• DOI:10.1002/lary.24363
• Corpus ID: 43663954

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

@article{Patel2014HowSP,
  title={How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?},
  author={Nitin J. Patel and Nancy M. Bauman},
  journal={The Laryngoscope},
  year={2014},
  volume={124}
}

• N. J. Patel, N. Bauman
• Published 1 June 2014
• Medicine
• The Laryngoscope

BACKGROUND Infantile hemangiomas (IH) show a characteristic growth pattern of proliferation and eventual involution during the first decade of life, and may be isolated lesions or part of a constellation of findings such as “PHACEs” (posterior fossa abnormalities, hemangioma, arterial lesions, cardiac and eye anomalies). Two-thirds of IH occur in the head and neck, and otolaryngologists are frequently asked to manage such lesions. While partial or complete involution is the expected natural outcome, 12% of IH require therapy during infancy to hasten involution. There is no FDA-approved treatment of IH, and management is largely based on expert opinion and observational studies. Propranolol’s efficacy in treating IH has virtually supplanted the traditional use of corticosteroids, largely due to the side effects associated with prolonged corticosteroid therapy. In support of this paradigm shift, preliminary results of the only prospective, randomized controlled study comparing propranolol to prednisolone show similar efficacy but significantly fewer serious adverse events (AEs) from propranolol (unpublished data). Recognizing that propranolol is not FDA approved for any pediatric indication, this article reviews the current practice of use for IH, focusing on pretreatment screening, outpatient versus inpatient initiation, dosing, use in PHACEs, and monitoring for AEs. LITERATURE REVIEW Propranolol is a nonselective beta-adrenergic antagonist with a favorable safety profile for use in the pediatric population akin to that in adults. Menezes noted an 18% incidence of AEs upon review of all series reporting 10 patients with IH who were treated with propranolol. AEs reported in another review of 1,175 patients with IH include sleep disturbances (3.7%), asymptomatic or unspecified hypotension (2.8%), somnolence (2.2%), cool or mottled extremities (1.7%), pulmonary symptoms including wheezing (1.4%), asymptomatic or unspecified bradycardia (0.9%), hypoglycemia (0.9%), gastroesophageal reflux or gastrointestinal upset (0.7%), symptomatic hypotension (0.3%), and symptomatic bradycardia (0.1%) (Table 1). While AEs are generally not life-threatening, the most concerning are those affecting blood glucose and the cardiac system. Much debate exists regarding whether propranolol for IH should be initiated on an inpatient basis or on an outpatient monitored basis. Proponents of outpatient initiation cite propranolol’s long track record of safe use in patients with cardiac indications, while inpatient proponents caution that such data cannot be extrapolated to patients with IH. In a review of over 50 infants with IH admitted for propranolol therapy, all had at least one low systolic or diastolic blood pressure (BP) recording and two-thirds had at least one simultaneous low systolic and diastolic BP measure, with 14% having concomitant bradycardia. Despite the high frequency of events, all were asymptomatic and none warranted a change in medication dosing. Propranolol’s greatest effect on BP occurs with the initial dose and peaks 2 hours after an oral dose, which serves as a valuable guideline for monitoring. Hypoglycemia is a well-recognized AE that is dose independent, and if severe may induce seizure activity. The mechanism is thought secondary to beta blockade of glucose mobilization during fasting states, and reports are nearly always associated with concomitant infection and/ or poor oral intake. Beta blockade may induce bronchoconstriction, particularly during respiratory illnesses. The lack of consensus regarding pretreatment workup, initiation, and dosing of propranolol for IH led to a multidisciplinary consensus conference to review all data and establish best practice guidelines. (NIHNIAMS-1R34AR060881). The team of 28 experts from From the Division of Otolaryngology (N.J.P.); and the Division of Otolaryngology, Children’s National Medical Center (N.M.B.), George Washington University, Washington, DC, U.S.A. Editor’s Note: This Manuscript was accepted for publication on July 25, 2013. Dr. Bauman receives National Institutes of Health (NIH) salary support for study of this topic (ClinicalTrials.gov identifiers: NCT00967226, NICHD, 5R21HD062959). The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Nancy M. Bauman, MD, FACS, FAAP, Children’s National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010. E-mail: [e-mail]