Optimizing Nebulized Ketamine for Postoperative Sore Throat Relief: A Placebo-Controlled Randomized Trial

Postoperative sore throat (POST) is a common complication following general anesthesia with endotracheal intubation, with reported incidences ranging from 20% to 90%, depending on patient characteristics, airway management techniques, endotracheal tube size, cuff pressure, duration of surgery, and methods of postoperative assessment. Although generally self-limiting, POST remains an important cause of postoperative discomfort, delayed recovery, and reduced patient satisfaction. Consequently, reducing the incidence and severity of POST has become an important quality indicator in perioperative care.

The pathophysiology of POST primarily involves mechanical trauma to the pharyngeal and laryngeal mucosa during laryngoscopy, endotracheal tube insertion, cuff inflation, and extubation. This mechanical injury triggers local inflammation, mucosal edema, and activation of peripheral nociceptors, resulting in postoperative pain and throat irritation.

Numerous pharmacological and non-pharmacological interventions have been investigated to prevent POST, including topical lidocaine, corticosteroids, magnesium sulfate, benzydamine hydrochloride, licorice, ketamine gargles, and nebulized ketamine. Among these strategies, nebulized ketamine has attracted increasing interest because it is non-invasive, easy to administer, inexpensive, and capable of delivering high local drug concentrations while minimizing systemic exposure.

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with well-established analgesic, anti-inflammatory, and antihyperalgesic properties. In addition to central analgesic effects, ketamine exerts peripheral actions through NMDA receptors located on airway mucosa and inflammatory cells, reducing local inflammatory responses and peripheral sensitization. Nebulized administration enables topical deposition throughout the upper airway, potentially preventing mucosal inflammation caused by endotracheal intubation.

Several randomized controlled trials and systematic reviews have demonstrated that nebulized ketamine significantly reduces both the incidence and severity of postoperative sore throat compared with placebo without producing clinically significant systemic adverse effects. However, nearly all previous clinical studies have evaluated a single dose of 50 mg. Whether a lower dose can provide equivalent clinical efficacy while further reducing the potential for dose-related adverse effects remains uncertain.