Anesthesia: Essays and Researches  Login  | Users Online: 452 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Home | About us | Editorial board | Ahead of print | Search | Current Issue | Archives | Submit article | Instructions | Copyright form | Subscribe | Advertise | Contacts


 
Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 10  |  Issue : 3  |  Page : 624-630  

Comparison of ropivacaine with levobupivacaine under epidural anesthesia in the lower limb orthopedic surgeries: A randomized study


1 Department of Anesthesiology and Critical Care, KGMU, Lucknow, Uttar Pradesh, India
2 Department of Anesthesiology and Critical Care, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
3 Department of Anesthesiology and Critical Care, Narayan Medical College and Hospital, Sasaram, Bihar, India

Date of Web Publication27-Sep-2016

Correspondence Address:
Raj Bahadur Singh
Department of Anaesthesiology and Critical Care, Narayan Medical College and Hospital, Sasaram, Bihar
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.191119

Rights and Permissions
   Abstract 


Context: Epidural anesthesia is nowadays considered as the gold standard anesthetic technique for lower limb orthopedic surgeries, and the present study was conducted to evaluate the efficacy of levobupivacaine and ropivacaine in terms of onset, duration of sensory and motor block with duration of postoperative analgesia in patients undergoing lower limb orthopedic surgeries under epidural anesthesia.
Aims: To compare the efficacy of 15 mL of levobupivacaine 0.5% with that of 15 mL of ropivacaine 0.75% in patients undergoing lower limb orthopedic surgeries under epidural anesthesia and to determine the better of the two agents with respect to onset, duration of sensory and motor blockade, postoperative analgesia, and adverse effects; if any.
Settings and Design: A double-blind randomized study.
Subjects and Methods: A total of seventy patients planned to undergo elective lower limb orthopedic surgeries fulfilling the criteria were enrolled in the study. Group I (n = 35): Received 15 mL 0.5% levobupivacaine epidurally. Group II (n = 35): Received 15 mL 0.75% ropivacaine epidurally.
Statistical Analysis: Statistical Analysis was done by Statistical Package for Social Sciences (SPSS Version 15.0) statistical analysis software. The values were represented in number (%) and mean ± standard deviation.
Results: Time to achieve sensory onset and motor onset were significantly lower in Group II (17.86 ± 2.51 and 23.14 ± 2.73) as compared to Group I (26.14 ± 2.45 and 31.43 ± 2.59) while the duration of sensory block was significantly higher in Group II (173.29 ± 6.29 min) as compared to Group I (156.71 ± 6.96 min). Although motor block duration of Group I (142.43 ± 8.43 min) was higher than that of Group II (141.43 ± 12.81 min), but this difference was not found to be statistically significant.
Conclusions: The inference drawn from this discussion, in general, indicated that both the drugs are comparable for block onset, quality, and duration along with similar hemodynamic profile when given in same concentration. However, relatively better response of ropivacaine for block onset and duration as obtained in the present study coupled with higher but statistically.

Keywords: Analgesia, epidural, levobupivacaine, motor, ropivacaine, sensory


How to cite this article:
Maheshwari V, Rasheed MA, Singh RB, Choubey S, Sarkar A. Comparison of ropivacaine with levobupivacaine under epidural anesthesia in the lower limb orthopedic surgeries: A randomized study. Anesth Essays Res 2016;10:624-30

How to cite this URL:
Maheshwari V, Rasheed MA, Singh RB, Choubey S, Sarkar A. Comparison of ropivacaine with levobupivacaine under epidural anesthesia in the lower limb orthopedic surgeries: A randomized study. Anesth Essays Res [serial online] 2016 [cited 2020 Jul 11];10:624-30. Available from: http://www.aeronline.org/text.asp?2016/10/3/624/191119




   Introduction Top


Epidural anesthesia is nowadays considered as the gold standard anesthetic technique for lower limb orthopedic surgeries. An epidural block is usually performed as a sole technique using local anesthetic agents or can be performed in combination with spinal or general anesthesia.

Epidural anesthesia has a high success rate and patient satisfaction.[1] There is evidence for reduced blood loss and low risk of other complications in orthopedic surgeries; hence in recent years, the epidural technique has gained widespread popularity and has been well accepted by both the patient and surgeon.[2]

The present study was conducted to evaluate the efficacy of levobupivacaine and ropivacaine in terms of onset, duration of sensory and motor block with the duration of postoperative analgesia in patients undergoing lower limb orthopedic surgeries under epidural anesthesia.


   Subjects and Methods Top


This was a randomized, double-blinded, prospective study carried out in the Department of Anesthesiology of a tertiary care teaching hospital over a period of 18 months. The study was done on the patients who were planned to undergo lower limb orthopedic surgeries under epidural anesthesia. A total of seventy patients planned to undergo elective lower limb orthopedic surgeries fulfilling the criteria were enrolled in the study.

Inclusion criteria were those who were American Society of Anesthesiologists (ASA) Grade I and II physical status, scheduled for elective lower limb orthopedic surgery, and age group of between 18 and 60 years. The exclusion criteria were patient refusal for epidural block/study, ASA III, IV, or V, history of allergy or hypersensitivity to any of the study drug, local skin sepsis, marked spinal deformities, patients with Cardio-vascular System (CVS), renal or hepatic dysfunction, neuromuscular disorders, morbid obesity, and with marked coagulopathies.

The study was approved by the Institutional Ethics Committee. Informed consent was obtained from all the patients before the procedure. After this, patients were randomized into two groups using computer-generated tables having 35 patients in each group.

  • Group I (n = 35): Received 15 mL 0.5% levobupivacaine epidurally
  • Group II (n = 35): Received 15 mL 0.75% ropivacaine epidurally.


Parameters studied were duration of sensory block (time of onset, duration, and recovery), duration of motor block (time of onset, duration, and recovery), degree of fall in arterial blood pressure and heart rate (HR), pain scores using visual analog scale (VAS), and adverse effects; if any.

Patients were asked to be nil per oral 6 h for solid foods and 2 h for clear fluids before surgery. All the patients in the study groups were premedicated with tablet diazepam 5 mg and tablet ranitidine 150 mg in the night before surgery. On arrival in the operating theater, an 18-gauge intravenous (i.v.) catheter was placed, and 500 mL of Ringer's lactate solution was infused. The standard monitoring was done throughout the study with noninvasive arterial blood pressure (NIBP), HR, continuous electrocardiogram, and pulse oximetry. One milligram of injection midazolam was administered intravenously as premedication. With the patient in the sitting position, under aseptic precautions, the L2–L3 or L3–L4 interspace was identified using the midline approach and was infiltrated with 2 ml of 2% lidocaine. The epidural space was identified with an 18-gauge Tuohy needle by the loss of resistance technique. A 20-gauge epidural catheter was then inserted 3–5 cm into the epidural space. Test dose with 3 ml of 2% injection xylocaine with adrenaline 1:200,000 was given after a negative aspiration test to detect any intravascular or intrathecal placement of the catheter. Using sealed-envelope assignment, patients were randomly allocated to receive 15 mL of 0.5% levobupivacaine (Group I; n = 35), 15 mL of 0.75% ropivacaine (Group II; n = 35). Sterile syringes with the study drug were prepared in a double-blind fashion by one of the doctors who was not involved in further patient management. An independent, blinded observer recorded the evolution of sensory and motor block every 5 min. The sensory level was assessed using the pinprick method, and readiness to surgery was defined as the complete loss of pinprick sensation at T10. The degree of motor block was evaluated with a four-point modified Bromage score. The scale consists of the following four scores:

  • 0 = No motor block (0% block)
  • 1 = Unable to raise extended legs (33% block)
  • 2 = Unable to flex knees (66% block)
  • 3 = Unable to flex ankle joint (100% block).


At the same time, NIBP and HR were also recorded every 5 min following the block.

In the recovery room, the degree of pain was assessed using VAS in which a score of “0” indicated “no pain” and a score of “10” indicated “worst pain” imaginable [Figure 1]. VAS measurements were obtained at baseline, 5, 10, 15, 30, 60, 120, 180, and 240 min intervals following the block. When VAS >4, epidural top ups were provided for postoperative analgesia. Patients in Group I received incremental boluses of the same drug which was used to induce the block, i.e., levobupivacaine 10 mL in a concentration of 0.125%. Patients in Group II received 10 mL ropivacaine 0.2% for postoperative analgesia.
Figure 1: Visual Analogue Scale

Click here to view


Clinically relevant hypotension (defined as decrease in systolic arterial blood pressure >30% from baseline) was treated with 6 mg of injection mephentermine i.v. boluses. Occurrence of any other undesirable side effect was also recorded. The volume of local anesthetic solution required, time required to achieve readiness to surgery, maximum level of sensory and motor block, time for the regression of sensory level by two segments and up to T12 were recorded in the study.

Sample size calculation

The sample size was calculated using the following formula:

n = Zα2 (1 − p1/p1+1 − p2/p2)/(ln [1 − e]) 2.

p1 =80% =0.80; p2 =0.60; Type 1 error α = 5%; Error - RR = 0.30; Power = 90% (approximately). Where, n = Sample size; e = Error in relative risk; α = Type 1 error; RR = Relative risk; p1= Proportion 1; p2= Proportion 2; Hence, sample size for each group = 30 + (10% data loss) =33.

It is decided to keep 35 samples in each group.


   Results Top


The present study was carried out at the Department of Anaesthesiology, Era's Lucknow Medical College, Lucknow, with an aim to compare the efficacy of 15 ml of levobupivacaine 0.5% with that of 15 ml of ropivacaine 0.75% in patients undergoing lower limb orthopedic surgeries under epidural anesthesia.

The two groups were matched for age, gender, body weight, and ASA grade [Table 1]. Both the groups were matched hemodynamically at the baseline [Table 2].
Table 1: Demographic profile and demographic profile and baseline characteristics

Click here to view
Table 2: Comparison of hemodynamic parameters at baseline

Click here to view


At baseline, mean HR was 85.43 ± 11.75 bpm in Group I as compared to 89.20 ± 12.06 bpm in Group II. Statistically, this difference was not significant (P = 0.190).

At different follow-up intervals, mean HR was lower as compared to baseline, in both the groups. At 120 min mean, HR was 84.66 ± 9.15 bpm in Group I and 88.57 ± 10.33 bpm in Group II.

Statistically, significant differences between two groups were observed at 15 min interval only, where Group I had mean values significantly higher as compared to that of Group II [Table 3].
Table 3: Comparison of mean heart rate between two groups at different time periods during study

Click here to view


In Group I, at baseline mean, HR was 85.43 ± 11.75 bpm which decreased to reach at 83.94 ± 11.67 bpm at 5 min, thus showing a decrease of 1.47 ± 1.77 bpm, though this change was nominal yet it was significant statistically (P < 0.05).

The decrease in HR showed a decline trend to reach at its nadir at 30 min when mean HR was 73.31 ± 11.62 bpm; thus, showing a mean decrease of 12.11 ± 3.55 bpm.

At 120 min, mean HR was 84.66 ± 9.15 bpm, the difference from baseline was 0.77 ± 4.74 bpm. At this time interval, the difference from baseline was found to be slightly below its baseline as compared to that but this difference was not found to be significant statistically.

Statistically, mean change in HR was significant statistically (P < 0.05) at all the follow-up intervals except at 120 min.

With respect to categorical changes, at all the time intervals, mean HR in Group I was within ± 20% baseline range [Table 3]a.
Table 3a: Within-group comparison of change in heart rate as compared to baseline (Group I)

Click here to view


In Group II, at baseline, mean HR was 89.20 ± 12.06 bpm. A significant decrease in HR was observed at 5 min interval itself (mean change 4.57 ± 2.99) (P < 0.05). The fall in HR continued to increase throughout the follow-up till 30 min when it reached to its nadir at 69.06 ± 7.56 bpm, thus showing a mean fall of 20.14 ± 7.87 bpm. At 120 min, mean HR was 88.57 ± 10.33, thus showing a mean change of only 0.63 ± 3.28 bpm.

Statistically, at all the time intervals except at 120 min, mean HR was significantly lower as compared to baseline (P < 0.05).

In terms of categorical change, at only 30 min from baseline, mean HR showed more than 20% decline from the baseline value [Table 3]b.
Table 3b: Within-group comparison of change in heart rate as compared to baseline (Group II)

Click here to view


At baseline, mean arterial pressure (MAP) was 97.92 ± 5.08 mmHg in Group I as compared to 99.10 ± 6.59 mmHg in Group II. Statistically, this difference was not significant (P = 0.404).

At different follow-up intervals except at 120 min, mean MAP was lower as compared to baseline, in both the groups. At 120 min, mean MAP was 97.99 ± 5.77 mmHg in Group I and 97.59 ± 5.32 mmHg in Group II.

Statistically, significant differences between two groups were observed at 10 min and 60 min intervals, at both these time intervals, Group I had mean values significantly higher as compared to that of Group II [Table 4].
Table 4: Comparison of mean arterial pressure between two groups at different time periods during study

Click here to view


In Group I, at baseline mean MAP was 97.92 ± 5.08 mmHg which decreased to reach at 96.84 ± 5.01 mmHg at 5 min, thus showing a decrease of 1.09 ± 0.81 mmHg, though this change was nominal yet it was significant statistically (P < 0.05).

The decrease in MAP showed a decline trend to reach at its nadir at 30 min when mean MAP was 85.83 ± 6.59 mmHg, thus showing a mean decrease of 12.10 ± 4.18 mmHg.

At 120 min, mean MAP was 97.99 ± 5.77 mmHg, the difference from baseline was 0.07 ± 4.02 mmHg.

Statistically, mean change in MAP was significant statistically at all the follow-up intervals (P < 0.05) except at 120 min.

With respect to categorical changes, at all the time intervals, mean MAP in Group I was within ± 20% baseline range [Table 4]a.
Table 4a: Within Group comparison of change in arterial pressure as compared to baseline (Group I)

Click here to view


In Group II, at baseline, mean MAP was 99.10 ± 6.69 mmHg. A significant decrease in mean MAP was observed at 5 min interval itself (mean change 2.07 ± 1.80) (P < 0.05). The fall in MAP continued to increase throughout the follow-up till 15 min when it reached to its nadir at 82.70 ± 7.30 mmHg, thus showing a mean fall of 16.40 ± 5.46 mmHg. At 120 min, mean MAP was 98.38 ± 5.57, thus showing a mean change of 0.72 ± 6.31 mmHg.

Statistically, at all the time intervals except at 120 min, mean MAP was significantly lower as compared to baseline (P < 0.05). At 120 min, mean MAP was found to be lower than its baseline value; however, at this time, interval difference was not found to be statistically significant.

In terms of categorical change, at all follow-up intervals, mean diastolic blood pressure was within ± 20% baseline range [Table 4]b.
Table 4b: Within-group comparison of change in mean arterial pressure as compared to baseline (Group II)

Click here to view


Both sensory and motor block onset times were significantly shorter in Group II as compared to Group I while the duration of sensory block was significantly longer in Group II as compared to Group I. Statistically, no significant difference between two groups was observed with respect to the duration of motor block [Table 5].
Table 5: Comparison of two groups with respect to achievement of sensory and motor block and total duration of block

Click here to view


No significant difference between two groups was observed with respect to minor side effects such as dry mouth, nausea/vomiting. No event of respiratory depression took place in either of two groups.

However, events of hypotension were higher in Group II (34.3%) as compared to Group I (14.3%), but this difference was not statistically significant (P = 0.051). An intervention of injection mephentermine 6 mg i.v. bolus was done whenever event of hypotension occurred in either of the groups [Table 6].
Table 6: Comparison of two groups for side effects

Click here to view


Time for the first analgesic need was significantly longer (P < 0.001) in Group II (6.43 ± 2.12 h) as compared to Group I (4.97 ± 0.89 h), and total number of epidural top ups in next 24 h was significantly higher (P < 0.001) in Group I (3.84 ± 1.24) as compared to Group II (2.24 ± 0.87) [Table 7].
Table 7: Comparison of two groups for postoperative top up doses

Click here to view



   Discussion Top


Over the years, regional blocks are being preferred over general anesthesia for the fact that they offer excellent pain control, reduced side-effects, and shortened stay in the postanesthesia care unit.[3],[4]

Levobupivacaine, the S (−) isomer of bupivacaine, has emerged as an option that could offer similar intensity and duration of block as bupivacaine can but with a safer toxicity profile [5],[6] owing to its faster protein binding rate,[7] Levobupivacaine has been recently introduced into the Indian market and is being widely used in various health set ups.

Despite lower toxicity, its onset time and duration of the neural blockade are not adequate; it might not be useful as a substitute. Data on this issue are scarce, especially from developing countries like India. It is essential to establish an undisputedly better efficacy of ropivacaine vis-a-vis levobupivacaine owing to economic reasons too as ropivacaine is almost five times costlier than levobupivacaine.[1]

In the present study, we selected two different dosages of local anesthetics – i.e., 0.5% levobupivacaine for comparison against 0.75% ropivacaine for comparison. The reason for this was a reported slower onset time for ropivacaine as compared to levobupivacaine for the same dose. However, an enhanced dose of ropivacaine (0.75%) has been shown to be comparable to a lower dose of levobupivacaine (0.5%).[8]

In both the groups, baseline HR was 85.43 ± 11.75 and 89.20 ± 12.06 in levobupivacaine and ropivacaine groups which dropped down to 83.94 ± 11.67 and 84.63 ± 11.82 bpm 5 min after induction, this trend of decrease continued till 60 min in postadministration interval. At 120 min, postadministration interval mean HR in levobupivacaine and ropivacaine groups was 84.66 ± 9.15 and 88.57 ± 10.33 bpm, respectively. At none of the time intervals, the difference between two groups was statistically significant (P > 0.05). In both the groups, mean change from baseline was significant statistically till 30 min interval (P < 0.05). At 120 min, both the groups had mean HR comparable to baseline and did not show a significant difference from baseline (P > 0.05).

Gupta et al.[9] had also found the same result that epidural 0.5% levobupivacaine shows maximum decline in HR at 30 min postadministration interval, with a mean change nearing 20% when used as an adjuvant with dexmedetomidine or fentanyl. In the present study, we witnessed a similar level of reduction in HR using 0.5% levobupivacaine alone. However, with respect to ropivacaine, the results obtained in the present study showed a difference from the observations of Bajwa et al.,[10] who showed that epidural administration of 0.75% ropivacaine epidurally shows a declining trend from around 75 min postadministration interval. HR lowering effect of epidural ropivacaine has been proven in animal studies 60 min after administration.[11] Thus, it can be seen that both the drugs have a similar effect on HR which varied under different conditions. As far as the present study is concerned, both the drugs showed a similar effect and did not differ significantly. For none of the drugs, any side effect in terms of bradycardia was noticed.

On evaluating MAP, at baseline, both the groups were matched showing mean values of 97.92 ± 5.08 in levobupivacaine and 99.10 ± 6.59 mmHg in ropivacaine groups. Following administration of drug, a fall in MAP values was observed in both the groups. However, fall in MAP was more rapid and of larger magnitude in ropivacaine as compared to levobupivacaine group. Between two groups, significant differences were observed at 10 min and 15 min postadministration intervals. The maximum reduction in MAP was noticed at 30 min in levobupivacaine and 15 min in ropivacaine group, thereafter an inclining trend was observed. At 120 min, both the drugs had mean HR close to baseline.

In the present study, sensory as well as motor block onset times were significantly lower in ropivacaine group as compared to levobupivacaine (P < 0.05). The sensory onset time in levobupivacaine was 26.14 ± 2.45 min as compared to 17.86 ± 2.51 min in ropivacaine group while mean motor onset time was 31.43 ± 2.59 min in levobupivacaine as compared to 23.14 ± 2.73 min in ropivavaine group. These observations are similar to that obtained by Casatiand Baciarello,[12] who reported a longer median range of onset time of surgical block was 30 min (5–60 min) with levobupivacaine as compared to 15 min (5–60 min) with ropivacaine using the same dose of both the drugs.

With respect to duration of sensory and motor blocks, although the sensory block duration was found to be significantly longer in ropivacaine group as compared to levobupivacaine group, with respect to postoperative analgesic needs too, ropivacaine required the first analgesic dose at a longer duration (6.43 ± 2.12 h) as compared to levobupivacaine (4.97 ± 0.89 h). The analgesic effect in terms of 24 h postoperative epidural top up dosages was also significantly lower in ropivacaine (2.24 ± 0.87) as compared to levobupivacaine group (P < 0.001).

Casati and Baciarello [12] reported that levobupivacaine 0.5% produces an epidural block of similar onset, quality, and duration as by the same volume of 0.5% bupivacaine with a motor block deeper than that produced by 0.5% ropivacaine.


   Conclusions Top


The inference drawn from this discussion, in general, indicated that both the drugs are comparable for block onset, quality, and duration along with similar hemodynamic profile when given in same concentration. However, relatively better response of ropivacaine for block onset and duration as obtained in the present study coupled with higher but statistically.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Grant SA, Nielsen KC, Greengrass RA, Steele SM, Klein SM. Continuous peripheral nerve block for ambulatory surgery. Reg Anesth Pain Med 2001;26:209-14.  Back to cited text no. 1
[PUBMED]    
2.
Gramke HF, de Rijke JM, van Kleef M, Raps F, Kessels AG, Peters ML, et al. The prevalence of postoperative pain in a cross-sectional group of patients after day-case surgery in a university hospital. Clin J Pain 2007;23:543-8.  Back to cited text no. 2
[PUBMED]    
3.
Liu SS, Strodtbeck WM, Richman JM, Wu CL. A comparison of regional versus general anesthesia for ambulatory anesthesia: A meta-analysis of randomized controlled trials. Anesth Analg 2005;101:1634-42.  Back to cited text no. 3
[PUBMED]    
4.
Liu SS, Wu CL. The effect of analgesic technique on postoperative patient-reported outcomes including analgesia: A systematic review. Anesth Analg 2007;105:789-808.  Back to cited text no. 4
[PUBMED]    
5.
Ethgen O, Bruyère O, Richy F, Dardennes C, Reginster JY. Health-related quality of life in total hip and total knee arthroplasty. A qualitative and systematic review of the literature. J Bone Joint Surg Am 2004;86-A: 963-74.  Back to cited text no. 5
    
6.
Kuzma PJ, Kline MD, Calkins MD, Staats PS. Progress in the development of ultra-long-acting local anesthetics. Reg Anesth 1997;22:543-51.  Back to cited text no. 6
[PUBMED]    
7.
Covino BJ, Wildsmith JA. Clinical pharmacology of local anesthetic agents. In: Cousins MJ, Bridenbaugh PO, editors. Neural Blockade in Clinical Anesthesia and Management of Pain. Philadelphia, PA: Lippincott-Raven; 1998. p. 97-128.  Back to cited text no. 7
    
8.
Sanders RD, Mallory S, Lucas DN, Chan T, Yeo S, Yentis SM. Extending low-dose epidural analgesia for emergency caesarean section using ropivacaine 0.75%. Anaesthesia 2004;59:988-92.  Back to cited text no. 8
[PUBMED]    
9.
Gupta K, Rastogi B, Gupta PK, Jain M, Gupta S, Mangla D. Epidural 0.5% levobupivacaine with dexmedetomidine versus fentanyl for vaginal hysterectomy: A prospective study. Indian J Pain 2014;28:149-54.  Back to cited text no. 9
  Medknow Journal  
10.
Bajwa SJ, Bajwa SK, Kaur J. Comparison of epidural ropivacaine and ropivacaine clonidine combination for elective cesarean sections. Saudi J Anaesth 2010;4:47-54.  Back to cited text no. 10
[PUBMED]  Medknow Journal  
11.
Bosmans T, Schauvliege S, Gasthuys F, Duchateau L, Marcilla MG, Gadeyne C, et al. Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs. Vet Anaesth Analg 2011;38:146-57.  Back to cited text no. 11
[PUBMED]    
12.
Casati A, Baciarello M. Enantiomeric local anesthetics: Can ropivacaine and levobupivacaine improve our practice? Curr Drug Ther 2006;1:85-9.  Back to cited text no. 12
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Subjects and Methods
   Results
   Discussion
   Conclusions
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1820    
    Printed6    
    Emailed0    
    PDF Downloaded130    
    Comments [Add]    

Recommend this journal