European Journal of Cardiovascular Medicine

Orthopedic procedures of the forearm and hand are frequently suited for regional anesthetic techniques. While the debate over the superiority of regional anesthesia versus general anesthesia has persisted for decades, there is emerging evidence suggesting that regional anesthesia may reduce major perioperative complications, including deep vein thrombosis (DVT), pulmonary embolism (PE), blood loss, respiratory complications, and even mortality. One of the most significant advantages of regional anesthesia is its efficacy in managing postoperative pain. Compared to other pain management strategies, regional anesthesia provides superior pain relief, especially after orthopedic procedures. Additionally, regional anesthesia has been associated with decreased intraoperative blood loss, which is another advantage in orthopedic surgeries. [1,2]

The use of regional anesthesia for extremity surgeries is preferred for several reasons. It eliminates the need for general anesthesia and, consequently, the risks associated with systemic toxicity due to anesthetic drugs and inhalational agents. Furthermore, it prevents adverse events during intubation, extubation, and the use of muscle relaxants, which may be risky in certain patients. Regional anesthesia is particularly advantageous for patients at high risk for general anesthesia, such as those with advanced age or existing respiratory and cardiac conditions, or chest wall deformities.[3,4]

In an effort to prolong the duration of anesthesia and enhance analgesia, various adjuvants have been incorporated into regional blocks. Drugs such as clonidine have been used for this purpose since the 1980s, particularly in attempts to extend the block duration and provide better analgesia. Studies have shown that clonidine, when used as an adjuvant in peripheral nerve and plexus blocks, effectively prolongs the block and provides significant analgesic benefits. Most of these studies, however, have used intermediate-acting local anesthetics such as mepivacaine, prilocaine, and lidocaine. [1,3,5-9]

Few studies have focused on the use of clonidine as an adjuvant to ropivacaine in plexus blocks, with mixed results—some studies report a significant prolongation of the block duration, while others show no notable difference. Moreover, there is a paucity of data on the effects of clonidine in the Asian population. This trial aims to evaluate the impact of adding clonidine to ropivacaine in a supraclavicular brachial plexus block, focusing on analgesic action, duration of sensory and motor block, and any associated hemodynamic changes, such as hypotension or bradycardia, as well as other adverse effects [1,3,5,7,9].

To evaluate the efficacy and safety of adding clonidine to ropivacaine in supraclavicular brachial plexus block by comparing postoperative analgesia duration, incidence of hemodynamic changes (hypotension, bradycardia), sedation levels, and other adverse effects between the two groups.

This prospective case series was conducted in the Department of Anesthesiology, Government Medical College, Thiruvananthapuram, over a period of three months. The study protocol was approved by the Research Methodology and Human Ethics Committee of the institution. Written informed consent was obtained from all participants prior to their enrollment.

Study design and setting

This was a prospective case series study conducted in the Department of Anesthesiology, Government Medical College, Thiruvananthapuram, over a period of 3 months. All patients provided written informed consent before enrollment.

Study population

A total of 110 patients belonging to ASA physical status I, II, or III undergoing orthopedic surgery of the forearm or hand were enrolled in the study. Patients were equally allocated to two groups (55 in each group) following informed consent.

Sample Size Calculation

The sample size has been calculated to select sample for the present study. The sample size has been calculated using the formula:

N= Z ² * (p) * (1-p)/c²

Where:

Z = Z value (e.g. 1.96 for 95% confidence level) 

The sample size was calculated for an alpha error of 5% and beta power of 80%. For the present study, the minimum sample size was calculated as 54 patients per each group totaling 108 patients.

However we could enroll a total of 110 patients in the study , with 55  patients in each group

Inclusion criteria

• ASA physical status I, II, or III
• Age > 18 years
• Undergoing orthopedic surgery of the forearm or hand

Exclusion criteria

• Mallampati class 4
• Contraindication to axillary brachial plexus block or study drugs
• Hemodynamic instability
• Significant neurological, psychiatric, neuromuscular, cardiovascular, pulmonary, renal, or hepatic disorders
• Alcohol or drug abuse
• Pregnancy or lactation
• Use of psychotropic or adrenergic medications
• Chronic analgesic therapy (other than NSAIDs)

Pre-operative evaluation

All patients underwent a thorough pre-anesthetic check-up, which included:

• Detailed history
• Age and weight
• Baseline heart rate and blood pressure
• Investigations: Hemoglobin, Total and Differential Count, Blood Urea, Routine Urine Examination, Chest X-ray
• Airway assessment
• Type of surgery (ORIF, external fixation, debridement, tendon repair)

Patient preparation

Patients were kept nil per oral for 8 hours and did not receive premedication. Written informed consent was obtained. Patients were alternately assigned to either Group A or B. No sedatives were given.

• Group A received 30 mL of 0.5% Ropivacaine + 1 mL (150 µg) clonidine (total 31 mL)
• Group B received 30 mL of 0.5% Ropivacaine + 1 mL of 0.9% saline (total 31 mL)

A supraclavicular brachial plexus block was administered using a peripheral nerve stimulator. The following were recorded at 1, 5, 10, 30, 60, 120, 180, 240, 360, and 480 minutes post-injection:

• Onset and duration of sensory and motor blocks
• Heart rate, blood pressure, and sedation score
• Duration of analgesia

Sedation and hemodynamic parameters

Sedation was scored from 1 (awake) to 4 (asleep, unarousable). The highest sedation score during the first 2 hours post-injection was used for analysis.

• Hypotension: Defined as >30% fall in mean blood pressure
• Bradycardia: Defined as heart rate <45 bpm
• Analgesic Effect: Measured as the time from injection to first analgesic request

Ethical Approval

The study protocol was approved by the Research Methodology and Human Ethical Committee, Government Medical College, Thiruvananthapuram, prior to commencement of the study.

Statistical analysis

Data analysis was performed using SPSS software version 10. Results are expressed as mean ± standard deviation, frequency, and percentages. The following statistical tests were used:

• Chi-square (χ²) test: For categorical data comparisons
• Student’s t-test: To compare means between groups
• Mann-Whitney U test: For non-parametric score comparisons

A p-value <0.05 was considered statistically significant.

The present study evaluated the efficacy of clonidine (150 µg) as an adjuvant to 0.5% ropivacaine for supraclavicular brachial plexus block in patients undergoing orthopedic surgery of the forearm or hand. Patients were randomized into two groups: Group A received 30 mL of 0.5% ropivacaine with 1 mL (150 µg) of clonidine, while Group B received 30 mL of 0.5% ropivacaine with 1 mL of normal saline.

1. Baseline characteristics

Table1: Summary of Baseline Characteristics of the study subjects

The baseline demographic and clinical characteristics were comparable between the two groups. The mean age was slightly higher in Group A (44.00 ± 14.42 years) compared to Group B (40.20 ± 15.32 years), though the difference was not statistically significant (p > 0.05). Both groups had an identical gender distribution, with 61.8% males and 38.2% females in each group (p > 0.05). ASA physical status classification showed a similar pattern, with the majority of patients in Grade I in both Group A (65.5%) and Group B (69.1%). Grades II and III were also evenly distributed, with no significant difference (p > 0.05). Comorbidities were present in 34.5% of patients in both groups. Diabetes mellitus was the most commonly observed comorbidity, seen in 9.1% of Group A and 14.5% of Group B patients [Table 1].

Table 2. Duration of Analgesia

The mean duration of analgesia was significantly longer in Group A (734.45 ± 28.28 minutes) compared to Group B (504.82 ± 21.84 minutes), with a highly significant p-value of < 0.001. This indicates that the addition of clonidine substantially prolonged the duration of postoperative analgesia, thereby enhancing patient comfort and reducing the need for additional analgesics [Table 2].

Table 3 . Sedation Score

Sedation scores were also notably higher in Group A (1.95 ± 0.73) than in Group B (1.16 ± 0.37), and the difference was statistically significant (p < 0.001, Mann–Whitney U test). Although the sedation was more pronounced in the clonidine group, it remained within a clinically acceptable range and did not result in any adverse respiratory events, suggesting an added benefit of anxiolysis[Table 3].

Hemodynamic Variability in Two Drugs 

1. Mean systolic BP

1. Mean diastolic BP

Hypotension was present in 4 patients (7.3%) of group A while it was seen only in 1.8% of patients of group B.  Although the figures seem to be of clinical importance, Chi square analysis showed  no statistically significant difference between the two groups[Figures 1,2].

1. Mean heart rate

Bradycardia was seen in 5 patients (9.0%) of group A and 2 patients(3.6%) of Group B. chi square analysis showed a p value >0.05 which means there is no statistically significant difference between the groups [Figure 3].

Concerning hemodynamic parameters, the systolic blood pressure ranged from 126.98 to 130.76 mmHg in Group A and 126.47 to 128.80 mmHg in Group B. The intergroup differences at various time intervals were not statistically significant (p > 0.05), indicating stable systolic blood pressure across both groups. Similarly, the diastolic blood pressure remained comparable between the groups, with Group A ranging from 77.24 to 80.00 mmHg and Group B from 78.62 to 80.62 mmHg (p > 0.05).

The addition of clonidine to ropivacaine for supraclavicular brachial plexus block significantly prolonged the duration of analgesia and produced mild, acceptable sedation without causing any significant hemodynamic disturbances. These findings support the use of clonidine as an effective and safe adjuvant in regional anesthesia for upper limb surgeries.

Patient Characteristics: This study aimed to assess the effect of adding clonidine to ropivacaine for supraclavicular brachial plexus block in patients undergoing orthopedic surgery of the forearm or hand. Only patients classified as ASA class 1, 2, and 3 were included in the study, with ASA class 4 patients excluded due to concerns about the potential morbidity from clonidine’s side effects such as hypotension and bradycardia. This selection criterion aligns with many other studies that have focused on patients within ASA classes 1, 2, and 3. The majority of patients in this study were classified as ASA class 1 and 2 (97.27%), which is reflective of the typical patient demographic for orthopedic surgeries related to fractures from road traffic accidents.

The mean age of patients in Group A was 44 years, while the mean age in Group B was 40.2 years. A similar pattern was observed for the gender distribution, with 61.80% males in both groups. This pattern is expected as patients undergoing surgery for fractures sustained in road traffic accidents tend to have a similar age and sex distribution. The comorbid conditions observed in both groups included diabetes, hypertension, and bronchial asthma, with no significant difference between the groups (p > 0.05). This similarity in baseline characteristics ensures comparability between the two groups for the purpose of assessing the effects of clonidine.

Postoperative Analgesia: In terms of postoperative analgesia, Group A, which received ropivacaine combined with clonidine, had a significantly longer time until the first analgesic request (734.45 ± 28.28 minutes) compared to Group B, which received ropivacaine alone (504.82 ± 21.84 minutes). This difference of 230 minutes suggests that clonidine contributed to a prolonged analgesic effect, consistent with the findings of El Saied et al. who reported a similar prolongation of analgesia, with a mean difference of 241 minutes (2).

The analgesic effect of clonidine is thought to arise from its systemic absorption after being injected perineurally, as clonidine is known to act on the central nervous system to prolong analgesia. Other studies have also supported the notion that clonidine can extend the duration of postoperative analgesia when added to local anesthetics. However, the mechanism by which clonidine enhances the duration of analgesia, whether via direct action on the plexus or through systemic absorption, continues to be a topic of investigation.

The addition of clonidine to ropivacaine not only extended the time to first analgesic request but also potentially decreased the total post-operative analgesic consumption, which could be beneficial in reducing the overall use of opioids and their associated side effects.

Hypotension: Regarding hypotension, there was a higher incidence in Group A (7.3%) compared to Group B (1.8%). In Group A, two patients required vasopressor support. However, Chi-square analysis showed that this difference was not statistically significant, meaning that clonidine did not significantly contribute to the occurrence of hypotension. This is in contrast to the findings of El Saied et al., who reported no hypotension in their study (2). It is possible that the small sample size or variability in individual responses contributed to the lack of statistical significance, despite the clinical importance of these observations.

Bradycardia: Similarly, bradycardia was observed in 9% of patients in Group A (ropivacaine-clonidine) compared to 3.6% in Group B (ropivacaine alone). While the figures show a higher incidence of bradycardia in the clonidine group, Chi-square analysis again revealed no statistically significant difference. This finding is consistent with the known side effect profile of clonidine, which can cause bradycardia due to its central sympatholytic action. However, similar to the hypotension findings, the observed difference between groups could be due to chance, as reported by El Saied et al., who found no cases of bradycardia in their cohort (2).

Sedation: Sedation was a notable side effect in this study, with 39 patients (70.90%) in Group A exhibiting a sedation score of 2 or more, compared to only 9 patients (16.36%) in Group B. This difference was statistically significant, and although sedation was more frequent in the clonidine group, it was generally mild and lasted no longer than 8-10 hours. Sedation can be considered a common side effect of clonidine, as it is an alpha-2 adrenergic agonist that exerts sedative effects through central mechanisms. In contrast, El Saied et al. found no significant difference in sedation scores between groups (2), suggesting that sedation could vary across studies depending on dosage, timing, and the specific population under investigation.

Despite the statistical significance in the incidence of sedation, it is unlikely to have any major clinical implications, as the sedation was generally short-lived and did not require any intervention. Additionally, clonidine's sedative effect may help avoid the use of other sedative medications during the perioperative period.

Other Side Effects: Other common side effects of clonidine, such as fainting and respiratory depression, were not observed in this study, which is in line with previous research that found these side effects to be rare when clonidine is used in the context of nerve blocks. The side effects reported in this study were generally mild and transient, and anesthesiologists should remain aware of these potential side effects, particularly in patients receiving clonidine as part of their analgesic regimen

The present study demonstrates that the addition of clonidine (150 µg) to 0.5% ropivacaine in supraclavicular brachial plexus block significantly enhances the duration of postoperative analgesia in patients undergoing orthopedic surgery of the forearm or hand. Patients receiving clonidine experienced markedly prolonged analgesia and mild yet clinically acceptable sedation, without any significant alterations in systolic or diastolic blood pressure. These results highlight clonidine's utility as a safe and effective adjuvant to ropivacaine in regional anesthesia, offering improved patient comfort and reducing the need for supplemental analgesics, with minimal risk of hemodynamic instability.

Conflict of interest: Nil

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