Trial Picks Best Preop Sedative for Kids’ Tonsil Surgery

Intranasal dexmedetomidine (Precedex) outperformed midazolam as anti-anxiety premedication for children age 12 and younger undergoing tonsillectomy and/or adenoidectomy in a randomized trial.

Children receiving intranasal midazolam were twice as likely to experience perioperative respiratory adverse events (PRAEs) than those in a saline control group (adjusted OR 1.99, 95% CI 1.18-3.35), according to Fangming Shen, MD, of Xuzhou Medical University in Jiangsu, China, and colleagues writing in JAMA Network Open.

Conversely, those receiving intranasal dexmedetomidine were significantly less likely to experience PRAEs compared to the control group (aOR 0.45, 95% CI 0.26-0.78).

When the two active-treatment groups were compared directly, midazolam was associated with dramatically higher risk of PRAEs incidence than dexmedetomidine (aOR, 4.44, 95% CI 2.54-7.76). No other serious clinical adverse events were observed.

Compared to control, children receiving dexmedetomidine were less prone to desaturation (aOR 0.46, 95% CI 0.25-0.84) and coughing (aOR 0.33, 95% CI 0.14-0.78). Midazolam was associated with a seven-fold increase in laryngospasm and more than tripled incidence of airway obstruction, compared to dexmedetomidine.

Liu and colleagues explained that the most common complication during pediatric anesthesia is perioperative respiratory adverse events. Minimizing the risk of these events is an important goal, the researchers continued, as they can lengthen hospitalization time, increase hospitalization cost, and cause varying degrees of physical and psychological trauma to children and parents.

Yet not all clinicians agree that dexmedetomidine, or indeed any premedication for anxiety, is called for in every case.

“[T]he study by Shen and colleagues may highlight more questions than answers,” Nicholas M. Dalesio, MD, and Sapna R. Kudchadkar, MD, PhD, both from Johns Hopkins University School of Medicine in Baltimore, said in an accompanying editorial.

“Two of the most important questions when discussing anesthesia and the developing brain are as follows: Is less more? Which outcomes matter most?” the editorialists wrote. “Nonpharmacologic approaches to preoperative anxiolysis and postoperative emergence agitation are well described. The anxiolytic medications we use are predictable when used alone, but polypharmacy creates complexity in the broad spectrum of children for whom we care.

“The benefits of dexmedetomidine in pediatric patients with [adenotonsillectomy] may seem clear, but the decision to administer any preoperative anxiolytic should never be automatic,” Dalesio and Kudchadkar continued. “Each and every medication should be carefully considered in the context of the individual child’s needs and risks.”

The pair also questioned certain aspects of the trial design and reporting. It “did not standardize the perioperative anesthetic medications” used in surgery, nor were treatments for “emergence delirium” described. Dalesio and Kudchadkar also noted “inconsistent” use of reversal agents for neuromuscular blockade and other agents.

“Without standardization of the anesthetic regimen, it is difficult to attribute any postoperative complications to just one preoperative medication,” the editorialists wrote.

Study Details

This single-center, double-blind randomized clinical trial was conducted using children 0 to 12 years of age who were undergoing elective tonsillectomy or adenoidectomy from October 2020 to June 2021 at the Children’s Hospital of Xuzhou Medical University.

A total of 384 children were enrolled (median age of 7 years and 59.1% boys). More than three-quarters of participants underwent tonsillectomy plus adenoidectomy while nearly all the rest only had the latter. Data were adjusted for age, sex, American Society of Anesthesiologists physical status, body mass index, obstructive sleep apnea, upper respiratory tract infection (URTI), and passive smoking. Children were excluded if they had known cardiopulmonary diseases, neuromuscular diseases, body mass index of 30 or greater, severe URTI, or allergies to either trial medication.

Participants were randomized in equal numbers to saline, dexmedetomidine, or midazolam as premedication. Intranasal midazolam was given at 0.1 mg/kg and intranasal dexmedetomidine at 2.0 μg/kg. Controls received saline in a 0.9% solution.

Limitations to the study cited by its authors included that, while the study’s investigators were blinded, experienced anesthesiologists could probably guess the assignments by observing patient behavior. Antagonists such as neostigmine were also not routinely used and neuromuscular transmission was not monitored. Sleep apnea status was assessed via clinical history rather than by polysomnography. Finally, the study did not evaluate the premedication’s anxiolytic efficacy directly, although Shen’s group reported that the dexmedetomidine group required less postoperative fentanyl.