European Journal of Cardiovascular Medicine

Anesthesiologists most commonly conduct brachial plexus blocks (BPBs), which offer anesthesia and analgesia for upper limb surgeries as well as for intensely painful situations. Investigating ways to increase pain relief while reducing the negative consequences of local anesthetic is worthwhile. To improve the quality and duration of anesthesia and postoperative analgesia, local anesthetics (LAs) have been utilized in conjunction with a variety of perineural adjuvants, such as dexamethasone [1, 2], clonidine [3], dexmedetomidine [4], opioids [5], and magnesium [6].

Although perineural opioid adjuvants have a disputed effect on BPB, systemic opioids have long been utilized to reduce pain during surgery. While some research has shown that adding opioids to BPB, such as morphine, fentanyl, alfentanil, buprenorphine, and meperidine, enhances sensory block, motor block, and analgesia, other research has not shown this impact [7-9].

Adult patients' acute postoperative pain has been successfully managed with the intravenous or oral administration of tramadol [10]. Tramadol is a distinct opioid that inhibits pain through two different mechanisms: μ receptor-mediated opioid action and α2-adrenergic and serotoninergic activity-mediated non-opioid action [11, 12]. Tramadol's monoaminergic action suppresses nociceptive transmission at the spinal level by blocking the descending pain pathways [13]. Through inhibiting K+ channels, tramadol also demonstrates LA characteristics [14]. Tramadol used intradermally produces local anesthetic for minor skin operations in clinical settings [15]. Numerous research works have detailed tramadol's benefits as a supplement to LA in BPB. Regarding tramadol's ability to increase analgesia when administered in BPB, these trials have produced conflicting results; whilst some have shown a benefit, others have shown none at all.

Study Design: This study was designed as a prospective, randomized, double-blinded, controlled trial conducted at Apex Trauma Centre, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh  between November 2022 to February 2024.

• Inclusion Criteria:

• Adult patients aged 18-65 years.
• Either sex weighing above 50 kg.
• ASA (American Society of Anesthesiologists) physical status I or II.
• Scheduled for elective upper extremity surgery under supraclavicular brachial plexus block.

• Exclusion Criteria:

• Patients refusal.
• Known allergy to local anesthetics, tramadol, or clonidine.
• Infection at the block site.
• Coagulopathy or bleeding disorders.
• Neuropathy or neurological deficits affecting the upper limb.
• ASA (American Society of Anesthesiologists) physical status III or IV.
• Pregnancy and Lactation.

Sample Size: 60

• Group-A (Tramadol) : Bupivacaine 0.5% Plain 25 ml + Inj.Tramadol 100mg
• Group-B (Clonidine) : Bupivacaine 0.5% Plain 25 ml + Inj.Clonidine 100 µg

Randomization and Blinding

Participants were randomly allocated into two groups using computer-generated randomization software. Allocation concealment was ensured through sealed opaque envelopes. Patients, surgeons, anesthesiologists, and outcome assessors were blinded to group allocation.

Supraclavicular Brachial Plexus Block Technique

• After securing iv line and applying standard ASA parameters (NIBP,ECG,SPO2,TEMPERATURE). The block was performed by experienced anesthesiologist with the patient in the supine position with head turned to opposite side of block to be performed.
• A high-frequency linear ultrasound probe was used to identify the brachial plexus and surrounding structures.
• After skin sterilization and local anesthesia, a direct ultrasound-guided technique was employed to administer the local anesthetic solution with all aseptic precaution.

Outcome Measures

• Primary Outcome:
• Duration of analgesia (time from block administration to first request for rescue analgesia).
• Secondary Outcomes:
• Pain scores at rest and with movement (measured using a visual analog scale or numerical rating scale).
• Duration of motor and sensory block.
• Incidence of adverse effects such as hypotension, bradycardia, sedation, nausea, and vomiting.

In a study examining the effect of tramadol or clonidine as adjuvants to local anesthetics in supraclavicular brachial plexus block for upper extremity surgery, you would typically consider several key variables:

Independent Variables:

• Type of adjuvant (tramadol, clonidine).
• Dosage of adjuvant.
• Type and dosage of local anesthetic.
• Patient demographics (age, sex, weight).
• Surgical procedure.

Dependent Variables:

• Onset and duration of sensory block.
• Onset and duration of motor block.
• Pain scores before, during, and after surgery.
• Duration of postoperative analgesia.
• Any adverse effects or complications.

Controlled Variables:

• Surgical technique.
• Patient's pre-existing medical conditions.
• Concurrent medications.
• Anesthetic technique.
• Environment factors (temperature, humidity, etc.).

Outcome Measures:

• Analgesic efficacy.
• Duration of sensory and motor block.
• Patient satisfaction.
• Incidence of adverse effects (e.g., hypotension, bradycardia, nausea, vomiting).
• Time to discharge from recovery room or hospital.

Monitoring Parameters:

• Hemodynamic parameters (blood pressure, heart rate).
• Oxygen saturation.
• Respiratory rate.
• Secondary Measures:
• Time to first request for analgesia.
• Total analgesic consumption in the postoperative period.
• Incidence of complications such as neurotoxicity or systemic toxicity.

Data Collection Methods:

• Patient interviews (pain scores, satisfaction).
• Clinical observations (onset and duration of blocks, adverse effects).
• Vital sign monitoring.
• Review of medical records.

Table 1: Demographic Data

Table 2: Onset of Anesthesia

Table 3: Baseline Vital Parameters

Table 4: Mean Time of 1st Rescue Analgesic Drug

Demographic Data

In Group Tramadol, 18 patients were male and 12 patients were female. In Group Clonidine, 19 patients were male and 11 (31.0%) patients were female. Association of Sex with Variables was not statistically significant (p=0.6596). In Group Tramadol, the mean Age (Years) (mean± s.d.) of patients was 38.4±9.67. In Group Clonidine, the mean Age (Years) (mean± s.d.) of patients was 36.08 ±9.94. Distribution of mean Age (Years) with Variables was not statistically significant (p=0.6892). In Group Tramadol, the mean Weight (kg) (mean± s.d.) of patients was 68.12±9.15. In Group Clonidine, the mean Weight (kg) (mean± s.d.) of patients was 66.92±7.11. Distribution of mean Weight (kg) with Variables was not statistically significant (p=0.3442). In Group Tramadol, the mean Height (cm) (mean± s.d.) of patients was 162.84±7.90. In Group Clonidine, the mean Height (cm) (mean± s.d.) of patients was 163.24±4.74. Distribution of mean Height (cm) with Variables was not statistically significant (p=0.4597). In Group Tramadol, the mean Duration of surgery (Min) (mean± s.d.) of patients was 95.0±34.28. In Group Clonidine, the mean Duration of surgery (Min) (mean± s.d.) of patients was 92.0±31.68. Distribution of mean Duration of surgery (Min) with Variables was not statistically significant (p=0.7220).

Onset of Anesthesia

In Group Tramadol, the mean Onset Sensory (min) block (mean± s.d.) of patients was 16.33±1.16. In Group Clonidine, the mean Onset Sensory (min) block (mean± s.d.) of patients was 13.10±2.03. Distribution of mean Onset Sensory (min) block with Onset was statistically significant (p<0.0001). In Group Tramadol, the mean Onset Motor (min) block (mean± s.d.) of patients was 22.70±1.60. In Group Clonidine, the mean Onset Motor (min) block (mean± s.d.) of patients was 16.86±1.94. Distribution of mean Onset Motor (min) block with Onset was statistically significant (p<0.0001).

Baseline Vital Parameters

In Group Tramadol, the mean PULSE (per min) (mean± s.d.) of patients was 82.52±4.50. In Group Clonidine, the mean PULSE (per min) (mean± s.d.) of patients was 84.20±8.15. Distribution of mean PULSE (per min) with VITALS was not statistically significant (p=0.3772). In Group Tramadol, the mean SBP (mmHg) (mean± s.d.) of patients was 124.48±6.69. In Group Clonidine, the mean SBP (mmHg) (mean± s.d.) of patients was 124.16±4.07. Distribution of mean SBP (mmHg) with VITALS was not statistically significant (p=0.8390). In Group Tramadol, the mean DBP (mmHg) (mean± s.d.) of patients was 80.84±3.97. In Group Clonidine, the mean DBP (mmHg) (mean± s.d.) of patients was 81.18±4.00. Distribution of mean DBP (mmHg) with VITALS was not statistically significant (p=0.3686). In Group Tramadol, the mean MAP (mmHg) (mean± s.d.) of patients was 94.84±4.5. In Group Clonidine, the mean MAP (mmHg) (mean± s.d.) of patients was 93.84±2.75. Distribution of mean MAP (mmHg) with VITALS was not statistically significant (p=0.3250). In Group Tramadol, the mean SPO2 (%) (mean± s.d.) of patients was 98.82±0.72. In Group Clonidine, the mean SPO2 (%) (mean± s.d.) of patients was 98.46±0.80. Distribution of mean SPO2 (%) with VITALS was not statistically significant (p=0.2121). In Group Tramadol, the mean RR (per min) (mean± s.d.) of patients was 14.80±1.40. In Group Clonidine, the mean RR (per min) (mean± s.d.) of patients was 15.02±1.10. Distribution of mean RR (per min) with VITALS was not statistically significant (p=0.6622).

Time of 1st Rescue Analgesic Drug

 In Group Tramadol, the mean Mean time of 1^st rescue analgesic (min) (mean± s.d.) of patients was 453.10±7.20. In Group Clonidine, the mean Mean time of 1^st rescue analgesic (min) (mean± s.d.) of patients was 584.48±26.90. Distribution of mean Mean time of 1^st rescue analgesic (min) with Variables was statistically significant (p<0.0001). Patients were observed for side effects like; hypotension, bradycardia, respiratory depression, nausea, vomiting and dizziness. The incidence of nausea and vomiting was 10% in tramadol group and nil in clonidine group.

Joshi Y et al 4 (2023) found that, In Group A, 70 % of patients were male and 30 % of patients were female. In groups B, 85 % of patients were male and 15% patients were female. In groups C, 60 % of patients were male and 40 % of patients were female.

We found that, Sex (M/F) was higher in Group Clonidine [19/11] compared to Group Tramadol [18/12] but this was statistically not significant (p=0.6596).

Joshi Y et al 4 (2023) showed that, the presents study has been carried out in 60 patients in the age group of 18 to 65 years belonging to ASA Grade I or II scheduled for upper extremity surgery under supraclavicular nerve SMIMER, Surat. The Distribution of patients with respect to age was comparable in all three groups (p>0.05). Mean age in Group A was 34.90±11.69 years, Group B was 38.75±11.77 years and Groups C was 37.50±13.77 years.

We found that, Weight (kg) was less in Group Clonidine [66.92±7.11] compared to Group Tramadol [68.12±9.15] but this was statistically not significant (p=0.3442). In our study, Age (Years) was higher in Group Tramadol [38.4±9.67] compared to Group Clonidine [36.08 ±9.94] but this was not statistically significant (p=0.6892).

Our study showed that, Height (cm) was more in Group Clonidine [163.24±4.74] compared to Group Tramadol [162.84±7.90] but this was not statistically significant (p=0.4597).

Joshi Y et al 4 (2023) observed that, the average mean duration of surgery was 112.50± 16.50 minutes in Group A, 112.50±16.50 minutes in Group B, and 124.50±28 minutes in Group C. The mean duration of surgery in three groups was comparable (p>0.05) he average mean duration of surgery was 112.50± 16.50 minutes in Group A, 112.50±16.50 minutes in Group B, and 124.50±28 minutes in Group C. The mean duration of surgery in three groups was comparable (p>0.05). We observed that, Duration of surgery (Min) was lower in Group Clonidine [92.0±31.68] compared to Group Tramadol [95.0±34.28] but this was not statistically significant (p=0.7220).

Joshi Y et al 4 (2023) showed that, the mean onset of sensory blockade was 21.75 ± 2.94 minutes in Groups A, 13.50 ± 2.35 minutes in Groups B and 14 ± 2.05 minutes in Group C. There was no statistically significant difference in onset of sensory block between Group B and Group C, but onset of sensory blockade was significantly longer in Group A as compared to Group B and Group C (p<0.05). Total duration of sensory block was significantly (p<0.05), prolonged in clonidine group (242 ± 30.37 minutes) and tramadol group (218 ± 20.42 minutes) as compared to control Group (170 ± 13.6 minutes). It was found that, Onset Sensory (min) block was most in Group Tramadol [16.33±1.16] compared to Group Clonidine [13.10±2.03] but this was statistically significant (p<0.0001).

We examined that, Pulse (per min) was higher in Group Clonidine [84.20±8.15] compared to Group Tramadol [82.52±4.50] but this was not statistically significant (p=0.3772). In our study, SBP (mmHg) was more in Group Tramadol [124.48±6.69] compared to Group Clonidine [124.16±4.07] but this was not statistically significant (p=0.8390). We found that, DBP (mmHg) was lower in Group Tramadol [80.84±3.97] compared to Group Clonidine [81.18±4.00] but this was not statistically significant (p=0.3686). Our study showed that, MAP (mmHg) was higher in Group Tramadol [94.84±4.5] compared to Group Clonidine [93.84±2.75] but this was not statistically significant (p=0.3250). Our study showed that, SPO2 (%) was more in Group Tramadol [98.82±0.72] compared to Group Clonidine [98.46±0.80] but this was not statistically significant (p=0.2121). We observed that, RR (per min) was lower in Group Tramadol [14.80±1.40] compared to Group Clonidine [15.02±1.10] but this was not statistically significant (p=0.6622).

Joshi Y et al 4 (2023) observed that, the Mean of Total Duration of Analgesia Was 206.5±8.45 Minutes in Group A, 426.5±32.16 Minutes in Group B and 632.45±89.9 Minutes in Group C. The Difference between Three Groups Was Statistically Highly Significant (P<0.001).

It was found that, Mean time of 1^st rescue analgesic (min) was most in Group Clonidine [584.48±26.90] compared to Group Tramadol [453.10±7.20] but this was statistically significant (p<0.0001).

This study suggests that, in comparison to tramadol, the addition of clonidine to bupivacaine in supraclavicular brachial plexus block results in a faster onset and longer duration of sensory and motor blockage. When it comes to side effects and hemodynamic alterations, both medications are similar. Clonidine prolongs analgesia longer than tramadol does, which lessens the need for further analgesics

1. block: a systematic review and meta-analysis of randomized trials. British journal of anaesthesia. 2014;112(3):427–39. Epub 2014/01/15. doi: 10.1093/bja/aet417 .
2. Knezevic N, Anantamongkol U, Candido K. Perineural dexamethasone added to local anesthesia for brachial plexus block improves pain but delays block onset and motor blockade recovery. Pain Physician. 2015;18:1–14.
3. Popping DM, Elia N, Marret E, Wenk M, Tramer MR. Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus blocks: a meta-analysis of randomized trials. Anesthesiology. 2009;111(2):406–15. Epub 2009/07/16. doi: 10.1097/ALN.0b013e3181aae897 .
4. Abdallah FW, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. British journal of anaesthesia. 2013;110(6):915–25. Epub 2013/04/17. doi: 10.1093/bja/aet066 .
5. Park CH. Comparison of morphine and tramadol in transforaminal epidural injections for lumbar radicular pain. The Korean journal of pain. 2013;26(3):265–9. Epub 2013/07/19. doi: 10.3344/kjp.2013.26.3.265 ; PubMed Central PMCID: PMCPMC3710940.
6. Mukherjee K, Das A, Basunia SR, Dutta S, Mandal P, Mukherjee A. Evaluation of Magnesium as an adjuvant in Ropivacaine-induced supraclavicular brachial plexus block: A prospective, double-blinded randomized controlled study. Journal of research in pharmacy practice. 2014;3(4):123–9. Epub 2014/12/24. doi: 10.4103/2279-042X.145387 ; PubMed Central PMCID: PMCPMC4262858.
7. Saryazdi H, Yazdani A, Sajedi P, Aghadavoudi O. Comparative evaluation of adding different opiates (morphine, meperidine, buprenorphine, or fentanyl) to lidocaine in duration and quality of axillary brachial plexus block. Advanced biomedical research. 2015;4:232 Epub 2015/12/09. doi: 10.4103/2277-9175.167901 ; PubMed Central PMCID: PMCPMC4647124.
8. Gormley WP, Murray JM, Fee JP, Bower S. Effect of the addition of alfentanil to lignocaine during axillary brachial plexus anaesthesia. British journal of anaesthesia. 1996;76(6):802–5. Epub 1996/06/01.
9. Fanelli G, Casati A, Magistris L, Berti M, Albertin A, Scarioni M, et al. Fentanyl does not improve the nerve block characteristics of axillary brachial plexus anaesthesia performed with ropivacaine. Acta anaesthesiologica Scandinavica. 2001;45(5):590–4. Epub 2001/04/20.
10. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs. 2000;60(1):139–76. Epub 2000/08/10.