Preliminary study of automated oxygen titration at birth for preterm infants.

OBJECTIVE: To study the feasibility of automated titration of oxygen therapy in the delivery room for preterm infants. DESIGN: Prospective non-randomised study of oxygenation in sequential preterm cohorts in which FiO2 was adjusted manually or by an automated control algorithm during the first 10 min of life. SETTING: Delivery rooms of a tertiary level hospital. PARTICIPANTS: Preterm infants <32 weeks gestation (n=20 per group). INTERVENTION: Automated oxygen control using a purpose-built device, with SpO2 readings input to a proportional-integral-derivative algorithm, and FiO2 alterations actuated by a motorised blender. The algorithm was developed via in silico simulation using abstracted oxygenation data from the manual control group. For both groups, the SpO2 target was the 25th-75th centile of the Dawson nomogram. MAIN OUTCOME MEASURES: Proportion of time in the SpO2 target range (25th-75th centile, or above if in room air) and other SpO2 ranges; FiO2 adjustment frequency; oxygen exposure. RESULTS: Time in the SpO2 target range was similar between groups (manual control: median 60% (IQR 48%-72%); automated control: 70 (60-84)%; p=0.31), whereas time with SpO2 >75th centile when receiving oxygen differed (manual: 17 (7.6-26)%; automated: 10 (4.4-13)%; p=0.048). Algorithm-directed FiO2 adjustments were frequent during automated control, but no manual adjustments were required in any infant once valid SpO2 values were available. Oxygen exposure was greater during automated control, but final FiO2 was equivalent. CONCLUSION: Automated oxygen titration using a purpose-built algorithm is feasible for delivery room management of preterm infants, and warrants further evaluation.

Automated control of oxygen titration in preterm infants on non-invasive respiratory support.

OBJECTIVE: To evaluate the performance of a rapidly responsive adaptive algorithm (VDL1.1) for automated oxygen control in preterm infants with respiratory insufficiency. DESIGN: Interventional cross-over study of a 24-hour period of automated oxygen control compared with aggregated data from two flanking periods of manual control (12 hours each). SETTING: Neonatal intensive care unit. PARTICIPANTS: Preterm infants receiving non-invasive respiratory support and supplemental oxygen; median birth gestation 27 weeks (IQR 26-28) and postnatal age 17 (12-23) days. INTERVENTION: Automated oxygen titration with the VDL1.1 algorithm, with the incoming SpO2 signal derived from a standard oximetry probe, and the computed inspired oxygen concentration (FiO2) adjustments actuated by a motorised blender. The desired SpO2 range was 90%-94%, with bedside clinicians able to make corrective manual FiO2 adjustments at all times. MAIN OUTCOME MEASURES: Target range (TR) time (SpO2 90%-94% or 90%-100% if in air), periods of SpO2 deviation, number of manual FiO2 adjustments and oxygen requirement were compared between automated and manual control periods. RESULTS: In 60 cross-over studies in 35 infants, automated oxygen titration resulted in greater TR time (manual 58 (51-64)% vs automated 81 (72-85)%, p<0.001), less time at both extremes of oxygenation and considerably fewer prolonged hypoxaemic and hyperoxaemic episodes. The algorithm functioned effectively in every infant. Manual FiO2 adjustments were infrequent during automated control (0.11 adjustments/hour), and oxygen requirements were similar (manual 28 (25-32)% and automated 26 (24-32)%, p=0.13). CONCLUSION: The VDL1.1 algorithm was safe and effective in SpO2 targeting in preterm infants on non-invasive respiratory support. TRIAL REGISTRATION NUMBER: ACTRN12616000300471.

Development and preclinical testing of an adaptive algorithm for automated control of inspired oxygen in the preterm infant.

OBJECTIVE: To assess the performance of a novel algorithm for automated oxygen control using a simulation of oxygenation founded on in vivo data from preterm infants. METHODS: A proportional-integral-derivative (PID) control algorithm was enhanced by (i) compensation for the non-linear SpO2-PaO2 relationship, (ii) adaptation to the severity of lung dysfunction and (iii) error attenuation within the target range. Algorithm function with and without enhancements was evaluated by iterative linking with a computerised simulation of oxygenation. Data for this simulation (FiO2 and SpO2 at 1 Hz) were sourced from extant recordings from preterm infants (n=16), and converted to a datastream of values for ventilation:perfusion ratio and shunt. Combination of this datastream second by second with the FiO2 values from the algorithm under test produced a sequence of novel SpO2 values, allowing time in the SpO2 target range (91%-95%) and in various degrees of hypoxaemia and hyperoxaemia to be determined. A PID algorithm with 30 s lockout after each FiO2 adjustment, and a proportional-derivative (PD) algorithm were also evaluated. RESULTS: Separate addition of each enhancing feature to the PID algorithm showed a benefit, but not with uniformly positive effects. The fully enhanced algorithm was optimal for the combination of targeting the desired SpO2 range and avoiding time in, and episodes of, hypoxaemia and hyperoxaemia. This algorithm performed better than one with a 30 s lockout, and considerably better than PD control. CONCLUSIONS: An enhanced PID algorithm was very effective for automated oxygen control in a simulation of oxygenation, and deserves clinical evaluation.

Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support.

OBJECTIVE: To evaluate the performance of a novel rapidly responsive proportional-integral-derivative (PID) algorithm for automated oxygen control in preterm infants with respiratory insufficiency. DESIGN: Interventional study of a 4-hour period of automated oxygen control compared with combined data from two flanking periods of manual control (4 hours each). SETTING: Neonatal intensive care unit. PARTICIPANTS: Preterm infants (n=20) on non-invasive respiratory support and supplemental oxygen, with oxygen saturation (SpO2) target range 90%-94% (manual control) and 91%-95% (automated control). Median gestation at birth 27.5 weeks (IQR 26-30 weeks), postnatal age 8.0 (1.8-34) days. INTERVENTION: Automated oxygen control using a standalone device, receiving SpO2 input from a standard oximeter and computing alterations to oxygen concentration that were actuated with a modified blender. The PID algorithm was enhanced to avoid iatrogenic hyperoxaemia and adapt to the severity of lung dysfunction. MAIN OUTCOME MEASURE: Proportion of time in the SpO2 target range, or above target range when in air. RESULTS: Automated oxygen control resulted in more time in the target range or above in air (manual 56 (48-63)% vs automated 81 (76-90)%, p<0.001) and less time at both extremes of oxygenation. Prolonged episodes of hypoxaemia and hyperoxaemia were virtually eliminated. The control algorithm showed benefit in every infant. Manual changes to oxygen therapy were infrequent during automated control (0.24/hour vs 2.3/hour during manual control), and oxygen requirements were unchanged (automated control period 27%, manual 27% and 26%, p>0.05). CONCLUSIONS: The novel PID algorithm was very effective for automated oxygen control in preterm infants, and deserves further investigation.