Adequate post-operative pain relief must be an integral part of administration of anaesthesia. In patients undergoing orthopedic surgeries, unrelieved postoperative pain not only results in immediate postoperative distress to patient, but also predisposes patient to development of chronic post-operative pain by central sensitization of nervous system. It causes exacerbation of acute nociceptive pain resulting in allodynia and hyperalgesia along with chronic pain syndromes [1].

Regional nerve blocks as primary anaesthetic technique plays an important role in modern anaesthesia practice in orthopedic surgeries. Regional nerve blocks provide excellent intra- operative analgesia that can be extended to post-operative period without any systemic side effects. Supraclavicular brachial plexus block being a versatile, reliable technique is quite effective in terms of performance, margin of safety, good intraoperative surgical conditions and postoperative analgesia. The block is performed at the level of distal trunk–proximal division of brachial plexus [2] area being more compact results in homogenous spread of drug throughout the plexus with a fast onset and complete block. 

Last several years have witnessed a tremendous increase in the use of USG guidance for regional anaesthesia, as it possesses the ability to visualize needle, nerve and adjacent vasculature and muscles in real time during performance of block, resulting in high success rates. Therefore, the use of peripheral nerve blocks for surgical anaesthesia and postoperative pain management has increased significantly with the advent of USG-guided techniques. 

USG for supraclavicular brachial plexus block has improved the success rate of block with excellent localization as well as improved safety rates and also brought down the complication rates [3]. Were the first to report the successful USG guided supraclavicular block utilizing linear array probe. 

With regards to the local anaesthetics, the low cardiovascular and neurological toxicity of levobupivacaine and ropivacaine has led to their widespread use in brachial plexus block. In a comparative study between ropivacaine, bupivacaine and mepivacaine [4] found no differences in the quality of sciatic nerve block as well as in the nerve block resolution times observed among the three groups. Compared to ropivacaine, levobupivacaine provides significantly longer duration of analgesia. Long duration of sensory block associated with good analgesia and less toxicity of levobupivacaine makes it better choice for peripheral nerve blocks [5]. 

Cacciapuoti, A. et al. [6] evaluated the effect of bupivacaine 0.5% (1 mg/kg), levobupivacaine 0.5% (1 mg/kg) and ropivacaine 0.75% (1.4 mg/kg) in 45 patients of both sexes in axillary brachial plexus block. The onset and duration of sensory, motor block and possible adverse events were recorded. Authors concluded that levobupivacaine when compared to ropivacaine, provides a significantly longer duration of analgesia. 

In another study [7], the different concentrations of bupivacaine (0.5%) and levobupivacaine (0.5% and 0.25%) were compared in sixty ASA physical status I–III patients, randomized to 3 study groups according to a computer-generated randomization list. In group B, 0.5% (n = 20) a three-in one block was performed with 20 mL of bupivacaine 0.5% (5 mg/mL), in group L 0.5% (n = 20) it was performed with 20 mL of levobupivacaine 0.5% (5 mg/mL) and in group L 0.25% (n =20) it was performed with 20 mL of levobupivacaine 0.25% (2.5 mg/ml). Sensory onset times were (mean (95% CI)) 27 min (20–33 min) in the B 0.5% group, 24 min (18–30 min) in the L 0.5% group and 30 min (23–36 min) in the L 0.25% group. 

The analgesic quality of the blockade was also not significantly different among the three groups. Whereas, a complete sensory block was achieved in significantly fewer patients in the levobupivacaine 0.25% group (p = 0.02). The duration of blockade was significantly shorter with levobupivacaine 0.25% compared with the other groups. In bupivacaine 0.5%, duration was 1053 min (802–1304 min); in levobupivacaine 0.5% group, duration was 1001 min (844–1158 min); and levobupivacaine 0.25% group had duration of 707 min (551–863 min) (p = 0.01). The authors recommended levobupivacaine 0.5% instead of bupivacaine 0.5% for the three-in-one block as supplement to spinal or general anaesthesia.   

In the study by Baskan, S.et al. [8] sixty adult patients undergoing open or closed shoulder surgery were enrolled in double-blind, randomized study and randomly allocated to receive 40 mL of 0.25% levobupivacaine (Group L, n = 30) or 0.25% bupivacaine (Group B, n = 30) in interscalene brachial plexus block through posterior approach. The mean onset time of motor and sensory block and onset time of complete motor and sensory block were documented in both groups. 

In both groups, mean onset time of sensory block was less than 5 min and mean onset time of complete sensory block was less than 25 min. The onset times for sensory block and complete sensory block were not statistically different between the groups (p>0.05). In both groups, mean onset time of motor block was less than 10 min but the mean onset time of complete motor block was more than 30 min. The onset times of motor block and complete motor block were not statistically different among the groups (p>0.05). 

After the injection of the local anaesthetic, 27% of group L and 87% of group B had complete motor block. Four patients in group L had no motor block. The authors concluded that 0.25% levobupivacaine and 0.25% bupivacaine have similar motor and sensory block onset times and qualities when used in posterior approach interscalene brachial plexus block and provide comfortable anaesthesia and analgesia for shoulder surgery. 

Kim, W. et al. [9] studied the block characteristics of the forty patients undergoing elective upper limb surgery using two different concentrations of levobupivacaine and randomized them into two groups: group I (0.375% levobupivacaine) and group II (0.5% levobupivacaine). All four main terminal nerves of the brachial plexus were blocked separately with 7 mL of levobupivacaine using USG guidance with nerve stimulation. The authors suggested that while performing brachial plexuses block with 0.375% or 0.5% levobupivacaine, there were no significant differences in the clinical efficacy, including the time to block onset, quality of block and patient satisfaction. 

Regarding the volume of the drug for USG guided supraclavicular block [10], 60 patients were randomly divided into two groups of 30 each. Group C received saline (2 ml) + 20 mL of 0.5% bupivacaine and group D received dexamethasone (8 mg) + 20 mL of 0.5% bupivacaine in supraclavicular brachial plexus block. The onset of sensory and motor block was significantly earlier in dexamethasone group (10.36±1.99 and 12±1.64) minutes compared to control group (12.9±2.23 and 18.03±2.41) minutes. The duration of sensory and motor block was significantly prolonged in dexamethasone group (366±28.11 and 337.33±28.75) minutes compared to control group (242.66±26.38 and 213±26.80) minutes. The VAS score was significantly lower in dexamethasone group after 210 min. The authors concluded that dexamethasone addition significantly increases the duration of analgesia in patients receiving low volume supraclavicular brachial plexus block. 

Similarly [11], evaluated the efficacy of tramadol or dexamethasone as an adjuvant to levobupivacaine in low volume ultrasound-guided supraclavicular brachial plexus block in terms of onset time of complete sensory and motor blockade, duration of motor blockade, duration of analgesia and any complication. Sixty consecutive patients of the American Society of Anaesthesiologists physical status class I and II posted for upper limb surgeries were recruited. Patients were divided into two groups of thirty patients each. Group T (tramadol) received 20 mL of 0.5% levobupivacaine with 100 mg tramadol and group D (dexamethasone) received 20 mL of 0.5% levobupivacaine with 8 mg dexamethasone under ultrasound guidance. The mean onset time of sensory block in group D was 5.80±1.97 min and in group T was 6.33±3.71 min (p = 0.490). The mean onset time of motor blockade following supraclavicular brachial plexus block in group D was 13±4.8 min and 15±5.3 min in group T (p = 0.039). The mean duration of analgesia was 1300.83 ±336 min and 820.47±239 min in group D and group T respectively (p<0.001). Patients in dexamethasone group had more prolonged duration of analgesia when compared to tramadol. The mean duration of motor blockade for group D was 1150.27±255 min and in Group T, mean duration of motor blockade was 764.63±226 min (p = 0.00). 

With the better understanding of pain pathophysiology and its adverse outcomes on postoperative recovery, the search for adjuvants to local anaesthetics for providing longer duration of action, good quality anaesthesia and lower incidence of systemic toxicity has become the need of the hour. Various adjuvants have been tried with local anaesthetics in an attempt to prolong analgesia following regional blocks. Adjuvants including epinephrine, clonidine [12-13], opioids [14], ketamine [5] and midazolam [16] have met with limited success. 

Recently, dexamethasone has been identified as clinically effective adjuvants, by inducing a degree of vasoconstriction, the drug acts by reducing local anaesthetic absorption. A more attractive theory holds that dexamethasone increases the activity of inhibitory potassium channels on nociceptive C-fibers (via glucocorticoid receptors) thus decreasing their activity. 

Baloda, R. et al. [17] observed the effect of dexamethasone on onset and duration of anaesthesia, when used as an adjuvant to levobupivacaine in supraclavicular brachial plexus block using blind approach. Sixty patients in the age group of 18-65 years belonging to ASA physical status I or II were included in the study. They were randomly allocated in two groups and each group included 30 patients. In group 1, patients received 30 mL of 0.5% isobaric levobupivacaine with 2 mL of isotonic sodium chloride. In group 2 patients received 8 mg (2 ml) dexamethasone in addition to 30 mL of 0.5% isobaric levobupivacaine. The mean time of onset of sensory blockade was 10.20±1.349 minutes in group 1 and 8.1667±0.985minutes in group 2 (p = 0.001). While the onset time of motor blockade was 15.033 ±0.889 minutes in group 1 and 13.76±2.045 minutes in group 2 (p = 0.003). The mean duration of sensory blockade was 657.2 ±8.382 minutes in group 1 and 923±12.905 minutes in group 2 (p = 0.001). Whereas the duration of motor blockade was 540 minutes±7.428 in group 1 and 798.83 ±15.010 minutes in group 2 (p = 0.001). The authors concluded that dexamethasone added to levobupivacaine for supraclavicular brachial plexus block reduces the time to onset of sensory and motor blockage and prolongs the duration of analgesia. 

The perineural dexamethasone has also been used in the dose of 8 mg in the study by Pani, N. et al. [18] The USG- guided supraclavicular brachial plexus block was given to sixty patients, randomly assigned into two groups. Group S (n = 30) received 2 mL normal saline with 25 mL levobupivacaine (0.5%) and group D (n = 30) received 2 mL of dexamethasone (8 mg) with 25 mL of levobupivacaine (0.5%) respectively. Time for the first rescue analgesia, number of rescue analgesics required in 24 h and different block characteristics was assessed. Time for request of the first rescue analgesia was 396.13±109.42 min in group S and 705.80±121.46 min in group D (p<0.001). The requirement for rescue analgesics was more in group S as compared to group D. The onset of sensory and motor block was faster in group D in comparison to group S. The mean duration of sensory and motor block was significantly longer in group D than group S. The addition of dexamethasone to levobupivacaine in supraclavicular brachial plexus block blockade prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block.

In the study by Nallam, S. R. et al. [19] comparison of efficacy of two doses of dexamethasone (4 mg vs. 8 mg) as an adjuvant to 35 mL levobupivacaine (0.5%) in interscalene brachial plexus block using nerve stimulation technique was done. The duration of analgesia was significantly prolonged in both group L (19.2±2.6 h) and group H (21.3±1.7 h) compared with group C (11.6±1.1 h) (p<0.05). Similarly, the duration of motor block was longer in both group L (26.6±2.8 h) and group H (28.4±2.2 h) compared to group C (18.6±3.1 h) (p<0.05). Postoperative analgesic consumption for the first 48 hours was significantly lower in group L (6.5 (4–8) doses) and in group H (5.5 (4–7) doses) vs. 9.5 (8–12) doses in group C (p = 0.01). The authors concluded that the addition of dexamethasone to levobupivacaine significantly prolonged the duration of the motor block and improved the quality of analgesia following interscalene block. There was no difference in the duration of analgesia and motor block between low-dose and high-dose dexamethasone. 

Persec, J. et al. [20] determined whether the addition of low-dose dexamethasone to levobupivacaine would prolong the duration of analgesia sufficiently to avoid additional intravenous analgesic use for the first 24 hours postoperatively. This randomized controlled study assessed seventy patients undergoing upper-extremity surgery. Patients were eligible if there 18 years or over with ASA physical status I, II or III. Patients were randomly assigned to receive 25 mL 0.5 % levobupivacaine plus 4mg dexamethasone (group 1) or 25 mL 0.5 % levobupivacaine plus 1 mL saline (group 2). Pain scores, analgesic consumption and time estimation at which they perceived that sensory and motor blockade started and resolved were recorded. Duration of sensory (1260 min. in group 1 vs. 600 min. in group 2) and motor (1200 min. in group 1 vs. 700 min. in group 2) blockade were significantly longer in group 1 (p = 0.02 and 0.012) respectively. Postoperative pain levels in group 1 were significantly lower (p<0.05) at different study intervals over a period of 24 h. Analgesia consumption was significantly lower (p = 0.003,0.002) in group 1; at six and 12 h. At 24 hours, only two patients compared with 17 in the levobupivacaine group required additional analgesia (p = 0.032). The authors concluded that single-shot low-dose dexamethasone in a mixture with levobupivacaine results in prolonged analgesia duration and less analgesic use compared with levobupivacaine alone. 

The meta-analysis by Kirkham, K. R. et al. [21] explores the optimal dose of perineural dexamethasone to prolong analgesia after brachial plexus blockade in adult patients undergoing upper limb surgery. Based on 33 randomized controlled trials, including a total of 2138 patients, subgroup analysis suggests that 4 mg of perineural dexamethasone represents a ceiling dose and prolongs analgesia by a mean period of 6 and 8 hours, when combined with short-/intermediate- or long-acting local anaesthetics, respectively and concluded that higher doses failed to provide additional analgesic duration. 

Therefore, the ceiling dose of perineural dexamethasone has been observed to be 4 mg. However, there is no consensus regarding the efficacy of dexamethasone in the dose less than 4 mg perineurally. Therefore, to observe the dose response relationship of perineural dexamethasone [22], eighty ASA physical status I-II patients scheduled for shoulder arthroscopy under general anaesthesia with ultrasound-guided interscalene brachial plexus block were randomly allocated to receive saline (control), dexamethasone 1 mg, 2 mg, 3 mg and 4 mg together with 20 mL ropivacaine 0.5%. The primary outcome was the duration of analgesia and secondary outcomes included rest and dynamic pain scores, analgesic consumption at 2 h, 24 h and 48 h postoperatively. Although the onset times of sensory and motor blockade were similar between groups, the duration of analgesia and motor blockade were significantly prolonged with increasing doses of perineural dexamethasone. 

The median (IQR (range)) duration of analgesia was significantly prolonged in a dose- dependent manner: control 685 (590–860 (453–1272)) min; 1 mg 835 (740–1110 (450–1375)) min; 2 mg 904 (710–1130 (525–1365)) min; 3 mg 965 (875–1025 (730–1390)) min; 4 mg 1023 (838–1239 (518– 1500)) min (p = 0.03). There was no difference in relation to secondary outcomes. The authors concluded that the minimal efficacy dose of perineural dexamethasone to increase the duration of analgesia by 60 min, 120 min, 180 min and 240 min was 0.8 mg, 0.96 mg, 1.80 mg and 3.40 mg respectively.

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20. Persec, J. et al. Low-dose dexamethasone with levobupivacaine improves analgesia after supraclavicular brachial plexus blockade. International Orthopaedics, vol. 38, no. 1, January 2014, pp. 101–105.

21. Kirkham, K.R. et al. Optimal dose of perineural dexamethasone to prolong analgesia after brachial plexus blockade: A systematic review and meta-analysis. Anesthesia and Analgesia, vol. 126, no. 1, January 2018, pp. 270–279.

22. Albrecht, E. et al. Dose–response relationship of perineural dexamethasone for interscalene brachial plexus block: A randomized, controlled, triple-blind trial. Anaesthesia, vol. 74, no. 8, August 2019, pp. 1001–1008.