CORONADO, CALIF. (FRONTLINE MEDICAL NEWS) – Studies of the most appropriate anesthetic agents for drug-induced sleep endoscopy are limited, but according to the best available evidence, local anesthetics appear to affect airway reflexes while inhalation anesthetics and opioids exaggerate dynamic airway collapse, so they may not be ideal.

Those are key conclusions from a systematic review of literature on the effects of commonly used anesthetic agents and opioids on the upper airway presented at the Triological Society’s Combined Sections meeting. Drug-induced sleep endoscopy (DISE) “is a great tool to assess upper airway dynamics in order to determine optimal surgical therapy for obstructive sleep apnea,” said Dr. Zarmina Ehsan, a pediatric pulmonary medicine fellow at Cincinnati Children’s Hospital Medical Center. “There’s a lack of understanding regarding how upper airway dynamics are altered by anesthetic agents, compared with normal sleep. This is important because this hinders the development of universal guidelines and protocols for the use of DISE.”

Using PubMed, EMBASE, and other sources, she and her associates conducted a qualitative systematic review of studies related to common anesthetic agents and opioids in the medical literature through September 2014. To be eligible for inclusion, a study must have evaluated the agent’s effect on the upper airway, must have contained an abstract, and must have been published in English. Studies with fewer than seven subjects, no original data, review articles, and those involving animals were excluded. The researchers reviewed 180 abstracts and included 56 full text articles in the final analysis, for a total study population of 8,540 patients. At the meeting Dr. Ehsan summarized the following findings by agent:

• Lidocaine. This agent is safe for topical use, has a rapid onset of action, and an intermediate duration of efficacy. Lidocaine acts on muscles “which are potent dilators and tensors of the pharyngeal and laryngeal structures,” she said. Of 10 studies included in the analysis, 7 assessed the impact of lidocaine on upper airway obstruction. Of these, three showed increased airway obstruction while four showed no significant effects. There were two studies on sleep parameters with conflicting results: One showed an increase in mean apnea duration with lidocaine use while the other did not. From this the researchers concluded that lidocaine does affect upper airway dynamics.

• Propofol. This lipophilic intravenous agent has a quick onset of action and acts by global central nervous system depression. Of 12 studies included in the analysis, 4 examined dose-response characteristics and showed a dose-dependent decrease in airway cross-sectional area with increased dosing of propofol. “So increasing your dose makes airway obstruction more likely,” Dr. Ehsan said. “The levels of obstruction were greatest at the base of tongue, and the closure was primarily in the anterior-posterior direction.” Three studies found that propofol caused a decrease in genioglossus electromyogram activity, while the remaining five studies assessed heterogeneous outcomes. “Overall, the studies showed that propofol had a dose-dependent effect on the upper airway with increasing doses making airway obstruction more likely,” she said.

• Dexmedetomidine (DEX). This agent is an alpha-2 adrenergic agonist with sedative, anxiolytic, and analgesic effects. It’s typically given as a 10-minute loading dose followed by a continuous infusion, and is recommended when you want to preserve spontaneous respiration. Of the four DEX-related studies that were included in the analysis, all demonstrated a minimal effect on upper airway cross-sectional area. “One of the studies looked at sleep parameters and concluded that DEX does approximate non-REM sleep without causing respiratory depression,” Dr. Ehsan added. “So overall, DEX was less likely to result in upper airway obstruction, compared with propofol.”

• Midazolam. This agent is commonly used for procedural sedation, with an onset of action within 1-3 minutes and a duration of 15-60 minutes. Of the six studies involving midazolam, two evaluated sleep staging. One reported lack of REM sleep and increased duration of stage N3 sleep , while the other study found that all sleep stages were observed at a lower dosage. The remaining four studies had heterogeneous outcomes. This led the researchers to conclude that midazolam “may lead to upper airway obstruction,” Dr. Ehsan said. “It’s unclear if this is dose dependent.”

• Pentobarbital. Of the two studies involving this short-acting barbiturate, one showed no effect on pharyngeal critical pressure or respiratory muscle function, while the other found that pentobarbital can increase the upper airway cross-sectional area. “So the effect of pentobarbital is unclear,” she said.

• Ketamine. This N-methyl-D-aspartate receptor has a rapid onset and a minimal effect on the central respiratory drive. Of the three studies involving ketamine, one found a 10% incidence of transient laryngospasm, one found that the incidence of transient laryngospasm was higher when it was delivered intramuscularly vs. intravenously, and one found that ketamine was safe in infants undergoing upper airway endoscopy. The researchers concluded that overall, ketamine “could be useful during DISE.”

• Inhalation anesthetics. There were 11 studies of these agents. Of these, six found that inhalation anesthetics caused upper airway collapse while five had heterogeneous outcomes. “Overall, a majority of studies found that inhalation anesthetics exaggerate dynamic airway collapse,” Dr. Ehsan said.

• Opioids. Of the nine studies involving these agents, six found that opioids caused upper airway obstruction; two found that they caused depression of upper airway reflexes, and one found that they caused a decrease in respiratory compliance. “Overall, opioids increase upper airway obstruction,” she said.

Dr. Ehsan acknowledged certain limitations of the analysis, including the fact that there was little information on sleep state approximated by many of these agents, “which makes it difficult to determine the ideal anesthetic protocol. There was substantial heterogeneity in outcomes, and few prospective studies comparing the ability of anesthetics to approximate natural sleep.” She recommended that future efforts focus on comparative effectiveness studies between the agents, as well as evaluate the impact of combining anesthetic agents. “This is important, because most DISE protocols use a combination of agents,” she said.

The meeting was jointly sponsored by the Triological Society and the American College of Surgeons

Dr. Ehsan reported having no relevant financial conflicts.

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