Abstract

BackgroundAlthough general anesthetics depress spontaneous respiration, the comprehensive effect of general anesthetics on respiratory function remains unclear. We aimed to investigate the effects of general anesthetics on spontaneous respiration in non-intubated mice with different types and doses of general anesthetic.MethodsAdult C57BL/6 J mice were administered intravenous anesthetics, including propofol and etomidate, and inhalational anesthetics, including sevoflurane and isoflurane in vivo at doses of 0.5-, 1.0-, and 2.0-times the minimum alveolar concentration (MAC)/median effective dose (ED50) to induce loss of the righting reflex (LORR). Whole-body plethysmography (WBP) was applied to measure parameters of respiration under unrestricted conditions without endotracheal intubation. The alteration in respiratory sensitivity to carbon dioxide (CO2) under general anesthesia was also determined. The following respiratory parameters were continuously recorded during anesthesia or CO2 exposure: respiratory frequency (FR), tidal volume (TV), minute ventilation (MV), expiratory time (TE), inspiratory time (TI), and inspiratory–expiratory time ratio (I/E), and peak inspiratory flow.ResultsSub-anesthetic concentrations (0.5 MAC) of sevoflurane or isoflurane increased FR, TV, and MV. With isoflurane and sevoflurane exposure, the CO2-evoked increases in FR, TV, and MV were decreased. Compared with inhalational anesthetics, propofol and etomidate induced respiratory suppression, affecting FR, TV, and MV. In 100% oxygen (O2), FR in the group that received propofol 1.0-times the ED50 was 69.63 ± 33.44 breaths/min compared with 155.68 ± 64.42 breaths/min in the etomidate-treated group. In the same groups, FR was 88.72 ± 34.51 breaths/min and 225.10 ± 59.82 breaths/min, respectively, in 3% CO2 and 144.17 ± 63.25 breaths/min and 197.70 ± 41.93 breaths/min, respectively, in 5% CO2. A higher CO2 sensitivity was found in etomidate-treated mice compared with propofol-treated mice. In addition, propofol induced a greater decrease in FR, MV, and I/E ratio compared with etomidate, sevoflurane, and isoflurane at equivalent doses (all P < 0.05).ConclusionsGeneral anesthetics differentially modulate spontaneous breathing in vivo. Volatile anesthetics increase FR, TV, and MV at sub-anesthetic concentrations, while they decrease FR at higher concentrations. Propofol consistently depressed respiratory parameters to a greater degree than etomidate.

Highlights

  • General anesthetics depress spontaneous respiration, the comprehensive effect of general anesthetics on respiratory function remains unclear

  • Sub‐anesthetic concentrations of volatile anesthetics increase FR, tidal volume (TV), and minute ventilation (MV) in wild type mice There were no measurable differences in respiratory activity among all experimental mice when exposed to room air, 100% O­ 2, 3% ­Carbon dioxide (CO2), and 5% ­CO2 conditions

  • Mice showed a reactive increase in FR, TV, and MV when exposed to 1 minimum alveolar concentration (MAC) sevoflurane and isoflurane with 100% ­O2 at the beginning

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Summary

Introduction

General anesthetics depress spontaneous respiration, the comprehensive effect of general anesthetics on respiratory function remains unclear. We aimed to investigate the effects of general anesthetics on spontaneous respiration in non-intubated mice with different types and doses of general anesthetic. More than 300 million major surgical procedures requiring general anesthesia or analgesics are conducted worldwide each year [1, 2]. General anesthetics and analgesics induce respiratory depression, which is a critical issue in clinical practice, especially for sedative procedures. Multiple studies have explored the depressant effect of opioids on respiration, but the effects of general anesthetics are not well elucidated [4, 5]. Even though a depressant effect is a commonly suggested effect of general anesthetics, significant differences are observed in respiratory behavior between general anesthetics. Respiratory frequency (FR) is significantly increased, and the overall apnea/hypopnea index is significantly decreased [9]

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