Table 7: Physiological data depending on optimized parameters

VdalV/VTalV VCO2br Ptp-esp CStatic Pplat Ptp-inspElas P
PEEPtot 8.17±5.07 11.48±6.84 11.06±6.22 19.1±6.33 8.06±5.88 10.64±8.16 0.002024
Pplat 33.22±4.53 35.32±7.19 36.47±7.6 37.24±5.35 32.91±3.98 34.99±7.1 0.073583
VdalV/VTalV 0.23±0.03 0.25±0.04 0.26±0.04 0.29±0.03 0.26±0.03 0.28±0.02 4.8528e-05
VCO2br 5.44±3.02 6.07±2.88 5.86±3.25 5.33±2.36 4.97±2.14 4.85±2.4 0.0065323
Ptp-esp -1.81±6.11 0.6±6.99 -0.26±1.58 5.69±8.17 -2.54±6.91 -1.95±5.82 0.032026
Ptp-inspElas 28.2±4.76 29.74±6.14 30.16±7.41 29.33±5.94 27.69±4.37 27.12±2.4 0.5356
CStatic 12.73±5.76 13.59±6.02 13.05±4.63 17.1±5.87 12.3±3.36 13.05±3.15 0.0027749
Silent Spaces Dependent [%] 8.28±6.71 4.49±5.35 7.36±8.8 1.25±1.41 6.84±7.49 5.74±6.53 0.062608

Multiple comparisons plots

Only those with significant ANOVA P above are displayed

## $PEEPtot

## 
## $VCO2br

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## $`Ptp-esp`

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## $CStatic