Correspondence

More on Propranolol for Hemangiomas of Infancy

N Engl J Med 2008; 359:2846-2847December 25, 2008

Article

To the Editor:

The response of infantile hemangiomas to propranolol reported in the letter by Léauté-Labrèze et al. (June 12 issue)1 catapulted the use of this treatment to first-line status among physicians managing this disease. Not included in their letter was a discussion about initiating and monitoring propranolol use, or about potential risks, which may be unique among these patients. The most common serious adverse effects are bradycardia and hypotension. Infants with very large hemangiomas or miliary hemangiomatosis are at risk for high-output cardiac compromise.2 Propranolol may mask the clinical signs of early cardiac failure and diminish cardiac performance. Propranolol may also blunt the clinical features of hypoglycemia. Sustained hypoglycemia in infancy has been associated with long-term neurologic sequelae.3 We know of two infants who had unrecognized side effects from propranolol.

We developed a treatment protocol to optimize safety: baseline echocardiography and 48-hour hospitalization or home nursing visits to monitor vital signs and blood glucose levels. Medication is given every 8 hours, with an initial dose of 0.16 mg per kilogram of body weight. If the vital signs and glucose levels remain normal, the dose is incrementally doubled to a maximum of 0.67 mg per kilogram (to a maximum daily dose of 2.0 mg per kilogram). Propranolol should be gradually tapered over a period of 2 weeks.

Elaine C. Siegfried, M.D.
William J. Keenan, M.D.
Saadeh Al-Jureidini, M.D.
Saint Louis University School of Medicine, St. Louis, MO 63104
siegfried@kidsderm.com

3 References

1. 1

   Leaute-Labreze C, Dumasde la Roque E, Hubiche T, Boralevi F, Thambo J-B, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649-2651
   Full Text | Web of Science | Medline

2. 2

   Gottschling S, Schneider G, Meyer S, Reinhard H, Dill-Mueller D, Graf N. Two infants with life-threatening diffuse neonatal hemangiomatosis treated with cyclophosphamide. Pediatr Blood Cancer 2006;46:239-242
   CrossRef | Web of Science | Medline

3. 3

   Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics 2008;122:65-74
   CrossRef | Web of Science | Medline

Author/Editor Response

After more than 40 years of clinical use in infants, there is no documented case of death or serious cardiovascular disease as a direct result of exposure to a beta-blocker.1 Side effects of beta-blockers are well known; these include transient bradycardia and hypotension that warrant close monitoring at the onset of treatment. Bronchospasm is usually seen as an exacerbation in patients with underlying reactive airways; a family history with regard to atopy or repeated wheezing should be obtained. Beta-blockers decrease lipolysis, glycogenolysis, and gluconeogenesis that predispose patients to hypoglycemia. They also mask some beta-sympathetic–related hypoglycemic symptoms. The first week of life is a critical period when neonates gradually reach their optimal milk intake and spontaneous hypoglycemia is more likely to develop; beta-blockers clearly should be avoided during this period. Most infants treated for an infantile hemangioma are older and have a normal food intake, and the conditions described in the article by Burns et al.2 do not apply.

A large multicenter study is in the planning stage. We hope that this study will lead to elaborate, reasonable, and objective recommendations concerning the use of beta-blockers in this indication.

Christine Léauté-Labrèze, M.D.
Eric Dumas de la Roque, M.D.
Alain Taïeb, M.D.
Bordeaux Children's Hospital, 33 076 Bordeaux, France
christine.labreze@chu-bordeaux.fr

2 References

1. 1

   Love JN, Sikka N. Are 1-2 tablets dangerous? Beta-blocker exposure in toddlers. J Emerg Med 2004;26:309-314
   CrossRef | Web of Science | Medline

2. 2

   Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics 2008;122:65-74
   CrossRef | Web of Science | Medline

Citing Articles (46)

Citing Articles

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   Serhan Küpeli. (2012) Use of Propranolol for Infantile Hemangiomas. Pediatric Hematology-Oncology120203073128002
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   Arin K. Greene. (2012) Current Concepts of Vascular Anomalies. Journal of Craniofacial Surgery 23:1, 220-224
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   Swee T. Tan, Tinte Itinteang, Philip Leadbitter. (2012) Reply to the letter to the Editor on “Low-dose propranolol for infantile haemangioma”. Journal of Plastic, Reconstructive & Aesthetic Surgery
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   Shoshana Greenberger, Siming Yuan, Logan A Walsh, Elisa Boscolo, Kyu-Tae Kang, Benjamin Matthews, John B Mulliken, Joyce Bischoff. (2011) Rapamycin Suppresses Self-Renewal and Vasculogenic Potential of Stem Cells Isolated from Infantile Hemangioma. Journal of Investigative Dermatology 131:12, 2467-2476
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   N. Leboulanger, A. Cox, E.-N. Garabedian, F. Denoyelle. (2011) Infantile haemangioma and β-blockers in otolaryngology. European Annals of Otorhinolaryngology, Head and Neck Diseases 128:5, 236-240
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   Janie Bertrand, Catherine McCuaig, Josée Dubois, Afshin Hatami, Sandra Ondrejchak, Julie Powell. (2011) Propranolol versus Prednisone in the Treatment of Infantile Hemangiomas: A Retrospective Comparative Study. Pediatric Dermatology 28:6, 649-654
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   N. Leboulanger, A. Cox, E.-N. Garabedian, F. Denoyelle. (2011) Hémangiomes infantiles et β-bloquants en ORL. Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale 128:5, 279-283
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   Christine J. Schupp, Johann-Baptist Kleber, Patrick Günther, Stefan Holland-Cunz. (2011) Propranolol Therapy in 55 Infants with Infantile Hemangioma: Dosage, Duration, Adverse Effects, and Outcome. Pediatric Dermatology 28:6, 640-644
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   Opeyemi O. Daramola, Robert H. Chun, John J. Nash, Beth A. Drolet, Paula E. North, John N. Jensen, Joseph E. Kerschner. (2011) Surgical treatment of infantile hemangioma in a multidisciplinary vascular anomalies clinic. International Journal of Pediatric Otorhinolaryngology 75:10, 1271-1274
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    Kamal Abdel-Elah Aly. (2011) Surgical treatment of craniofacial haemangioma in children. Annals of Pediatric Surgery 7:4, 133-138
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    Yu-Wen Chen, Chin-Chen Chu, Yu-Chung Chen, Ching-Hsia Hung, Yung-Tsung Li, Jhi-Joung Wang. (2011) Lidocaine for prolonged and intensified spinal anesthesia by coadministration of propranolol in the rat. Neuroscience Letters 503:1, 63-67
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    Paulo Morais, Sofia Magina, Mário Mateus, Eunice Trindade, José Miguel Jesus, Filomena Azevedo. (2011) Efficacy and safety of propranolol in the treatment of parotid hemangioma. Cutaneous and Ocular Toxicology 30:3, 245-248
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    Nina Ni, Rudolph S. Wagner, Paul Langer, Suqin Guo. (2011) New Developments in the Management of Periocular Capillary Hemangioma in Children. Journal of Pediatric Ophthalmology & Strabismus 48:5, 269-276
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    Bogdan Cichy. (2011) Skuteczność propranololu w leczeniu naczyniaka niemowlęcego i naczyniakowatości limfatycznej. Pediatria Polska 86:4, 372-375
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    Aaron Davis, Steven M. Cohen, Scott E. Pautler, Karina Billiris-Findlay, David A. Eichenbaum. (2011) Beta blocker use and age-related macular degeneration. Acta Ophthalmologicano-no
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    Silvan Azzopardi, Thomas Christian Wright. (2011) Novel Strategies for Managing Infantile Hemangiomas. Annals of Plastic Surgery1
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    Lawrence H.C. Kim, Marcia Hogeling, Orli Wargon, Ashish Jiwane, Susan Adams. (2011) Propranolol: useful therapeutic agent for the treatment of ulcerated infantile hemangiomas. Journal of Pediatric Surgery 46:4, 759-763
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    Eric M. Jaryszak, Rahul K. Shah, Nancy M. Bauman, Rebecca J. Howell, Christopher T. Rossi, Diego A. Preciado. (2011) Unexpected pathologies in pediatric parotid lesions: Management paradigms revisited. International Journal of Pediatric Otorhinolaryngology 75:4, 558-563
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    Stamatios Peridis, Gemma Pilgrim, Ioannis Athanasopoulos, Konstantinos Parpounas. (2011) A meta-analysis on the effectiveness of propranolol for the treatment of infantile airway haemangiomas. International Journal of Pediatric Otorhinolaryngology 75:4, 455-460
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    Lorea Bagazgoitia, Antonio Torrelo, Juan Carlos López Gutiérrez, Ángela Hernández-Martín, Paula Luna, Marta Gutiérrez, Antonio Baño, Amalia Tamariz, Margarita Larralde, Roser Alvarez, Nuria Pardo, Eulalia Baselga. (2011) Propranolol for Infantile Hemangiomas. Pediatric Dermatology 28:2, 108-114
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    Swee T. Tan, Tinte Itinteang, Philip Leadbitter. (2011) Low-dose propranolol for infantile haemangioma. Journal of Plastic, Reconstructive & Aesthetic Surgery 64:3, 292-299
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    Arelis Burgos-Zavoda, Joseph Morelli, Joanna M. Burch. 2011. Vascular birthmarks. , 574-576.
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    Gretta Fridman, Eric Grieser, Robert Hill, Nausheen Khuddus, Tom Bersani, Charles Slonim. (2011) Propranolol for the Treatment of Orbital Infantile Hemangiomas. Ophthalmic Plastic & Reconstructive Surgery1
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    Daniel H. Fulkerson, Nnenna G. Agim, George Al-Shamy, Denise W. Metry, Shayan A. Izaddoost, Andrew Jea. (2010) Emergent medical and surgical management of mediastinal infantile hemangioma with symptomatic spinal cord compression: case report and literature review. Child's Nervous System 26:12, 1799-1805
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    N Mistry, K Tzifa. (2010) Use of propranolol to treat multicentric airway haemangioma. The Journal of Laryngology & Otology 124:12, 1329-1332
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26. 26

    K. A. Horii. (2010) Infantile Hemangiomas: Propranolol Rx & Hypoglycemia. AAP Grand Rounds 24:5, 64-64
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27. 27

    Mai Thy Truong, Jonathan A. Perkins, Anna H. Messner, Kay W. Chang. (2010) Propranolol for the treatment of airway hemangiomas: A case series and treatment algorithm. International Journal of Pediatric Otorhinolaryngology 74:9, 1043-1048
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    Jugpal S. Arneja, Peggy N. Pappas, Tor A. Shwayder, Marc L. Cullen, Cristie J. Becker, Fasahat H. Hamzavi, John D. Roarty, David N. Madgy, John D. Baker. (2010) Management of Complicated Facial Hemangiomas with β-Blocker (Propranolol) Therapy. Plastic and Reconstructive Surgery 126:3, 889-895
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    Karina T. Canadas, Eric D. Baum, Stella Lee, Samuel T. Ostrower. (2010) Case report: Treatment failure using propanolol for treatment of focal subglottic hemangioma. International Journal of Pediatric Otorhinolaryngology 74:8, 956-958
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    Juliette Mazereeuw-Hautier, Peter H. Hoeger, Sarah Benlahrech, Amir Ammour, Pierre Broue, Julie Vial, Gerard Ohanessian, Christine Léauté-Labrèze, Marc Labenne, Pierre Vabres, Jochen Rössler, Christine Bodemer. (2010) Efficacy of Propranolol in Hepatic Infantile Hemangiomas with Diffuse Neonatal Hemangiomatosis. The Journal of Pediatrics 157:2, 340-342
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    Jin Fong Cheng, Glen A Gole, Timothy J Sullivan. (2010) Propranolol in the management of periorbital infantile haemangioma. Clinical & Experimental Ophthalmology 38:6, 547-553
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    LM Buckmiller, GT Richter, JY Suen. (2010) Diagnosis and management of hemangiomas and vascular malformations of the head and neck. Oral Diseases 16:5, 405-418
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    Sheilagh M. Maguiness, Ilona J. Frieden. (2010) Current Management of Infantile Hemangiomas. Seminars in Cutaneous Medicine and Surgery 29:2, 106-114
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    A.P. Zimmermann, S. Wiegand, J.A. Werner, B. Eivazi. (2010) Propranolol therapy for infantile haemangiomas: Review of the literature. International Journal of Pediatric Otorhinolaryngology 74:4, 338-342
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    Lisa M. Buckmiller, Patrick D. Munson, Umesh Dyamenahalli, Yuemeng Dai, Gresham T. Richter. (2010) Propranolol for infantile hemangiomas: Early experience at a tertiary vascular anomalies center. The Laryngoscope 120:4, 676-681
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    M Naouri, T Schill, A Maruani, F Bross, G Lorette, J Rossler. (2010) Successful treatment of ulcerated haemangioma with propranolol. Journal of the European Academy of Dermatology and Venereology
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    Stephen Maturo, Christopher Hartnick. (2010) Initial experience using propranolol as the sole treatment for infantile airway hemangiomas. International Journal of Pediatric Otorhinolaryngology 74:3, 323-325
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    Mehryar Taban, Robert A. Goldberg. (2010) Propranolol for Orbital Hemangioma. Ophthalmology 117:1, 195-195.e4
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    Alberto Marsciani, Roberta Pericoli, Rita Alaggio, Massimo Brisigotti, Gianluca Vergine. (2010) Massive response of severe infantile hepatic hemangioma to propanolol. Pediatric Blood & Cancer 54:1, 176-176
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    Will J. M. Holmes, Anuj Mishra, Cath Gorst, Se-Hwang Liew. (2010) Propranolol as First-Line Treatment for Infantile Hemangiomas. Plastic and Reconstructive Surgery 125:1, 420-421
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    Kjetil Guldbakke, Ole-Martin Rørdam, Theis Huldt-Nystrøm, Helle Hanssen, Finn Høivik. (2010) Behandling av infantilt hemangiom med propanolol. Tidsskrift for Den norske legeforening 130:18, 1822-1824
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    H. Löffler, C. Kosel, H. Cremer, W. Kachel. (2009) Die Propranolol-Therapie in der Behandlung problematischer Hämangiome. Der Hautarzt 60:12, 1013-1016
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    Lisa M Buckmiller. (2009) Propranolol treatment for infantile hemangiomas. Current Opinion in Otolaryngology & Head and Neck Surgery 17:6, 458-459
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    Chris G. Jephson, Francesca Manunza, Samira Syed, Nikki A. Mills, John Harper, Ben E.J. Hartley. (2009) Successful treatment of isolated subglottic haemangioma with propranolol alone. International Journal of Pediatric Otorhinolaryngology 73:12, 1821-1823
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    Bogdan Cichy. (2009) Propranolol w leczeniu naczyniaków – stary lek, nowe zastosowanie i wiele wątpliwości. Pediatria Polska 84:6, 583-585
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    Lisa Buckmiller, Umesh Dyamenahalli, Gresham T. Richter. (2009) Propranolol for airway hemangiomas: Case report of novel treatment. The Laryngoscope 119:10, 2051-2054
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