Aerosolized albuterol is frequently administered to mechanically ventilated neonates by metered dose inhaler (MDI) and a reservoir device. These reservoirs are often placed between the Y-piece and endotracheal tube, thereby creating mechanical dead space and increasing the risk of rebreathing carbon dioxide (CO(2)). The objectives of this study were: 1) to quantify CO(2) accumulation in two commonly used reservoirs (ACE(R), Aerochamber(R)-MV) and a bidirectional nonreservoir actuator (Airlife(R) Minispacer) during mechanical ventilation of a neonatal lung model; and 2) to determine the effect of tidal volume (V(T)) on CO(2) accumulation. We hypothesized that the accumulation of CO(2) in these devices is clinically insignificant at the small tidal volumes used in mechanically ventilated premature neonates. The model was constructed to simulate CO(2) exhalation by a ventilated neonate and consisted of a neonatal ventilator circuit (rate = 40/min; peak inspiratory pressure (PIP) = 20 cm H(2)0) attached to a reservoir/actuator and neonatal test lung. The ventilator delivered inspiratory gas (room air) to the test lung, which was vented into the atmosphere by a small adjustable leak. Expiration was simulated by manually ventilating 7.1% CO(2) (partial pressure of CO(2) (PCO(2)) = 48 mm Hg) back through the model. Accumulation of CO(2) within the reservoir/actuator was measured using an end-tidal CO(2) monitor. Each 4-min experiment was conducted at three V(T) (7.5 mL, 15 mL, and 25 mL), and the median PCO(2) was calculated in 0.5-min increments. For V(T) = 7.5 mL, CO(2) accumulated slowly in the ACE(R) and Minispacer(R) and reached a maximum at 4.0 min (PCO(2) = 2.3 mm Hg and 7.3 mm Hg, respectively). In contrast, the Aerochamber(R)-MV rapidly reached a PCO(2) of 9.5-10.0 mm Hg by 1-1. 5 min. A similar trend occurred with V(T) = 15 mL; however, higher partial pressures (approximately 10-12 mm Hg) were achieved with all devices. At V(T) = 25 mL, PCO(2) rose rapidly with the ACE(R), Aerochamber(R)-MV, and Minispacer(R), reaching peaks of 17.2, 12.3, and 20.3 mm Hg, respectively (P < 0.05). In conclusion, accumulation of CO(2) in reservoir/actuator depends on V(T) as well as the chamber design and internal volume. Due to the short duration of use when administering drugs via MDI, accumulation of CO(2) in these devices is not likely to be clinically relevant for the majority of ventilated newborns.