Sigh ventilation versus conventional protective ventilation in cardiac surgery: a proof-of-concept randomized controlled trial

Abstract

Lung protective ventilation is crucial for preventing ventilator-induced lung injury in cardiac surgery. The protective role of a low tidal volume (V T ) has been established, whereas the added protection afforded by lung recruitment remains uncertain. We investigated whether sigh breaths could provide additional lung protection, when added to protective ventilation with low V T . This randomized, assessor-blinded, phase 2 proof-of-concept trial enrolled 192 patients undergoing elective on-pump cardiac surgery from February to August 2024. Patients were randomly allocated in a 1:1 ratio to receive sigh ventilation (sigh breaths plus protective ventilation with low V T ; 96 patients) or conventional ventilation (protective ventilation with low V T ; 96 patients). Sigh breaths targeting a plateau pressure of 35 cmH 2 O (or 40 cmH 2 O for BMI >35 kg/m2) were delivered once every 6 min. Perioperative respiratory mechanics and gas exchange were monitored. The primary outcome was postoperative oxygenation, a marker of lung injury, as measured by the time-weighted average SpO 2 /FiO 2 ratio during the first postextubation hour. There were 9 predefined secondary outcomes, including the severity of respiratory failure within postextubation day 7. All 192 patients completed the trial (53% male; median age, 64 [55–72] years). Perioperatively, sigh ventilation produced sustained improvements in oxygenation and respiratory system compliance, together with reductions in driving pressure and mechanical power (All P interaction<0.001). After extubation, the mean time-weighted SpO 2 /FiO 2 ratio was higher in the sigh ventilation group (380 ± 86 vs 338 ± 93; mean difference 42.1, 95% CI [16.7 to 67.5]; P=0.001). The severity and occurrence of respiratory failure was reduced in the sigh ventilation group compared with conventional ventilation group (common odds ratio for lower severity 2.2; 95% CI [1.2 to 3.8]; P=0.007). There was no difference in adverse events of interest between groups. In patients undergoing on-pump cardiac surgery, adding sigh breaths was safe and resulted in a statistically significant improvement in postoperative oxygenation. Nevertheless, the clinical importance of this finding is uncertain because oxygenation was adequately maintained in both groups. Reduction in driving pressure and mechanical power, together with findings in secondary outcomes, suggest additional lung protection and justify future trials. Trial Registration: ClinicalTrials.gov (NCT06248320); registered on January 30, 2024.