Research On Clinical Safety And Influence Factors Of Danhong Injection Based On Hospital Centralized Monitoring

1. BackgroundTraditional Chinese medicine injection has the characteristics of high bioavailability, fast action, and can promote traditional Chinese medicine treatment of critical patients. But in the process of clinical application,the security problems brought about by traditional Chinese medicine injections caused attention. Danhong injection produced by ShanDong BuChang pharma is one of commonly used traditional Chinese medicine injections, but with its widely clinical use, cases of adverse drug reaction and adverse events were frequently reported., According to reports,the occurrences of adverse drug reaction and adverse events have relations to the improper use of Danhong injection. Therefore, it is necessary that a large sample of clinical cases was observed. It can ensure the clinical characteristics of Danhong injection adverse reactions occurence and influencing factors of Danhong injection adverse reactions occurrence.2. ObjectiveUnderstand the characteristics of the clinical use of Danhong injection and the clinical characteristics of adverse reactions occurrence. Ensure the influencing factors, providing realbasis for safe clinical use of Danhong injection, provide references and guidance for further in-depth study.3. Method3.1 With data of 38 hospitals centralized monitoring trials in drug-scoures,multicenter, prospective and non-controlled hospital as background, Systematically classify and standardize the Information of 30888 cases of hospital centralized monitoring (general information of patients, specific drug information).3.2 Using the nested case-control design, selecting variables related to adverse drug reaction, using classic logistic regression modeling, screening the suspected factors releated to adverse drug reaction cases.3.3 Using weighted propensity score method to balance the possible confounding factors related, further validating the suspicious factors that influence the causal relationship of adverse drug reaction occurrence, making the results more close to the real world.4. Results4.1 The clinical characteristics of the 30888 concentrated monitoring cases using Danhong injection: Danhong injection is not only used in hospital of traditional Chinese medicine and departments of traditional Chinese medicine, but also in the department of cardiovascular internal medicine and the department of neurology in comprehensive hospital; the number of male patients is slightly higher than the female.The patients are aged from 50 to 80, and about 15.94% of them have personal drug and food allergy history. The way of deliver Danhong include static drops, muscle injection and intravenous injection, and acupoint injection. Static drops is mostly used,but acupoint injection is not mentioned in specifications. About half of the patients(accounted for 51.57%), at their first time to use Danhong injection, single average dose is 30 ml. According to the syndrome differentiation of traditional Chinese medicine most case is the phlegm-stasis in channels, blood stasis, Qi and Yin deficiency;4.2 The clinical characteristics of adverse reaction cases: adverse reaction and adverse events is 115, the quantity of adverse reaction cases is 108; The incidence of adverse reactions was 0.35%, as the occasional; It occurs slightly more in women than in men,mostly at the age of 60-70; the rate of adverse is mostly at the age of 10-20 and the age of 80-90, They belong nonage and old man. Adverse reaction involving multiple systems and organs,a total of 169 cases of ADR, most frequency for skin rashes,accounts for 18.52%. This indicates that the adverse reactions of injection is mainly typel rapid anaphylaxis or pseudoallergy reaction. The occurrence frequency of clinical manifestations are skin rash, itching, dizziness,headache,shallow phlebitis,heart palpitations,flush,breath,chills,and so on.The shallow phlebitis, gastric bowel to bilge gas, sweat, local numbness, clammy skin, purple purple are not mentioned in the specification.The symptoms of all cases of adverse drug reaction (except 1 case record is unknown) are recovered or improved after drug withdrawal/decrement or symptomatic treatment.4.3 Analyzing cases with adverse drug reaction and without adverse drug reaction by Chi-square test, we found: There are statistical differences between cases with adverse drug reaction and without adverse drug reaction among the following 17 factors : family history of allergies, history of allergies to cephalosporins, history of allergies to amino sugar glycosides, whether it is the first time to use Dan red injection, gender factors, history of individual drug and food allergy, history of allergic disease, history of penicillin allergy, history of sulfa drug allergy, history of proprietary Chinese medicine allergy, drug use frequency, the static drop speed,combined nmda potassium magnesium, combined thymosin, combined glucosamine,combined celecoxib. These differences may have relations with the ADR cases, and worth further attention.4.4 After designing with NCCS and analyzing with the Logistic regression model,we sereening out following 6 significant risk factors: cephalosporin allergy,proprietary Chinese medicine allergy, combined nmda potassium magnesium,combined thymosin, combined celecoxib, combined bisoprolol fumarate pesos.4.5 Applying GBM propensity score methods for further analysis on the relation between the occurrence of ADR cases and the 6influence factors after preliminary screening. The result shows that Cephalosporin allergy,proprietary Chinese medicine allergy, share nmda potassium magnesium, share thymosin, share celecoxib are dangerous factors that influencing the adverse reaction Danhong injection.5. Conclusion5.1The majority of Danhong users are the elderly, and the way used to injecting are static drops, intramuscular injection, static injection, acupuncture point injection and so on; When using Danhong injection, the clinical use of a single dosage, use frequency and dripping speed should be adjusted in accordance with the specification;In most of the Clinical cases,Danhong injection is used with other drugs;The syndrome patterns occurred most are phlegm-stasis in channels, blood stasis and qi stagnation, qi and Yin deficiency.5.2 Danhong injection is clinical safe for use. The incidence of adverse reaction of Danhong injection is 0.35%, with no severe adverse reaction; Adverse reaction involving multiple systems and organs, with skin rashes happened most. Other 31 clinical manifestations of adverse reaction include urticant, dizziness, headache,etc. Among the 31 clinical manifestations,in which 12 cases are not mentioned in the specifications, such as Shallow phlebitis, gastric bowel to bilge gas, sweat, and can provide references for the for revision of Dan red injection's specification. All cases of ADRs are recovered or improved after using Danhong injection.5.3 The factors of ADR are cephalosporin allergy, proprietary Chinese medicine allergy history, combined nmda potassium magnesium, combined thymosin,,combined celecoxib. So when using Danhong injection, attention must be paid to the patient's medical history, and should be careful when using the above three drugs together.5.4 GBM propensity score method is applicable to the research on the adverse reaction influence factors of Chinese medicine injection.