End-Tidal Control Versus Manual Control of Inhalational Anesthesia Delivery: A Randomized Controlled Noninferiority Trial

Abstract

BACKGROUND: Precise anesthesia delivery helps ensure amnesia, analgesia, and immobility. Conventionally, the end-tidal anesthetic concentration is maintained through manual adjustment of the fresh gas flow and anesthetic vaporizer output. Some anesthesia delivery systems can deliver and maintain clinician-selected end-tidal anesthetic agent (EtAA) concentration using a modified closed-loop system. We evaluated the performance of an End-tidal Control (EtC) system on the Aisys CS2 anesthesia machine (GE HealthCare). We hypothesized EtC anesthetic delivery would be noninferior to manually controlled anesthetic delivery. METHODS: The Multi-site Anesthesia randomized controlled STudy of End-tidal control compared to conventional Results (MASTER) Trial evaluated anesthetic delivery in 210 adult patients receiving inhaled anesthesia. Patients were randomized to either EtC or manual control (MC) anesthetic delivery. The primary objective was to determine whether, compared to conventional anesthesia practice, EtC achieves and maintains clinician-specified EtAA and end-tidal oxygen (Eto 2) concentrations within defined noninferiority limits. Noninferiority was concluded if the lower limit of the 95% confidence interval (CI) of the difference between the percent duration within the acceptable range (5% of steady state or a margin of ~10% of each agent’s minimum alveolar concentration) for EtC and MC was ≥ −5% for both EtAA and Eto 2 . Secondary objectives included performance measures: response time: time required to attain 90% of the first desired EtAA, overshoot: amount the controller (or vaporizer delivery) exceeded the desired EtAA, and accuracy: average deviation from the desired EtAA. RESULTS: EtC achieved and sustained targeted EtAA and Eto 2 concentrations within the noninferiority threshold. The EtAA was within 5% of the desired value 98% ± 2.05% of the time with EtC compared to 45.7% ± 31.7% of the time with MC (difference 52.3% [95% CI, 45.9%–58.6%], P < .0001). For Eto 2, EtC was within the noninferiority limit 86.3% ± 22.8% of the time compared with MC at 41% ± 33.3% (P < .0001, difference 45.3% [95% CI, 36.1%–54.5%]). The median response time for achieving 90% of the initial EtAA desired value was 75 seconds with EtC and 158 seconds with MC (P = .0013). EtC exhibited a median overshoot of 6.64% of the selected EtAA concentration, whereas MC often failed to reach the clinician’s desired value. The difference in median percent deviation from desired EtAA value was 15.7% ([95% CI, 13.5%–19.0%], P < 0001). CONCLUSIONS: EtC achieves and maintains the EtAA and Eto 2 concentration in a manner that is noninferior to manually controlled anesthesia delivery.