Comparison of Two Doses of Dexmedetomidine for Supraclavicular Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Dexmedetomidine is commonly used as an additive in supraclavicular brachial plexus block (SBPB). Due to its adverse effects such as bradycardia and hypotension, finding the appropriate dose of dexmedetomidine is the question. AIMS: We aimed to compare two commonly used doses of dexmedetomidine (1 μg/kg and 2 μg/kg) added to levobupivacaine in ultrasound-guided SBPB in terms of its effect on duration of analgesia, hemodynamics, and associated adverse effects. SETTINGS AND
DESIGN: This randomized, double-blinded prospective study was conducted over a period of 1.5 years in our tertiary care hospital.
MATERIALS AND METHODS: Clearance from the Institutional Ethical Committee and Clinical Trial Registry of India was taken. Ninety patients' physical status American Society of Anesthesiologists Classes I and II undergoing upper limb surgeries under SBPB were included in this study. Patients in Group I received 1 μg/kg dexmedetomidine, whereas patients in Group II received 2 μg/kg dexmedetomidine added to 20 cc levobupivacaine. The primary outcome measure was the duration of analgesia after administering the block. Secondary outcomes included effect on hemodynamics, duration of blockade, and adverse effects. STATISTICAL ANALYSIS: Statistical analysis was carried out using Stata Version 10. Unpaired t-test and Chi-square test were used.
RESULTS: The duration of analgesia and sensory and motor blockade were similar in both the groups. The heart rate (HR) and mean arterial pressure were statistically lower in Group II. The incidence of bradycardia and hypotension was more in Group II.
CONCLUSIONS: Increasing the dose of dexmedetomidine does not prolong the duration of analgesia, but it is associated with lower HR and blood pressure. Incidence of hypotension and bradycardia is also more. Hence, a lower dose of 1 μg/kg dexmedetomidine added to 0.5% levobupivacaine is a good balance between safety and efficacy.

INTRODUCTION

Brachial plexus block (BPB) is a common anesthetic technique used for upper limb surgeries. The major limitation of this technique is the fixed duration of sensory blockade and analgesia. Perineural catheters are expensive and are associated with infection.[1] Alternative to perineural catheters and adjuvants can be used.

Various adjuvants that are used are opioids, clonidine, dexamethasone, tramadol, etc.[2] Lately, dexmedetomidine, a highly selective α2 adrenergic agonist, has been used as an adjuvant to local anesthetics. Various clinical trials performed in both animals and humans have shown dexmedetomidine to be safe when used as an adjuvant to local anesthetic in subarachnoid, caudal, epidural, and BPBs.[345] Dexmedetomidine has been used in a dose ranging from 30 to 100 μg in human BPBs.[56] There have been contradictory reports regarding the safety of dexmedetomidine on increasing its dose. Nallam et al. in their study stated an increase in hypotension and bradycardia with a dose of 2 μg/kg, whereas Das et al. concluded a dose of 100 μg to be safe.[57] Hence, we designed this randomized controlled trial to compare 2 μg/kg dexmedetomidine with 1 μg/kg dexmedetomidine added to levobupivacaine, as these two doses are most commonly used. This is the first study to compare these two doses of the drug in ultrasound-guided supraclavicular BPB (SBPB).

The primary outcome measure was the duration of analgesia. Secondary outcomes included the effect on hemodynamics, onset and duration of sensory and motor blockade, and adverse effects.

MATERIALS AND METHODS

After Institutional Ethical Committee approval, this study was registered in Clinical Trial Registry of India. One hundred patients' physical status American Society of Anesthesiologists Classes I and II undergoing forearm/hand orthopedic surgeries were screened for this double-blinded randomized controlled study [Figure 1]. This study was conducted over a period of 1½ years between April 2016 and December 2017 in our tertiary care hospital. Patients with a history of cardiac, respiratory, hepatic, psychiatric, or renal disorder, patients on alpha agonists, and patients with known local anesthetic allergy were excluded from the study. All the patients were explained about the procedure and were made familiar with visual analog score. Written informed consent was obtained from the patients.

Figure 1

Consort statement

The patients were shifted to the operating room and standard monitors such a noninvasive blood pressure, peripheral oxygen saturation (SPO2), and electrocardiogram were connected. A 20-gauge intravenous (IV) cannula was inserted in the nonoperative arm and 5 ml/kg/h Ringer's lactate started.

The patients were randomized into two groups such as Groups I and II based on random numbers generated using MS Excel software (MS Office 7). The patient was placed in supine position with the head turned to contralateral side. After infiltrating 2 ml of 1% lignocaine subcutaneously, ultrasound-guided SBPB was performed by a trained anesthesiologist well versed in the procedure. The needle was targeted to reach the corner pocket between the first rib and subclavian artery and drug injected in aliquots of 3 ml. The spread of injected drug was observed in real time to achieve a satisfactory spread of the drug around the brachial plexus.

Patients in Group I received 20 cc 0.5% levobupivacaine with 1 μg/kg dexmedetomidine diluted to 1 ml with NS, while patients in Group II received 20 cc 0.5% levobupivacaine with 2 μg/kg dexmedetomidine. Both drugs were prepared by a staff nurse in a similar manner and were administered by an anesthesiologist not involved in making clinical assessment of the patients perioperatively. Patients were also not aware of the drugs administered to them. Total volume was 21 cc in both the groups.

Baseline values of hemodynamics: heart rate (HR), mean arterial pressure (MAP), and SPO2 were assessed for all the patients at baseline and after every 15 min till 3 h. Motor and sensory blockade was assessed every 3 min by the pinprick method in the dermatomal areas corresponding to median, radial, ulnar, and musculocutaneous nerve. Grading of sensory blockade was taken as grade 0: sharp pin felt, Grade 1: blunting of sensation, and Grade 2: no sensation. Grading of motor blockade was done as 0 = normal motor function with full flexion and extension of elbow, wrist, and fingers, 1 = decrease motor strength with the ability to move fingers and/or wrist only, and 2 = complete motor blockade with the inability to move fingers. Onset of motor/sensory blockade was the time between administration of local anesthetic to the Grade 2 motor/sensory blockade in any of the respective nerve territories. The block was considered a failure if the required blockade was not achieved after 30 min.

After the surgery, the patient was kept in the postoperative ward where the staff on duty assessed the pain hourly till 24 h. Pain score >4 was treated with iv paracetamol 1 g. Duration of analgesia was the time between the administration of local anesthetic till the requirement of first rescue analgesia. The total duration of the blockade was taken from the time of administration of a drug to the complete resolution of the anesthesia on all the nerves.

Any adverse effects, such as bradycardia (HR <40) and hypotension (MAP <60 mmHg), were noted. Bradycardia was treated with 0.02 mg/kg atropine while hypotension was treated with rapid infusion of 10 ml/kg Ringer's lactate. Other adverse effects such as nausea, vomiting, dryness of mouth, and complications such as pneumothorax, hematoma, local anesthetic toxicity, and postblock neuropathy were noted till 48 h postoperatively.

Statistical analysis

Statistical analyses were carried out using Stata version 10 (Stata Corp, Houston, Texas, USA). Appropriate statistical tests were applied after checking for the normality condition of continuous variables. Unpaired t-test was used to compare the duration of analgesia, blockade, and hemodynamics at various time periods. Chi-square test was used for testing association between two categorical variables. P < 0.05 was considered statistically significant.

Sample size was calculated on the basis of mean difference of duration of analgesia in a pilot study conducted on thirty patients over a period of 2 months. It was observed that the mean duration of analgesia was 12.25 h (standard deviation [SD] of 2.50 h) and 13.85 h (SD of 2.48 h) in Groups I and II, respectively. At 5% level of significance and 90% power to detect a clinically significant difference of 1.6 h, the estimated sample size was 45 patients in each group.

RESULTS

One hundred patients scheduled for upper limb surgeries were screened for this study. Four patients refused to participate and six patients had to be excluded due to incomplete blockade [Figure 1]. We analyzed a total of ninety patients.

Demographics

Table 1 presents the baseline demographic and surgical characteristics of patients in two groups. There was no significant difference (P > 0.05) between the two groups.

Table 1

Demographics and surgical characteristics

Analgesia and block characteristics

Table 2 presents the analgesia and blockade in two groups. The time of first rescue analgesia was similar in both Group I (13.40 ± 2.6 h) and Group II (13.8 ± 2.36 h). This was not statistically significant (P = 0.072). The total number of paracetamol doses required for rescue analgesia in both the groups in 24 h was also similar (P = 0.844).

Table 2

Comparison of analgesia and blockade between two groups

The average time for onset and duration of sensory and motor blockade was similar in both the groups. HR and MAP decreased significantly on increasing the dose [Figures 2 and 3]. The incidence of bradycardia (8 vs. 2) and hypotension (6 vs. 2) was more in Group II [Table 3]. Other adverse effects such as nausea, vomiting, dryness of mouth, and complications such as pneumothorax, hematoma, local anesthetic toxicity, and postblock neuropathy in the intra- and post-operative periods were not observed in any of the subjects.

Figure 2

Trend of heart rate over 3 h

Figure 3

Trend of mean arterial pressure over time

Table 3

Comparison of adverse effects

DISCUSSION

Our study shows no dose-dependent increase in duration of analgesia and sensory or motor blockade in the groups. A higher dose was associated with effects such as bradycardia and hypotension. Hence, according to us, a dose of 1 μg/kg seems to have a good balance between stable hemodynamics and satisfactory analgesia.

Dexmedetomidine is an alpha agonist with a higher selectivity for α2 receptors than α1. It has sedative, analgesic, and sympatholytic effects that blunt many of the cardiovascular responses seen during the perioperative period.[7] Although dexmedetomidine has been used frequently in peripheral nerve blocks, the mechanism of action of α2 adrenoceptor agonist is poorly understood. According to Marhofer et al., the prolongation of peripheral nerve block is mainly caused by local mechanisms, as systemic administration of the same dose did not increase the duration of action considerably. The local mechanisms include decreased norepinephrine release and α2 receptor-independent inhibitory effect on nerve fiber action potentials.[8]

Due to its clinical effects on sedation, hemodynamics, and analgesia, finding the optimum dose is the question. Various doses ranging from 30 to 100 μg dexmedetomidine have been used perineurally in human BPBs. We have compared 1 and 2 μg/kg of dexmedetomidine as these doses have been commonly used in human studies.

Kaygusuz et al. studied the effects of adding dexmedetomidine 1 μg/kg to levobupivacaine in BPB. They found that adding dexmedetomidine shortens the onset time and increases the duration of motor, sensory block and analgesia.[9]

Kaur et al. added 1 μg/kg dexmedetomidine to 0.25% levobupivacaine in SBPB shortening the onset of motor and sensory blockade and increasing the sensory, motor block and analgesia duration. They hypothesized that dexmedetomidine may be helpful in reducing the total concentration of levobupivacaine from 0.5% to 0.25%.[10]

Kathuria et al. added dexmedetomidine as an adjuvant to ropivacaine in SBPB. They found that addition of dexmedetomidine (50 μg) to 30 ml ropivacaine 0.5% in ultrasound-guided SBPB resulted in a quick onset and prolonged duration of blockade and analgesia.[11] All of these studies used a single dose and did not attempt to compare the various doses.

Keplinger et al. assessed the dose dependency of dexmedetomidine when added to ropivacaine for ulnar nerve block.[12] In their study, all volunteers received a block with 22.5 mg ropivacaine alone (R) or mixed with 50/100/150 μg dexmedetomidine. There was a significant dose-dependent increase in the mean duration (SD) of analgesia with dexmedetomidine: 8.7 h, 16.4 h (50 μg), 20.4 h (100 μg), and 21.2 h (150 μg). Brummett et al. have demonstrated a dose-dependent increase in analgesic effects of perineural dexmedetomidine (0.5, 2, 6, and 20 μg/kg) for sciatic nerve blocks on rats.[13]

Lately in a study done by Nallam et al., the authors have compared two doses of dexmedetomidine (1 μg/kg vs. 2 μg/kg) as an adjuvant to 0.5% levobupivacaine in peripheral nerve stimulator-guided SBPB. The concluded that increasing the dose increased analgesic duration and the incidence of adverse effects like bradycardia and hypotension.[7] In our study, we did not find an increase in analgesic duration. This could be due to the precise deposition of the drug using ultrasound, irrespective of the dosage used. The increase in adverse effects could be due to the systemic absorption of greater amount of drug leading to its central action. Dexmedetomidine acts centrally be stimulating α2 inhibitory neurons in the medullary vasomotor center of the brainstem causing a reduction in sympathetic outflow. In a study done by Esmaoglu et al., both HR and MAP decreased over time.[14]

We used ultrasound in our study has which is now considered the gold standard of regional anesthesia. Hence, the local anesthetic volume used was lower: 20 cc, unlike few other studies where the volume of local anesthetic was as high up to 40 cc.

There are some limitations of our study. We did not study the plasma levels of the drug after the block, hence cannot comment if the effect was due to perineural action or systemic absorption. Our sample size was small and hence more randomized controlled trials are required to validate our results.

CONCLUSION

1 μg/kg dexmedetomidine added perineurally to levobupivacaine in SBPB is a safer dose than 2 μg/kg with less sedation, bradycardia, and comparable analgesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.