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Anesth Essays Res. 2017 Jul-Sep; 11(3): 730–739.
PMCID: PMC5594798

To Evaluate the Efficacy of Fentanyl and Dexmedetomidine as Adjuvant to Ropivacaine in Brachial Plexus Block: A Double-blind, Prospective, Randomized Study

Abstract

Context:

Anesthesia and analgesia for surgeries to the upper extremity are commonly provided using brachial plexus anesthesia. There are limited or almost no studies comparing the use of ropivacaine with fentanyl to ropivacaine with dexmedetomidine.

Aims:

To compare the efficacy of fentanyl and dexmedetomidine as adjuvants to ropivacaine for brachial plexus block among patients undergoing upper limb orthopedic surgeries.

Settings and Design:

This was a prospective, randomized, double-blinded study.

Subjects and Methods:

The patients were randomly divided into three groups of 35 each using computerized randomization table. Group I patients received 3 mg/kg of 0.75% ropivacaine with 1 μg/kg of fentanyl diluted with normal saline (NS) to make a total volume of 35 ml. Group II patients received 3 mg/kg of 0.75% ropivacaine with 1 μg/kg of dexmedetomidine diluted with NS to make a total volume of 35 ml. Group III patients received 3 mg/kg of 0.75% ropivacaine with NS making a total volume of 35 ml.

Statistical Analysis Used:

Statistical analysis was performed using Statistical Package for Social Sciences, version 15.0. Analysis of variance followed by independent samples t-test was performed for parametric data, and Kruskal–Wallis test followed by Mann–Whitney U-test was performed for nonparametric data.

Results:

Mean motor and sensory block onset time was minimum in Group I and maximum in Group III while mean duration of sensory and motor block was maximum in Group I and minimum in Group III. Time taken for first rescue analgesic dose was also maximum in Group I and minimum in Group III.

Conclusions:

It can be concluded that 3 mg/kg of 0.75% ropivacaine along with 1 μg/kg of fentanyl diluted with NS to make a total volume of 35 ml was the most efficacious regimen for brachial plexus block among patients undergoing upper limb orthopedic surgeries.

Keywords: Analgesia, brachial plexus, bupivacaine, dexmedetomidine, fentanyl, ropivacaine

INTRODUCTION

Anesthesia and analgesia for surgeries to the upper extremity are commonly provided using brachial plexus anesthesia, which are a suitable alternative and a valuable addition to general anesthesia. Brachial plexus block has a long history existing till date, providing surgical anesthesia and postoperative analgesia.[1]

Bupivacaine is frequently used as the local anesthetic for brachial plexus anesthesia because it offers the advantage of providing a long duration of action and a favorable ratio of sensory to motor neural block.[1,2,3] One of the first local anesthetic agents that emerged as a possible replacement for bupivacaine was ropivacaine.

Ropivacaine is a long-acting amide local anesthetic with a potentially improved safety profile when compared to bupivacaine.[4,5]

There has always been a search for adjuvant in regional nerve block with the drugs that prolong the duration of analgesia but with lesser adverse effects. The search for the ideal additive continues and leads us to try the novel α2 adrenergic agent dexmedetomidine and an opioid fentanyl.

Dexmedetomidine and fentanyl are two such adjuvant drugs that have been used in combination with bupivacaine or ropivacaine to enhance the analgesic efficacy of the drugs and that facilitate early achievement and prolongation of block. A number of studies have evaluated the efficacy of both the drugs,[6,7,8] either independently or in combination with other adjuvants. There are limited or almost no studies comparing the use of ropivacaine with fentanyl to ropivacaine with dexmedetomidine. Considering the low side effect and excellent postoperative analgesic efficacy of two drugs, it is essential to carry out a comparative evaluation of two drugs for their adjuvant use with ropivacaine in supraclavicular block among patients undergoing upper limb orthopedic surgeries.

SUBJECTS AND METHODS

The present study was carried out in the Department of Anesthesiology at a tertiary care medical college, with an aim to compare the efficacy of fentanyl and dexmedetomidine as adjuvants to ropivacaine for brachial plexus block among patient undergoing upper limb orthopedic surgeries. For this purpose, a prospective study was planned in which a total of 105 patients scheduled to undergo upper limb orthopedic surgery were enrolled as per the design shown below.

  • Type of study: Prospective, randomized, double-blinded study
  • Duration of study: 18 months.

Inclusion criteria

  • Adult patients aged between 18 and 55 years
  • American Society of Anesthesiologists Physical Status I–II
  • Scheduled for elective upper limb orthopedic surgeries under supraclavicular block.

Exclusion criteria

  • Lack of patient's consent
  • Patients with anticipated difficult intubation: Mallampati Grade III and IV
  • Any other comorbidities (chronic obstructive pulmonary disease, ischemic heart disease, hypertension, diabetes mellitus, renal/hepatic dysfunction, etc.)
  • Morbid obesity (body mass index >35)
  • Patients with a known contraindication to any of the study drugs.

Sample size estimation

The sample size was calculated using the formula:

An external file that holds a picture, illustration, etc.
Object name is AER-11-730-g001.jpg

Where

σ1= 48.36

σ2= 59.13

d = 48.36

α = Type I error (5%)

β = Type II error (20%)

Power of the study = 80%

Data loss = 10%

Sample size came out to be n = 35 each group.

After obtaining clearance from the Hospital Ethical Committee, 105 patients in the age group of 18–55 years scheduled for upper limb orthopedic surgeries under brachial plexus block were included in this study.

The patients were visited a day before surgery for preanesthetic review and standard institutional preoperative advice.

Informed consent was obtained from all the patients enrolled in the study and asked to remain nil orally 6 h before surgery.

On the day of surgery, all patients after evaluation were taken to the operation theater. Monitors were attached and baseline parameters (heart rate [HR], blood pressure [BP], SpO2, and electrocardiogram) were recorded.

Intravenous line was secured with 18-gauge cannula and the patient was preloaded with 20 ml/kg of Ringer's lactate and premedicated with 2 mg of midazolam intravenously.

On the day of surgery, all patients were admitted to the preanesthesia block area of the main operating room and were premedicated with 2 mg of midazolam intravenously.

The patient is positioned supine with the head turned about 30° to the contralateral side. The interscalene groove was palpated at its most inferior point, which is just posterior to the subclavian artery pulse; the latter can be felt in a plane just medial to the midpoint of the clavicle. After a skin wheal with local anesthetic, a 22-gauge, 1.5-in needle was directed just above and posterior to the subclavian pulse and directed caudally at a very flat angle against the skin. The needle was advanced until a paresthesia was encountered or muscle contraction of the forearm is noted. If contraction was still observed or palpated with the stimulator voltage decreased to 0.5 mA, then 25–40 ml of local anesthetic was injected. If the rib was encountered without a paresthesia or if blood was encountered, the needle was withdrawn, and the landmarks as well as the plane of the needle insertion path were reevaluated.

Study groups

The patients were randomly divided into three groups, of 35 each using computerized randomization table.

  • Group I patients received 3 mg/kg of 0.75% ropivacaine with 1 μg/kg of fentanyl diluted with normal saline (NS) to make a total volume of 35 ml
  • Group II patients received 3 mg/kg of 0.75% ropivacaine with 1 μg/kg of dexmedetomidine diluted with NS to make a total volume of 35 ml
  • Group III patients received 3 mg/kg of 0.75% ropivacaine with NS making a total volume of 35 ml.

The baseline parameters were evaluated before administration of sample drug and after administration every 5 min for 30 min or until onset of block and thereafter every 30 min during the surgery and then every hourly for 12 h.

Pain was assessed using a 10-point visual analog scale (VAS), in which a score of “0” shall indicate “no pain” and a score of “10” “worst pain imaginable.” The VAS measurements were obtained at baseline [Figure 1].

Figure 1
Visual analog scale

Sensory block evaluation

It was done using pinprick method. The following chart was used to locate the level of block. Sensory onset was considered to be achieved when there was dull sensation to pinprick along the distribution of any of the above-mentioned nerves. Complete sensory blockage was considered when there was complete loss of sensation to pinprick.

Sensory blockage was graded as follows:

  • Grade 0: Sharp pain felt
  • Grade I: Analgesia, dull sensation felt
  • Grade II: Anesthesia, no sensation felt.

Duration of sensory block was determined by noting the time when there was return of dull sensation to pinprick.

Motor block evaluation

It was done using modified Bromage scale criteria as detailed below:

An external file that holds a picture, illustration, etc.
Object name is AER-11-730-g003.jpg

Onset of motor blockage was considered when at least Grade I Bromage motor blockage was achieved. Peak motor block was considered when Grade III Bromage blockage was achieved.

Duration of motor blockage was determined by noting the time the patients was able to first move the fingers.

Side effects such as bradycardia, hypotension, headache, and convulsion were looked for.

Blockage was considered to have failed when sensory anesthesia was not achieved within 30 min. General anesthesia was given subsequently to these patients and was excluded from the study.

Times for recording

  • T0: Before administration of the drug
  • T1: Immediately after administration of the drug
  • T2: 5 min after administration of the drug
  • T3: 10 min after administration of the drug
  • T4: 15 min after administration of the drug
  • T5: 30 min after administration of the drug
  • T6: 60 min after administration of the drug
  • T7: 120 min after administration of the drug
  • T8: 180 min after administration of the drug
  • T9: 240 min after administration of the drug.

At all the above-mentioned time periods, hemodynamic parameters, namely, HR, noninvasive BP, respiratory rate [RR], and SpO2, were also monitored in the contralateral limb.

Hypotension (defined by decrease in mean arterial pressure below 20% of the baseline or systolic BP [SBP] <90 mmHg) was treated with injection mephentermine 6 mg/ml.

Bradycardia (HR <50 bpm) was treated with injection atropine 0.6 mg/ml.

Respiratory depression (RR <8 bpm or SpO2 < 95%) was treated with oxygen supplementation and respiratory support if required.

Postoperatively, time for first rescue analgesic was also noted.

Statistical analysis

Data so obtained were subjected to statistical analysis using Statistical Package for Social Sciences, version 15.0. Analysis of variance followed by independent samples t-test was performed for parametric data, and Kruskal–Wallis test followed by Mann–Whitney U-test was performed for nonparametric data. Categorical outcomes were evaluated using Chi-square test. The confidence level of the study was kept at 95%; hence, a P < 0.05 indicated statistically significant association.

RESULTS

The present study was carried out with the aim to compare the efficacy of fentanyl and dexmedetomidine as adjuvants to ropivacaine for brachial plexus block among patient undergoing upper limb orthopedic surgeries. For this purpose, a total of 105 patients scheduled to undergo upper limb orthopedic surgery were enrolled in the study and were allocated to three groups [Table 1].

Table 1
Group-wise distribution of patients

Table 2 compares the baseline demographic and general characteristics of patients in three groups. At baseline, all the groups had motor block level 0. Till 5 min, no motor block was seen in a group. Initiation of blockade to level 1 was observed in Group I at 10 min. At 15 min, median block level was 1 in Group I as compared to 0 in the other two groups. In Group I, median block level of 3 was achieved at 25th min itself, whereas in Group II, this level could be achieved at 30 min. In Group III, median block level of 3 could be achieved at 120 min. In Group I, median block level of 3 remained consistent from 25 to 300 min intervals, whereas in Group II, median level 3 could be maintained from 30 to 240 min intervals, whereas in Group III, this median level was seen only between 120 and 240 min intervals. Except for baseline and 5, 10, and 120 min intervals, the block levels in Groups I and II were significantly higher as compared to that in Group III (P < 0.05) [Table 3].

Table 2
Demographic profile and general characteristics
Table 3
Comparison of motor block levels at different time intervals

Between Groups I and II, a statistically significant difference was observed starting from 10 to 30, 300, and 540 min intervals.

Between Groups I and III, a statistically significant difference was observed at all time intervals, except at baseline and 5, 120, and 540 min intervals.

Between Groups II and III, a statistically significant difference was observed at all intervals, except from baseline to 15 and 120 min intervals [Table 4]. Initiation of median block level at higher level was earlier in Groups I and II as compared to Group III and its maintenance was also prolonged in Groups I and II as compared to Group III. A significant difference among groups was observed throughout the study period, except at baseline and 60, 120, 240, and 540 min [Table 5]. Between Groups I and II, statistically, significant differences were observed at 5, 10, 15, 300, 360, and 420 min intervals. At all these intervals, Group I had values of higher order as compared to Group II. Between Groups I and III, statistically, significant differences were observed from 5 to 25 min and from 240 to 480 min intervals. At all these intervals, values were of higher order in Group I as compared to that in Group III. Between Groups II and III, statistically, significant differences were observed from 10 to 25 min and from 240 to 480 min intervals. At all these intervals, values were of higher order in Group II as compared to that in Group III [Table 6].

Table 4
Between-group comparison (Mann-Whitney U-test)
Table 5
Comparison of sensory block levels at different time intervals
Table 6
Between-group comparison (Mann-Whitney U-test)

Mean motor and sensory block onset time was minimum in Group I and maximum in Group III while mean duration of sensory and motor blocks was maximum in Group I and minimum in Group III. Time taken for first rescue analgesic dose was also maximum in Group I and minimum in Group III. Statistically, a significant difference was observed among groups with respect to all the parameters (P < 0.001) [Table 7]. On between-group comparison of motor and sensory block onset and duration as well as for time taken for first rescue analgesic dose, a significant difference was observed for all the between group comparisons (P < 0.001) [Table 8]. In Group III, median pain scores were significantly higher as compared to the other two groups at all time intervals up to 8 h and then at 11 h. Median pain scores were of similar order in Groups I and II throughout the period of study except at 9 h [Table 9]. With respect to pain scores, statistically, no significant difference was observed between Group I and Group II for the entire duration of follow-up (P > 0.05). However, Group III had significantly higher pain scores as compared to Group I at all time intervals, except at 2, 9, and 12 h. Group III also had significantly higher pain scores as compared to Group II at all time intervals, except at 2, 9, 10, and 12 h [Table 10].

Table 7
Onset and duration of blocks
Table 8
Between-group comparison (independent samples t-test)
Table 9
Comparison of postoperative pain scores at different time intervals
Table 10
Between-group comparison (Mann-Whitney U-test)

Mean HR in different groups ranged from 73.4 ± 5.4 bpm (Group II at 180 min) to 88.8 ± 11.0 bpm (Group I at 5 min). Statistically, no significant difference among groups was observed at any of the time intervals, except for 180 min where mean value was minimum in Group II (73.4 ± 5.4) and maximum in Group I (77.2 ± 5.4 bpm) (P = 0.018). No categorical change in HR requiring an intervention was recorded [Table 11]. Between-group comparison of HR showed statistically no significant difference for all the comparisons, except at 120 and 180 min when mean value of Group I was significantly higher as compared to that of Group II [Table 12].

Table 11
Comparison of heart rate in different groups at different time intervals
Table 12
Between-group comparison (independent samples t-test)

Mean SBP ranged from 118.4 ± 11.3 (Group II at 240 min) to 133.7 ± 8.9 (Group II at 5 min). Statistically, no significant differences were observed among the groups at any time interval (P > 0.05) [Table 13]. Between-group comparison did not reveal a statistically significant difference for any of the comparisons (P > 0.05) [Table 14].

Table 13
Comparison of systolic blood pressure in different groups at different time intervals
Table 14
Between-group comparison (independent samples t-test)

Mean DBP ranged from 67.7 ± 5.2 (Group II at 180 min) to 81.2 ± 15.7 (Group I at baseline). Statistically, no significant differences were observed among the groups at any time interval (P > 0.05). No hypotensive or hypertensive event was recorded throughout the study [Table 15]. Between-group comparison did not reveal a statistically significant difference for any of the comparisons (P > 0.05) [Table 16].

Table 15
Comparison of diastolic blood pressure in different groups at different time intervals
Table 16
Between-group comparison (independent samples t-test)

DISCUSSION

Regional anesthesia is the preferred choice of an anesthetist for upper limb surgeries, and brachial plexus block is one of the most commonly used blocks for this purpose. The major consideration for an anesthetist while selecting a pharmacological option during regional anesthesia is not only to provide adequate and timely sensory and motor block to facilitate the surgical procedure but also to augment the postoperative analgesic efficacy of the drug being used. Safety of use, speedy and adequacy of block, and postoperative pain control thus decide the usefulness of a pharmacological option by an anesthetist. Emergence of ropivacaine over bupivacaine is one of the decisions guided by concerns regarding safety of drug use. No doubt, ropivacaine produces less cardiac as well as central nervous system toxic effects; however, it produces less motor block as compared to bupivacaine.[9,10] Thus, addition of adjuvants is a decision guided by need to speed up block achievement, increase its efficiency by increasing the block level and blockade time and quality of postoperative recovery. For this purpose, a number of drugs are being tried and tested. In the present study, two such adjuvant options fentanyl and dexmedetomidine as adjuvants to ropivacaine with an aim to evaluate whether addition of these drugs increases the efficacy in terms of achievement of block, block quality, its subsidization, and side effects if any. Interestingly, while ropivacaine is claimed to be better than bupivacaine in terms of cardiotoxicity,[11,12,13] still there is limited literature comparing the adjuvant use of drugs with ropivacaine.

The dose selection of drugs was based on the historic evidence regarding optimally used drugs that are reportedly safe to use. In the present study, we used 3 mg/kg of 0.75% ropivacaine which was supplemented with either 1 μg/kg of fentanyl or 1 μg/kg of dexmedetomidine diluted with NS to make a total volume of 35 ml.[14,15]

In the present study, achievement of motor block with Bromage score 2 was earliest in fentanyl group and latest in control group. Thus, use of adjuvants in all the groups showed an early block achievement. Median score of 2 was achieved by 20 min in fentanyl group as compared to 30 min in the other two groups. Mean onset of motor block was also shortest in fentanyl group followed by dexmedetomidine group and longest in control group. As far as the sustenance of motor block was concerned, it was sustained at a median score of 2 up to 360 min in fentanyl and dexmedetomidine groups as compared to 300 min in control group. Thus, mean duration of block was >6 h (369.4 ± 36.9 min) in fentanyl group, followed by a little below 6 h in dexmedetomidine group (323.7 ± 48.1) and <5 h (274.3 ± 68.7 h) in control groups. Thus, with respect to motor block, addition of adjuvants not only speeds up the time for achievement of block but also helps retain it for a substantial time. Upper limbs are important functional organs that involve motion, a longer motor block helps restrict this function up to a substantial time during postoperative period and helps stabilize the operative procedure, while an early achievement of block helps initiate the operative procedure earlier.

With respect to sensory block too, median Grade II was achieved within 10 min in fentanyl group as compared to 15 min in dexmedetomidine and control groups. However, sustenance median Grade II was observed to be similar in both fentanyl and dexmedetomidine groups (up to 360 min), whereas in control group, this sustenance was observed only till 240 min. Mean onset time to achieve sensory block was 9.0 ± 1.8 min in fentanyl group followed by 11.9 ± 2.6 min in dexmedetomidine group as compared to 19.0 ± 5.3 min in control group. Mean duration of sensory blockade in fentanyl group was 425.7 ± 42.4 min followed by 378.3 ± 59.6 min in dexmedetomidine and 300 ± 54.4 min in control group.

The findings in the present study are in agreement with the observations in a number of studies too where addition of fentanyl and dexmedetomidine has been shown to prolong the motor block and sensory block duration.[6,7,8,16,17,18] However, contradictory views have been presented by some workers that have even questioned the usefulness of such addition. However, these contradictions are often caused by several confounders or are marred by the adequacy of sample. For example, a study by Fanelli et al.[19] showed no significant difference in time taken to achieve readiness of surgery between ropivacaine alone or ropivacaine with fentanyl. However, this study had only 15 samples in each group and showed a high within-group variability in the achievement of blockade (5–40 min). In the present study, this within-group variability was shorter (10–30 min) and the sample size was three times larger (n = 45 in each group) than the study in question. The studies confounded by smaller sample size have failed to show a significant impact of adjuvant use on onset and duration of blocks.[17,20] Recent studies even with smaller sample size have shown a better efficacy of adjuvant use.[7,21,22] The studies with larger sample sizes have shown a positive and significant usefulness of adjuvants.[18] The present study had a sample size of 35 patients in each group which was relatively larger than the studies in question and hence has greater power to explain the variances and differentiate between groups.

In the present study, fentanyl was seen to act as a better adjuvant as compared to dexmedetomidine for achievement and duration of sensory and motor blockade. However, in some recent studies, dexmedetomidine has been shown to reduce the onset time for motor and sensory block and increase the duration of sensory and motor blocks as compared to fentanyl.[14,15] In the present study, both the drugs showed excellent analgesic efficacy that was superior to the solitary use of ropivacaine. Between two test groups, fentanyl had a better pain control as compared to dexmedetomidine. Mean time taken for first analgesic need was 7.54 ± 0.51 h in fentanyl group as compared to 5.43 ± 0.78 h in dexmedetomidine and 4.03 ± 0.75 h in control group. Ropivacaine itself has a better safety as compared to bupivacaine; however, it loses the analgesic efficacy in trade off for a better cardiac-friendly profile and it is the reason why adjuvants are used to enhance the analgesic effect to have a better postoperative control of pain.[6,7,8]

Altogether, both the drugs did not produce any potential side effect to be recorded as an event and can be termed as safe drugs. Studies comparing adjuvant use of dexmedetomidine and fentanyl with other drugs and through other routes have mostly shown dexmedetomidine to be better both in terms of onset and duration of block as well as in terms of analgesic effect;[14,17,23,24,25] however, the present study did not show any superior efficacy of dexmedetomidine over fentanyl which as already discussed earlier might be attributed to the highly selective nature of dexmedetomidine, drug-interaction and configurational variances of brachial plexus anatomy. Unfortunately, there is no comparable study using the same design as used in the present study, and hence, empirical applicability of results obtained in the present study is to be validated. No doubt, addition of either of two drugs provided a beneficial effect and showed no side effects for either of them; hence, both the drugs can be recommended for use as adjuvants to ropivacaine for speeding up the block onset, prolonging the block duration, and having a better and sustained analgesic effect. Further studies to highlight the differences between two drugs are recommended.

CONCLUSIONS

On the basis of above observations, it can be concluded that 3 mg/kg of 0.75% ropivacaine with 1 μg/kg of fentanyl diluted with NS to make a total volume of 35 ml was the most efficacious regimen for brachial plexus block among patients undergoing upper limb orthopedic surgeries, although postoperative pain score was comparable for both the adjuvants, i.e., fentanyl and dexmedetomidine. Both the adjuvant combinations were safe to use and had hemodynamic stability similar to ropivacaine alone. Considering these observations, ropivacaine with fentanyl could be recommended as an anesthetic for choice for better block and postoperative analgesic characteristics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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