|Year : 2019 | Volume
| Issue : 2 | Page : 82-88
Efficacy of nalbuphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block in upper limb surgeries: A prospective randomized double-blind study
Kavita Jain, Surendra Kumar Sethi, Suman Gupta, Arvind Khare
Department of Anaesthesiology, Jawaharlal Nehru Medical College and Hospital, Ajmer, Rajasthan, India
|Date of Submission||30-Apr-2019|
|Date of Acceptance||01-Jul-2019|
|Date of Web Publication||28-Aug-2019|
Dr. Surendra Kumar Sethi
Department of Anaesthesiology, Jawaharlal Nehru Medical College and Hospital, JLN Medical College Circle, Near Kala Bagh, Ajmer - 305 001, Rajasthan
Source of Support: None, Conflict of Interest: None
Background: The benefit of postoperative analgesia in regional block is short lived due to limited duration of action of local anesthetics. Various adjuvants have been tried to enhance the duration of analgesia. The aim of this study was to evaluate the analgesic efficacy and safety of nalbuphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block.
Methods: A prospective, randomized, double-blind study was conducted on 100 patients of American Society of Anesthesiologists physical status I/II aged 18–70 years scheduled for upper limb surgeries under USG supraclavicular brachial plexus block. The patients were randomly allocated into two groups of 50 each to receive either 20 ml of 0.5% ropivacaine with 1 ml of normal saline (Group A) or 20 ml of 0.5% ropivacaine with 1 ml (10 mg) of nalbuphine (Group B). The onset and duration of sensory and motor block, duration of analgesia, and side effects were noted.
Results: There was no significant difference in mean onset of sensory and motor blocks between the two groups; but in Group B, there was significantly longer duration of sensory block (401.20 ± 19.963 vs. 387.60 ± 29.731 min, P = 0.009), longer duration of motor block (333.20 ± 20.941 vs. 323.00 ± 26.283 min, P = 0.03), and prolonged duration of analgesia (502.60 ± 22.751 vs. 441.20 ± 30.815 min, P < 0.0001) as compared to Group A. No significant side effects were observed in any of the two groups (P > 0.05).
Conclusion: Nalbuphine (10 mg) used as an adjuvant to 0.5% ropivacaine for supraclavicular brachial plexus block prolonged the duration of both sensory and motor blockade along with the duration of postoperative analgesia without any increase in side effects.
Keywords: Analgesia, brachial plexus block, nalbuphine, ropivacaine, ultrasound guided
|How to cite this article:|
Jain K, Sethi SK, Gupta S, Khare A. Efficacy of nalbuphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block in upper limb surgeries: A prospective randomized double-blind study. Indian Anaesth Forum 2019;20:82-8
|How to cite this URL:|
Jain K, Sethi SK, Gupta S, Khare A. Efficacy of nalbuphine as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block in upper limb surgeries: A prospective randomized double-blind study. Indian Anaesth Forum [serial online] 2019 [cited 2020 Jan 21];20:82-8. Available from: http://www.theiaforum.org/text.asp?2019/20/2/82/265647
| Introduction|| |
Pain is an important issue to be addressed by an anesthesiologist. The effective pain management leads to earlier mobilization with reduced risk of deep venous thrombosis, less risk of cardiac complications, shortened hospital stay, and increased patient satisfaction. Regional anesthesia has important advantage of postoperative pain-free period. With the increasing use of ultrasound, a dramatic upsurge has been seen in regional anesthesia particularly for upper limb surgeries. Ultrasound-guided (USG) brachial plexus block allows operator to visualize anatomical variations and local anesthetic (LA) spread at right location, and it is possible to administer the block in easy, quick, safe, and effective way.,
Ropivacaine, an amide LA, has decreased potential for the central nervous system toxicity and cardiotoxicity due to reduced lipophilicity which provides wider safety margin., Due to brief duration of action of LAs, various adjuvants along with LAs have been tried to extend the duration of analgesia in regional blocks. Peripheral opioid administration prolongs analgesia without producing systemic side effects. Nalbuphine is a mixed k-agonist-μ-antagonist opioid with a moderate analgesic effect when compared to morphine. Easy availability, low cost, and less side effects make it more suitable than other commonly used opioids.
Very few studies have been conducted to evaluate the efficacy of nalbuphine as an adjuvant to ropivacaine in peripheral nerve blocks (PNBs). We hypothesized that nalbuphine, when used as an adjuvant to LA, would improve the efficacy of block in terms of prolonging the duration of intraoperative and postoperative analgesia with minimal side effects. Hence, the present study was undertaken to assess the analgesic efficacy and safety of nalbuphine (10 mg) as an adjuvant to 0.5% ropivacaine for ultrasound-guided supraclavicular brachial plexus block.
| Methods|| |
After approval of the institutional ethical committee, this prospective, double-blind, randomized trial was conducted on hundred patients of the American Society of Anesthesiologists (ASA) physical status I and II of both gender, aged 18–70 years, scheduled for various upper limb orthopedic surgeries after obtaining written informed consent from each patient. Patients who had not given consent, patients with coagulopathy, infection at the site of block, preexisting peripheral neuromuscular disease, and allergy to any of the study drugs i.e., nalbuphine or ropivacaine were excluded from the study.
The patients were randomly allocated into two groups of 50 each using computer-generated table of random numbers. The allocation concealment was done using sequentially numbered closed opaque-sealed envelope technique. Group A (plain ropivacaine group) received 20 ml of 0.5% ropivacaine with 1 ml of normal saline and Group B (nalbuphine group) received 20 ml of 0.5% ropivacaine with 1 ml (10 mg) of nalbuphine (total volume of study drug is 21 ml in both groups). A resident anesthesiologist, who was not involved in the study process, prepared the syringes loaded with the study drugs for supraclavicular block and the another anesthesiologist who performed the block and observed the patient thereafter was unaware about the contents of the loaded syringes for the purpose of double blinding so both the anesthesiologist who prepared the drugs and the observer who performed the block as well as assessed the results, were blinded [Figure 1].
All the patients had undergone preanesthetic evaluation with complete history, physical examination, and routine investigations on the day before surgery. A 10-cm visual analog scale (VAS) was also explained to all patients where 0 corresponds to no pain and 10 indicates the worst imaginable pain. All the patients were kept nil per oral for a minimum of 6 h before surgery.
On arrival of patients in operation theater, fasting status, consent, and preanesthetic checkup were confirmed, and standard ASA monitors including pulse oximetry (SpO2), electrocardiography, and noninvasive blood pressure were attached. Baseline pulse rate (PR), oxygen saturation, and blood pressure were recorded. An intravenous (IV) access was established using 18–20 G IV cannula on the nonoperative arm, and crystalloid infusion (Ringer lactate) was started at the rate of 6–8 ml/kg. IV midazolam 0.01 mg/kg was given to relieve anxiety. The patients were placed in the supine position with head turned 45° to the opposite side and adduction of ipsilateral arm.
All the patients received brachial plexus block through the supraclavicular approach using a 8–13 MHz linear high-frequency ultrasound transducer. Under all aseptic precautions, transducer probe was placed in supraclavicular region above the clavicle to obtain best possible transverse view of the subclavian artery and brachial plexus. A 22 G needle was inserted by “in plane approach” and advanced toward the corner pocket which is present between the first rib inferiorly, subclavian artery medially, and plexus superiorly. LA solution was injected after negative aspiration into the corner pocket, and spread of LA was observed. Thereafter, the needle was repositioned to distribute the solution around all nerve trunks within the plexus sheath with frequent negative aspiration. The time of injection given was noted. All the patients were given supplemental oxygen via oxygen mask at 4 L/min. The primary outcome parameter was duration of analgesia while secondary outcome parameters were onset of sensory and motor block, duration of sensory and motor block, hemodynamics, and side effect or complications.
The sensory block was assessed every 5 min interval till 30 min after injection, by pinprick test with a blunt 23 G hypodermic needle in the appropriate area, using a 3 point scale: 0 - normal sensation; 1 - loss of sensation of pinprick (analgesia); 2 - loss of sensation of touch (anesthesia). The onset time of sensory block was the time from injection till loss of pinprick sensation (Score 1) while the time for the complete sensory block (TCSB) was the time from injection till loss of sensation of touch (Score 2). The duration of the sensory block was defined as the duration from loss of touch sensation till it reappears (Score < 2). Duration of analgesia was defined as time interval between TCSB and VAS > 3 or patient's first demand for recue analgesia in postoperative period.
The motor block was evaluated at 5 min interval till 30 min after injection by asking the patient to move elbow, wrist, and fingers using a 3-point scale: 0 - normal motor function with full flexion and extension of elbow, wrist, and fingers; 1 - reduced 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 the time from injection till motor strength decreased to Score 1. The time for complete motor block was the time from injection up to complete motor blockade (TCMB) with inability to move fingers (Score 2). The total duration of the motor block was duration from TCMB till ability to move fingers (Score <2).
The intraoperative vital parameters including PR, systolic blood pressure (SBP), diastolic blood pressure (DBP), and SpO2 were recorded at 5-min intervals and in postoperative period hourly up to 24 h. Patients were followed up to 24 h postoperatively to rule out complications of nerve blockade such as pneumothorax, nerve injury, or LA systemic toxicity or secondary to addition of additive like bradycardia (PR <60 bpm), nausea, vomiting, dizziness, or respiratory depression. Postoperative pain was assessed using VAS, and injection diclofenac sodium 75 mg intramuscularly was given as rescue analgesic when VAS >3. Patients with inadequate sensory and motor blockade beyond 30 min following the injection were excluded from the study, and surgery was done under general anesthesia.
For sample size calculation, we conducted a pilot study on ten patients (5 patients in each group), and standard computer programs computed that approximately 45 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% dropout rate, the final sample size was determined to retain a total of hundred patients for better validation of results. The obtained data were expressed as mean ± standard deviation or number and percentage. Statistical analysis was performed using statistical program SPSS 20.0 Software for social science (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 as statistically significant.
| Results|| |
Both groups were comparable with respect to the demographic profile for age, sex ratio, weight, ASA physical status, and duration of surgery [Table 1]. The baseline PR, SBP, DBP, and SpO2 were also comparable between the groups with no statistically significant difference (P > 0.05).
Onset time for sensory block was found to be lower in nalbuphine group (Group B) (6.26 ± 1.337 min) as compared to plain ropivacaine group (6.58 ± 1.247 min), but it was statistically insignificant (P > 0.05). Onset time of motor block was also shorter in the nalbuphine group (Group B) (15.26 ± 1.70 min) as compared to plain ropivacaine group (Group A) (15.40 ± 1.471 min) with statistically no significant difference, (P > 0.05) [Table 2].
Quality of sensory blockade was better in nalbuphine group but showed no statistically significant difference (P > 0.05). The number of patients with Grade 1 and Grade 2 sensory blockade were greater in Group B as compared to Group A at 5, 20, and 25 min intervals after the injection [Table 3]. The duration of sensory blockade in nalbuphine group (Group B) was 401.20 ± 19.963 min and in plain ropivacaine group (Group A) was 387.60 ± 29.731 min with P = 0.009, which was statistically significant. The mean duration of motor block was 323.00 ± 26.283 min in patients of Group A when compared to 333.20 ± 20.941 min in Group B, and difference was statistically significant (P = 0.03). When comparing the duration of analgesia, a highly significant difference was noted between Group A and Group B (P < 0.0001). The duration of analgesia was 502.60 ± 22.751 min in Group B as compared to 441.20 ± 30.815 min in Group A [Table 2] and [Figure 2].
|Table 3: Comparison of quality of sensory blockade at various time intervals in two groups|
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The mean PR, SBP, DBP, and SpO2 did not deviate significantly from their baseline values in perioperative period in both the groups (P > 0.05). Hemodynamic parameters were also compared between the two groups at various time intervals and were found to be comparable (P > 0.05) [Figure 3].
Patients were monitored for side effects postoperatively for first 24 h. In Group A, 2 (4%) and 1 (2%) patients complained of nausea and vomiting, respectively. None of the patients complained of dizziness in Group A. In Group B, 3 (6%) and 2 (4%) patients complained of nausea and vomiting, respectively. One (2%) patient complained of dizziness. Side effects were compared in both groups, and no statistical significant difference was noted (P = 0.65) [Figure 4].
| Discussion|| |
The supraclavicular brachial plexus block is an efficient regional anesthetic technique used for upper arm surgeries as it has rapid-onset, predictable, and dense anesthesia in comparison to other approaches due to compact arrangement of plexus at this location. A volume of 20 ml of 0.5% ropivacaine was taken in our study as this was found to be an adequate concentration and volume for giving ultrasound-guided supraclavicular block as used in some previous studies. Various adjuncts are added to LA to increase the efficacy and duration of block while minimizing the systemic adverse effects along with a reduction in total dose of LA.,,,,
It has been hypothesized that opioids act directly on the peripheral nervous system due to possible centripetal axonal transport of opioids into the substantia gelatinosa after perineural injection., Different opioids have been added to LA to improve the quality and duration of PNBs, but the preferred analgesics for postoperative analgesia are those that cause minimal side effects including respiratory depression, drowsiness or sedation, nausea, and vomiting without compromising on pain relief. Various studies have been done to evaluate efficacy of combining opioids with LAs for PNB. Wajima et al. in their study showed that continuous infusion of butorphanol locally into the brachial plexus sheath provided a better analgesic effect to that of continuous IV systemic injection.
Nalbuphine is a mixed k-agonist-μ-antagonist opioid with a moderate analgesic effect and minimal respiratory depression. The easy availability, low cost, and improved analgesia with nalbuphine render it more satisfactory for day care surgery than other opioids. Nalbuphine had been used safely via various routes without any report of neurotoxicity in several studies.,,,
Chiruvella et al. compared 5 mg or 10 mg of nalbuphine added to 0.375% levobupivacaine, with regard to the duration of analgesia in patients undergoing upper limb surgeries under supraclavicular brachial plexus block and they concluded that a higher dose (10 mg) of nalbuphine hastens the onset and prolongs the duration of sensorimotor blockade and analgesia, without any significant side effects. Similarly, Gupta et al., had also used 10 mg nalbuphine in their study safely without any appreciable complications. Although a higher dose (20 mg) of nalbuphine was used by Abdelhaq and Elramely in their study for brachial plexus block in patients undergoing elective forearm and hand surgery, no significant adverse effects were noted apart from a significant increase in duration of analgesia. In our study, we chose 10 mg nalbuphine as an adjuvant to LA.
Although previous studies have compared the effects of adding nalbuphine to various LAs such as lignocaine, bupivacaine, and levobupivacaine, very few studies have used ropivacaine as a LA in their study. The objectives of this study were to assess the analgesic efficacy and safety of 10 mg nalbuphine as an adjuvant to 0.5% 20 ml ropivacaine for ultrasound-guided supraclavicular brachial plexus block in terms of onset and duration of sensory and motor block, duration of analgesia, hemodynamic variations, and side effects.
In this study, we found that the onset time of sensory and motor block were faster in the nalbuphine group as compared to plain ropivacaine group but showed statistically no significant difference (P > 0.05). Similar results in onset of block were observed by Abdelhaq et al. who evaluated the effect of adding 20 mg nalbuphine to 25 ml 0.5% bupivacaine for ultrasound-guided supraclavicular block. They used higher dose of nalbuphine in their study, but onset of block was comparable in both groups. Gupta et al. and Das et al. also assessed the analgesic efficacy of 10 mg nalbuphine as an adjuvant to bupivacaine and levobupivacaine, respectively, for brachial plexus block and found comparable results in both groups regarding onset of block (P > 0.05). However, in contrast, Nazir and Jain observed statistically significant shorter time to onset of sensory and motor blockade using 30 mL of 0.375% bupivacaine with 10 mg nalbuphine. The time of onset of block depends on many factors such as lipid solubility and pKa of drug, fraction of nonionized drug (depends on pH of solution and surrounding medium), and nerve fiber size. In our study, we did not measure the pH of solution after mixing of nalbuphine with ropivacaine.
Our study demonstrated significantly longer duration of sensory and motor block as well as duration of analgesia in nalbuphine group. Similar findings were observed by Abdelhaq and Elramely, Gupta et al., Das et al., and Nazir and Jain in their studies.,,, These studies were in accordance to our results, showing addition of nalbuphine to LAs increases the duration of block and analgesia. Various mechanisms of action have been proposed to explain the analgesic effect of nalbuphine. It activates the spinal and supraspinal opioid receptors leading to adequate analgesia with cardiovascular stability, minimal sedation, less physical dependence, less respiratory depression, as well as less nausea and vomiting. Apart from μ-opioid-based spinal and supraspinal analgesia, inhibition of neuronal serotonin uptake leads to augmentation of the spinal inhibitory pathways for pain. Stimulation of opiate receptors on neurons of the central nervous system leads to an inhibition of intracellular adenylyl cyclase, an opening of potassium channels, and closing the calcium channels. This leads to hyperpolarization of the cell membrane potential and inhibition of action potential transmission of ascending pain pathways.
No significant hemodynamic variations from their baseline values were seen in both groups. Side effects such as nausea and vomiting were observed in both groups, but incidence was comparable and nonsignificant. All these patients were managed by IV ondansetron 4 mg, and there was no need of further intervention. In either group, none of the patients had sedation, respiratory depression, pneumothorax, pruritus, urinary retention, or any neurological sequelae. The side effect profile was almost similar to previous studies.,,,
There were some limitations of our study that single dose of nalbuphine and LA i.e., single-shot PNB (sPNB) was used which could not provide long-term benefit to the patient as evidence suggested that continuous PNBs offer advantages over sPNBs, including a longer duration of analgesia and are indicated mainly for perioperative analgesia. Although assessment of pain by VAS is simple, it is highly subjective as all the patients had dissimilar pain tolerances and various patients misunderstood how to use it properly and patients sometimes needed specific instructions during their pain assessment which may have caused bias in our results.
| Conclusion|| |
Addition of 10 mg nalbuphine to LA ropivacaine for ultrasound-guided supraclavicular brachial plexus block prolongs the duration of both sensory and motor block and the duration of postoperative analgesia without significantly increasing the adverse effects. Thus, nalbuphine can be used as a safe adjuvant to ropivacaine for ultrasound-guided supraclavicular brachial plexus block.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]