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

Abstract

SummaryThe purpose of this study was to review published studies (identified by a Medline-assisted search) on the effect of £ 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.Keywords Ventilation: hypoxia, systematic review. [16][17][18], the results obtained do not vary. The emphasis on audiovisual stimulation might also be questioned; simply watching television appears to prevent the marked depression by low-dose anaesthetic [13], yet painful electric shock has no effect [19].An alternative possibility is that variability across anaesthetic agents is simply due to different agents used [21]; but that variability within studies examining a single anaesthetic agent may be due to study conditions. The factors in study conditions which have received most attention are ramp vs. step hypoxia, the level of background carbon dioxide and the presence or absence of subject stimulation [23][24][25]. It would be desirable, though challenging, to conduct a single, large study incorporating all these study factors and employing all the common volatile agents to assess the contribution of each factor to variability. In the absence of such a study, a quantitative systematic review of the published literature is appropriate. It is perhaps interesting that, after more than 30 years of work in this field, no review exists which systematically documents published results on the effect of low dose volatile agents on the acute hypoxic ventilatory response.The purpose of this study was to search, collect and document relevant publications in the field and then explore the data for the main factors influencing the result...

Effect of low dose inhaled anaesthetic agents on the ventilatory response to carbon dioxide in humans: a quantitative review

“…This quantitative review (taken together with the results of a previous review [15]) suggests the blunting effect of anaesthetics occurs at the peripheral chemoreceptors. If this is the case, it is important to consider some possible mechanisms at cellular level.…”

“…This review (together with the results of a previous review [15]) helps define two separate sites of possible interactions for these variables. Future research could be directed towards specific areas such as interactions at the carotid body (e.g.…”

“…Currently, it is believed that chemoreception to hypoxia involves membrane depolarisation of carotid body glomus cells by inhibition of K + channels. Depolarisation initiates Ca 2+ influx (via voltage-gated channels) and the resulting rise in intracellular Ca 2+ causes neurotransmitter release The mean effect of low dose anaesthetics on hypoxic ventilatory response (value taken from a previous review [15]), and on the hypercapnic ventilatory response (values taken from the mean of all values in Tables 1 and 2). The hypoxic standardised response represents the hypoxic response in the presence of anaesthetic agent, expressed as a fraction of the response with no anaesthetic.…”

“…The source of this variability is unclear but another debate concerning variability has unfolded with respect to the effect of low dose anaesthetics on the ventilatory response to hypoxia. I have previously reviewed this debate in detail [15]. Some of the factors purported to contribute to the variability of hypoxic response (notably the anaesthetic agents themselves, the state of arousal of the subjects studied, and the methods used to administer the gaseous stimulus) may also be relevant to the hypercapnic response.…”

Hypoxia: developments in basic science, physiology and clinical studies

“…isoflurane and sevoflurane) obtund the chemoreflex much less than others (e.g. halothane) [19][20][21][22][23][24].…”