Safety and tolerance of propranolol in neonates with severe infantile hemangiomas: a prospective study

Abstract

Although the efficacy of propranolol for the treatment of infantile hemangiomas (IHs) has been well documented, there is a paucity of clinical data regarding the safety and tolerance of propranolol in neonates. A prospective study of 51 patients less than 30 days of age with severe IH was conducted. All patients were admitted to the hospital for monitoring during initial propranolol treatment at day 0 with dose adjustments at days 7 and 28. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose (BG) levels and potential side effects were evaluated during treatment. There were significant decreases in mean heart rate and SBP after the initiation of propranolol therapy (P < 0.05). In contrast, no significant differences in mean DBP and BG levels were observed after each dose during hospitalization (P > 0.05). Bradycardia and hypotension were noted in at least 1 recorded instance in 11.8% and 5.9% of patients, respectively. These hemodynamic changes were not persistent and were asymptomatic. Two patients who had a history of neonatal pneumonia reported severe bronchial hyperreactivity during treatment. This study demonstrated that propranolol administered to properly selected young infants was safe and well tolerated. However, close monitoring should be considered in high-risk young patients.Infantile hemangiomas are the most common vascular tumor in children. If left untreated, the typical characteristic evolution of these tumors is rapid postnatal proliferation, stabilization and slow, spontaneous involution. IHs may be located on any region of the body but are mostly located on the skin of the head, face and neck. Although IHs are usually harmless, approximately 12-24% of IHs have complications. The most commonly occurring complication is ulceration, followed by visual compromise, airway obstruction, auditory canal obstruction and cardiac failure 1 . In many such cases, early intervention may be justified to potentially arrest the growth of the lesion, reduce associated complications, and avoid years of psychosocial concerns.Previously, the standard treatment options for IH included laser, surgical excision or medical therapies such as corticosteroids. The options in life-threatening cases include treatment with vincristine, interferon-α or cyclophosphamide 1 . Unfortunately, none of these therapeutic modalities is ideal due to their restrictions or potentially serious side effects, such as temporary growth retardation, increased risk of infection and behavioral changes 2, 3 . In June 2008, Leaute-Labreze et al. 4 reported their serendipitous discovery that oral propranolol was effective in the management of severe IHs. Subsequently, a growing number of studies further demonstrated that propranolol stops growth and induces an IH regression that is much better and safer than other treatments, including corticosteroids [5][6][7][8][9] . Currently, propranolol has been adopted as a first-line therapy for problematic IHs. Regardless of subtype or depth, the largest increase in ...

Propranolol Treatment for Infantile Hemangiomas: Short-Term Adverse Effects and Follow-Up to Age Two

“…In our study, 70 (16.0%) patients experienced AEs, and the frequencies of the top 4 AEs, from high to low, were as follows: 27 (38.8%) diarrhea, 11 (15.7%) sleep problem, 5 (7.1%) increased stool frequency, and 4 (5.7%) emotion problem. There were only 2 (2.9%) respiratory problems in our study, which may occur because children with a history of neonatal pneumonia are more likely to have respiratory disorder [27]; however, all patients included in our study did not have such a history. There was no asymptomatic hypotension or bradycardia observed; because we did not measure blood pressure in the routine follow-up [28, 29], hand-held pulse oximeter was used by parents for self-test and out-patient care.…”

Intolerable side effects during propranolol therapy for infantile hemangioma: frequency, risk factors and management

“…In this regard, there is evidence suggesting that the blood-brain barrier in young infants is immature and selectively permeable and differs substantially from that of adults; this difference may facilitate the penetration of propranolol 27 . In addition, recent studies demonstrated that young infants who have a history of apnea or neonatal pneumonia appear to be at higher risk for bronchial hyperreactivity after the initiation of β-blocker treatment 28 , 29 . Bronchial hyperreactivity is a direct effect of non-selective β-blockers (e.g., prapranolol) due to β 2 -AR blockade.…”

Effects of Propranolol on Neurodevelopmental Outcomes in Patients with Infantile Hemangioma: A Case-Control Study

“…Although propranolol treatment is effective in both arresting growth and causing involution, irreversible sequelae may have already occurred. These observations, together with the work presented here, promote the recommendation that, in patients with severe IHs, oral propranolol should be administered as early as possible to avoid potential complications [ 36 , 37 ].…”