Introduction
The supraclavicular block is a regional anesthetic technique for upper extremity surgeries [1, 2, 3, 4, 5, 6]. It is a suitable alternative to general anesthesia [4, 6]. Local anesthetic drugs used in supraclavicular blocks provide good regional anesthesia, but these drugs have short-term effects. For this purpose, various adjuvants have been used to improve the quality and increase the length of the effect of local anesthetic drugs in supraclavicular block technique [3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ,13, 14, 15, 16, 17]. Although several studies have evaluated the efficacy of local anesthetics with adjuvant drugs, there is no consensus on a single drug for local anesthetics to increase block quality [8, 20]. 
Therefore, this study aims to compare the effect of dexmedetomidine-lidocaine and lidocaine-normal saline on the duration of sensory-motor blockade and hemodynamic parameters of supraclavicular block technique in upper extremity orthopedic surgeries.
Methods
This double-blind, randomized, controlled clinical trial was conducted on patients undergoing upper extremity fracture repair by the supraclavicular block technique in Poursina Hospital in Rasht, Iran. 
Inclusion criteria were age 18-60 years, type Ι-II elbow, and radial, and ulnar fractures according to the American Society of Anesthesiologists guidelines. Exclusion criteria were treatment with alpha-adrenoceptor agonists or antagonists, hypersensitivity to the drugs used in the study, coagulation disorders, pregnancy, peripheral neuropathy, liver, kidney or lung diseases, substance abuse, failure to develop complete sensory-motor blockade, and the need for general anesthesia during surgery. 
Patients were randomly assigned to two groups of lidocaine-dexmedetomidine (30 mL of 1.5% lidocaine plus 1 μg/kg of dexmedetomidine) and lidocaine-normal saline (30 mL of 1.5% lidocaine plus normal saline) using quadruple blocks. The total volume of solutions in both groups was 35 mL. One day before the surgery, the patients were visited by an anesthesiologist. After inserting an 18-gauge intravenous cannula in the healthy hand, 5 mL/kg normal saline solution was injected during 15-30 minutes. Then, patients underwent premedication with midazolam 0.02 mg/kg and fentanyl 1 μg/kg. The supraclavicular block method was performed under sterile conditions by a linear probe with high accuracy (SonoTouch) at a 10 MHz frequency. Pinprick test and Bromage scale were used to assess sensory and motor blockades, respectively. Evaluation of sensory blockade was performed every minute after injection in the areas innervated by the median, ulnar, radial, and musculocutaneous nerves until complete sensory blockade. The onset of sensory blockade was determined when a vague sensation was created, and the complete sensory blockage was determined when there was a complete loss of sensation. After recording the onset time of sensory and motor blockades, the amount of blockade, pain level based on the Verbal Rating Scale (VRS), and hemodynamic parameters (mean arterial pressure and heart rate) were measured every 5 minutes to 15 minutes, every 15 minutes to 60 minutes, and then every 30 minutes until the end of the surgery (Nine time points). Patients were also monitored for any side effects such as nausea and vomiting, hypotension, bradycardia, and hypoxia throughout the surgery. Finally, patients were compared in two groups regarding the onset time of sensory-motor blockade, duration of sensory-motor blockade and analgesia, hemodynamic parameters, and side effects. Data analyses were performed in SPSS v.21 (IBM Corp., Armonk, NY, USA). P<0.05 was considered statistically significant.
Results
Participants were 61 patients with a mean age of 43.90±10.92 years. Most of them were male, and had a body mass index value of 25.80±2.80 kg/m2. Regarding the mean arterial pressure (MAP), results showed a significant difference between the two groups at all time points (P<0.001) except before the blockade and five minutes after the blockade (Figure 1).  Regarding the heart rate, there was a significant difference between the two groups at all time points (P<0.001) except before the blockade and five and ten minutes after the blockade. There was a significant difference in MAP between the time points in each group and between the two groups (P<0.001). 
Regarding the onset time and duration of sensory and motor blockades, it was observed that the blockades were initiated faster and the blockade duration was longer in the lidocaine-dexmedetomidine group than in the lidocaine-normal saline (P<0.001).
Discussion
Although dexmedetomidine is commonly used in peripheral nerve blocks, the mechanism of action of this alpha-2 adrenergic receptor agonist is not clear. Based on the studies, the possible reason for the prolonged sensory and motor blockades caused by dexmedetomidine is vasoconstriction through the effect on alpha adrenergic receptors or creating peripheral analgesia by reducing the release of norepinephrine and increasing potassium conductance in C and A-Delta neurons responsible for transmitting pain signals, while analgesia and sedation occur centrally by inhibiting the release of substance P in the pain pathway located in the dorsal root ganglion and the locus coeruleus [21]. Studies have shown that dexmedetomidine increases the duration of analgesia and sensory-motor blockade regardless of the used dose [4, 6, 18]. 
Regarding the changes in intraoperative hemodynamic parameters in our study, there was a reduction in heart rate and MAP after the block in both groups, which was significantly more in the dexmedetomidine group than in the other group. The reason for this decrease may be the inhibition of sympathetic activity, resulting a decline in blood pressure and heart rate following the post-synaptic activity of the adrenoceptor in the central nervous system. The transient hypertensive response occurs due to the stimulation of α-2B subtype receptors in vascular smooth muscles. Bradycardia is a reflective response to this transient response and continues due to central sympathetic inhibition. Although hypotension and bradycardia are common side effects of dexmedetomidine, the baroreceptor reflex and heart rate response in the presence of dexmedetomidine are well preserved. Therefore, hypotension and bradycardia can be easily treated in these patients [20].
It can be concluded that adding 1µ/kg of dexmedetomidine to lidocaine in supraclavicular block method accelerates the onset of sensory and motor blockades and prolongs the blockade and postoperative analgesia without causing significant side effects such as hypotension and bradycardia. The findings of the present study can be helpful for anesthesiologists in choosing the best alternative drug with low side effects.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Ethics Committee of the Guilan University of Medical Sciences (Code: IR.GUMS.REC.1395.112) and was registered by the Iranian Registry of Clinical Trials (ID: IRCT201607276280N9). All ethical principles were considered in this study. All participants were informed about the study process and their information was kept confidential.

Funding
This study was funded by Guilan University of Medical Sciences.

Authors’ contributions
Study concept and design: Bahram Naderi Nabi, Abbas Sedighinejad, Mohammad Haghighi and Samaneh Ghazanfar Tehran; Acquisition, analysis, or interpretation of data: Mohammad Haghighi, Zahra Atrkarroushan and Mohammad Reza Habibi; Drafting the manuscript: Mohammad Reza Habibi and Samaneh Ghazanfar Tehran; Editing & Review: Mehran Soleymanha, Ahmadreza Mirbolook and Mohammad Reza Habibi; Investigation and resources: Mohammad Haghighi, Bahram Naderi Nabi and Abbas Sedighinejad; Statistical analysis: Zahra Atrkarroushan; supervision: Bahram Naderi Nabi.

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgements
The authors would like to thank the personnel of the Anesthesia Research Center of Guilan University of Medical Sciences and all patients for their cooperation in this study.

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