36 Chapter 2 for 2x24 hours, and a similar difference in time in TR was seen (71.2% vs. 61.4%, P < 0.001). Different TRs (range 80-95%) were used between participating centres which make results potentially more generalisable but also harder to interpret, as a different target range will influence controller performance. Finally, the last study showed that the 30-second pause was superior to manual control and non-inferior to the 180-second pause, with similar increases in TR time.26 CLAC is not designed to treat acute SpO2 deterioration; the algorithm will raise an alarm and cease operation if low SpO2 values occur. Also, suspending action after an adjustment might be undesirable, as an algorithm could also use SpO2 feedback to try to resolve hypoxia more swiftly and diminish subsequent overshoot. Closed-loop Inspired Oxygen Control (CLiO2) 18 How it works The first algorithm for AOC to be embedded in a neonatal ventilator was CLiO2 available in the AVEA ventilator (Vyaire Medical, Mettawa, United States). This algorithm, a hybrid of rule-based and proportional-derivative control with an adaptive element, runs through a large set of instructions each second.37 The algorithm starts with SpO2 validation, and determination of the status of oxygenation (normoxic, hyperoxic or hypoxic). After a change in oxygenation status for ≥ 3 seconds (to filter out short fluctuations), an initial FiO2 adjustment is made, proportional to the magnitude of the error. For the CLiO2 algorithm, the SpO2 error is calculated in relation to the upper and lower limits of the TR in hyperoxia and hypoxia, respectively, rather than the mid-point. The timing and magnitude of further FiO2 adjustments are then determined in relation to the SpO2 error (via a proportional term), the SpO2 trend (via a derivative term) and the baseFiO2 (via an adaptive component). The FiO2 increments will be amplified if SpO2 is deviating further from the TR limits, and with progressively smaller increments as SpO2 approaches the TR. With the CLiO2 algorithm, the adjustments in FiO2 rarely lead to an FiO2 below baseFiO2; only long-lasting periods of mild hyperoxia will result in an FiO2 below the base value. BaseFiO2 is updated periodically after at least 5 minutes, using the last 300 FiO2 values that meet specific conditions. The average of these values is limited to ±10% of the current baseFiO2 and then again averaged with the current baseFiO2. 37
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