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The Analgesic Efficacy of Dexmedetomidine as an Adjunct to Local Anesthetics in Supraclavicular Brachial Plexus Block: A Randomized Controlled Trial

Bharti, Neerja DNB; Sardana, Dinesh K. MD; Bala, Indu MD

doi: 10.1213/ANE.0000000000001006
Regional Anesthesia: Research Report

BACKGROUND: This study was designed to assess the effects of dexmedetomidine on the onset and duration of block and postoperative analgesia during supraclavicular brachial plexus block in patients undergoing upper limb surgeries.

METHODS: Sixty adult patients undergoing upper limb and hand surgeries were randomly allocated into 2 groups. The control group received equal volumes of 0.75% ropivacaine and 2% lidocaine with adrenaline, whereas the dexmedetomidine (dexmed) group received 1 μg/kg dexmedetomidine along with equal volumes of 0.75% ropivacaine and 2% lidocaine with adrenaline. A total volume of 0.5 mL/kg was administered in ultrasound-guided supraclavicular brachial plexus block in both groups. Patients were observed for hemodynamic stability, onset and duration of sensory and motor blockade, duration of analgesia, postoperative pain, and adverse effects.

RESULTS: The onset time of motor blockade was shortened and the duration of sensory, as well as motor, block was significantly prolonged in the dexmed group (P < 0.0001). The duration of postoperative analgesia was also longer in the dexmed group compared with the control group (median [interquartile range], 12 [10.5–13.5] hours and 17 [10.5–19.5] hours in control and dexmed group, respectively [95% confidence interval, −5 {−5, −4}, P < 0.0001]). The requirement for rescue analgesic during the 24-hour postoperative period was less in the dexmed group (P < 0.0001). Postoperative pain scores were comparable among groups except at 8 and 10 hours, when pain scores were lower in the dexmed group. Patients receiving dexmedetomidine were more sedated for 2 hours than the control group patients (P < 0.0001). No episode of bradycardia, hypotension, respiratory depression, or dizziness was reported.

CONCLUSIONS: We conclude that the addition of dexmedetomidine to ropivacaine-lidocaine prolonged the duration of supraclavicular brachial plexus block and improved postoperative analgesia without significant adverse effects in patients undergoing upper limb surgeries.

From the Department of Anesthesia and Intensive Care, PGIMER, Chandigarh, India.

Accepted for publication August 7, 2015.

Funding: None.

The authors declare no conflicts of interest.

The work has been presented at the international conference of Association of South-East Asian Pain Societies in Singapore, May 2013.

Address correspondence to Neerja Bharti, DNB, Department of Anesthesia and Intensive Care, PGIMER, Chandigarh 160012, India. Address e-mail to bhartineerja@yahoo.com.

The supraclavicular brachial plexus block may be used for surgical anesthesia alone or in conjunction with general anesthesia for managing perioperative pain in patients undergoing upper extremity surgery. Various adjuvants, including opioids,1,2 midazolam,3 magnesium sulfate,4 dexamethasone, and neostigmine,5 have been added to local anesthetics in an attempt to increase the duration of block and postoperative analgesia with the risk of various adverse effects. The efficacy of α2-adrenoceptor agonists has been established in a variety of regional anesthesia techniques.6 Clonidine, when added to lidocaine, prolonged the duration of anesthesia and analgesia after brachial plexus block,7 although the results with long-acting local anesthetics have been somewhat less impressive.8

Dexmedetomidine is a selective α2-adrenoceptor agonist and is approximately 8 times more potent than clonidine.9 In a study comparing the effect of dexmedetomidine, with clonidine added to lidocaine during Bier’s block, it was reported that dexmedetomidine was superior to clonidine in the quality of anesthesia, tourniquet tolerance, and postoperative analgesia.10 Dexmedetomidine is also reportedly safe and effective when administered with long-acting local anesthetics in peripheral nerve blocks.11,12 No significant histopathologic abnormalities were reported after intrathecal or perineural administration of dexmedetomidine.12,13

Various clinical trials have found that administration of dexmedetomidine with local anesthetics in neuraxial and peripheral nerve blocks prolonged the duration of sensory and motor blockade.13–18 However, there are limited data available on the use of dexmedetomidine in brachial plexus block. The aim of this study was to assess the effects on onset time and block duration and the postoperative analgesia of dexmedetomidine added to a ropivacaine-lidocaine mixture for supraclavicular brachial plexus block.

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METHODS

This prospective randomized double-blind study was approved by our Institutional Ethical Review Committee after reviewing the toxicity data regarding patient safety and the perineural use of dexmedetomidine administration by qualified experts. The study has been registered with the Clinical Trial Registry of India (Registration no CTRI/2013/12/004209).

After receiving written informed consent from the patients, 60 adults (20–60 years of age), ASA physical status I and II, scheduled for upper limb and hand surgeries were included. Patients receiving adrenoreceptor agonist or antagonist, having any neurologic deficit in the upper limb, history of cardiac disease, renal or hepatic failure, allergy to local anesthetics, and pregnant women were excluded from the study. All patients received 5 mg diazepam orally the night before surgery and were asked not to take any solids for 8 hours and liquids for 2 hours before surgery.

Patients were randomly allocated to 2 groups by using a computer-generated random number table. The group allocation was concealed in sealed opaque envelopes, which were opened just before administration of the block. The control group received equal volumes of 0.75% ropivacaine and 2% lidocaine with adrenaline (1:2,00,000), whereas the dexmed group received 1 μg/kg of dexmedetomidine along with equal volumes of 0.75% ropivacaine and 2% lidocaine with adrenaline. The drug solutions were prepared by an anesthesiologist not involved in data collection and administered as a single injection of 0.5 mL/kg up to a maximum of 40 mL.

The supraclavicular block was performed according to the previously described technique.19 The patient was placed in a supine position with the head turned 45° to the contralateral side. After skin sterilization, an ultrasound probe was placed in the coronal plane in the supraclavicular fossa to visualize the brachial plexus. After anesthetizing the skin and the subcutaneous tissue with 2 to 4 mL 2% lidocaine, a 22-gauge 50-mm insulated block needle (Stimuplex, B. Braun, Melsungen, Germany) was placed at the outer end of the probe and advanced along the long axis of the probe until the tip of the needle was located lateral to the round pulsating hypoechoic subclavian artery on the top of hyperechoic first rib. The appropriate needle position was confirmed by neurostimulation, and the study drug was injected under ultrasound guidance. The block performance time (time elapsed from probe positioning to the end of local anesthetic injection) and the number of attempts were recorded. Complications, including vascular puncture, Horner’s syndrome, pneumothorax, and phrenic nerve palsy, were noted. All blocks were done by experienced anesthesiologists who had performed at least 10 blocks with the research technique before beginning the study. Patients and the anesthesiologist performing the block were unaware of the group assignment.

Patients’ heart rate (HR), noninvasive blood pressure, and oxygen saturation were recorded at baseline, after administration of the block, and then every 5 minutes until the end of the surgery. Any episode of hypotension (20% decrease in mean arterial pressure in relation to baseline values), bradycardia (HR < 50 beats/min), or hypoxemia (SpO2 <90%) was recorded. Sensory block was assessed by pinprick sensation using a 3-point scale (0–2, 0 = normal sensation, 1 = decreased pain sensation to pinprick, 2 = loss of pain sensation to pinprick) in the median, ulnar, radial, and musculocutaneous nerve locations every 5 minutes for 30 minutes. Motor block was assessed by finger abduction (radial nerve), thumb and fifth finger pinch (median nerve), thumb and second finger pinch (ulnar nerve), and flexion of the elbow (musculocutaneous nerve) at the same time intervals. The onset time of sensory block (time since administration of block until loss of pain sensation in all 4 nerve territories) and motor block (time since administration of block until absence of movements in the hand and forearm) were recorded. A successful block was defined as complete sensory and motor blockade in all regions assessed within 30 minutes of local anesthetic injection. Anesthetic failure in the surgical area was controlled by local anesthetic infiltration. If the patient experienced pain during surgery, this was controlled by local anesthetic (2% lidocaine with adrenaline) infiltration or IV fentanyl 1 to 2 μg/kg. Surgical effectiveness was defined as surgery without patient discomfort and the need for supplementation of the block. Sensory and motor blocks were assessed every 30 minutes after the surgery until block resolution. Duration of sensory block was defined as the time interval between the administration of the block and the complete resolution of anesthesia on all nerves. Duration of motor block was defined as the time interval between the administration of the block and the recovery of complete motor function of the hand and forearm.

After completion of surgery, the patients were monitored in the postanesthesia care unit for 24 hours by an anesthesiologist blinded to the patient’s group allocation. HR and blood pressure were recorded every 30 minutes for 2 hours, every 1 hour for 6 hours, every 2 hours until 12 hours, and then at 24 hours postoperatively. Postoperative pain was assessed at the same time using visual analog scale (VAS, 0–10, 0 = no pain, 10 = maximum imaginable pain). Injection diclofenac 1 mg/kg IV was given if VAS was >4. If pain persisted after 30 minutes of administration of diclofenac then IV tramadol 1 mg/kg was administered. The duration of analgesia (time between administration of block and first rescue analgesic) and the total analgesic requirement in the 24 hours after surgery were noted. Postoperative sedation was assessed by using a 4-point scale (1 = wide awake; 2 = mild sedation, responding to verbal command; 3 = moderate sedation, responding to glabellar tap; 4 = deep sedation, responding to deep painful stimulus). The incidence of postoperative nausea and vomiting (PONV) was recorded using a 4-point objective score (1 = no PONV; 2 = mild nausea, no vomiting; 3 = excessive nausea or vomiting; 4 = vomiting ≥2 times). Any side effects of dexmedetomidine such as dry mouth, hypotension, bradycardia, and dizziness were recorded. Patients were followed up for 7 days for any neurologic deficit.

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Statistical Analysis

Statistical analysis was performed using statistical software SAS 9.4 (SAS Institute Inc., Cary, NC). The normally distributed data were compared with independent 2-sample t test, whereas the categorical or skewed data were compared by Mann-Whitney U test. HR and blood pressure were compared with repeated-measures analysis of variance followed by post hoc analysis with Bonferroni correction. The onset and duration of block, duration of analgesia, pain scores, and sedation scores were compared by Mann-Whitney U test. Survival analysis was performed for onset of sensory block, the onset of motor block, duration of sensory block, duration of motor block, and duration of analgesia. The confidence intervals for differences between group medians were calculated by Hodges-Lehmann estimate for a Wilcoxon rank sum test using PROC NPAR1WAY of SAS 9.4. The sample size was calculated on the basis of a pilot study taking a mean value of 800 min and SD 240 min for the duration of postoperative analgesia using a 2-group t test with a 0.05 2-sided significance level. A 25% difference in the duration of the postoperative analgesia was considered a clinically relevant difference. For a power of 0.9, we required 27 patients in each group. A total of 60 patients were recruited in the study to compensate for possible dropouts.

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RESULTS

Fifty-four patients completed the study. Three patients refused regional anesthesia, whereas 2 patients in the control group and 1 patient in the dexmed group were excluded from the analysis because they were discharged home on the same day after surgery. Therefore, 27 patients in each group were analyzed.

The groups were comparable with respect to demographic data and the duration of surgery (Table 1). The surgical procedures were mainly reconstructive surgeries of forearm and hand in both groups. The block performance time and the number of attempts required to perform the block were also comparable between groups. Two patients in the dexmed group had an inadequate block at 30 minutes and required block supplementation with local anesthetics. Two patients in the control group were very anxious and required midazolam supplementation during the intraoperative period. None of the patients required fentanyl or block supplementation during surgery in either of the 2 groups.

Table 1

Table 1

The addition of dexmedetomidine to ropivacaine-lidocaine mixture decreased the onset time of motor block (Table 2). The duration of sensory block and motor block was significantly prolonged in the dexmed group compared with the control group (P < 0.0001). The duration of postoperative analgesia was also prolonged in the dexmed group than control group (median [interquartile range], 12 [10.5–13.5] hours and 17 [10.5–19.5] hours in the control and dexmed group, respectively, [95% confidence interval −5 {−5, −4}, P < 0.0001]).

Table 2

Table 2

The total requirement of diclofenac during the 24-hour postoperative period was significantly less in the dexmed group compared with control group (median [interquartile range], 2 [1–3] doses and 2 [1–3] doses in the control and dexmed group, respectively, P < 0.0001). None of the patients required tramadol. Postoperative pain scores were comparable in both groups except at 8 and 10 hours postoperatively, when the VAS scores were lower in the dexmed group compared with the control group (Fig. 1).

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Figure 4

Figure 4

Heart rate and mean arterial pressure were lower in the dexmed group compared with the control group at each point of time, except at base line (Figs. 2 and 3). However, no episode of hypotension or bradycardia was reported. Although the patients in the dexmed group were sedated at 30, 60, and 90 minutes and 2 hours (Fig. 4), they were easily arousable. None of the patients had respiratory depression or hypoxia. After 2 hours, no sedation was observed in either group. None of the patients had dizziness or PONV.

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DISCUSSION

In the present study, we found that the addition of dexmedetomidine to a ropivacaine-lidocaine mixture in supraclavicular brachial plexus block significantly prolonged block duration, as well as postoperative analgesia, and reduced the requirement of a rescue analgesic in patients undergoing upper limb surgeries. Furthermore, the onset time of motor block was shorter in patients receiving dexmedetomidine.

In a recent meta-analysis (total 4 trials, 1 on supraclavicular block),14–17 Abdallah and Brull20 reported that administration of dexmedetomidine as a part of brachial plexus block resulted in significant prolongation of motor block duration and an increase in time to first analgesic request compared with local anesthetic alone. Dexmedetomidine hastened sensory block onset when used intrathecally but not perineurally. A recent study using dexmedetomidine and ropivacaine for interscalene block also demonstrated an increase in block duration and lower pain scores in patients receiving dexmedetomidine compared with those in a control group.21

The mechanism by which α2-adrenergic receptor agonists produce analgesia is likely to be multifactorial. Peripherally, α2-agonists produce analgesia by reducing the release of norepinephrine and causing α2-receptor–independent inhibitory effects on nerve fiber action potentials. Centrally, they produce analgesia by the inhibition of substance P release in the nociceptive pathway at the level of dorsal root neuron and by the activation of α2-adrenoceptors in the locus coeruleus.6,22 Brummett et al.11 showed that the analgesic effect of perineural dexmedetomidine is caused by enhancement of a hyperpolarization-activated cation channel, which prevents the returning of nerve from a hyperpolarized state to a resting membrane potential state for subsequent firing.

Hypotension and bradycardia are considered to be the most prominent adverse effects of α2-agonists. Esmaoglu et al.14 reported that the addition of 100 μg dexmedetomidine to 0.5% levobupivacaine caused bradycardia (HR <50 beats/min) in 7 of 30 patients. In the present study, although we noticed lower HRs (50–60 beats/min) in the dexmed group, none of our patients had bradycardia or hypotension. This may be because we used a smaller dose of dexmedetomidine. Similarly, other studies using a similar dose of dexmedetomidine found no episode of hypotension or bradycardia in patients receiving dexmedetomidine.16–18 No other adverse effects, including dizziness, pruritus, respiratory depression, or hypoxemia, were reported.

The safety of the perineural administration of dexmedetomidine has been well established in experimental studies. An animal study showed that perineural administration of dexmedetomidine up to 40 μg/kg had no effect on either nerve axons or myelin sheaths and might even attenuate the acute perineural inflammation induced by bupivacaine without causing nerve damage.12 In humans, dexmedetomidine has been safely used up to 2 μg/kg in neuraxial blocks.23 We cautiously used a lower dose of dexmedetomidine in the present study. No neurologic deficit was observed in any patient receiving dexmedetomidine.

Inadequate block was observed in 2 patients in the dexmed group. One patient was obese and another had nerve deformity due to leprosy. However, other complications, such as vascular puncture, Horner’s syndrome, and pneumothorax, were not reported in either of the 2 groups.

One limitation of our study is that we used a combination of ropivacaine and lidocaine. The theoretical basis of using a mixture of local anesthetics was to compensate for the short duration of action of lidocaine and the long latency of ropivacaine. An additional limitation of our study is that we did not measure the plasma levels of dexmedetomidine. However, we used 1 μg/kg dexmedetomidine for perineural administration; this dose has been safely used IV for postoperative analgesia. In addition, we did not take systemic control, because it has been proven in experimental studies that the analgesic effect of perineural dexmedetomidine is peripheral not central.24,25 A recent study in human volunteers has also shown similar results.26

We conclude that the addition of dexmedetomidine (1 μg/kg) to local anesthetics in supraclavicular block prolongs block duration and postoperative analgesia. Although decreased HR and blood pressure, as well as increased sedation, was noted in the dexmed group, there were no significant adverse events. Further studies are needed to determine the efficacy and safety of dexmedetomidine in other peripheral nerve blocks.

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DISCLOSURES

Name: Neerja Bharti, DNB.

Contribution: This author helped design the study, conduct the study, analyze the data, and prepare the manuscript.

Attestation: Neerja Bharti attests to the integrity of the original data and the analysis reported in this manuscript

Name: Dinesh K. Sardana, MD.

Contribution: This author helped conduct the study, collect the data, and analyze the data.

Attestation: Dinesh K. Sardana attests to the integrity of the original data and the analysis reported in this manuscript. Dinesh K. Sardana is the archival author.

Name: Indu Bala, MD.

Contribution: This author helped design the study, and prepare the manuscript.

Attestation: Indu Bala approved the final manuscript.

This manuscript was handled by: Terese T. Horlocker, MD.

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