This retrospective study reviewed patients with infant hemangioma who were admitted to the Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University from January 2014 to October 2021. The inclusion criteria were as follows: (1) patients were superficial infantile hemangioma in the proliferative stage (1-2months old), (2) patients were hospitalized for treatment, (3) patients were at the initial diagnosis and treating the disease for the first time, (4) patients were treated with timolol maleate solution or propranolol. The exclusion criteria were as follows: (1) patients had systemic disease, (2) patients were allergies to β adrenergic blockers, (3) patients with incomplete data.
The study was approved by the Ethical Committee of School and Hospital of Stomatology, China Medical University (No. K2020026), and the retrospective procedures were in accordance with the ethical standards. The general information of cases and tumor, treatment methods, treatment effects, the time for treatment to be effective, and adverse reactions of the cases were obtained by electronic medical records.
Treatments and Grouping
The cases reviewed in the study were divided into three groups according to the different drugs and the different methods of drug administration. Group NM: timolol maleate solution administrated by nano-microneedle technology, once a day, Group MS: timolol maleate drops dipped with a medical swab, twice a day, Group PO: propranolol 1.0 ~ 1.5mg/kg orally, once a day. The detailed treatment process of these three methods is as follows:
The cases in Group NM were treated with timolol maleate solution once a day with nano-microneedle technology. The operation methods are as follows: (1) Wash the surface of the tumor and surrounding skin with normal saline, (2) After the surface is air-dried naturally, timolol maleate drops were dipped in a medical cotton swab, (3) the osmometer is placed vertically on the surface of the tumor and electropuncture point by point. After 1-2 seconds of treatment at each acupuncture point, move 5mm laterally, which is the width of a chip, perform a little acupuncture and puncture the hemangioma lesion area point by point. Repeat this step twice for each treatment, (4) Wet compress with normal saline for 30 minutes.
In Group MS, a small amount of timolol maleate drops were dipped in a medical cotton swab and applied locally to the hemangioma lesion area, with BID once in the morning and evening.
Children in Group PO was given propranolol 1.0～1.5 mg/kg orally, once a day. The general hospitalization is 5 days, during which blood pressure and heart rate are closely monitored, and the electrocardiogram is recorded and evaluated daily. If there is no obvious adverse reaction during hospitalization, the child can be discharged from the hospital for further treatment. Before being discharged from the hospital, the nurses provided health guidance on medication, effect observation and adverse reaction observation to the family members of the children. After being discharged from the hospital, the family members of the children are required to take medications as required, record the occurrence of adverse reactions, and take the children back to the hospital to check their health and medication conditions every month. At each follow-up, relevant information is collected, and the follow-up nurse understands the patient's condition and gives relevant health guidance.
In the Group NM and MS, it should be noted that for children with periorbital hemangioma, cornea and conjunctiva should be avoided. Besides, the nurse observes the changes in skin, breathing, and heart rate after each medication, and records the changes in heart rate before and after medication and during sleep. If the heart rate is lower than the above lower limit, the medication should be stopped immediately. At the same time, pay attention to whether there are abnormalities in diet and sleep.
Efficacy evaluation criteria
The outcomes of each patient were divided into four levels according to the Achauer’ standard analysis , which evaluated the outcome based on improvement of volume, color, and texture: I level, poor (0 to 25 percent), II level, fair (26 to 50 percent), III level, good (51 to 75 percent), and 4, excellent (76 to 100 percent).
Drug safety evaluation
The occurrence of systemic and local adverse reactions was recorded according to clinical observation during treatment. The observed adverse reactions mainly included vomiting, diarrhea, hypoglycemia, low blood pressure, low heart rate, and local imitation from medication, etc.
The effective rate, the cure rate and the rate of adverse reactions was calculated as following: The effective rate = the number of cases with outcome II level and above / the number of the all cases. The cure rate = the number of cases with outcome IV level / the number of the all cases. The rate of adverse reactions = the number of cases with adverse reactions / the number of the all cases.
The time for treatment to be effective is defined as the time for the treatment effect to reach III level and above.
Statistical Package for Social Sciences (SPSS 22.0 for Windows) was used to conduct data analyses. Significance for all statistical tests was set to be the level of 0.05 (2-tailed). Normality and homogeneity of variances were first tested for each continuous variable. Univariate analysis, Chi-square tests and nonparametric-test were operated to describe distributions in different groups.