Comparing Efficacy of Perineural Dexmedetomidine with Intravenous Dexmedetomidine as Adjuvant to Levobupivacaine in Supraclavicular Brachial Plexus Block.

BACKGROUND: Prolonging postoperative analgesia using various adjuvants has become a trend in regional anesthesia practice. There are literally no studies where different routes of dexmedetomidine have been compared in supraclavicular block. We compared perineural dexmedetomidine and intravenous (i.v.) dexmedetomidine when used as an adjuvant with levobupivacaine using a nerve stimulator-guided supraclavicular block.
METHODOLOGY: Sixty patients of either sex, aged between 18 and 60 years, belonging to the American Society of Anesthesiologists Physical Status Classes I and II posted for upper limb surgeries under supraclavicular brachial plexus block were enrolled for a prospective observational study. The patients were categorized into two groups: Group levobupivacine with perineural dexmedetomedine (LDP) received 20 mL of 0.5% levobupivacaine plus 10 mL of 2% lignocaine plus 1 μg.kg-1 dexmedetomidine perineurally, and Group levobupivacaine with intravenous dexmedetomedine (LDV) received 20 mL of 0.5% levobupivacaine plus 10 mL of 2% lignocaine and 1 μg.kg-1 dexmedetomidine in 50 mL of normal saline administered as infusion over 10 min and given 10 min before start of the supraclavicular block. Onset and duration of sensory and motor blocks, hemodynamic variables, adverse effects, and duration of analgesia were assessed.
RESULTS: Demographic profile, onset and duration of sensory and motor block, and duration of analgesia were comparable in both the groups. The incidence of hypotension was high in Group LDV compared to Group LDP, which was found to be statistically significant (LDP - 2, LDV - 11, P < 0.005). Twelve patients in LDV group had Ramsay sedation score >3 whereas In LDP group two patients had Ramsay Sedation score >3 which was statistically significant (LDP - 2, LDV - 12, P < 0.002).
CONCLUSION: The i.v. dexmedetomidine is equally effective as compared to perineural dexmedetomidine with respect to onset and duration of block and duration of analgesia but has greater hemodynamic instability. Copyright:

INTRODUCTION

Supraclavicular brachial plexus block has been the choice of anesthesia for upper limb surgeries over the past few decades. Since then, array of techniques and newer drugs with higher safety profile are being introduced, which has led to decrease mortality and morbidity in patients and at the same time eased the life of clinicians.

Levobupivacaine has gained more attention in recent past in the peripheral nerve blocks due to its lesser cardiotoxic side effects when compared to bupivacaine.[1]

The use of α2 agonists with local anesthetics has proven to reduce their overall dosage and thereby reduce the risk of local anesthetic toxicity. They have also shown to improve the quality of anesthesia and to prolong the postoperative analgesia without increasing adverse effects.[234] Being an imidazole compound, dexmedetomidine has higher selectivity and more specificity to α2 receptors. Perineural dexmedetomidine when added to levobupivacaine has shown to potentiate its effects, providing better quality of anesthesia and postoperative analgesia.[5] Intravenous (i.v.) dexmedetomidine, when used during regional anesthesia, has shown to prolong sensory and motor blockade in addition to sedation and postoperative analgesia.[67] The present study was designed to evaluate the efficacy of i.v. and perineural dexmedetomidine when added to levobupivacaine during supraclavicular brachial plexus block.

METHODOLOGY

A prospective observational study was carried out between February and December 2018 after approval from the institutional ethics committee in January 2018. Written informed consent was obtained before the start of the surgery.

Sixty patients of either sex, between 18 and 60 years, belonging to the American Society of Anesthesiologists Physical Status (ASA-PS) Classes I and II posted for upper limb surgeries under supraclavicular brachial plexus block were enrolled for the study. The patients who refused to give consent, those having severe systemic illness and bleeding disorders, pregnant women, and those who had local site infection, allergic to study drugs, peripheral neuropathy, or motor neuron disorders, and those who had partial sensory and motor blocks and surgeries which lasted >2 h or <30 min were excluded from the study. The first 30 patients who fulfilled the inclusion and exclusion criteria were categorized into Group LDP and the next 30 patients into Group LDV.

Group LDP: 20 mL of 0.5% levobupivacaine plus 10 mL 2% lignocaine plus 1 μg.kg-1 dexmedetomidine perineurally

Group LDV: 20 mL of 0.5% levobupivacaine plus 10 mL 2% lignocaine and 1 μg.kg-1 dexmedetomidine in 50 mL of normal saline administered as infusion over 10 min and given 10 min before the start of the supraclavicular block.

The patients were premedicated with 0.5 mg of tablet alprazolam and 150 g of tablet ranitidine on the previous night of surgery and were allowed to fast for 8 h for solids and 2 h for liquids. On the day of surgery, all patients were inserted 20-gauge i.v. cannula on the nonoperative limb and were coloaded with 10–15 mL of Ringer lactate solution. Baseline vitals such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation were recorded before block performance. The patients in Group II received 1 μg.kg-1 dexmedetomidine in 50 mL normal saline which was administered over 10 min, and block in these patients was performed after 10 min of infusion.

Both group patients (I and II) were placed in a desired position (supine, head turned to opposite side, lowering the shoulder, and elbow flexed), and block was performed using nerve stimulator technique (Stimuplex R Dig RC., B Braun Medical Inc., Malaysia). Once the desired distal response was seen at current intensity of 0.5 mA, drug was injected slowly with frequent aspirations while carefully observing patients.

Sensory block was assessed using pinprick method. Sensory block was assessed along radial, ulnar, median, and musculocutaneous nerve and was considered complete when there was a complete loss of sensation. Sensory block was graded using a 3-point scale: 0 – normal, 1 – loss of sensation to pinprick (analgesia), and 2 – loss of sensation to touch (anesthesia). Onset of sensory block was defined as the time interval between the completion of local anesthetic injection and loss of touch sensation (Grade 2); duration of sensory block was defined as the time interval after the completion of local anesthetic injection to complete resolution of sensation (Grade 0).

Motor block was assessed using 3-point modified Bromage scale: grade 0 − normal motor function with full extension and flexion of elbow, wrist, and fingers, Grade 1 − decreased motor strength, with ability to move only fingers, and Grade 2 − complete motor block with inability to move elbow, wrist, and fingers.[8] Onset of motor block was defined as the time interval between completion of local anesthetic injection and loss of complete motor power (Grade 2); duration of motor block was defined as the interval between completion of local anesthetic injection and complete resolution of motor power (Grade 0). The duration of analgesia was defined as the time interval between completion of local anesthetic injection and the first analgesic request.

The sensory and motor blocks were assessed every 5 min for 30 min after injection of local anesthetic. The block was considered failure when patients had complete sensation and motor power (Grade 0) even after 30 min of local anesthetic injection. Such patients were given general anesthesia and excluded from the study. The block was considered incomplete when patient experienced pain (Grade 1) along with one of the dermatomes and such patients were supplemented with injection fentanyl.

The patients were assessed for sedation using Ramsay sedation score. HR, saturation (SpO2), SBP, and DBP were assessed every 5 min for the first 30 min and every 15 min till the end of surgery.

Pain was assessed postoperatively using visual analog scale (VAS) 0–10, and patients with VAS ≥ 4 received injection diclofenac sodium 75 mg as rescue analgesia and the time was also noted. The time interval between local anesthetic injection and the first analgesic dosage was considered as the duration of analgesia.

Postoperatively, the patients were monitored for sedation and vital parameters (HR, SpO2, SBP, and DBP) every hourly until block resolution. The patients were monitored for adverse effects such as hypotension (20% decrease from baseline), bradycardia (<50 bpm), hypoxia (SpO2 < 90), and nausea and vomiting both intra- and post-operatively.

Statistics

The sample size was calculated from previous study where the onset of sensory block was taken as one of the variables. If a difference of 1.03 min, between two groups, is considered significant with 0.8 taken as standard deviation, 25 patients in each group were needed to detect a statistically significant difference at 80% power and alpha = 0.05. Considering the dropout rate and better validation of the results, 30 were chosen for each group. Statistical analysis was performed using The data was analysed using Statistical Package for the Social Sciences (SPSS) Version 20.0 software (SPSS Inc., Chicago, IL, USA). Data were represented as mean ± standard deviation, numbers, and percentages. Age, onset and duration of sensory and motor blocks, hemodynamic parameters, and duration of surgery were analyzed using independent Student's t-test. Sex ratio and ASA-PS classes were compared using the Chi-square test. P < 0.05 was considered statistically significant, and P < 0.01 was considered highly significant.

RESULTS

Sixty patients posted for upper limb surgeries under supraclavicular block satisfying the inclusion criteria were considered for this observational study. First 30 eligible patients were assigned into Group LDP, and the second eligible 30 patients into Group LDV. Patients who had received general anesthesia due to inadequate block were dropped out from the study and were not considered in analysis.

Demographic profile such as age, sex ratio, and ASA-PS was compared in both groups including surgical characteristics such as duration of surgery and type of surgeries [Table 1]. Baseline vital parameters were compared in both the groups [Table 2].

Table 1

Demographic data and surgical characteristics

Demographic profile	Group LDP (n=30)	Group LDV (n=30)	P
Age (years)	37.53±11.2	42.63±13.9	0.12
Weight (kg)	59.57±8.1	60.07±8.3	0.81
Sex ratio (males/females)	21/9	22/8	0.77
ASA grading (I/II)	19/11	12/18	0.07
Type of surgery
Lower end of humerus	11	11	0.13
Radius and ulna	18	15
Hand	1	4
Duration of surgery (min)	76.67±33.6	76.50±28.7	0.98

Parametric data expressed as mean±SD, categorical data (sex, type of surgery) expressed as frequency (%) using Pearson’s Chi-square analysis P<0.05: Statistically significant. LDP=Levobupivacaine perineural dexmedetomidine, LDV=Levobupivacaine intravenous dexmedetomidine. ASA=American Society of Anesthesiologists, n=Number of patients, SD=Standard deviation

Table 2

Baseline vitals

Vital signs	Mean±SD		P
	Group LDP (n=30)	Group LDV (n=30)
HR (bpm)	90.00±10.3	8.83±11.2	0.67
SBP (mmHg)	128.97±15.7	129±13.6	0.99
DBP (mmHg)	81.07±8.2	81.30±8.0	0.87
Saturation (SpO2)	97.80±1.2	98.10±0.8	0.25

P<0.05: Statistically significant. LDP=Levobupivacaine perineural dexmedetomidine, LDV=Levobupivacaine intravenous dexmedetomidine, SD=Standard deviation, n=Number of patients, SBP=Systolic blood pressure, DBP=Diastolic blood pressure, HR=Heart rate

The mean duration of onset of sensory and motor blocks in Group LDP was 7.58 ± 1.6 min and 9.22 ± 2.6 min, respectively, whereas, in Group LDV, the mean duration of onset of sensory and motor blocks was 7.06 ± 2.0 min and 10.10 ± 2.83 min, respectively. The results were statistically insignificant.

The duration of sensory and motor blocks and duration of analgesia were comparable in both the groups. The mean duration of sensory block was 511.67 ± 76.13 min in Group LDP compared to 491.33 ± 69.11 min in Group LDV. The mean duration of motor block in Group LDP was 492.50 ± 93.22 min and in Group LDV was 464.17 ± 88.86 min. The mean duration of analgesia was 590.33 ± 103.17 in Group LDP and 563.33 ± 112.16 min in Group LDV [Table 3].

Table 3

Block characteristics and opioid consumption

Variables	Mean±SD		P
	Group LDP (n=30)	Group LDV (n=30)
Onset of sensory block (min)	7.58±1.6	7.06±2.0	0.27
Onset of motor block (min)	9.22±2.6	10.10±2.83	0.22
Duration of sensory block (min)	511.67±76.13	491.33±69.11	0.28
Duration of motor block (min)	492.50±93.22	464.17±88.86	0.23
Duration of analgesia (min)	590.33±103.17	563.33±112.16	0.33

LDP=Levobupivacaine perineural dexmedetomidine, LDV=Levobupivacaine intravenous dexmedetomidine, SD=Standard deviation, n=Number of patients, P=Significance (P<0.05)

The incidence of hypotension was high in Group LDV compared to Group LDP, which was found to be statistically significant (LDP – 2, LDV – 11, P < 0.005). Hypotension was treated with 500 mL of bolus normal saline and small doses of injection mephentermine. Three patients in LDV Group had bradycardia but none in LDP Group. Only one patient required injection atropine, whereas the other two were made to wake up. Twelve patients in LDV group had ramsay sedation score >3 whereas in LDP group two patients had ramsay Sedation score >3 which was statistically significant. (LDP – 2, LDV – 12, P < 0.002) [Table 4].

Table 4

Incidence of side effects during intra- and postoperative period

Side effects	Group LDP (n=30), n (%)	Group LDV (n=30), n (%)	P
Hypotension	2 (7)	11 (37)	0.005*
Bradycardia	0	3 (9)	-
Respiratory depression	1 (3)	3 (9)	0.30
Sedation >3	2 (7)	12 (40)	0.002*
Nausea and vomiting	0	0	0.48
LA toxicity	0	0	-
Neurological deficit	0	0	-

LDP=Levobupivacaine perineural dexmedetomidine, LDV=Levobupivacaine intravenous dexmedetomidine. Data expressed as frequency (%) using Pearson’s Chi-square analysis. n=Number of patients, LA=Local anesthetic, P=Significance (P<0.05)

Respiratory depression was seen in one of the patients in LDP group and three in LDV group which was treated by supplemental oxygen and nasopharyngeal airway.

None of the patients had nausea, vomiting, or any other side effects during intra- or postoperative monitoring.

DISCUSSION

In our study, we demonstrated that perineural and i.v. dexmedetomidine when used with levobupivacaine were equally effective in prolonging sensory and motor block and duration of analgesia. However, i.v. dexmedetomidine group had higher hemodynamic instability when compared to perineural group.

Levobupivacaine, an S(-) enantiomer of bupivacaine, has been increasingly used in various regional techniques. Several studies have shown levobupivacaine and bupivacaine to have similar block characteristics when used during peripheral nerve blocks.[91011] The use of adjuvants (opioids, epinephrine, and α2 agonists) along with levobupivacaine has shown to increase the duration and quality of regional anesthesia.[12]

Some studies have shown that dexmedetomidine scored better than clonidine with respect to block quality and postoperative analgesia; henceforth, we decided to use dexmedetomidine with levobupivacaine for our study.[1314]

Dexmedetomidine, α2 agonists, a dextrorotatory S-enantiomer of medetomidine having high-α2 selectivity when compared to clonidine, is being currently used in the peripheral nerve block along with various local anesthetics. Its action in the peripheral nerve block is found to be multifactorial. It is known to reduce the release of norepinephrine and inhibit nerve action potentials,[1516] mainly by decreasing the release of norepinephrine. Action through α2 adrenergic receptors present peripherally is responsible for its analgesic action. Its other pharmacologic effects such as sedation and anxiolysis provide added benefits for the patients receiving peripheral nerve blocks.[17]

A study done by Esmaoglu et al. showed that addition of dexmedetomidine to lignocaine for i.v. regional anesthesia improved quality of anesthesia and postoperative analgesia without causing side effects. Studies done by Kaur et al. and Abdallah et al. showed when dexmedetomidine used as an adjuvant with various local anesthetics improved the quality of anesthesia and reduced postoperative analgesic requirement.[318] These above studies reflect that there is a possibility of peripheral presence of α2 adrenergic receptors and the drug can be used perineurally.

Similarly, i.v. dexmedetomidine prolongs the local anesthetic duration through inhibition of norepinephrine release and stimulation of α2 in locus coeruleus, which is the site of descending medullospinal noradrenergic pathway. This stimulation terminates propagation of pain signal leading to analgesia.

Esmaoglu et al. in their study used 40 mL of 0.5% of levobupivacaine with 100 μg of dexmedetomidine, but we considered 20 mL of 0.5% levobupivacaine with 10 mL of 1% lignocaine, considering peripheral action of dexmedetomidine.[12] Our study demonstrated dexmedetomidine to reduce dosage of local anesthetics in the peripheral nerve block.

Studies have shown 2 μg.kg-1 of dexmedetomidine to be the effective dosage in prolonging peripheral nerve block, irrespective of the route administered. A study was done by Jung et al. showed that 2 μg.kg-1 of dexmedetomidine when used perineurally was the most optimal dosage for brachial plexus block after they compared with 1 and 1.5 μg.kg-1 of dexmedetomidine. However, general anesthesia was used which cannot be generalized and also more hemodynamic instability was noted. A study done by Kang et al. showed that i.v. dexmedetomidine at a dose of 2.0 μg.kg-1 significantly increased the duration of analgesia when compared with 0.5 μg.kg-1, 1 μg.kg-1, and placebo in patients undergoing arthroscopic shoulder surgery under brachial plexus block. However, with this dosage, more use of ephedrine was reported and block characteristics were not completely evaluated.[19] Similar to various studies, we considered using weight-based dosing of dexmedetomidine. We considered 1 μg/kg of dexmedetomidine in both perineural and i.v. groups to avoid the difference of results shown in the above studies. However, our study showed that demographic profile and block characteristics were comparable in both the groups, but more hemodynamic instability was observed with i.v. group. Further trials have to be done regarding the optimal dose for both perineural and i.v. routes in brachial plexus block.

Some of the studies which have compared perineural and intravenous dexmedetomidine have shown conflicting results when used during peripheral nerve block. Abdallah et al. demonstrated that both perineural and i.v. dexmedetomidine can effectively prolong the interscalene block analgesic duration and reduce the opioid consumption without prolonging motor blockade, which was in accordance with our study.[20]

There was a study done on healthy volunteers where, for the first time, perineural (low dose, 20 μg) and i.v. dexmedetomidine were used for ulnar nerve blockade for sensory blockade. Results showed that perineural dexmedetomidine prolonged sensory blockade more than that of systemic administration. This study could not be generalized as it was done on healthy volunteers than patients.[21]

The incidence of hypotension and sedation was more in i.v. group when compared with perineural group. In our study, higher incidence of hypotension may be attributed to speed of injection and dosage of the drug and also preoperative hydration status in our patients. We administered infusion over 10 min and used 1 μg.kg-1. Maybe, lower dosage and prolonged infusions are advisable in the future studies to provide hemodynamic stability without compromising block effect and postoperative analgesia.

The average sedation score was observed to be 3.83 ± 0.55 in the i.v. group and 2.38 ± 0.35 in the perineural group, which prevented from using further sedatives and made both surgeon and patient comfortable. Studies have shown less incidence of hypoxia, which can reflect in the results of our study.[22]

Limitations of our study were that it was prospective observational study and the possibility of bias cannot be ruled out. The use of ultrasound in place of nerve stimulator might have reduced levobupivacaine dosage. Plasma concentration of dexmedetomidine and norepinephrine would have helped to get a clear picture on hemodynamic effects when used along with different routes. We recommend more randomized multicenter study to be considered to know efficacy of i.v. dexmedetomidine when used with different local anesthetics in supraclavicular brachial plexus block.

CONCLUSION

Perineural dexmedetomidine is more effective than i.v. dexmedetomidine when used along with levobupivacaine in patients undergoing supraclavicular brachial plexus block. It hastens the onset of sensory and motor blocks and prolongs the duration of sensory and motor blocks. It prolongs the duration of analgesia with desirable sedation and stable hemodynamic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.