ABSTRACT
BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.
ABSTRACT
Abdominal inflation with CO2 is used to facilitate laparoscopic surgeries, however, providing adequate mechanical ventilation in this scenario is of major importance during anesthesia management. We characterized high-frequency percussive ventilation (HFPV) in protecting from the gas exchange and respiratory mechanical impairments during capnoperitoneum. In addition, we aimed to assess the difference between conventional pressure-controlled mechanical ventilation (CMV) and HFPV modalities generating the high-frequency signal intratracheally (HFPVi) or extrathoracally (HFPVe). Anesthetized rabbits (n = 16) were mechanically ventilated by random sequences of CMV, HFPVi, and HFPVe. The ventilator superimposed the conventional waveform with two high-frequency signals (5 Hz and 10 Hz) during intratracheal HFPV (HFPVi) and HFPV with extrathoracic application of oscillatory signals through a sealed chest cuirass (HFPVe). Lung oxygenation index ([Formula: see text]/[Formula: see text]), arterial partial pressure of carbon dioxide ([Formula: see text]), intrapulmonary shunt (Qs/Qt), and respiratory mechanics were assessed before abdominal inflation, during capnoperitoneum, and after abdominal deflation. Compared with CMV, HFPVi with additional 5-Hz oscillations during capnoperitoneum resulted in higher [Formula: see text]/[Formula: see text], lower [Formula: see text], and decreased Qs/Qt. These improvements were smaller but remained significant during HFPVi with 10 Hz and HFPVe with either 5 or 10 Hz. The ventilation modes did not protect against capnoperitoneum-induced deteriorations in respiratory tissue mechanics. These findings suggest that high-frequency oscillations combined with conventional pressure-controlled ventilation improved lung oxygenation and CO2 removal in a model of capnoperitoneum. Compared with extrathoracic pressure oscillations, intratracheal generation of oscillatory pressure bursts appeared more effective. These findings may contribute to the optimization of mechanical ventilation during laparoscopic surgery.NEW & NOTEWORTHY The present study examines an alternative and innovative mechanical ventilation modality in improving oxygen delivery, CO2 clearance, and respiratory mechanical abnormalities in a clinically relevant experimental model of capnoperitoneum. Our data reveal that high-frequency oscillations combined with conventional ventilation improve gas exchange, with intratracheal oscillations being more effective than extrathoracic oscillations in this clinically relevant translational model.