Paradoxical effect of oxygen administration on breathing stability following post‐hyperventilation apnoea in lambs

Abstract

Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body activity, and yet earlier experiments in neonates have shown that PB incidence may be increased following the application of hyperoxia. To clarify this paradox, we studied the changes in the pattern of PB that occur following administration of oxygen in a lamb model of PB. PB was induced in eleven of seventeen anaesthetized lambs following passive hyper‐ventilation with air. When oxygen was administered during PB, the pattern was first enhanced, as evidenced by a sudden decrease in the ratio of the ventilatory duration to the apnoeic pause duration, and then suppressed, as evidenced by a progressive return to stable breathing which was associated with an increase in minute ventilation. Five of the six lambs that did not show PB following passive hyperventilation with air could be made to do so if oxygen was substituted for air as the inspired gas following passive hyperventilation. Five of the eleven lambs that showed PB following hyperventilation with air responded to the application of oxygen during PB by switching to a gross form of episodic breathing consisting of long apnoeic pauses followed by equally long periods of breathing during which minute ventilation fell progressively with time. We conclude that when applied against a background of arterial hypoxaemia, oxygen has a destabilizing influence on ventilation in that (a) it accentuates the unstable breathing that occurs during PB, (b) it induces PB in lambs that exhibited stable breathing in air, and (c) it may precipitate episodic breathing.

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb

“…For example, in preterm infants, the waxing and waning pattern of PB that is characteristic of the adult is replaced by a more or less abrupt on-off pattern that shows little change in tidal volume during the breathing phase (42); this pattern resembles that seen in hibernating animals (34). Furthermore, although the response to hyperoxic inspired gas applied during PB is generally similar in adults and infants (17,27,51) in that the instability is transiently enhanced as evidenced by the immediate increase in the duration of the apneic pause, incidental observations show that the response to hypoxia applied during PB in preterm infants (44) is apparently opposite to that of adults (48). In the preterm infant, PB is suppressed by hypoxic inspired gas, whereas it is enhanced in adults.…”

“…When a comparison is made between experimental animal models of PB and infants, further major discrepancies are revealed. Unlike in human infants (and adults), spontaneous PB has not been reported in intact experimental animals and cannot be induced during exposure to hypoxic inspired gas (11, 21), even though hypoxic stimulus of the carotid bodies, consistently implicated in PB (11,25,50,51), is at a maximum during hypoxia; curiously, in animals, PB appears only after the return to room air after hypoxic exposure.Although theoretical models of the respiratory control system have been proposed that support the view that PB involves the activity of central and peripheral chemoreceptors either individually or in concert (25, 31), it is not clear whether all of the conditions/discrepancies cited above can be accounted for by one theoretical model. Nor are there experimental tests currently available to determine which chemosensitive receptor systems are responsible for a particular type of instability.…”

“…When a comparison is made between experimental animal models of PB and infants, further major discrepancies are revealed. Unlike in human infants (and adults), spontaneous PB has not been reported in intact experimental animals and cannot be induced during exposure to hypoxic inspired gas (11,21), even though hypoxic stimulus of the carotid bodies, consistently implicated in PB (11,25,50,51), is at a maximum during hypoxia; curiously, in animals, PB appears only after the return to room air after hypoxic exposure.…”

“…In this study, we test the predicted effect of hypoxia applied during PB in a newborn lamb model of PB our laboratory has established in earlier studies (50,51). In addition, because there is theoretical evidence that CO 2 administration should suppress PB in adult humans (31,33) and because CO 2 administration has recently been used clinically in an attempt to control breathing instability in both adults (2,32,47) and infants (1), we also examined the effect of CO 2 administration on PB.…”

“…In both models, we demonstrated that the unstable breathing pattern of PB was transiently exacerbated by administration of hyperoxic inspired air in a setting in which the initial conditions included hypoxemia at the peripheral chemoreceptors. We interpreted this observation in terms of hyperoxic inspired gas increasing the loop gain (LG), or more specifically the plant gain (for oxygen), of the respiratory control system (4,50,51), such that increments in ventilation cause larger changes in arterial PO 2 (Pa O 2 ) than if air were the inspired gas. This observation suggests that if we were to adopt the opposite strategy and apply hypoxic inspired air during PB in the lamb, we would transiently reduce or even suppress the ventilatory instability of PB as a result of a reduction of the LG of the respiratory control system to Ͻ1.…”