OBJECTIVE To evaluate the safety of epinephrine hydrochloride injection(EHI) given by nebulized inhalation in guinea pigs with the off-label drug use. METHODS The actual dose of inhalation administration was determined by establishing a nebulized administration drug concentration assay. The systemic allergic reactions and respiratory toxicity of EHI after nebulized inhalation were evaluated by guinea pigs using the allergy test protocol with the combination of frequency and dose of epinephrine hydrochloride administration and allergy test. Thirty-two guinea pigs were randomly divided into 4 groups according to body weight: negative control group(equal volume of saline), positive control group(sensitizing dose: 20 mg·kg-1 ovalbumin), low dose group(sensitizing dose: 15.5 μg·kg-1 EHI) and high dose group(sensitizing dose: 31 μg·kg-1 EHI). The excitation dose of each group was two times the sensitization dose, at the time of excitation, the symptoms of allergic reaction were observed. After excitation, blood and alveolar lavage fluid were collected, whole blood was collected for hematological testing and isolated serum and alveolar lavage fluid were used for IgE testing. Bronchial and lung tissues were taken for histological testing and immunohistochemistry after dissection. RESULTS Using a nebulizer device to administer EHI to guinea pigs at a clinically equivalent dose at 3.95 min of administration. The guinea pigs in all groups showed normal weight gain during sensitization administration. At the time of excitation, the guinea pigs in the positive control group showed strong positive allergic reactions, while the guinea pigs in the negative control group, low dose group and high dose group showed no significant allergic reactions. Compared with the negative control group, eosinophils in the blood of the positive control guinea pigs were significantly higher(P<0.05) and the IgE content in the serum and alveolar lavage fluid was significantly increased(P<0.05 or P<0.01). Histopathological results showed that inflammatory cells infiltrated in the lung tissue of the positive control guinea pigs after excitation, and a large number of erythrocytes and exudate appeared in the alveoli. The immunohistochemical indiacated that the inflammatory symptoms in the lung tissues of the positive guinea pigs were associated with an increase in B lymphocytes. The hematological indexes, serum IgE content, immunohistochemical and histological examination results of guinea pigs in the low and high dose groups were not significantly different from those of the negative control group. CONCLUSION No allergic reaction and no respiratory toxicity occurred in guinea pigs given EHI by nebulization, and the administration of EHI by nebulized inhalation off-label drug use is safe and feasible.

The diagnosis and management of congenital heart disease (CHD), the most common inborn defect, has been a tremendous success of modern medicine. With the development of diagnostic techniques, surgical procedures and interventional techniques, more than 90% of CHD children can survive to adulthood. Consequently, the prevalence of patients with CHD has shifted away from infancy and childhood towards adulthood. Adult CHD cardiology is now encompassing not only young or middle-aged adults but also patients aged above 60 years. Standardized guidelines can provide good theoretical support for the comprehensive management of adult CHD. Ten years after the European Society of Cardiology guidelines for the management of grown-up CHD released in 2010, the new version was officially released in August 2020. The new version of guidelines updated the classification and stratification of diseases, comprehensive intervention methods and intervention timing, and put forward some new concepts, new intervention standards and methods. For adult CHD that has not been repaired or needs to be repaired again, the indication and mode of surgical intervention and perioperative management have a great impact on the prognosis. The new version of the guidelines provides a detailed description of the surgical and intervention indications and methods for different diseases, and clarifies the management methods for high-risk groups. This article attempts to interpret this newly updated guideline from the perspective of a surgeon, sort out several key diseases introduced by the guideline, and strives to provide a concise and actionable guideline for domestic counterparts.