Safety of perioperative dexamethasone administration in children: time for reflection?

Abstract

The first reported human therapeutic use of cortisone occurred in 1948. The patient was a 29-yr-old woman being treated at the Mayo Clinic for severe rheumatoid arthritis. After 60 days of treatment, her rheumatoid symptoms had improved, but treatment was terminated due to side effects such as hirsutism, acne, and hostile ideation. Thus, it was notable that this first trial of therapeutic corticosteroid therapy was terminated due to complications from the drug. The purpose of this editorial is to review the current evidence for the safety profile of dexamethasone, a synthetic corticosteroid, given that the drug is now widely used in the perioperative period in both children and adults. Concerns may linger in the minds of some anesthesiologists that potential side effects from even a single modest dose of dexamethasone might be important. Is there any evidence to support these fears? Are children at any more or less risk than adults for potential side effects? Is dose size and frequency an important consideration? Is there clear enough evidence to answer these questions in 2013, or is more research required? Dexamethasone, a synthetic corticosteroid, is the product of research conducted by both the Schering Corporation and Merck Laboratories, as published in 1958. Over the following two decades, the use of dexamethasone as a potent anti-inflammatory agent was explored, and the drug was soon found to be beneficial in such clinical situations as third molar extraction and acute laryngotracheobronchitis (croup). The potent antiemetic action of dexamethasone was somewhat slower to be recognized, even though this had been shown in early studies. Dexamethasone found a role in the prevention of chemotherapy-induced vomiting in the 1980s, but it took another decade or more before the implications for the control of postoperative nausea and vomiting (PONV) were fully appreciated. The Society for Ambulatory Anesthesia has critically evaluated the evidence for appropriate prevention and management of PONV, and the ensuing guidelines recommend dexamethasone as an effective prophylactic antiemetic in children at a dose of 150 lg kg, up to 5 mg. Other perioperative effects of dexamethasone in children have focused on analgesia after procedures such as tonsillectomy and orchidopexy. The various benefits of dexamethasone are so well accepted that this drug is now used very widely in the perioperative period, usually as a single modest dose. Is there any evidence that this practice carries any significant risk – particularly in pediatric patients? The majority of evidence addressing harm from the use of corticosteroids comes from non-anesthetic literature. For example, corticosteroids are a mainstay in the treatment of asthma. In asthmatic children, daily oral or inhaled corticosteroids have been linked to decreased growth. Clinicians have also been concerned that corticosteroids may be associated with peptic ulceration, but the evidence suggests this to be more myth than reality. Corticosteroid-related psychological adverse effects are also possible in children, and they can manifest as aggressive behaviour and attention deficit hyperactivity disorder. This has been shown in studies on children undergoing long-term high-dose corticosteroid therapy for acute lymphoblastic leukemia and inflammatory bowel disease. Sleep disturbance has also been reported, but this has been shown to occur primarily in patients receiving K. Yee, MD R. G. Cox, MBBS (&) Department of Anesthesia, Alberta Children’s Hospital, University of Calgary, 2888 Shaganappi Trail N.W., Calgary, AB T3B 6A8, Canada e-mail: robin.cox@albertahealthservices.ca