Periodic breathing triggered by hypoxia in normal awake adults. Modification by naloxone

Breathing patterns in six normal awake subjects were monitored noninvasively during progressive hypoxia accomplished with the administration of nitrogen at 2, 4, 6, and 8 L/min by nasal cannula. The lowest value of arterial oxygen saturation (SaO2) of 88 +/- 4 percent (mean +/- SD) was achieved with nitrogen at 8 L/min. At baseline, tidal volume (VT) and frequency were fairly regular; with nitrogen at 2 and 4 L/min, some subjects showed minor fluctuations of VT. At 6 and 8 L/min, periodic breathing with marked oscillations of VT, apneas, hypopneas, and intermittent large tidal breaths were consistently observed. Inspired oxygen concentration fluctuated because of the variations of tidal breaths provoked when periodic breathing took place and enhanced fluctuation in SaO2. A randomized, double-blind crossover design was used to assess the effect of pretreatment with naloxone on this periodicity. In contrast to the irregular breathing pattern observed with pretreatment with placebo, the breathing pattern after pretreatment with naloxone was regular during nasal administration of nitrogen except at 8 L/min, when minor fluctuations in VT with occasional hypopneas and large tidal breaths occurred. On another day, irregular and periodic breathing with apneas or hypopneas (or both) produced by nasal nitrogen at 8 L/min was eliminated or blunted by short-term intravenous administration of naloxone. On another day, electroencephalographic monitoring corroborated visual observations made in the previous studies that the hypoxic subjects were awake during the breathing alterations. Thus, awake adults develop irregular and periodic breathing during induction of mild hypoxia produced by nasal administration of nitrogen. The irregularity in breathing appears to be mediated through release of endorphins, since the effect is blunted or eliminated by pretreatment or short-term treatment with naloxone.