Effects of Intralaryngeal Carbon Dioxide and Acetazolamide on the Laryngeal Chemoreflex

Abstract

Sudden infant death syndrome is the leading cause of death in infants in the United States. The laryngeal chemoreflex (LCR) is thought to contribute to its pathogenesis. In adult animals, increasing levels of intralaryngeal CO2 result in a decrease in ventilatory activity. Intravenous acetazolamide (AZ) abolishes this response. The purpose of this study was to determine the effects of intralaryngeal CO2 and AZ on the LCR and respiratory physiology of piglets under normoxic and hypoxic conditions. We applied 0% or 10% CO2 in a randomized order to the larynx of 26 piglets. Intubation via tracheotomy prevented inhalation of the gas mixtures. Laryngeal stimulation was performed under normoxic conditions (PaO2 of >70 mm Hg) in 15 animals and under hypoxic conditions (PaO2 of 50 to 65 mm Hg) in 11 animals both with and without intravenous AZ (5 mg/kg). Respiratory and cardiovascular response data were recorded. Ten percent intralaryngeal CO2 has no significant effect on mean baseline respiratory rate, systemic PaCO2 or PaO2 levels, or apnea duration (p > .05). The use of AZ (versus no AZ) resulted in significantly higher baseline respiratory rates (64 versus 51 breaths per minute; p = .016), a decreased baseline systemic PaCO2 level (38.8 versus 45.9 mm Hg; p < .001), a higher baseline PaO2 level (97.9 versus 82.8 mm Hg; p < .001), shorter mean apnea durations (15.5 versus 24.8 seconds; p = .001), a higher lowest O2 saturation level after the stimulus (78.0% versus 68.4%; p = .003), and fewer profound apneas (10 of 90 versus 41 of 90 trials; p < .001). We conclude that 10% intralaryngeal CO2 does not decrease ventilatory activity in piglets and has no significant effect on the LCR. Acetazolamide, however, appears to have a protective effect against the LCR, resulting in shorter and less severe apneas. The protective effect of AZ against the LCR appears to be related to its ability to stimulate the respiratory drive and increase oxygenation at baseline.

The laryngeal chemoreflex: An evaluation of the normoxic response

“…In most infant animals, this response is relatively short‐lived, and resumption of respirations is followed by a return to cardiovascular stability 15–17, 22. In some animals, however, the respiratory drive remains depressed and prolonged and often fatal apneas ensue 23–27. It is also possible to elicit the laryngeal chemoreflex using organic stimuli, such as carbohydrates and milk 14, 28–31.…”

“…The laryngeal chemoreflex‐induced apnea usually lasts less than 10 seconds 15–17, 22. In some animals, the response can last longer, resulting in severe hypoxia and potentially death 23–27. Severe or fatal laryngeal chemoreflex responses are seen only in the very young, and have been shown to be present in a variety of species 19, 29, 32–35.…”

“…Previous studies have shown that stimulation of the laryngeal chemoreflex under hypoxic conditions (commonly referred to as the hypoxic laryngeal chemoreflex) is more likely to produce a profound or fatal response than stimulation of the reflex under normoxic conditions 23–27, 36. In an effort to better understand determinants of response severity, another study was performed in which several physiologic parameters were measured serially during the hypoxic laryngeal chemoreflex 36.…”

Determinants of Fatal Apnea Responses to Acid Stimulation of the Larynx in Piglets

“…Specifically, it has been observed that two young animals that undergo laryngeal chemostimulation under seemingly similar physiologic conditions can have marked differences in response severity. 10,[14][15][16][17] Some animals may recover uneventfully, and others may have profound or fatal responses. When laryngeal stimulation is performed under hypoxic conditions, one of two responses has been observed: a shorter, more transient response or a more profound, fatal response.l'' It has been shown that when laryngeal stimulation is performed under normoxic conditions, resumption of respiration occurs when the PaC02 reaches a certain threshold.l'' In that study, severity of response, as defined by apnea duration, was associated with the Pa02 at the time respiration was resumed.…”

“…However, the results are not UnIformly profound; the reasons for this are not fully understood. [14][15][16][17][18] One explanation for the lack of uniformly fatal responses to hypoxic stimulation may be that during prestimulation hypoxia, the ventilatory drive is stimulated and remains stimulated during the LCR, resulting in shorter and milder responses.P However, this does not explain why some animals respond to hypoxic stimulation with profound and fatal apneas and why others have more transient and milder responses. It is also plausible that it is the rate of change in Pa02 during the LCR, rather than the value of the end-apnea Pa02, that determines the response severity, as both of these factors appear to~e associated with response severity in the normoxic model.…”