The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: a quantitative review

The purpose of this study was to review published studies (identified by a Medline-assisted search) on the effect of < or = 0.2 minimal alveolar concentration (MAC) halothane, isoflurane, enflurane and sevoflurane on the acute hypoxic ventilatory response in healthy subjects. Each article was examined for the anaesthetic agent, speed of hypoxic stimulus, background carbon dioxide and subject stimulation (audiovisual or painful). Analysis of variance was used to assess the significance of the influence of each of these factors on the standardised hypoxic response (the acute hypoxic ventilatory response in l.min(-1) in the presence of anaesthetic, expressed as a fraction of the response without anaesthetic). There were 37 separate studies within 21 published articles. The main factor influencing standardised hypoxic response was anaesthetic agent (p < 0.002). A second influential factor was subject stimulation (p < 0.014), but the interaction term of agent and stimulation was also significant (p < 0.039), suggesting that the influence of stimulation varied with the agent used. Speed of hypoxia and background carbon dioxide had no influence. In contrast to previous authors' assertions that study conditions have a major impact on the acute ventilatory response to hypoxia, this review suggests that the main determinant is simply the anaesthetic agent used. The review also highlights important gaps in the research literature, which may direct future research in this field. In particular, it would seem important to investigate the influence of arousal when different anaesthetic agents are used.