APNEA FOLLOWING NORMOCAPNIC MECHANICAL VENTILATION IN AWAKE MAMMALS - A DEMONSTRATION OF CONTROL-SYSTEM INERTIA

1. Inhibition of inspiratory muscle activity from volume-related feedback during mechanical ventilation has been shown previously. To determine if this neuro-mechanical inhibition displays a memory effect, the duration of expiration immediately following cessation of mechanical ventilation was assessed in eight normal subjects. The subjects were passively mechanically ventilated via a nasal mask until the end-tidal CO2 (P(ET,CO2)) was a minimum of 30 mmHg and inspiratory effort was no longer detected, as evidenced by stabilization of mouth pressure and disappearance of surface diaphragm EMG activity. The ventilator output was held constant at a mean tidal volume (V(T)) of 1.0 l and breath duration of 4.6 s and P(ET,CO2) was increased 1-1.5 mmHg/min (via increased inspired CO2 fraction, F(I,CO2)) until inspiratory muscle activity returned. The P(ET,CO2) at which activation first occurred was defined as the CO2 recruitment threshold (P(CO2,RT)). The mechanical ventilation protocol was repeated and the P(ET,CO2) increased 1-1.5 mmHg/min until it was a mean of 1.1 mmHg above spontaneous P(ET,CO2) and 3.6 mmHg below P(CO2,RT). After 4.6 min of mildly hypercapnic mechanical ventilation, the mechanical ventilation was terminated. 2. Following termination of mechanical ventilation, the duration of the subsequent apnoea was 14.6 +/- 2.8 s (mean +/- S.E.M.) or 453 +/- 123 % > spontaneous T(E) and 178 +/- 62% > the T(E) chosen by the subject during 'assist control' ventilation at V(T) = 1.0 l. 3. To test the hypothesis that the apnoea following cessation of mechanical ventilation was due to a vagally mediated memory effect, the study was repeated in five double-lung transplant patients with similar P(CO2,RT) to normal subjects. These pulmonary vagally denervated patients also displayed an apnoea (14.5 +/- 4.0 s) upon cessation of mechanical ventilation (at a P(ET,CO2) 2.0 mmHg > eupnoea and 2.4 mmHg < P(CO2,RT)), that was 367 +/- 162 % > spontaneous T(E). 4. We also found significant apnoea in the awake dog immediately following mildly hypercapnic passive mechanical ventilation, and this was similar before and after bilateral vagal blockade (15.7 +/- 1.3 and 19.7 +/- 4.7 s, respectively). 5. We conclude that neuromechanical inhibition of inspiratory muscle activity, produced by passive mechanical ventilation at high V(T), exhibits a memory effect reflected in T(E) prolongation, which persists in the face of substantial increases in chemoreceptor stimuli. This effect is not dependent on vagal feedback from lung receptors. 6. We hypothesize that this persistent apnoea represents an inherent 'inertia', characteristic of the ventilatory control system. This inertia contributes to the prolongation of apnoea, independently of the specific mechanism which initiated the apnoea and may explain why apnoeas are commonly terminated at higher P(a,CO2)s than those at initiation.