Effect of Tulobuterol Patch Versus Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: A Randomized Controlled Trial

Abstract

BACKGROUND: Perioperative respiratory adverse events are common in children. We aimed to evaluate the effect of the transdermal β-2 agonist, tulobuterol, compared with that of placebo on the incidence of perioperative respiratory adverse events in pediatric patients undergoing tonsillectomy. METHODS: In this triple-blinded (patient, anesthesia provider, and outcome assessor) randomized controlled trial, 188 patients were randomly allocated to receive tulobuterol or a placebo. The tulobuterol groups received a tulobuterol patch (1 mg) masked with a bandage, whereas the placebo only received the bandage. The assigned bandage was applied to the patients 8 to 10 hours before the surgery. The primary outcome was the occurrence of any perioperative respiratory adverse events: oxygen desaturation <95%, airway obstruction, laryngospasm, bronchospasm, severe coughing, or stridor. The outcomes were evaluated using the average relative effect test, which estimates the effect of individual components of a composite outcome and then averages effects across components. RESULTS: A total of 88 and 94 patients who received tulobuterol and placebo, respectively, were analyzed. The incidence of any perioperative respiratory adverse event was lower with tulobuterol (n = 13/88; 14.7%) than that with the placebo (n = 40/94; 42.5%), with an estimated average relative risk (95% confidence interval) across components of 0.35 (0.20–0.60; P < .001). The symptoms of airway obstruction were lower with tulobuterol (n = 8/88; 9.0%) than that with the placebo (n = 32/94; 34.0%), with relative risk (95% CI) of 0.31 (0.17–0.56; P < .001). The occurrence of severe coughing was lower with tulobuterol (n = 1/88; 1.1%) than that with the placebo (n = 8/94; 8.5%), with relative risk (95% CI) of 0.15 (0.03–0.68; P = .014). CONCLUSIONS: In preschool children undergoing tonsillectomy, the preoperative application of a tulobuterol patch could decrease the occurrence of perioperative respiratory adverse events. Further studies are needed to elucidate the effect of the tulobuterol patch in a broad spectrum of pediatric anesthesia.

Beta Agonists for Prevention of Respiratory Adverse Events in Children Undergoing Adenotonsillectomy: Long-Acting, Short Acting, or Not Acting

“…9 When aiming to reduce PRAEs in a clinically significant manner, and to change routine clinical practice, the most effective method will be to target the highest-risk patient group, namely those with known reactive airway disease or those with a current or recent upper respiratory tract infection. While somewhat interesting, the current study by Kim et al 1 does not support the use of a more onerous and costly method of delivering a beta agonist compared with the more available, cheaper, and the easier-to-perform method of direct inhalation of albuterol in the immediate perioperative setting. Sometimes, it is better to keep things simple and safe.…”

“…The authors' observation of PRAEs in 42.5% of the control group reinforces the inconsequential nature of the criteria being used to define the outcomes. In the study by Kim et al, 1 and in previous studies investigating the preemptive use of beta agonists, the reduction in PRAEs was observed as a reduction in minor events of coughing and obstruction, while the most critically important adverse events of laryngospasm and bronchospasm were, in contrast to the inhaled route, not different between the treatment and placebo groups when using the patch.…”

“…However, perhaps the most significant issue with the design of the study by Kim et al 1 is reflected in the definition of PRAEs and the potential for mitigation using a beta agonist. A transitory oxygen desaturation <95%, particularly in a cohort prone to obstructive sleep apnea and frequent nocturnal desaturation, is hardly considerable as a significant adverse event.…”

“…Adenotonsillectomy is one of the most common surgical interventions in children, and while generally safe, it is associated with a risk of significant adverse events. In this issue, Kim et al 1 report a prospective randomized controlled study comparing preoperative use of a tulobuterol (long-acting beta agonist) dermal patch with placebo on the incidence of perioperative respiratory adverse events (PRAEs) in children undergoing adenotonsillectomy. Similar to previous studies, they defined PRAEs to include: “(1) oxygen desaturation <95%, (2) airway obstruction, presence of airway obstruction in combination with snoring noise and/or respiratory efforts, (3) laryngospasm, complete airway obstruction with associated muscle rigidity of the abdominal and chest wall, (4) bronchospasm, increased respiratory effort particularly during expiration and wheeze on auscultation, (5) severe coughing, a series of pronounced, persistent severe coughs lasting more than 10 s, and (6) postoperative stridor, high-pitched sound during breathing in the postoperative period.”…”

“…The study by Kim et al 1 invites discussion on study design and methods of statistical reporting. As with most prospective studies, the sample size is determined by the relative frequency of the outcome variable.…”