|Year : 2020 | Volume
| Issue : 2 | Page : 188-196
Efficacy of adding ketamine, dexamethasone, and epinephrine with bupivacaine in ultrasound-guided supraclavicular brachial plexus block
Maha Y Youssef, Sherif F.H Elsayed, Enas A Abd El-Mottalb, Gehan A Tarabai
Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||16-Jul-2019|
|Date of Acceptance||15-Jan-2020|
|Date of Web Publication||27-Jun-2020|
MD Maha Y Youssef
Department of Anaesthesia and Surgical Intensive Care Department, Faculty of Medicine, Mansoura University, Mansoura
Source of Support: None, Conflict of Interest: None
Background Supraclavicular brachial plexus block is an effective anesthesia for upper limb surgery as it provides anesthesia and postoperative analgesia. Various adjuvants were added to local anesthetics to achieve dense and prolonged blocks.
Objective The aim of this study is to compare the effect of adding ketamine, dexamethasone, or epinephrine to bupivacaine on onset time, duration of sensory and motor block, intraoperative and postoperative hemodynamic stability, patient satisfaction, and any adverse effects.
Patients and methods This study was carried out on four groups of patients. Patients were anaesthetized by ultrasound-guided supraclavicular brachial plexus block; group B was anaesthetized by an injection of 20 ml bupivacaine (0.5%) plus 2 ml of saline; group K received 20 ml bupivacaine (0.5%) and ketamine 1.5 mg/kg; group D received 20 ml bupivacaine (0.5%) and dexamethasone 8 mg; and group E received 20 ml bupivacaine and epinephrine (5 μg/ml). Patients were assessed for the onset and duration of sensory and motor block. Intraoperative and postoperative analgesia were assessed by visual analog scale, and intraoperative and postoperative sedation was assessed according to Culebras scale.
Results Group D showed a shorter onset of sensory and motor blocks compared with the other groups. Group D showed statistically significant longer duration of analgesia compared with the other groups. There was significant decrease in postoperative analgesic requirement in group D during the first 24 h postoperatively compared with the other groups.
Conclusion Dexamethasone with bupivacaine in supraclavicular brachial plexus block has a longer duration of sensory and motor blocks and less requirement of rescue analgesia in the first 24 h postoperatively.
Keywords: dexamethasone, ketamine and epinephrine, regional anesthesia, supraclavicular brachial plexus block, ultrasound technique
|How to cite this article:|
Youssef MY, Elsayed SF, Abd El-Mottalb EA, Tarabai GA. Efficacy of adding ketamine, dexamethasone, and epinephrine with bupivacaine in ultrasound-guided supraclavicular brachial plexus block. Res Opin Anesth Intensive Care 2020;7:188-96
|How to cite this URL:|
Youssef MY, Elsayed SF, Abd El-Mottalb EA, Tarabai GA. Efficacy of adding ketamine, dexamethasone, and epinephrine with bupivacaine in ultrasound-guided supraclavicular brachial plexus block. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 Jul 7];7:188-96. Available from: http://www.roaic.eg.net/text.asp?2020/7/2/188/287996
| Introduction|| |
In modern anesthesia practice, peripheral nerve blocks provide intraoperative anesthesia and also prolonged postoperative analgesia without major systemic side effects .
Upper limb surgeries are usually performed under brachial plexus block. There are variable approaches to the brachial plexus block, but the supraclavicular approach is an easy and appropriate method for anesthesia and analgesia in surgeries below the shoulder joint .
Recently, ultrasound-guided technology has been used for many types of peripheral nerve blocks in both adult and children . It has the advantages of elevating the success rate by easier identification of the site of the nerve, correct deposition of the local anesthetic around the nerve, and decreasing the incidence of complication associated with this block.
Using the local anesthetics alone for supraclavicular brachial plexus block provides good operative conditions but have the disadvantage of shorter duration of postoperative analgesia. Various adjuvants such as opioids, dexmedetomidine, dexamethasone, midazolam, ketamine, etc., were added to local anesthetics in brachial plexus block to achieve quick and prolonged block ,.
Bupivacaine is a highly potent aminoamide local anesthetic that blocks the peripheral afferent nerves by acting on voltage-dependent sodium channels thereby preventing the generation of action potential. Bupivacaine is being used for intraoperative anesthesia and postoperative analgesia.
Ketamine is a noncompetitive antagonist of the N-methyl-D aspartate receptor. It is used as a premedication, and for inducing sedation, induction, and maintenance of general anesthesia. Local anesthetic and analgesic properties have been reported for ketamine. Intravenous administration of low-dose ketamine decreases postoperative opioid use and improves analgesia . Ketamine has been added to epidural lidocaine or bupivacaine to prolong the duration of regional anesthesia and postoperative analgesia ,.
Corticosteroids are widely used in peripheral nerve blocks for acute pain control. They produce analgesia by stopping transmission of nociceptive, myelinated c-fibers and decreasing ectopic neuronal discharges. They produce this effect by changing the function of potassium channels in excitable cells .
Several clinical studies have evaluated the effectiveness of dexamethasone on plexus, femoral and sciatic blocks ,,.
Epinephrine increases the duration of anesthesia and analgesia by two mechanisms. First, the presence of alpha-type receptors that take part in the transmission of nociceptive stimuli at the spinal level emphasizes a possible direct action of alpha-adrenergic agonists on the neural tissue. Second, epinephrine as a vasoconstrictor is used to constrict vessels by their action on alpha-type receptors, thereby reducing vascular absorption of the local anesthetic .
| Patients and methods|| |
With local Ethics and Medical Committee (IRB) approval of Mansoura University under reference number of MFM-IRB-(MS/16.08.17) on 28/9/2016, a double-blinded, randomized, prospective clinical study was planned with an informed written consent from 120 patients with the American Society of Anesthesiologists physical status grades 1 and 2. Patients were aged between 20 and 50 years and were undergoing elective upper limb surgery below the shoulder joint at Mansoura University Hospitals.
Patients with diabetes mellitus, peripheral neuropathy, known allergy to any of the study drugs, coagulopathy, infection at the site of block, pregnancy, and those on beta blockers were excluded from the study.
A prior G-power analysis was done to estimate the study sample size. A power of 80% was estimated with type 1 error of 0.05 to get an analgesic difference between groups of ∼30% to yield a total sample size of 110 cases. A dropout of 5% of cases was expected; therefore, a total number of 120 cases were needed (30 cases per group) .
In all, 120 patients were randomly allocated by computer-generated tables and by the use of closed opaque envelopes method into four equal groups: each group contains 30 patients. To achieve blinding, all the studied solutions were prepared in identical covered syringes by an anesthesiologist not participating in the technique and through patient data collection.
- Control group (C group): n=30 patients:
- Patients underwent ultrasound-guided supraclavicular brachial plexus block using 20 ml bupivacaine only (0.5% concentration) plus 2 ml saline; the total volume is 22 ml.
- Ketamine group (K group): n=30 patients:
- Patients underwent ultrasound-guided supraclavicular brachial plexus block using 20 ml bupivacaine only (0.5% concentration) plus ketamine (1.5 mg/kg) with a maximum dose of 100 mg; the total volume is 22 ml.
- Dexamethasone group (D group): n=30 patients:
- Patients underwent ultrasound-guided supraclavicular brachial plexuses block using 20 ml bupivacaine only (0.5% concentration) plus dexamethasone (8 mg); the total volume is 22 ml.
- Epinephrine group (E group): n=30 patients:
- Patients underwent ultrasound-guided supraclavicular brachial plexus block using 20 ml bupivacaine only (0.5% concentration) plus epinephrine (1 : 200 000) (5 µg/ml); the total volume is 22 ml.
| Methods|| |
- Patients were subjected to preoperative history taking, clinical examination, and basal laboratory investigation in the form of complete blood count, coagulation profile, and renal and liver function tests.
- Midazolam 0.04 mg/kg was administrated intravenously to all patients as premedication, 5 min before giving the block.
- On arrival of the patient to the operating room:
- Routine anesthesia monitoring, including noninvasive arterial blood pressure, pulse oximetry, and electrocardiography were applied.
- Baseline vital signs were recorded.
- Peripheral intravenous line (18–20 G) was inserted in the nonoperative upper limb and all patients received a single dose of prophylactic antibiotic after sensitivity test within 1 h before start of surgery and crystalloid volume loading (10–20 ml/kg).
Technique of ultrasound-guided brachial plexus block: The skin of the supraclavicular fossa was disinfected with a povidone–iodine solution of 10%. The probe of the ultrasound was positioned in a coronal oblique plane in the supraclavicular fossa to perform an exploratory scan. The brachial plexus was visualized as a group of round or oval hypoechoic nodules (trunks and/or divisions) surrounded by a hyper-reflective fascial sheath, superficial and lateral to the round pulsating hypoechoic subclavian artery. A 22-G needle is attached to the LA syringe and then introduced lateral to the ultrasound probe, and parallel to the long axis of the probe, in the same direction as the ultrasound beam. Once the needle penetrated the brachial plexus sheath and its tip was positioned among the nerves, after a negative aspiration, the tested solution was injected at the site for more than 3–5 min. Local anesthetic dispersion at the time of injection was seen by ultrasound. If the spread did not reach some part of the plexuses, the needle tip position was readjusted to produce a suitable anesthetic distribution ([Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5]).
|Figure 1 Left supraclavicular brachial plexus (yellow arrows). Note the supraclavicular artery (SA) lying on the first rib (white arrows) (compare with the figure of postanesthetic injection) .|
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|Figure 2 Right supraclavicular brachial plexus (yellow arrows). Note the supraclavicular artery (SA) lying on the first rib (white arrows) (compare with the figure of postanesthetic injection) .|
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|Figure 3 Preanesthetic injection: ‘corner pocket’ (*), plexus=yellow arrows, FR=first rib, SA=subclavian artery, P=pleura; compare with the next figure .|
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|Figure 4 Right supraclavicular brachial plexus (yellow arrows). Local anesthetic (dashed lines) has been deposited in the ‘corner pocket’ (*). Note the nerves now appear to be floating on the anesthetic: FR=first rib SA=subclavian artery .|
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|Figure 5 Local anesthetic surrounding nerves. Postanesthetic injection .|
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Heart rate, mean arterial blood pressure, respiratory rate, and oxygen saturation were monitored before performing the block (basal) and continued intraoperatively at intervals of 15, 30, 45, and 60 min and then every half an hour till the end of surgery and then 30 and 60 min postoperatively and 2, 6, 12, and 24 h postoperatively.
Sensory block was assessed by disappearance of sensation to pin prick over the C5-T1 dermatomes at 0, 5, 10, 15, 20, and 30 min.
Onset of motor block: the time from injection to the inability of the patient to move his/her fingers or raise their hand. Motor block was monitored at 0, 10, 20, and 30 min by assessing the motor functions as: flexion at the elbow (musculocutaneous nerve), extension of the elbow and the wrist (radial nerve), opposition of the thumb and index finger (median nerve), and opposition of the thumb and small finger (ulnar nerve). Motor block was graded according to the modified Bromage scale for the upper limb: grade 0=normal motor function with full flexion and extension of elbow, wrist and fingers; grade 1=decreased motor strength with ability to move the fingers; grade 2=complete motor block with inability to move fingers.
Analgesic duration: its time up to the first analgesic requirement.
Total dose of rescue analgesia: rescue analgesic was intramuscular administration of 75 mg diclofenac when the pain score was 4 or more.
Visual analog score (VAS): VAS is a 10 cm line with 0 at one end representing no pain and 10 cm on the other end representing the worst pain, measured every 15, 30, 45, 60, 90, and 120 min and at 1st, 6th, 12th, and 24th hour postoperatively. We gave rescue analgesia 75 mg diclofenac intramuscular when the pain score was 4 or more.
Degree of sedation was assessed by the sedation scale described by Culebras et al.  as follows: (a) awake and alert, (b) sedated, responding to verbal stimulus, (c) sedated, responding to mild physical stimulus, (d) sedated, responding only to moderate or severe physical stimulus. It was measured intraoperatively and then 1, 6, 12, 24 h after the block.
Intraoperative and postoperative complications:
- Hypotension: was defined as a decrease in systolic blood pressure more than 20% of the baseline value or systolic blood pressure less than 100 mmHg; hypotension was treated with a bolus dose of ephedrine intravenous (5 mg bolus) and crystalloid fluids.
- Bradycardia: a pulse rate of less than 50 beat /min and was treated with bolus doses of 0.2–0.5 mg atropine.
- Hypoxia: oxygen saturation less than 90% treated by supplemental oxygen.
- Convulsion: if occurred was treated with diazepam (0.1–0.2 mg/kg) or thiopentone (2–3 mg/kg).
- Allergic reactions: if suspected, treated by hydrocortisone 100 mg intravenous.
- Nausea and vomiting: treated by metoclopramide 10 mg intravenous.
The collected data were coded and analyzed using the SPSS (the Statistical Package for Social Sciences), version 15 for Windows (SPSS Inc., Chicago, Illinois, USA). Qualitative data were mentioned as number and percent. Comparison between groups was done by c2 test. Quantitative data were presented as mean±SD. F test (one-way analysis of variance) was used to compare between more than two groups and post-hoc test (LSD) was used to compare between groups. Nonparametric data were presented as minimum–maximum and median. Mann–Whitney test was used for differentiation between groups. Kruskal–Wallis test was used to compare between more than two groups. P value less than 0.05 was considered to be statistically significant.
| Results|| |
One hundred and twenty patients were randomized to receive supraclavicular brachial plexus block ultrasound guided with either bupivacaine alone (group B), Bupivacaine mixed with Epinephrine 5 µg/ml (group E), Bupivacaine mixed with Ketamine 1.5 mg/kg (group K), or Bupivacaine mixed with 8 mg Dexamethasone (group D), There were eight cases of failed block excluded from the study.
All studied groups showed no significant differences as regard demographic data (age, sex and ASA status) and duration of surgery ([Table 1]).
Group D showed statistically significant shorter onset of sensory and motor block compared to other groups as following, there was no significant difference between group B, group E and group K ([Table 2]). Onset of motor block was statistically significant shorter in group D compared to other groups, also there was no significant difference between group B & group E and group K ([Table 2]).
|Table 2 Onset of (sensory, motor) block (min), analgesic duration (h), and number of rescue analgesia in first 24 h|
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Group D showed statistically significant longer duration of analgesia compared to other groups, there was no significant difference between group B & group E and group K ([Table 2]).
There was significant decrease in post-operative analgesic requirement in group D during first 24 hours post- operatively compared to other groups ([Table 2]).
There were no statistically significant differences between the four groups in heart rate (HR), mean arterial blood pressure (MAP), respiratory rate and oxygen saturation that were measured intra-operative and post-operative.
There was significant increase in VAS in group B and group E compared to other groups after the 6th hour post-operatively ([Table 3]). While VAS increased significantly in group K compared to other groups after 12th hour post-operatively ([Table 3]).
There was significant increase in sedation score in group K intraoperatively & extended for 6th hours postoperatively compared to other groups ([Table 4]).
Complications: There were no significant differences between studied groups and no serious complications related to certain group than the other ([Table 5]). There were 4 cases of postoperative nausea & vomiting. 2 cases in group B and the other 2 cases in group k and no cases in group D.
| Discussion|| |
The present study demonstrated that dexamethasone as an adjuvant to bupivacaine in ultrasound-guided supraclavicular brachial plexus block has the advantage of rapid onset and prolonged duration of analgesia, in comparison with other used adjuvants such as epinephrine or ketamine.
A lot of studies are consistent with these results; the meta-analysis conducted by Choi et al.  evaluated the effect of adding dexamethasone (with doses from 4 to 10 mg) to different local anesthetics (including bupivacaine 0.5%) in brachial plexus blockade and confirmed the same result. Also Kim et al.  assessed the effect of adding dexamethasone (5 mg) to 10 ml of levobupivacaine (0.5%) for brachial plexus block (interscalene approach). They concluded that adding dexamethasone to levobupivacaine enhanced significantly postoperative analgesia in brachial plexus block.
Shrestha et al.  found that addition of dexamethasone (8 mg) as adjuvant to bupivacaine 0.5% in supraclavicular brachial plexus block had significant rapid-onset and longer duration of analgesia.
In the study of Movafegh et al. , they found that addition of dexamethasone (8 mg) to lignocaine 1.5% prolongs duration of analgesia significantly without change in onset time.
There are many theories that explain the mechanism of analgesic action of dexamethasone when added to local anesthetics; one of these theories is suppression of C-fiber transmission of pain signals  Another theory is systemic absorption of dexamethasone ; also, local vasoconstriction with slow systemic absorption of local anesthetics is an explanation . Actually, there is no exact explanation for the mechanism of action of dexamethasone in the prolongation of analgesic effect of local anesthetics.
An et al.  added dexamethasone locally to the sciatic nerve in mice and concluded that it prolongs the analgesic effect of local anesthetic when injected perineurally and not when given intravenous or intramuscular.
Also, Kawanishi et al.  concluded that perineural and not intravenous administration of dexamethasone (4 mg) significantly increases the duration of postoperative analgesia as a result of single-shot interscalene block with 20 ml of ropivacaine 0.75%.
On the contrary, Abdallah et al.  found that the analgesic effect of intravenous dexamethasone seems similar to perineural dexamethasone.
In our study, we found that there was no significant change in the onset of motor and sensory block or duration of analgesia with the addition of ketamine (1.5 mg/kg), but the severity of pain was significantly reduced postoperatively, so the total dose of rescue analgesics is decreased in the first 24 h postoperatively.
This is supported by the study of Ismael et al. , who found that: adding ketamine (25 μg/kg) to 0.5% bupivacaine in infraclavicular brachial plexus blockade did not improve the onset of sensory and motor blockade. Also, the study by Lee et al.  had similar results. They added 30 mg of ketamine to ropivacaine (30 ml of 0.5% concentration) in brachial plexus block (interscalene approach) and found that the onset and duration of anesthesia or analgesia did not change.
Another study done by Sabra et al.  showed that ketamine (2 mg/kg) added to 25 ml of bupivacaine 0.25% for axillary brachial plexus blockade did not improve the onset and duration of anesthesia or analgesia.
The decreased VAS in the postoperative period caused by the addition of ketamine to bupivacaine is supported by the study of Sabra et al. , who showed that ketamine added to bupivacaine for axillary brachial plexus blockade increased the duration of postoperative analgesia compared with bupivacaine alone and decreased the consumption of postoperative analgesia without significant adverse effects.
Also, Lashgarinia et al.  found that addition of ketamine (2 mg/kg) to lidocaine 1.5% (5 mg/kg) improved the analgesic effect and prolonged the duration of postoperative analgesia. According to them, the analgesic effect could be the result of the local anesthetic effect of ketamine at the level of surgical trauma.
In contrary to this result, Lee et al.  showed that 30 mg of ketamine added to 30 ml ropivacaine (0.5%) for the brachial plexus blockade did not improve postoperative analgesia.
Rahimzadehndish et al.  compared the analgesic effects of peri-femoral nerve infusion of ketamine plus ropivacaine versus ropivacaine alone, after elective knee surgery under spinal anesthesia. They reported that addition of ketamine 1 mg/kg to 0.1% ropivacaine did not improve postoperative pain relief in the first 48 h after the operation.
Zohar et al.  reported that ketamine added to local bupivacaine did not enhance analgesia after wound infiltration following cesarean section.
The variable effect of ketamine in different studies may be due to different ketamine concentrations, type of LA and site of injection .
Analgesic effects are supported by different mechanisms. Ketamine binds to opiate receptors and interacts with cholinergic and adrenergic receptors. It can block N-methyl-D-aspartate excitation of central neurons. Ketamine has a local anesthetic effect through the prevention of action potential conduction by its effect on sodium and potassium channels in the nerve membranes. Ketamine has anti-inflammatory effect that inhibits the early postoperative inflammatory response significantly. It acts through different mechanisms on the cellular level causing decreased production of cytokines and interferes with regulation of inflammatory mediators. The systemically absorbed amount of ketamine exerts inhibition of central sensitization .
This study documented a nonsignificant change in the onset or duration of sensory and motor blockade with addition of epinephrine 5 μg/ ml. This is consistent with the study of Schoenmakers et al. , which found no significant increase in the duration of postoperative analgesia by adding epinephrine 5 μg/ ml to 60 ml ropivacaine (0.75%) for popliteal nerve block.
Another study supports these results done by Weber et al. , who used epinephrine 5 µg/ml as an adjuvant to 20 ml ropivacaine 0.5% to perform femoral nerve block as postoperative analgesia during total knee replacement and found no change in onset or duration of analgesia.
On the contrary, using high dose of epinephrine with local anesthetic is found to have a positive impact on the onset and duration of sensory and motor blockades. This was proven in the study by Dogru et al. , who compared the effect of using epinephrine, in high dose (200 µg) versus in low dose (25 µg), with 1.5% lidocaine during axillary brachial plexus blockades and found that high-dose epinephrine prolonged the motor block by 25 min and prolonged the sensory block by 40 min, while low-dose epinephrine prolonged the motor block by 10 min only and prolonged the sensory block by 30 min.
Another result similar to Dogru et al.  is the result of the study of Neal  who added epinephrine, by the same high dose (200 µg), to 40 ml of mepivacaine 1% for brachial plexus block (infraclavicular approach) and the result was prolonged duration of motor block by 60 min.
The variable effect of epinephrine in different studies may be due to different epinephrine concentrations and the type of local anesthetic itself .
In this current study, sensory block duration lasted longer than motor block in all groups. Nathan and Sears  explained that by higher requirements of motor fibers than small sensory fibers that cause early return of motor function, so the duration of motor block is shorter.
In the current study, there were no significant differences between the four groups as regards hemodynamics and respiratory parameters including heart rate, mean arterial blood pressure, respiratory rate, and oxygen saturation values. This is in correlation with the study conducted by Akkaya et al. , who used in their study levobupivacaine alone and with dexamethasone in bilateral transversus abdominis plane block. They found that there is no significant difference in these parameters in both studied groups. The current study agrees with the study conducted by El-Baradey and Elshmaa , who assessed the effectiveness of adding either dexamethasone or midazolam in comparison with epinephrine 5 μg/kg to 30 ml bupivacaine 0.5% in supraclavicular brachial plexus block.
The current study has shown that there was significant difference of sedation score between ketamine group and other groups intraoperatively and postoperatively. Patients who received ketamine were sedated intraoperatively with comfortable sedative effect throughout the surgery, the probable explanation based on systemic absorption of ketamine.
In agreement with this study, the study by Weir and Fee  observed a significant sedation in patients who received epidural ketamine with bupivacaine and they attributed this to the lipid solubility and extensive intravascular absorption of ketamine from the epidural space. The same explanation was also stated by Sabra et al. .
The present study showed that there was no major cardiovascular, respiratory, or neurological complications observed in the studied groups. This was with the results of Shrestha et al. , who compared the analgesic efficacy of local anesthetic with and without dexamethasone in supraclavicular brachial plexus block with no complications observed and in correlation with the study conducted by El-Baradey and Elshmaa , who assessed the effectiveness of adding either dexamethasone or midazolam in comparison with epinephrine 5 μg/kg to 30 ml bupivacaine 0.5% in supraclavicular brachial plexus block.
Limitations of this study were that it did not include measurement of plasma level of the studied drugs to obtain the correlation with their therapeutic action, aiming to decrease adverse effects.
Recommendations of this study include comparing the effect of various doses of ketamine as an adjuvant as well as using epinephrine as an adjuvant to bupivacaine local anesthetic in studies with a large sample size.
| Conclusion|| |
Dexamethasone (8 mg) as an adjuvant to 20 ml bupivacaine (0.5%) for supraclavicular brachial plexus block has longer duration of sensory and motor blocks and less requirement of rescue analgesia in the first 24 h postoperatively, compared with ketamine (1.5 mg/kg) and epinephrine 1 : 200 000 (5 μg/ml).
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]