Volatile Anaesthetic Depression of the Carotid Body Chemoreflex-Mediated Ventilatory Response to Hypoxia: Directions for Future Research

Abstract

In assessing whether volatile anaesthetics directly depress the carotid body response to hypoxia it is necessary to combine in meta-analysis studies of when it is “functionally isolated” (e.g., recordings are made from its afferent nerve). Key articles were retrieved (full papers in English) and subjected to quantitative analysis to yield an aggregate estimate of effect. Results from articles that did not use such methodology were assessed separately from this quantitative approach, to see what could be learned also from a nonquantitative overview. Just 7 articles met the inclusion criteria for hypoxia and just 6 articles for hypercapnia. Within these articles, the anaesthetic (mean dose 0.75, standard deviation (SD) 0.40 minimum alveolar concentration, MAC) statistically significantly depressed carotid body hypoxic response by 24% (P = 0.041), but a similar dose (mean 0.81 (0.42) MAC) did not affect the hypercapnic response. The articles not included in the quantitative analysis (31 articles), assessed qualitatively, also indicated that anaesthetics depress carotid body function. This conclusion helps direct future research on the anaesthetic effects on putative cellular/molecular processes that underlie the transduction of hypoxia in the carotid body.

Influence of propofol on isolated neonatal rat carotid body glomus cell response to hypoxia and hypercapnia

“…Whilst chemoreceptor function may be immature in new born animals maturational differences in the hypoxic response in rat carotid bodies largely disappear by 10–15 days (Donnelly and Kholwadwala, 1992). Despite these considerations there is a concordance of results obtained with respect to anaesthetic sensitivity of carotid body responses between rats (neonatal and adult) and human ventilatory responses, which is striking (Karanovic et al, 2010; Pandit, 2014).…”

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO2chemosensitivity

“…The literature is inconsistent, and differences have been reported with different anesthetic agents, concentrations, and species investigated (Groeben et al 2003;Hirshman et al 1977;Knill et al 1983;Martin-Body and Sinclair 1985;Pandit 2014). Recognizing the potential for halogenated anesthetics to alter breathing, ventilatory responsiveness, and mechanisms of chemosensitivity is critical when interpreting the results of studies conducted under anesthesia.…”

Inhaled carbon dioxide causes dose-dependent paradoxical bradypnea in animals anesthetized with pentobarbital, but not with isoflurane or ketamine

“…but only one anesthetized state" (Perouansky, 2012) clearly does not apply to the respiratory effects of anesthetic drugs. For example, opioids (Dahan, 2007;Dahan et al, 2008;Eckenhoff and Helrich, 1958), barbiturates (Eckenhoff and Helrich, 1958;Goldberg and Milic-Emili, 1977;Siafakas et al, 1983) and volatile anesthetics (Gautier et al, 1987;Pandit, 2005Pandit, , 2007Pandit, , 2014Pandit et al, 1999;Pandit and Moreau, 2005) each have distinct patterns and mechanisms of respiratory depression.…”

“…In response to these anesthetic drugs, the PaCO 2 ventilation response curve is both flatter and is shifted to the left (with both an increased apneic PaCO 2 threshold and an increased hyperpnic PaCO 2 threshold) (Lumb, 2010). While these anestheticmediated effects are predominantly marked for opioids (Dahan, 2007;Dahan et al, 2008;Eckenhoff and Helrich, 1958) and barbiturates (Eckenhoff and Helrich, 1958;Goldberg and Milic-Emili, 1977;Siafakas et al, 1983), they are more limited for volatile anesthetics, where there is a more pronounced effect on the ventilatory response to hypoxia than to hypercarbia (Gautier et al, 1987;Pandit, 2005Pandit, , 2007Pandit, , 2014Pandit et al, 1999;Pandit and Moreau, 2005). Other anesthetic drugs, most notably ketamine, do not significantly depress spontaneous ventilation (Gautier and Gaudy, 1978).…”