|Year : 2020 | Volume
| Issue : 4 | Page : 163-169
Fentanyl and clonidine as adjuncts to a mixture of local anesthetics in potentiating postoperative analgesia in supraclavicular block: A randomized controlled study
Anisha Puri1, Gurchand Singh2, Anita Madan3
1 Department of Anesthesiology, Maharishi Markandeshwar, Ambala, Haryana, India
2 Department of ENT, Maharishi Markandeshwar, Ambala, Haryana, India
3 Deparment of Obstetrics and Gynaecology, Government Medical College, Amritsar, Punjab, India
|Date of Submission||16-Aug-2019|
|Date of Acceptance||24-Feb-2020|
|Date of Web Publication||29-Dec-2020|
Dr. Anisha Puri
E-21, Medical College Campus, Mullana, Ambala - 133 203, Haryana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Brachial plexus block is popular for upper limb surgeries as it is effective for postoperative analgesia.
Aims: The aim of the study was to compare fentanyl and clonidine as adjuncts to a mixture of local anesthetics in potentiating postoperative analgesia in the supraclavicular block.
Materials and Methods: Sixty patients of the American Society of Anesthesiologist I and II undergoing upper limb surgeries lasting more than 30 min were included and randomly divided into two groups of 30 each. In clonidine (C) group, patients received 10 ml of 0.5% bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200,000) and 1 μg/kg clonidine diluted till 35 cc with normal saline. In fentanyl (F) group, patients received 10 ml of 0.5% bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200,000) and 1 μg/kg fentanyl diluted till 35 cc with normal saline. Patients were observed for onset and duration of sensory and motor blockade, duration of analgesia, postoperative pain, and adverse effects.
Results: The mean onset of sensory block was faster in Group F (8.43 ± 2.897 min) as compared to 13.17 ± 2.451 min in Group C. The difference between the two groups was statistically strongly significant (P < 0.0001). There was a significant reduction in the onset of motor block in Group F (14.67 ± 1.84 min) compared to (18.17 ± 2.45 min) Group C with P < 0.0001 (statistically strongly significant). There was a significant increase in the duration of analgesia in Group C (16.63 ± 2.04 h) compared to Group F (8.79 ± 1.50 h) with P < 0.0001. There was bradycardia (pulse did not fall below 60) in two patients of Group C (treated with atropine intravenous [i.v.]). Two patients of Group F complained of nausea and vomiting once in the early hours of surgery for which ondansetron i.v. was given. There were no significant side effects in either of the groups.
Conclusion: Both clonidine and fentanyl establish a good safety profile. Fentanyl ensures a faster onset of sensory and motor blockade, while clonidine ensures a longer duration of sensory and motor blockade as well as prolonged analgesia.
Keywords: Clonidine, fentanyl, local anesthetics, supraclavicular block
|How to cite this article:|
Puri A, Singh G, Madan A. Fentanyl and clonidine as adjuncts to a mixture of local anesthetics in potentiating postoperative analgesia in supraclavicular block: A randomized controlled study. Int J Crit Illn Inj Sci 2020;10:163-9
|How to cite this URL:|
Puri A, Singh G, Madan A. Fentanyl and clonidine as adjuncts to a mixture of local anesthetics in potentiating postoperative analgesia in supraclavicular block: A randomized controlled study. Int J Crit Illn Inj Sci [serial online] 2020 [cited 2021 Feb 26];10:163-9. Available from: https://www.ijciis.org/text.asp?2020/10/4/163/305301
| Introduction|| |
Upper limb orthopedic surgeries are preferably done under regional anesthesia nowadays. Regional anesthesia is safer and allows a better surgical field. It has minimal systemic and hemodynamic involvement, decreased incidence of postoperative nausea and vomiting, and better analgesia both intraoperatively and postoperatively. Regional anesthesia fastens the ambulation and discharge of the patient., Thus, regional anesthesia is preferred over general anesthesia wherever it is possible. Supraclavicular brachial plexus block for the upper limb is comparable with spinal anesthesia of the lower limb. It is due to the fact that it is given lateral to the subclavian artery on the first rib, below the clavicle where the nerve fibers of brachial plexus are compactly placed. The duration of intra- and postoperative analgesia is dependent on the local anesthetic used. Local anesthetics can interrupt the transmission of the action potential of excitable membranes by binding to receptors in the Na+ channels. Lignocaine has a quick action but only till 1–1.5 h. It causes vasodilatation which is antagonized by adding a vasoconstrictor. Adrenaline added to lignocaine delays absorption and prolongs the action by delaying absorption. On the other hand, bupivacaine has a slow onset, but it prolongs the duration of analgesia. However, bupivacaine is cardiotoxic hence can be disastrous in patients in supraclavicular block where major vessels are very closely placed to the brachial plexus., Hence, combining lignocaine and bupivacaine is better than using an individual drug, as it combines the better qualities of both the drugs and side effects can be avoided. Large volumes of local anesthetics required to produce desirable effects may result in systemic side effects.
Local anesthetics can provide analgesia up to 4–8 h. Hence, they are of limited use in patients where we want to provide postoperative analgesia and short analgesia duration postoperatively is the biggest problem in upper limb surgeries. Hence, the use of adjuvant to increase the duration of supraclavicular brachial plexus block and decrease the dose of local anesthetics is a better and safer option to prolong analgesia.,,, Various adjuvants available include epinephrine, dexamethasone, magnesium sulfate, morphine, tramadol, midazolam, ketamine, neostigmine, fentanyl, and clonidine.,
Increase in the duration of motor and sensory block was observed on the addition of clonidine and fentanyl with local anesthetics in various clinical trials., Very little literature is available about the comparison between alpha-2 agonist and opioid as adjuncts to local anesthetic agents in brachial plexus block., Hence, we compared clonidine and fentanyl in a dose of 1 μg/kg each as adjuncts to local anesthetic agents for the enhancement of supraclavicular nerve block for upper limb surgery.
| Materials and methods|| |
It was a randomized, double-blind study conducted at a tertiary care hospital after obtaining consent of the ethical committee. Sixty adult patients of the American Society of Anesthesiologist (ASA) Class I and II weighing 40–70 kg of either sex, belonging to 25–60 years of age, and undergoing upper limb surgeries lasting more than 30 min were included and divided into two groups of 30 each using numbers generated by the computer randomly. Preparation of local anesthetic mixture with adjunct drugs and labeling of drugs by random number generated by computer was done by anesthetists not involved in the procedure of block or data collection. In the clonidine group (Group C), patients received 10 ml of 0.5% bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200,000) and 1 μg/kg clonidine diluted up to 35 cc with normal saline. In fentanyl group (Group F), patients received 10 ml of 0.5% bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200,000) and 1 μg/kg fentanyl diluted up to 35 cc with normal saline. We excluded diabetics, hypertensives, and patients with nephrology or hepatic disorder and pregnant patients. The sample size was calculated using 0.05 as alpha level and 0.90 beta level from data of earlier studies to obtain the required power of 0.80.
After obtaining informed written consent from the patient for participation and publishing of de-identified aggregate data, an intravenous (i.v.) line was secured with 18 G cannula and infusion was started with ringer's lactate i.v. Baseline blood pressure, heart rate, respiratory rate, and SpO2 were noted. We did not take surrogate consent or include patients in our study where surrogate consent was needed. In the operation theater, all routine monitors such as noninvasive blood pressure, pulse oximetry, and electrocardiogram were attached and all vitals mentioned above were once again recorded. Ondansetron 4 mg i.v. was given as premedication.
The patient was placed in the supine position with the head turned away from the side to be blocked. The arm to be anesthetized was adducted, and the hand was extended along the side toward the ipsilateral knee as far as possible. Using the classic technique approach, the midpoint of the clavicle was identified and marked. The posterior border of the sternocleidomastoid was palpated easily when the patient raised the head slightly. Palpating the belly of the anterior scalene muscle moving toward the interscalene groove with the fingers, a mark was made at approximately 1.5–2.0 cm posterior to the midpoint of the clavicle. By palpating the subclavian artery at this site, landmark was confirmed. The area was cleaned with povidone-iodine solution. The area was then draped properly. After appropriate preparation and injection of a skin wheal, 24-G needle was inserted at the point of entry above the midpoint of the clavicle in the backward–inward–downward direction. Although the direction of the needle was toward the first rib, it was not always necessary to touch the rib. Paresthesia in the forearm or hand was elicited. Thirty-five milliliter of the local anesthetic solution with clonidine or fentanyl as an adjunct was injected after negative aspiration for air or blood followed by a 2 min massage to provide an even distribution of the drug. After injection of the mixture of drugs prepared, we noted the time of injection of drugs in supraclavicular brachial plexus block, time of onset of sensory and motor block, duration of sensory and motor block, and duration of analgesia.
The onset of sensory blockade was monitored every minute for the first 15 min then every 5 min till 30 min and then every 15 min till complete surgical anesthesia.
Motor blockade was assessed by the technique described by modified Bromage on the 3-point scale. It was assessed 5 min till 30 min and then every 15 min till complete motor blockade. The duration of motor block was assessed every 1 h, till the ability to move fingers only.
A descriptive statistical analysis was carried out. Data were collected, tabulated, coded, and analyzed using SPSS for windows version 16.0 (SPSS Inc., Chicago, USA).
The results obtained on continuous measurements were presented in mean ± standard deviation (minimum–maximum) and the results on categorical measurements were presented in number (%). Student's t-test (two tailed, independent) was used to find the significance of study parameters on a continuous scale between the two groups. P < 0.05 was considered statistically significant.
| Results|| |
In the present study, both the groups were comparable in the demographic data with respect to age, gender, weight, and ASA grade. The duration of surgery was also comparable among the two groups.
The mean onset of sensory block was faster in Group F than in Group C.
There was a significant reduction in the onset of motor block in Group F compared to Group C.
The duration of sensory blockade was found to be longer in the clonidine group compared to fentanyl.
The duration of motor block was longer in the clonidine group compared to fentanyl group and was found to be clinically and statistically strongly significant.
In the present study, there was a significant prolongation of the duration of analgesia in Group C compared to Group F.
| Discussion|| |
Upper limb trauma has become a common injury in the modern scenario, especially with growing agricultural dependency on machines. Hence, regional nerve blocks are a boon in today's world. They can be given in full stomach patients and without any risk of drug interactions. General anaesthesia may lead to haemodynamic responses like hypertension, arrhythmias, tachycardia, wound dehiscence, increased intraocular and intracranial pressure that are avoided in regional brachial plexus block., The cost factor is also less with a regional block. Another advantage of using regional anesthesia is postoperative analgesia that can be prolonged by the addition of an adjuvant. This helps in decreasing psychological effects that may cause anxiety and distress which may cause autonomic symptoms of nausea and sweating. There is less risk of deep-vein thrombosis and chest infections in pain-free patients. Adjuvants such as dexmedetomidine, adrenaline, neostigmine, midazolam, magnesium sulfate, clonidine, and steroids and opioids including morphine, fentanyl, and tramadol are used in peripheral nerve blocks for the improvement of quality and duration of block avoiding the higher and toxic dose of individual local anesthetic.
Anesthesia of entire upper extremity and perioperative analgesia are provided by supraclavicular brachial plexus block in an easy way without any systemic side effects. While catheter-based techniques allow for sustained pain management during the peri-operative period, they can present challenges related to patient management, catheter displacement, and increased infection risk. Hence, using adjuvant to local anesthetics is a better and safer option to prolong the analgesia. Alpha-2 agonists have analgesic, anxiolytic, sedative, and sympatholytic properties, which make it a better choice for local anesthetic. The addition of clonidine or fentanyl to local anesthetics produces analgesia, sedation with minimal side effects. Their use is established as onset is rapid with prolonged analgesia.
In our study, we compared 10 ml of 0.5% bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200,000) and 1 μg/kg Clonidine diluted up to 35 cc with normal saline versus 10 ml of 0.5% bupivacaine + 20 ml of 2% lignocaine with adrenaline (1:200,000) and 1 μg/kg fentanyl diluted up to 35 cc with normal saline as taken by Rustagi et al. We took a dose of 1 μg/kg of fentanyl as was taken by a study by Paluvad and Manne. We took a dose of 1 μg/kg of clonidine as was taken by a study by Patil and Singh.
The demographic data in terms of age, weight, and duration of surgery were comparable in both the groups in our study [Table 1].
Brachial plexus block is suitable to patients of all age groups, as shown by Bhattarai et al. in their study on brachial block comprising patients of ages ranging between 2.6 and 90 years. However, in our study, we included patients of age group 25–60 yearsb as difficulty in obtaining cooperation for regional blocks in children has made regional anesthesia an uncommon sole anesthetic technique, although it has been considered ideal for surgical procedures in the upper limbs.
The mean onset of sensory block was faster in Group F (8.43 ± 2.89 min) as compared to Group C (13.17 ± 2.45 min) [Table 2] and the onset time of motor block was also faster (14.67 ± 1.84 min) in Group F than in Group C (18.17 ± 2.45 min) [Table 3] which was found to be strongly significant clinically and statistically (P < 0.001). Our results were in accordance with the study done by Ahmed who observed that the addition of fentanyl to a mixture of local anesthetics produced rapid onset of sensory (8.9 ± 2.9 min) and motor block (8.3 ± 2.7 min) compared to clonidine (sensory being 11.9 ± 2.7 min; motor being 9.8 ± 2.1 min) added as an adjuvant in brachial plexus.
Pöpping et al. used clonidine doses ranging from 90 to 150 μg in brachial plexus block and found the onset time of sensory block of clonidine to be 12.8 ± 1.84 min. The values and the results are in concurrence with our study.
Our study also correlates with the study done by Jafa et al. who found that the addition of 75 μg fentanyl into the supraclavicular brachial plexus block shortened the onset time of block (10.2 ± 1.15 min) and time to achieve complete block (21.8 ± 4.6 min). Moharari et al. showed that the combination of 75 μg fentanyl and 1.5% lidocaine solution accelerated the onset of sensory and motor blockade during interscalene block. Regarding the possible mechanisms for accelerating the onset of sensory and motor blockade by fentanyl in this study, they suggested that fentanyl might block the nerve conduction in the spinal roots. It means that the action of opioids injected into the perineural sheath may be more central due to diffusion or the axonal transport into epidural and subarachnoid spaces.
The mean duration of sensory block in our study was longer in Group C (10.83 ± 1.08 h) as compared to 5.66 ± 1.82 h in Group F [Table 4]. The duration of motor block in our study was also found to be longer (9.10 ± 1.06 h) in Group C than (4.40 ± 0.63 h) in Group F [Table 5], and the difference between the two groups was found to be statistically and clinically significant (P < 0.001).
Our study was also in accordance with the study done by Ahmed, who also found that the clonidine group showed longer duration of sensory (558 ± 66.4 min) and motor block (574.3 ± 40.9 min) compared with the fentanyl group where the duration of sensory block was 364.5 ± 33.3 min and duration of motor block was 388.2 ± 34.8 min.
Our study showed sensory blockade for a longer duration than a motor block which is similar to a study by de Jong and Wagman This is due to the fact that small fibers need less concentration of local anesthetic than large fibers. Large motor fibers require greater concentration of minimal effective concentration of local anesthetic than the small one (sensory fibers). Hence, sensory blockade is longer than the motor block and pain is felt only after the return of motor function.
The duration of analgesia was the time between the onset of action and first complaint of pain (Visual Analog Scale more than or equal to 4) and patients received the first dose of rescue analgesic. The mean duration of analgesia [Table 6] was longer in the clonidine group (16.63 ± 2.04 h) compared to the fentanyl group (8.79 ± 1.50 h) and was statistically strongly significant. A study conducted by Ahmed also found that the duration of analgesia was longer in the clonidine group (14.4 ± 1.3 h) compared to the fentanyl group (10.9 ± 1.5 h) which was in accordance with our study. Specific peripheral effects of clonidine are less because alpha-2 adrenoreceptors are not present on the axon of a normal peripheral nerve. The action of clonidine in peripheral nerve blocks may be explained by four mechanisms. They include direct peripheral nerve action, anti-inflammatory effect, analgesia that is centrally mediated vasoconstriction due to alpha-2 adrenoreceptor. Dalle et al. postulated that clonidine raises the action potential initiating threshold causing a block in conduction by causing hyperpolarisation generated by Na+-K+ during repetitive stimulation. Kosugi et al. studied complete action potential (CAPs) in the frog sciatic nerve and found that clonidine acts by inhibiting CAP.
Pöpping et al. found clonidine to be beneficial for prolonged duration of analgesia with all local anesthetics. El Saied AH et al. also showed an increase in analgesic duration from 587 to 828 min when clonidine was used for axillary plexus blockade.
Nishikawa et al. postulated three mechanisms for the analgesia produced by peripheral application of fentanyl. First, fentanyl acts directly on the peripheral nervous system. Primary afferent tissues (dorsal roots) have been found to contain opioid binding sites. Due to the presence of bidirectional axonal transport of opioid binding protein, fentanyl acts on the dorsal horn. This could account for the analgesic effect of fentanyl. Second, fentanyl may diffuse from the brachial plexus sheath to epidural and subarachnoid spaces and then bind with the opioid receptor of the dorsal horn. Third, fentanyl potentiates the action of local anesthetic by analgesia mediated by an opioid receptor that leads to fentanyl uptake into the systemic circulation.
During our study, we did not notice any significant change in systolic and diastolic blood pressure, and no patient in either group had hypotension (defined by decrease in blood pressure by 30%) and only two patients of clonidine group had bradycardia (defined by decrease in pulse rate by 20%) and required atropine i.v. This was statistically insignificant (P > 0.05) which is similar to a study conducted by Eisenach et al. Culebras et al. found that 150 μg of clonidine added to 40 cc 0.5% sensorcaine produced hemodynamic changes. The hemodynamic changes observed with the study of Culebras et al. were due to the huge dose of clonidine used in their study.
We observed a higher sedation score with the clonidine group (1.86 ± 0.34) compared to the fentanyl group (1.76 ± 0.43), but the difference between the two groups was clinically and statistically insignificant (P > 0.05). The result of our study is matched with the study done by Shah Alam et al. in 2008 who also showed that the prevalence of sedation was higher in the clonidine-bupivacaine group (40%) than fentanyl-bupivacaine group (33%) and they did not find any significant difference. No patient of any group had sedation score >2. This was in accordance with the publication of Neal et al. on upper extremity regional anesthesia that postulated that side effects (hypotension, bradycardia, sedation) do not occur up to a dose of 1.5 μg/kg or a maximum dose of 150 μg or less for clonidine, and in our study, we used a dose of 1 μg/kg clonidine as an adjuvant.
As evident from [Table 7], we also observed nausea and vomiting in two patients with fentanyl who were treated with ondansetron 4 mg i.v. There were no other hemodynamic changes or complications. No patient of clonidine group had similar complaints. Hasan et al. also found no significant side effects on hemodynamic and respiratory parameters on adding opioids to local anesthetics and got minimal incidence of nausea and vomiting. Since we used very less dose of opioid and alpha-2 agonist as adjuvant, adverse effects are minimal.
The novelty of our study established is that fentanyl has a faster onset of sensory and motor blockade, while clonidine has a longer duration of sensory and motor blockade as well as prolonged analgesia. Both the drugs have a good safety profile and can be conveniently used to prolong duration of analgesia in the supraclavicular block.
Little sample size is the limitation of our study. Studies with bigger sample sizes are required for confirmation of our results; also, modern techniques like ultrasound were not available which would have reduced the dose of anesthetic agents.
| Conclusion|| |
We conclude that both clonidine and fentanyl in 1μg/kg as adjuvants to a mixture of local anaesthetics are without any side effects . Fentanyl has a faster onset of sensory and motor blockade, while clonidine ensures a longer duration of sensory and motor blockade as well as prolonged analgesia
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Research quality and ethics statement
This study was approved by the local Institutional Review Board / Ethics Committee. The authors followed applicable EQUATOR Network (http://www.equator-network.org/) guidelines, during the conduct of this research project.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]