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Wahdan AS, Moussa AA, Farag MAF, Alayyaf HA, Mohamed MM. Postoperative analgesic effect of adding neostigmine to levobupivacaine in ultrasound-guided spermatic cord block for testicular sperm extraction surgery. J Anaesthesiol Clin Pharmacol 2025; 41:333-339. [PMID: 40248777 PMCID: PMC12002689 DOI: 10.4103/joacp.joacp_14_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 03/12/2024] [Accepted: 03/12/2024] [Indexed: 04/19/2025] Open
Abstract
Background and Aims Providing postoperative pain management in patients who underwent scrotal surgeries is achieved using several methods, one of which is the ultrasound-guided spermatic cord block (US-SCB). To enhance anesthesia quality and extend analgesia postoperatively, several agents have been added in conjunction with local agents. This study targeted assessing the results of combining neostigmine with levobupivacaine in US-SCB for providing perioperative analgesia in patients undergoing testicular sperm extraction (TESE) surgery. Material and Methods This double-blind, randomized controlled study was performed for 112 subjects undergoing TESE operation using general anesthesia. They were randomly and equally divided into two groups. All participants received bilateral US-SCB after induction of general anesthesia by 19 mL of levobupivacaine 0.5% combined with 1 mL of neostigmine 500 μg in (group N) or 1 mL of normal saline in (group C). The first analgesic dose request time and the amount of analgesic consumed in the first 24 h were the main points of comparison in both groups. Results The mean postoperative analgesia duration was noticeably increased in the N group compared to the C group, with a value of 480 ± 41.34 min versus 404 ± 34.14 min, independently (P < 0.001). Moreover, the total amount of postoperative analgesic consumption was remarkably decreased in group N when compared to group C without statistically remarkable divergence concerning complications between both groups. Conclusion Adding neostigmine to a local anesthetic solution in US-SCB proved to detain the first analgesic request postoperatively with reduced perioperative analgesia consumption, without significant side effects.
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Affiliation(s)
- Amr Samir Wahdan
- Department of Anesthesia, Surgical ICU and Pain Management, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Abdelhady Moussa
- Department of Andrology, Sexology and STDS, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt
| | | | - Hasan Abdullah Alayyaf
- Department of Anesthesia and Pain Management, Al-Hada Armed Forces Hospital, Taif, Saudi Arabia
| | - Mennatallah Magdi Mohamed
- Department of Anesthesia, Surgical ICU and Pain Management, Faculty of Medicine, Cairo University, Cairo, Egypt
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Hassanin AA, Youssef IA, Mohamed HAA, Hanna GA. Effect of adding neostigmine to bupivacaine for ultrasound-guided supraclavicular brachial plexus block in forearm surgeries a randomized, blinded, controlled study. EGYPTIAN JOURNAL OF ANAESTHESIA 2023. [DOI: 10.1080/11101849.2023.2165890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Affiliation(s)
- Abeer A.M. Hassanin
- Department of Anesthesia and Intensive Care, Faculty of Medicine, Minia University, Minya, Egypt
| | - Ibrahim A. Youssef
- Department of Anesthesia and Intensive Care, Faculty of Medicine, Minia University, Minya, Egypt
| | - Heba A. A. Mohamed
- Department of Anesthesia and Intensive Care, Faculty of Medicine, Minia University, Minya, Egypt
| | - George A. Hanna
- Department of Anesthesia and Intensive Care, Faculty of Medicine, Minia University, Minya, Egypt
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Nestor CC, Ng C, Sepulveda P, Irwin MG. Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review. Anaesthesia 2021; 77:339-350. [PMID: 34904711 DOI: 10.1111/anae.15641] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2021] [Indexed: 12/19/2022]
Abstract
Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.
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Affiliation(s)
- C C Nestor
- Department of Anaesthesiology, University of Hong Kong, Hong Kong, China
| | - C Ng
- Department of Anaesthesiology, University of Hong Kong, Hong Kong, China
| | | | - M G Irwin
- Department of Anaesthesia and Pain Medicine, Hospital Base San Jose, Los Lagos, Chile
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Edinoff AN, Fitz-Gerald JS, Holland KAA, Reed JG, Murnane SE, Minter SG, Kaye AJ, Cornett EM, Imani F, Khademi SH, Kaye AM, Urman RD, Kaye AD. Adjuvant Drugs for Peripheral Nerve Blocks: The Role of NMDA Antagonists, Neostigmine, Epinephrine, and Sodium Bicarbonate. Anesth Pain Med 2021; 11:e117146. [PMID: 34540646 PMCID: PMC8438710 DOI: 10.5812/aapm.117146] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 01/02/2023] Open
Abstract
The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and inflammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse effects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic effects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor antagonists are a viable option for patients with opioid resistance and neuropathic pain due to their affinity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its effect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic effects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more efficiently crosses lipid membranes of peripheral nerves. However, more research is needed to show the efficacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes.
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Affiliation(s)
- Amber N. Edinoff
- Louisiana State University Health Science Center Shreveport, Department of Psychiatry and Behavioral Medicine, Shreveport, LA, USA
| | - Joseph S. Fitz-Gerald
- Louisiana State University Health Science Center Shreveport, Department of Psychiatry and Behavioral Medicine, Shreveport, LA, USA
| | - Krisha Andrea A. Holland
- School of Allied Health, Louisiana State University Shreveport, Department of Physical Therapy, Shreveport, LA, USA
| | - Johnnie G. Reed
- School of Allied Health, Louisiana State University Shreveport, Department of Physical Therapy, Shreveport, LA, USA
| | - Sarah E. Murnane
- School of Allied Health, Louisiana State University Shreveport, Department of Physical Therapy, Shreveport, LA, USA
| | - Sarah G. Minter
- School of Allied Health, Louisiana State University Shreveport, Department of Physical Therapy, Shreveport, LA, USA
| | - Aaron J. Kaye
- Medical University of South Carolina, Department of Anesthesiology and Perioperative Medicine, Charleston, SC, USA
| | - Elyse M. Cornett
- Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, USA
| | - Farnad Imani
- Pain Research Center, Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Adam M. Kaye
- Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Department of Pharmacy Practice, Stockton, CA, USA
| | - Richard D. Urman
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Alan D. Kaye
- Louisiana State University Shreveport, Department of Anesthesiology, Shreveport, LA, USA
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Local Anesthetic Additives for Regional Anesthesia: a Review of Current Literature and Clinical Application. CURRENT ANESTHESIOLOGY REPORTS 2019. [DOI: 10.1007/s40140-019-00334-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Schäfer M, Mousa SA, Shaqura M, Tafelski S. [Background and current use of adjuvants for regional anesthesia : From research to evidence-based patient treatment]. Anaesthesist 2019; 68:3-14. [PMID: 30645692 DOI: 10.1007/s00101-018-0522-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.
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Affiliation(s)
- M Schäfer
- Klinik für Anästhesiologie mit S. op. Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland.
| | - S A Mousa
- Klinik für Anästhesiologie mit S. op. Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland
| | - M Shaqura
- Klinik für Anästhesiologie mit S. op. Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland
| | - S Tafelski
- Klinik für Anästhesiologie mit S. op. Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland
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Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017; 5:307-323. [PMID: 28868303 PMCID: PMC5561500 DOI: 10.12998/wjcc.v5.i8.307] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 05/03/2017] [Accepted: 05/19/2017] [Indexed: 02/05/2023] Open
Abstract
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal, microspheres and cyclodextrin systems) and further studies with other drugs (adenosine, neuromuscular blockers, dextrans).
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Effect of warming bupivacaine 0.5% on ultrasound-guided axillary plexus block. Randomized prospective double-blind study. Orthop Traumatol Surg Res 2017; 103:71-75. [PMID: 27894852 DOI: 10.1016/j.otsr.2016.10.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 10/11/2016] [Accepted: 10/27/2016] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To evaluate the effect of warming bupivacaine 0.5% on ultrasound-guided axillary brachial plexus block. STUDY DESIGN Prospective, randomized, double-blind. PATIENTS AND METHODS Eighty patients undergoing elective or emergency surgery beyond the distal third of the upper limb were divided into two groups of 40 patients: the warm group received 15mL bupivacaine 0.5% heated to 37°C; the cold group received 15mL 0.5% bupivacaine stored for at least 24hours in the lower compartment of a refrigerator at 13-15°C. Onset and duration of sensory and motor blocks were evaluated every 5minutes for 40minutes. Postoperative pain was evaluated at 1, 3, 6, 12 and 24hours. Effective analgesia time was recorded as the interval between anesthetic injection and the first analgesia requirement (VAS>30mm). RESULTS Time to onset of sensory and motor block was significantly shorter in the warm group, and mean duration of sensory and motor block and of postoperative analgesia significantly longer. CONCLUSION Warming bupivacaine 0.5% to 37°C accelerated onset of sensory and motor block and extended action duration.
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Opperer M, Gerner P, Memtsoudis SG. Additives to local anesthetics for peripheral nerve blocks or local anesthesia: a review of the literature. Pain Manag 2015; 5:117-28. [DOI: 10.2217/pmt.15.2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
SUMMARY A multitude of studies have focused on individual additives to local anesthetics and their effect on quality, onset, duration, spread and selectivity, as well as the potential toxic effects of their use. This review aims to give a broad overview of the current evidence in this developing field, based on beneficial and adverse effects of these drugs. We discuss the limitations of the available data and hope to convey implications and future perspectives for clinicians and researchers alike.
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Affiliation(s)
- Mathias Opperer
- Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA
- Department of Anesthesiology, Paracelsus Medical University, Müllnerhauptstraße 48, 5020 Salzburg, Austria
| | - Peter Gerner
- Department of Anesthesiology, Paracelsus Medical University, Müllnerhauptstraße 48, 5020 Salzburg, Austria
| | - Stavros G Memtsoudis
- Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA
- Department of Anesthesiology, Paracelsus Medical University, Müllnerhauptstraße 48, 5020 Salzburg, Austria
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White PF, White LM, Monk T, Jakobsson J, Raeder J, Mulroy MF, Bertini L, Torri G, Solca M, Pittoni G, Bettelli G. Perioperative care for the older outpatient undergoing ambulatory surgery. Anesth Analg 2012; 114:1190-215. [PMID: 22467899 DOI: 10.1213/ane.0b013e31824f19b8] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
As the number of ambulatory surgery procedures continues to grow in an aging global society, the implementation of evidence-based perioperative care programs for the elderly will assume increased importance. Given the recent advances in anesthesia, surgery, and monitoring technology, the ambulatory setting offers potential advantages for elderly patients undergoing elective surgery. In this review article we summarize the physiologic and pharmacologic effects of aging and their influence on anesthetic drugs, the important considerations in the preoperative evaluation of elderly outpatients with coexisting diseases, the advantages and disadvantages of different anesthetic techniques on a procedural-specific basis, and offer recommendations regarding the management of common postoperative side effects (including delirium and cognitive dysfunction, fatigue, dizziness, pain, and gastrointestinal dysfunction) after ambulatory surgery. We conclude with a discussion of future challenges related to the growth of ambulatory surgery practice in this segment of our surgical population. When information specifically for the elderly population was not available in the peer-reviewed literature, we drew from relevant information in other ambulatory surgery populations.
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Affiliation(s)
- Paul F White
- Department of Anesthesia, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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Abstract
PURPOSE OF REVIEW To present a review of the literature on the importance and the clinical characteristics relevant to adjuvants added to local anaesthetics in neuraxial and peripheral nerve blocks. RECENT FINDINGS In neuraxial anaesthesia, both opioids and alpha-2 receptor agonists have beneficial effects. Intrathecally, fentanyl and sufentanil not only improve the postoperative analgesia but also make it possible to allow a decrease in the local anaesthetic dose. When clonidine or dexmedetomidine was added to intrathecal local anaesthetics, the regression of sensory, motor block increased dose-dependently and postoperative analgesia was prolonged. The potency of intrathecal clonidine: dexmedetomidine seems to be 10: 1. In peripheral nerve block, when opioid was combined with local anaesthetics, no increased improvement in analgesia was reported in comparison with systemic controls in most of the studies, except buprenorphine. Also clonidine is controversial as an analgesic adjuvant. Special factors, such as type of local anaesthetics, block of upper or lower limb, are important for its the beneficial effect. Other adjuvants, except neuraxial low-dose neostigmine, are of minor importance. SUMMARY Opioids and alpha-2 receptor agonists are important as neuraxial adjuvants to improve the quality of peroperative and postoperative analgesia in high-risk patients and in ambulatory procedures. In peripheral nerve blocks, however, some benefit is found only when clonidine is added to local anaesthetics under certain circumstances.
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Neal JM, Gerancher JC, Hebl JR, Ilfeld BM, McCartney CJL, Franco CD, Hogan QH. Upper extremity regional anesthesia: essentials of our current understanding, 2008. Reg Anesth Pain Med 2009; 34:134-70. [PMID: 19282714 PMCID: PMC2779737 DOI: 10.1097/aap.0b013e31819624eb] [Citation(s) in RCA: 204] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Brachial plexus blockade is the cornerstone of the peripheral nerve regional anesthesia practice of most anesthesiologists. As part of the American Society of Regional Anesthesia and Pain Medicine's commitment to providing intensive evidence-based education related to regional anesthesia and analgesia, this article is a complete update of our 2002 comprehensive review of upper extremity anesthesia. The text of the review focuses on (1) pertinent anatomy, (2) approaches to the brachial plexus and techniques that optimize block quality, (4) local anesthetic and adjuvant pharmacology, (5) complications, (6) perioperative issues, and (6) challenges for future research.
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Affiliation(s)
- Joseph M Neal
- Department of Anesthesiology, Virginia Mason Medical Center, Seattle, WA, USA.
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Klein SM, Nielsen KC. Brachial plexus blocks: infusions and other mechanisms to provide prolonged analgesia. Curr Opin Anaesthesiol 2007; 16:393-9. [PMID: 17021488 DOI: 10.1097/01.aco.0000084477.59960.92] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
PURPOSE OF REVIEW Regional anesthesia has numerous benefits for upper extremity surgery such as improved analgesia, opioid sparing and reduced side effects. However, many of these advantages are lost after block regression. Recently, several strategies such as continuous ambulatory local anesthetic infusions and adjuvants that may potentiate analgesia after a brachial plexus block have been described and investigated. This review will highlight and place in context this recent work. RECENT FINDINGS Current investigations have demonstrated that brachial plexus analgesia can be extended by combining existing solutions and technology. This has been most evident in the use of ambulatory continuous peripheral nerve blocks such as the interscalene, infraclavicular and axillary approaches. Accomplishing this safely in an outpatient setting requires the use of basic infusion pumps, patient education and a mechanism for follow-up after discharge. This strategy has prolonged pain relief and facilitated major operations on an outpatient basis. An alternative to this strategy is to combine adjuvants such as opioids, clonidine, ketamine and neostigmine to potentiate the effects of local anesthetics. These additives have had mixed results. The most promising solutions are the alpha-2-adrenergic agonists but further investigation is necessary to confirm their efficacy and quantify their appropriate dose and side effects. SUMMARY The advances and techniques recently described demonstrate that prolonging analgesia after brachial plexus blocks is possible. This may be accomplished via several different approaches and mechanisms resulting in improved patient analgesia and side effects.
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Affiliation(s)
- Stephen M Klein
- Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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Abstract
Adjuvants are compounds which by themselves have undesirable side-effects or low potency but in combination with opioids allow a reduction of narcotic dosing for postoperative pain control. Adjuvants are needed for postoperative pain management due to side-effects of opioid analgesics, which hinder recovery, especially in the increasingly utilized ambulatory surgical procedures. NMDA antagonists have psychomimetic side-effects at high doses, but at moderate doses do not cause stereotypic behavior but allow reduction in opioid dose to obtain better pain control. Alpha-2 adrenergic agonists cause sedation, hypotension and bradycardia at moderate doses, but at low doses can be opioid sparing especially in spinal administration. Gabapentin-like compounds have low potency against acute pain, but in combination with opioids allow a reduction in opioid dose with improved analgesia. Corticosteroids may have only a limited role as adjuvants while acetylcholine esterase inhibitors may have too many side-effects. Newer adjuvants will be needed to reduce opioid dose and concomitant side-effects, even more as same day surgeries become more routine.
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Affiliation(s)
- Asokumar Buvanendran
- Department of Anesthesiology, 1653 W Congress Parkway, # 739, Rush University Medical Center, Chicago, IL 60612, USA.
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Abstract
Neostigmine is a parasympathomimetic agent that has been recently investigated for use as an adjunct analgesic agent in the perioperative and peripartum period. A number of studies have investigated the intrathecal, epidural, caudal and intra-articular routes of administration of this agent, as well as the addition of neostigmine to local anaesthetics used for brachial plexus block and intravenous regional anaesthesia. While the intrathecal administration of neostigmine produced useful analgesic effects in the postoperative period in some studies, the high incidence of adverse events, mainly nausea and vomiting, limit the clinical usefulness of this route of administration. Several studies investigated the postoperative analgesic effects of epidural neostigmine using a number of different regimens. Overall, this route of administration appeared to improve postoperative analgesia in most studies without increasing the incidence of adverse events, and merits further research. Neuraxial administration of neostigmine appears to be safe in the obstetric population, with no reported adverse effects in the mother or fetus. While intrathecal administration is limited by a high incidence of nausea and vomiting in this patient population, the epidural route appears more promising and requires further investigation. The addition of neostigmine to caudal local anaesthetics was associated with improved postoperative analgesia in a number of studies. A dose of 2 microg/kg proved to be effective in several studies but was associated with an increased incidence of vomiting in some studies. Intra-articular administration of neostigmine 500microg produced a useful analgesic effect in the postoperative period in several studies and was not associated with an increase in the incidence of adverse effects. Studies investigating the efficacy of adding neostigmine to the local anaesthetics used for brachial plexus block and intravenous regional anaesthesia reported conflicting results. Further studies are required to determine the place of the administration of neostigmine by these routes.
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Affiliation(s)
- Ashraf S Habib
- Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
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Abstract
Despite many medical advances, the incidence of postoperative nausea and vomiting (PONV) and postdischarge nausea and vomit-ing (PDNV) remains high. Sequelae such as dehydration, wound dehiscence, bleeding and others, contributed to increased healthcare costs and patient dissatisfaction. This article reviews the literature regarding the anatomy of emesis, the predictors of PONV and various treatments.
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Affiliation(s)
- Karen Stanley Williams
- Department of Anesthesiology and Critical Care, George Washington University Medical Center, 900 23rd Street, N.W., Washington DC 20037, USA.
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Boselli E, Guillier M, Freney J, Mazoyer MA, Casoli E, Renaud FRN, Rimmelé T, Chassard D, Allaouchiche B. Antibacterial Activity of Clonidine and Neostigmine In Vitro. Anesth Analg 2005; 101:121-4, table of contents. [PMID: 15976217 DOI: 10.1213/01.ane.0000153500.68193.f7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We conducted an in vitro study to investigate the antibacterial activity of clonidine and neostigmine on common microorganisms encountered during infectious complications after regional anesthesia. Standardized suspensions of Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli were incubated during 1, 3, 6, and 24 h at 37 degrees C with concentrations of 37.5, 75, and 150 microg/mL of clonidine and 125, 250, and 500 microg/mL of neostigmine. After 24 h incubation at 37 degrees C, the colony counts were compared by two-way analysis of variance. The mean colony counts for S. aureus decreased significantly from control as the exposure to clonidine increased (P < 0.05), with a approximately 100% kill at 6 h for the largest concentration (150 microg/mL) and at 24 h for the intermediate concentration (75 microg/mL). Similar results were observed for S. epidermidis, with a approximately 100% kill at 6 h for the largest concentrations (75 and 150 microg/mL). No bactericidal activity of clonidine was observed for E. coli and no bactericidal activity of neostigmine was observed for any of the tested strains. In the conditions of this experiment, clonidine, but not neostigmine, exhibited a concentration-dependent and time-dependent bactericidal activity in vitro on the microorganisms most frequently encountered in infectious complications after regional anesthesia.
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Affiliation(s)
- Emmanuel Boselli
- Service d'Anesthésie-Réanimation, Department of Anesthesiology, Hôpital Edouard Herriot, 5 place d'Arsonval, 69437 Lyon cedex 03, France.
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Abstract
Postoperative pain remains a major problem. A multi-modal analgesic approach is recommended to optimize pain management and reduce opiate-related adverse effects. Several analgesic adjuncts have been investigated, and many have proved to have a useful analgesic effect. This article reviews the literature regarding use of analgesic adjuncts in the perioperative period.
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Affiliation(s)
- Ashraf S Habib
- Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710, USA
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Abstract
Interest in the use of regional anaesthesia, particularly peripheral nerve blocks (PNBs) and continuous PNBs, has increased in recent years. Accompanying this resurgence in interest has been the development of new local anaesthetics and additives designed to enhance block duration and quality. This manuscript provides a literature-based review on accepted uses of local anaesthetics and adjuncts for a variety of regional anaesthesia techniques. A brief review of local anaesthetic pharmacodynamics describes the action of these drugs in preventing nerve depolarisation, thus blocking nerve impulses. Toxic adverse effects of local anaesthetics, specifically CNS and cardiac manifestations of excessive local anaesthetic blood concentrations and the direct neurotoxic properties of local anaesthetics, are discussed generally and specifically for many commonly used local anaesthetics. Clinically useful ester and amide local anaesthetics are evaluated individually in terms of their physical properties and toxic potential. How these properties impact on the clinical uses of each local anaesthetic is explored. Particular emphasis is placed on the long-acting local anaesthetic toxic potential of racemic bupivacaine compared with levobupivacaine and ropivacaine, which are both levorotatory stereoisomers. Guidelines for using ropivacaine and mepivacaine, based on the authors' experience using advanced regional anaesthesia in a busy practice, is provided. Finally, epinephrine (adrenaline), clonidine and other local anaesthetic additives and their rationale for use is covered along with other future possibilities.
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Klein S, Nielsen K. Curr Opin Anaesthesiol 2003; 16:393-399. [DOI: 10.1097/00001503-200308000-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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Bouderka MA, Al-Harrar R, Bouaggad A, Harti A. [Neostigmine added to bupivacaine in axillary plexus block: which benefit?]. ANNALES FRANCAISES D'ANESTHESIE ET DE REANIMATION 2003; 22:510-3. [PMID: 12893374 DOI: 10.1016/s0750-7658(03)00184-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Recent study showed that neostigmine (500 microg) by intra-articular produces postoperative analgesia without adverse effect. The author's goal was to determine whether 500 microg of neostigmine added to bupivacaine in axillary plexus block could prolonged postoperative analgesia without increasing the incidence of side effects. METHODS Ninety patients scheduled for orthopedic or plastic surgery with axillary plexus block were randomly assigned to one of 3 groups : group 1 (TGr n = 30) received saline solution (1 ml) in the axillary plexus, group 2 (NAGr n = 30) received 500 microg (1 ml) neostigmine in the axillary plexus and group 3.500 microg neostigmine subcutaneously (NSGr n = 30). We evaluated visual analog pain scores (VAS), the consumption of the ketoprofene, nausea and vomiting incidence during the first 24 h. ANOVA, Kruskall Wallis and Fisher tests were used for statistical analysis. A p value of <0.05 was considered significant. RESULTS The VAS score was lower in NAGr (21 +/- 18) vs NSGr (31 +/- 14) and control group TGr (45 +/- 2) (p < 0.05). The consumption of the ketoprofene is 127 +/- 65 mg in NAGr vs 150 +/- 53 mg in NSGr and 200 +/- 50 mg in group TGr (p = 0.02). Incidence of nausea and vomiting was 3.5% in NAGr vs 6.8% in NSGr and 0% for TGr. CONCLUSION Neostigmine combined to a mixture of lidocaine and bupivacaine prolongs postoperative analgesia after axillary plexus block.
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Affiliation(s)
- M A Bouderka
- Département d'anesthésie-réanimation, CHU Ibn-Rochd, Casablanca, Maroc.
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Roelants F, Rizzo M, Lavand'homme P. The effect of epidural neostigmine combined with ropivacaine and sufentanil on neuraxial analgesia during labor. Anesth Analg 2003; 96:1161-1166. [PMID: 12651677 DOI: 10.1213/01.ane.0000050480.73209.9c] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Spinal neostigmine produces analgesia without respiratory depression or hypotension but provokes major gastrointestinal side effects. Epidural injection of this drug, however, appears to induce analgesia devoid of such side effects. In this study, we evaluated the effect of a bolus of epidural neostigmine on the duration and magnitude of analgesia in early labor and assessed its eventual sparing effect on subsequent local anesthetic requirements. Epidural neostigmine methylsulfate (maximal dose 4 microg/kg) was added to 10 mL of ropivacaine 0.1%, with and without sufentanil 10 microg, to initiate analgesia. Twenty minutes after injection, pain score, sensory level, and motor block were assessed. Time until request for supplemental epidural medication was also recorded. Patient-controlled epidural analgesia with ropivacaine 0.1% was used for epidural supplementation. Maternal and fetal side effects were closely recorded. Neostigmine (4 microg/kg), when added to ropivacaine 10 mg, provided equivalent analgesia to ropivacaine 20 mg but was less effective than sufentanil 10 microg for the initiation of labor epidural analgesia. Further, neostigmine did not modify the subsequent patient-controlled epidural analgesia local anesthetic requirements during labor. No hemodynamic instability, additional motor block, or bothersome side effects were recorded. IMPLICATIONS The combination of epidural neostigmine (4 microg/kg) with the local anesthetic ropivacaine, with or without sufentanil, does not significantly enhance neuraxial analgesia during labor. Such a dose, however, has no bothersome side effects.
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Affiliation(s)
- Fabienne Roelants
- Department of Anesthesiology, Université Catholique de Louvain, St. Luc Hospital, Brussels, Belgium
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Kuntz F, Bouaziz H, Bur ML, Boileau S, Merle M, Laxenaire MC. [Comparison between 1.5% lidocaine with adrenaline and 1.5% plain mepivacaine in axillary brachial plexus block]. ANNALES FRANCAISES D'ANESTHESIE ET DE REANIMATION 2001; 20:693-8. [PMID: 11695288 DOI: 10.1016/s0750-7658(01)00453-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVES To evaluate the distribution of sensory blockade, the onset time and the duration of the axillary plexus block obtained after the administration of 40 mL of 1.5% lignocaine with adrenaline or 40 mL of plain 1.5% mepivacaine. STUDY DESIGN Prospective, randomised, comparative, double blind study. PATIENTS AND METHODS One hundred and fifty five patients undergoing hand surgery were randomised into two groups: in group L, 73 patients were given 1.5% lignocaine with 1/200,000 adrenaline and in group M, 82 patients received 1.5% mepivacaine. The entire volume was injected on the first evoked motor activity obtained for a current less than 0.5 mA. Sensory and motor block of each of the four major nerves of the hand and forearm were assessed using light touch and motor strength respectively. The block was considered complete when all nerves were anaesthetised (median, radial, musculocutaneous and ulnar). RESULTS The percentage of complete sensitive blockade was 22% in group L and 24% in group M. Complete motor blockade was respectively 27% in group L and 40% in group M. The median time required to obtain a complete sensory blockade was 18 min for both group. The median time required to obtain a complete motor blockade was 17 min in-group L and 16 min in-group M. The duration of the sensory blockade was not different for both groups (i.e., 255 +/- 76 min versus 231 +/- 70 min in group L and M respectively. The duration of the motor blockade was longer in group L compared to group M (199 +/- 64 min versus 231 +/- 74 min respectively, p < 0.05). CONCLUSION Following axillary plexus block, 1.5% mepivacaine improves neither the extension nor the duration of sensory blockade achieved by 1.5% lignocaine with adrenaline.
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Affiliation(s)
- F Kuntz
- Service d'anesthésie-réanimation chirurgicale, hôpital Central, 29, avenue du Maréchal de Lattre-de-Tassigny, 54035 Nancy, France
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Iskandar H, Guillaume E, Dixmérias F, Binje B, Rakotondriamihary S, Thiebaut R, Maurette P. The enhancement of sensory blockade by clonidine selectively added to mepivacaine after midhumeral block. Anesth Analg 2001; 93:771-5. [PMID: 11524354 DOI: 10.1097/00000539-200109000-00043] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clonidine added to local anesthetics results in an increased duration of anesthesia or analgesia after brachial plexus block. We investigated the effect of selective application of clonidine to the median and musculocutaneous nerves during midhumeral block, a technique allowing selective nerve blocks with the use of different local anesthetics. Initially, 58 patients scheduled for hand surgery were prospectively enrolled to receive a midhumeral block. These patients were randomly allocated into two groups. The Control group (n = 28) received 10 mL of plain mepivacaine 1.5% for each nerve (median, musculocutaneous, ulnar, and radial). The Clonidine group (n = 30) received 10 mL of plain mepivacaine 1.5% for each nerve, but the median and musculocutaneous nerves also received a dose of 50 microg clonidine. One patient in the Control group and two patients in the Clonidine group with a failed block were therefore excluded from the analysis. The onset time of surgical anesthesia was recorded. The durations of sensory and motor blocks were checked every 15 min. The plasma mepivacaine concentration was analyzed from 10 patients in each group. Onset times for complete sensory block were similar between the two groups. Adding 50 microg clonidine to the median and musculocutaneous nerves resulted in a significant increase in the duration of sensory block in these nerves (P < 0.0001). Recovery of motor block was not different between the two groups. No significant difference was found between the two groups in the mean plasma mepivacaine concentration.
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Affiliation(s)
- H Iskandar
- Clinique Chirurgicale Bordeaux-Mérignac, Mérignac, France.
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Lack of peripheral analgesia mediated by intraplantar administration of neostigmine in carrageenan-injected rats. Eur J Anaesthesiol 2001. [DOI: 10.1097/00003643-200105000-00004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Reply to Dr. Sessler. Reg Anesth Pain Med 2000. [DOI: 10.1097/00115550-200005000-00025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Murphy DB, McCartney CJ, Chan VW. Novel analgesic adjuncts for brachial plexus block: a systematic review. Anesth Analg 2000; 90:1122-8. [PMID: 10781465 DOI: 10.1097/00000539-200005000-00023] [Citation(s) in RCA: 167] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This article reviews current evidence for the efficacy of adding novel analgesic adjuncts to brachial plexus block, the goal of which is to prolong analgesic effect without the disadvantage of systemic side effects or prolonged motor block. It may also allow for a reduction in the total dose of local anesthetic used. Novel adjuncts studied to date include opioids, clonidine, neostigmine, and tramadol. Twenty-four studies were reviewed and assessed by using specific inclusion criteria, and only those studies satisfying these criteria were included in the final assessment. Satisfactory studies were then assessed for inclusion of a systemic control group to determine peripheral effect, as opposed to possible systemic effect, of an adjunct administered peripherally. Evidence regarding the analgesic benefit of opioid adjuncts remains equivocal and more evidence is required before their routine use can be recommended. Clonidine appears to have significant analgesic benefit and to cause minimal adverse effects when used in doses up to 150 microg. Data regarding other drugs, such as tramadol and neostigmine, are not sufficient to allow for any recommendations, and further studies are required.
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Affiliation(s)
- D B Murphy
- Department of Anaesthesia and Pain Management, Toronto Western Hospital University Health Network, Toronto, Canada
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Bouaziz H, Kinirons BP, Macalou D, Heck M, Dap F, Benhamou D, Laxenaire MC. Sufentanil Does Not Prolong the Duration of Analgesia in a Mepivacaine Brachial Plexus Block: A Dose Response Study. Anesth Analg 2000. [DOI: 10.1213/00000539-200002000-00027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Bouaziz H, Kinirons BP, Macalou D, Heck M, Dap F, Benhamou D, Laxenaire MC. Sufentanil does not prolong the duration of analgesia in a mepivacaine brachial plexus block: a dose response study. Anesth Analg 2000; 90:383-7. [PMID: 10648326 DOI: 10.1097/00000539-200002000-00027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
UNLABELLED To date, results of studies evaluating the efficacy of opioids and local anesthetic combinations in the brachial plexus are inconclusive. We examined whether increasing sufentanil in doses of 5, 10, and 20 microg decreased onset time or increased duration of an axillary brachial plexus block. Ninety-two patients scheduled for carpal tunnel release under axillary brachial plexus block were enrolled in the study. Patients were randomized to receive axillary plexus block with 40 mL 1.5% mepivacaine and saline (Group 1), sufentanil 5 microg (Group 2), 10 microg (Group 3), or 20 microg (Group 4). Onset and duration of sensory and motor block were measured. Opioid-related side effects were recorded. The addition of sufentanil did not improve speed of onset or increase the duration of sensory or motor block. Paradoxically, duration of sensory and motor block was longest in the control group: sensory, 241 min (188-284) and motor, 234 min (128-305), and decreased with increasing doses of sufentanil in Group 4: sensory, 216 min (115-315) and motor, 172 min (115-260) (P < 0.05). Side effects occurred in 55% of patients belonging to Groups 2 and 4, and in 60% of the patients in Group 3. In contrast, only 10% of the patients reported side effects in the control group. We conclude that sufentanil added to mepivacaine does not increase the onset or prolong the duration of an axillary plexus block. Furthermore, the addition of sufentanil was associated with a frequent incidence of side effects. IMPLICATIONS This study demonstrates that the addition of sufentanil in a dose-dependent manner to 1.5% mepivacaine in the axillary plexus does not improve onset or duration of blockade, and that this admixture is associated with an increased incidence of side effects.
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Affiliation(s)
- H Bouaziz
- Département d'Anesthésie-Réanimation, CHU Hôpital Central, Nancy, France.
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