Effects of Depth of Propofol and Sevoflurane Anesthesia on Upper Airway Collapsibility, Respiratory Genioglossus Activation, and Breathing in Healthy Volunteers.

BACKGROUND: Volatile anesthetics and propofol impair upper airway stability and possibly respiratory upper airway dilator muscle activity. The magnitudes of these effects have not been compared at equivalent anesthetic doses. We hypothesized that upper airway closing pressure is less negative and genioglossus activity is lower during deep compared with shallow anesthesia. METHODS: In a randomized controlled crossover study of 12 volunteers, anesthesia with propofol or sevoflurane was titrated using a pain stimulus to identify the threshold for suppression of motor response to electrical stimulation. Measurements included bispectral index, genioglossus electromyography, ventilation, hypopharyngeal pressure, upper airway closing pressure, and change in end-expiratory lung volume during mask pressure drops. RESULTS: A total of 393 attempted breaths during occlusion maneuvers were analyzed. Upper airway closing pressure was significantly less negative at deep versus shallow anesthesia (-10.8 ± 4.5 vs. -11.3 ± 4.4 cm H2O, respectively [mean ± SD]) and correlated with the bispectral index (P < 0.001), indicating a more collapsible airway at deep anesthesia. Respiratory genioglossus activity during airway occlusion was significantly lower at deep compared with light anesthesia (26 ± 21 vs. 35 ± 24% of maximal genioglossus activation, respectively; P < 0.001) and correlated with bispectral index (P < 0.001). Upper airway closing pressure and genioglossus activity during airway occlusion did not differ between sevoflurane and propofol anesthesia. CONCLUSIONS: Propofol and sevoflurane anesthesia increased upper airway collapsibility in a dose-dependent fashion with no difference at equivalent anesthetic concentrations. These effects can in part be explained by a dose-dependent inhibiting effect of anesthetics on respiratory genioglossus activity.

A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2.

BACKGROUND: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery. METHODS: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity. RESULTS: Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium-based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-à-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16:1 (95% CI, 10 to 26:1) for the reversal of ketamine and 3:1 (95% CI, 2 to 5:1) for the reversal of etomidate. CONCLUSIONS: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.

Anesthesia and increased hypercarbic drive impair the coordination between breathing and swallowing.

BACKGROUND: Coordination between breathing and swallowing helps prevent aspiration of foreign material into the respiratory tract. The authors examined the effects of anesthesia and hypercapnia on swallowing-breathing coordination. METHODS: In a randomized controlled crossover study, general anesthesia with propofol or sevoflurane was titrated using an up-down method to identify the threshold for suppression of the motor response to electrical stimulation of the forearm. Additional measurements included bispectral index, genioglossus electromyogram, ventilation (pneumotachometer), and hypopharyngeal pressure. During wakefulness and at each level of anesthesia, carbon dioxide was added to increase the end-tidal pressure by 4 and 8 mmHg. A swallow was defined as increased genioglossus activity with deglutition apnea and an increase in hypopharyngeal pressure. Spontaneous swallows were categorized as physiological (during expiration or followed by expiration) or pathological (during inspiration or followed by an inspiration). RESULTS: A total of 224 swallows were analyzed. Anesthesia increased the proportion of pathological swallows (25.9% vs. 4.9%) and decreased the number of swallows per hour (1.7±3.3 vs. 28.0±22.3) compared to wakefulness. During anesthesia, hypercapnia decreased hypopharyngeal pressure during inspiration (-14.1±3.7 vs. -8.7±2 mmHg) and increased minute ventilation, the proportion of pathological swallows (19.1% vs. 12.3%), and the number of swallows per hour (5.5±17.0. vs. 1.3±5.5). CONCLUSIONS: Anesthesia impaired the coordination between swallowing and respiration. Mild hypercapnia increased the frequency of swallowing during anesthesia and the likelihood of pathological swallowing. During anesthesia, the risk for aspiration may be further increased when ventilatory drive is stimulated.