# Assessment of the autonomic response to a high dose CO2 inhalation challenge based on heart rate variability and skin conductance in a healthy population

**Authors:** Hanna-Dalia Laar, Hanna M.T. Carlman, Robert J. Brummer, Julia Rode

PMC · DOI: 10.1016/j.ibneur.2025.10.014 · 2025-10-27

## TL;DR

This study shows that inhaling high levels of CO2 causes both physical and psychological reactions in healthy people.

## Contribution

The study provides new insights into autonomic responses to CO2 inhalation using HRV and skin conductance in healthy individuals.

## Key findings

- CO2 inhalation increased parasympathetic activity as shown by HRV changes.
- Skin conductance indicated increased sympathetic activity during CO2 inhalation.
- CO2 inhalation also triggered psychological responses like panic symptoms.

## Abstract

Stress induction tests such as carbon dioxide (CO2) inhalation challenges, are often used in research of anxiety and panic disorders. Physiological parameters of the autonomic response, e.g., heart rate variability (HRV) and skin conductance (SC), are often measured alongside questionnaires for evaluation. Previous studies have shown varied results on CO2 inhalation-induced physiological reactivity and further knowledge is of interest. The aim of this study was to explore the effects of a 35 % CO2 inhalation test on HRV frequencies and SC, in healthy subjects; and to set those into relation with subjective psychological ratings. In this single-blinded, repeated measures study, healthy subjects underwent a 35 % CO2 inhalation challenge, whereof the first and third double vital capacity inhalations were with normal air and the second with 35 % CO2. HRV (low and high frequency) and SC (as electrodermal activity (EDA)) were measured throughout. CO2 inhalation resulted in a significant increase of HRV’s high and very high frequencies compared to the first air inhalation (median difference + 0.0001633; + 0.0000348) and of HRV’s very high and very low frequencies compared to the last air inhalation (+ 0.0000321; + 0.0000154). Mean and maximum SC increased significantly during the CO2 inhalation compared to both air inhalations (mean difference to first air inhalation + 1.151; + 1.964; to last air inhalation + 0.5751; +1.484), but also between the separate air inhalations (+ 0.5754; + 0.4799). The HRV results indicate increased parasympathetic activity, while the SC results indicate increased sympathetic activity during CO2 inhalation. SC only minorly correlated with provoked panic symptoms (EDA minimum to VAS minimum r = −0.559, and not between any other EDA and VAS/PSL measure). While those results seem contradictory, this study confirms that a 35 % CO2 inhalation challenge in young healthy adults, provokes a physiological as well as psychological reaction.

•Double vital capacity inhalations with 35 % CO2 induced distinct autonomic response.•35 % CO₂ inhalation evoked both physiological and psychological responses.•High frequency HRV changes suggest increased parasympathetic activity due to CO2.•Skin conductance changes suggest increased sympathetic activity during CO2 challenge.

Double vital capacity inhalations with 35 % CO2 induced distinct autonomic response.

35 % CO₂ inhalation evoked both physiological and psychological responses.

High frequency HRV changes suggest increased parasympathetic activity due to CO2.

Skin conductance changes suggest increased sympathetic activity during CO2 challenge.

## Linked entities

- **Chemicals:** CO2 (PubChem CID 280)
- **Diseases:** anxiety (MONDO:0005618)

## Full-text entities

- **Diseases:** anxiety (MESH:D001007), panic disorders (MESH:D016584)
- **Chemicals:** CO2 (MESH:D002245)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12617614/full.md

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Source: https://tomesphere.com/paper/PMC12617614