Effect of dexmedetomidine as adjuvant in ropivacaine-induced supraclavicular brachial plexus block: A prospective, double-blinded and randomized controlled study.

BACKGROUND AND AIMS: Different additives have been used to prolong brachial plexus block. We evaluated the effect of adding dexmedetomidine to ropivacaine for supraclavicular brachial plexus blockade. The primary endpoints were the onset and duration of sensory and motor block and duration of analgesia.
MATERIALS AND METHODS: A total of 84 patients (20-50 years) posted for elective forearm and hand surgery under supraclavicular brachial plexus block were divided into two equal groups (Group R and RD) in a randomized, double-blind fashion. In group RD (n = 42) 30 ml 0.5% ropivacaine +1 ml (100 μg) of dexmedetomidine and group R (n = 42) 30 ml 0.5% ropivacaine +1 ml normal saline were administered in supraclavicular block. Sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, postoperative visual analog scale (VAS), hemodynamics and side-effects were recorded for each patient.
RESULTS: Though with similar demographic profile in both groups, sensory and motor block in group RD (P < 0.05) was earlier than group R. Sensory and motor block duration and time to first analgesic use were significantly longer and the total need for rescue analgesics was lower in group RD (P < 0.05) than group R. Post-operative VAS value at 12 h were significantly lower in group RD (P < 0.05). Intra-operative hemodynamics were significantly lower in group RD (P < 0.05) without any appreciable side-effects.
CONCLUSION: It can be concluded that adding dexmedetomidine to supraclavicular brachial plexus block increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side-effects.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Peripheral nerve block as an anesthetic technique plays an important role in modern regional anesthesia. The most important prerequisites for the use of peripheral regional anesthesia in daily clinical practice are success rate and safety. Upper limb surgeries below the shoulder joint are mostly performed under peripheral blocks such as the brachial plexus block. Peripheral nerve blocks not only provide intra-operative anesthesia, but also extend analgesia in the post-operative period without major systemic side-effects by minimizing stress response and using minimal anesthetic drugs.[1]

Ropivacaine is an amino-amide local anesthetic that blocks the peripheral afferents acting on voltage dependent Na+ channels. It is less cardiac and central nervous system toxic than other long acting local anesthetics like bupivacaine.[2] Local anesthetics alone for supraclavicular brachial plexus block provide good operative conditions, but have a shorter duration of postoperative analgesia. Hence, various adjuvants such as opioids,[3] clonidine,[4] neostigmine, dexamethasone,[5] midazolam,[6] etc., were added to local anesthetics in brachial plexus block to achieve quick, dense and prolonged block, but the results are either inconclusive or associated with side-effects.

Dexmedetomidine is highly selective (8 time more selective than clonidine),[7] specific and potent α2-adrenergic agonist having analgesic, sedative, antihypertensive, and anesthetic sparing effects when used in systemic route.[8] Adding dexmedetomidine to local anesthetics during peripheral nerve blockade[9] and regional anesthesia[10] procedures may also prove efficacious for the surgical patients. In human study, dexmedetomidine has also shown to prolong the duration of the block and post-operative analgesia when added to local anesthetic in various regional blocks.[1112]

Our current study was designed to test the hypothesis that dexmedetomidine when added as an adjuvant to ropivacaine in supraclavicular brachial plexus block enhanced the duration of sensory and motor block, duration of analgesia and quality of block.

MATERIALS AND METHODS

After obtaining permission from institutional ethics committee, written informed consent was taken. Totally 84 adult patients were randomly allocated to two equal groups (n = 42 in each group) using computer generated random number list. American Society of Anesthesiologists (ASA) physical status I and II, aged between 20 and 50 years of both sexes undergoing elective orthopedic surgeries of elbow, forearm and hand under supraclavicular brachial plexus block were enrolled in the study. Patients in group R received 30 ml of 0.5% ropivacaine +1 ml normal saline for supraclavicular block. Group RD received 30 ml 0.5% ropivacaine + 1 ml (100 μg) of dexmedetomidine for the same block.

Exclusion criteria

Patient refusal, any known hypersensitivity or contraindication to ropivacaine, dexmedetomidine; pregnancy, lactating mothers, hepatic, renal or cardiopulmonary abnormality, alcoholism, diabetes, long-term analgesic therapy, bleeding diathesis, local skin site infections were excluded from the study. Patients having a history of significant neurological, psychiatric, or neuromuscular disorders were also excluded.

In pre-operative assessment, the patients were enquired about any history of drug allergy, previous operations or prolonged drug treatment. General examination, systemic examinations and assessment of the airway were done. Pre-operative fasting of minimum 6 h was ensured before operation in all day care cases. All patients received premedication of tablet diazepam 10 mg orally the night before surgery as per pre-anesthetic check-up direction to allay anxiety, apprehension and for sound sleep. The patients also received tablet ranitidine 150 mg in the previous night and in the morning of operation with sips of water.

All patients were clinically examined in the pre-operative period, when whole procedure was explained. 10 cm visual analog scale (VAS) (0, no pain and 10, worst pain imaginable) was also explained during the pre-operative visit. All patients are investigated for Hb%, Total leukocyte count, differential leukocyte count, erythrocyte sedimentation rate, platelet count, blood sugar, blood urea, serum creatinine and liver function tests. A 12 lead electrocardiography (ECG) and chest X-ray were also taken. On entering, the patient in the operative room standard intra-operative monitors like ECG, pulse oximeter, non-invasive blood pressure were attached and baseline parameter were recorded. Philips Intelleview MP20 monitor was used for this purpose. Intravenous (i.v) infusion of Ringers’ lactate started and oxygen given at 3 L/min through a face mask. All patients received injection midazolam 0.04 mg/kg before procedure.

After proper explanation of technique and positioning interscalene groove was identified where a mark was made approximately 1.5-2.0 cm posterior to the mid-clavicle point. The stimulation frequency was set at 1 Hz and the intensity of the stimulating current was initially set to deliver 2 mA and was then gradually decreased. The 22-gauge 5 cm, insulated, stimuplex® a needle was used. The position of the needle was considered to be acceptable when an output current <0.5 mA still elicited a slight distal motor response in the forearm and hand. On negative aspiration for blood, a total volume of 31 ml solution was injected slowly as per allotment of the group and drug. The anesthesiologist performing supraclavicular block was unaware of the constituent of the drug and allotment of the group and similarly resident doctors keeping records of different parameters were also unaware of group allotment. Thus, blinding was properly maintained.

Sensory and motor blockade were assessed every 2 min after completion of injection until 30 min and then every 30 min after the end of surgery until first 12 h, thereafter hourly until the block had completely worn off. Sensory blockade of each nerve was assessed by pinprick. Onset time of motor blockade was defined as the time interval between the end of local anesthetic injection and paresis in all of the nerve distributions.

The duration of sensory block was defined as the time interval between the onset of sensory block and the first post-operative pain. The duration of motor block was defined as the time interval between the onset of motor block and complete recovery of motor functions. After 30 min, if the block was considered to be adequate, surgery commenced. Injection diclofenac sodium (rescue analgesic) 75 mg was given intramuscularly when VAS ≥3 cm. Number of injection diclofenac given to each patient during first 24 h of the post-operative period was recorded.

Statistical analysis

Sample size was estimated using first rescue analgesic requirement among two groups as the main primary variable. The average duration in each group was 120 min and to detect a difference of 10% (i.e., 12 min), at the P < 0.05 level, with a probability of detecting a difference this large, if it exists, of 80% (1 — beta = 0.80). On the basis of previous study assuming within group standard deviation of 18 min and we needed to study at least 36 patients per group to be able to reject the null hypothesis that the population means of the groups are equal with probability (power) 0.80. Raw data were entered into a Microsoft Excel spreadsheet and analyzed using standard statistical software SPSS® statistical package version 18.0 (SPSS Inc., Chicago, IL, USA). Categorical variables were analyzed using the Pearson's Chi-square test. Normally, distributed continuous variables were analyzed using the independent sample t-test and P < 0.05 was considered as statistically significant.

RESULTS AND ANALYSIS

We recruited 42 subjects per group, more than the calculated sample size. There were no dropouts. However, excluding subjects who failed blocks, 40 patients in the dexmedetomidine group (RD) and 40 in the normal saline group (R) were eligible for effectiveness analysis. The difference in the number of valid blocks in the two groups was not statistically significant.

The age, sex distribution, body weight, ASA status and duration of surgery in the two groups were found to be comparable [Table 1]. Indications for different upper limb orthopedic surgeries were also similar and have no clinical significance (P > 0.05) [Table 2]. Onset of both sensory and motor block was earlier in RD group than group R [Table 3], but they were not clinically significant (P > 0.05). Whereas, Table 4 shows that sensory and motor block durations are significantly greater in the group receiving dexmedetomidine (RD) (P < 0.05) than group R.

Table 1

Comparison of demographic data between the two study groups

Table 2

Indications of upper limb orthopedic surgery for two groups

Table 3

Onset time for sensory and motor block

Table 4

Duration of sensory and motor block

The mean time from block placement to first request for pain medication, i.e., the duration of analgesia was 846.67 min in the dexmedetomidine group, but 544.07 min in the normal saline group. This difference (about 302.6 min) was highly significant (P < 0.001) statistically as well as clinically [Table 4 and Figure 1].

Figure 1

Duration of sensory and motor block

Table 5 and Figure 2 shows that group RD required less number of diclofenac sodium injection as rescue analgesics than patients in group R (control group) in first 24 h of post-operative period, and the difference is statistically highly significant (P < 0.01).

Table 5

Rescue analgesic requirement in post-operative period (no. of IM diclofenac sodium injections)

Figure 2

Number of intramuscular diclofenac injection as rescue analgesic in first 24 h post-operative period

Figure 3 shows that VAS score was of much higher value in group R than RD group. Again group RD suffered from bradycardia, [Table 6] which was statistically higher (P < 0.05) than group R. Other side-effects were quiet comparable (P > 0.05) among two groups.

Figure 3

Comparison of visual analog scale score among groups RD and group R

Table 6

Comparison of side effects

DISCUSSION

Supraclavicular blocks are performed at the level of the brachial plexus trunks. Here, almost the entire sensory, motor and sympathetic innervations of the upper extremity are carried in just three nerve structures (trunks), confined to a very small surface area. Consequently, typical features of this block include rapid onset, predictable and dense anesthesia along with its high success rate.[13] Local anesthetics alone for supraclavicular brachial plexus block provide good operative conditions but have a shorter duration of postoperative analgesia. Hence various drugs such as opioids,[3] clonidine,[4] neostigmine, dexamethasone,[5] midazolam,[6] magnesium[14] etc., were used as adjuvant with local anesthetics in brachial plexus block to achieve quick, dense and prolonged block, but the results are either inconclusive or associated with side-effects.

Dexmedetomidine; a highly selective, α2-adrenergic agonist; has analgesic, sedative, anesthetic sparing effects when used in systemic route.[8] Use of dexmedetomidine as an adjuvant mixed with local anesthetics has been performed with neuraxial anesthesia in both adult and pediatric patients.[1516] Mixing dexmedetomidine as adjuvant with local anesthetics during peripheral nerve and nerve plexus blockade has recently been practiced by anesthesiologists.[1112]

In this prospective, randomized, and double-blinded trial, we had compared the effect of 1 ml of dexmedetomidine and placebo as an adjuvant to 30 ml 0.50% ropivacaine in supraclavicular brachial plexus block, on the onset time and duration of sensory and motor block as well as on the post-operative rescue analgesic (injection diclofenac sodium) requirement.

The demographic profile, between two groups, which was statistically insignificant (P > 0.05) of our patients was quite similar with other research investigations and provided us the uniform platform to evenly compare the results obtained. A study on the role of dexmedetomidine for post-operative analgesia was conducted by Gupta et al. in a total of 100 patients yielded similar results.[17] The mean duration of surgery and tourniquet time were almost comparable in both groups with no significant statistical difference [Table 1].

From Table 2, it is quite evident that indications of surgical procedures were almost similar in both groups and had no statistical significance. The onset time of sensory block (14.71 ± 3.70 min in RD group vs. 15.17 ± 5.09 min in R group) was similar in the two groups (P = 0.70) [Table 3]. These findings correlate with the studies of Rancourt et al.[18] However Ammar and Mahmoud,[10] Kaygusuz et al.[19] in their studies, found significantly earlier onset of sensory block in the RD group than in the group R. The onset time of motor block (19.96 ± 1.28 min in RD group vs. 20.26 ± 1.28 min in group R) was also similar in the two groups (P = 0.40). On the contrary, Ammar and Mahmoud,[10] Gandhi et al.[20] in their study found that motor block onset was hastened by the use of dexmedetomidine adjuvant in brachial plexus block with bupivacaine. Again in a study conducted by Marhofer et al.[21] in 36 volunteers it has been found that dexmedetomidine as adjuvant though produced early onset of motor block, sensory block was not different from the control group or i.v group.

In our study, the duration of sensory block (846.67 ± 102.09 min in group RD vs. 544.07 ± 55.40 min in group R) was significantly longer in the dexmedetomidine group than in the control group (P < 0.001). The duration of motor block (624.2 ± 200.9 min in RD group vs. 516.8 ± 155.85 min in R group) was also significantly longer in the dexmedetomidine group than in the control group (P < 0.015). These findings lend support to the observations of various earlier studies by Ammar and Mahmoud,[10] Esmaoglu et al.,[11] Rancourt et al.,[18] Marhofer et al.[21]

In our study, mean duration of sensory block (analgesia) and motor block in the dexmedetomidine plus ropivacaine group were 14.11 h (846.67 min) and 10.40 h (624.2 min) respectively. While mean duration of analgesia and motor block in the dexmedetomidine plus bupivacaine group were 2.99 h and 2.59 h respectively, in the study conducted by Ammar and Mahmoud.[10] Again the median duration of sensory and motor block in the dexmedetomidine plus levobupivacaine group in infraclavicular brachial plexus block were 14.78 h and 12.88 h respectively, in the study by Esmaoglu et al.[11]

In our study, patients of RD group required significantly less number of diclofenac sodium injection in first 24 h of post-operative period than the patients R group (P < 0.01). This finding correlates with the studies of Kaygusuz et al.[19] Kaygusuz et al. found that 11 patients of levobupivacaine group required 75 mg intramuscular injection of diclofenac sodium as rescue analgesic, whereas dexmedetomidine plus levobupivacaine group required nothing and the result was also statistically significant.[19] Reduced requirement of rescue analgesic in the dexmedetomidine group during first 24 h of post-operative period is because of prolonged duration of sensory block. Again Ammar and Mahmoud[10] also experienced statistically much less amount (4.9 mg vs. 13.6 mg) of i.v morphine administration as rescue analgesic in bupivacaine, dexmedetomidine group while comparing with plain bupivacaine group in infraclavicular brachial plexus block.

In group RD, bradycardia was observed in four patients and all of these patients were managed with atropine. There was no such episode of bradycardia in group R. Side-effects-including pneumothorax, Horner syndrome though noted in both groups, but the difference was not statistically insignificant (P > 0.05). Esmaoglu et al.[11] also found significant bradycardia in dexmedetomidine plus levobupivacaine group than levobupivacaine alone. However, they found significant hypotension with dexmedetomidine group, which was absent in our study.

Ropivacaine and Dexmedetomidine dose was chosen as per recommendation in the text book as well as experience of our previous researchers.[10222324] While writing this discussion we have found the reference of lowest possible volume (10 ml) and concentration (0.375%) of ropivacaine for post-operative analgesia by Iwata et al.[25] However, we had used a higher concentration and much higher volume for intra-as well as post-operative analgesia.

Several hypothesized mechanisms of action have been suggested to explain the analgesic effect of dexmedetomidine. Some of these include vasoconstriction around the injection site,[26] direct suppression of impulse propagation through neurons as a result of a complex interaction with axonal ion channels or receptors,[27] local release of enkephalin-like substances,[28] a decrease in localized proinflammatory mediators[29] and an increase in anti-inflammatory cytokines through an α2-adrenoceptor-mediated mechanism.[30]

Finally, unsuccessful block was encountered in two patients (5%) in each group in our study, which is quite comparable to previous studies using nerve stimulator guided approaches to supraclavicular brachial plexus blockade.[31]

We do conclude that addition of 100 mcg dexmedetomidine to ropivacaine 0.50% solution in supraclavicular brachial plexus block prolongs the duration of sensory and motor blockade reduces the requirement of rescue analgesic in the post-operative period, but has no appreciable effect on the onset time of sensory and motor blockade.