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Table of Contents  
ORIGINAL ARTICLE
Year : 2011  |  Volume : 5  |  Issue : 2  |  Page : 147-152  

A double-blind study on analgesic effects of fentanyl combined with bupivacaine for extradural labor analgesia


1 Department of Anesthesia and Critical Care, St. Stephen's Hospital, New Delhi, India
2 Department of Anesthesia and Critical Care, NSCB Medical College, Jabalpur, India
3 Department of Community Medicine, GRMC Medical College, Gwalior, Madhya Pradesh, India
4 Department of Anesthesia and Critical Care, Sushruta Trauma Centre, New Delhi, India

Date of Web Publication9-Apr-2012

Correspondence Address:
Gaurav S Tomar
Department of Anesthesia and Critical Care, St. Stephen's Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.94754

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   Abstract 

Background : The intermittent technique of labor extradural analgesia has been showing promising results over other techniques. This study was done to assess and compare the efficacy of two different doses of fentanyl mixed with low doses of bupivacaine in intermittent labor extradural analgesia.
Materials and Methods: 90 ASA grade I-II parturients in active labor with a cervical dilatation of 3-5 cm were randomly allocated to three different groups:

  1. Group A: 10 ml bupivacaine 0.125% + fentanyl 10 μg (1 μg/ml).
  2. Group B: 10 ml bupivacaine 0.125% + fentanyl 20 μg (2 μg/ml).
  3. Group C: 10 ml bupivacaine 0.125% (the control group).

All patients were preloaded with 10-15 ml/kg Lactated Ringer's solution. Labor analgesia was maintained by intermittent boluses of the drug combination.
Results: The mean time of the onset of analgesia was significantly lower (P<0.05) and the duration of analgesia was significantly higher (P<0.01) in Group B when compared with Groups A and C (P<0.001). Patient satisfaction was considerably better in Group B (P<0.01). However, in both groups, the progression of labor was found to be slightly more prolonged than Group C. The level of the sensory and motor block was comparable in both the groups and was at the T8-T10 level; it was comparable and the level of motor blockade (Bromage score = 0, 1) in each group was also not significant (P>0.05).
Conclusion: The addition of fentanyl (2 μg/ml) to bupivacaine 0.125% decreases the time of the onset of analgesia and increases the duration of analgesia and level of maternal satisfaction during labor as compared to fentanyl (1 μg/ml).

Keywords: Fentanyl, intermittent extradural technique, labor analgesia


How to cite this article:
Tomar GS, Godwin RB, Gaur N, Sethi A, Narang N, Kachhwaha V, Kriplani T C, Tiwari A. A double-blind study on analgesic effects of fentanyl combined with bupivacaine for extradural labor analgesia. Anesth Essays Res 2011;5:147-52

How to cite this URL:
Tomar GS, Godwin RB, Gaur N, Sethi A, Narang N, Kachhwaha V, Kriplani T C, Tiwari A. A double-blind study on analgesic effects of fentanyl combined with bupivacaine for extradural labor analgesia. Anesth Essays Res [serial online] 2011 [cited 2019 May 22];5:147-52. Available from: http://www.aeronline.org/text.asp?2011/5/2/147/94754


   Introduction Top


The joy of child birth is always accompanied with a fear of pain. A negative birth experience is associated with subsequent infertility, and women's experiences should therefore be considered seriously in the provision of maternity care. [1] The concept of a walking epidural during labor is worthwhile as confining a parturient to bed may lead to painful and prolonged labor with higher incidences of abnormal presentations and fetal distress. [1],[2] Nowadays, it's considered to be the gold standard for labor pains. Epidural analgesia has been used extensively in developed countries and now getting popular in developing countries like India, etc., with some modification in the traditional epidural technique.

Over the past 10 years, there have been remarkable changes in the field of obstetric anesthesia. Anesthesiologists have improved upon their techniques to alleviate pain during labor while at the same time increasing the safety for both mother and the baby. Newer techniques such as combined spinal-epidural anesthesia, continuous epidural infusions, walking epidurals, and patient-controlled epidural analgesia (PCEA) are now available.

In contrast, continuous infusion extradural analgesia (CIEA) has been associated with significant motor blockade. [3] However, newer modalities, such as CSE and PCEA, are more expensive, technically more difficult, and associated with an increased incidence of side effects such as nausea, vomiting, and pruritus along with the use of opioids. [4] Although rarely meningitis has also been reported. [5]

The greatest advantage of implementing intermittent lumbar extradural for labor analgesia is the lack of need of a volume elastomeric extradural infusion pump, making its role worthwhile in conducting deliveries in emergency settings, and primary, secondary, and tertiary health centers of developing countries (India, etc.) where these facilities are not easily available but do have the human resources to provide the intermittent top-ups.

Our study was designed to evolve an appropriate dose combination of bupivacaine and fentanyl in extradural labor analgesia using an intermittent bolus technique and to evaluate the maternal and neonatal outcomes with its effect on the progress of labor.


   Materials and Methods Top


After obtaining approval from the institutional ethics committee, the present study was conducted after taking informed written consent from all the parturients.

A total of 90 patients were randomly assigned to one of the two intervention groups A and B, and control group C:

  • Group A (n=30): 10 ml of 0.125% bupivacaine and 1 μg/ ml fentanyl as a first bolus followed by intermittent top-ups of 0.0625% bupivacaine 10 ml + fentanyl 1 μg/ ml at visual analog score (VAS) ≥3.
  • Group B (n=30): 10 ml of 0.125% bupivacaine and 2 μg/ ml fentanyl as a first bolus followed by intermittent top-ups of 0.0625% bupivacaine 10 ml + fentanyl 2 μg/ ml at VAS≥3.
  • Group C (n=30): 10 ml of 0.125% bupivacaine as a first bolus followed by intermittent top-ups of 0.0625% bupivacaine 10 ml at VAS≥3.
Patients were explained regarding the possible risks and complications. Women were placed in a left lateral position when the cervix was 3-5 cm dilated and with strict aseptic precautions; the mid-lumbar extradural space L3-L4/L4-L5 was identified by using a loss of resistance technique with a 16-18 G Tuohy needle and an epidural catheter (Perifix 16 G or 18 G catheter; B. Braun, Melsungen, Germany) was sited 4-5 cm in the space. The epidural test dose was avoided in the study.

This was a prospective, double-blind, hospital-based study done from - August 10, 2009, December 10, 2009. A total of 90 patients admitted in the obstetric labor room were selected for the study of 200 cases. A time-based simple random sampling technique was used. Subjects and other study personnel were blinded as per group assignment.

Inclusion criteria were full-term (37-42 weeks) parturients of ASA class I and II having fixed cephalic presentation and cervical dilatation of 3-5 cm in spontaneous labor.

Exclusion criteria - were parturients with PIH, preterm labor, breech presentation, history of previous cesarean delivery, bad obstetric history, bleeding dyscrasia, and spinal deformities, patients on anticoagulants, hypotensive patients, morbid obese and elderly patients >35 years of age and patients having cervical dilatation >5 cm before epidural catheter insertion, patients having allergy to local anesthetics and opioids, and patients who refused on consent agreement were excluded from this study.

Data collection

For the collection of samples, all the variables were assessed and a pretested semistructured Performa was used containing information regarding sociodemographic details of patient variables.

  • Preoperative data collection: A complete preanesthetic evaluation was carried out, and maternal baseline pulse rate, blood pressure, respiratory rate, and SpO 2 and fetal heart rate were recorded.
  • Drug preparation and top-up administration: The drug solution containing the analgesic was prepared by an OT assistant or a junior resident. The top-up administration on the request of analgesia by the parturient by recording VAS was given by the resident (junior/senior) on duty. These were completely blinded from the study.
After collection, data were put in an Excel sheet and analyzed with the intention to treat using SPSS, 17 th version.

Statistical analysis used

The statistical significance for categorical variables was determined by Chi-square analysis. Fisher's exact t-test was used in case one or more expected cell count was less than 5. For continuous variables, a two-sample t-test was applied. Differences among the group means were compared using analysis of variance. Results were expressed as mean±SD (standard deviation). A P value <0.05 was considered statistically significant.

Taking a sample size of 30 in each group with a = 0.05, the power of the study is approximately 80%.

In Group A (n=30), the first dose of 10 ml containing 0.125% bupivacaine mixed with 1 μg/ml fentanyl (0.0001%) was administered via the catheter into the epidural space. In Group B (n=30), the first dose containing a similar concentration of bupivacaine along with 2 μg/ml fentanyl (0.0002%) was given. Top-up doses (10 ml containing 0.0625% bupivacaine with a similar concentration of fentanyl respective to each group) were given when patient's VAS ≥3. After each drug administration, patient vitals (pulse, BP, RR, SPO 2 ), maximum sensory/motor blockade level achieved, and fetal heart rate were monitored at 5, 10, 15, 30, 45, 60, 90, 120, 150, 180 min intervals or till delivery. Following every top-up dose, patients were monitored carefully for 10 min to detect any weakness or inadequacy of analgesia.

Motor blockade was assessed by the modified Bromage score [6] (0 = no impairment; 1 = unable to raise extended leg but able to move knees and foot; 2 = unable to raise extended leg as well as flex knees, but able to move foot; 3 = not able to flex ankle, feet, or knees) which was determined every 60 min during the first stage of labor. Maximum levels of sensory blockade achieved were assessed by the pinprick method and ice cube method.

Observed parameters were onset of analgesia, duration of analgesia, and time to the first top-up requirement assessed by VAS and verbal pain score (VPS) for pain at every 10 min, numbers of top-ups required, duration of the first and second stage of labor, mode of delivery, and APGAR score at 1 and 5 min.

On the day after delivery, maternal satisfaction level assessed by parturient acceptance regarding the quality of analgesia throughout labor was assessed by the following scoring system: 0, failure; 1, incomplete; 2, good; 3, excellent; and not possible to evaluate (NPE) due to delivery by cesarean section. [6],[7] All the obstetricians, attending the parturient were asked regarding the maintenance of maternal expulsive power during the second stage of labor.


   Results Top


The onset and duration of analgesia when compared to the intervention groups A and B was found to be statistically significant (P<0.0001). Twenty parturients in Group B had profound analgesia within 10 min; in Group A, it took around 15-20 min to achieve maximum analgesia while in Group C, maximum analgesia was seen after 20-30 min [Table 1]. VAS and VPS showed a faster onset of complete analgesia in Group B. The duration of analgesia of the first bolus dose (time interval between the bolus dose and the first maternal analgesia request) was higher in Group B (i.e., 120±20.26 min as compared to 100±10.04 min of Group A and 75±12.24 min of Group C).
Table 1: Comparison of various studied parameters among three groups

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The duration and progression of labor (first and second stage) from the insertion of the epidural (i.e., study time) was found to be slightly prolonged by approximately less than 15 min in Group B as compared to Groups A and C that was statistically nonsignificant (P>0.05). There was no difference in the degree of sensory blockade as assessed by the pinprick method or ice cube method, maximum at the T 8 level in around 60% parturients, and motor blockade assessed by the modified Bromage score (score = 0) in among 93.34% parturients in Group A and 90% parturients of Group C which means that they were able to walk up to a certain distance and were able to void by themselves. Only two parturients in Group A and three parturients in Group B had a score = 1 as compared to eight (26.67%) parturients of the control group that was statistically significant (P=0.024; [Table 1]). APGAR scores at 1 and 5 min were found to be comparable and statistically nonsignificant in both intervention groups (P=0.99; [Table 1]). Top-up requirements because of shorter duration of action was quite higher in control group C than intervention groups A and B in the order of C > A > B (P=0.001; [Table 2]).
Table 2: Comparison of duration of labor and amount of drugs used among three groups

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The total dose of bupivacaine and fentanyl used in our study was 67.42±20.25 mg bupivacaine and 74.34±30.34 μg fentanyl in Group A, 53.20±18.15 mg bupivacaine and 65.12+25.65 μg fentanyl in Group B, and 76.24±12.34 mg bupivacaine in the control group C which was statistically significant (P<0.05; [Table 2]).

There was one accidental dural puncture in Group B and the patient was excluded from the study.

The mode of delivery was spontaneous, i.e., normal vaginal delivery (NVD) in both the intervention groups; only one patient in Group A (3.33%), two in Group B (6.66%), and four parturients in Group C (13.34%) were converted to cesarean section because of the prolongation of the labor (statistically nonsignificant P value, 0.337).

Maternal nausea and vomiting were reported in two cases (6.66%) in Group B and in one parturient (3.33%) in Group A as compared to nil among control group C [Table 1]. The incidence of urinary retention (13.34%) and hypotension (6.66%) was quite higher in the control group than any intervention group. Fetal distress was reported in one fetus in Groups A and C (3.33%), and two in Group B (6.66%).

The maternal satisfaction level was significantly higher (90%) in Group B; 20 parturients reported excellent analgesia, while 7 explained a good score when compared to a 60% satisfaction level in Group A and just 40% in the control group (P<0.0001; [Table 1]).


   Discussion Top


In this prospective, randomized, double-blind study between two different doses of fentanyl for labor analgesia; doses chosen were based on a pilot study assessing clinical impression of efficacy, motor blockade, and duration of action. We decreased the volume and concentration of the drug injected extradurally, keeping in view the difference in demographic data (age, height) in the Indian population as compared to the western parturients [Table 3]. [7],[8],[9] Our aim was to minimize the concentration of the local anesthetic along with an appropriate dose of the opioid, so as to provide maximal labor analgesia along with active maternal participation during labor without affecting fetal well-being.
Table 3: Comparison of anthropometric variables and age of parturients between three groups

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The test dose was avoided in this study because in a laboring patient, maternal heart rate variability from the pain of uterine contractions may confuse the interpretation of the heart rate response, and intravenous epinephrine may have deleterious effects on the uterine blood flow. [10],[11]

The time interval from the initial bolus dose to the maternal analgesia request in our study was significantly increased in Group B. The longer latency to demand for analgesia in parturients of Group B could be attributed to a comparatively higher concentration of the opioid (fentanyl) used with the diluted low concentration of the local anesthetic (bupivacaine) since an increase in doses of the opioid and local anesthetic is directly proportional to the quality and duration of satisfactory analgesia and anesthesia but inversely to the time of the onset of block. [7]

The VAS and VPS at 10 min were lower in Group B indicating an early onset of analgesia. There was no difference in the degree of motor blockade in both intervention groups.

In our study, 93.33% parturients in Group A and 90% in Group B were mobile during 25-50% of the study time. Ambulation was achieved in 70% of the fentanyl epidural group and 68% in the bupivacaine, epinephrine, and fentanyl (BEF) group by Breen et al. [8] The incidence of sparing of motor blockade in both intervention groups in the present study is likely explained by the use of a lower concentration bupivacaine solution. Because motor blockade is considered undesirable during labor analgesia, the potential local anesthetic (bupivacaine) sparing effect of an intermittent bolus technique may be more clinically relevant than other continuous extradural techniques such as CIEA, PCEA, and CSEA. [3]

Several mechanisms have been proposed to explain the advantages of bolus compared with the continuous infusion of extradural solutions. When injected as a bolus through a multiorifice epidural catheter, the solution exits the distal end of the epidural catheter through all the orifices. [12] In contrast, when a continuous infusion of the same volume is injected through the catheter, it primarily exits through the proximal orifice. Another possible explanation of reduced bupivacaine consumption with the bolus technique may be the distribution of solutions in extradural space which is nonuniform but which spreads uniformly when delivered in large volumes with high injectable pressure. [13]

Our most significant findings were the reduction in the number of boluses and the overall reduction in the local anesthetic use in Group B (2 μg/ml fentanyl). [14],[15],[16] Local anesthetic sparing by a magnitude of 15-20% is also characteristic of PCEA [17] whereby patients self-administer the local anesthetic according to their level of pain. However, a potential criticism of the PCEA system is that patients will only demand a bolus when developing pain as the sensory block regresses. This is compounded by the lag time between the administration and action of epidural drugs. In contrast, regular intermittent bolus administration endeavors to prevent pain by injecting the local anesthetic at time intervals chosen so that the majority of patients remain pain free. [17],[18],[19]

In addition to bupivacaine, we found a dose sparing effect of fentanyl. [3],[14],[15],[20],[21] The systemic absorption of extradural fentanyl may result in fetal depression. [22],[23] In Group B, there were two reported cases of fetal bradycardia seen as compared to group A in which only one case was seen. Incidence maternal side effects like urinary retention and hypotension were quite higher in the control group than any intervention group that possibly justified with the higher consumption of the local anesthetic (bupivacaine). Maternal analgesia satisfaction was higher (90% reported good/excellent) in Group B (with 2 μg/ml fentanyl group) than in Group A (1 μg/ml fentanyl) showing a 60% satisfied level which was merely 40% in Group C. This difference was found to be clinically significant when measured by a 100-mm VAS and VPS. [24],[25]

There are few limitations in our study. By study design, subjects randomized to each group were nulliparae and multiparae; in multiparae there was lesser drug requirement because of shorter duration of labor as compared to nulliparae. In the current study, the salutary effect of the intermittent bolus technique was higher in women with longer duration of labors and in nulliparae. So, its use was found to be of greater significance in primigravida or nulliparous women. [16] Another limitation is a small sample size.

In summary, we found that 2 μg/ml extradural fentanyl is better than 1 μg/ml when combined with bupivacaine in the intermittent bolus technique, as it leads to faster onset, longer duration of analgesia, higher maternal satisfaction, and lesser drug requirement of the local anesthetic with a comparable side effect profile.


   Acknowledgment Top


The authors are thankful to Dr. (Prof.) Rekha Mahendra, MD; Dr. Shankar Agrawal, MD, Department of Anesthesiology and Critical Care, NSCB Medical College, Jabalpur, Madhya Pradesh, India.

 
   References Top

1.Mendez-Bauer C, Arroyo J, Garcia Ramos C, Menendez A, Lavilla M, Izquierdo F, et al. Effects of standing position on spontaneous uterine contractility and other aspects of labor. J Perinat Med 1975;3:89-100.  Back to cited text no. 1
    
2.Flynn AM, Kelly J, Hollins G, Lynch PF. Ambulation in labor. Br Med J 1978;2:591-3.  Back to cited text no. 2
    
3.Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg 2006;102:904-9.  Back to cited text no. 3
    
4.Norris MC, Grieco WM, Borkowski M, Leighton BL, Arkoosh VA, Huffnagle HJ, et al. Complications of labor analgesia: Epidural versus combined spinal epidural analgesia techniques. Anesth Analg 1994;79:529-37.  Back to cited text no. 4
    
5.Harding SA, Collis RE, Morgan BM. Meningitis after combined spinal-extradural anaesthesia in obstetrics. Br J Anaesth 1994;73:545-7.  Back to cited text no. 5
    
6.Bromage PR. A comparison of the hydrochloride and carbon dioxide salt of lidocaine and prilocaine in epidural analgesia. Acta Anaesthesiol Scand Suppl 1965;16:55-69.  Back to cited text no. 6
    
7.Gupta S, Raiger LK, Raman V. Ambulatory labor Analgesia - Comparison of two regional techniques. Indian J Anaesth 2002;46:44-8.  Back to cited text no. 7
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8.Breen TW, Shapiro T, Glass B, Payne DF, Oriol NE. Epidural anaesthesia for labor in an ambulatory patient. Anesth Analg 1993;77:919-24.  Back to cited text no. 8
    
9.Cohen SE, Yeh JY, Riley ET, Vogel TM. Walking with labor epidural analgesia: The impact of bupivacaine concentration and a lidocaine-epinephrine test dose. Anesthesiology 2000;92:387-92.  Back to cited text no. 9
    
10.Norris MC, Ferrenbach D, Dalman H, Fogel ST, Borrenpohl S, Hoppe W, et al. Does epinephrine improve the diagnostic accuracy of aspiration during labor epidural analgesia?. Anesth Analg 1999;88:1073-6.  Back to cited text no. 10
    
11.Hood DD, Dewan DM, James FM 3 rd . Maternal and fetal effect of epinephrine in gravid ewes. Anesthesiology 1986;64:610-3.  Back to cited text no. 11
    
12.Kayner AM, Shankar KB. Epidural infusion: continuous or bolus? Anesth Analg 1999;89:534.  Back to cited text no. 12
    
13.Hogan Q. Distribution of solution in the epidural space: Examination by cryomicrotome section. Reg Anesth Pain Med 2002;27:150-6.  Back to cited text no. 13
    
14.Murphy JD, Henderson K, Bowden MI, Lewis M, Cooper GM. Bupivacaine versus bupivacaine plus fentanyl for epidural analgesia: Effect on maternal satisfaction. BMJ 1991;302:564-7.  Back to cited text no. 14
    
15.Lyons G, Columb M, Hawthorne L, Dresner M. Extradural pain relief in labor: Bupivacaine sparing by extradural fentanyl is dose dependent. Br J Anaesth 1997;78:493-7.  Back to cited text no. 15
    
16.Chua SM, Sia AT. Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labor. Can J Anaesth 2004;51:581-5.  Back to cited text no. 16
    
17.Boutros A, Blary S, Bronchard R, Bonnet F. Comparison of intermittent epidural bolus, continuous epidural infusion and patient controlled-epidural analgesia during labor. Int J Obstet Anesth 1999;8:236-41.  Back to cited text no. 17
    
18.Bogod DG, Rosen M, Rees GA. Extradural infusion of 0.125% bupivacaine at 10 ml h-1 to women during labor. Br J Anaesth 1987;59:325-30.  Back to cited text no. 18
    
19.Smedstad KG, Morison DH. A comparative study of continuous and intermittent epidural analgesia for labor and delivery. Can J Anaesth 1988;35:234-41.  Back to cited text no. 19
    
20.James KS, McGrady E, Quasim I, Patrick A. Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labor. Br J Anaesth 1998;81:507-10.  Back to cited text no. 20
    
21.Celleno D, Capogna G. Epidural fentanyl plus bupivacaine 0.0125% for labor: Analgesic effects. Can J Anaesth 1988;35:375-8.  Back to cited text no. 21
    
22.Loftus JR, Hill H, Cohen SE. Placental transfer and neonatal effects of epidural sufentanil and fentanyl administered with bupivacaine during labor. Anesthesiology 1995;83:300-8.  Back to cited text no. 22
    
23.Kumar M, Paes B. Epidural opioid analgesia and neonatal respiratory depression. J Perinatol 2003;23:425-7.  Back to cited text no. 23
    
24.Singer AJ, Thode HC Jr. Determination of the minimal clinically significant difference on a patient visual analog satisfaction scale. Acad Emerg Med 1988;5:1007-11.  Back to cited text no. 24
    
25.Nikkola E, Läärä A, Hinkka S, Ekblad U, Kero P, Salonen M. Patient-controlled epidural analgesia in labor does not always improve maternal satisfaction. Acta Obstet Gynecol Scand 2006;85:188-94.  Back to cited text no. 25
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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