Efects of high dose ambroxol on acute lung injury after liver transplantatio_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LEI Lianhui ¹ , WEI Zhongyu ¹ , YU Senyang ² , WANG Yugui ¹ , CHENG Rui ¹ , YANG Yang ¹ , ZANG Yunjin ¹

Intensive Care Unit，General Hospital of Armed Police Forces.Beijing，100039，ChinaCorresponding author：LEI Lian-hui，E-mail：Leilianhui@163.com;

Corresponding author：

LEI Lianhui, Email: Leilianhui@163.com

Keywords：

Ambroxol; Acute lung injury; Liver transplantation; Cytokines

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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（P lt;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，P lt;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.

Citation： LEI Lianhui,WEI Zhongyu,YU Senyang,WANG Yugui,CHENG Rui,YANG Yang,ZANG Yunjin. Efects of high dose ambroxol on acute lung injury after liver transplantatio. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(5): 334-337. doi: Copy

1.	陈刚，叶启发，刘慎微，等.肝移植术后早期并发成人呼吸窘迫综合征的原因及其防治.中华器官移植杂志，2000，21：123.
2.	Romanini BM，Sandri MG，Tosi M，et al.Ambroxol for prophylaxis and treatment of broncho-pulmonary complications after chest surgery.Int J Clin Res，1996，2：123-127.
3.	Laoag-Fernandez JB，Fernandez AM，Maruo T.Antenatal use of ambroxol for the prevention of infant respiratory distress syndrome.J Obstet Gynaecol Res，2000，26：307-312.
4.	张清，袁世荧，姚尚龙.大剂量沐舒坦对急性呼吸窘迫综合征患者抗氧化能力的影响.临床麻醉学杂志，2004，3：135-137.
5.	吴红涛，麻晓林，蒋耀光.沐舒坦针剂治疗兔创伤性急性肺损伤的实验研究.创伤外科杂志，2005，1：57-60.
6.	白春学，孙波，主编.急性呼吸窘迫综合征.上海：复旦大学出版社，2005，56-57.
7.	郑树森，主编.肝脏移植.北京：人民卫生出版社，2001，339-345.
8.	陈晓峰，丁嘉安，高文，等.开胸术后发生急性呼吸窘迫综合征的病因探讨及治疗.中华外科学杂志，2003，41：906-908.
9.	Quinlan GJ，Mumby S，Lamb NJ，et al.Acute respiratory distress syndrome secondary to cardiopulmonary bypass：do compromised plasma iron-binding anti-oxidant protection and thiol levels influence outcome?Crit Care Med，2000，28：2271-2276.
10.	Stettner S，Ledwozy WA.The effect of Ambroxol on bleomycin-induced changes in phospholipid composition of rat lung surfactant.Acta Physiol Hung，1995，83：181-187.
11.	张波，刘又宁.溴环己胺醇对通气机导致肺损伤保护作用的研究.中华医学杂志，2000，80：51-53.
12.	Wesierska-Gadek J，Goetz AE.Role of PARP on iNOS pathway during endotoxin-induced acute lung injury.Intensive Care Med，2004，30：1421-1431.
13.	Schott R，Chaouat A，Launoy A，et al.Improvement of pulmonary hypertension after liver transplantation.Chest，1999，115：1748-1749.
14.	Slutsky AS.Acute lung injury（ALI） and the acute respiratory distress syndrome（ARDS）.Transfusion Alternatives in Transfusion Medicine，2004，6（suppl）：45.
15.	Kopko PM，Marshall CS，Mackenzie MR，et al.Transfusion-related acute lung injury，report of aclinical look-back investigation，JAMA，2002，287：1968-1971.
16.	Markart P，Schmidt R，Ruppert C，et al.Ischemic and endotoxin pre-conditioning reduce lung reperfusion injury-induced surfactant alterations.J Heart Lung Transplant， 2005，24：1680-1689.
17.	顾小萍，徐福涛，仇毓东，等.原位肝移植大鼠供肝冷缺血时间对受体肺损伤的影响.国际麻醉学与复苏杂志，2006，1：22-24.
18.	Barsness KA，Bensard DD，Partrick DA，et al.IL-1beta induces an exaggerated pro-and anti-inflammatory response in peritoneal macrophages of children compared with adults.Pediatr Surg Int，2004，20：238-242.
19.	Farivar AS，Krishnadasan B，Naidu BV，et al.Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury.Ann Thorac Surg，2003，76：253-259.
20.	刘昌，宋宇龙，刘峰，等.大鼠供肝冷缺血时间与肝移植术后受者肺损伤的关系.中华器官移植杂志，2006，3：138-141.

1. 陈刚，叶启发，刘慎微，等.肝移植术后早期并发成人呼吸窘迫综合征的原因及其防治.中华器官移植杂志，2000，21：123.
2. Romanini BM，Sandri MG，Tosi M，et al.Ambroxol for prophylaxis and treatment of broncho-pulmonary complications after chest surgery.Int J Clin Res，1996，2：123-127.
3. Laoag-Fernandez JB，Fernandez AM，Maruo T.Antenatal use of ambroxol for the prevention of infant respiratory distress syndrome.J Obstet Gynaecol Res，2000，26：307-312.
4. 张清，袁世荧，姚尚龙.大剂量沐舒坦对急性呼吸窘迫综合征患者抗氧化能力的影响.临床麻醉学杂志，2004，3：135-137.
5. 吴红涛，麻晓林，蒋耀光.沐舒坦针剂治疗兔创伤性急性肺损伤的实验研究.创伤外科杂志，2005，1：57-60.
6. 白春学，孙波，主编.急性呼吸窘迫综合征.上海：复旦大学出版社，2005，56-57.
7. 郑树森，主编.肝脏移植.北京：人民卫生出版社，2001，339-345.
8. 陈晓峰，丁嘉安，高文，等.开胸术后发生急性呼吸窘迫综合征的病因探讨及治疗.中华外科学杂志，2003，41：906-908.
9. Quinlan GJ，Mumby S，Lamb NJ，et al.Acute respiratory distress syndrome secondary to cardiopulmonary bypass：do compromised plasma iron-binding anti-oxidant protection and thiol levels influence outcome?Crit Care Med，2000，28：2271-2276.
10. Stettner S，Ledwozy WA.The effect of Ambroxol on bleomycin-induced changes in phospholipid composition of rat lung surfactant.Acta Physiol Hung，1995，83：181-187.
11. 张波，刘又宁.溴环己胺醇对通气机导致肺损伤保护作用的研究.中华医学杂志，2000，80：51-53.
12. Wesierska-Gadek J，Goetz AE.Role of PARP on iNOS pathway during endotoxin-induced acute lung injury.Intensive Care Med，2004，30：1421-1431.
13. Schott R，Chaouat A，Launoy A，et al.Improvement of pulmonary hypertension after liver transplantation.Chest，1999，115：1748-1749.
14. Slutsky AS.Acute lung injury（ALI） and the acute respiratory distress syndrome（ARDS）.Transfusion Alternatives in Transfusion Medicine，2004，6（suppl）：45.
15. Kopko PM，Marshall CS，Mackenzie MR，et al.Transfusion-related acute lung injury，report of aclinical look-back investigation，JAMA，2002，287：1968-1971.
16. Markart P，Schmidt R，Ruppert C，et al.Ischemic and endotoxin pre-conditioning reduce lung reperfusion injury-induced surfactant alterations.J Heart Lung Transplant， 2005，24：1680-1689.
17. 顾小萍，徐福涛，仇毓东，等.原位肝移植大鼠供肝冷缺血时间对受体肺损伤的影响.国际麻醉学与复苏杂志，2006，1：22-24.
18. Barsness KA，Bensard DD，Partrick DA，et al.IL-1beta induces an exaggerated pro-and anti-inflammatory response in peritoneal macrophages of children compared with adults.Pediatr Surg Int，2004，20：238-242.
19. Farivar AS，Krishnadasan B，Naidu BV，et al.Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury.Ann Thorac Surg，2003，76：253-259.
20. 刘昌，宋宇龙，刘峰，等.大鼠供肝冷缺血时间与肝移植术后受者肺损伤的关系.中华器官移植杂志，2006，3：138-141.

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Efects of high dose ambroxol on acute lung injury after liver transplantatio

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