Subjective and physiological responses to the 35% carbon dioxide challenge in healthy and non-clinical control populations: a meta-analysis and systematic review

ABSTRACT

Background/Rationale: The carbon dioxide (CO₂) challenge has been reliably used in laboratory settings as a panicogen in clinical populations. However, the magnitude of these effects on healthy and non-clinical control populations are not clear. The aim of this meta-analysis and systematic review is to provide quantitative estimates of those effects. Specifically, the current paper will evaluate the relative efficacy of the CO₂ challenge in eliciting both subjective and physiological arousal in healthy and non-clinical control populations.

Method: A total of 16 articles with 35 independent samples were included in the meta-analysis, while 37 studies with 74 independent samples were included in the systematic review.

Results: Both the meta-analysis and systematic review found the CO₂ challenge to elicit an increase in subjective distress via self-reported anxiety and fear. Physiological responses via blood pressure and heart rate were heterogeneous in studies sampled, with no significant changes observed across studies. Moderator analyses revealed the variations in findings may be attributed to participant screening and invasive sampling.

Discussion: Findings highlight the CO₂ challenge as a useful tool in the provocation of subjective distress. Implications for both the use of the CO₂ challenge and its anticipated effects in healthy and non-clinical control populations are discussed.

KEYWORDS:

• Carbon dioxide test
• heart rate
• blood pressure
• anxiety
• fear
• healthy

Acknowledgements

The authors would like to thank Nayyarain Ismail and Mira Battaion for their assistance with the preparation of this manuscript. The authors would also like to thank Dr. Leslie Atkinson for his ongoing guidance and support in our research.

Disclosure statement

No potential conflict of interest was reported by the authors.

Conflict of interest

No conflict of interest was reported by the authors in association with this paper.

ORCID

Jenny J. W. Liu http://orcid.org/0000-0003-2213-1346

Kristin Vickers http://orcid.org/0000-0001-5977-0251

Notes

1. All the studies reviewed and included in the current paper used a mixture of 35% CO₂-enriched air balanced with 65% oxygen.

2. The 35% CO₂ challenge (single-breath, vital-capacity inhalation) will be referred to as the CO₂ challenge throughout the rest of the paper.

3. Studies had multiple reasons for exclusion (e.g., study did not include a healthy control group and used administration of 7% CO₂). The most consistent reason selected by the raters was recorded in the event of multiple exclusionary reasons.

4. Visual inspection of the forest plot suggested that the results of Shufflebotham et al. (2009) may have influenced the effects. We re-ran the same analysis without this study and the results did not differ.

5. Visual inspection of the forest plot suggested that the results of Shufflebotham et al. (2009) may have influenced the effects. We re-ran the same analysis without this study and the results did not differ.