European Journal of Cardiovascular Medicine

Regional anesthesia plays a pivotal role in modern anesthetic practice, particularly for patients undergoing upper limb surgeries. Among the various regional techniques available, the supraclavicular brachial plexus block (SBPB) is widely used due to its effective and reliable anesthesia for the shoulder, arm, and hand1,2. The choice of local anesthetic and its adjuvants significantly influences the efficacy and safety of this technique. Levobupivacaine, a long-acting amide local anesthetic, has gained prominence due to its lower cardiotoxicity profile compared to its racemic counterpart, bupivacaine3. However, the addition of adjuvants to local anesthetic solutions has been shown to enhance the onset, duration, and quality of nerve block, improving patient outcomes and reducing postoperative analgesic requirements4.

Dexmedetomidine and clonidine, both α-2 adrenergic agonists, have emerged as popular adjuvants in regional anesthesia5. These agents exert their effects through central and peripheral mechanisms, producing analgesia, sedation, and a reduction in the need for opioids6. Despite their similar mechanisms of action, the clinical efficacy of dexmedetomidine compared to clonidine as an adjunct to local anesthetics, particularly in the context of SBPB, remains a subject of ongoing investigation7.

Dexmedetomidine is a more selective α-2 agonist, offering greater sedation and analgesia with fewer cardiovascular side effects than clonidine, which has a broader spectrum of α-2 and α-1 receptor activity8. Recent studies have suggested that dexmedetomidine may provide faster onset times and longer durations of sensory and motor blocks compared to clonidine, potentially making it a more favorable adjuvant in regional anesthesia. However, conflicting evidence exists regarding their comparative efficacy in nerve blocks.

This study aims to compare the clinical effects of dexmedetomidine and clonidine as adjuvants to 0.25% levobupivacaine in ultrasound-guided supraclavicular brachial plexus block for elective upper limb surgeries.

Study Design

This was a prospective, randomized, double-blind, comparative study conducted at department of Anaesthesiology,Government General Hospital/Government Medical College, Anantapuramu, during the period from  June 2023 to February 2024. The study aimed to compare the efficacy of dexmedetomidine and clonidine as adjuvants to 0.25% levobupivacaine for ultrasound-guided supraclavicular brachial plexus block in patients undergoing elective upper limb surgeries.

Inclusion Criteria

Adult patients (aged 18-65 years) of either gender.

ASA physical status I and II.

Scheduled for elective upper limb surgeries under regional anesthesia.

Written informed consent provided by the patient or their guardian.

Exclusion Criteria

Patients with a history of allergies to local anesthetics or the study drugs.

Patients with cardiovascular, renal, or hepatic diseases.

Pregnancy or lactating women.

History of neurologic disorders or infections at the site of the block.

Uncooperative patients or those unable to provide informed consent.

Sample Size Calculation

Based on previous studies, a sample size of 30 patients per group was calculated to provide 80% power to detect a significant difference in block onset and duration at a 5% significance level. This resulted in a total of 60 patients for the study.

Randomization and Blinding

Patients were randomly assigned into two groups using a computer-generated randomization list. Group LD (Dexmedetomidine) received 1 μg/kg of dexmedetomidine as an adjuvant to 0.25% levobupivacaine, while Group LC (Clonidine) received 1 μg/kg of clonidine as an adjuvant to 0.25% levobupivacaine. Both groups were blinded to the study, and the same volume of the drug mixture was administered to each patient. An anesthesiologist who was not involved in the study outcomes performed the block and monitored the patients.

Anesthetic Technique

After ensuring adequate intravenous access, all patients received preoperative monitoring including ECG, non-invasive blood pressure, and pulse oximetry. An ultrasound-guided supraclavicular brachial plexus block was performed using a linear probe with the patient in a semi-recumbent position. A single injection of 20 mL of 0.25% levobupivacaine with either dexmedetomidine (Group LD) or clonidine (Group LC) was administered at the brachial plexus using a 22-gauge needle.

Outcome Measures

Primary Outcome:

Onset time of sensory and motor blocks (measured from the time of injection to complete block, defined as loss of sensation to pinprick for sensory block and inability to move the hand or fingers for motor block).

Duration of sensory block (time from onset to complete recovery of sensation).

Duration of motor block (time from onset to complete recovery of motor function).

Duration of analgesia (time from block onset until the patient requests analgesia).

Secondary Outcome:

Cardiovascular parameters: heart rate, systolic blood pressure, and diastolic blood pressure were measured at baseline, 5, 10, 15, 30, and 60 minutes post-block.

Side effects including bradycardia, hypotension, nausea, vomiting, and respiratory depression were recorded.

Statistical Analysis

The data were analyzed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation, and categorical variables were presented as frequencies and percentages. Between-group comparisons of continuous variables were performed using the independent t-test for parametric data and the Mann-Whitney U test for non-parametric data. Categorical variables were compared using the chi-square test. A p-value < 0.05 was considered statistically significant.

Ethical Considerations

The study was approved by the Institutional Ethics Commitee of Government Medical College, Ananthapuramu. All patients provided written informed consent prior to inclusion in the study..

Demographic Distribution of Study Population:

A total of 60 patients were enrolled in the study, with 30 patients assigned to the Levobupivacaine + Dexmedetomidine (LD) group and 30 patients assigned to the Levobupivacaine + Clonidine (LC) group. The age distribution in the LD group ranged from 21 to 60 years, with the majority of patients falling in the 31-40 year age group (40%). In the LC group, the highest percentage of patients were in the 41-50 year age group (30%). The overall gender distribution showed a higher number of females (58.3%) than males (41.7%), with a predominance of females in the LC group (63.3%) compared to the LD group (53.3%). ASA status revealed that most patients in both groups had ASA I status (46.7% in LD and 40.0% in LC), with ASA II patients comprising the remainder (53.3% in LD and 60.0% in LC). The Chi-Square analysis showed no statistically significant difference between the groups in terms of age, gender, or ASA status (p = 0.16).

Table 1: Demographic Distribution of Study Population

Anthropometric and Surgical Details:

The mean height in the LD group was 162.13 ± 5.85 cm, and in the LC group, it was 159.96 ± 4.35 cm, with no significant difference between the groups (p = 0.10). The mean weight in the LD group was 58.80 ± 6.49 kg, while in the LC group, it was 56.63 ± 5.27 kg, also showing no significant difference (p = 0.21). The duration of surgery was comparable between the groups, with the LD group having a mean duration of 99.46 ± 32.18 minutes and the LC group having a mean of 105.53 ± 34.59 minutes (p = 0.48).

Table 2: Anthropometric and Surgical Details

Onset and Duration of Blocks:

The onset of sensory block in the LD group occurred significantly faster (5.16 ± 2.16 minutes) compared to the LC group (7.86 ± 2.99 minutes), with a highly significant difference (p = 0.0002). Similarly, the onset of motor block was faster in the LD group (10.33 ± 3.61 minutes) compared to the LC group (12.83 ± 4.86 minutes), with a statistically significant difference (p = 0.02). The duration of sensory block in the LD group was significantly longer (725 ± 10.42 minutes) compared to the LC group (693.33 ± 18.47 minutes) (p = 0.001). The LD group also had a longer duration of motor block (715 ± 9.74 minutes) compared to the LC group (615 ± 13.33 minutes) (p = 0.001). Furthermore, the duration of analgesia was significantly prolonged in the LD group (710 ± 6.48 minutes) compared to the LC group (619 ± 17.09 minutes) (p = 0.001).

Table 3: Onset and Duration of Blocks

Cardiovascular Parameters – Heart Rate:

Heart rate measurements at various time points post-block were significantly lower in the LD group compared to the LC group. At 5 minutes, the heart rate in the LD group was 66.40 ± 9.77 beats per minute (bpm), whereas in the LC group, it was 91.78 ± 9.91 bpm (p = 0.001). Similar trends were observed at subsequent time points, with the LD group showing lower heart rates at 10 minutes (61.43 ± 5.58 bpm vs. 89.75 ± 10.75 bpm), 15 minutes (60.67 ± 5.76 bpm vs. 88.75 ± 9.43 bpm), 20 minutes (57.63 ± 5.57 bpm vs. 88.97 ± 8.75 bpm), 25 minutes (59.40 ± 6.08 bpm vs. 88.13 ± 8.74 bpm), and 30 minutes (57.93 ± 5.68 bpm vs. 86.41 ± 9.53 bpm), with all comparisons showing highly significant differences (p < 0.001). At 2 hours, heart rate was 64.13 ± 6.26 bpm in the LD group compared to 84.09 ± 10.23 bpm in the LC group (p = 0.001). At 4 hours, the heart rate in the LD group was 67.41 ± 7.67 bpm, while in the LC group, it was 90.59 ± 11.24 bpm (p = 0.001). However, no significant difference was observed at 6 hours (p = 0.65) or 8 hours (p = 0.25).

Table 4: Cardiovascular Parameters – Heart Rate

Cardiovascular Parameters – Systolic Blood Pressure (SBP):

The systolic blood pressure was significantly lower in the LD group at multiple time points compared to the LC group. At 5 minutes, the SBP in the LD group was 147.78 ± 9.87 mmHg, whereas it was 152.63 ± 9.62 mmHg in the LC group (p = 0.01). The SBP continued to be significantly lower in the LD group at 10 minutes (132.38 ± 11.32 mmHg vs. 151.50 ± 9.80 mmHg), 15 minutes (136.44 ± 11.43 mmHg vs. 149.31 ± 11.11 mmHg), and 20 minutes (126.59 ± 12.06 mmHg vs. 148.31 ± 11.13 mmHg) (all p < 0.05). The differences persisted at 25 minutes (p = 0.01), 30 minutes (p = 0.01), and 2 hours (p = 0.00). At 4 hours, the SBP remained lower in the LD group (105.28 ± 12.01 mmHg) compared to the LC group (136.88 ± 13.57 mmHg) (p = 0.02). However, the differences were less pronounced at 6 hours (p = 0.05).

Table 5: Cardiovascular Parameters – Systolic Blood Pressure (SBP)

Cardiovascular Parameters – Diastolic Blood Pressure (DBP):

Diastolic blood pressure measurements showed a similar pattern, with significantly lower DBP in the LD group across all time points. At 5 minutes, the DBP was 89.22 ± 5.19 mmHg in the LD group compared to 85.81 ± 5.29 mmHg in the LC group (p = 0.01). This trend continued at 10 minutes (p = 0.03), 15 minutes (p = 0.00), 20 minutes (p = 0.00), and 25 minutes (p = 0.00), with the LD group consistently showing lower DBP values. At 30 minutes, the DBP in the LD group was 66.00 ± 4.77 mmHg compared to 82.38 ± 6.75 mmHg in the LC group (p = 0.00). At 2 hours, the DBP was significantly lower in the LD group (70.31 ± 5.93 mmHg) compared to the LC group (80.00 ± 6.43 mmHg) (p = 0.04). The differences remained significant at 4 hours (p = 0.03) and 6 hours (p = 0.01), with the LD group showing lower values. At 24 hours, DBP was significantly higher in the LC group (81.16 ± 6.62 mmHg) compared to the LD group (87.09 ± 5.18 mmHg) (p = 0.00).

Table 6: Cardiovascular Parameters – Diastolic Blood Pressure (DBP)

Statistical Analysis:

The statistical analysis summary revealed that the LD group showed significant differences in onset and duration of sensory and motor blocks, duration of analgesia, heart rate, systolic blood pressure, and diastolic blood pressure compared to the LC group.

The primary aim of this study was to compare the efficacy of dexmedetomidine and clonidine as adjuvants to 0.25% levobupivacaine for ultrasound-guided supraclavicular brachial plexus block in patients undergoing elective upper limb surgeries. Both dexmedetomidine and clonidine are α2-adrenergic agonists that enhance the effects of local anesthetics, but their comparative efficacy and impact on sensory and motor block onset, duration, and cardiovascular parameters have not been extensively studied in this specific context.

Onset of Sensory and Motor Blocks

Our results indicate that dexmedetomidine significantly shortened the onset time for both sensory and motor blocks compared to clonidine. This finding aligns with previous studies suggesting that dexmedetomidine, through its action on α2 receptors, enhances the release of endogenous opioids and promotes local anesthetic action, leading to a faster onset. This is consistent with the observations in other studies (Tripathi et al11., 2016; Swami et al15., 2012), where dexmedetomidine accelerated the onset of regional blocks, improving its clinical applicability, particularly in surgeries requiring rapid anesthesia. The faster onset in the dexmedetomidine group (LD group) offers significant clinical advantages, as it can facilitate quicker surgical preparation and patient comfort.

Clonidine, while also an effective adjuvant, showed a slower onset compared to dexmedetomidine. This finding could be attributed to pharmacokinetic differences between the two drugs, with clonidine having a less potent central nervous system effect at the dosages used in this study, as highlighted by Dharmarao & Holyachi14 (2018).

Duration of Sensory and Motor Blocks

The duration of sensory and motor blocks was significantly prolonged in the dexmedetomidine group compared to clonidine. This prolonged block duration is clinically advantageous, especially in upper limb surgeries, where extended postoperative analgesia is often required. Our findings are consistent with studies by Pehora et al10. (2017) and Sreeja et al13. (2020), which reported a prolonged block duration with dexmedetomidine due to its action on α2-adrenergic receptors. This prolonged effect provides sustained analgesia, thereby improving patient comfort post-surgery and reducing reliance on supplementary analgesics, as shown by Pehora et al10. (2017). The prolonged analgesia could also reduce opioid consumption and its associated side effects, an important benefit in current clinical practice.

Analgesia Duration

Dexmedetomidine provided significantly longer analgesia compared to clonidine, which is in agreement with existing literature (Lomate & Mane9, 2020; Tripathi et al11., 2016). The mechanism by which dexmedetomidine extends analgesia is likely related to its central and peripheral analgesic effects, including inhibition of pain transmission at the spinal cord level and modulation of nociceptive pathways, as seen in studies by Pehora et al10. (2017) and Dharmarao & Holyachi14 (2018). This extended analgesic effect supports its use in surgical procedures where prolonged pain relief is necessary.

Cardiovascular Effects

A significant finding in this study was that dexmedetomidine induced more favorable cardiovascular effects, such as a lower heart rate and blood pressure, compared to clonidine. The lowering of heart rate and blood pressure in the LD group may reflect the potent central sympatholytic effects of dexmedetomidine, which reduces sympathetic outflow (Lomate & Mane9, 2020). This could be beneficial for patients with pre-existing cardiovascular conditions or those who require more controlled hemodynamic management during surgery. The impact of dexmedetomidine on cardiovascular parameters has been reported in other studies, including Swami et al15. (2012), where a similar reduction in sympathetic activity was observed.

While clonidine also has sympatholytic effects, its impact on cardiovascular parameters was less pronounced compared to dexmedetomidine. This could be attributed to differences in the α2 receptor subtypes activated by each drug and the degree of central nervous system penetration, as suggested by Iyer et al12. (2021).

Safety and Side Effects

Both dexmedetomidine and clonidine were well-tolerated in this study, with no significant adverse effects observed in either group. Previous research has also indicated that both drugs are generally safe when used as adjuvants in regional anesthesia (Tripathi et al11., 2016; Sreeja et a13., 2020). However, potential side effects such as hypotension and bradycardia were observed, particularly in the dexmedetomidine group, though these were managed appropriately. As noted by Pehora et al10. (2017), while dexmedetomidine has cardiovascular effects, these can be safely managed in most patients, though caution is warranted in those with significant cardiovascular comorbidities.

Dexmedetomidine appears to be a superior adjuvant to clonidine when used with levobupivacaine in ultrasound-guided supraclavicular brachial plexus blocks for elective upper limb surgeries. Dexmedetomidine offers faster onset, prolonged block duration, and more favorable cardiovascular effects, making it a promising alternative to clonidine for regional anesthesia. Further studies with larger sample sizes and a broader patient population are needed to validate these findings and to assess the long-term safety and efficacy of these combinations in different surgical settings.

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