A Retrospective Study on Off-Label Drug Use in Dose of Ambroxol Hydrochloride Injection in Perioperative Period among Patients for Stanford Type A Aortic Dissection in Guangdong General Hospital between 2005 and 2014_Chinese Journal of Evidence-Based Medicine

Authors：

 ZHOUJing ¹ , CHENWen-ying ¹ , LAOHai-yan ¹ , ZENGYing-tong ¹ , LINLu ¹ , LIYou-ping ³ ,  YANGMin ^1,2

1. Department of Pharmacy, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, China;
2. Guangdong Provincial Cardiovascular Research Institute, Guangzhou 510080, China;
3. Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding?author：

YANGMin, Email: mnmyang@aliyun.com

Keywords：

Ambroxol hydrochloride injection; Stanford type A aortic dissection; Perioperative period; Off-label drug use in dose; Retrospective study

DOI：

10.7507/1672-2531.20160156

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Objective To 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. Methods All 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. Results a) 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. Conclusion AHI 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.

Citation： ZHOUJing, CHENWen-ying, LAOHai-yan, ZENGYing-tong, LINLu, LIYou-ping, YANGMin. A Retrospective Study on Off-Label Drug Use in Dose of Ambroxol Hydrochloride Injection in Perioperative Period among Patients for Stanford Type A Aortic Dissection in Guangdong General Hospital between 2005 and 2014. Chinese Journal of Evidence-Based Medicine, 2016, 16(9): 1014-1019. doi: 10.7507/1672-2531.20160156 Copy

1.	American Society of Hospital Pharmacists. ASHP statement on the use of medications for unlabeled uses. Am J Hosp Pharm, 1992, 49(8): 2006-2008.
2.	廣東省藥學會.藥品未注冊用法專家共識, 2010-03-18.
3.	Beeh KM, Beier J, Esperester A, et al. Antiinflammatory propertiesof ambroxol. Eur J Med Res, 2008, 13(12): 557-562.
4.	Malerba M, Ragnoli B. Ambroxol in the 21^st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol, 2008, 4(8): 1119-1129.
5.	Paleari D, Rossi GA, Nicolini G, et al. Ambroxol: a multifacetedmolecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov, 2011, 6(11): 1203-1214.
6.	周婧, 陳文穎, 勞海燕, 等.廣東省人民醫院2012年鹽酸氨溴索注射劑超說明書用藥情況調查.中國循證醫學雜志, 2014, 14(9): 1030-1037.
7.	Mészáros I, Mórocz J, Szlávi J, et al. Epidemiology and clinicopathology of aortic dissection. Chest, 2000, 117(5): 1271-1278.
8.	Hiratzka LF, Bakris GL, Beckman JA, et al. guidelines for the diagnosis and management of patients with Thoracic Aortic Disease. J Am CollCardiol, 2010, 55(14): e27-e129.
9.	Krahenbuhl ES, Immer FF, Stalder M, et al. Technical advances improved outcome in patients undergoing surgery of the ascending aorta and/or aortic arch: Ten years, experience. Eur J CardiothoracSurg, 2008, 34(3): 595-599.
10.	周婧, 陳文穎, 楊敏.鹽酸氨溴索對Stanford A型主動脈夾層急診手術后的肺保護作用.中國醫院藥學雜志, 2014, 34(23): 66-70.
11.	中國醫師協會胸外科醫師分會, "胸外科圍手術期肺部并發癥"研討會.胸外科圍手術期肺部并發癥防治專家共識.中華胸心血管外科雜志, 2009, 25(4): 217-218.
12.	陳淵, 馬彬, 楊克虎, 等.圍手術期使用鹽酸氨溴索對肺保護作用的系統評價.中國循證醫學雜志, 2009, 9(5): 558-564.
13.	Wang S, Huang D, Ma Q, et al. Does ambroxol confer a protective effect on the lungs in patients undergoing cardiac surgery or having lung resection? Interact Cardiovasc Thorac Surg, 2014, 18(6):830-834.
14.	Wang X, Wang L, Wang H, et al. Perioperative Lung Protection Provided by High-Dose Ambroxol in Patients with Lung Cancer. Cell Biochem Biophys, 2015, 73(2): 281-284.
15.	Assessment report as adopted by the PRAC and considered by the CMDh with all information of a commercially confidential nature deleted: Ambroxol and bromhexine containing medicinal products. 2015.
16.	McAlister FA, Bertsch K, Man J, et al. Incidence of and risk factors for pulmonary complications after nonthoracic surgery. Am J Respir Crit Care Med, 2005, 171(5): 514.
17.	Canet J, Gallart L, Gomar C, et al. Prediction of Postoperative Pulmonary Complications in a Population-based Surgical Cohort. Anesthesiology, 2010, 113(6): 1338-1350.
18.	Qaseem A, Snow V, Fitterman N, et al. Risk Assessment for and Strategies To Reduce Perioperative Pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline from the American college of physicians. Ann Intern Med, 2006, 144(8): 575-580.
19.	勞海燕, 王啟儀, 楊敏, 等.廣東省人民醫院超說明書用藥臨床管理方法與流程研究.中國循證醫學雜志, 2014, 14(9): 1025-1029.

1. American Society of Hospital Pharmacists. ASHP statement on the use of medications for unlabeled uses. Am J Hosp Pharm, 1992, 49(8): 2006-2008.
2. 廣東省藥學會.藥品未注冊用法專家共識, 2010-03-18.
3. Beeh KM, Beier J, Esperester A, et al. Antiinflammatory propertiesof ambroxol. Eur J Med Res, 2008, 13(12): 557-562.
4. Malerba M, Ragnoli B. Ambroxol in the 21^st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol, 2008, 4(8): 1119-1129.
5. Paleari D, Rossi GA, Nicolini G, et al. Ambroxol: a multifacetedmolecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov, 2011, 6(11): 1203-1214.
6. 周婧, 陳文穎, 勞海燕, 等.廣東省人民醫院2012年鹽酸氨溴索注射劑超說明書用藥情況調查.中國循證醫學雜志, 2014, 14(9): 1030-1037.
7. Mészáros I, Mórocz J, Szlávi J, et al. Epidemiology and clinicopathology of aortic dissection. Chest, 2000, 117(5): 1271-1278.
8. Hiratzka LF, Bakris GL, Beckman JA, et al. guidelines for the diagnosis and management of patients with Thoracic Aortic Disease. J Am CollCardiol, 2010, 55(14): e27-e129.
9. Krahenbuhl ES, Immer FF, Stalder M, et al. Technical advances improved outcome in patients undergoing surgery of the ascending aorta and/or aortic arch: Ten years, experience. Eur J CardiothoracSurg, 2008, 34(3): 595-599.
10. 周婧, 陳文穎, 楊敏.鹽酸氨溴索對Stanford A型主動脈夾層急診手術后的肺保護作用.中國醫院藥學雜志, 2014, 34(23): 66-70.
11. 中國醫師協會胸外科醫師分會, "胸外科圍手術期肺部并發癥"研討會.胸外科圍手術期肺部并發癥防治專家共識.中華胸心血管外科雜志, 2009, 25(4): 217-218.
12. 陳淵, 馬彬, 楊克虎, 等.圍手術期使用鹽酸氨溴索對肺保護作用的系統評價.中國循證醫學雜志, 2009, 9(5): 558-564.
13. Wang S, Huang D, Ma Q, et al. Does ambroxol confer a protective effect on the lungs in patients undergoing cardiac surgery or having lung resection? Interact Cardiovasc Thorac Surg, 2014, 18(6):830-834.
14. Wang X, Wang L, Wang H, et al. Perioperative Lung Protection Provided by High-Dose Ambroxol in Patients with Lung Cancer. Cell Biochem Biophys, 2015, 73(2): 281-284.
15. Assessment report as adopted by the PRAC and considered by the CMDh with all information of a commercially confidential nature deleted: Ambroxol and bromhexine containing medicinal products. 2015.
16. McAlister FA, Bertsch K, Man J, et al. Incidence of and risk factors for pulmonary complications after nonthoracic surgery. Am J Respir Crit Care Med, 2005, 171(5): 514.
17. Canet J, Gallart L, Gomar C, et al. Prediction of Postoperative Pulmonary Complications in a Population-based Surgical Cohort. Anesthesiology, 2010, 113(6): 1338-1350.
18. Qaseem A, Snow V, Fitterman N, et al. Risk Assessment for and Strategies To Reduce Perioperative Pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline from the American college of physicians. Ann Intern Med, 2006, 144(8): 575-580.
19. 勞海燕, 王啟儀, 楊敏, 等.廣東省人民醫院超說明書用藥臨床管理方法與流程研究.中國循證醫學雜志, 2014, 14(9): 1025-1029.

Chinese Journal of Evidence-Based Medicine

A Retrospective Study on Off-Label Drug Use in Dose of Ambroxol Hydrochloride Injection in Perioperative Period among Patients for Stanford Type A Aortic Dissection in Guangdong General Hospital between 2005 and 2014

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