Pallid Breath-Holding Spells With Glycopyrrolate

Breath-holding spells are a common childhood disorder that typically present before 12 months of age. Whereas most cases are benign, some patients have very severe cases associated with bradycardia that can progress from asystole to syncope and seizures. Treatment studies have implicated the use of several therapies, such as oral iron, fluoxetine, and pacemaker implantation. This is a retrospective study of patients treated with glycopyrrolate for pallid breath-holding spells. Clinical data from 4 patients referred to pediatric cardiology who saw therapeutic benefit from treatment using glycopyrrolate were reviewed to evaluate for clinical response to the drug. Two twin patients, whose symptoms began at 5 months of age, experienced a decrease in breathholding frequency after 1 month. A patient diagnosed at 7 months of age experienced a decrease in frequency of spells. A patient diagnosed at 10 months of age reported cessation of syncope shortly after initiation of glycopyrrolate and complete resolution of breath-holding spells during prolonged treatment. This case study of 4 patients with pallid breath-holding offers evidence that glycopyrrolate may be beneficial in treating breathholding spells and has a safer side-effect profile than pacemaker implantation. Breath-holding spells are a common pediatric disorder, usually occurring between 6 months and 4 years of age.1 The spells, characterized as nonepileptic, paroxysmal anoxic syncope that often leads to seizures, are provoked by external emotional stimuli, such as pain, anger, crying, or excitement. Breath-holding spells are classified into 3 types based on a child’s coloration: cyanotic, pallid, or mixed.2 The cause is unknown, but a genetic pattern of autosomal dominance with variable penetrance has been identified.3 Diagnosed clinically, breath-holding spells are described as a sequence of emotional provocation, noiseless expiration accompanied by apnea, color change, and syncope resulting from autonomic dysfunction.2 Although autonomic dysfunction is the common underlying problem, cyanotic breathholding spells result from overactivity of the sympathetic nervous system, whereas pallid breath-holding spells are the result of increased parasympathetic tone.4 The natural course of breath-holding spells is usually transient, with cessation by early toddler years.5 Long-term prognosis is generally excellent, with the expectation of normal development. The standard of care is reassurance for most patients, but children with severe sequelae require further treatment. Various medical treatments have been studied. Walsh et al reported that fluoxetine decreased the frequency of breath-holding spells in 5 of 6 patients, with complete resolution in 3 patients.4 Iron-deficiency anemia has also been linked to breath-holding spells, with Department of Pediatrics, Medical University of South Carolina Children’s Hospital, Charleston, South Carolina Drs Williams and Cain conceptualized and designed the study and drafted the initial manuscript; Dr Cain reviewed and revised the manuscript; and both authors approved the final manuscript as submitted. www.pediatrics.org/cgi/doi/10.1542/peds.2014-2456 DOI: 10.1542/peds.2014-2456 Accepted for publication Jan 9, 2015 Address correspondence to Nicole Cain, MD, Department of Pediatrics, MUSC Children’s Hospital, EH 629, 165 Ashley Ave, Charleston, SC 29425. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2015 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. CASE REPORT PEDIATRICS Volume 135, number 5, May 2015 by guest on October 23, 2017 http://pediatrics.aappublications.org/ Downloaded from complete or partial remission of symptoms in 84% of patients treated with iron sulfate.6 In severe cases, permanent pacing has been used as treatment of prolonged bradycardia and asystole.1 A few clinicians have noted anecdotal success in the treatment of breathholding spells with anticholinergic agents, including glycopyrrolate. Normally used in anesthesia to reduce oral secretions, glycopyrrolate is a synthetic anticholinergic drug with longer-acting properties than atropine that provides treatment against cardiac inhibition in severe recurrent breath-holding spells.5 In 1 case report, the use of glycopyrrolate resulted in resolution of syncope in 1 patient with severe recurrent spells without the significant side effects seen with cardiac pacemaker implantation.5 In our retrospective study, we examine the use of glycopyrrolate in 4 patients with similar recurrent syncope and bradycardia and report that glycopyrrolate is beneficial and is an alternative treatment modality.