|Year : 2019 | Volume
| Issue : 2 | Page : 206-213
Hyaluronidase versus adrenaline as an adjuvant to bupivacaine in ultrasound-guided supraclavicular brachial plexus block for upper limb surgeries
Shereen Elsayed, Fatma M Ahmed, Osama Y.A Khalifa
Department of Anaesthesia, Faculty of Medicine, Zagazig University, Zagazig, Egypt
|Date of Submission||01-Jan-2019|
|Date of Acceptance||04-Mar-2019|
|Date of Web Publication||12-Jun-2019|
Department of Anaesthesia, Faculty of Medicine, Zagazig University, Zagazig
Source of Support: None, Conflict of Interest: None
Context Ultrasound-guided supraclavicular brachial plexus block is the most preferred technique for upper limb surgeries. Adjuvants are usually added to local anaesthetics to increase their analgesic effect and duration.
Aim The aim of this study was to compare the effect of hyaluronidase or adrenaline as an adjuvant to bupivacaine in supraclavicular brachial plexus block for upper limb surgeries.
Patients and methods This is a randomized controlled clinical trial. Ninety adult patients undergoing elective unilateral upper limb surgeries below the level of the shoulder were randomly allocated to three groups of 30 patients each. Hyaluronidase group ‘H’ received 40 ml of bupivacaine of 0.375% solution+3000 IU of hyaluronidase, Adrenaline group ‘A’ received 40 ml of bupivacaine of 0.375% solution+5 μg/ml (200 μg) of adrenaline and control group ‘C’ received 40 ml of bupivacaine of 0.375% solution. The outcome measures included time to achieve complete sensory block (primary outcome), duration of sensory and motor block, duration of analgesia, the time of first request for analgesia and total dose of postoperative rescue analgesia administration. The collected data were analysed using SPSS, version 20.
Results Time to reach complete sensory block was significantly shorter in the hyaluronidase group than in the adrenaline and control groups (15.5±6.2 vs. 22.7±7.1, 24.2±6.4, respectively); the adrenaline group showed significant longer duration of motor block (645.3±163.8 vs 523.3±148.7, 530.2±158.8 respectively), and significant longer duration of analgesia (724.3±171.3 vs. 575.7±157.6, 581.8±169.3, respectively).
Conclusion Hyaluronidase decreases the block onset time with minimal effect on block duration or postoperative analgesia; moreover, adrenaline has prolonged block duration and postoperative analgesia with minimal influence on block onset time.
Keywords: adrenaline, anaesthesia, bupivacaine, hyaluronidase, supraclavicular brachial plexus block
|How to cite this article:|
Elsayed S, Ahmed FM, Khalifa OY. Hyaluronidase versus adrenaline as an adjuvant to bupivacaine in ultrasound-guided supraclavicular brachial plexus block for upper limb surgeries. Res Opin Anesth Intensive Care 2019;6:206-13
|How to cite this URL:|
Elsayed S, Ahmed FM, Khalifa OY. Hyaluronidase versus adrenaline as an adjuvant to bupivacaine in ultrasound-guided supraclavicular brachial plexus block for upper limb surgeries. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Oct 14];6:206-13. Available from: http://www.roaic.eg.net/text.asp?2019/6/2/206/260139
| Introduction|| |
Brachial plexus blocks are useful and widely used for anaesthesia and postoperative pain control for upper limb surgery ,. Several approaches have been used; each of them has its own advantages and disadvantages . The supraclavicular nerve block is the easiest and ideal, as it blocks most of the branches of the brachial plexus, and this results in rapid onset and high success rates for surgery and analgesia of the upper limb surgery (with the exception of the shoulder) .
The success of brachial plexus blocks was greatly improved with the introduction of ultrasound (US)-guided techniques, by allowing the anaesthesiologist to visualize the brachial plexus and needle during injection, and this can reduce the incidence of complications .
Nowadays, many adjuvant drugs have been used with local anaesthetic drugs to obtain rapid, intense and prolonged brachial plexus block .
Adrenaline has been used for more than a century as an adjunct to local anaesthetics on the basis that adrenaline results in vasoconstriction, which decreases tissue blood flow and results in slower drug clearance from the target site .
Both hyaluronan and chondroitin ‘the main components of the intercellular cement’ are depolymerized by hyaluronidase, which reversibly and temporarily liquefies this interstitial barrier ,, and it also has antiadhesion and antiscar properties ; hence, hyaluronidase is used in ophthalmic surgery, as it increases spread, dispersion of the local anaesthetic agent and accelerates the onset of the peribulbar, retrobulbar and subcutaneous infiltration blocks ,.
In our study, we hypothesized that hyaluronidase as an adjuvant to local anaesthetic would reduce time to reach complete sensory block of the upper limb after supraclavicular brachial plexus block compared with adrenaline–local anaesthesitic drug mixture.
| Patients and methods|| |
This prospective randomized controlled clinical study was carried out in Zagazig University Hospitals after the approval of the Institutional Review Board (IRB) of Zagazig Faculty of Medicine number (ZU-IRB # 3948/5-9-2017). The study was registered in the Pan African Clinical Trial Registry with identification number PACTR201710002718112.
The sample size was calculated to be 90 cases divided into three groups, 30 in each group, calculated using open Epi program. At the confidence interval of 95% and power of test 80%, the analgesic duration in the hyaluronidase group was 610.2±237.4, whereas in the control group, it was 759±226.2 .
Adult patients 20–60 years old, scheduled for elective unilateral upper limb surgeries below the level of the shoulder, and who were classified as American Society of Anesthesiologists (ASA) I and ASA II were included in this study. Patients who refused to participate in the study or those who presented with pregnancy, neurological deficit involving the brachial plexus, severe respiratory disease, disturbed conscious level, chronic renal failure, ASA grade III and IV, any bleeding disorder and patients on any anticoagulants, having any local infection at the injection site, on chronic steroid use or having a history of allergy to local anaesthetics or hyaluronidase or adrenaline were excluded from this study.
The patients were divided randomly by a computer-generated randomization table into three groups: hyaluronidase group ‘H’ patients received 40 ml of bupivacaine of 0.375% solution+3000 IU of hyaluronidase, adrenaline group ‘A’ patients received 40 ml of bupivacaine of 0.375% solution+5 μg/ml (200 μg) of adrenaline and control group ‘C’ patients received 40 ml of bupivacaine of 0.375% solution.
Intravenous access was secured in the nonoperating hand, 5 l/min of oxygen was delivered via a facemask and 1 mg midazolam and 50 μg fentanyl were administered intravenously for patient comfort while performing the block.
On entering the patient into the operating room, standard monitors such as ECG, pulse oximetry, noninvasive blood pressure and end-tidal CO2 monitor were attached, and baseline parameters were recorded.
The supraclavicular brachial plexus block was performed using a transportable US system (MTurbo; FUJIFILM Sonosite Inc., Bothwell, Washington, USA) with superficial linear array 8–12 MHz transducer to obtain the images of the brachial plexus in the transverse and longitudinal planes.
Patients lay down supine with the head turned to the contralateral side and ipsilateral shoulder kept down, and the arm was adducted by the assistant with a flexed elbow. Sterile preparation of the skin and the US probe was carried out; the transducer was placed in the sagittal plane behind the middle-third of the clavicle in the supraclavicular fossa to visualize the brachial plexus. The brachial plexus either appeared as three hypoechoic circles with hyperechoic outer rings or as a grape-like cluster of five to six hypoechoic circles, lateral and superior to the subclavian artery, between the anterior and middle scalene muscles at the lower cervical region. A 22-G, 80-mm stimulatory insulated needle (Stimuplex D; B-Braun AG, Melsungen, Germany) was attached to the nerve locator (NM-20; Inmed Equipment, Pvt Ltd, Vadodara, Gujarat, India), and then introduced lateral and parallel to the long axis of the US probe. Once the needle penetrated the brachial plexus sheath and its tip was located among the nerves, the nerve locator was turned on and set to deliver a 1.0 mA current at 1 Hz frequency and 0.1 ms of a pulse width. When motor responses in the triceps or biceps were obtained, the current was decreased slowly. The tip of the needle was adequately positioned close to the plexus when the muscle responses were maintained visible at 0.5 mA. After a negative aspiration, the local anaesthetic (40 ml of bupivacaine 0.375% solution and additives drugs (hyaluronidase in a dose of 3000 IU or adrenaline in a dose of 5 μg/ml) was injected at the site for over 3–5 min.
During the surgery, additional rescue analgesia as intravenous ketamine or sedation as intravenous midazolam was administered according to the patient’s need, and the total injected dose was recorded.
The following parameters were studied:
This is the time interval from skin infiltration to the last local anaesthetic injection.
Time to achieve complete sensory block (primary outcome)
This was the time to reach a loss of sensation in the pinprick test at all four nerves’ distribution (or time to reach 0 in the sensory block grade). Sensory block was assessed in the distribution of each of the major peripheral nerves (radial, ulnar, median and musculocutaneous nerve), by pinprick using a sterile blunt-end 25 G needle at 0, 2, 5, 10, 15, 20 and 30 min after the block.
The sensory block was graded according to a three-point scale: 0=complete block (no sensation), 1=partial block (decreased sensation), 2=no block (normal sensation) .
It was assessed for each of the four nerves’ distribution, and the maximal sensory score was 8 points.
For motor block assessment
The extent of motor block was tested at 0, 2, 5, 10, 15, 20 and 30 min after the block by assessing the following motor functions: extension of the elbow and the wrist or thumb abduction by radial nerve stimulation, but ulnar nerve stimulation result in thumb adduction, flexion at the elbow (musculocutaneous nerve), opposition of the thumb and small finger or thumb adduction (ulnar nerve) and opposition of the thumb and index finger (median nerve).
The motor block was graded according to a three-point scale: 0=complete block (paralysis), 1=partial block (decreased muscle activity), 2=no block (full muscle activity) .
It was assessed for each of the four nerves (ulnar, radial, ulnar and muculocutaneous); the maximal sensory score was 8 points, and thus the total sensorimotor score was 16 points.
Surgical anaesthesia was achieved when the total sensorimotor score was less than or equal to 2 points with a sensory score less than or equal to 1 point .
Total performance time
This was the sum of needling time and the time to achieve surgical anaesthesia .
Duration of analgesia
This was the time from the last local anaesthetic injection to the first report of postoperative pain at the surgical site, that is, visual analogue scale (VAS) of at least 4, with first analgesic requirement (rescue analgesia) by the patient .
During the procedure, anaesthesia was considered satisfactory if the patient was not complaining of any discomfort or pain and if sedation was not needed.
Postoperative follow-up was carried out in the recovery room and in the postoperative ward. The analgesic duration was noted according to 0–10 VAS for pain at every half an hour for the first 8 h and then hourly until 24 h. If the patient complained of pain and VAS score reached four, additional analgesics were given to the patient in the form of diclofenac sodium at a dose of 50 mg intramuscularly, and 10 mg nalbufin intravenously.
The total amount of diclofenac sodium and nalbufin given to each patient during the first 24 h of the postoperative period was calculated and recorded.
Duration of motor block
This was considered as the time from the last local anaesthetic injection to complete motor function recovery in the hand and forearm.
Management of unsuccessful block
If there was an inadequate block or patchy block, the block was supplemented by general anaesthesia and was recorded.
Patients were asked to rate their opinions and experience of the anaesthesia by using a seven-point Likert scale question (1=extremely unsatisfied, 4=fair, 7=very satisfied) .
The collected data were coded and analysed using SPSS, version 20 (IBM, Armonk, NY, USA). For quantitative variables’ summarization, we used mean±SD, frequencies and percentages for categorical variables. Analysis of variance test and χ2-test were used when appropriate. P value less than 0.05 was considered statistically significant.
| Results|| |
A total of 100 patients who presented for elective forearm or hand surgery were checked for eligibility in the study. Four patients declined to participate in the study and six patients didn’t meet the study selection criteria as shown in ([Figure 1]). Ninety patients were enrolled in the study. Randomization allocation resulted in 30 patients receiving US-guided supraclavicular brachial plexus block with 3000 IU hyaluronidase and bupivacaine in a dose of 40 ml of 0.375% solution, 30 patients receiving US-guided supraclavicular brachial plexus block with 5 μg/ml adrenaline and 40 ml of 0.375% bupivacaine and 30 patients receiving US-guided supraclavicular brachial plexus block with 40 ml of 0.375% bupivacaine only. Only 28 patients completed the follow up and analysis in hyaluronidase group as two patients converted to general anaesthesia due to the need for graft, same thing happened in adrenaline group and only 27 patients completed the follow up and analysis in control group as three patients showed inadequate block and converted to general anaesthesia.
As shown in [Table 1], there is no significant difference in the three groups as regards the age, sex, weight and surgical characteristics.
Time to reach complete sensory block, time to achieve surgical anaesthesia and the total performance time were significantly shorter in the hyaluronidase group; as regards needling time, the number of patients under surgical anaesthesia after 30 min and the number of patients who required conversion to general anaesthesia, there were no significant differences between the studied groups ([Table 2]). The total consumed amount of ketamine and midazolam was nearly the same between the three groups ([Table 2]).
|Table 2 Onset of complete sensory block, block performance and drug details|
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In [Table 3], the adrenaline group showed a significantly longer duration of sensory block, motor block and analgesia. The number of patients needing rescue analgesics and postoperative total amount of opioid and nonopioid analgesics consumed showed no significant difference in the three groups. Moreover, patient satisfaction with anaesthesia and analgesia was good in all groups.
|Table 3 Duration of block and analgesia, postoperative opioid and nonopioid consumption and patient satisfaction after supraclavicular block in the three groups|
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| Discussion|| |
In this study, we tried to overcome the problem of prolonged onset time of sensory and motor block after US-guided supraclavicular brachial plexus block, which has many undesirable effects on the patient and health resources; moreover, increasing the duration of block and prolonged postoperative analgesia are very beneficial to decrease the need for systemic analgesics, both opioids and nonopioids, to avoid their harmful side effects.
Many adjuvants to local anaesthetics were tried, aiming to decrease brachial plexus block onset time, such as dexmedetomidine, clonidine, dexamethasone and magnesium. Studies applied on dexmedetomidine and clonidine as adjuvants showed acceptable results in terms of decreased block onset time, but others did not succeed to show good results ,.
Hyaluronidase is successfully used as an adjuvant to local anaesthetics in ocular blocks wherein it can shorten block onset time and improve quality of anaesthesia , with minimal reported side effects ; in this study, no adverse effects were observed with hyaluronidase use.
The literature dealing with hyaluronidase usage in regional anaesthesia reveals great variability in doses and methodology; this indicates high success rate and safety of hyaluronidase use .
This study showed that the addition of 3000 IU of hyaluronidase to 40 ml of 0.375% bupivacaine solution during US-guided supraclavicular brachial plexus block significantly shortened the onset time of complete sensory block, time to achieve surgical anaesthesia and total performance time than the addition of 5 μg/ml adrenaline to 40 ml of 0.375% bupivacaine or bupivacaine alone, without significant effect of hyaluronidase on block or analgesia duration.
In this study, surgical anaesthesia was assessed using the 16-point scale, which has proven to be a good method to evaluate surgical anaesthesia after brachial plexus block in a lot of studies ,,,.
Koh et al.  said that addition of 100 IU/ml of hyualuronidase to ropivacaine 0.5% during US-guided axillary brachial plexus block significantly decreased the time to reach complete sensory block and surgical anaesthesia, thereby decreasing the time of onset of anaesthesia than the control group; this agrees with the result of this study, However, the duration of sensory block was shorter in the hyaluronidase group than in the control group, whereas the duration of motor block and ropivacaine analgesia were also decreased, but without statistical significance. The difference between both studies may be attributed to using two different local anaesthetics with different pharmacokinetics and drugs interactions; moreover, the site of block was different in both studies.
In a study by Krediet et al. , addition of hyaluronidase to local anaesthetic had no measurable effects on a motor or sensory block of single injection axillary brachial plexus block.
In a study by Said , addition of 1500 IU hyaluronidase to 20 ml ropivacaine 1% during supradavicular brachial plexus block did not increase the speed of onset of anaesthesia, but it produced a significant reduction in the duration of anaesthesia.
In a study by Keeler et al. , addition of 3000 IU hyaluronidase to 0.5% bupivacaine for axillary brachial plexus block significantly shortened the duration of the sensory and motor block; the block was carried out using landmark-guided technique without the aid of nerve stimulator or US.
In this study, there was no difference in the number of patients requiring additional analgesia or conversion to general anaesthesia between the three groups.
In agreement with a former study by Koh et al. , this study found that there was no difference in the total amount of opioid and nonopioid postoperative analgesia consumption. In this study, postoperative diclofenac sodium and nalbufin 24 h consumption was around 75 and 20 mg, respectively, in all groups; moreover, the overall patient satisfaction was good in all groups.
Adrenaline when used as an adjuvant to local anaesthetics decreases their absorption by its vasoconstriction effect and hence decreases their systemic toxicity and prolongs the duration of anaesthesia; however, the expected side effects limit its use. In this study, no side effects were recorded from its usage.
In this study, there was a significant increase in the duration of sensory and motor block and bupivacaine analgesia in the adrenaline group than in the hyaluronidase group and control group, without any significant effect on anaesthesia onset time.
Chawda and Sharma  concluded that 90 μg clonidine has a more rapid onset of sensory and motor block and prolonged postoperative analgesia when compared with 200 μg adrenaline as an adjuvant during supraclavicular block.
In a study by Kumar and Suresh , addition of clonidine to bupivacaine in supraclavicular brachial plexus block provides a significant improvement in postoperative analgesia than adrenaline added to bupivacaine.
Elbaradey and Elshmaa  found that, in comparison with midazolam and adrenaline, adding dexamethasone to bupivacaine in supraclavicular brachial plexus block accelerated onset time of anaesthesia with longer duration of analgesia.
Song et al.  said that 1 μg/kg dexmedetomidine or 200 μg adrenaline as an adjuvant to 40 ml of 1% mepivacaine solution prolonged the duration of sensory and motor block with no significant difference between both groups when compared with the control; moreover, they found no significant difference in the onset of block between the three groups; these results correlate with this study as regards adrenaline.
In this study, we expect very small variation in the time for scanning to get an acceptable US image because the block was carried out by a single person.
| Conclusion|| |
This study suggests that hyaluronidase as an adjuvant to bupivacaine decreases the onset time of supraclavicular brachial plexus block with minimal effect on block duration or postoperative analgesia; moreover, adrenaline, as an adjuvant to bupivacaine, has prolonged duration of a block and postoperative analgesia with minimal influence on block onset time. Both adjuvants have a small influence on the consumption of postoperative analgesia.
Although we observed no adverse effects related to the use of adrenaline or hyaluronidase, we recommend further randomized controlled studies with larger sample size and a longer period of follow-up.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]