Cell Biochem Biophys DOI 10.1007/s12013-015-0590-z
ORIGINAL PAPER
Perioperative Lung Protection Provided by High-Dose Ambroxol in Patients with Lung Cancer Xin Wang • Lei Wang • Huayong Wang Hao Zhang
•
Ó Springer Science+Business Media New York 2015
Abstract The purpose is to observe the clinical effect of large doses of ambroxol hydrochloride in lung protection during the perioperative period of lung cancer operation. Fifty-six lung cancer patients who have undergone openthoracic pulmonary lobectomy were divided randomly into two groups, and were given normal and large doses of ambroxol hydrochloride, respectively, during their perioperative period. Statistics based on post-operation clinical observations were analyzed in terms of ease of expectoration and expectoration properties, duration of antibiotics dependence, occurrence of lung complications, and adverse reactions related to ambroxol hydrochloride. On the third and the seventh day, the experimental group showed signs of improvement in terms of ease of expectoration and expectoration properties, compared with the controlled group. In terms of occurrence of post-operation lung complications and duration of antibiotics dependence, the experimental group also performed better. Using large doses of ambroxol hydrochloride would result in better clinical effects than using normal doses in preventing post-operation complications, and its clinical value in lung protection during lung cancer perioperative period calls for further research and promotion.
Introduction
Keywords Ambroxol hydrochloride Lung cancer Complications Antibiotics
Patients and Methods
Wang Xin and Wang Lei have contributed equally to the study and should be considered as co-first authors. X. Wang L. Wang (&) H. Wang H. Zhang Department of Thoracic Surgery, Xuzhou Central Hospital, Jiefang Road No. 199, Xuzhou City, Jiangsu Province, China e-mail: [email protected]
This study aimed to determine whether large dose of ambroxol Hydrochloride could result in better perioperative protection of the lung during lung cancer surgery. This study included 56 lung cancer patients, who received lobectomy after thoracotomy. These patients were randomized into two groups. During perioperative period, control group received conventional dose of ambroxol Hydrochloride, and treatment group received a dose of ambroxol Hydrochloride 1000 mg a day. The patient-related data were recorded and analyzed on day 3 and day 7 postoperatively. Both sets of data concluded that the sputum was thinner and more easily to be expectorated in control group than that in treatment group. We recorded and compared the incidence of pulmonary infection and atelectasis and the duration of antibiotic treatment. The result indicated that all three parameters were decreased in the treatment group when compared to those in control group. Therefore, we concluded that the clinical efficacy of an increased dose of ambroxol Hydrochloride was better than that of conventional dose in preventing post-operative complications in lung cancer patients.
This research was approved by the Medical Ethics Commission of Xuzhou Central hospital. Inclusion criteria were as follows: (a) patients with pathologically or physically confirmed primary lung cancer; (b) any surgical contraindications were ruled out during the preoperative examinations; (c) no lung infections or atelectasis were found during the preoperative examinations; (d) no expectorant drug had been used in the previous 2 weeks; (e) no history of ambroxol allergy; and (f) signed informed consents.
123
Cell Biochem Biophys
The 56 patients were equally randomized into two groups: the intervention group (N = 28) and the control group (N = 28). The clinical data of these two groups are summarized in Table 1. The differences between the two groups were not shown to be significant (P [ 0). Before surgery, general anesthesia was achieved by both an intravenous anesthetic technique and the use of a double-lumen endotracheal tube. Using a posterolateral incision, we performed the anatomic lobectomy and the dissection of mediastinal lymph nodes. After the surgery, second-generation cephalosporin antibiotics were used to prevent potential infections. Post-surgery, ambroxol 30 mg was inhaled three times a day. In the intervention group, ambroxol 500 mg was also intravenously administered twice a day (Ambroxol Hydrochloride Injection; Boehringer Ingelheim Espana, S.A.). In the control group, however, ambroxol 30 mg was intravenously injected twice a day. The difficulty in expectoration and the nature of the sputum were recorded on the third and seventh post-operative day. Routine blood tests were performed daily after the surgery. For patients with normal white blood cell count and body temperature and without rales on lung auscultation, chest X-ray was performed on the same day. If the chest X-ray showed no lung infection or atelectasis, antibiotics were stopped, and then the duration of antibiotic use was recorded. The post-operative lung complications as well as the adverse reactions of ambroxol were observed.
Data Analysis Data were analyzed using the SPSS software. The measurement data are presented as X ± SD, and the intergroup comparison was performed using independent sample t test. The count data were compared using v2 test. A value of P \ 05 was considered statistically significant.
Results The difficulty in expectoration and the nature of the sputum on the third and seventh post-operative day in these two groups are summarized in Tables 2 and 3. Statistics shows that there are significant improvements in the intervention group. Sputum became thinning and could be coughed out easily in 3 and 7 days after surgery. This suggests that preoperative application of a high-dose of ambroxol can make patients sputum diluted and easy to cough up. After the surgery, the duration of antibiotic use and the incidences of lung infections/atelectasis are shown in Table 4. The duration of post-operative antibiotic use of the patients in the intervention group was shorter than the duration of the patients in the control group. This suggests that preoperative application of a high-dose of ambroxol can shorten the duration of post-operative antibiotic use. No nausea, vomiting, or other common adverse reactions of ambroxol were observed in either groups.
Discussion The aim of perioperative lung protection is to prevent the post-operative lung complications. Mechanical ventilation, squeezing during the operation, and the effects of anesthetic drugs may cause lung tissue injuries and therefore the disordered ventilation/perfusion ratio and decreased pulmonary surfactant (PS), resulting in lung complications [1, 2]. The control group was given ambroxol 30 mg twice a day, which is the recommended dose of the drug, as stated by the manufacturers. According to expert consensus on the prevention and treatment of perioperative lung complication in the thoracic surgeries, the intervention group was given ambroxol 500 mg twice a day [3]. Recent studies have found that this high a dose of ambroxol not only can clear sputum but is also effective in promoting the
Table 1 General data of 56 patients with primary lung cancer who had received open surgery Group
N
Intervention group
28
Control group
28
Gender
Lesion location
Pathologic type
Left lung
Right lung
Squamous cancer
History of smoking
COPD
Obesity
Adenocarcinoma
Yes
No
Yes
No
Yes
No
M
F
18
10
63.36 ± 4.41
15
13
20
8
18
10
9
19
5
23
15
13
65.14 ± 4.19
12
16
18
10
17
11
11
17
7
21
t
-1.5543
v2
0.66
123
Age
0.64
0.33
0.08
0.31
0.42
Cell Biochem Biophys Table 2 Clinical symptoms on the third post-operative day
Table 3 Clinical symptoms on the seventh post-operative day
Group
N
Difficulty in expectoration Easy
Relatively difficult
Difficult
Clear
Relatively clear
Thick
Intervention group
28
19
6
3
17
8
3
Control group
28
7
11
10
8
12
8
v2
10.78
6.32
P value
\0.05
\0.05
Group
N
Difficulty in expectoration
Nature of the sputum
Easy
Relatively difficult
Difficult
Clear
Relatively clear
Thick
Intervention group
28
24
3
1
23
5
0
Control group v2
28
14
10 8.20
4
15
10 6.35
3
\0.05
P value
Table 4 Duration of antibiotic usage and incidences of lung complications after the surgery
Nature of the sputum
Group
N
Date of antibiotic usage
\0.05
Lung infection
Atelectasis
Yes
No
Yes
No
Intervention group
28
5.75 ± 1.62
2
26
1
27
Control group
28
7.14 ± 1.46
8
20
6
22
t
-3.3761
v2 P value
synthesis and release of PS, fighting against oxidative damage, and preventing an inflammatory response [4]. Use of a higher dose of ambroxol, for perioperative lung protection in surgeries for lung cancer, has the following advantages in addition to its conventional clinical efficacies. It can enhance the activity of choline-phosphatidyl transferase, stimulate the synthesis and release of PS in alveolar epithelial type II cells, lower the alveolar surface tension, and thus prevent alveolar collapse [5]. A higher dose of ambroxol can fight against oxidation and clear oxygen free radicals; thus reducing the lung injuries caused by oxidation, and thereby protecting the lungs [6]. Finally, a higher dose can inhibit the release of various inflammatory cells and inflammatory mediators and thus relieve the lung damage caused by the inflammation [7]. In addition, ambroxol has a synergistic effect to increase the concentrations of antibiotics in lung tissue and plasma and thus shorten the duration of post-operative antibiotic use in combination with antibiotics [8]. In summary, compared with a conventional dosage, a high-dose treatment with ambroxol has superior clinical effectiveness in preventing the post-operative complications. Therefore, ambroxol has an important role in the perioperative lung protection during the surgeries for lung cancer and warrants further research.
\0.05
4.38
4.67
\0.05
\0.05
Furthermore, our study showed that the high-dose ambroxol can decrease the sputum viscosity, making expectoration easier, which reduced the occurrence of postoperative lung complications and the use of post-operative antibiotics. No adverse reaction was noted after the use of the conventional and high-dose ambroxol. Nevertheless, our study was limited by its small sample size. Larger clinical studies using more systematic approaches should be conducted to explore the specific usage, withdrawal standards, and adverse reactions of ambroxol.
Conclusion Lung cancer patients are susceptible to complications such as lung infection and atelectasis. Analysis suggests that this may be due to several reasons. Many patients have been chronicle smokers prior to operation, and the toxics from tobacco have disrupted the proper functioning of their respiratory systems and caused higher excretion in respiratory tracts [9]. The mechanical manipulations of lungs involved in operations can cause material lung damages, hamper blood circulation in lungs, and therefore cause partial disturbance of ventilation–perfusion ratio, lower concentration of actives on the surface of alveoli, and possibly partial
123
Cell Biochem Biophys
atrophy in alveoli, the lung’s tissues [10]. The insertion of a tracheal cannula in the anesthetizing process can damage the mucous membrane of trachea, and narcotic drugs can have an impact on epithelial cells transmitter of respiratory tracts [11]. This leads to higher post-operation bronchus excretion, lower clearing capacity of bronchus mucous membrane, and rising resistance in small airways [11]. Oxidative stress from high concentration of oxygen inhaled during the operation can cause the body to produce huge amounts of oxygen radicals that adversely affect post-operation recovery [12]. Post-operation, patients dare not cough forcefully for fear of pain, which hinders effective expectoration [13]. Finally, patients with malignant tumors often suffer from a decline in immunity, especially those who have undergone radiotherapy or chemotherapy [14]. These groups all have high risks of incurring post-operation infective diseases. Effective prevention of post-operation lung complications is essential for the recovery of lung cancer patients. Successful prevention depends closely upon qualified treatment procedures. To facilitate recovery of lung cancer patients, clinicians and scholars of chest surgery have long sought for safer and more effective post-operation treatments. Clinical practices to prevent post-operation lung complications include tapping the patients’ backs, urging them to cough forcefully and atomization inhalation in order to assist expectoration, as well as ambroxol hydrochloride, the usual dose of which is 30 mg bid. In recent years, large-dose ambroxol hydrochloride treatment has captured many clinicians’ attention, and we have conducted relevant clinical researches, shifting the dose to 500 mg ivgtt bid. Statistical analysis of our research data shows that patients who receive large-dose ambroxol hydrochloride treatment have easier and thinner expectoration after operation, lower rates of post-operation lung complications, and shorter dependence on antibiotics. Our conclusion coincides with those reached by other scholars in the same field. We argue that clinical effects from large doses of ambroxol hydrochloride in preventing post-operation complications are better than regular-dose treatments, and its value in clinical use to protect lungs during lung cancer perioperative periods warrants promotion. Post-operation lung complications are not limited to lung cancer patients but also occur in patients who have undergone other chest surgeries, such as benign lung tumors, esophageal cancer, and pneumothorax operations. In some cases, patients may have lung complications after operations on the abdomen, cranium, or other parts of the body. There are many similitudes and similarities between these complications and those suffered by lung cancer patients. Therefore, we predict that for many non-lung cancer patients, large doses of ambroxol hydrochloride could be applied to prevent post-operation complications
123
during peri-operation periods as well. These topics all require further probing by us and clinicians alike. Acknowledgments Thanks to the Xuzhou central hospital which supported this study. Conflict of interest
All authors have no conflicts of interest.
References 1. Hayes, J. P., Williams, E. A., Goldstraw, P., et al. (1995). Lung injury in patients following thoracotomy. Thorax, 50, 990–991. 2. Hohlfeld, J., Fabel, H., & Hamm, H. (1997). The role of pulmonary surfactant in obstructive airways disease. European Respiratory Journal, 10, 482–491. 3. Chinese Medical Association branch of Thoracic Surgeons. (2009). Symposium on the perioperative lung complication in the thoracic surgeries. Expert consensus on the prevention and treatment of perioperative lung complication in the thoracic surgeries. Chinese Journal of Thoracic and Cardiovascular Surgery, 25, 217–218. 4. Beeh, K. M., Beier, J., Esperester, A., et al. (2008). Antiinflammatory properties of ambroxol. European Journal of Medical Research, 13, 1420–1422. 5. Tan, L. J., Liu, Y. Q., Xu, S. T., et al. (2000). Role of ambroxol in protection of the decrease of ps in lung injury after thoracotomy. Journal of Shanghai Medical University, 27, 484–487. 6. Kupczyk, M., & Kuna, P. (2002). Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties. Pol Merkur Lekarski, 12, 248–252. 7. Gupta, P. R. (2010). Ambroxol-Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India, 27, 46–48. 8. Derelle, J., Bertolo-Houfiez, E., Marchal, F., et al. (1998). Respiratory evolution of patient with mucoviscidosis treated with mucolytic agents plus domase alfa. Archives de Pediatrie, 5, 371–377. 9. Maurer, C. C., & Syrigos, K. N. (2006). Biology of tobacco and smoking. In K. N. Syrigos, C. M. Nutting, & C. Roussoc (Eds.), Tumors of the chest-biology, diagnosis and management (pp. 23–39). New York: Springer. 10. Du, J. J., & Peng, Z. M. (2003). Thoracic surgery complications (pp. 74–81). Beijing: Military medical science press. 11. Luo, W. B., Wu, G. D., & Peng, X. F. (2013). Effect of different doses of ambroxol Hydrochloride in the prevention of lung complications in patients undergoing lung surgery. China Medical Herald, 10, 71–72. 12. Rao, X. H., Liu, Y. H., Liang, J. S., et al. (2013). Investigation of the complication in patients with lung cancer after surgery by using larger dose of ambroxol. Medical Innovation of China, 1, 6–7. 13. Tang, M. G., Zhang, J. W., Wang, H. Y., et al. (2012). Observation of curative effect on continuously-pumped large dose of Ambroxol in patients with lung cancer and COPD after pulmonary lobotomy. China Medical Herald, 9, 86–87. 14. Yang, Y., & Wang, D. H. (2009). The clinical effect of high doses ambroxol on pneumonia in patients with abdomen or thorax malignant neoplasms in postoperative period. Journal of Tianjin Medical University, 02, 271–273.
ORIGINAL PAPER
Perioperative Lung Protection Provided by High-Dose Ambroxol in Patients with Lung Cancer Xin Wang • Lei Wang • Huayong Wang Hao Zhang
•
Ó Springer Science+Business Media New York 2015
Abstract The purpose is to observe the clinical effect of large doses of ambroxol hydrochloride in lung protection during the perioperative period of lung cancer operation. Fifty-six lung cancer patients who have undergone openthoracic pulmonary lobectomy were divided randomly into two groups, and were given normal and large doses of ambroxol hydrochloride, respectively, during their perioperative period. Statistics based on post-operation clinical observations were analyzed in terms of ease of expectoration and expectoration properties, duration of antibiotics dependence, occurrence of lung complications, and adverse reactions related to ambroxol hydrochloride. On the third and the seventh day, the experimental group showed signs of improvement in terms of ease of expectoration and expectoration properties, compared with the controlled group. In terms of occurrence of post-operation lung complications and duration of antibiotics dependence, the experimental group also performed better. Using large doses of ambroxol hydrochloride would result in better clinical effects than using normal doses in preventing post-operation complications, and its clinical value in lung protection during lung cancer perioperative period calls for further research and promotion.
Introduction
Keywords Ambroxol hydrochloride Lung cancer Complications Antibiotics
Patients and Methods
Wang Xin and Wang Lei have contributed equally to the study and should be considered as co-first authors. X. Wang L. Wang (&) H. Wang H. Zhang Department of Thoracic Surgery, Xuzhou Central Hospital, Jiefang Road No. 199, Xuzhou City, Jiangsu Province, China e-mail: [email protected]
This study aimed to determine whether large dose of ambroxol Hydrochloride could result in better perioperative protection of the lung during lung cancer surgery. This study included 56 lung cancer patients, who received lobectomy after thoracotomy. These patients were randomized into two groups. During perioperative period, control group received conventional dose of ambroxol Hydrochloride, and treatment group received a dose of ambroxol Hydrochloride 1000 mg a day. The patient-related data were recorded and analyzed on day 3 and day 7 postoperatively. Both sets of data concluded that the sputum was thinner and more easily to be expectorated in control group than that in treatment group. We recorded and compared the incidence of pulmonary infection and atelectasis and the duration of antibiotic treatment. The result indicated that all three parameters were decreased in the treatment group when compared to those in control group. Therefore, we concluded that the clinical efficacy of an increased dose of ambroxol Hydrochloride was better than that of conventional dose in preventing post-operative complications in lung cancer patients.
This research was approved by the Medical Ethics Commission of Xuzhou Central hospital. Inclusion criteria were as follows: (a) patients with pathologically or physically confirmed primary lung cancer; (b) any surgical contraindications were ruled out during the preoperative examinations; (c) no lung infections or atelectasis were found during the preoperative examinations; (d) no expectorant drug had been used in the previous 2 weeks; (e) no history of ambroxol allergy; and (f) signed informed consents.
123
Cell Biochem Biophys
The 56 patients were equally randomized into two groups: the intervention group (N = 28) and the control group (N = 28). The clinical data of these two groups are summarized in Table 1. The differences between the two groups were not shown to be significant (P [ 0). Before surgery, general anesthesia was achieved by both an intravenous anesthetic technique and the use of a double-lumen endotracheal tube. Using a posterolateral incision, we performed the anatomic lobectomy and the dissection of mediastinal lymph nodes. After the surgery, second-generation cephalosporin antibiotics were used to prevent potential infections. Post-surgery, ambroxol 30 mg was inhaled three times a day. In the intervention group, ambroxol 500 mg was also intravenously administered twice a day (Ambroxol Hydrochloride Injection; Boehringer Ingelheim Espana, S.A.). In the control group, however, ambroxol 30 mg was intravenously injected twice a day. The difficulty in expectoration and the nature of the sputum were recorded on the third and seventh post-operative day. Routine blood tests were performed daily after the surgery. For patients with normal white blood cell count and body temperature and without rales on lung auscultation, chest X-ray was performed on the same day. If the chest X-ray showed no lung infection or atelectasis, antibiotics were stopped, and then the duration of antibiotic use was recorded. The post-operative lung complications as well as the adverse reactions of ambroxol were observed.
Data Analysis Data were analyzed using the SPSS software. The measurement data are presented as X ± SD, and the intergroup comparison was performed using independent sample t test. The count data were compared using v2 test. A value of P \ 05 was considered statistically significant.
Results The difficulty in expectoration and the nature of the sputum on the third and seventh post-operative day in these two groups are summarized in Tables 2 and 3. Statistics shows that there are significant improvements in the intervention group. Sputum became thinning and could be coughed out easily in 3 and 7 days after surgery. This suggests that preoperative application of a high-dose of ambroxol can make patients sputum diluted and easy to cough up. After the surgery, the duration of antibiotic use and the incidences of lung infections/atelectasis are shown in Table 4. The duration of post-operative antibiotic use of the patients in the intervention group was shorter than the duration of the patients in the control group. This suggests that preoperative application of a high-dose of ambroxol can shorten the duration of post-operative antibiotic use. No nausea, vomiting, or other common adverse reactions of ambroxol were observed in either groups.
Discussion The aim of perioperative lung protection is to prevent the post-operative lung complications. Mechanical ventilation, squeezing during the operation, and the effects of anesthetic drugs may cause lung tissue injuries and therefore the disordered ventilation/perfusion ratio and decreased pulmonary surfactant (PS), resulting in lung complications [1, 2]. The control group was given ambroxol 30 mg twice a day, which is the recommended dose of the drug, as stated by the manufacturers. According to expert consensus on the prevention and treatment of perioperative lung complication in the thoracic surgeries, the intervention group was given ambroxol 500 mg twice a day [3]. Recent studies have found that this high a dose of ambroxol not only can clear sputum but is also effective in promoting the
Table 1 General data of 56 patients with primary lung cancer who had received open surgery Group
N
Intervention group
28
Control group
28
Gender
Lesion location
Pathologic type
Left lung
Right lung
Squamous cancer
History of smoking
COPD
Obesity
Adenocarcinoma
Yes
No
Yes
No
Yes
No
M
F
18
10
63.36 ± 4.41
15
13
20
8
18
10
9
19
5
23
15
13
65.14 ± 4.19
12
16
18
10
17
11
11
17
7
21
t
-1.5543
v2
0.66
123
Age
0.64
0.33
0.08
0.31
0.42
Cell Biochem Biophys Table 2 Clinical symptoms on the third post-operative day
Table 3 Clinical symptoms on the seventh post-operative day
Group
N
Difficulty in expectoration Easy
Relatively difficult
Difficult
Clear
Relatively clear
Thick
Intervention group
28
19
6
3
17
8
3
Control group
28
7
11
10
8
12
8
v2
10.78
6.32
P value
\0.05
\0.05
Group
N
Difficulty in expectoration
Nature of the sputum
Easy
Relatively difficult
Difficult
Clear
Relatively clear
Thick
Intervention group
28
24
3
1
23
5
0
Control group v2
28
14
10 8.20
4
15
10 6.35
3
\0.05
P value
Table 4 Duration of antibiotic usage and incidences of lung complications after the surgery
Nature of the sputum
Group
N
Date of antibiotic usage
\0.05
Lung infection
Atelectasis
Yes
No
Yes
No
Intervention group
28
5.75 ± 1.62
2
26
1
27
Control group
28
7.14 ± 1.46
8
20
6
22
t
-3.3761
v2 P value
synthesis and release of PS, fighting against oxidative damage, and preventing an inflammatory response [4]. Use of a higher dose of ambroxol, for perioperative lung protection in surgeries for lung cancer, has the following advantages in addition to its conventional clinical efficacies. It can enhance the activity of choline-phosphatidyl transferase, stimulate the synthesis and release of PS in alveolar epithelial type II cells, lower the alveolar surface tension, and thus prevent alveolar collapse [5]. A higher dose of ambroxol can fight against oxidation and clear oxygen free radicals; thus reducing the lung injuries caused by oxidation, and thereby protecting the lungs [6]. Finally, a higher dose can inhibit the release of various inflammatory cells and inflammatory mediators and thus relieve the lung damage caused by the inflammation [7]. In addition, ambroxol has a synergistic effect to increase the concentrations of antibiotics in lung tissue and plasma and thus shorten the duration of post-operative antibiotic use in combination with antibiotics [8]. In summary, compared with a conventional dosage, a high-dose treatment with ambroxol has superior clinical effectiveness in preventing the post-operative complications. Therefore, ambroxol has an important role in the perioperative lung protection during the surgeries for lung cancer and warrants further research.
\0.05
4.38
4.67
\0.05
\0.05
Furthermore, our study showed that the high-dose ambroxol can decrease the sputum viscosity, making expectoration easier, which reduced the occurrence of postoperative lung complications and the use of post-operative antibiotics. No adverse reaction was noted after the use of the conventional and high-dose ambroxol. Nevertheless, our study was limited by its small sample size. Larger clinical studies using more systematic approaches should be conducted to explore the specific usage, withdrawal standards, and adverse reactions of ambroxol.
Conclusion Lung cancer patients are susceptible to complications such as lung infection and atelectasis. Analysis suggests that this may be due to several reasons. Many patients have been chronicle smokers prior to operation, and the toxics from tobacco have disrupted the proper functioning of their respiratory systems and caused higher excretion in respiratory tracts [9]. The mechanical manipulations of lungs involved in operations can cause material lung damages, hamper blood circulation in lungs, and therefore cause partial disturbance of ventilation–perfusion ratio, lower concentration of actives on the surface of alveoli, and possibly partial
123
Cell Biochem Biophys
atrophy in alveoli, the lung’s tissues [10]. The insertion of a tracheal cannula in the anesthetizing process can damage the mucous membrane of trachea, and narcotic drugs can have an impact on epithelial cells transmitter of respiratory tracts [11]. This leads to higher post-operation bronchus excretion, lower clearing capacity of bronchus mucous membrane, and rising resistance in small airways [11]. Oxidative stress from high concentration of oxygen inhaled during the operation can cause the body to produce huge amounts of oxygen radicals that adversely affect post-operation recovery [12]. Post-operation, patients dare not cough forcefully for fear of pain, which hinders effective expectoration [13]. Finally, patients with malignant tumors often suffer from a decline in immunity, especially those who have undergone radiotherapy or chemotherapy [14]. These groups all have high risks of incurring post-operation infective diseases. Effective prevention of post-operation lung complications is essential for the recovery of lung cancer patients. Successful prevention depends closely upon qualified treatment procedures. To facilitate recovery of lung cancer patients, clinicians and scholars of chest surgery have long sought for safer and more effective post-operation treatments. Clinical practices to prevent post-operation lung complications include tapping the patients’ backs, urging them to cough forcefully and atomization inhalation in order to assist expectoration, as well as ambroxol hydrochloride, the usual dose of which is 30 mg bid. In recent years, large-dose ambroxol hydrochloride treatment has captured many clinicians’ attention, and we have conducted relevant clinical researches, shifting the dose to 500 mg ivgtt bid. Statistical analysis of our research data shows that patients who receive large-dose ambroxol hydrochloride treatment have easier and thinner expectoration after operation, lower rates of post-operation lung complications, and shorter dependence on antibiotics. Our conclusion coincides with those reached by other scholars in the same field. We argue that clinical effects from large doses of ambroxol hydrochloride in preventing post-operation complications are better than regular-dose treatments, and its value in clinical use to protect lungs during lung cancer perioperative periods warrants promotion. Post-operation lung complications are not limited to lung cancer patients but also occur in patients who have undergone other chest surgeries, such as benign lung tumors, esophageal cancer, and pneumothorax operations. In some cases, patients may have lung complications after operations on the abdomen, cranium, or other parts of the body. There are many similitudes and similarities between these complications and those suffered by lung cancer patients. Therefore, we predict that for many non-lung cancer patients, large doses of ambroxol hydrochloride could be applied to prevent post-operation complications
123
during peri-operation periods as well. These topics all require further probing by us and clinicians alike. Acknowledgments Thanks to the Xuzhou central hospital which supported this study. Conflict of interest
All authors have no conflicts of interest.
References 1. Hayes, J. P., Williams, E. A., Goldstraw, P., et al. (1995). Lung injury in patients following thoracotomy. Thorax, 50, 990–991. 2. Hohlfeld, J., Fabel, H., & Hamm, H. (1997). The role of pulmonary surfactant in obstructive airways disease. European Respiratory Journal, 10, 482–491. 3. Chinese Medical Association branch of Thoracic Surgeons. (2009). Symposium on the perioperative lung complication in the thoracic surgeries. Expert consensus on the prevention and treatment of perioperative lung complication in the thoracic surgeries. Chinese Journal of Thoracic and Cardiovascular Surgery, 25, 217–218. 4. Beeh, K. M., Beier, J., Esperester, A., et al. (2008). Antiinflammatory properties of ambroxol. European Journal of Medical Research, 13, 1420–1422. 5. Tan, L. J., Liu, Y. Q., Xu, S. T., et al. (2000). Role of ambroxol in protection of the decrease of ps in lung injury after thoracotomy. Journal of Shanghai Medical University, 27, 484–487. 6. Kupczyk, M., & Kuna, P. (2002). Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties. Pol Merkur Lekarski, 12, 248–252. 7. Gupta, P. R. (2010). Ambroxol-Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India, 27, 46–48. 8. Derelle, J., Bertolo-Houfiez, E., Marchal, F., et al. (1998). Respiratory evolution of patient with mucoviscidosis treated with mucolytic agents plus domase alfa. Archives de Pediatrie, 5, 371–377. 9. Maurer, C. C., & Syrigos, K. N. (2006). Biology of tobacco and smoking. In K. N. Syrigos, C. M. Nutting, & C. Roussoc (Eds.), Tumors of the chest-biology, diagnosis and management (pp. 23–39). New York: Springer. 10. Du, J. J., & Peng, Z. M. (2003). Thoracic surgery complications (pp. 74–81). Beijing: Military medical science press. 11. Luo, W. B., Wu, G. D., & Peng, X. F. (2013). Effect of different doses of ambroxol Hydrochloride in the prevention of lung complications in patients undergoing lung surgery. China Medical Herald, 10, 71–72. 12. Rao, X. H., Liu, Y. H., Liang, J. S., et al. (2013). Investigation of the complication in patients with lung cancer after surgery by using larger dose of ambroxol. Medical Innovation of China, 1, 6–7. 13. Tang, M. G., Zhang, J. W., Wang, H. Y., et al. (2012). Observation of curative effect on continuously-pumped large dose of Ambroxol in patients with lung cancer and COPD after pulmonary lobotomy. China Medical Herald, 9, 86–87. 14. Yang, Y., & Wang, D. H. (2009). The clinical effect of high doses ambroxol on pneumonia in patients with abdomen or thorax malignant neoplasms in postoperative period. Journal of Tianjin Medical University, 02, 271–273.
