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Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 155-160

Comparison of combination of ketamine hydrochloride and propofol with fentanyl citrate and propofol for patients undergoing endoscopic retrograde cholangiopancreatography

Department of Anaesthesiology, Gujarat Cancer and Research Institute, B. J. Medical College, Ahmedabad, Gujarat, India

Date of Submission25-Nov-2019
Date of Acceptance25-Nov-2019
Date of Web Publication23-Jan-2020

Correspondence Address:
Dr. Damini Sanjay Makwana
Department of Anaesthesiology, Gujarat Cancer and Research Institute, B. J. Medical College, Ahmedabad, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/BJOA.BJOA_6_19

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Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a lengthy diagnostic/therapeutic procedure performed for various pancreatic-biliary disorders often involving high-risk patients. The aim of our study is to compare the ketamine hydrochloride and fentanyl citrate with propofol for patients undergoing ERCP. Patients and Methods: In this prospective randomized study, 100 consenting patients undergoing ERCP were randomly allocated into two groups of 50 each: Group PK received ketamine 1 mg/kg and Group PF received fentanyl 1 mcg/kg. Sedation (based on the Ramsay Sedation Score), blood pressure (BP), heart rate (HR), peripheral oxygen saturation (SpO2), recovery time, total propofol consumed, quality of analgesia, endoscopist and patient's satisfaction score, and various complications were recorded. Results: The sedative and analgesic effects did not differ among both the groups. The mean HR in the PK Group was higher than Group PF. The decrease in the mean arterial BP was much more in the PF Group. SpO2did not differ in both the groups. Total propofol consumption was higher in PF Group than PK. Moreover, the recovery time was longer in the PK Group compared to Group PF. Patients' and endoscopists' satisfaction score showed no significant difference between the two groups. Conclusion: We concluded that ketamine and fentanyl are equally efficacious with propofol for sedation in patients undergoing ERCP. Recovery time was shorter in the propofol-fentanyl regimen compared to the propofol-ketamine regimen.

Keywords: Endoscopic retrograde cholangiopancreatography, fentanyl, ketamine, propofol, satisfaction, sedation

How to cite this article:
Prem K, Patel J, Makwana DS, Talukdar J, Thakkar J M. Comparison of combination of ketamine hydrochloride and propofol with fentanyl citrate and propofol for patients undergoing endoscopic retrograde cholangiopancreatography. Bali J Anaesthesiol 2019;3:155-60

How to cite this URL:
Prem K, Patel J, Makwana DS, Talukdar J, Thakkar J M. Comparison of combination of ketamine hydrochloride and propofol with fentanyl citrate and propofol for patients undergoing endoscopic retrograde cholangiopancreatography. Bali J Anaesthesiol [serial online] 2019 [cited 2023 Mar 22];3:155-60. Available from: https://www.bjoaonline.com/text.asp?2019/3/3/155/276626

  Introduction Top

Sedation and analgesia comprise an important element of endoscopic procedures.[1] Endoscopic retrograde cholangiopancreatography (ERCP) is a lengthy diagnostic and therapeutic procedure performed for pancreaticobiliary disorders in prone or semi-prone position and potentially uncomfortable that needs moderate-to-deep sedation or even general anesthesia (GA) to facilitate high success rate and avoid patient's discomfort.[2],[3] Unsecured airway, high risk of aspiration, and endoscope introduced orally (shared airway) make it difficult to appropriately treat any airway obstruction/apnea.[2],[3],[4]

Sedation for gastrointestinal endoscopic procedures has gained much interest in recent years. Sedation ensures comfort for the patients and endoscopists during the procedure. According to the American Society of Anesthesiologists (ASA), sedation is defined as a continuum of progressive impairment in consciousness ranging from minimal to moderate, deep sedation and GA.[1] Sedation reduces pain, discomfort, and stress and can produce amnesia in patients undergoing unpleasant and prolonged procedures such as ERCP. Sedation techniques that are used for this procedure should be in such a way that, despite to create analgesia also prevent cough while maintaining spontaneous breathing and hemodynamic stability.

Many drugs individually or in combination with each other such as propofol, ketamine, fentanyl, remifentanil, dexmedetomidine, benzodiazepines, meperidine, and etomidate are used.[2],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18] Using a single anesthetic agent in ERCP leads to inadequate analgesia and sedation. Thus, a combination of various drugs provides complete and balanced anesthesia with an advantage such as lower dosages, fewer side effects, and high potency. Despite using different drugs and variant combinations, still, the search for ideal drug combination with minimum side effects continues. The purpose of this study is to compare propofol-ketamine hydrochloride and propofol-fentanyl citrate combination for ERCP procedure in terms of sedation score, recovery time, total requirement of propofol, complications, as well as patients' and endoscopists' satisfaction.

  Patients and Methods Top

After obtaining institutional ethical committee approval and written informed valid consent, this prospective, randomized controlled study was conducted on 100 patients of ASA Class I and II, aged 18–70 years of either sex undergoing ERCP procedure. Patients of ASA grade >II; pregnant patients; body mass index of >30 kg/m 2; history of chronic obstructive pulmonary disease; difficult airway; neurological, mental, and heart disease; patient with full stomach; emergency need for ERCP; history of allergy; or contraindication to the drug used in the study were excluded from the study.

A thorough clinical examination of the patient was performed including complete blood count, serum electrolytes, chest X-ray, renal and liver function test, and 12-lead electrocardiogram (ECG). Visual Analog Scale (VAS) scale and satisfaction scale were explained to each patient during the preoperative visit.

We randomly divided 100 patients into two groups equally. Group 1 (PK) received propofol 1 mg/kg and ketamine 1 mg/kg, while Group 2 (PF) received propofol 1 mg/kg and fentanyl 1 mcg/kg intravenously. This was followed by an infusion of propofol 100 mg in 100 ml normal saline (NS) for both the groups and was adjusted to achieve the Ramsay Sedation Score (RSS) of 4–5. An RSS of <4 was considered as insufficient sedation, and a bolus dose of propofol 0.5 mg/kg was administered.

All the procedures were carried out in the left lateral position. Glycopyrrolate bromide 0.004 mg/kg and ondansetron 0.15 mg/kg were given prior to the procedure. For oxygen supplementation, a nasal cannula at an oxygen flow rate of 3 L/min was placed. We recorded heart rate (HR), systolic blood pressure (BP), diastolic BP, mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), ECG, and RSS score at induction, 5 min, 10 min, 15 min, 20 min, 30 min after the induction, at the end of procedure, and then at recovery. Propofol infusion was discontinued at the end of procedure and the total propofol requirement was recorded. The recovery time was defined as the time from the discontinuation of infusion to achieve the modified Aldrete's score of ≥9. The recovery time was recorded. The quality of analgesia was recorded postprocedure by VAS score. Mark 0 represents no pain and 10 represents the worst possible pain. Endoscopist and patient satisfaction levels were determined based on a Likert scale [4] from 0 to 10. Side effects such as bradycardia, tachycardia, hypertension, hypotension, hypoxia nausea and vomiting, and emergence were recorded.

Statistical analysis was done by data in the text and tables are statistically described in terms of mean ± standard deviation or frequencies (number of cases) and percentages when appropriate. Microsoft Excel was used to generate graphs and tables. For comparing categorical data, a Chi-square test was performed. Yates correction equation was used instead when the expected frequency is <5. An unpaired t-test was used to compare two population means. P < 0.05 was considered statistically significant. Statistical analysis was carried out by SPSS (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.) and GraphPad (GraphPad Prism version 7.00 for Windows, GraphPad Software, La Jolla California USA) sofwares.

  Results Top

Group PK received propofol-ketamine, while Group PF propofol-fentanyl for ERCP. We observed sedation score, total propofol consumption, recovery time, patient and endoscopist satisfaction, and various complications. In terms of age, gender, weight, duration of the procedure, and basic parameters, the two groups are comparable and statistically insignificant [Table 1]. [Table 2] shows that there was no significant difference between the two groups. In both the groups, sedation was considered adequate.
Table 1: Demographic and basic clinical parameters of the patients

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Table 2: Comparison of sedation score

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[Figure 1] depicts that the mean HR in Group PF was lower compared to Group PK after induction and at 5 min which was statistically significant, but at other times, there was no significant difference between the two groups. [Figure 2] shows that the MAP was significantly lower in the PF Group than in the PK Group. Although the MAP decreased in both the groups during the intraoperative period, the decrease was much more significant in the fentanyl group than the ketamine group. After 20 min, there was no significant difference in both the groups. [Figure 3] shows SpO2 in both the groups. At 5 min in fentanyl group, there was decrease in SpO2 up to 96.8 ± 3.68, while in ketamine group, at all the time, SpO2 was maintained. After 5 min, there was no significant difference in both the groups.
Figure 1: Comparison of heart rate at different time intervals

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Figure 2: Changes in mean arterial pressure mmHg

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Figure 3: Change in peripheral oxygen saturation in both the groups

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[Table 3] shows, The total drug consumed in terms of calculated propofol was higher in Group PF compared with Group PK (176.9 ± 50.28 vs. 153.7 ± 57.16 mg, P = 0.033). The recovery time was significantly longer in Group PK compared with Group PF (11.12 ± 2.75 vs. 9.72 ± 3.02 min, P = 0.017). In terms of postprocedural VAS [Table 4], there was no significant difference in the PK and PF Ggroups (P = 0.433). There was no difference between the two groups with regard to endoscopist and patient satisfaction (P = 0.823 and P = 0.610, respectively).
Table 3: Comparison of propofol consumption and recovery time in both the groups

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Table 4: Comparison of postprocedural Visual Analog Scale and satisfaction score

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[Figure 4] depicts that desaturation occurred in 8 patients (16%) in Group PF compared to only two patients (4%) in PK Group, but this difference was not statistically significant. In PF Group, nine patients (18%) had bradycardia, whereas only 1 patient (2%) in PK Group had bradycardia which was statistically significant (P = 0.019). Tachycardia was observed in three patients (6%) in Group PK and only in one patient (2%) in PF Group which was statistically insignificant. Hypotension was recorded in 12 patients (24%) in Group PF and in three patients (6%) in PK Group which was statistically significant (P = 0.025). Hypertension was noted in two patients (4%) in Group PK, whereas none in PF Group. The frequency of postoperative nausea and vomiting (PONV) was five patients (10%) in PK Group and three patients (6%) in PF Group. In Group PK, five patients experienced emergence, while none had in Group PF.
Figure 4: Comparison of adverse events in both the groups

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  Discussion Top

ERCP has to meet several requirements such as safe sedation, satisfaction, least complications, and early recovery. Certain painful procedures may also be performed during ERCP such as palliative stenting, stone removal, visualization of the pancreaticobiliary tract, laser lithotripsy, and sphincterotomy.[4],[19] This procedure should be carried out under GA or deep sedation for immobility, analgesia, and patient comfort. Deep sedation under anesthesiologist supervision instead of GA has some advantages. However, major risks in deep sedation constitute unintended GA and apnea. Anesthesia for deep sedation can be administered by anesthetic or nonanaesthetic health-care personnel, but careful monitoring is mandatory.[15]

However, its narrow therapeutic window with a possible risk of apnea is the main concern. Thus, the adequate experience of those who can administer various anesthetic agents and early detection of overdosing are mandatory for patient's safety.[16] In our institute, deep sedation for ERCP is performed by trained anesthetic personal.

Cardiorespiratory events are major complications of sedation in ERCP. Hence, monitoring is much more demanding and sophisticated. Therefore, monitoring of respiration, cardiac rhythm, and noninvasive BP measurement are mandatory. In our study, we used clinical assessment tool RSS for sedation, ECG, noninvasive BP, and SpO2. Amornyotin et al.[20] concluded that the use of Narcotrend system monitoring compared with clinical monitoring in patients undergoing deep sedation with propofol for ERCP helped to reduce sedation-related complications but did not increase the success rate, lower propofol consumption, or shorten the recovery time.

Propofol, when used alone as a sole agent, leads to deep sedation and dangerous side effects needing cardiopulmonary support, so reducing its dose by coadministering adjuvant drugs to provide optimal sedation with less complication. Various drug combinations were tried by many authors previously. We used propofol 1 mg/kg for induction and 100 mg in 100 ml NS with ketamine and fentanyl as adjutants at the dose of 1 mg/kg and 1 mcg/kg, respectively. The propofol infusion rate was adjusted to achieve an RSS of 4–5, while a rescue dose of propofol bolus 0.5 mg/kg was given when RSS was ≤3. Rescue dose of propofol was not required in any patients which suggest that induction dose was adequate. We did not administer any other sedatives, such as midazolam, during induction.

Gorji et al.[4] compared the sedative and analgesic effect of propofol-fentanyl versus propofol-ketamine for ERCP. They used ketamine 0.5 mg/kg and fentanyl 50–100 mcg with propofol 0.5 mg/kg in a loading dose followed by 75 mcg/kg/min in an infusion to achieve RSS of >3. Hasanein and El Sayed [2] did a study for ERCP in obese patients and compared infusion of ketamine-propofol preparation at 1:4 ratio and propofol-fentanyl preparation after a bolus dose of propofol 0.5 mg/kg. They adjusted infusion rate to achieve RSS of 5. Aydogan et al.[18] compared propofol-ketamine with propofol alone in upper gastrointestinal endoscopy. They also used supplementary propofol 0.5–1 mg/kg if needed.[18] Patients in both the groups did not differ significantly with respect to the demographic data and duration of the procedure. There were no statistically significant differences between the baseline hemodynamic parameters.

Continuous infusion of the propofol was used to maintain a steady state of sedation. The RSS score has been used to assess the level of sedation. The result showed that there was no difference between both the groups in terms of sedation score. Gorji et al.[4] observed that there was no difference between the two groups with regard to the sedation score while Hasanein and El Sayed [2] concluded that a 1:4 ratio of ketamine-propofol resulted in better sedation quality than that of fentanyl-propofol combination. Heidari and Loghmani [10] assessed the effect of ketamine-fentanyl with propofol-remifentanil for ERCP and showed that there was no significant difference among both the groups (P = 0.07); they used RSS 6-point sedation scale.

While considering hemodynamic parameters, HR may increase, decrease, or remain unchanged when anesthesia is maintained with propofol with a decrease in MAP by 10%–40%.[21] Ketamine increases HR by 0%–59% after induction, due to an increase in central sympathetic tone and release of nor-epinephrine, it also causes an increase in BP by 0%–40%. Fentanyl causes dose-dependent decrease in HR. However, the effect of individual drugs on HR and BP counteracts each other when used in combination.

In our study, the mean HR at 1 and 5 min after induction was increased in the PK Group than in the PF Group, but at other times, there was no significant difference. An increase in the HR in the PK Group can be explained on the basis of cardio stimulant effect of ketamine, while fentanyl leads to decrease in HR due to its myocardial depressing effect. In the present study, MAP decreased in both the groups after induction as well as during the intraoperative period but was much more in Group PF.

Singh Bajwa et al.[5] compared propofol-ketamine and propofol-fentanyl and concluded that there was an increase in HR in the PK Group than in the PF Group at induction. Khutia et al.[7] compared the combination of propofol and fentanyl infusion and propofol with ketamine infusion in the pediatric short-term procedures. In their study, in Group PF, more hypotension was seen compared to PK Group. Akhondzadeh et al.[14] showed that there was no significant difference among the two groups in terms of hemodynamics characteristics.

In the current study, the total drug consumed in terms of calculated propofol was higher in Group PF compared with Group PK, which was 176.9 ± 50.28 mg and 153.7 ± 57.16 mg, respectively. The recovery time were significantly longer in PK Group compared to Group PF, 11.12 ± 2.75 and 9.72 ± 3.02 min, respectively. Slower clearance of ketamine in comparison with fentanyl is probably responsible for this. Khutia et al.[7] showed that the amount of propofol needed to achieve a deep sedation level was much lower in case of the KP Group than the FP Group. Gorji et al.[4] study showed no significant difference in PK and PF Groups. The redistributive nature of propofol suggests that patients who have regained their baseline level of consciousness after propofol will be unlikely to exhibit any new adverse events.[6] Thus, after the patients achieved modified Aldrete score ≥9 in the recovery room, they were discharged.

Postoperative pain relief endoscopists' and patients' satisfaction scores which showed no significant difference between both the groups. Gorji et al.[4] and Akhondzadeh et al.[14] reported similar results in accordance with ours. Cocktail sedation containing propofol provides faster recovery time and better patients' satisfaction for patients undergoing ERCP. However, mild degree of desaturation may still develop.[16]

In our study, desaturation (SpO2<90%) occurred in 8 patients (16%) in the PF Group compared to 2 patients (4%) in the PK Group, but this difference was not significant. No patient required emergency intubation. There was a higher incidence of bradycardia in the Group PF than in the KP Group, which was statistically significant. Hypotension was observed in 12 patients in PF Group which was corrected by fluid administration. None of the patients required any vasopressors' support to maintain BP. The frequency of PONV, emergence reaction, and nystagmus were more in the PK Group than in the Group PF.

Emergence reaction and vomiting are considered to be significant adverse effects with ketamine usage.[21] Other studies reported that ketamine-propofol combination provided better sedation with less hemodynamic and respiratory complications for sedating obese patients.[2]

The limitation of the study was that we did not measure respiratory rate, as the semi-prone position makes it difficult to count the respiratory rate accurately. In the present study, the effect on respiratory function was judged only by SPO2, which may lead to missing subclinical respiratory depression. We could not monitor EtCO2, bispectral index, or other advance monitoring for sedation. The study duration was short, and there was no follow-up after discharge.

  Conclusion Top

Both propofol-ketamine and propofol-fentanyl provide adequate sedation with minimal hemodynamic changes. Both patients and endoscopists were satisfied with either group's result. The recovery time was less in the fentanyl group than in the ketamine group. Propofol consumption was less in the ketamine group.

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There are no conflicts of interest.

  References Top

Chainaki IG, Manolaraki MM, Paspatis GA. Deep sedation for endoscopic retrograde cholangiopacreatography. World J Gastrointest Endosc 2011;3:34-9.  Back to cited text no. 1
Hasanein R, El Sayed W. Ketamine/propofol versus fentanyl/propofol for sedating obese patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Egypt J Anaesth 2013;29:207-11.  Back to cited text no. 2
Goudra BG, Singh PM, Sinha AC. Outpatient endoscopic retrograde cholangiopancreatography: Safety and efficacy of anesthetic management with a natural airway in 653 consecutive procedures. Saudi J Anaesth 2013;7:259-65.  Back to cited text no. 3
Gorji FB, Amri P, Shokri J, Alereza H, Bijani A. Sedative and analgesic effect of propofol-fentanyl versus propofol-ketamine during endoscopic retrograde cholangiopancreatography: A double-blind randomized clinical trial. Anesth Pain Med 2016;6:e39835.  Back to cited text no. 4
Singh Bajwa SJ, Bajwa SK, Kaur J. Comparison of two drug combinations in total intravenous anesthesia: Propofol-ketamine and propofol-fentanyl. Saudi J Anaesth 2010;4:72-9.  Back to cited text no. 5
Miner JR, Burton JH. Clinical practice advisory: Emergency department procedural sedation with propofol. Ann Emerg Med 2007;50:182-7, 187.e1.  Back to cited text no. 6
Khutia SK, Mandal MC, Das S, Basu SR. Intravenous infusion of ketamine-propofol can be an alternative to intravenous infusion of fentanyl-propofol for deep sedation and analgesia in paediatric patients undergoing emergency short surgical procedures. Indian J Anaesth 2012;56:145-50.  Back to cited text no. 7
[PUBMED]  [Full text]  
Amornyotin S, Kachintorn U, Chalayonnawin W, Kongphlay S. Propofol-based deep sedation for endoscopic retrograde cholangiopancreatography procedure in sick elderly patients in a developing country. Ther Clin Risk Manag 2011;7:251-5.  Back to cited text no. 8
Fabbri LP, Nucera M, Marsili M, Al Malyan M, Becchi C. Ketamine, propofol and low dose remifentanil versus propofol and remifentanil for ERCP outside the operating room: Is ketamine not only a “rescue drug”? Med Sci Monit 2012;18:CR575-80.  Back to cited text no. 9
Heidari SM, Loghmani P. Assessment of the effects of ketamine-fentanyl combination versus propofol-remifentanil combination for sedation during endoscopic retrograde cholangiopancreatography. J Res Med Sci 2014;19:860-6.  Back to cited text no. 10
Abdalla MW, El Shal SH, El Sombaty AI, Abdalla NM, Zeedan RB. Propofol dexmedetomidine versus propofol ketamine for anesthesia of ERCP. Egypt J Anaesth 2015;31:97-105.  Back to cited text no. 11
Haytural C, Aydınlı B, Demir B, Bozkurt E, Parlak E, Dişibeyaz S, et al. Comparison of Propofol, Propofol-Remifentanil, and Propofol-Fentanyl Administrations with Each Other Used for the Sedation of Patients to Undergo ERCP. Biomed Res Int 2015;2015. Published online 2015 Oct. 21. doi:10.1155/2015/465465.  Back to cited text no. 12
Ramkiran S, Iyer SS, Dharmavaram S, Mohan CV, Balekudru A, Kunnavil R. BIS Targeted Propofol Sparing Effects of Dexmedetomidine Versus Ketamine in Outpatient ERCP: A Prospective Randomised Controlled Trial. J Clin Diagn Res 2015;9:UC07-12.  Back to cited text no. 13
Akhondzadeh R, Ghomeishi A, Nesioonpour S, Nourizade S. A comparison between the effects of propofol-fentanyl with propofol-ketamine for sedation in patients undergoing endoscopic retrograde cholangiopancreatography outside the operating room. Biomed J 2016;39:145-9.  Back to cited text no. 14
Ikeuchi N, Itoi T, Gotoda T, Kusano C, Kono S, Kamada K, et al. Feasibility of non-anesthesiologist-administered propofol sedation for emergency endoscopic retrograde cholangiopancreatography. Gastroenterol Res Pract 2015;2015. Published online 2015 March 29. doi:10.1155/2015/685476.  Back to cited text no. 15
Angsuwatcharakon P, Rerknimitr R, Ridtitid W, Kongkam P, Poonyathawon S, Ponauthai Y, et al. Cocktail sedation containing propofol versus conventional sedation for ERCP: A prospective, randomized controlled study. BMC Anesthesiol 2012;12:20.  Back to cited text no. 16
Song JC, Lu ZJ, Jiao YF, Yang B, Gao H, Zhang J, et al. Etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol: A randomized clinical trial. Int J Med Sci 2015;12:559-65.  Back to cited text no. 17
Aydogan H, Aydogan T, Uyanıkoglu A, Kucuk A, Yuce HH, Karahan MA, et al. Propofol-ketamine combination has shorter recovery times with similar hemodynamics compared to propofol alone in upper gastrointestinal endoscopy in adults: A randomized trial. Acta Med Mediterr 2013;29:259.  Back to cited text no. 18
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Amornyotin S, Chalayonnawin W, Kongphlay S. Deep sedation for endoscopic retrograde cholangiopancreatography: A comparison between clinical assessment and Narcotrend (TM) monitoring. Med Devices (Auckl) 2011;4:43-9.  Back to cited text no. 20
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4]


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