Variable | Baseline | Day 1 | Day 5 | Day 10 | Missing values % | p-value | ||
Group | Time | Group×time | ||||||
Tidal volume | <0.001 | <0.001 | <0.001 | |||||
L | ||||||||
HFO-TGI group | 0.46±0.05 | 0.46±0.05 | 0.47±0.06 | 0.50±0.07 | 15.2 | |||
CMV group | 0.45±0.06 | 0.44±0.06 | 0.45±0.05 | 0.46±0.07 | 18.2 | |||
mL·kg−1 PBW | ||||||||
HFO-TGI group | 6.5±0.6 | 6.4±0.6 | 6.7±0.7§ | 7.2±1.2*,+,§,ƒ | 15.2 | |||
CMV group | 6.5±0.5 | 6.4±0.5 | 6.3±0.4 | 6.4±0.6 | 18.2 | |||
Ventilation rate breaths·min−1 | 0.046 | <0.001 | 0.003 | |||||
HFO-TGI group | 27.6±4.3 | 27.8±4.4 | 27.6±4.3 | 26.0±5.2 | 15.2 | |||
CMV group | 27.2±5.3 | 27.2±5.3 | 28.2±3.8 | 27.6±5.5 | 18.2 | |||
Peak pressure cmH2O | 0.46 | <0.001 | <0.001 | |||||
HFO-TGI group | 43.4±6.1 | 42.5±5.5* | 39.6±7.4+,§ | 35.3±9.5+,§ | 15.2 | |||
CMV group | 41.2±5.6 | 39.5±5.3+ | 39.8±6.0 | 37.2±7.0 | 18.2 | |||
P̄aw cmH2O | 0.41 | <0.001 | 0.001 | |||||
HFO-TGI group | 21.7±2.9 | 21.6±2.9* | 18.9±2.8+,§ | 16.7±4.2*,+,§ | 15.2 | |||
CMV group | 20.3±3.3 | 19.7±3.0 | 19.6±3.2 | 17.9±3.1 | 18.8 | |||
Plateau pressure cmH2O | <0.001 | <0.001 | <0.001 | |||||
HFO-TGI group | 30.9±4.2 | 30.7±4.2 | 26.3±3.2*,+,§ | 24.0±5.6*,+,§ | 15.2 | |||
CMV group | 29.9±3.0 | 29.7±3.1 | 29.3±4.5 | 27.4±4.1 | 18.2 | |||
External PEEP cmH2O | 0.81 | <0.001 | 0.03 | |||||
HFO-TGI group | 14.3±2.5 | 14.2±2.5 | 12.0±2.6+,§ | 10.1±3.0+,§,ƒ | 15.2 | |||
CMV group | 13.1±3.0 | 12.9±3.3 | 12.1±3.2 | 10.5±2.8+,§ | 18.2 | |||
Compliance mL·cmH2O−1 | <0.001 | <0.001 | <0.001 | |||||
HFO-TGI group | 30.3±8.1 | 30.4±8.2 | 37.6±9.8*,+,§ | 43.3±11.8*,+,§ | 15.2 | |||
CMV group | 28.8±5.3 | 28.3±5.5 | 28.4±6.6 | 30.0±8.9 | 18.2 | |||
FI,O2 % | 0.57 | <0.001 | 0.007 | |||||
HFO-TGI group | 81.9±13.9 | 81.6±13.8* | 65.0±12.7+,§ | 57.2±15.8+,§ | 8.3 | |||
CMV group | 76.1±14.2 | 74.1±14.8 | 69.5±17.3 | 61.3±17.9+,§ | 15.8 | |||
Pa,O2 mmHg | <0.001 | <0.001 | <0.001 | |||||
HFO-TGI group | 75.5±17.7 | 77.9±19.5 | 108.0±37.4*,+,§ | 114.8±37.9*,+,§ | 8.3 | |||
CMV group | 78.2±12.7 | 78.5±12.7 | 85.4±22.8 | 90.1±28.6 | 15.8 | |||
Pa,O2/FI,O2 mmHg | 0.007 | <0.001 | <0.001 | |||||
HFO-TGI group | 96.5±31.3 | 99.5±31.6 | 175.2±74.1*,+,§ | 222.9±108.1*,+,§ | 8.3 | |||
CMV group | 106.9±27.7 | 110.5±28.2 | 135.0±61.6 | 163.5±76.1 | 15.8 | |||
Oxygenation index | 0.21 | <0.001 | 0.01 | |||||
HFO-TGI group | 26.4±13.5 | 25.6±13.4 | 13.6±7.7*,+,§ | 12.6±15.1+,§ | 15.2 | |||
CMV group | 21.1±8.9 | 19.9±8.8 | 19.1±10.3 | 14.7±8.8 | 18.8 | |||
Pa,CO2 mmHg | 0.03 | 0.048 | 0.14 | |||||
HFO-TGI group | 47.6±8.4 | 47.2±8.2 | 46.9±8.3 | 46.3±10.7 | 8.3 | |||
CMV group | 47.5±8.0 | 47.4±8.0 | 50.0±9.9 | 50.3±18.9+,§ | 15.8 | |||
pHa | 0.001 | <0.001 | <0.001 | |||||
HFO-TGI group | 7.33±0.07 | 7.33±0.07 | 7.39±0.07+,§ | 7.40±0.07*,+,§ | 8.3 | |||
CMV group | 7.30±0.08 | 7.31±0.08 | 7.36±0.09+,§ | 7.36±0.08 | 15.8 | |||
Shunt fraction | 0.02 | <0.001 | <0.001 | |||||
HFO-TGI group | 0.46±0.12 | 0.45±0.13 | 0.29±0.12*,+ | 0.26±0.15*,+ | 8.3 | |||
CMV group | 0.42±0.09 | 0.42±0.09 | 0.37±0.13 | 0.33±0.13 | 15.8 | |||
MAP mmHg | 0.16 | 0.02 | <0.001 | |||||
HFO-TGI group | 81.7±13.2 | 79.9±13.5 | 81.5±11.9 | 83.4±9.5 | 8.3 | |||
CMV group | 77.3±11.0 | 79.1±11.9 | 82.4±9.7 | 80.1±12.8 | 15.8 | |||
CVP mmHg | 0.89 | <0.001 | 0.63 | |||||
HFO-TGI group | 10.8±4.1 | 11.7±4.2+ | 11.3±3.4 | 10.3±3.1 | 8.3 | |||
CMV group | 10.1±3.4 | 10.8±3.6+ | 11.8±4.2 | 11.4±4.5 | 15.8 | |||
Heart rate beats·min−1 | 0.58 | 0.02 | 0.31 | |||||
HFO-TGI group | 98.9±18.9 | 96.6±19.8 | 90.1±17.4+ | 95.9±14.9 | 8.3 | |||
CMV group | 98.9±16.7 | 97.7±16.6 | 92.3±14.2 | 93.4±15.4 | 15.8 | |||
Cardiac index L·min−1·m−2 | 0.12 | <0.001 | 0.65 | |||||
HFO-TGI group | 4.0±1.03 | 4.0±1.0 | 3.7±0.9 | 3.8±0.5 | 12.9 | |||
CMV group | 4.1±0.9 | 4.2±0.8 | 4.0±0.7 | 4.1±1.0 | 21.1 | |||
DO2I mL·min−1·m−2 | 0.46 | <0.001 | 0.18 | |||||
HFO-TGI group | 460.0±122.7 | 475.3±133.5+ | 431.3±105.5 | 443.3±116.8 | 12.9 | |||
CMV group | 489.8±134.8 | 495.7±130.0 | 444.9±81.6§ | 419.8±78.1+,§ | 21.1 | |||
Scv,O2 % | 0.14 | 0.09 | 0.30 | |||||
HFO-TGI group | 70.7±8.8 | 71.4±8.5 | 72.8±5.8 | 71.6±8.7 | 8.3 | |||
CMV group | 70.7±6.6 | 71.0±6.7 | 71.0±6.0 | 71.9±4.3 | 15.8 | |||
Lactate mmol·L−1 | 0.12 | <0.001 | 0.32 | |||||
HFO-TGI group | 2.5±1.8 | 2.3±1.8 | 1.9±1.1 | 1.5±0.8 | 8.3 | |||
CMV group | 2.8±2.8 | 2.8±2.5 | 2.2±2.1 | 1.6±0.8 | 15.8 | |||
Fluid balance# L·day−1 | 0.63 | <0.001 | 0.47 | |||||
HFO-TGI group | 2.03±1.65 | 2.34±2.34 | 1.04±1.48§ | 0.81±1.73§ | 8.3 | |||
CMV group | 2.07±1.71 | 2.56±2.04 | 1.07±1.55§ | 0.72±1.68§ | 15.8 | |||
Noradrenaline¶ μg·kg−1·min−1 | 0.38 | 0.03 | 0.12 | |||||
HFO-TGI group | 0.19±0.16 | 0.22±0.23 | 0.15±0.13 | 0.09±0.11 | 8.3 | |||
CMV group | 0.19±0.16 | 0.19±0.17 | 0.15±0.15 | 0.12±0.16 | 15.8 | |||
SOFA score | 0.02 | <0.001 | 0.03 | |||||
HFO-TGI group | 11.7±2.7 | 11.5±2.7 | 10.4±3.7 | 7.4±4.6*,+,§,ƒ | 8.3 | |||
CMV group | 12.1±2.6 | 11.9±2.7 | 11.9±4.2 | 10.0±3.8 | 15.8 |
Data are presented as mean±sd, unless otherwise stated. Data originate from physiological measurements performed during conventional mechanical ventilation in each one of the 125 patients (intention-to-treat analysis), within 2 h before randomization (baseline), and between 09:00 and 10:00 h on days 1–10 post-randomisation. Detailed data on physiological endpoints and the Sequential Organ Failure Assessment (SOFA) score are presented in fig. 3. Pressure, volume and respiratory rate values were those displayed by the ventilator. Respiratory compliance was calculated as tidal volume divided by the end-inspiratory to end-expiratory plateau airway pressure difference [7, 12]. For both groups, analysed data corresponded to 11 consecutive time-points, i.e. at baseline and on the morning of each of the first 10 days post-randomisation. For between-group comparisons at each time-point, we used the Bonferroni correction, i.e. we multiplied the obtained p-values by 11. The 11 time-points resulted in a total of 55 within-group pairwise comparisons; thus, we multiplied p-values from within-group comparisons by 55. The handling of missing values is summarised in the online supplementary material. HFO: high-frequency oscillation; TGI: tracheal gas insufflation; CMV: conventional mechanical ventilation; PBW: predicted body weight; P̄aw: mean airway pressure; PEEP: positive end-expiratory pressure; FI,O2: inspiratory oxygen fraction; Pa,O2: arterial oxygen tension; Pa,CO2: arterial carbon dioxide tension; pHa: arterial pH; MAP: mean arterial pressure; CVP: central venous pressure; DO2I: oxygen delivery index; Scv,O2: central venous oxygen saturation. #: baseline values correspond to the fluid balance of the preceding 24 h; other values correspond to the fluid balance of days 1, 5 and 10. ¶: baseline infusion rate was the infusion rate recorded just prior to randomisation; other infusion rates are the average infusion rates of days 1, 5 and 10; during days 1–10, all patients of both groups required a noradrenaline infusion for ≥1 h to maintain a MAP of ≥70 mmHg. *: p<0.05 versus CMV group at that particular time-point; +: p<0.05 versus baseline; §: p<0.05 versus day 1; ƒ: p<0.05 versus day 5.