Isoflurane promotes early spontaneous breathing in ventilated intensive care patients: A post hoc subgroup analysis of a randomized trial

Abstract

Background: Spontaneous breathing is desirable in most ventilated patients. We therefore studied the influence of isoflurane versus propofol sedation on early spon taneous breathing in ventilated surgical intensive care patients and evaluated poten tial mediation by opioids and arterial carbon dioxide during the first 20 h of study sedation. Methods: We included a single-center subgroup of 66 patients, who participated in a large multi-center trial assessing efficacy and safety of isoflurane sedation, with 33 patients each randomized to isoflurane or propofol sedation. Both sedatives were titrated to a sedation depth of −4 to −1 on the Richmond Agitation Sedation Scale. The primary outcome was the fraction of time during which patients breathed spontaneously. Results: Baseline characteristics of isoflurane and propofol-sedated patients were well balanced. There were no substantive differences in management or treatment aside from sedation, and isoflurane and propofol provided nearly identical sedation depths. The mean fraction of time spent spontaneously breathing was 82% [95% CI: 69, 90] in patients sedated with isoflurane compared to 35% [95% CI: 22, 51] in those assigned to propofol: median difference: 61% [95% CI: 14, 89], p < .001. After ad justments for sufentanil dose and arterial carbon dioxide partial pressure, patients sedated with isoflurane were twice as likely to breathe spontaneously than those se dated with propofol: adjusted risk ratio: 2.2 [95%CI: 1.4, 3.3], p < .001. Conclusions: Isoflurane compared to propofol sedation promotes early spontaneous breathing in deeply sedated ventilated intensive care patients. The benefit appears to be a direct effect isoflurane rather than being mediated by opioids or arterial carbon dioxide.