Sleep disturbances as an adverse effect of propranolol use in children with infantile hemangioma
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Sleep disturbances as an adverse effect of propranolol use in children with infantile hemangioma Ellen M. S. Xerfan1,2 · Monica L. Andersen3 · Anamaria S. Facina2 · Sergio Tufik3 · Jane Tomimori1,2 Received: 26 November 2019 / Accepted: 30 December 2019 © Children’s Hospital, Zhejiang University School of Medicine 2020
Infantile hemangiomas (IHs) are the most prevalent benign vascular tumor in children, with an estimated rate of 5–10%. Most IHs resolve spontaneously after the proliferation stage, but about 12–24% develop with sequelae and complications which require pharmacological interventions [1]. The beta blocker propranolol is considered as the first-line treatment for complicated cases of IHs [2]. Sleep problems are known to be a possible side effect of treatment with propranolol and other beta blockers. However, little is known about these effects specifically in children being treated for IH. We are, therefore, writing to highlight these possible adverse effects in children, particularly in those using beta blockers to treat IHs. Further research is warranted to evaluate how different doses of medication affect the severity of sleep disturbances in children of different ages. Lipophilic beta blockers, such as propranolol, have high penetration of the blood–brain barrier, making them more likely to cause sleep impairment and agitation. Moreover, the blood–brain barrier in infants is immature and selectively permeable, which may facilitate even greater penetration of the drug [1, 3] and make sleep impairment more prevalent in children being treated for IHs. A meta-analysis study compared the effects of oral propranolol and other therapeutic options on the central nervous system (CNS) and sleep in patients under 6 years old with IH [4]. This analysis concluded that propranolol may have a safer profile in terms of CNS effects than corticosteroids, * Monica L. Andersen [email protected] 1
Programa de Pós‑Graduação em Medicina Translacional, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
2
Departamento de Dermatologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
3
Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
but have greater effects on the CNS and sleep-related events when compared to placebo and other non-corticosteroid drugs [4]. Considering these findings, despite there being no statistically significant results, the authors recommended that CNS and sleep-related events should be monitored more closely in IH patients treated with oral propranolol [4]. In another meta-analysis, 371 adverse events were reported in 1189 patients using propranolol for IH, with changes in sleep being the most common adverse effects (n = 136), including fatigue, insomnia, nightmares, night restlessness and sleep disturbances [5]. A retrospective study reviewed a total of 343 patients on propranolol treatment for IH, distributed into two groups—15 starting treatment before 5 weeks of age (group 1) and 328 after 5
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