|Year : 2016 | Volume
| Issue : 1 | Page : 36-41
The effects of adding neostigmine to supraclavicular brachial plexus block for postoperative analgesia in chronic renal failure patients: a prospective randomized double-blinded study
Khaled Elbahrawy, Alaa El-Deeb
Department of Anesthesiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||09-Jun-2015|
|Date of Acceptance||13-Dec-2015|
|Date of Web Publication||15-Jun-2016|
Department of Anesthesiology, Faculty of Medicine, Mansoura University, Mansoura 5333
Source of Support: None, Conflict of Interest: None
Background Brachial plexus block is a popular technique for surgery of the upper extremity. Supraclavicular approach is the most consistent method for surgery below the shoulder joint. Neostigmine is often used as an adjuvant for local anesthetics in regional anesthesia.
Patients and methods Ninety-three patients of ASA physical status III with chronic renal failure were randomly allocated to three groups according to brachial plexus block solution. The control group received 20 ml of 0.5% bupivacaine added to 10 ml of normal saline solution and the two neostigmine groups received 250 and 500 μg of neostigmine (groups N250and N500, respectively). The block was performed guided by ultrasound. Patients were monitored in the operation theater for ECG, heart rate, respiratory rate, noninvasive blood pressure, and SpO2. Characteristics of the blocks, duration of analgesia, and adverse effects were assessed. If the patient felt pain before or during surgery, the patient was excluded from study and additional lidocaine was used. Postoperative pain was assessed using the visual analogue scale. The postoperative rescue analgesic used was tramadol. Complications of brachial plexus block were reported.
Results Patients showed no significant difference with respect to patients' age, sex, weight, and duration of surgery. The onsets of sensory and motor blockade were significantly shorter in patients receiving 500 μg neostigmine. The duration of sensory and motor blockade and hemodynamics were comparable in the three groups. The postoperative rescue analgesic requirement and mean pain score were significantly less in group N500than in the N250and control groups. Complications of the block did not vary among groups.
Conclusion Addition of neostigmine to supraclavicular brachial plexus block in chronic renal failure patients has no effect on duration of block. However, 500 μg neostigmine resulted in rapid onset of sensory and motor blockade and enhancement of postoperative analgesia, with no significant side effects.
Keywords: brachial plexus block, chronic renal failure, neostigmine
|How to cite this article:|
Elbahrawy K, El-Deeb A. The effects of adding neostigmine to supraclavicular brachial plexus block for postoperative analgesia in chronic renal failure patients: a prospective randomized double-blinded study. Res Opin Anesth Intensive Care 2016;3:36-41
|How to cite this URL:|
Elbahrawy K, El-Deeb A. The effects of adding neostigmine to supraclavicular brachial plexus block for postoperative analgesia in chronic renal failure patients: a prospective randomized double-blinded study. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2020 Jan 28];3:36-41. Available from: http://www.roaic.eg.net/text.asp?2016/3/1/36/184076
| Introduction|| |
Brachial plexus block is a popular regional nerve block. It is commonly used for anesthesia and analgesia in upper extremity surgery . Anesthetic management for creation of arteriovenous fistula in patients with chronic renal failure is governed by the presence of risk factors such as hypertension, ischemic heart disease, diabetes, chronic pulmonary disease, anemia, coagulopathy, metabolic acidosis, and/or hyperkalemia . Brachial plexus block is an effective anesthesia technique in upper extremity vascular access procedures in patients with end-stage renal disease. Without visualization of the anatomy, brachial plexus block may prove challenging or carry a risk for vascular or nerve injury . A regional anesthetic brachial plexus block results in vasodilatation and improved short-term and long-term fistula flow compared with the infiltration of local anesthetic alone . Various adjuncts have been added to local anesthetic solutions aiming at increasing its efficacy and duration. Systemic adverse effects and prolonged motor block are avoided, along with a reduction in total dose of local anesthetic used. Adjuncts such as epinephrine, bicarbonate, opioids, clonidine, neostigmine, and tramadol have been injected concomitantly with the local anesthetic solution . Neostigmine is often used as an adjuvant for local anesthetics in regional anesthesia as well as intra-articularly following knee arthroscopy ,. Neostigmine is a parasympathomimetic drug that inhibits cholinesterase enzyme reversibly. It stimulates both nicotinic and muscarinic receptors by interfering with the breakdown of acetylcholine . Neostigmine has been used clinically to improve muscle tone in patients having myasthenia gravis. In anesthesia, it has been used to reverse the effects of nondepolarizing muscle relaxants at the end of an operation . Neostigmine has been used as an additive to local anesthetics to prolong analgesic effect. Although there is good evidence for a spinal action of neostigmine, some authors deny its peripheral mechanism of action ,. The analgesic effectiveness of intrathecal neostigmine is well known ,. This might be due to inhibition of muscarinic presynaptic glutamatergic afferents, resulting in an increase in endogenous acetylcholine. These cholinergic neurons terminate in nearby primary afferents, which represent muscarinic receptors. Thus, muscarinic receptor antagonists can reverse analgesic effects of intrathecal neostigmine ,. Spinal neostigmine alone uniformly produces analgesia in large doses (100–200 μg), but it also results in significant dose-dependent nausea due to spread in cerebrospinal fluid to brainstem sites and is not responsive to standard antiemetics . Day et al.  demonstrated peripheral muscarinic receptors. Some experimental and clinical studies reported analgesic effectiveness of intra-articular neostigmine ,,. Intra-articular injection of neostigmine in rats produces moderate analgesia to thermal stimuli, which is allegedly reversible with intra-articular atropine . Preclinical data suggest peripheral antinociceptive effects of acetylcholine . In contrast, some authors reported that neostigmine has no role in the periphery .
The effects of neostigmine on brachial plexus block in chronic renal failure patients have not been investigated. In this study, we assess the effects of adding varying doses of neostigmine to the characteristics of local anesthetic in those patients. The primary outcome is duration of sensory block. The secondary outcomes include onset of sensory and motor block, hemodynamics, and side effects.
| Patients and Methods|| |
This study was conducted in main Mansoura University Hospital from February to May 2015. The study was approved by the Research Ethics Committee. Adult patients with chronic renal failure on dialysis (ASA physical status III) scheduled for superfialization of basalic vein under brachial plexus block were included in the study. Patients with allergy to local anesthetics, those having infection at the site of needle insertion, those having international normalized ratio more than 1.5, coagulopathy, or severe pulmonary disease, patients who refused to participate, and/or those having epilepsy were excluded from the study. Patients underwent dialysis early in the morning or the day before surgery. Patients were randomly allocated to three groups based on a computer-generated sequence, which was kept in sealed envelopes. Immediately before the surgery, the envelope was opened by a pharmacist who had no role in the data collection or analysis. Patients, anesthetists, surgeons, and nurses were completely blinded to the patients' allocation. The brachial plexus block was performed in all groups guided by ultrasound. The control group received 20 ml of 0.5% bupivacaine (5 mg/ml) added to 10 ml of normal saline solution (the control group, group C) to a total volume of 30 ml, and the neostigmine groups received 20 ml of 0.5% bupivacaine (5 mg/ml) with 250 and 500 μg of neostigmine (groups N250 and N500, respectively). The solution for block was prepared in similar-looking 30 ml syringes. Patients were monitored in the operation theater for ECG, heart rate, respiratory rate, noninvasive blood pressure, and SpO2.
With the patients in the supine position and head tilted to the contralateral side of the operated side, a linear, high-frequency transducer (CX50 POC; Royal Philips, Amsterdam, The Netherlands) was placed in the supraclavicular fossa superior to the clavicle and angled slightly toward the thorax. Interscalene groove and subclavian artery should be easily identified. The brachial plexus appears as multiple hypoechoic disks just superficial and lateral to the subclavian artery. The first rib should also be identified as a hyperechoic line just deep to the artery. The pleura may be identified adjacent to the rib and can be distinguished from bone by its movement with breathing. The skin was anesthetized, and the 22-G blunt-tipped needle was inserted just cephalad to the ultrasound transducer in a posterior and caudad direction. After careful aspiration for the nonappearance of blood, 30 ml of the local anesthetic solution was injected in 5-ml increments while visualizing local anesthetic spread around the brachial plexus. The intercostobrachial nerve (T2) was blocked with 5 ml of 2% lidocaine with 1 : 200 000 adrenaline to avoid tourniquet pain. After 30 min, if the block was considered to be adequate, the surgery was commenced. Characteristics of the blocks, including the onset and duration of sensory and motor blocks, were assessed along with the duration of analgesia and adverse effects. Hemodynamic parameters were recorded basally, immediately after block, every 15 min during operation, and then at 1, 3, 6, 12, and 24 h postoperatively.
A three-point scale was used to test sensory block for cervical C5, C6, C7, and C8 and thoracic T1 dermatomes using the pin-prick test (0 = loss of sensation to light touch, 1 = loss of sensation to pinprick, and 2 = normal sensation) .
Motor block was tested by means of thumb abduction and wrist extension (radial nerve), thumb adduction and ulnar deviation of the hand (ulnar nerve), flexion of the elbow in supination (musculocutaneous), and thumb opposition and wrist flexion (median nerve). The Lovett rating scale was used to assess motor block (0 = absent movement, 1 = paresis, and 2 = normal movement) ,.
Sensory and motor block were assessed every 5 min after completion of injection until 30 min, and then every 30 min after the end of surgery until the block had completely worn off. Complete nerve block was defined as the time from injection to either reduction in sensibility to 30% or less (sensory), or to reduction of muscle power less than or equal to zero according to the Lovett rating scale (motor). If patient felt pain before or during surgery, the patient was excluded from study and additional lidocaine was used. Postoperative pain was assessed using the visual analogue scale, where 0 represented no pain and 10 represented the worst pain, at 1, 2, 4, 8, 12, and 24 h postoperatively. Patients who had visual analogue scale score 4–7 and 8–10 were administered 0.25 and 0.5 mg/kg of tramadol intravenously, respectively, as rescue analgesia, with maximum 100 mg/day. Complications of brachial plexus block, including ipsilateral phrenic nerve palsy, Horner's syndrome, recurrent laryngeal nerve palsy, pneumothorax, and subclavian artery puncture, as well as side effects of neostigmine, such as nausea, vomiting, and bradycardia, were reported.
Data distribution was tested for normality using the Kolmogorov–Smirnov test. Normally distributed data were subjected to parametric tests. Data values were expressed as frequency (%), means ± SD, or medians (ranges). The analysis of the data was performed to test statistically significant difference between groups. Differences between groups were analyzed using analysis of variance, followed by the least significant difference test for the post-hoc comparison. Numerical variables have been compared between groups using the independent sample t-test. The c 2-test was used for qualitative data. A P value less than 0.05 was considered significant. The statistical analysis of data was performed using Excel program and Statistical Package for Social Science, version 17 (SPSS Inc., Chicago, Illinois, USA).
A previous study showed that the duration of sensory block of brachial plexus block in end-stage renal failure was 7.5 ± 2.6 . Considering 30% reduction in the duration of sensory block after use of neostigmine, a sample size of 28 patients in each group is required to detect an a-error of 0.05 and a power of 80%. We included more patients (10%) for a final sample size of 93 participants to compensate dropping out during the study.
| Results|| |
Ninety-five chronic renal failure patients admitted for superficialization of basalic vein were assessed for eligibility. Two patients were excluded because of liver failure and refusal to participate. Ninety-three patients were randomized into three groups. After initial randomization, two patients were considered dropouts due to the need for additional lidocaine and therefore not subjected to statistical analysis ([Figure 1]).
With respect to patients' age, sex, weight, and duration of surgery, there was no statistically significant difference ([Table 1]).
The onset of sensory block was significantly shorter in the patients receiving 500 μg neostigmine (group N500) compared with the other two groups ([Table 2]). The onset of motor block showed similar earlier onset in group N500([Table 3]).
When compared with the control group, patients in group N250 showed earlier onsets of sensory and motor blockade and later onsets when compared with group N500. However, such change did not reach statistical significance ([Table 2] and [Table 3]). The duration of sensory and motor blockade was comparable in the three groups ([Table 4]).
The hemodynamics, including heart rate and mean blood pressure, in the three groups showed no significant differences ([Figure 2] and [Figure 3], respectively).
The postoperative rescue analgesic requirement was significantly less in group N500 than in the N250 and control groups ([Table 5]). Moreover, mean pain score was significantly less in group N500 than in the N250 and control groups at 1, 2, and 4 h, postoperatively ([Figure 3]).
There was no statistically significant difference among the three groups as regards incidence of Horner's syndrome, respiratory distress, dryness of the mouth, nausea/vomiting, and Horner's syndrome ([Table 5]) ([Figure 4]).
|Figure 4: Visual analogue scale (mean ± SD). *Significant when compared with the control group.|
Click here to view
| Discussion|| |
Brachial plexus block is the most advantageous or effective choice in creating a vascular access for hemodialysis . Brachial plexus nerve blocks have analgesic and opioid-sparing benefits in upper extremity surgery. Single-injection techniques are limited by the pharmacological duration and therapeutic index of local anesthetics .
In this study, we compared the characteristics of brachial plexus block with 0.5% bupivacaine alone and with 250 or 500 μg of neostigmine in end-stage renal failure patients. The main finding of this study was that the addition of 500 μg of neostigmine resulted in more rapid onset of sensory and motor block and in decreased analgesic requirement. However, it did not augment the duration of sensory or motor block.
This study showed that the duration of sensory or motor block of brachial plexus block with 0.5% bupivacaine in end-stage renal failure patients was not affected by addition of either 250 or 500 μg of neostigmine. In agreement with our results, Bouaziz et al.  concluded that adding neostigmine to a mepivacaine axillary plexus block does not prolong postoperative sensory block.
In this study, the postoperative rescue analgesic requirement as well as mean pain score was statistically significantly less in group N500 when compared with other groups. In agreement with this, Yang et al. and Gentili et al. , reported that intra-articular injection of 500 mg of neostigmine in patients undergoing arthroscopic meniscus repair resulted in a significant difference in pain intensity postoperatively, in total consumption of intravenous rescue analgesics, and first request for analgesic.
Beckett et al.  and Bone et al.  also showed that administration of 500 μg of neostigmine intra-articularly or in axillary brachial plexus block anesthesia resulted in lower pain scores and less rescue analgesic during the first 24 h postoperatively.
This study showed no significant side effects from the addition of 250 or 500 μg neostigmine to brachial plexus block with 0.5% bupivacaine in end-stage renal failure patients. In accordance with these results, Yang et al. and Gentili et al. , reported no significant side effect associated with either intramuscular or intra-articular administration of 0.5 mg neostigmine. They also noticed that the incidence of nausea, vomiting, and bradycardia was not statistically different between patients who did and those who did not receive neostigmine.
Moreover, Liu et al.  documented no complications such as nerve injury or puncture of the axillary vessels with ultrasound-guided axillary brachial plexus block in patients with chronic renal failure. Moreover, Lee et al.  reported a lower incidence of hemidiaphragmatic paralysis with ultrasound-guided interscalene block.
In contrast with our results, Bouaziz et al.  reported a relatively high incidence of side effects with the addition of neostigmine to a mepivacaine axillary plexus block. This might be attributed to the nonuse of ultrasound guidance in that study. In conclusion, the addition of neostigmine to supraclavicular brachial plexus block in chronic renal failure patients has no effect on the duration of block. However, the addition of 500 μg of neostigmine resulted in a rapid onset of sensory and motor blockade and enhancement of postoperative analgesia, with no significant side effects.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shrestha BR, Maharjan SK, Tabedar S. Supraclavicular brachial plexus block with and without dexamethasone – a comparative study. Kathmandu Univ Med J 2003; 1:158–160.
Alsalti RA, el-Dawlatly AA, al-Salman M, Jommaa S, Amro K, Dweiri MA, Jasser MT. Arteriovenous fistula in chronic renal failure patients: comparison between three different anesthetic techniques. Middle East J Anaesthesiol 1999; 15:305–314.
Maliakal T, Patel S, Hadzic A. Ultrasound guidance to facilitate low interscalene brachial plexus block in a patient with indwelling hemodialysis catheter. Can J Anaesth 2009; 56:551–552.
Macfarlane AJ, Kearns RJ, Aitken E, Kinsella J, Clancy MJ. Does regional compared to local anaesthesia influence outcome after arteriovenous fistula creation? Trials 2013; 14:263.
Lalla RK, Anant S, Nanda HS. Verapamil as an adjunct to local anaesthetic for brachial plexus blocks. Med J Armed Forces India 2010; 66:22–24.
Alagol A, Calpur OU, Usar PS, Turan N, Pamukcu Z. Intraarticular analgesia after arthroscopic knee surgery: comparison of neostigmine, clonidine, tenoxicam, morphine and bupivacaine. Knee Surg Sports Traumatol Arthrosc 2005; 13:658–663.
Dogan N, Erdem AF, Erman Z, Kizilkaya M. The effects of bupivacaine and neostigmine on articular cartilage and synovium in the rabbit knee joint. J Int Med Res 2004; 32:513–519.
Brenner GM. Pharmacology
. Philadelphia, PA: W.B. Saunders Company; 2000.
Welbanks L. Compendium of pharmaceuticals and specialties
. 25th ed. Toronto: Canadian Pharmacists Association; 2000.
Hwang JH, Hwang KS, Leem JK, Park PH, Han SM, Lee DM. The antiallodynic effects of intrathecal cholinesterase inhibitors in a rat model of neuropathic pain. Anesthesiology 1999; 90:492–499.
Lauretti GR, de Oliveira R, Reis MP, Juliâo MC, Pereira NL. Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia. Anesthesiology 1999; 90:1534–1538.
Naguib M, Yaksh TL. Characterization of muscarinic receptor subtypes that mediate antinociception in the rat spinal cord. Anesth Analg 1997; 85:847–853.
Wanke E, Bianchi L, Mantegazza M, Guatteo E, Mancinelli E, Ferroni A. Muscarinic regulation of Ca 2+
currents in rat sensory neurons: channel and receptor types, dose–response relationships and cross-talk pathways. Eur J Neurosci 1994; 6:381–391.
Day NS, Berti-Mattera LN, Eichberg J. Muscarinic cholinergic receptor-mediated phosphoinositide metabolism in peripheral nerve. J Neurochem 1991; 56:1905–1913.
Buerkle H, Boschin M, Marcus MA, Brodner G, Wüsten R, Van Aken H. Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model. Anesth Analg 1998; 86:1027–1032.
Yang LC, Chen LM, Wang CJ, Buerkle H. Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy. Anesthesiology 1998; 88:334–339.
Gentili M, Enel D, Szymskiewicz O, Mansour F, Bonnet F. Postoperative analgesia by intraarticular clonidine and neostigmine in patients undergoing knee arthroscopy. Reg Anesth Pain Med. 2001; 26:342-347.
Ferreira SH, Duarte ID, Lorenzetti BB. Molecular base of acetylcholine and morphine analgesia. Agents Actions Suppl 1991; 32:101–106.
Schäfer M, Analgesic effects of neostigmine in the periphery. Anesthesiology 2000; 92:1207–1208.
Boezaart AP, Borene SC. Functional evaluation of motor responses for upper limb blocks. In: Hadzic A, editor. Textbook of regional anesthesia and acute pain management
, 1st ed. New York: McGraw-Hill; 2007. 373–385.
Singh S, Aggarwal A. A randomized controlled double-blinded prospective study of the efficacy of clonidine added to bupivacaine as compared with bupivacaine alone used in supraclavicular brachial plexus block for upper limb surgeries. Indian J Anaesth 2010; 54:552–557.
Misiolek HD, Kucia HJ, Knapik P, Werszner MM, Karpe JW, Gumprecht J. Brachial plexus block with ropivacaine and bupivacaine for the formation of arteriovenous fistula in patients with end-stage renal failure. Eur J Anaesthesiol 2005; 22:473–475.
Choi S, Rodseth R, McCartney CJ. Effects of dexamethasone as a local anaesthetic adjuvant for brachial plexus block: a systematic review and meta-analysis of randomized trials. Br J Anaesth 2014; 112:427–439.
Bouaziz H, Paqueron X, Bur ML, Merle M, Laxenaire MC, Benhamou D. No enhancement of sensory and motor blockade by neostigmine added to mepivacaine axillary plexus block. Anesthesiology 1999; 91:78–83.
Beckett N, Parks L, McNamee D, Milligan KR. Postoperative analgesia following knee arthroscopy: an assessment of intra-articular neostigmine. Anaesthesia 2002; 57:1146–1147.
Bone HG, Van Aken H, Booke M, Bürkle H. Enhancement of axillary brachial plexus block anesthesia by co administration of neostigmine. Reg Anesth Pain Med 1999; 24:405–410.
Liu FC, Lee LI, Liou JT, Hui YL, Lui PW. Ultrasound-guided axillary brachial plexus block in patients with chronic renal failure: report of sixteen cases. Chang Gung Med J 2005; 28:180–185.
Lee JH, Cho SH, Kim SH, Chae WS, Jin HC, Lee JS, Kim YI. Ropivacaine for ultrasound-guided interscalene block: 5 mL provides similar analgesia but less phrenic nerve paralysis than 10 mL. Can J Anaesth 2011; 58:1001–1006.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]