|Year : 2016 | Volume
| Issue : 3 | Page : 176-180
Nalbuphine as an adjuvant to 0.5% bupivacaine for ultrasound-guided supraclavicular brachial plexus blockade
Kumkum Gupta1, Manish Jain1, Prashant K Gupta2, Bhawana Rastogi1, Azka Zuberi1, Mahesh Narayan Pandey1
1 Department of Anaesthesiology and Critical Care, Subharti Medical College, Swami Vivekanand University, Meerut, Uttar Pradesh, India
2 Department of Radio diagnosis and Interventional Imaging, Subharti Medical College, Swami Vivekanand University, Meerut, Uttar Pradesh, India
|Date of Web Publication||10-Jan-2017|
108-109, Chanakyapuri, Shastri Nagar, Meerut - 250 004, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Brachial plexus block is a reliable, regional anesthetic technique for upper arm surgeries. Opioid agonist-antagonists are also used as adjuvant to enhance the analgesia of bupivacaine. The present study was aimed to assess the analgesic efficacy and safety of nalbuphine as an adjuvant to 0.5% bupivacaine for brachial plexus block. Patients and Methods: Sixty adult patients of American Society of Anesthesiologists physical status I and II of both genders were randomized into two groups of thirty patients each to receive either 20 mL of 0.5% bupivacaine with 1 mL of normal saline (Group 1) or 20 mL of 0.5% bupivacaine with 1 mL of nalbuphine 10 mg (Group 2) for brachial plexus block under ultrasound guidance. Patients were observed for onset and duration of sensory and motor block with duration of pain relief as primary end points while occurrence of any adverse effect due to technique or nalbuphine was noted as secondary outcome. Results: The ultrasound guided the visualization of the nerves, needle, and spread of local anesthetic at brachial plexus block site. Nalbuphine did not affect the onset time of block but enhanced the duration of sensory and motor block. The duration of postoperative analgesia was 481.53 ± 42.45 min in Group 2 and 341.31 ± 21.42 min in Group 1, with statistically highly significant difference (P < 0.001). There were no hemodynamic variations and no complication of technique or adverse effects due to nalbuphine occurred. Conclusion: Nalbuphine 10 mg has significantly extended the duration of analgesia of brachial plexus block with no adverse effects.
Keywords: Brachial plexus block, bupivacaine, nalbuphine, supraclavicular approach, ultrasound guidance
|How to cite this article:|
Gupta K, Jain M, Gupta PK, Rastogi B, Zuberi A, Pandey MN. Nalbuphine as an adjuvant to 0.5% bupivacaine for ultrasound-guided supraclavicular brachial plexus blockade. Indian J Pain 2016;30:176-80
|How to cite this URL:|
Gupta K, Jain M, Gupta PK, Rastogi B, Zuberi A, Pandey MN. Nalbuphine as an adjuvant to 0.5% bupivacaine for ultrasound-guided supraclavicular brachial plexus blockade. Indian J Pain [serial online] 2016 [cited 2020 Aug 14];30:176-80. Available from: http://www.indianjpain.org/text.asp?2016/30/3/176/198024
| Introduction|| |
Supraclavicular brachial plexus blockade is an efficient regional anesthetic technique for upper arm surgeries. It is a reliable, alternative to general anesthesia for certain group of patients as it is devoid of undesired effects of general anesthesia and stress of laryngoscopy. The postoperative period is also free from pain, nausea, vomiting, and respiratory depression. The supraclavicular approach is chosen for brachial plexus block as here it is enclosed in a fascial sheath that extends from neck to the axilla. 
The success of brachial plexus block relies on nerve localization, needle placement, and deposition of local anesthetic solution at right place by a single injection of local anesthetic.  The conventional blind technique relies on surface landmarks before needle insertion and elicitation of paresthesia while ultrasound guidance detects the anatomical variants of brachial plexus and related anatomical structures, accurate needle placement, and monitoring of drug spread in the appropriate tissue planes with painless performance. Ultrasound increases the success rate and reduces the injury to adjacent structures. ,, It also minimized the local anesthetic volume, thereby reducing the incidences of their systemic toxicity. 
Bupivacaine relieved pain by blocking the transmission of pain signals to the dorsal horn, but it has definite risks of systemic toxicity, especially with brachial plexus block. Various adjuvants are used to augment the analgesic efficacy while reducing the dose and incidence of adverse reactions related to local anesthetics. 
Opioids have an antinociceptive effect at the central or spinal cord levels. Stimulation of opioid receptors on neurons of central nervous systems leads to the inhibition of neuronal serotonin uptake which leads to augmentation of spinal inhibitory pain pathways; however, it is still unclear whether functional opioid receptors exist in peripheral tissue.  Many opioids such as tramadol and fentanyl have been added as adjuvants to local anesthetics by different routes, including brachial plexus block, to enhance the analgesic efficacy. Opioids effect either by action on opioid receptors or finally by their systemic absorption.
Nalbuphine, an opioid agonist-antagonist, is used as adjuvant to local anesthetic for various regional anesthetic techniques due to its affinity to κ-opioid receptors to enhance the duration of analgesia. It is widely studied as an adjuvant to local anesthetics in central neuraxial techniques by epidural, caudal, and intrathecal routes.  However, after research in literature, we did not find much published data studying the effect of nalbuphine as an adjuvant to local anesthetics in peripheral nerve blocks.
The present study was undertaken to assess the clinical efficacy and safety of nalbuphine as an adjuvant to 0.5% bupivacaine for supraclavicular brachial plexus block under ultrasound guidance for various forearm and hand surgeries.
| Patients and Methods|| |
After approval of the Institutional Ethics Committee, sixty patients of American Society of Anesthesiologists (ASA) physical status I to II of both gender, aged 18-58 years with body mass index (BMI) <25 kg/m 2 , scheduled for elective forearm and hand surgeries in orthopedic and plastic surgical operation theaters, were enrolled for this prospective, randomized, double-blind control study, after obtaining written informed consent from each patient.
Patients with clinically significant coagulopathy, infection at the injection site, allergy to local anesthetics, preexisting neuromuscular, severe cardiovascular, or pulmonary disease, renal or hepatic disorder, refusal to technique, or inability to visualize the brachial plexus with ultrasound guidance or failure of block were excluded from the study. Patients taking medications with psychotropic or receiving chronic analgesic therapy other than simple analgesics were also excluded from the study. Visual analog scale (VAS) was explained to all patients where 0 corresponds to no pain and 10 indicates the worst unbearable pain.
Patients were randomized according to computer-generated random number table into two equal groups of thirty patients each. Patients of Group 1 received 20 mL of 0.5% bupivacaine with 1 mL of normal saline and patients of Group 2 received 20 mL of 0.5% bupivacaine with 1 mL of nalbuphine 10 mg for brachial plexus blockade under ultrasound guidance by supraclavicular approach.
The study drug solutions were in similar volume of 21 mL, to maintain the blindness of study and were prepared by a resident anesthetist who was not involved for data collection of the patients. The anesthetist performing the block was also blinded to the study groups, and all observations were done by the same investigator.
All patients were admitted before the day of surgery, and fasting of 6 h was ensured. On arrival in the operation theater, intravenous access was established and lactated ringer solution was infused at the rate of 6-8 mL/kg and monitors for noninvasive blood pressure, heart rate, electrocardiogram (ECG), and pulse oximetry (SpO 2 ) were commenced to monitor the perioperative vital parameters of patients.
Patients lie down supine with head turned 45° to the contralateral side with adduction of ipsilateral arm. The supraclavicular brachial plexus block was performed using a transportable ultrasound system (SonoSite MicroMax; SonoSite Inc., Bothell, WA, USA) with 38 mm 8-13 MHz linear high-frequency transducer (HFL-38) to obtain the images of brachial plexus in the transverse and longitudinal planes. 
Under all aseptic precautions, the ultrasound transducer was placed in sagittal plane in the supraclavicular fossa to visualize the brachial plexus between the anterior and middle scalene muscles. The block was performed with a 23-G 40 mm short beveled echogenic needle for optimal control and visibility. The predetermined volume of 21 mL of the study drug solution was administered around the brachial plexus after negative aspiration to avoid accidental intravascular injection, and spread of drug solution was observed in tissue planes under ultrasound imaging. Distension of brachial plexus sheath was regarded as an indication of successful block. A 3-min massage was performed to facilitate an even drug distribution. All patients were given supplemental oxygen using ventimask.
The onset of sensory block was assessed by pinprick method using 25-G hypodermic needle in the appropriate area using a 3-point scale for pain (2 - sharp pain, 1 - blunt pain, and 0 - no pain) and compared to same stimulation on contralateral arm. The onset time of sensory block was the time from completion of the injection to first loss of pinprick sensation in any dermatome (C5-T1), and duration of postoperative analgesia was defined when patient demanded the rescue analgesia.
Motor weakness was assessed by hand grip and movement at the elbow, wrist, and fingers, using a modified Bromage scale (Grade 0 - normal motor function, able to raise the extended arm to 90°; Grade 1 - able to flex the elbow and move the fingers but unable to raise the extended arm; Grade 2 - unable to flex the elbow but able to move the fingers; Grade 3 - complete motor block).  The onset time of motor block was the time from completion of the injection to reduction of muscle force to Grade 2. Motor block was also assessed by thumb abduction (radial nerve), thumb adduction (ulnar nerve), and thumb opposition (median nerve). Duration of motor block was taken from onset of motor block to complete recovery of full muscle power and was determined by asking the patients to note the time when they could first move their fingers of blocked limb.
Patients were assessed for onset of sensory and motor blockade at every 5 min interval till desired surgical anesthesia achieved with time 0 min being the time of completion of the injection. If after 30 min of study drug infiltration at block site, any major nerve involved in the planned surgical intervention, had a sensitivity of more than 30%, was separately blocked and patients were excluded from the study.
Intraoperative vital parameters of blood pressure, heart rate, respiratory rate, and peripheral oxygen saturation were monitored initially at 5 min interval until 30 min and then at 10 min interval until completion of surgery. Patients were observed for any incidence of hypotension, bradycardia, fall in peripheral oxygen saturation, any discomfort, nausea, vomiting, shivering, pruritus, pain, or any other adverse effect and were managed according to clinical protocol.
Postoperative pain was assessed using 10-point VAS, 0 - no pain to 10 - worst pain at 1 h interval till demand of rescue analgesia (VAS ≥3). Injection tramadol 100 mg with ondansetron 4 mg was given intravenously as rescue analgesic.
Study population size and statistical analysis
Sample size was calculated with standard computer programs which computed that approximately 24-27 patients should be included in each group to detect clinically significant difference (>20%) in duration of block and postoperative analgesia between the groups with alpha error of 0.05 with 80% 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, considering the latter as the best predictor. Statistical analysis was performed using statistical program SPSS 20.0 Software for social science (SPSS INC, Chicago, IT, 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|| |
The present study evaluated the clinical efficacy and safety of nalbuphine as an adjuvant to 0.5% bupivacaine for supraclavicular brachial plexus block under ultrasound guidance for various forearm and hand surgeries. Data of all patients were included for statistical analysis.
Patients of both groups were comparable with respect to the demographic profile for age, sex distribution, ASA physical status, BMI, and duration of operational factors of forearm and hand surgeries [Table 1].
The ultrasound helped visualize the nerves, needle, and spread of study drug solution at the brachial plexus block site and brachial plexus block was successful in all patients and surgery could be performed uneventfully.
The baseline vital parameters of heart rate, systemic blood pressure, and oxygen saturation were comparable between the groups. Intraoperatively, hemodynamic changes did not reveal any significant difference between the groups and all patients remained hemodynamically stable throughout the surgery.
Onset of sensory and motor block was rapid in patients of nalbuphine group but showed no statistically significant difference (P > 0.05). Patients of nalbuphine group also showed delayed sensory block regression. The mean duration of motor block was 257.69 ± 30.19 min in patients of Group 1 when compared to Group 2 (278.53 ± 34.61 min), and difference was statistically significant (P = 0.038). The duration of analgesia in patients of Group 2 was 481.53 ± 42.45 min and in patients of Group 1 was 341.31 ± 21.42 min with P < 0.001. When comparing the duration of analgesia, a statistically highly significant difference was found between the groups [Table 2].
|Table 2: Sensory and motor blockade characteristics of brachial plexus block|
Click here to view
None of the patients required rescue analgesia intraoperatively. Pain score was significantly lower in patients of Group 2 (mean 1.44) when compared to Group 1 (mean 5.6) at 6 h postoperatively. Quality of analgesia was also better when nalbuphine was used as adjuvant.
Perioperative hemodynamic parameters of blood pressure, heart rate, and ECG were stable. The respiratory rate and peripheral oxygen saturation were comparable between the groups. There was no complaint of difficulty in breathing or any clinical evidence of diaphragmatic palsy or pneumothorax in any patient. No complications of anesthetic technique or drug-related adverse effects such as nausea, vomiting, pruritus, or dry mouth were observed in any patient.
| Discussion|| |
Brachial plexus blockade is commonly performed regional anesthetic technique for forearm and hand surgeries, and its blockage provides good surgical anesthesia. It is most compactly arranged in supraclavicular region, and hence smaller volume of local anesthetic drug produces reliable and intense block with optimal tourniquet coverage. Supraclavicular approach is easy to perform even if arm is immobilized.
During the present study, the brachial plexus was successfully blocked under ultrasound guidance, and the anatomical variations of important structures, individual nerves, and accurate needle placement could be visualized at brachial plexus site before infiltration of study drug solutions.
Most studies have shown effective surgical anesthesia with negligible side effects with ultrasound guidance as compared to conventional techniques. Neal et al. concluded that there was significant reduction in the frequency of complication of nerve injury, vascular puncture, and hemi-diaphragmatic paresis under ultrasound guidance.  Sαinz López et al. demonstrated that ultrasound guidance enabled the use of reduced dose of local anesthetic for supraclavicular brachial plexus block to minimize the risks of the systemic toxicity of local anesthetic drugs.  In the present study, we have used only 100 mg of bupivacaine to establish the effective block and our assessment was in accordance to their findings.
Different opioids' medications have been added to local anesthetic to improve the quality and duration of postoperative analgesia of peripheral nerve blocks.  Many previous studies have attempted to determine whether the addition of opioid to local anesthetics would improve the clinical efficacy of peripheral nerve blocks and demonstrated that different types of opioids act well on peripheral nerve through stimulation of opioid receptor, but they were associated with unacceptable adverse effects. Tramadol and fentanyl were commonly used as adjuvant to local anesthetic drug in brachial plexus block.  Systemic review of various adjuvants for brachial plexus block suggested that the nalbuphine appeared to possess greater analgesic efficacy with minimal adverse effects.
Nalbuphine is a mixed k-agonist and μ-antagonist opioid, and its affinity to k-opioid receptors results in analgesia, sedation, and cardiovascular stability with minimal respiratory depression. It may potentiate local anesthetic action through central opioid receptor-mediated analgesia by peripheral uptake of nalbuphine to systemic circulation.
Young et al. demonstrated that opioid receptors and various macromolecules in the nerve undergo axonal flow.  Opioids penetrate the nerve membrane and act at the dorsal horn. Laudren showed that proteins undergo bidirectional axonal transport and speculated that these receptors circulate endorphins, their endogenous ligands, in addition to exogenous opioids which prove that opioids act directly on peripheral nervous system. 
The present study revealed that addition of nalbuphine 10 mg with 20 mL of 0.5% bupivacaine significantly enhanced the quality of supraclavicular brachial plexus block and increased the duration of sensory and motor block, but it did not affect the onset time of the blockade.
There is a great similarity between butorphanol and nalbuphine regarding the chemical nature and mode of action on opioid receptors, and inhibition of neuronal serotonin uptake which leads to augmentation of the spinal inhibitory pathways for pain.
Acharya et al. studied the effect of 2 mg butorphanol as an adjuvant to bupivacaine in supraclavicular nerve block to the patients scheduled for elective surgery upper limb and concluded that butorphanol prolongs the duration of brachial plexus block. 
In the present study, there was also a significant increase in the duration of analgesia in patients who received nalbuphine as an adjuvant (481.53 ± 42.45 min) as compared to another group (341.31 ± 21.42 min). This enhancement may be due to the synergistic action of nalbuphine with bupivacaine.
Viel et al. showed that injection buprenorphine into the brachial plexus sheath using supraclavicular technique is an efficient way to control postoperative pain after upper limb surgery. 
Youssef and ElZayyat compared the effect of nalbuphine with tramadol as adjuvants to lidocaine in intravenous regional anesthesia and concluded that both nalbuphine and tramadol were comparable, but nalbuphine was more effective than tramadol for prolonging the duration of postoperative analgesia. 
Abdelhaq and Elramely  also used 20 mg nalbuphine as adjuvant to 25 mL of 0.5% bupivacaine for supraclavicular brachial plexus block for upper arm surgeries and concluded that nalbuphine has significantly increased the duration of both sensory and motor block along with prolonged postoperative analgesia. In the present study, we observed the statistically enhanced duration of sensory and motor block along with duration of analgesia even in reduce doses of 10 mg nalbuphine with 20 ml of 0.5% bupivacaine for upper arm surgeries.
The benefits of nalbuphine were not associated with any hemodynamic variability or any adverse event. As nalbuphine is agonist to κ receptor and antagonist to μ receptors, it is devoid of pruritus, nausea, vomiting, and respiratory depression. The intraoperative changes in vital parameters and oxygen saturation showed insignificant difference between the groups during the present study. Patients were comfortable due to painless performance and no immediate postoperative pain or side effects.
| Conclusion|| |
Nalbuphine 10 mg as an adjuvant to 0.5% bupivacaine for supraclavicular brachial plexus block in patients undergoing various forearm and hand surgeries is associated with enhanced duration of analgesia without any adverse effect. There was no incidence of technique-related complications because of ultrasound guidance. Nalbuphine may be one more addition to the expanding list of adjuvants to local anesthetics.
The authors would like to acknowledge the all technical staff of orthopedic and surgical operation theaters and patients who gave consent for enrolment for the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Neal JM, Gerancher JC, Hebl JR, Ilfeld BM, McCartney CJ, Franco CD, et al.
Upper extremity regional anesthesia: Essentials of our current understanding, 2008. Reg Anesth Pain Med 2009;34:134-70.
Dureja GP. Ultrasound guidance in regional anesthetic: Is it the gold standard? Editorial. J Anaesth Clin Pharmacol 2007;23:119-20.
Marhofer P, Greher M, Karpal S. Ultrasound guidance in regional anesthesia. Br J Anesth 2005;95:226-30.
Denny NM, Harrop-Griffiths W. Location, location, location! Ultrasound imaging in regional anaesthesia. Br J Anaesth 2005;94:1-3.
Duggan E, El Beheiry H, Perlas A, Lupu M, Nuica A, Chan VW, et al.
Minimum effective volume of local anesthetic for ultrasound-guided supraclavicular brachial plexus block. Reg Anesth Pain Med 2009;34:215-8.
Förster JG, Rosenberg PH. Clinically useful adjuvants in regional anaesthesia. Curr Opin Anaesthesiol 2003;16:477-86.
Fields HL, Emson PC, Leigh BK, Gilbert RF, Iversen LL. Multiple opiate receptor sites on primary afferent fibres. Nature 1980;284:351-3.
Gunion MW, Marchionne AM, Anderson TM. Use of the mixed agonist-antagonist nalbuphine in opioid based analgesia. Acute Pain 2004;6:29-39.
Perlas A, Lobo G, Lo N, Brull R, Chan VW, Karkhanis R. Ultrasound-guided supraclavicular block: Outcome of 510 consecutive cases. Reg Anesth Pain Med 2009;34:171-6.
Cline E, Franz D, Polley RD, Maye J, Burkard J, Pellegrini J. Analgesia and effectiveness of levobupivacaine compared with ropivacaine in patients undergoing an axillary brachial plexus block. AANA J 2004;72:339-45.
Sáinz López J, Prat Vallribera A, Seguí Pericas M, Samà Pujolar A, Calleja Abad M, Sabater Recolons J, et al.
Ultrasound-guided supraclavicular brachial plexus block with small volumes of local anesthetic: Technical description and analysis of results. Rev Esp Anestesiol Reanim 2006;53:400-7.
Kaabachi O, Ouezini R, Koubaa W, Ghrab B, Zargouni A, Ben Abdelaziz A. Tramadol as an adjuvant to lidocaine for axillary brachial plexus block. Anesth Analg 2009;108:367-70.
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. Adv Biomed Res 2015;4:232.
Young WS 3 rd
, Wamsley JK, Zarbin MA, Kuhar MJ. Opioid receptors undergo axonal flow. Science 1980;210:76-8.
Laudren PM. Axonal transport of opiate receptors in capsaicin-sensitive neurons. Brain Res 1984;68:413.
Acharya R, Jena M, Mishra S, Rath SK. Effect of butorphanol versus placebo as adjuvant to bupivacaine for supraclavicular brachial plexus blockade. Int J Appl Pharm 2014;6:8-10.
Viel EJ, Eledjam JJ, De La Coussaye JE, D′Athis F. Brachial plexus block with opioids for postoperative pain relief: Comparison between buprenorphine and morphine. Reg Anesth 1989;14:274-8.
Youssef MM, ElZayyat NS. Lidocaine-nalbuphine versus lidocaine-tramadol for intravenous regional anesthesia. Ain Shams J Anaesthesiol 2014;7:198-204.
Abdelhaq MM, Elramely MA. Effect of nalbuphine as adjuvant to bupivacaine for ultrasound-guided supraclavicular brachial plexus block. Open J Anesthesiol 2016;6:20-6.
[Table 1], [Table 2]