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Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing TonsillectomiesThe REACT Randomized Clinical Trial

Educational Objective
To determine whether inhaled albuterol sulfate (salbutamol sulfate) premedication decreases the risk of perioperative respiratory adverse events in children undergoing anesthesia for tonsillectomy.
1 Credit CME
Key Points

Question  Does the use of albuterol sulfate (salbutamol sulfate) premedication reduce rates of perioperative respiratory adverse events in children aged 1 to 8 years undergoing anesthesia for tonsillectomy?

Findings  In this randomized clinical trial of 479 children, perioperative respiratory adverse events were observed in 67 of 241 of children receiving albuterol and 114 of 238 receiving placebo. Laryngospasm, coughing, and oxygen desaturation each occurred significantly more often in the placebo group.

Meaning  The benefits of albuterol premedication should be considered when planning anesthesia for children undergoing tonsillectomy, alongside other strategies for reducing the risk of perioperative respiratory adverse events in this high-risk population.

Abstract

Importance  Tonsillectomy is a common pediatric procedure for the treatment of sleep-disordered breathing and chronic tonsillitis. Up to half of children having this procedure experience a perioperative respiratory adverse event.

Objective  To determine whether inhaled albuterol sulfate (salbutamol sulfate) premedication decreases the risk of perioperative respiratory adverse events in children undergoing anesthesia for tonsillectomy.

Design, Setting, and Participants  A randomized, triple-blind, placebo-controlled trial (the Reducing Anesthetic Complications in Children Undergoing Tonsillectomies [REACT] trial) was conducted at Perth Children’s Hospital (formerly Princess Margaret Hospital for Children), the only tertiary pediatric hospital in Western Australia. Participants included 484 children aged 0 to 8 years who were undergoing anesthesia for tonsillectomy. The study was conducted between July 15, 2014, and May 18, 2017.

Interventions  Participants were randomized to receive either albuterol (2 actuations, 200 μg) or placebo before their surgery.

Main Outcomes and Measures  Occurrence of perioperative respiratory adverse events (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing, and stridor) until discharge from the postanesthesia care unit.

Results  Of 484 randomized children (median [range] age, 5.6 [1.6-8.9] years; 285 [58.9%] boys), 479 data sets were available for intention-to-treat analysis. Perioperative respiratory adverse events occurred in 67 of 241 children (27.8%) receiving albuterol and 114 of 238 children (47.9%) receiving placebo. After adjusting for age, type of airway device, and severity of obstructive sleep apnea in a binary logistic regression model, the likelihood of perioperative respiratory adverse events remained significantly higher in the placebo group compared with the albuterol group (odds ratio, 2.8; 95% CI, 1.9-4.2; P < .001). Significant differences were seen in children receiving placebo vs albuterol in laryngospasm (28 [11.8%] vs 12 [5.0%]; P = .009), coughing (79 [33.2%] vs 27 [11.2%]; P < .001), and oxygen desaturation (54 [22.7%] vs 36 [14.9%]; P = .03).

Conclusions and Relevance  Albuterol premedication administered before tonsillectomy under general anesthesia in young children resulted in a clinically significant reduction in rates of perioperative respiratory adverse events compared with the rates in children who received placebo. Premedication with albuterol should be considered for children undergoing tonsillectomy.

Trial Registration  Australian New Zealand Clinical Trials Registry identifier: ACTRN12614000739617

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Article Information

Accepted for Publication: January 18, 2019.

Corresponding Author: Britta S. von Ungern-Sternberg, MD, PhD, Department of Anaesthesia and Pain Management, Perth Children’s Hospital, 15 Hospital Ave, Nedlands WA 6009, Australia (britta.regli-vonungern@health.wa.gov.au).

Published Online: April 22, 2019. doi:10.1001/jamapediatrics.2019.0788

Author Contributions: Dr von Ungern-Sternberg and Dr Hall had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: von Ungern-Sternberg, Sommerfield, Slevin, Zhang, Hall.

Acquisition, analysis, or interpretation of data: Slevin, Drake-Brockman, Hall.

Drafting of the manuscript: von Ungern-Sternberg, Sommerfield, Drake-Brockman, Hall.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Drake-Brockman, Zhang.

Obtained funding: von Ungern-Sternberg, Slevin, Zhang, Hall.

Administrative, technical, or material support: von Ungern-Sternberg, Slevin, Drake-Brockman.

Supervision: von Ungern-Sternberg, Sommerfield, Slevin, Hall.

Conflict of Interest Disclosures: Dr von Ungern-Sternberg reported receiving grants from the Perth Children’s Hospital (PCH) Foundation and Australia and New Zealand College of Anaesthetists (ANZCA), and other support from the PCH Foundation during the conduct of the study. Dr Sommerfield reported receiving grants from the PCH Foundation and from Australian and New Zealand College of Anaesthetists during the conduct of the study. Ms Slevin reported receiving grants from the PCH Foundation and ANZCA during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by the PCH Foundation and an ANZCA project grant. The position held by Dr von Ungern-Sternberg is partly funded by the PCH Foundation, the Stan Perron Charitable Trust, and the Callahan Estate. Dr Hall was supported by a National Health and Medical Research Council fellowship.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2.

Additional Contributions: We acknowledge the assistance of our colleagues within the Department of Anaesthesia and Pain Management at PCH and the support of the ANZCA. Anoop Ramgolam, PhD (Telethon Kids, Institute Perth, Australia), assisted with data analysis. There was no financial compensation.

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