Propranolol Therapy For Infantile Hemangiomas Research Articles

Safety of Prior Propranolol Therapy for Infantile Hemangioma.

Propranolol has been the primary treatment for infantile hemangioma (IH) since 2008. Prior studies have investigated the effects in late childhood of propranolol therapy given in infancy for IH, including neurocognitive dysfunction, sleep disorders, and hypoglycemia. However, few studies have determined the risk of these adverse effects later in life. Using the TrinetX database, we studied the risk of growth impairment, sleep disorders, learning disabilities, and diabetes mellitus in children aged 10-17 years who had received propranolol for IH in infancy. The maximum age of 17 years was chosen for the study, as propranolol was established as a treatment for IH in 2008. The results showed no statistically significant risk of growth impairment, sleep disorders, learning disabilities, or diabetes mellitus in IH patients treated with propranolol. These findings support existing evidence that propranolol therapy given in infancy for IH is not associated with long-term adverse effects up to age 17 years in the studied patient population.

Regimen for accelerated propranolol initial dosing (RAPID).

Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.

Oral Propranolol Therapy for Infantile Hemangioma: Long-term Follow-up.

β-blocker therapy is currently the treatment of choice for infantile hemangiomas (IH), albeit with limited data on long-term treatment outcomes. Herein, authors treated 67 IH lesions in 47 patients with oral propranolol at 2 mg/kg/d for a median of 9 mo and followed them up for a median of 48 mo. While no maintenance therapy was required for 18 lesions (26.9%), the rest needed maintenance therapy. Both treatment regimens had comparable efficacy (83.3±23.9% and 92.0±13.8%) but chances of IH recurrence was higher in lesions requiring maintenance therapy. Also, patients treated at ≤5 mo of age had a significantly better response and a lower recurrence rate than patients treated at >5 mo of age (95.0±7.9% vs. 87.0±17.5%, p=0.05). Authors' experience suggests that longer durations of maintenance therapy offered no added advantage to the overall improvement of IH while treatment initiation at an earlier age showed better improvement and lower recurrence rates.

Combination of Laser Therapy and Oral Propranolol Therapy for Infantile Hemangioma

Combination of Laser Therapy and Oral Propranolol Therapy for Infantile Hemangioma

Safety assessment of propranolol for infantile hemangioma: a study in an Asian population

ABSTRACT Objective To evaluate the safety of initiating and maintaining propranolol therapy for infantile hemangioma (IH) and the safety of different doses. Methods The retrospective analysis included 336 consecutive cases of infants with IH treated between January 2016 and October 2017. The patients were assessed in the hospital at the initiation of the therapy and later in outpatient settings during the therapy. The monitoring included blood pressure (BP), heart rate (HR), blood glucose, hepatic and renal function, myocardial enzymes and serum lipids. Cardiac examinations in the outpatient follow-up included electrocardiography, ultrasound echocardiography, height, weight and head circumference. Results Propranolol decreased BP and HR at the initiation of treatment. The incidences of sinus bradycardia and hypoglycemia increased with the time of administration. Mean height, weight and head circumference were not affected during the treatment. The incidence of PR prolongation was 0%–5.7%. The effect of propranolol on the cardiovascular system, metabolism and physical development was not affected by its dose. Conclusion Oral propranolol is a safe treatment for IH. Serious side effects were not observed. Attention should be paid to the side effects during clinical treatment.

Enhanced efficacy of propranolol therapy for infantile hemangiomas based on a mesoporous silica nanoplatform through mediating autophagy dysfunction

Infantile hemangioma is one of the most common vascular tumors, which might result in morbidity and mortality without timely intervention. Propranolol is currently the first-line therapy for hemangiomas, but its potential side effects and high frequency of administration make it urgent to develop a suitable drug delivery system for propranolol. In the present study, we formulated a propranolol delivery system based on mesoporous silica nanoparticles (PRN@MSN) and investigated the interplay between autophagic activities mediated by nanoparticles and improved therapeutic efficacy of PRN@MSN. The results showed that PRN@MSN nanoparticles exhibited higher cytotoxicity compared with free propranolol in vitro and in vivo, which could induce excessive autophagosome accumulation through increased autophagosome formation and impaired autophagic degradation. Inhibition of autophagy in the early stage could attenuate the cytotoxicity of PRN@MSN. ROS generation was essential for nanoparticle-mediated autophagy and cytotoxicity, and PRN@MSN-induced autophagy dysfunction could enhance endoplasmic reticulum (ER) stress in hemangioma stem cells. Our study revealed a promising PRN delivery system based on a mesoporous silica nanoplatform that could induce autophagy dysfunction with excessive autophagosome accumulation to promote the therapeutic efficacy of PRN therapy. PRN@MSN drug delivery system combined with autophagy modulation may act as a promising treatment pattern in the treatment of hemangiomas.

Topical timolol as adjunct therapy to shorten oral propranolol therapy for infantile hemangiomas.

First-line therapy for infantile hemangiomas (IH) is oral propranolol, a systemic beta-blocker with the risk of rare but serious adverse effects. Topical timolol presents an attractive off-label alternative with good tolerability, but sequential therapy with propranolol followed by timolol is not well studied. Here, we report effects of topical timolol preceding or following oral propranolol as adjunct therapy for IH. A retrospective chart review of 559 patients with IH seen at the pediatric dermatology clinic of a tertiary care center between December 2008 and January 2018. Children were grouped by treatment received: propranolol only, timolol only, propranolol to timolol, timolol to propranolol to timolol, and timolol to propranolol. Patient demographics, clinical/treatment characteristics, and pairwise differences were explored between groups. Among all patients treated with propranolol, those who received propranolol followed by timolol received the shortest duration of oral propranolol and were the youngest at the time of propranolol completion. These patients received propranolol for a median of 2.2months duration (P=0.006) and were a median of 1.7months younger (P=0.007) compared with patients who received oral propranolol only. None had treatment failure defined as requiring propranolol reinitiation, compared with 13% of patients in the propranolol only group (P=0.036). Sequential therapy with oral propranolol followed by topical timolol for IH may help minimize potential adverse effects of systemic beta-blockers by reducing the duration of propranolol therapy and facilitating successful taper at a younger age without an increase in treatment failures.

Safety assessment during initiation and maintenance of propranolol therapy for infantile hemangiomas.

Propranolol is an effective method of treatment for infantile hemangiomas (IH). A recent concern is a shift of the therapy into outpatient settings. The aim of the study was to evaluate the safety of initiating and maintaining propranolol therapy for IH. The study involved 55 consecutive children with IH being treated with propranolol. The patients were assessed in the hospital at the initiation of the therapy and later in outpatient settings during and after the therapy. Each time, the following monitoring methods were used: physical examination, cardiac ultrasound (ECHO), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and biochemical parameters: blood count, blood glucose, aspartate transaminase (AST), alanine transaminase (ALT), and ionogram. The therapeutic dose of propranolol was 2.0 mg/kg/day divided into 2 doses. Four children were excluded during the qualification or the initiation of propranolol; a total of 51 patients were subject to the final analysis. All the children presented clinical improvement. There was a significant reduction in the mean HR values only at the initiation of propranolol. There were no changes in HR during the course of the therapy. Blood pressure values were within normal limits. Both systolic and diastolic values decreased in the first 3 months. Bradycardia and hypotension were observed sporadically, and they were asymptomatic. Electrocardiography did not show significant deviations. The pathological findings of the ECHO scans were not a contraindication to continuing the therapy. There were no changes in biochemical parameters. Apart from 1 symptomatic case of hypoglycemia, other low glucose episodes were asymptomatic and sporadic. The observed adverse effects were mild and the propranolol dose had to be adjusted in only 6 cases. Propranolol is effective, safe and well-tolerated by children with IH. The positive results of the safety assessment support the strategy of initiating propranolol in outpatient settings. Future studies are needed to assess the benefits of the therapy in ambulatory conditions.

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

Currently, propranolol is the most preferred systemic therapy for problematic infantile hemangiomas (IHs). However, the side effects such as bronchial hyperreactivity may be intolerable. The aim of this study was to evaluate the frequency, risk factors and management of intolerable side effects (ISEs) during propranolol therapy. In total, 1260 children were studied. The incidence of ISEs was 2.1% (26 patients). Severe sleep disturbance was the most common reason for propranolol cessation, accounting for 65.4% of cases. In total, 23 and 3 patients received atenolol and prednisolone as second-line therapy, respectively. Treatment response was observed in 92.3% (24/26) of cases (showing excellent or good response to therapy). No toxicity-related permanent treatment discontinuation occurred during atenolol or prednisolone therapy. In the univariate analysis, younger age, premature birth, and lower body weight were associated with ISEs (P < 0.05). In the multivariate analysis, only age (95% confidence interval [CI]: 1.201–2.793, P = 0.009) and body weight (95% CI: 1.036–1.972, P = 0.014) were associated with ISEs. Our study suggests that ISEs are rare in patients with IHs who are treated with propranolol. Predictive factors for ISEs include younger age and lower body weight. Atenolol and prednisolone are effective and safe alternatives to propranolol in the treatment of refractory IHs.

Is Hospitalization Necessary for Propranolol Initiation for Infantile Hemangiomas

Although propranolol therapy for infantile hemangiomas (IHs) has been used for 6 years (FDA approved 2 years ago), there is no standardized initiation

Experience with Holter monitoring during propranolol therapy for infantile hemangiomas

Although adverse events in children treated with propranolol have proven rare, the appropriate methods of assessing cardiovascular risk and monitoring for toxicity when the medication is used for infantile hemangiomas remain unclear. We sought to analyze Holter monitor reports of otherwise healthy patients on propranolol for infantile hemangiomas to determine the incidence of sustained arrhythmias and to evaluate the utility of Holter monitoring in the outpatient setting. We retrospectively reviewed the charts of patients with infantile hemangioma who underwent 24-hour Holter monitoring after initiation or dose escalation of propranolol between 2011 and 2014. In all, 43 patients aged 1.8 to 36.2 months, with 44 Holter monitor reports, were included in the study. No sustained arrhythmias were revealed. The treatment plan was not altered in any patient based on the Holter monitor report. This was a retrospective study design. Our study suggests that Holter monitoring may be unnecessary in otherwise healthy patients with infantile hemangioma older than 12 weeks who are treated with propranolol in the outpatient setting.

Propranolol Therapy for Infantile Hemangioma and Proposed Protocol for Initiation of Therapy

Received: December 05, 2014| Published: December 26, 2014 Infantile hemangiomas (IHs) are the most common vascular tumors of infancy, found in approximately 5-10 % of all newborns and infants up to 1 year. IHs are self limited and in most of the cases no intervention is needed. Approximately 10% of all IHs require medical intervention, include those involving areas such as: face (periorbital, perinasal, perioral) or sites at high risk for ulceration (skin folds, anogenital area), causing airway obstruction, dysfunction, hemorrhage or disfigurement [1].

Propranolol Therapy for Infantile Hemangioma and Proposed Protocol for Initiation of Therapy

Propranolol Therapy for Infantile Hemangioma and Proposed Protocol for Initiation of Therapy

Propranolol therapy for infantile hemangioma is less toxic but longer in duration than corticosteroid therapy

Background Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. Objective To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. Methods A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular abnormality clinic at the authors' institution between October 2007 and February 2012 was performed. Anthropometric measures (height and BMI) and blood pressure were analyzed. Results A total of 290 visits (119 patients) to the pediatric vascular abnormality clinic were reviewed. Of these, 18 patients received medical treatment and their anthropometry was analyzed. BMI percentile increased significantly in patients treated with corticosteroids (P=0.0039). Corticosteroid treatment also resulted in a significant decrease in height percentile (P=0.0078). Anthropometric measures did not cross percentiles in children treated with propranolol. A significant decrease in systolic blood pressure was noted in the propranolol group (P=0.03), but no hypotensive values were recorded. Median treatment duration was significantly longer when patients received propranolol (372 versus 133 days; P=0.0033). Conclusion Propranolol for the treatment of infantile vascular abnormalities does not share the unfavourable effects on patient anthropometry that corticosteroids exhibit; however, a longer duration of therapy is required.

Ultrasound in Assessing the Efficacy of Propranolol Therapy for Infantile Hemangiomas

This study was aimed at assessing the efficacy of propranolol treatment in infantile hemangiomas (IHs) by ultrasound. Thirty-one patients with IHs were administered propranolol and were assessed by ultrasound before treatment, 3 mo after treatment and at the end of treatment. Longitudinal and transverse diameters, as well as thickness of hemangiomas measured by clinical observation differed significantly (p < 0.05) from measurements obtained by ultrasound. Ultrasound also revealed that longitudinal and transverse diameters, thickness, vascular density, blood flow velocity (arterial and venous) and arterial peak systolic blood flow velocity of hemangiomas were significantly decreased (p < 0.05) after treatment compared with before treatment. The resistive index and systolic/diastolic blood flow velocity in IHs were significantly higher (p < 0.05) after treatment than before treatment. In conclusion, ultrasound can evaluate the efficacy of propranolol at the termination of therapy.

Propranolol therapy for infantile hemangioma is less toxic but longer in duration than corticosteroid therapy.

Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular abnormality clinic at the authors' institution between October 2007 and February 2012 was performed. Anthropometric measures (height and BMI) and blood pressure were analyzed. A total of 290 visits (119 patients) to the pediatric vascular abnormality clinic were reviewed. Of these, 18 patients received medical treatment and their anthropometry was analyzed. BMI percentile increased significantly in patients treated with corticosteroids (P=0.0039). Corticosteroid treatment also resulted in a significant decrease in height percentile (P=0.0078). Anthropometric measures did not cross percentiles in children treated with propranolol. A significant decrease in systolic blood pressure was noted in the propranolol group (P=0.03), but no hypotensive values were recorded. Median treatment duration was significantly longer when patients received propranolol (372 versus 133 days; P=0.0033). Propranolol for the treatment of infantile vascular abnormalities does not share the unfavourable effects on patient anthropometry that corticosteroids exhibit; however, a longer duration of therapy is required.

Twenty‐Four‐Hour Hospitalization for Patients Initiating Systemic Propranolol Therapy for Infantile Hemangiomas—Is It Indicated?

In recent years, oral propranolol has risen from serendipitous discovery to first-line, albeit off-label, therapy for infantile hemangiomas (IHs). This retrospective study explored the utility of a 24-hour hospitalization for the initiation of propranolol therapy in children with problematic IHs by evaluating the effects of systemic propranolol on hemodynamics and blood sugar levels. Thirty-one children were admitted to the hospital to begin oral propranolol at a dose of 2 mg/kg/per day. Heart rate (HR), blood pressure (BP), and blood glucose (BG) measurements were obtained at baseline and 1 to 3 hours before and after each dose of propranolol. No caregivers reported any adverse effects during the hospitalization. On average, HR decreased by 5 beats per minute (bpm) (p < 0.01) and systolic BP decreased by 4 mmHg (p < 0.01) after propranolol administration. There was no statistically significant change in diastolic BP or BG with propranolol therapy. Over the first three doses of propranolol we saw statistically significant attenuation of the effects of propranolol on HR, with HR approaching baseline values during the hospitalization (p = 0.04). We did not see statistically significant changes in BP over the course of three doses of propranolol. This study suggests that 24-hour hospitalization with hemodynamic monitoring may not be necessary for safe initiation of propranolol therapy in otherwise healthy infants. Parental education on frequent feedings to decrease the chance of hypoglycemia may be as effective as 24-hour hospitalization.

Variable response to propranolol therapy for infantile hemangiomas

Since propranolol was accidentally discovered to induce involution of hemangiomas, it is being used by many clinicians with a favourable response. We present our experience with use of propranolol and report three infants with hemangiomas who were treated with propranolol. First infant had a marked involution of the lesion; second infant had a appreciable response while the third infant had a initial minimal response with progressive increase in size of the lesion.

Oral Propranolol Therapy for Infantile Hemangiomas Beyond the Proliferation Phase: A Multicenter Retrospective Study

Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions' growth or those older than 12 months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t-test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120 months (mean 28 mos, median 22 mos). The duration of propranolol therapy ranged 1 to 8 months (mean 3.6 mos). The mean visual analog scale score before the treatment was 6.8 ± 2.15, and mean reduction in the visual analog scale score at the assessment was 2.6 ± 1.74 (p < 0.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (p < 0.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post-proliferative phase, and should be considered as the first-line therapy in that setting.

Initial Experience With a Multidisciplinary Strategy for Initiation of Propranolol Therapy for Infantile Hemangiomas

To outline a safe, standardized protocol for outpatient initiation of propranolol therapy for infantile hemangiomas. Retrospective review. Academic tertiary care pediatric hospital. Forty-nine infantile hemangioma patients were offered propranolol therapy and included in the study. Any patients requiring hospital admission were excluded. Screening consisted of cardiology evaluation, including electrocardiography and, when indicated, echocardiography. Target initiation dose was 2 to 3 mg/kg/d divided into 3 doses. Blood pressure and heart rate were initially monitored at baseline and 1 and 2 hours in clinic following initial dosing. A 3-hour time point was later added. Families received standardized instructions regarding home heart rate monitoring, side effects, and fasting. Outpatient propranolol therapy was safely initiated in 39 of 44 patients (89%). Five patients required brief admission: 1 with clinical signs/symptoms of heart failure, 3 having airway involvement, and 1 for social reasons. Propranolol administration transiently reduced blood pressure; the maximal decrease occurred at 2 hours, prompting addition of a 3-hour time point to ensure recovery. No patients exhibited symptomatic hypotension, bradycardia, or heart failure. In most children with infantile hemangiomas, propranolol therapy can be safely initiated as an outpatient. Careful cardiovascular evaluation by an experienced clinician is essential for pretreatment evaluation, inpatient admission (when necessary), blood pressure and heart rate monitoring following initial dosing, and parent education. This standardized multidisciplinary outpatient initiation plan reduces the cost of initiating therapy compared with inpatient strategies while still providing appropriate monitoring for potential treatment complications. Further evaluation of propranolol therapy efficacy at the current dosing and duration of treatment continues.