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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 650-660

Pharmacodynamic evaluation of dexmedetomidine as an additive drug to bupivacaine in ultrasound-guided interscalene brachial plexus block


1 Department of Anesthesiology and IC, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

Date of Submission25-Sep-2019
Date of Decision25-Sep-2019
Date of Acceptance14-Nov-2019
Date of Web Publication10-Feb-2020

Correspondence Address:
BSc, MSc Ain E.A.A Hassan
Departments of Anesthesiology and IC, Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, 11754
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_77_19

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  Abstract 


Introduction Dexmedetomidine, a novel α2 agonist, is widely used as an adjuvant to local anesthetic in peripheral nerve blocks to decrease the time of onset and increase the duration of the block.
Aim We have conducted this study to compare three different doses of dexmedetomidine as an additive to 0.5% bupivacaine in interscalene brachial plexus block guided by ultrasound for upper limb surgery.
Patient and Methods Sixty patients aged (21–60 years, ASA I, II) were divided into three groups. Group I received 15 ml 0.5% bupivacaine+50 µg dexmedetomidine (BD50). Group II received 15 ml 0.5% bupivacaine+100 µg dexmedetomidine (BD100). Group III received 15 ml 0.5% bupivacaine+150 µg dexmedetomidine (BD150). Onset of sensory and motor block, visual analog scale, total analgesic need, sedation level, side effects and complications, hemodynamic variables (systolic and diastolic blood pressure and heart rate), and stress response [cortisol, blood glucose, C-reactive protein (ultrasensitive)] were recorded for each patient.
Results The onset time for sensory and motor blocks in intergroups comparisons showed nonsignificant difference between groups II and III. The results showed a highly significant difference in visual analog scale score after 12 and 24 h postoperatively in group I than in groups II and III (P<0.001). Six patients in group I required rescue analgesia whereas in groups II and III no patients required rescue analgesia in the first 24 h postoperatively. The sedation score was higher in groups II and III than in group I. No serious side effects were observed in all groups except bradycardia in one (5%) patient in group II and two (10%) patients in group III and it was clinically insignificant.
Conclusion By comparing the outcomes of using different doses of dexmedetomidine, we may conclude that the use of 100 µg dexmedetomidine carries the best benefits of dexmedetomidine with little hazards and side effects.

Keywords: bupivacaine, dexmedetomidine, ultrasound-guided interscalene brachial plexus


How to cite this article:
Hassan AE, Mahmoud MS, Farran HA, Eldesoky GA, Mahmoud RH. Pharmacodynamic evaluation of dexmedetomidine as an additive drug to bupivacaine in ultrasound-guided interscalene brachial plexus block. Sci J Al-Azhar Med Fac Girls 2019;3:650-60

How to cite this URL:
Hassan AE, Mahmoud MS, Farran HA, Eldesoky GA, Mahmoud RH. Pharmacodynamic evaluation of dexmedetomidine as an additive drug to bupivacaine in ultrasound-guided interscalene brachial plexus block. Sci J Al-Azhar Med Fac Girls [serial online] 2019 [cited 2020 Feb 29];3:650-60. Available from: http://www.sjamf.eg.net/text.asp?2019/3/3/650/278043




  Introduction Top


Pain after orthopedic surgery can be intense, and its management poses a challenge to both anesthesiologists and orthopedic surgeons. Peripheral nerve block (PNB) is a suitable alternative to general anesthesia especially for 1-day case surgery [1]. Interscalene approach of the brachial plexus block (BPB) similar to the supraclavicular and infraclavicular blocks provide a reliable, safe, effective, and low-cost procedure with satisfactory postoperative analgesia for the upper limb surgery [2].

Dexmedetomidine has shown great affinity as an alphaa-2 adrenoreceptor agonist which has been associated with prolonged analgesia after the administration of local anesthesia in a variety of routes and mechanisms, including neuraxial, perineural, intraarticular, and possibly even intravenous [3]. Among these, the perineural route for dexmedetomidine has been the subject of increasing interest as the potential to significantly prolong the duration of analgesia after single-injection PNBs can have important wide-ranging benefits for patients and providers alike, especially within the setting of ambulatory surgery [4].

Sedation accompanies the use of dexmedetomidine through its action on the locus coeruleus. Sedation with dexmedetomidine was similar to natural sleep; in fact, it promoted REM sleep. It is known to produce ‘conscious and cooperative sedation.’ Sedative properties of dexmedetomidine are attributable to its lipophilic nature resulting in systemic absorption when administered perineurally [3].


  Patients and randomization Top


This prospective, single-blinded study was carried out on 60 adult patients undergoing surgery at the shoulder and proximal humerus region. The patients were of both sexes, aged between 21 and 60 years. Exclusion criteria include ASA physical status III and more, any bleeding tendency or patient on oral anticoagulants, neurological deficits involving brachial plexus, local infection at the site of injection, patients receiving psychotropic drugs or chronic analgesic therapy and known allergy to one of the study elements.

After obtaining permission from the Institutional Ethics Committee of Al-Zahraa university Hospital, Al-Azhar University, written informed consent was taken from all the participants after proper explanation of the study procedure and the expected outcome in their own language. The study was carried out from August 2017 to January 2019. The patients were randomly allocated (using file number) into three equal groups of 20 patients (n=20) each.
  • Group I (BD50, n=20): 15 ml of bupivacaine 0.5% (Markyrene 0.5%, sigmatec) mixed with 50 µg dexmedetomidine (Dextomid, vial; Neon Laboratories Ltd., Maharashtra, India) plus 1 ml normal saline injected into the interscalene groove guided by ultrasound (total volume 16.5 ml).
  • Group II (BD100, n=20): 15 ml of bupivacaine (0.5%) (Markyrene 0.5%, sigmatec) mixed with 100 µg dexmedetomidine (Dextomid, vial; Neon) plus 0.5 ml normal saline injected into the interscalene groove guided by ultrasound (total volume 16 5 ml).
  • Group III : (BD150, n=20): 15 ml of bupivacaine 0.5% (Markyrene 0.5%, sigmatec) mixed with 150 µg dexmedetomidine (Dextomid, vial, Neon) injected into the interscalene groove guided by ultrasound (total volume 16.5).


Outcome measurements

Primary outcome measures were the efficacy (onset and intensity) of sensory and motor block.

Secondary outcome measures were visual analog scale (VAS) and rescue analgesia (dose consumption of diclofenac by each patient during the first 24 h of the postoperative period), sedation levels, possible side effects and hemodynamic variables (systolic blood pressure, diastolic blood pressure, and heart rate), and stress response [cortisol, blood glucose, C-reactive protein (CRP) (ultrasensitive)].


  Materials and methods Top


Echogenic needle [Locoplex L (a short (35 mm), broad (22 G)].

Drugs: bupivacaine 0.5% (Markyrene 0.5%, vial 20 ml, manufactured by sigmatec). Dexmedetomidine hydrochloride [Dextomid 100 μg (1 ml) and 200 μg (2 ml), manufactured by Neon].

SonoScape A6 portable ultrasound machine with a linear probe of high frequency (6–13 MHz).

Emergency equipment and resuscitation drugs (e.g. atropine, epinephrine, ephedrine, intralipid 20%, etc.) were kept ready in the operative room.

All patients were instructed to fast preoperatively for a period of 6–8 h and to start balanced diet 2 h postoperatively

Sensory assessment: onset of sensory block was defined as the time from injection to onset of analgesia and measured in five-time intervals by the pin prick method [0=no block (normal sensation), 1=partial block (decreased sensation)]. Complete block (no sensation), along the distribution of the shoulder and the humerus (10, 15, 20, 25, and 30 min).

Motor assessment: onset of motor block is the time from injection to the inability of the patient to abduct his shoulder. Motor block was measured at five-time interval after the block (10, 15, 20, 25, and 30 min). Assessment of the motor blockade was done using the Bromage three-point score (0=normal abduction, 1=decreased movement, moves shoulder but not normal, 2=unable to abduct shoulder).

Sedation level was evaluated by Richmond Agitation and Sedation Scale [5].



During anesthesia, interscalene block was excellent if there was no discomfort or pain, good (mild pain or discomfort, no need for additional analgesics), fair (pain that required additional analgesics), or poor (moderate or severe pain that needed fentanyl or general anesthesia).

In the circumstance of inadequate action of the block, the block was supplemented with general anesthesia. In case the surgery was unduly prolonged, and the effect of the block wore off, rescue analgesia with intravenous hypnotic (propofol 2 mg//kg) and analgesic (fentanyl 50 μg) was given.

Statistical analysis

Recorded data were analyzed using the Statistical Package for the Social Sciences, SPSS, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage. The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the P value was considered significant as the following: P value less than 0.05 was considered significant; P value less than 0.001 was considered as highly significant; P value more than 0.05 was considered insignificant.

Sample size justification

MedCalc, version 12.3.0.0 program (Ostend, Belgium) was used for the calculation of the sample size, statistical calculator based on 95% confidence interval and power of the study 80% with α error 5%. Based on Joseph et al. [6] the sample size was calculated according to these values producing a minimal sample size of 57 cases, which was enough to find such difference. Assuming a dropout ratio of 5%, the sample size was 60 cases, subdivided into three groups, 20 cases in each group.


  Results Top


Demographic data and duration of surgery showed no statistically significant difference between groups ([Table 1]).
Table 1 Comparison between groups according to demographic data

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As regards the onset of sensory block the analysis showed significant difference data between groups in two time intervals (10 and 15 min). The onset time of sensory block was earliest in group III (BD 150 μg)> group II (BD 100 μg)>group I (BD 50 μg) (P value at 15 min 0.034). In the other three time intervals (20, 25, 30 min), the data was not significant as the interscalene plexus block was established. Intergroup comparison showed nonsignificant difference between groups II and III (P>0.05) ([Figure 1]).
Figure 1 Comparison between groups according to the onset of sensory block (min).

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The onset of motor block was earlier and significant in group II (BD 100 μg) and group III (BD 150 μg) than in group I (BD 50 μg) at 10 min interval (P=0.037). Intergroup the onset of motor block was nonsignificant between groups II and III at 10 min interval (P>0.05). At 15 min interval, there was no statistically significant difference between groups. In the remaining time intervals, interscalene plexus block was established, so the data was not significant ([Figure 2]).
Figure 2 Comparison between groups according to the onset of motor block (min).

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As regards the VAS score the results showed that after 2 h postoperatively, there was no significant difference between groups till 4 h postoperatively, the data showed significant difference in group I (BD 50 μg) than in group II (BD 100 μg) and group III (BD 150 μg) (P=0.002). The results show highly significant difference after 12 and 24 h postoperatively in group I than in groups II and III (P<0.001). Intergroup shows no significant difference between groups II and III at all time points ([Figure 3]).
Figure 3 Comparison between groups according to the postoperative VAS score. VAS, visual analog scale.

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Postoperative distribution of patients according to VAS more than or equal to 5 showed that six patients in group I (BD 50 μg) required rescue analgesia (diclofenac) in the first 24 h postoperatively, whereas in group II (BD 100 μg) and group III (BD 150 μg) no patient required rescue analgesia in the first 24 h postoperatively and the difference was statistically highly significant (P<0.001).

The modified Richmond Sedation Scale scores increased over time intraoperatively in all three groups. There were highly significant differences in sedation (P<0.001), and there was difference in the slope of the curves for the sedation scores over time. The sedation was higher in group II (BD 100 μg) and group III (BD 150 μg) than in group I (BD 50 μg). There was no significant difference between groups II and III ([Figure 4]).
Figure 4 Comparison of sedation level between groups according to modified Richmond sedation score.

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The effect of group assignment over time (including difference at baseline) was significant for systolic blood pressure. Statistically significant difference between groups was found according to % change of systolic blood pressure from baseline which is as follows at 15 min to at 90 min. There was significant difference between groups at baseline (P=0.002). The % change from the baseline for systolic blood pressure at 30 min was higher in group III (BD 150 μg) than in group I (BD 50 μg) and group II (BD 100 μg) (P value for % change from the baseline at 30 min was 0.045). But this was clinically insignificant and no treatment was required.

The effect of group assignment over time (excluding difference at baseline) was significant for diastolic blood pressure. There was no significant difference between groups at baseline (P=0.208). Statistically significant difference between groups according to % change of diastolic blood pressure from baseline is as follows at 5 min to at 90 min. At 30 min the % change of diastolic blood pressure from baseline was lower in group III (BD 150 μg) than in group I (BD 50 μg) and group II (BD 100 μg) (P=0.44). But this was clinically insignificant.

The effect of group assignment over time (including the difference at baseline) was significant for pulse rate. The groups showed significant difference in pulse rate at baseline (P=0.003). There was statistically significant difference between groups according to % change of pulse at 5 min, at 15 min, and at 90 min, but were lower in group III (BD 150 μg) than in group I (BD 50 μg) and group II (BD 100 μg) (P value at 5 min, 15 min, and 90 min, 0.039, 0.30, and 0.048, respectively). There were no noted adverse effects associated with lower heart rate and no case required treatment.

There was no statistically significant difference between groups according to the level of glucose [30 min (P=0.168), 12 h (P=0.256), and 24 h (P=0.261) postoperatively], cortisol [30 min (P=0.253), 12 h (P=0.131), and at 24 h (P=0.175) postoperatively], and C-peptide [30 min (P=0.116), 12 h (P=0.092), and 24 h (P=0.058) postoperatively).


  Discussion Top


Dexmedetomidine, as an alpha-2 adrenoceptor agonist, has been associated with prolonged analgesia after the administration of local anesthesia in a variety of routes and mechanisms, including neuraxial, perineural, intraarticular, and possibly even intravenous. Among these routes, the perineural route for dexmedetomidine has been the subject of increasing interest because it can significantly prolong the duration of analgesia after single-injection PNB. Thus, it can have important wide-ranging benefits for patients and providers [4]. Experimental and clinical studies, with various doses of dexmedetomidine between 20 and 150 mg as an additive to local anesthetics, have been published [1].

In the present study, the onset of sensory block was investigated, and the results showed that there is statistically significant difference between groups after 10 min (P=0.021) and after 15 min (P=0.034). But there was no clinically significant difference between three groups.

The results of Keplinger et al. [1] were consistent with our results who investigated 24 volunteers in four study groups of six. All volunteers received an ulnar nerve block with 22.5 mg ropivacaine alone, or mixed with 50, 100, or 150 μg dexmedetomidine. The block onset time decreased significantly in a dose-dependent manner (P<0.05).

In a match with our findings, Das et al. [7] studied 30 ml 0.5% ropivacaine+1 ml (100 μg) of dexmedetomidine and 30 ml 0.5% ropivacaine+1 ml normal saline administered in supraclavicular block. The result showed that the onset of sensory block was earlier in the dexmedetomidine group than the ropivacaine-only group, but they were not clinically significant (P>0.05).

In agreement with our results, Singh et al. [8] compared the addition of dexmedetomidine (1 μg/kg) to bupivacaine in supraclavicular BPB. The mean time for the onset of sensory block in the dexmedetomidine group was 11.26±1.53 min and in the bupivacaine only group was 19.08±1.7 min. Statistical analysis showed that the time for onset of sensory block in the dexmedetomidine group was significantly faster when compared with the bupivacaine only group (P<0.001).

Our results were also in agreement with a study done by Joseph et al. [6] comparing three different doses of dexmedetomidine. Group A (n=20) bupivacaine (30 ml) with dexmedetomidine (30 μg). Group B (n=20) bupivacaine (30 ml) with dexmedetomidine (50 μg). Group C (n=20) bupivacaine (30 ml) with dexmedetomidine (100 μg). The onset time of sensory and motor block was shortened in a dose-dependent manner: sensory A (16.3±3.31 min)>B (12.4±2.5 min)>C (7.35±1 min).

On the other hand a study of Zhang et al. [9], who studied the perineural administration of two different doses (50 and 100 μg) of dexmedetomidine in combination with ropivacaine prolongs axillary BPB. The results demonstrated no difference in the sensory onset time among the groups: dexmedetomidine (50 μg) 15.46±3.67 min and dexmedetomidine (100 μg) 13.34±6.43 min. This difference with our findings might have occurred as the neural tissue to connective tissue ratio decreases as the brachial plexus travel from the central to the peripheral.

Our results disagreed with Bhaskarbabu et al. [10], who compared the postoperative analgesic efficacy and safety of dexmedetomidine (50 μg) for brachial plexus blockade along with bupivacaine and lignocaine. The time of onset of sensory was almost similar in both the groups (10±2 control group vs. 9±1.5 dexmedetomidine group), P value more than 0.05. The study used adrenaline mixed with local anesthetic; this may have resulted in a decrease of systemic absorption of dexmedetomidine.

Also, Saraf et al. [3] assessed the effect of different doses of dexmedetomidine with ropivacaine in BPB (group RD 1 0.75% ropivacaine 19 ml+25 μg dexmedetomidine and group RD 2 0.75% ropivacaine 19 ml+50 μg dexmedetomidine). The onset of motor and sensory block was not statistically different among the groups. There was no statistical difference found between the two ropivacaine groups, therefore concluded that 0.75% does not add benefit and that 0.5% ropivacaine should be used to perform BPBs.

In this study, the onset of motor block showed statistically significant difference between groups after 10 min (P=0.037). Complete block was achieved after 15 min in all the three groups and for that there was no clinically significant difference between the three groups.

Supporting our results Joseph et al. [6] compared three different doses of dexmedetomidine (30, 50, 100 μg) to know the optimal dose of dexmedetomidine as adjuvant to bupivacaine in supraclavicular BPB for upper limb orthopedic surgeries. They found that the mean onset time of motor blockade in the 30 μg group (20.4±2.7 min) was significantly longer than the 50 μg group (16.15±2.89 min) which was significantly longer than the 100 μg group (12.15±2.81 min). Also, Reddy et al. [11] evaluated 50 or 100 µg of dexmedetomidine added to 0.5% levobupivacaine. They found that addition of 100 µg dexmedetomidine to 0.5% levobupivacaine hastens the onset of motor block compared with 50 µg dexmedetomidine in supraclavicular BPB.

Contrary to the present results, Das et al. [7] stated that the onset of motor block was earlier with 100 µg dexmedetomidine group than with the control group (19.96±1.28 vs. 20.26±1.28, P>0.05), but they were not clinically significant. Also, Kumari et al. [12] compared the effect of adding two different doses of dexmedetomidine to ropivacaine. They found that 2 µg/kg has motor block earlier than 1 µg/kg (7.38±0.97 vs. 5.42±1.21 min). This difference was statistically significant (P<0.001).

On the other hand, in the study by Keplinger et al. [1] the motor block onset time was unaffected by the dose of dexmedetomidine [50 μg; 0.4 h (0.3–2.0 h), 100 μg; 0.8 h (0.3–2.0 h), and 150 μg 0.4 h (0.1–1.0 h)]. In this study they investigated only six volunteers in each study group which made the study had some limitation and affect the results. Also, Zhang et al. [9] compared 50 and 100 μg dexmedetomidine with ropivacaine axillary BPB reported that the motor block onset time was similar in each group [motor block onset time (min) 50 μg; 16.66±6.99, 100 μg; 14.00±5.07]. That occurred possibly because of the different local anesthetics from our study.

Despite the variability in dexmedetomidine doses used, it is noteworthy to mention that a significant decrease in pain score and dose consumption of rescue analgesia was observed even with the lowest doses of dexmedetomidine, namely, 3 mg for intrathecal and 30 mg of peripheral administration. In the present study, pain scores assessed by VAS and the results showed that there was statistically high significant differences between the groups; BD50 and BD100 and BD150 at 12 and 24 h (P<0.001). And no significant difference between groups BD100 and BD150 at all time points. Also, the dose consumption of diclofenac as a rescue analgesia was highly significant in group BD50 and there was no significant difference between groups; BD100 and BD150 in the first 24 h postoperatively (P<0.001).

Similar results were observed by Reddy et al. [11] who evaluated 120 patients undergoing upper limb surgeries under BPB by 50 or 100 µg of dexmedetomidine added to 0.5% levobupivacaine. They concluded that the addition of 100 μg dexmedetomidine to 0.5% levobupivacaine produced a longer duration of analgesia compared with 50 μg dexmedetomidine in supraclavicular BPB. Duration of analgesia (min), 50 µg dexmedetomidine; 784.6±139.8, 100 µg dexmedetomidine 1041.6±140.2 (P<0.0001). Rescue analgesia in the form of diclofenac sodium injection was needed to be given to 20 (33.33%) patients in the 50 μg dexmedetomidine group

The Joseph et al. [6] study agreed with our finding. They compared three different doses of dexmedetomidine (30 µg ‘A,’, 50 µg ‘B,’ 100 µg ‘C’) to know the optimal dose of dexmedetomidine as adjuvant to bupivacaine. C group duration of analgesia (736±67.1 min) was significantly longer than that of B group (642±76.5 min) and the duration of analgesia for B group was significantly longer than that of group A (480±81.3 min). They concluded that dexmedetomidine 100 µg is an optimal dose to provide prolonged postoperative analgesia without much significant side effects.

In disagreement with our results, Fritsch et al. [13] conducted a study on patients who went under ultrasound-guided interscalene blocks using either 12 ml of 0.5% ropivacaine or 0.5% ropivacaine plus 150 μg dexmedetomidine. There were no differences in analgesic usage between the two groups. The total opioid analgesic dose for the first 24 h was lower in the dexmedetomidine group when compared with the ropivacaine group, but this result was not statistically significant [19.4 (SD, 15.7) vs. 23.3 (19.8) mg, P=0.39]. However, one of the limitations of this study was that when assessing the first 20 patients it was clear that patients requested analgesics despite having sensory and motor blocks with objective testing.

In the present study, the sedation score showed highly significant difference between groups. The mean±SD was (−0.90±0.72) for group I (−1.85±0.70) for group II, and (−1.90±0.72) for group III. And the sedation score ranged from (−2_0) for group I (−3_−1) for group II, and (−3_−1) for group III.

Spurthi and George [14] concluded that the quality of sedation produced by alpha-2 agonists differed from the sedation produced by drugs such as midazolam and propofol that acted on gamma-aminobutyric acid receptors. Sedation produced by alpha-2 agonists reflects decreased sympathetic nervous system activity, resulting in a calm patient who can be easily aroused to full consciousness.

Similar results were observed by Keplinger et al. [1], who assessed the dose dependency of dexmedetomidine when injected with ropivacaine for peripheral nerve blockade. The volunteers received an ulnar nerve block with 22.5 mg ropivacaine mixed with 50, 100, or 150 μg dexmedetomidine. Perineural application of dexmedetomidine caused clinically relevant sedation in a dose-dependent manner (P<0.001). The maximum sedation score was −4, observed in two volunteers in the 150 μg dexmedetomidine group. A study by Joseph et al. [6] which compared three different doses of dexmedetomidine (30, 50, 100 µg) in BPB concluded that the 100 µg group achieved more sedation level than the 50 µg group and the 50 µg group achieved more sedation level than the 30 µg group: [100 µg (4.65±10.4)>50 µg (3.8±1.15)>30 µg (2.95±1.05)].

On the other hand, Fritsch et al. [13] added 150 µg dexmedetomidine to 0.5% ropivacaine in the interscalene brachial plexus blockade. There was no significant difference in sedation (P=0.054), and there was no difference in the slope of the curves for the sedation scores over time (P=0.91). Patients in this study were subjected to elective shoulder surgery under general anesthesia which might affected the outcome of the sedation score.

The adverse events have been the most focused point when dexmedetomidine was used as an adjuvant for the BPB, because they were the most important evidence to judge the safety. Regarding our results, it is noteworthy that intraoperative hemodynamics change mostly did not need any special intervention. One patient in 100 µg group and two patients in the 150 µg group developed bradycardia. No other side effects or complications could be observed among the groups. Most of the studies showed reversible bradycardia less than 10% which was comparable to our study.

Our results agreed with a study done by Ozalp et al. [15] who evaluated the analgesic efficacy and side effects of dexmedetomidine (1 µg/ml) when added to patient-controlled interscalene analgesia with ropivacaine 0.2%. They concluded that the addition of dexmedetomidine 1 µg/ml to patient-controlled interscalene analgesia with ropivacaine provided similar pain scores while reducing local anesthetic consumption (P<0.05) and without causing any major side effects.

In a randomized trial, Vorobeichik et al. [16] noted that the side effects were transient, reversible, did not require any intervention, and did not cause any long-term consequence in any of the patients, when using perineural dexmedetomidine to enhance the quality of brachial plexus nerve blocks.

Also, in agreement with the results of the current study Kumari et al. [12] found no complications related to BPB using a nerve stimulator when using two different doses of dexmedetomidine (1 and 2 μg/kg) in supraclavicular BPB.

On the other hand, in disagreement with our study Zhang et al. [9] investigated the effects of adding dexmedetomidine in two different doses (50 and 100 µg) to ropivacaine on the efficacy of axillary BPB. Their study showed that by enhancement dose of dexmedetomidine, the side effects were increased. Bradycardia was observed in all the patients that received 100 µg dexmedetomidine; therefore, atropine was administrated to the nine patients. Moreover, six patients and three patients showed hypertension and hypotension, respectively. However, in patients who received 50 µg dexmedetomidine, only eight patients exhibited bradycardia, four patients received atropine, and two patients showed hypotension. It was suggested that this effect might be attributed to the use of 40 ml of 0.33% ropivacaine which is a relatively large dose. Also, the study was conducted in the axillary brachial plexus region which is a relatively vascular area than the interscalene brachial plexus region.

Also, Dhama et al. [17] evaluated the effect of two different doses of dexmedetomidine (25 and 50 µg) with ropivacaine in supraclavicular brachial plexus blockade. They found that dexmedetomidine-induced sympathetic block might have resulted in bradycardia and hypotension. Although all patients responded to ephedrine and atropine a higher dose of dexmedetomidine can cause hemodynamic instability. In this study, paresthesia-based technique had been used (classical approach, injecting drug solution posterolateral into the subclavian artery) which might have led to some intra-arterial injection resulting in hemodynamic instability.

Regarding systolic blood pressure, the results of the current study showed that there was a statistically significant difference between the three studied groups from baseline to after 15 min (P=0.024). Also, there was a statistically significant difference between the groups according to percentage change of systolic blood pressure from the baseline after 15 min to after 90 min (P value at 30 min 0.045). These results were clinically insignificant.

The diastolic blood pressure was affected, and the results of the current study showed that there was statistically significant difference between the three studied groups after 5 min (P=0.022), after 30 min (P=0.020), after 60 min (P=0.042), and after 75 min (P=0.024). Also, there was statistically significant difference between groups according to percentage change of the diastolic blood pressure from baseline after 5 min to after 90 min (P value at 30 min 0.044).

In agreement with the results of the current study was the study by Lomate et al. [18] who studied the use of 1 μg/kg dexmedetomidine in BPB. They stated that systolic arterial blood pressure levels during the period of anesthesia, that is, from 15 to 120 min were lower in the dexmedetomidine group than those in the control group (P<0.05), but it was clinically insignificant. Also, the diastolic arterial blood pressure levels during the period of anesthesia, that is, from 60 to 120 min were also significantly lower in the dexmedetomidine group than those in the control group (P<0.05). However, it was also clinically insignificant. In randomized trials by Vorobeichik et al. [16] investigating the addition of dexmedetomidine to local anesthetic in BPB. It has been found that dexmedetomidine increased the incidences of hypotension (P<0.0001) by increasing the dose. However, the effect of dexmedetomidine on blood pressure was moderate. The hypotensive effect was transient, reversible, and did not require any intervention. A double-blinded randomized trial was carried out to evaluate the effect of 50 or 100 µg of dexmedetomidine by Nallam et al. [19]. It was found that the incidence of hypotension was statistically not significant between the groups. This happened because they used 0.5% levobupivacaine which does not affect hemodynamics as bupivacaine does. A study by Das et al. [7] evaluated the effect of ropivacaine plus 100 μg dexmedetomidine in BPB. They found an insignificant hypotension effect with dexmedetomidine. Ropivacaine is more preferred because it is less cardiotoxic than other long-acting local anesthetics like bupivacaine.

The effect of dexmedetomidine on patients’ heart rate was also studied. Our results showed that there was a statistically significant difference between the three studied groups from baseline to after 45 min. Also, a statistically significant difference was observed between groups according to percentage change of the pulse after 5 min (P=0.030), 15 min (P=0.030), and 90 min (P=0.048) but these values were clinically insignificant.

The results of the present study were supported by the results of the study performed by Lomate et al. [18], who evaluated the efficacy of dexmedetomidine added to local anesthetics in infraclavicular BPB. They found that the heart rate during the period of anesthesia, that is, from 15 to 120 min was lower in the dexmedetomidine group than those in the control group (P<0.05). It was also clinically insignificant. No patient developed bradycardia.

On the other hand, Zhang et al. [9] evaluated the hypothesis that adding dexmedetomidine to ropivacaine prolongs axillary BPB. Side effects were significantly higher with the dexmedetomidine 100 μg group compared with the dexmedetomidine 50 μg group. In dexmedetomidine 100 μg group (n=15), bradycardia was observed in all patients, and nine of them were treated with atropine. In the 50 μg group (n=15), bradycardia was observed in eight patients, and four of them were treated with atropine. In this study they used 40 ml of ropivacaine which may affect hemodynamic responses especially with such large doses. Furthermore, Patki et al. [20] studied the postoperative analgesia by ropivacaine with dexmedetomidine as an adjuvant in supraclavicular BPB. They found that in the dexmedetomidine group, patients showed lower heart rate and reduced mean arterial pressure, which may be related with the systemic absorption of dexmedetomidine. Presynaptic activation of alpha-2 adrenoreceptors in the central nervous system inhibits the release of norepinephrine, terminating the prolongation of pain signals and their postsynaptic activation. Therefore, it reduces heart rate and blood pressure. Bradycardia is a reflex response to this transient response, and it persists subsequently due to central sympathetic inhibition. Baroreceptor reflex and heart rate response to pressor agent is well preserved with the use of dexmedetomidine, confirming hemodynamic stability.Fritsch et al. [13] tested the hypothesis that dexmedetomidine added to ropivacaine would safely enhance the duration of analgesia without adverse effects when compared with ropivacaine alone. The study found that dexmedetomidine 150 μg had significantly lower heart rates at all time points. Although bradycardia was more frequent in the dexmedetomidine group, there were no noted adverse effects associated with the lower heart rate.

The stress response to surgery is characterized by increased secretion of pituitary hormones and activation of the sympathetic nervous system. Insulin concentrations may decrease after the induction of anesthesia, and during surgery there is a failure of insulin secretion to match the catabolic, hyperglycemic response. Regarding the level of blood glucose, the results of the current study showed that the plasma concentration of glucose showed no statistically significant difference from the preoperative levels. Also, the release of corticotropin from pituitary stimulates cortisol secretion from the adrenal cortex. Cortisol secretion from the adrenal cortex increases rapidly after the start of surgery. Regarding the level of blood cortisol, the results of the current study showed that the plasma concentration of cortisol showed no statistically significant difference from the preoperative levels.

Yun et al. [21] found that the capillary glucose blood level was maintained at a similar level to the baseline until 24 h postoperatively in diabetes mellitus patients in whom dexmedetomidine was administered intraoperatively without change in blood glucose level. On the contrary, Görges et al. [22] evaluated and compared the effects of three different doses of dexmedetomidine (0.25/0.50/0.75 μg/kg and placebo) on blood glucose in children undergoing elective surgery. They found that the increases in blood glucose over time were significant within all four groups compared with the baseline, consistent with sympathetic surgical stimulation. And there was a suggestion of dose-related attenuation by dexmedetomidine by 30 min. This study suffered from a serious limitation, compared with our study, that the group age was not selected.

Important factors for the assessment of inflammation are ultrasensitive CRP, TNF-α, and IL-10. A stress response in the body can stimulate the secretion of CRP (an acute-phase protein). In the current study, acute-phase response triggered by the stress response was evaluated based on CRP levels. The result showed that the plasma concentration of CRP showed no statistically significant difference from preoperative levels.

In agreement to our results, Wan et al. [23] carried out a study to evaluate the effects of different doses of dexmedetomidine on analgesic efficacy and inflammatory cytokines in patients with laparoscopic surgery. Patients were divided into control group (group A) and three experimental groups with different doses of dexmedetomidine (group B: 0.25 µg/kg; group C: 0.5 µg/kg and group D: 1 µg/kg). They found that the CRP in in dexmedetomidine groups were significantly lower than those in the control group. And IL-10 in groups C and D were overtly higher than those in the other two groups, indicating that the use of dexmedetomidine suppressed body’s inflammation and protected it from invasion of pathogens. They concluded that medium dosage of dexmedetomidine cannot only effectively relieve the pain of laparoscopic patients but also regulated the secretion of inflammatory cytokines.


  Conclusion Top


We hypothesis that a dose of 100 µg of dexmedetomidine may be an ideal adjuvant to 0.5% bupivacaine for interscalene BPB as regards the onset of sensory block, onset of motor block, VAS score, rescue analgesia, sedation level, side effects and complications, hemodynamic variables, and stress response.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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