European Journal of Cardiovascular Medicine

Ultrasound-guided regional block reduces the time taken for block placement, and can improve success rates (1). By using a perineural catheter and continuous infusion, analgesic effect of a block can be prolonged however problems including migration, spontaneous dislodgement, backflow of local anaesthetic and pump dysfunction which can lead to an overall rate of insufficient analgesia of up to 40% (2).  Addition of an adjunct (adjuvant) agent to the local anaesthetic can prolong the duration of analgesia (3) without the use of a perineural catheter or any continuous infusion.

Perineural dexamethasone (4) can prolong the duration of single-injection peripheral nerve block when added to the local anesthetic solution. Postulated systemic mechanisms of action along with theoretical safety concerns have prompted the investigation of intravenous dexamethasone as an alternative. We aimed to confirm that addition of intravenous dexamethasone will prolong the duration of analgesia after supraclavicular block when compared with perineural dexamethasone for ambulatory upper extremity surgery.

Written informed consent was obtained from all patients. Inclusion criteria included adult patients of ASA physical status 1–3 scheduled for elective upper limb orthopaedic surgery receiving supraclavicular brachial plexus block from January 2023 to December 2023. Exclusions included: patient refusal of block or inability to consent; patients taking greater than 60 mg oral morphine equivalents per day; pregnancy; type 2diabetes mellitus with peripheral neuropathy; patients with an allergy to amide local anaesthetics or dexamethasone; or a contra-indication to supraclavicular block including coagulopathy, local infection or severe lung disease.

The study was prospective, randomised, double-blinded involving hundred patients. Patients were allocated to the two groups at random and in equal ratios. The randomised treatment allocation schedule was created by the statistician and stored by the pharmacy; the schedule included a single block of 100 potential subjects. Randomisation occurred after informed consent was obtained and before study drug preparation.

After randomisation, all patients arrived for same-day surgery and received a pre-operative ultrasound-guided supraclavicular block using a 6–13 MHz  25-mm linear array transducer (M-Turbo; Sonosite Inc, Bothell, WA, USA), performed by one of the four anaesthesiologists. All were highly experienced in the technique. Sedation for block insertion was achieved using intravenous fentanyl up to 100 μg and midazolam up to 4 mg.

Patients in the perineural dexamethasone group received a block injection with 18 ml bupivacaine 0.5% mixed with 8 mg preservative-free dexamethasone in saline 0.9% to a volume of 20 ml. We gave 5 ml saline 0.9% intravenously over 3 min at the time of the block. Patients in the intravenous dexamethasone group received 18 ml bupivacaine 0.5% mixed with 2 ml saline 0.9%, to a volume of 20 ml, and 8 mg intravenous dexamethasone mixed with saline 0.9% to a total volume of 5 ml administered as above.  The dose of dexamethasone was chosen in line with recent studies (5,6).

After completion of the block, patients remained fully monitored until their transfer to the operating theatre.

Sensory and motor block were assessed every 5 min for a total of 30 min.

For those patients who remained in hospital, the analgesic regimen for the first 24 h after arrival in the post-anaesthesia care unit (PACU) consisted of intravenous tramadol 100 mg every 12 hourly.

Dexamethasone is not approved as a perineural adjuvant in the USA or in Europe. As a component of the institutional review board approval process, the literature on the safety of its use in this setting was presented (7), reviewed and ultimately determined to be acceptable for trial in human subjects.

Our primary outcome was the block duration, defined as the time from injection until the patient detected complete resolution of sensory blockade in the incision area. Our secondary outcomes were: opioid consumption in standard intravenous tramadol equivalents from PACU arrival until 24 h later; time from block insertion until first administration of opioid analgesic; visual analogue scores on a 0–10 scale for pain at rest at the incision site; nausea, recorded on a 0–10 scale; administration of ‘rescue’ anti-emetic medication in the first 24 h after PACU arrival; patient satisfaction with overall pain management on a 0–10 scale; and adverse events occurring in the first 7 days from block insertion.

Pain scores were assessed by using the Kruskal–Walli’s test. Proportions were compared by using the Pearson chi-square test;

The results were analyzed using Chi-square test for the qualitative variables and unpaired t-test for the quantitative variables.

OBSERVATIONS AND RESULTS

Sum of sixty subjects who underwent surgical procedure under USG guided supraclavicular brachial plexus block been analyzed with equal distribution of 100 patients among A, B group.A of (n = 50 )   Patients got  18ml of Bupivacaine 0.5% +  diluted with NS. B of (n = 50)   Patients got 18ml of Bupivacaine 0.5% + Dexamethasone (2ml) given perineurally.

Among the total cases, age distribution in Group A, 23 - between 18 – 30 yrs, 11 - between 31 – 40 yrs, 6 each - between 41 – 50 yrs and 51 to 65 yrs.

Similarly the age distribution in Group B, 14 - between 18 – 30 yrs, 10 - between 31 – 40 yrs,      15 - between 41 – 50 yrs and 11 cases were between 51 to 65 years as explained in  Figure 3.

FIGURE 2 : Gender Distribution

Group A had 30 male cases and 20 females. In Group B, there were 32 males and 18 female cases as explained in Figure 4.

Mean of heart rate at various intervals from baseline, 3 minutes to 120 minutes have been calculated for both the Groups. 

The mean heart rate showed statistical significance during 9th minute (p value = 0.026), 12th minute (p value = 0.070), 20th minute (p value = 0.000), 30th minute (pvalue = 0.001), 40th minute (pvalue = 0.000), 50th minute (pvalue = 0.001), 70th minute (pvalue = 0.019), 80th minute (pvalue = 0.000), 100th minute (pvalue = 0.000), 120th minute (pvalue = 0.005) as explained in Figure 5.

Mean SBP @ various intervals from baseline, 3 minutes to 120 minutes have been calculated for both the Groups.

The mean systolic blood pressure showed statistical significance during 6th minute (p value = 0.097), 9th minute (pvalue =0.001), 15th minute (pvalue =0.018), 30th minute (pvalue =0.001), 80th minute (pvalue =0.024), 100th minute (p value =0.007), 110th minute (pvalue =0.000) 120th minute (pvalue =0.000) as explained in Figure 6.

Mean of DBP at various intervals from baseline, 3 minutes to 120 minutes have been calculated

The mean diastolic blood pressure showed statistical significance during 9th minute (pvalue =0.001), 15th minute (pvalue =0.032), 30th minute (pvalue =0.002), 40th minute (pvalue =0.030), 90th minute (pvalue = .023), 120th minute (pvalue =0.001) as explained in Fig 7.

Mean of MAP at various time intervals from baseline, 3 minutes to 120 minutes have been calculated.

The mean MAP showed statistical significance during 15th minute (pvalue =0.014), 30th minute (pvalue =0.000), 50th minute (pvalue =0.009), 70th minute (pvalue = .001), 90th Minute (p value = .026) & 120th minute (p value = 0.002) as explained in Figure 8.

TABLE 1: Sensory Onset Comparison

Mean sensory onset has been calculated, found statistically insignificant between both the groups. (p value = 0.0001) as explained vide Figure 1.

TABLE 2: Motor Block Onset

Time for motor block onset has been calculated. Found significant statistically between both A & B (p value = 0.0001) . It was found that Group B had fastest motor block onset time than Group A as explained in Table 5.

TABLE 3: Comparison Of Duration Of Motor Blockade

Motor block duration has been calculated for both, found significant statistically between both A, B (p value = 0.0001). It was found that Group B had highest duration of motor block on comparing with Group A as explained vide Table 6.

Mean of VAS

60 minutes to 300 minutes have been calculated found significant statistically during 210th minute (pvalue =0.041) as explained as figure 10.

TABLE 4: Comparison Of Rescue Analgesia

Mean of rescue analgesia, significant statistically. (p value = .000). Rescue analgesia time, A > B, as explained in table 7.

Table 5 : Side Effects Distribution

Compared to placebo, perineural dexamethasone as an adjunct to local anesthetic drugs increase the duration of analgesia by 6.7 h [8]. However, it is unclear whether this is a result of systemic dexamethasone absorption. Local anesthetic effects might explain this difference, considering that the duration of analgesia was longer in the perineural dexamethasone group compared to the intravenous dexamethasone group. However, the impact of perineural dexamethasone on the duration of analgesia was found to be more modest than previously estimated [9] .

Dexamethasone is a synthetic glucocorticoid which inhibits the release of inflammatory mediators such as interleukins and cytokines. The perineural dexamethasone acts additionally on local glucocorticoid receptors to cause local vasoconstriction and thereby decreases the systemic absorption of LA. Other potential mechanisms may be suppression of C-fibre-mediated pain signal transmission and upregulation of neuronal potassium channels (13).

Compared with intravenous dexamethasone, perineural dexamethasone was found to only increase the duration of analgesia by 54 minutes. The study conducted by Morales-Muñoz et al. [10] thus appears to be an outlier. Although efforts were made to determine why their results differed so considerably from those of the rest of the studies, no reasonable explanation was found.

On the contrary, Martinez et al. study showed no clear benefit of perineural administration of dexamethasone over intravenous administration, and perineural route is not licenced until now (14).

A potential concern regarding the use of perineural dexamethasone is neurotoxicity of the drug. Animal studies have raised concerns regarding the potential neurotoxic effects of dexamethasone [11]. Despite this, caution against labelling dexamethasone as neurotoxic based on animal cell culture studies due to methodological flaws. Perineural dexamethasone has been used for many causes of acute and chronic pain with no signs of increased neurotoxicity [12]. Consistent with other meta-analyses examining perineural steroids, no concerns linking the use of perineural steroids with poor neurological outcomes were found in our study.

This study has certain limitations.

Although the primary outcome (duration of analgesia) was assessed in all the studies, there was a lack of standardization regarding how this was defined or assessed. For example, some studies defined it as the time to the first pain sensation, while others defined it as the time to the first analgesia request. Furthermore, the methods of collecting the data were different between the studies; for example, some utilized retrospective telephone interviews, while others utilized patient self-report diaries. Heterogeneity may have also resulted from differences in the exact nature of the surgery as well as differences in surgical techniques.

Another limitation of this study was the lack of clarity on how researchers handled the time to first analgesia for the patients did not require rescue analgesia.

Perineural dexamethasone as an adjunct to bupivacaine resulted in a greater duration of USG supraclavicular brachial plexus block when compared with intravenous dexamethasone.

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