ObjectiveTo retrospectively analyze off-label drug use (OLDU) situation of ambroxol hydrochloride injection (AHI) among inpatients in the Guangdong General Hospital in 2012, so as to provide references for AHI OLDU. MethodsAll medical orders of AHI for inpatients in the Guangdong General Hospital in 2012 were included, and OLDU was judged according to drug labels. We summarized situation of drug use in all departments, analyzed OLDU incidence in administration path and in dose, calculated prescribed daily dose (PDD) and utilization index (DUI) in each department to evaluate the degree of OLDU in dose. Resultsa) A total of inpatients 138 227 patient-days who used AHI were included. OLDU occurred in all departments in this hospital and the total OLDU incidence was 67.06%. b) OLDU in dose occurred in 71.43% of the departments (25/35) with an incidence of 29.53%; the top 4 departments were cardiac surgery intensive care unit department (CICU) (97.74%), cardiac surgery department (97.51%), pediatric cardiac surgery department (72.30%) and pediatric intensive care unit department (PICU) (70.28%) in order. c) The PDDs in CICU department, cardiac surgery department, PICU departments, pediatric cardiac surgery department, oncological surgery ward, neurosurgery ward and intensive care unit (ICU) were higher than the defined daily dose (DDD), of which, the DUI/cDUI in CICU, cardiac surgery department, PICU and pediatric cardiac surgery department were 1 to 3 times higher than normal level. d) No relevant adverse drug reaction/adverse event (ADR/AE) reports were received in this hospital in 2012. ConclusionAHI is widely used in the Guangdong General Hospital, and AHI OLDU is commonly-seen. Further studies should be conducted to analyze the influence factors of AHI OLDU in dose and to evaluate the rationality of its application.
Objective To assess the effectiveness and safety of an aerosol inhalation of ambroxol in accessory treatment of pneumonia. Methods Biomedical databases, including MEDLINE, EMbase, The Cochrane Central Register of Controlled Trials (CENTRAL), CBM-disk and CNKI were searched. Randomized controlled trials (RCTs) and quasi-RCTs that compare aerosol inhalation of ambroxol with placebo or other aerosol inhalation regimens were collected. A critical quality assessment and Meta-analysis were performed for included studies. Results Thirteen RCTs were included and all of them were carried out in China. None of the trials described the method of randomization, allocation concealment, blind, and follow-up. With Juni scales, 13 trials scored C degree. Compared with the control group, aerosol inhalation of ambroxol improved total improvement rate and symptoms, and shortened hospital stay. Although statistical difference was not found in some comparisons, all trials showed beneficial tendency. We didn’t find any RCTs describing the safety of ambroxol aerosol inhalation. Conclusion Because of the low quality of RCTs on ambroxol aerosol inhalation for pneumonia, no reliable conclusion can be drawn from our Meta-analysis. Well-designed RCTs and economic evaluation are urgently needed to evaluate the value and safety of aerosol inhalation of ambroxol in treating pneumonia.
Objective To assess the efficacy of ambroxol on acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods The randomized controlled study involving ambroxol on ALI/ARDS were searched and identified from Cochrane Library, PubMed, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, WanFang Resource Database, and Chinese Journal Fulltext Database. The quality of the chosen randomized controlled studies was evaluated, and then the valid data was extracted for meta-analysis. Results Ten articles were included, all in Chinese, including 459 cases ofpatients ( 233 cases in experimental group,226 cases in control group) , with baseline comparability between the various experiments. Systematic review showed that in ALI/ARDS patients, high-dose ambroxol was in favor to improve PaO2 [ WMD =12. 23, 95% ( 9. 62, 14. 84) , P lt; 0. 0001] and PaO2 /FiO2 [ WMD = 32. 75,95% ( 30. 00, 35. 51) , P lt;0. 0001] , reduce lung injury score [ WMD = - 0. 49, 95% ( - 0. 66, - 0. 33) ,P lt;0. 0001] , decrease the duration of mechanical ventilation [ WMD = - 2. 70, 95% ( - 3. 24, - 1. 12) ,P lt;0. 0001] and the length of ICU stay [ WMD= - 2. 70, 95% ( - 3. 37, - 2. 04) , P lt;0. 0001] , and lower mortality [ OR=0. 46,95%( 0. 22, 1. 00) , P = 0. 05] . Conclusions The existing clinical evidence shows that, compared with conventional therapy, high-dose ambroxol plus can significantly improve PaO2 , PaO2 /FiO2 , lung injury score, duration of mechanical ventilation, length of ICU stay and mortality in ALI/ARDS patients. Due to the quality of research and the limitations of the study sample, there likely to exist a bias,and may affect the strength of result, so we expect more high-quality, large-scale randomized controlled clinical trial to verify.
Objective To evaluate the efficacy and safety of domestic ambroxol hydrochloride injection in the treatment of lower respiratory tract infection. Methods A total of 120 patients with respiratory tract infections were included and randomized into the treatment group (ambroxol hydrochloride injection 30mg, iv, q12h) and the control group (mucosolvan ampoule 30mg, iv, q12h). The duration of treatment was 6 days. Results 118 patients completed the trial, 59 in each group. From Day 1 to Day 6, the severity scores of cough, sputum amount, difficulty in expectoration and rales were similar between the two groups (Pgt;0.05), but a significant difference was observed in the nature of sputum (Plt;0.05). The total effective rates of the treatment group and the control group were 96.6% (FAS analysis and PP analysis) or 93.3% (FAS analysis), and 94.9% (PP analysis), respectively. There was no significant difference between the two groups (Pgt;0.05). The incidence of adverse effects was comparable between the two groups (1.7% vs. 0%, Pgt;0.05), and no severe adverse effect was observed. Conclusion The efficacy of domestic ambroxol hydrochloride injection in the treatment of lower respiratory infection was equal to that of mucosolvan ampoule, and it can even further improve the nature of sputum. Ambroxol hydrochloride was as safe as mucosolvan ampoule.
Objective To investigate the effects of high dose ambroxol on patients with acute lung injury（ALI） after liver transplantation.Methods Thirty patients with ALI after liver transplantation were divided randomly into an ambroxol group and a control group.On the base of routine treatment，the patients were treated by intravenous infusion with high dose ambroxol of 15 mg/kg once a day for 7 days in the ambroxol group and with normal saline of same volume in the control group.The arterial blood gas analysis was performed and IL-1，IL-10 and TNF-α were measured before and 1 day，3 day and 7 day after the treatment.Length of stay in ICU were recorded and death rate in one year were followed-up.Results After the 1 days，3 days and 7 days of treatment，PaO2 and PaO2/FiO2 were improved in both groups with more significant improvement in the ambroxol group（Plt;0.05）.Before treatment，no differences of IL-1，IL-10 and TNF-α level were found between the two groups.But the level of IL-1 and TNF-α decreased significantly in the ambroxol group compared with the control group after 1 day treatment，and no differences were found after 3 day and 7 day.The level of IL-10 increased in both groups，but significantly in the ambroxol group after 1 day.The lenght of ICU stay in the ambroxol group was shorter than that in the control group[（8.2±5.6）d vs（11.4±6.5）d，Plt;0.05].Two died in the ambroxol group and 3 in the control group with no significant difference.Conclusion High dose ambroxol can improve blood gas exchange and decrease the lenght of ICU stay in ALI patients after liver transplantation，through its inhibitory effects on inflammatory response by down-regulation of IL-1，TNF-α and up-regulation of IL-10.
Objective To observe the protective effects of ambroxol hydrochloride ( AMB) on rabbit model of acute lung injury ( ALI) induced by oleic acid and explore its mechanisms. Methods The ALI model of rabbit was induced by oleic acid. Twenty-four Japanese white rabbits were divided into three groups randomly, ie. a normal saline group ( NC group) , an ALI group and an ALI plus ambroxol injection group ( AMB group) . The pathological changes and apoptotic index ( AI) in lung tissue, Caspase-3 activity in lung tissue homogenate were observed 6 hours after the intervention. Serum activity of superoxide dismutase ( SOD) and serum levels of malonaldehyde ( MDA) , interleukin-1β( IL-1β) , and tumor necrosis factor-α ( TNF-α) were measured simutanously. Results The pathological injury of lung in the AMB group was milder than that in the ALI group. Both the AI in lung tissue and Caspase-3 activity in homogenate in the AMB group were lower than those in the ALI group significantly ( P lt;0. 01, P lt;0. 05 respectively) , butwere higher than those in the NC group( both P lt; 0. 01) . The activity of SOD in serum measured 6 hours after AMB intervention was higher while the serum levels of MDA, IL-1βand TNF-αin serum were lower ( P lt;0. 01) than those in the ALI group significantly ( all P lt;0. 01) . Conclusions Ambroxol hydrochloride has protective effects on oleic acid-induced acute lung injury. The mechanisms may be related to inhibition of oxidative stress and suppression of cytokines synthesis ( IL-1βand TNF-α) , the activity of the Caspase-3,and the apoptosis of lung tissue.
Objective To observe the effects of ambroxol injection on mucosal surface structure of trachea injured by intratracheal instillation of amikacin. Methods 280 Wistar rats were randomly divided into four groups( n = 70 in each group) , ie. a normal control group, a normal saline group( intratracheally instilled normal saline) , an amikacin group ( intratracheally instilled amikacin) , and an ambroxol group ( intratracheally instilled amikacin and ambroxol simultaneously) . At the time points of 2, 12, 24, 48, 72 hours six animals in each group were killed and the samples of 1/3 lower segment of trachea were collected and observed by scanning electron microscope. Endotracheal intubation were made on other 6 animals to collecte broncho-alveolar lavage fluid ( BALF) for leucocyte count. Results Compared with the normal control group, elevated leucocyte count was observed in all other groups, various grades of swelling of the cilia were revealed, followed by more or less cilia laid flat with adjacent cilia conglutinated. Then partial cell membrane on top of some cilia bulged out. In terms of injury, the normal saline group was the most mild, and the amikacin group was most serious with the highest leucocyte count. All the parameters were relieved in ambroxol group. Conclusions Intratracheal instillation of amikacin causes acute injury of the ultrastructure of mucosal surface cilia. Ambroxol can promote the recovery process and alleviate inflammation of airway.
ObjectiveTo investigate the effect of ambroxol hydrochloride on c-Jun N-terminal kinase (JNK) signal pathway in gastric aspiration lung injury. MethodsForty healthy male Sprague Dawley rats were randomly divided into a control group, an injury group, a SP600125 (JNK specific inhibitor) group and an ambroxol group. The model of gastric aspiration lung injury was established by aspiration of gastric contents. The rats in the SP600125 group preoperatively received intravenous injection of JNK specific inhibitor SP600125 (3 mg/100 g). The rats in the ambroxol group received intravenous injection of ambroxol hydrochloride (50 mg/kg) 2 hours after the damage occurred. The neutrophil count and malondialdehyde (MDA) activity in bronchoalveolar lavage fluid (BALF), the lung wet weight/dry weight ratio (W/D), and myeloperoxidase (MPO) activity were measured. The protein expressions of JNK and phosphorylated JNK (p-JNK) and inducible nitric oxide synthase (iNOS) in lung tissue were detected by Western blot method. The changes of lung tissue structure were observed under light microscope. ResultsIn the injury group, the neutrophil counts and MDA activity in BALF, W/D, MPO activity, p-JNK and iNOS protein expression increased significantly, lung tissue appeared obvious histopathological injury compared with the control group. In the SP600125 group and the ambroxol group, neutrophil count and MDA activity in BALF, lung W/D, MPO activity, p-JNK and iNOS protein expression were significantly decreased compared with the injury group (P < 0.05), and the damage of the lung tissue pathology was reduced. The expression of JNK protein in lung tissue was not different in all groups (P > 0.05). ConclusionsJNK is involved in inflammatory reaction of gastric aspiration lung injury. The protective effect of ambroxol may be related to the inhibition of JNK signaling pathway and the inhibition of iNOS expression.
ObjectiveTo investigate the situation of off-label drug use in dose (OLDUD) of ambroxol hydrochloride injection (AHI) in perioperative period among patients for stanford type A aortic dissection in Guangdong General Hospital, so as to provide references for the rational application of AHI in clinical practice. MethodsAll medical orders of AHI for patients had aortic arch replacement for Stanford type A aortic dissection in Guangdong General Hospital between January 2005 and December 2014 were included. The patients were divided into a mild OLDUD ( < 450 mg) group, a moderate OLDUD (450 mg≤OLDUD < 900 mg) group, and a high OLDUD (≥900 mg)group. The preoperative and postoperative features, incidence of PPCs, mortality, incidence of reintubation, time of mechanical ventilation, time stay in ICU, time stay in hospital and the overall costs among three groups were compared by SPSS 22.0 software. Resultsa) A total of 549 patients were included. The incidence of OLDUD was 99.82%. The most common PMDDs were 450 mg (n=358) and 900 mg (n=88). b) The three groups were well matched for perioperative and operative variables. c) The incidence of preoperative drug use was 8.6%. The incidences (5.5% vs. 7.7% vs. 15.7%, P=0.022) and maximum doses (180 mg vs. 300 mg vs. 450 mg, P=0.014) of preoperative drug use were statistically different in mild OLDUD, moderate OLDUD and high OLDUD groups. The days of preoperative drug use were not different (3 d vs. 2.5 d vs. 2 d, P=0.307). The days of postoperative drug use (9.5 d vs. 13 d vs. 19 d, P < 0.001) and postoperative drug use in maximum doses (7 d vs. 8 d vs. 7 d, P=0.005) were different. d) The incidence of PPCs was 100%, and the mortality (8.2% vs. 6.6% vs. 9.0%, P=0.696) was not statistically different among mild OLDUD, moderate OLDUD and high OLDUD groups. However the incidence of reintubation (14.3% vs. 13.8% vs. 27%, P=0.009), time of mechanical ventilation (37 h vs. 50 h vs. 114 h, P < 0.001), time stay in ICU (138 h vs. 178.5 h vs. 316 h, P < 0.001), time stay in hospital (25 d vs. 27 d vs. 34 d, P=0.001) and the overall costs (¥ 0.17 million vs. ¥ 0.19 million vs. ¥ 0.25 million, P < 0.001) were different among three groups. Moreover, they were all increasing along with the dose of AHI. ConclusionAHI cannot improve the prognosis of patients having aortic arch replacement for Stanford Type A Aortic Dissection in a dose-dependent manner. Further well-designed prospective studies should be conducted to verification or falsification.
ObjectiveTo explore the effect of respiratory support in Community Respiratory Support Center on patients with chronic obstructive pulmonary disease (COPD) in stable phase. MethodsSixty-four GOLD gradeⅢpatients with stable COPD over age of 55 years were randomly divided into two groups.A respiratory support group received respiratory support in Community Respiratory Support Center, including health education, long-term oxygen therapy (LTOT), long-term ambroxol for atomization, long-term budesonide and formoterol for inhalation.A control group were prescribed budesonide and formoterol for inhalation when recruited, informed LTOT and long-term ambroxol for atomization at home, and follow-up visits to clinic every month. ResultsAfter 24 months of treatment in the respiratory support group, SpO2, PaO2, FEV1%pred, 6MWD, BMI, and ALB increased, mMRC, CAT, Hb, PaCO2 decreased (P < 0.05).While in the control group, FEV1%pred decreased, mMRC and CAT increased (P < 0.05), other indexes did not change significantly (P > 0.05).The times of acute exacerbation and hospitalization of the respiratory support group was less than that in the control group(P < 0.05). ConclusionsEstablishing Community Respiratory Support Center will benefit patients with stable COPD correct hypoxemia, slow the deterioration of lung function, improve the nutritional status of patients, and can also increase patients compliance to treatment.