Entrainment of respiration in humans by periodic lung inflations: Effect of state and CO₂

Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory activity and the onset of a mechanical breath. We examined the entrainment response to mechanical ventilation of normal humans over a range of machine rates during wakefulness and during isocapnic and hypercapnic NREM sleep. Wakefulness facilitated 1:1 entrainment of the respiratory rhythm to the mechanical ventilator over a wider range of machine frequencies than during NREM sleep (p < 0.001); isocapnic and hypercapnic conditions did not differ (p = 0.95). To evaluate the Hering-Breuer reflexes in the resetting of the respiratory rhythm during sleep, we examined changes in neural inspiratory time (T₁) as the relationship between inspiratory efforts and onset of machine inflations changed. As inspiratory efforts extended into the machine inflation cycle, neural T₁ shortened. We conclude that entrainment responses of normal humans to mechanical ventilation differ depending on state, but mild increases in respiratory drive caused by CO₂ stimulation do not affect these entrainment responses. Furthermore, the changes in neural T₁ are consistent with observations in animal studies in which Hering-Breuer reflexes mediated entrainment.