|Year : 2017 | Volume
| Issue : 2 | Page : 112-118
Buprenorphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block: A randomized, double-blind, prospective study
Neena Jain, Arvind Khare, Shubham Khandelwal, Pooja Mathur, Maina Singh, Veena Mathur
Department of Anesthesiology, Jawaharlal Nehru Medical College, Ajmer, Rajasthan, India
|Date of Web Publication||6-Sep-2017|
Department of Anaesthesiology, Jawaharlal Nehru Medical College, Ajmer - 305 001, Rajasthan
Source of Support: None, Conflict of Interest: None
Context: Ultrasound-guided supraclavicular brachial plexus block is ideal for upper limb surgical procedures. Buprenorphine used as an adjuvant to ropivacaine may prolong analgesia. Aims: The aim is to assess the analgesic efficacy and safety of buprenorphine added to 0.5% ropivacaine solution. Settings and Design: This prospective, double-blind, randomized study was conducted on 60 adult patients of the American Society of Anesthesiologists physical Status I and II undergoing various upper limb surgeries under ultrasound-guided supraclavicular brachial plexus block. Subjects and Methods: Patients were allocated into two groups of 30 each to receive either 30 ml 0.5% ropivacaine with 1 ml buprenorphine (0.3 mg) (Group B) or 30 ml 0.5% ropivacaine with 1 ml normal saline (Group C) for supraclavicular brachial plexus block. Onset, duration, and quality of sensory block and motor block; duration of analgesia and side effects were observed. Results: The mean duration of analgesia was significantly longer in Group B (868.2 ± 77.78 min) than in Group C (439.3 ± 51.19 min). The mean duration of motor and sensory block were significantly longer in Group B (451.8 ± 57.18 min) and (525.8 ± 50 min), respectively, than in Group C (320.5 ± 43.62 min) and (373 ± 53.78 min), respectively (P < 0.05). Conclusions: Addition of buprenorphine to ropivacaine for ultrasound-guided supraclavicular brachial plexus block prolonged the duration of sensory and motor blockade and postoperative analgesia without an increase in side effects.
Keywords: Analgesia, brachial plexus block, buprenorphine, ropivacaine, ultrasound
|How to cite this article:|
Jain N, Khare A, Khandelwal S, Mathur P, Singh M, Mathur V. Buprenorphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block: A randomized, double-blind, prospective study. Indian J Pain 2017;31:112-8
|How to cite this URL:|
Jain N, Khare A, Khandelwal S, Mathur P, Singh M, Mathur V. Buprenorphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block: A randomized, double-blind, prospective study. Indian J Pain [serial online] 2017 [cited 2019 Jul 21];31:112-8. Available from: http://www.indianjpain.org/text.asp?2017/31/2/112/214116
| Introduction|| |
Regional anesthesia techniques provide important advantages over general anesthesia (GA) such as excellent pain control, reduced side effects, and shortened stay in the postanesthesia care unit for upper limb surgeries., Ultrasound-guided technique of supraclavicular brachial plexus block picks up any abnormal anatomical variations, provides real-time imaging guidance during needle advancement and local anesthetic spread, improves the quality of block and the success rate, reduces local anesthetic dose and is devoid of complications such as intravascular injection and inadvertent pneumothorax.,
However, these early advantages can be short-lived and limited by the relatively brief duration of action of currently available local anesthetics (LAs), potentially resulting in block resolution before the period of worst postoperative pain. To overcome this, many opioids have been tried with local anesthetics to prolong intraoperative anesthesia and postoperative analgesia.,, Peripheral opioid administration improves regional anesthesia without centrally mediated side effects.
Ropivacaine an LA, having similar pharmacology to bupivacaine; however has a wider safety margin due to its reduced lipophilicity resulting in decreased potential for the central nervous system toxicity and cardiotoxicity.,,,,
Buprenorphine, a lipophilic opioid has high molecular weight, high affinity for μ receptor, longer duration of action,,,, is easily available and is cost-effective, also possesses lesser degree of significant side effects such as respiratory depression and sedation when compared to other opioids.,
After thorough research in literature, we found very few published data studying the effect of buprenorphine as an adjuvant to ropivacaine for peripheral nerve blocks.
Therefore, the present study was undertaken to study the effects of addition of 0.3 mg buprenorphine to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block.
| Subjects and Methods|| |
After approval from the Hospital Ethical Committee, this prospective, double-blind, randomized study was conducted on sixty consenting adult patients of the American Society of Anesthesiologists (ASA) physical status I and II in the age group 18–60 years, posted for various upper limb orthopedic surgeries under ultrasound-guided supraclavicular brachial plexus block.
Nonconsenting patients, patients with peripheral neuropathy, coagulation disorders, known allergy to the drugs used in the study, local infection at site of injection, and history of seizures were excluded from the study. After satisfying inclusion and exclusion criteria, a thorough preoperative evaluation was performed. The patients were briefed about the technique of ultrasound-guided supraclavicular block to be performed, its advantages over GA and also about the associated complications. Informed consent was obtained from every patient before the study, and they were familiarized with the use of visual analog scale (VAS) scoring system (0: no pain and 10: maximum/worst imaginable pain). The patients were kept fasting 8 h before surgery.
Patients were randomized according to the computer-generated random number table into two equal groups of thirty patients each. Both groups received similar volume of 31 ml solution prepared by an independent anesthetist not involved in data collection. Group B received 30 ml injection 0.5% ropivacaine (ropin 0.5% 20 ml) and 1 ml injection buprenorphine (0.3 mg) (buprigesic 0.3 mg/ml 2 ml) whereas Group C received 30 ml injection 0.5% ropivacaine and 1 ml normal saline [Figure 1]. The anesthetist performing the block was blinded to the study groups and all observations were done by the same investigator.
On arrival of patients in operation theater, standard monitors such as pulse oximetry, electrocardiography (ECG), and noninvasive blood pressure (NIBP) were connected. Baseline pulse rate, oxygen saturation, and blood pressure were recorded. An intravenous cannula was secured and fluid was started. Injection midazolam 0.01 mg/kg intravenously was given to relieve anxiety. Oxygen was administered at rate of 3–5 L/min with face mask. Constant verbal contact was maintained while performing the block. The patients were placed in supine position with a pillow, arms adducted and head tilted 45° to the opposite side. Supraclavicular brachial plexus block was performed using an ultrasound system using a 8–13 MHz linear high-frequency transducer to obtain images of brachial plexus in transverse plane.
The site was marked and cleaned with 5% povidone-iodine and spirit and draped. Transducer probe was coated with sterile gel and placed in supraclavicular region above the clavicle. Probe was moved laterally or medially and rocked back and forth until the best possible transverse view of the subclavian vessels and brachial plexus was obtained. Once the artery, rib, pleura, and plexus were simultaneously in view, an 18 gauge needle was inserted by “in plane” approach from the lateral side of the probe and placed above the plexus.
A predetermined volume (31 ml) of local anesthetic solution was injected after negative aspiration into the corner pocket which is present between the first rib inferiorly, supraclavicular artery medially, and nerves superiorly. Spread of local anesthetic was observed as distension of brachial plexus sheath and nerves started floating [Figure 2].
|Figure 2: Ultrasound-guided image of supraclavicular brachial plexus by a linear high-frequency transducer right supraclavicular brachial plexus (yellow arrow), subclavian artery lying on the first rib, P = pleura, *corner pocket. Lateral to medial, in plane approach of needle (white arrow) advancing toward the corner pocket|
Click here to view
Thereafter, the needle was repositioned to distribute the solution around all nerve trunks and divisions within the plexus sheath. Needle was removed and area was cleaned with sterile paper towel and sealed with sterile dressing.
Heart rate, NIBP, and oxygen saturation were recorded at 5 min intervals throughout the procedure during intraoperative period and postoperatively hourly up to 15 h. The following observations were made – onset, duration, and quality of sensory block and motor block; duration of analgesia; any complications/side effects and supplementation with sedation/GA.
Assessment of sensory block was done at 5 min intervals till 30 min after injection in the appropriate area by pinprick test with a blunt 23 G hypodermic needle, using a 3point scale (0 - normal sensation, 1 - loss of sensation of prick [analgesia], and 2 - loss of sensation of touch [anesthesia]) and compared to same stimulation on contralateral arm. The onset time of sensory block was the time from injection till the sensory block score reached one while the time for the complete sensory block (TCSB) was the time from injection till the sensory block score reached two. The total duration of the sensory block was duration of the time between TCSB till the time when the score reached <2 in the postoperative period.
Assessment of motor block was done at 5 min intervals till 30 min after injection by modified Bromage 3-point score (0 - normal motor function with full flexion and extension of elbow, wrist, and fingers, 1 - decrease motor strength with ability to move fingers and/or wrist only, and 2 - complete motor blockade with inability to move fingers). The onset time of the motor block was time from injection till the motor block score reached one. The time for complete motor block (TCMB) was time from injection till the motor block score reached two. The total duration of the motor block was duration of the time between TCMB till the time when the score reached <2.
Duration of analgesia was measured as time interval between complete sensory block (TCSB) till VAS ≥3 or patient demanded for postoperative analgesic.
The block was considered failed if complete sensory and/or motor block was not achieved after 30 min and GA was given. During the procedure, complications, if any, including vessel injury, hematoma, nausea and vomiting, dyspnea, fall in respiratory rate or oxygen saturation, any symptom/sign of local anesthetic toxicity, ECG changes, and sedation were monitored and recorded. VAS assessment was done every 5 min for the first 30 min; then half hourly for the first 8 h then every 1 hourly till patient complained of pain equivalent to a VAS score of 4.
Study population size and statistical analysis
Sample size was calculated based on previous study by Patil et al., which computed that approximately 25 patients should be included in each group to detect clinically significant difference in onset and duration of block and postoperative analgesia between the groups with alpha error of 0.05 with 90% power and 95% confidence limit. Assuming a 5% drop out rate, the final sample size was determined to retain sixty patients for better validation of results.
The obtained data are expressed as mean and standard deviation. Statistical analysis was performed using statistical program SPSS 20.0 Software (SPSS Inc., Chicago, IL, USA) for comparing observed data by Student's t-test, Chi-square test, and Mann–Whitney U-test. P < 0.05 was considered statistically significant.
| Results|| |
Both the groups were comparable with regards to age, ASA physical status, sex ratio, and duration of surgery [Table 1]. Baseline heart rate, oxygen saturation, and mean arterial pressure were comparable between the groups.
The mean onset time for sensory block was significantly faster in the Group B (8.60 ± 2.82 min) as compared to Group C (10.67 ± 3.02 min). The mean onset time of motor block was significantly shorter in the Group B (11.13 ± 1.89 min) as compared to the Group C (14.13 ± 2.60 min) [Figure 3].
|Figure 3: Bar chart showing comparison of onset of sensory and motor block|
Click here to view
The mean duration of sensory blockade (duration of surgical anesthesia) was significantly longer in Group B (525.8 ± 50.00 min) as compared to Group C (373.0 ± 53.78 min). The mean duration of motor blockade was significantly longer in Group B (451.8 ± 57.18 min) as compared to Group C (320.5 ± 43.62 min). The mean duration of analgesia (time to rescue analgesia) was significantly longer in Group B (868.2 ± 77.78 min) as compared to Group C (439.3 ± 51.19 min) [Figure 4] and [Table 2].
The patients in group B had significantly higher grades of sensory and motor block as observed at different time intervals starting from 5 min after the injection. Thus, the quality of sensory and motor block (rapidity to achieve dense blockade) was significantly better in group B as compared to Group C (P< 0.05) [Figure 5] and [Figure 6].
The intraoperative mean heart rate, mean blood pressure, and oxygen saturation did not deviate significantly from their baseline values at most of the time intervals throughout the surgery in both the groups with P > 0.05. The intraoperative mean heart rate, mean blood pressure, and oxygen saturation were also compared between both the groups at various time intervals and were found to be comparable throughout the intraoperative period. There were five patients in Group B who complained of nausea and vomiting [Figure 7] as compared to two patients in Group C [Figure 8] which were statistically insignificant (P = 0.2276).
| Discussion|| |
Supraclavicular brachial plexus block is a commonly performed regional anesthetic technique for forearm and hand surgeries, and provides good surgical anesthesia. The nerve trunks are most compactly arranged in supraclavicular region, and hence smaller volume of the local anesthetic drug produces rapid, reliable, and intense block with high success rate., Supraclavicular approach is easy to perform even if the arm is immobilized.
During this study, the supraclavicular block was performed by ultrasound technique which conferred unmatched precision and utmost safety to the procedure leading to successful blocks in almost all the patients and avoiding the dreadful complications of the procedure such as intravascular injection and pleural puncture.
Ropivacaine, a long-acting anesthetic is a pure S(−) enantiomer, unlike bupivacaine which makes it less lipophilic and less likely to penetrate large myelinated Aβ motor fibers, resulting in a relatively reduced motor blockade. The reduced lipophilicity is also associated with decreased potential for the central nervous system toxicity and cardiotoxicity.,,,, Hence, we preferred ropivacaine over bupivacaine in our study.
Various opioids have been tried successfully as adjuvants in peripheral nerve blocks.,, Buprenorphine, an opioid agonist-antagonist, is a semi-synthetic derivative of an opiate alkaloid thebaine that has a unique cyclopropylmethyl group. It possesses a significantly distinct profile from other opioids, being a μ, δ, and nociceptin opioid receptor (NOP) agonist and κ-opioid receptor antagonist. It has partial agonism on μ-opioid receptor (μ-OR), showing a high affinity but low intrinsic activity. By binding to the receptor, it induces the activation of a second messenger, the G protein, which is same for all opioid receptors. The binding capacity for the μ-OR and slow dissociation determines its longest duration of action of all opioid drugs ,,,,,, leading to lesser requirements of other modalities of analgesia in postoperative period. Hence, we preferred buprenorphine over other opioids.
Our study demonstrated significantly faster onset of sensory and motor block in buprenorphine group. This can be attributed to high analgesic potency determined by its high lipid solubility which leads to faster penetration of lipid membranes, binding to receptors, and hastening of block. Similar results in the onset of sensory block were observed by Behr et al. and in the onset of motor block by Singam et al. and Patil et al. but the P value was insignificant in both the studies. All of these studies used buprenorphine with different local anesthetic agents. Behr et al. studied the effect of adding buprenorphine to levobupivacaine, whereas Singam et al. and Patil et al. studied the effect of adding buprenorphine to bupivacaine and a combination of bupivacaine and lignocaine, respectively.
Our study demonstrated significantly longer durations of sensory and motor block in group receiving buprenorphine as an adjunct. Orthopedic surgeries can be of prolonged duration. Thus, prolonged sensory and motor blockade along with prolonged analgesia are of utmost importance in these surgeries. Patients receiving buprenorphine also demonstrated significantly longer duration of analgesia up to two times than the control group. Prolonged duration of analgesia by buprenorphine can be explained by its high binding capacity and affinity for μ receptors. It dissociates slowly from its receptors which results in longer duration of action. Similar findings of prolongation of duration in sensory and motor block and duration of analgesia were observed by Sarkar et al., Singam et al., Patil et al., and other studies.,,
It has been studied that perineurally administered opioids exert their analgesic effect through both central and peripheral mechanisms.,, The mechanisms for centrally mediated analgesia have been postulated to be its easy penetration through the axonal myelin and nerve membrane and then centripetal axonal transport of opioids into substantia gelatinosa and alternatively, diffusion from the brachial plexus sheath to extradural and subarachnoid spaces and then bind with opioid receptors in the dorsal horn., Various mechanisms have been proposed for peripheral action. First, buprenorphine has recently been shown to interact with the opioid receptor like-1 receptor , which has distinct pharmacological characteristics, activation of which leads to inhibition of the enzyme adenylate cyclase, calcium-channel conductance,, and activation of inwardly rectifying potassium channels., The analgesic effect of buprenorphine is the effect of the suppression of spinal synaptic transmission by alteration of these two ion channels., Second, it can only be partially explained by migration of buprenorphine from the proximal to the distal part of the neuron along the axoplasm, to reach the active place in response to the inflammatory factor  as this process takes days to develop. The most plausible explanation of the intense action of buprenorphine peripherally is potent property of buprenorphine as a local anesthetic. By binding to intramembranous part of receptor, it mediates the tonic and concentration-dependent blockade of Na + channels and electrically induced action potential in the terminal endings of C-fibers is blocked. This property is greater than other opioids and several local anesthetics. Another potentially attractive explanation is its systemic absorption and antihyperalgesic effect (phenomenon specific for buprenorphine) mediated by its agonistic effect on NOP receptors.
We observed that five patients in buprenorphine group (Group B) complained of nausea and vomiting as compared to two patients in plain ropivacaine group (Group C) for which injection ondansetron 4 mg intravenously was given. Hence, it was observed that side effects in both the groups were not statistically significant (P< 0.2276). None of the patients in either group complained of pruritus, urinary retention, sedation, respiratory depression, pneumothorax, or any neurological sequelae. Buprenorphine being a μ-receptor partial agonist, leads to all opioid effects: analgesia, sedation, euphoria, and respiratory depression, but to a lesser degree than morphine and other opioids, which increases the safety margin compared to classical opioids.,,, It has a dose-ceiling effect on respiratory depression, but not on analgesia. The relative incidence of respiratory depression does not increase after increasing the dose substantially and achieves a plateau effect.,,, It has antagonistic effect on δ and κ-opioid receptors, which explains its less sedative and psychotomimetic effect than morphine or fentanyl.
The contribution of naloxone in reversal of severe respiratory depression produced by overdosing of buprenorphine still remains controversial. It has been studied that particularly very high doses of naloxone >2–4 mg followed by infusion are needed for reversal. Reversal may be short lived or complete reversal even may not be achieved owing to partial agonism on μ receptor, high affinity, slow dissociation of buprenorphine from its receptors, and short-lived action of naloxone., For trainees and novices, the use of generalized central nervous stimulants such as doxapram (single injection or infusion) has been advocated which ensures almost complete reversal.,
| Conclusion|| |
Addition of 1 ml (0.3 mg) buprenorphine to 0.5% ropivacaine 30 ml, shortens the onset of sensory and motor block, prolongs the duration of sensory block, motor block and analgesia significantly, without increasing the adverse effects. The use of ultrasound averts any technique related complications. Thus, buprenorphine can be used as an ideal and safe adjuvant to ropivacaine for ultrasound-guided supraclavicular brachial plexus block in patients undergoing upper limb surgery.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2]