eISSN: 1731-2531
ISSN: 1642-5758
Anaesthesiology Intensive Therapy
Current issue Archive Manuscripts accepted About the journal Editorial board Journal's reviewers Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank

vol. 52
Review paper

Adjuvants in peripheral nerve blocks – the current state of knowledge

Wojciech Gola
Marek Zając
Adam Cugowski

Department of Anaesthesiology and Intensive Therapy, St. Lukas Specialist Hospital in Końskie, Poland
Anaesthesiol Intensive Ther 2020; 52, 4: 323–329
Online publish date: 2020/10/23
Article file
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Regional anaesthetic techniques are an essential element in acute and postoperative pain management [1]. Perineural deposition of a local anaesthetic leads to reversible blockade of sodium channels and temporary inhibition of nociceptive conduction. Nerve conduction blockade is based on the all-or-none law; hence, regional anaesthesia is the most efficacious form of analgesia. The benefits of regional analgesic techniques are particularly noticeable in trauma-orthopaedic, large-joint reconstructive and thoracic surgical procedures (Table 1) [2].
Depending on the local anaesthetic (LA) used, the duration of analgesia is limited to a maximum of 12–16 hours. For most scheduled procedures (usually performed between 8 a.m. and 3 p.m.), the blocking effect ends in the late evening or night [3, 4]. In most departments, compared to daytime, night hours are associated with a smaller staffing of medical personnel who can respond quickly to pain reported by the patient, which creates a risk of lack of optimal pain control. The imperative in the treatment of postoperative pain is to provide the patient with optimal analgesia and comfort, especially during the period of the most severe complaints, i.e. on the first postoperative day, including night hours. Hence, many techniques are used in clinical practice to prolong standard analgesia after perineural deposition of LA. These techniques include:
• continuous nerve/plexus block followed by an infusion of a local anaesthetic,
• liposomal forms of local anaesthetics,
• intravenous or perineural delivery of adjuvants.
Continuous peripheral nerve blocks are widely used in clinical practice. Despite many advantages, there are also many factors significantly limiting their routine use (Table 2) [5–7]. Apart from organizational or logistics problems regarding care and supervision, the limitations are predominantly associated with high continuous block failure rates. Their causes can be divided into primary and secondary. The former mainly include the factors related to difficulties during implantations of continuous block sets. The latter encompass the factors that affect the functioning of a correctly established set: dislocation or spontaneous migration of the catheter, as well as LA leaks along the catheter working channel. Secondary factors are the main reason for the failure of continuous blocks. According to current literature, spontaneous migration or LA leakage occurs in 30–40% of correctly implemented sets [5, 6]. An important element affecting the effectiveness of continuous infusion is the proper pump operation. Moreover, the risk of systemic toxicity of local anaesthetics, likely to occur during their continuous perineural delivery, should be taken into consideration.
The use of liposomal forms of LAs is limited by registration issues, availability and price of drugs; hence, it is not a routine method used to prolong the peripheral block. Liposomal bupivacaine has not been approved for use by the European Union. In the USA, it has been approved for infiltrative anaesthesia, and only for interscalene brachial plexus blocks [8, 9]. Intravenous or perineural use of adjuvants is another measure to prolong regional block. In the literature, there is an arbitrary classification of drugs that prolong the peripheral block into “old” and “new” adjuvants (Table 3). The “old” adjuvants include adrenaline, sodium bicarbonate, clonidine, buprenorphine, tramadol, midazolam and magnesium sulphate, while dexamethasone and dexmedetomidine are among the “new” adjuvants.


Adrenaline is one of the oldest adjuvants used in clinical practice. Administered perineurally, it does not directly affect nerve conduction, but it causes a decrease in the absorption of LA into blood vessels, as a result, the time of LA contact with nerve fibres is prolonged. It is most often used in a dose of 2.5–5 µg mL-1 of LA solution. Prolonged block after perineural adrenaline deposition ranges from 33 to 100 mins (average: 60 mins) [10]. Applied as an adjuvant, adrenaline is a relatively safe drug. Studies in rats have not showed an increase in the percentage of either histological or functional nerve damage after perineural administration of a mixture of lidocaine and adrenaline [11]. It should be remembered, however, that adrenaline may potentiate the vasoconstrictor effect, especially in relation to long-acting LAs, thus prolonging the toxic effect of LA on axons [12, 13]. This is particularly important in the case of patients with pre-existing blood supply disorders, e.g. diabetes [14]. The addition of adrenaline to LA is mainly used as an indicator of the intravascular administration of LA. Adrenaline also limits the distribution of LA to the central compartment, thus reducing the risk of local anaesthetic systemic toxicity [12, 15]. Due to the negligible effect of prolonging block duration, adrenaline is currently used mainly as an adjuvant to improve the safety profile of the LA and an indicator of unintended intravascular delivery of LA.


Sodium bicarbonate (NaHCO3–) is used as an adjuvant to accelerate the block onset. The mechanism of action of sodium bicarbonate is to increase the pH of the solution and thus facilitate the dissociation of the LA to an alkaline form, which is fat-soluble and diffuses into the nerve fibre, where re-ionization and reversible blocking of sodium channels occur. The use of sodium bicarbonate as an adjuvant does not increase the duration of analgesia but can only shorten the time of its occurrence [16]. The most common problem associated with the use of NaHCO3– in a solution is the precipitation of LA. To avoid this, the right dose of adjuvant in the solution should be used [16]. For lidocaine, the standard dose should be 1 mL NaHCO3– per 10 mL LA, and in the case of bupivacaine, 0.1 mL NaHCO3– per 10 mL LA. No clinical effect has been demonstrated for the bicarbonate-ropivacaine combination [18].


-2 adrenoreceptor agonists are a group of drugs that have a sedative and analgesic effect. Two substances from this group are mainly used in clinical practice, i.e. clonidine and dexmedetomidine, which are characterized by, among others, different binding selectivities for -1 and -2 receptors. Clonidine was primarily used as an antihypertensive agent. It has a much lower selectivity for -2 receptors, compared to dexmedetomidine. Dexmedetomidine is an S-enantiomer of medetomidine, primarily used in veterinary medicine. It is characterized by much greater selectivity for -2 adrenergic receptors (-2 : -1 = 1600 : 1), which makes it practically a pure agonist of this receptor subpopulation. For comparison, the selectivity of clonidine for -2 adrenergic receptors over -1 adrenergic receptors is only 200 : 1 [19]. The clinical effect following the intravenous administration of -2 adrenoceptor agonists is the result of their effect on both peripheral and central -2 receptors. The sedative effect is associated with the stimulation of receptors located in the locus coeruleus in the brainstem. However, the analgesic effect is associated with the stimulation of receptors located in the dorsal root of the spinal cord, which inhibits the secretion of stimulants, substance P and glutamine [20]. Common side effects of this drug group include hypotension and bradycardia [20–22]. Under physiological conditions, the expression of -2 receptors in peripheral nerve axons is absent [23]. Therefore, after perineural supply in addition to LA, clonidine and dexmedetomidine prolong analgesia time in a multidirectional and extremely complex mechanism, both by direct action on the peripheral nerve, but also by central influence [20]. The direct effect on peripheral fibres results, among others, from the properties similar to LA and inhibition of the formation of action potential in type C fibres, as well as hyperpolarization associated with the activation of intracellular cationic current (acting on cyclic nucleotide-gated cation (CNG) channels [20]. In the case of clonidine, a reduction in central redistribution of LA by -1 adrenergic receptor-mediated vasoconstriction has also been suggested [24].


As an addition to medium- and long-acting LAs, clonidine in a dose of 150 µg increases the analgesia duration in the range of 74–169 mins (122 mins on average) [20]. However, after perineural administration of clonidine, the risk of hypotension, bradycardia, as well as excessive sedation is significantly higher [21, 22]. In addition, a greater potential for neurotoxicity after combining clonidine with ropivacaine has been observed in animal model studies, as compared to ropivacaine alone [25].


Dexmedetomidine used together with LA in a dose of 50–60 µg prolongs the analgesia duration from 5 to 7 hours (average: 6 hours) [26]. However, episodes of hypotension and bradycardia are significantly more frequent [26–28]. At a dose of 0.5 µg kg-1, after both perineural and intravenous administration, dexmedetomidine shows a similar action profile in terms of prolonged analgesia [28]. The study in an animal model has shown neuroprotective effects of peripherally administered dexmedetomidine. The addition of this drug to ropivacaine almost halves the neurotoxicity of LA [29].


Inflammation induces the expression of opioid receptors in peripheral nerve fibres and on immune response cells. In addition, significant amounts of endogenous opioids are released, which is aimed at balancing and silencing the increased nociception process induced by inflammation. Nevertheless, the trauma and inflammation-induced ability to express opioid receptors and the production of endogenous opioids by the immune system is a time-delayed process and usually takes up to 96 hours after injury [30]. The injury to the nerve tissue in the dorsal root ganglion (DRG) results in an increased production of opioid receptors, followed by their axonal transport in microtubules towards the peripheral nerve endings, where they are incorporated into the nerve fibre membrane.
Over the years, numerous studies have been conducted to determine the benefits of perineural delivery of opioids as adjuvants to LA, but it is still extremely difficult to determine whether the analgesic effect after perineural administration of opioids is the result of their effect only on the peripheral opioid receptors, or is a central action occurring after redistribution of the drug to the central compartment. The explanation of this problem is extremely important from the clinical point of view. The pure peripheral effect of an opioid, in addition to improving anti-nociception, would also be associated with reduced incidences of side effects of this group of drugs. Otherwise, with the significant coexistence of central influence, perineural administration would have no clinical validity. The analysis of studies and reports on the effectiveness and benefits of perineural opioid delivery brings ambiguous results and does not allow recommending this form of delivery of these drugs [31, 32]. An exception is buprenorphine, which has been shown to extend the duration of analgesia after being deposited perineurally in combination with LA.


Buprenorphine is a partial agonist of the mi type opioid receptors. The distinguishing feature of buprenorphine is high receptor affinity and lipophilicity, which allows it to easily penetrate the neuronal membrane. Used perineurally in a dose of 0.1–0.3 mg as an addition to LA, it increases the duration of analgesia from 6.44 to 10.85 hours (8.5 hours on average) [33, 34]. This effect is not observed in the case of block with the use of LA alone and systemic delivery of buprenorphine, which clearly indicates the peripheral mechanism of the drug action. However, it should be remembered that perineural administration of buprenorphine induces postoperative nausea and vomiting (PONV), which significantly limits its use in clinical practice [33].

Corticosteroids (Dexamethasone)

The mechanism responsible for prolonging block duration after the use of dexamethasone as an adjuvant to LA is multidirectional and extremely complex (Table 4) [35, 36]. Administered perineurally with LA, dexamethasone in a dose of 4 mg prolongs the effect of short- and medium-acting LAs by 3–5 hours (average: 4 hours), and of long-acting LAs by 7–9 hours (average: 8 hours) [37]. Moreover, an increase in the dose of dexamethasone has not been found to cause a statistically significant difference in action [38]. In addition to lengthening the duration of analgesia, the use of dexamethasone shortens the onset time of block [27], and, which has been observed in studies on animal models, has a protective effect on the nerve cells [39]. It is worth noting, however, that after adding dexamethasone to ropivacaine, the former crystallizes in the solution, which creates a potential danger for the patient, making this combination not applicable in clinical practice (such a reaction was not observed for lidocaine and bupivacaine) [40]. Current studies show that intravenous administration of dexamethasone has an equivalent effect of prolonged analgesia as perineural delivery [41]. In the case of intravenous route, the optimal effect of prolonged analgesia is obtained by administering a dose of 0.1–0.2 mg kg-1 one hour prior to surgery [1]. An important benefit associated with this administration route of dexamethasone is also a reduction in the incidence of PONV [42]. Moreover, the use of dexamethasone before induction of general anaesthesia has been demonstrated to significantly reduce the patient’s need for both intraoperative and postoperative opioids [1, 43, 44]. In patients administered iv dexamethasone to increase peripheral block duration, or as a co-analgesic, no increase in the percentage of neurological complications, infections, or prolonged wound healing was observed, but only a small, transient, clinically insignificant increase in blood glucose levels [27]. A common limitation of preoperative intravenous administration of dexamethasone may be the frequent occurrence (50–70%) of severe, burning perineal pain, especially when the drug is administered quickly at a low volume. This can be prevented by diluting the drug in 50 mL 0.9% NaCl and giving it by intravenous infusion over 10–15 minutes [1, 43, 44].


Tramadol is a weak MOR agonist. It is distinguished by an inhibitory effect on noradrenaline reuptake and a stimulating effect on the secretion of serotonin in the CNS [45]. Both noradrenaline and serotonin are extremely important substances in the descending anti-nociceptive system of the spinal cord. As an adjuvant to LA, tramadol has been used both in epidural anaesthesia and in nerve and plexus blocks [46, 47]. At present, due to contradictory reports regarding the effectiveness of perineural tramadol delivery, it is not recommended to use this adjuvant in routine clinical practice [48, 49].


Ketamine is a N-methyl-D-aspartate (NMDA) receptor antagonist, which only slightly prolongs the peripheral nerve block. Due to high incidences of adverse effects, such as hallucinations, dizziness, nausea and vomiting, perineural administration of this drug is not recommended [49, 50].


Midazolam, a water-soluble benzodiazepine, is an indirect γ-aminobutyric acid receptor agonist. Initially studied as an adjuvant of spinal and epidural anaesthesia, midazolam has not been approved for perineural use due to its neurotoxicity and lack of clinically significant evidence of prolonging the duration of LA [49, 51].


Intravenous regional anaesthesia (IVRA) was first described in 1908 by the father of regional anaesthesiology August Bier [52]. This quite simple and safe technique of anaesthesia is most often used for minor and short soft tissue procedures on the forearm and hand, much less frequently for the lower leg and foot procedures. IVRA is also indicated for the management of the complex regional pain syndrome (CRPS) [53]. To optimize analgesia, increase tourniquet tolerance and prolong postoperative analgesia, the use of an intravenous adjuvant to LA may be considered. Over the years, many different substances have been used for this purpose, including opioids, -2 adrenergic receptor agonists, striated muscle relaxants, neostigmine, alkalizing drugs (NaHCO3), non-steroidal anti-inflammatory drugs, and corticosteroids [17]. Most evidence and scientific reports support the use of non-steroidal anti-inflammatory drugs as adjuvants to IVRA. Most studies concern ketorolac: its addition to lidocaine in a dose of 20 mg significantly improves tourniquet tolerance and extends the time of postoperative analgesia without inducing any significant adverse effects [54, 55].
As for opioids (fentanyl, sufentanil, morphine) as adjuvants to IVRA, most studies do not confirm improvement of the analgesic effect and, therefore, their use is not recommended [56]. The addition of 50–100 mg tramadol to a 0.5% lidocaine solution accelerates the occurrence of sensory block and increases tourniquet tolerance [57]. Nevertheless, the use of tramadol as an adjuvant of IVRA is limited by an intense pain during injection and skin changes (urticaria) developing at the injection site of the mixture of LA with tramadol [57]. Studies on the use of -2 adrenergic receptor agonists as an addition to a 0.5% lidocaine solution may indicate improvement in tourniquet tolerance and postoperative analgesia. The use of dexmedetomidine in a dose of 0.5 μg kg-1 with a 0.5% lidocaine solution accelerates sensory and motor blocks, increases tourniquet tolerance, improves analgesia, and extends tourniquet tolerance time [58]. Similar effects have not been observed after clonidine (2 μg kg–1), with a significant decrease in blood pressure additionally observed in this group after the release of the tourniquet [59].
Neuromuscular blocking agents may be added to LA in IVRA to achieve deeper motor block required for bone surgery. Non-depolarizing neuromuscular blocking agents, such as atracurium, pancuronium and mivacurium, are most commonly used in clinical practice [60, 61]. Furthermore, one of the indications for IVRA is the management of complex regional pain syndrome (CRPS). Due to the pathophysiology of this disease entity, adjuvants with the potential of chemical sympathectomy are used. They inhibit the post-ganglionic adrenergic neurons, the storage of noradrenaline in synaptic vesicles (guanethidine, reserpine), and the secretion of noradrenaline (bretylium). The clinical trials on guanethidine in CRPS did not demonstrate evident benefits compared to placebo [62]. Otherwise, the bretylium effects reducing pain severity and improving limb blood flow were more pronounced [53].


Due to numerous limitations and problems associated with continuous nerve and plexus blocking techniques, the use of adjuvants is a good and safe way to prolong postoperative analgesia – both in intravenous and perineural administration routes (Table 5). Of all the adjuvants used in clinical practice, the most optimal clinical effect with the best safety profile is that of dexamethasone. Perineural administration in a dose of 4 mg and intravenous supply (one hour before surgery) in a dose of 0.1–0.2 mg kg-1 are equivalent and, in the case of block with long-acting LA, increase the time of analgesia by an average of 8 hours. This gives the clinician an opportunity to provide patient comfort and optimal pain management throughout the first postoperative day, including night hours. An additional benefit of intravenous dexamethasone is the reduction in postoperative nausea and vomiting. When deciding on perineural delivery of an adjuvant, it should be borne in mind that none of the drugs discussed in this study (except for adrenaline) has been approved for perineural administration and all will then be used off label – except as indicated in the summary of product characteristics. It should also be remembered that the perineural route is restricted only for medications without preservatives. Considering the above and the clinical efficacy and safety profile, the authors of this study recommend iv dexamethasone as the adjuvant of choice for nerve and plexus blocks. In the case of IVRA, non-steroidal anti-inflammatory drugs are still the adjuvants of choice, the addition of which to lidocaine extends the time of tourniquet tolerance and prolongs postoperative analgesia, without inducing adverse side effects. Ketorolac is the representative of this group with the best documented activity in IVRA. Unfortunately, it is not available in Poland.

1. Funding: none.
2. Conflict of interest: none.
1. Misiołek H, Zajączkowska R, Daszkiewicz A, et al. Postoperative pain management – 2018 consensus statement of the Section of Regional Anaesthesia and Pain Therapy of the Polish Society of Anaesthesiology and Intensive Therapy, the Polish Society of Regional Anaesthesia and Pain Therapy, the Polish Association for the Study of Pain and the National Consultant in Anaesthesiology and Intensive Therapy. Anaesthesiol Intensive Ther 2018; 50: 173-199. doi: 10.5603/AIT.2018.0026.
2. Kopp SL, Børglum J, Buvanendran A, et al. Anesthesia and analgesia practice pathway options for total knee arthroplasty: an evidence-based review by the American and European Societies of Regional Anesthesia and Pain Medicine. Reg Anesth Pain Med 2017; 42: 683-697. doi: 10.1097/AAP.0000000000000673.
3. Gadsden J, Hadzic A, Gandhi K, et al. The effect of mixing 1.5% mepivacaine and 0.5% bupivacaine on duration of analgesia and latency of block onset in ultrasound-guided interscalene block. Anesth Analg 2011; 112: 471-476. doi: 10.1213/ANE.0b013e3182042f7f.
4. Fredrickson MJ, Abeysekera A, White R. Randomized study of the effect of local anesthetic volume and concentration on the duration of peripheral nerve blockade. Reg Anesth Pain Med 2012; 37: 495-501. doi: 10.1097/AAP.0b013e3182580fd0.
5. Salinas FV. Location, location, location: continuous peripheral nerve blocks and stimulating catheters. Reg Anesth Pain Med 2003; 28: 79-82. doi: 10.1053/rapm.2003.50033.
6. Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg 2011; 113: 904-925. doi: 10.1213/ANE. 0b013e3182285e01.
7. Salviz EA, Xu D, Frulla A, et al. Continuous interscalene block in patients having outpatient rotator cuff repair surgery: a prospective randomized trial. Anesth Analg 2013; 117: 1485-92. doi: 10.1213/01.ane.0000436607.40643.0a.
8. Vandepitte C, Kuroda M, Witvrouw R, et al. Addition of liposome bupivacaine to bupivacaine HCl versus bupivacaine HCl alone for interscalene brachial plexus block in patients having major shoulder surgery. Reg Anesth Pain Med 2017; 42: 334-341. doi: 10.1097/AAP.0000000000000560.
9. Abildgaard JT, Lonergan KT, Tolan SJ, et al. Liposomal bupivacaine versus indwelling interscalene nerve block for postoperative pain control in shoulder arthroplasty: a prospective randomized controlled trial. J Shoulder Elbow Surg 2017; 26: 1175-1181. doi: 10.1016/j.jse.2017.03.012.
10. Tschopp C, Tramèr MR, Schneider A, Zaarour M, Elia N. Benefit and harm of adding epinephrine to a local anesthetic for neuraxial and locoregional anesthesia: a meta-analysis of randomized controlled trials with trial sequential analyses. Anesth Analg 2018; 127: 228-239. doi: 10.1213/ANE.0000000000003417.
11. Komatsu T, Takenami T, Nara Y, et al. Epinephrine administered with lidocaine solution does not worsen intrathecal lidocaine neurotoxicity in rats. Reg Anesth Pain Med 2013; 38: 140-144. doi: 10.1097/AAP. 0b013e318279499d.
12. Partridge BL. The effects of local anesthetics and epinephrine on rat sciatic nerve blood flow. Anesthesiology 1991; 75: 243-250. doi: 10.1097/00000542-199108000-00012.
13. Palmer GM, Cairns BE, Berkes SL, Dunning PS, Taylor GA, Berde CB. The effects of lidocaine and adrenergic agonists on rat sciatic nerve and skeletal muscle blood. Anesth Analg 2002; 95: 1080-1086. doi: 10.2147/lra.s203569.
14. Pietraszek P. Regional anaesthesia induced peripheral nerve injury. Anaesthesiol Intensive Ther 2018; 50: 367-377. doi: 10.5603/AIT. 2018.0049.
15. Neal JM, Barrington MJ, Fettiplace MR, et al. The third American Society of Regional Anesthesia and Pain Medicine practice advisory on local anesthetic systemic toxicity: executive summary 2017. Reg Anesth Pain Med 2018; 43: 113-123. doi: 10.1097/AAP. 0000000000000720.
16. Capogna G, Celleno D, Laudano D, Giunta F. Alkalinization of local anesthetics. Which block, which local anesthetic? Reg Anesth 1995; 20: 369-377.
17. Hadzic A. Textbook of Regional Anesthesia and acute pain management, 1st Edition. NY: McGraw-Hill Medical, New York 2006; 137-138.
18. Ramos G, Pereira E, Simonetti MP. Does alkalinization of 0.75% ropivacaine promote a lumbar epidural block of higher quality? Reg Anesth Pain Med 2001; 26: 357-62. doi.org/10.1053/rapm.2001. 24257.
19. Su F, Hammer GB. Dexmedetomidine: pediatric pharmacology, clinical uses and safety. Expert Opin Drug Saf 2011; 10: 55-66. doi: 10.1517/14740338.2010.512609.
20. Pöpping DM, Elia N, Marret E, Wenk M, Tramèr MR. Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus blocks: a meta-analysis of randomized trials. Anesthesiology 2009; 111: 406-415. doi: 10.1097/ALN.0b013e3181aae897.
21. Beaussier M, Weickmans H, Abdelhalim Z, Lienhart A. Inguinal herniorrhaphy under monitored anesthesia care with ilioinguinal-iliohypogastric block: The impact of adding clonidine to ropivacaine. Anesth Analg 2005; 101: 1659-62. doi: 10.1213/01.ANE.0000184046. 64631.50.
22. Bernard JM, Macaire P. Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology 1997; 87: 277-284. doi: 10.1097/00000542-199708000-00014.
23. Eisenach JC, De Kock M, Klimscha W. Alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology 1996; 85: 655-674. doi: 10.1097/00000542-199609000- 00026.
24. Eisenach JC, Gebhart GF. Intrathecal amitriptyline. Antinociceptive interactions with intravenous morphine and intrathecal clonidine, neostigmine, and carbamylcholine in rats. Anesthesiology 1995; 83: 1036-1045. doi: 10.1097/00000542-199511000-00017.
25. Williams BA, Hough KA, Tsui BY, Ibinson JW, Gold MS, Gebhart GF. Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in comparison with ropivacaine. Reg Anesth Pain Med 2011; 36: 225-230. doi: 10.1097/AAP.0b013e3182176f70.
26. Abdallah FW, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. Br J Anaesth 2013; 110: 915-925. doi: 10.1093/bja/aet066.
27. Albrecht E, Vorobeichik L, Jacot-Guillarmod A, Fournier N, Abdal-
28. lah FW. Dexamethasone is superior to dexmedetomidine as a perineural adjunct for supraclavicular brachial plexus block: systematic review and indirect meta-analysis. Anesth Analg 2019; 128: 543-554. doi: 10.1213/ANE.0000000000003860.
29. Abdallah FW, Dwyer T, Chan VW, et al. IV and perineural dexmedetomidine similarly prolong the duration of analgesia after interscalene brachial plexus block: a randomized, three-arm, triple-masked, placebo-controlled trial. Anesthesiology 2016; 124: 683-695. doi: 10.1097/ALN.0000000000000983.
30. Kim BS, Choi JH, Baek SH, Lee DH. Effects of intraneural injection of dexmedetomidine in combination with ropivacaine in rat sciatic nerve block. Reg Anesth Pain Med 2018; 43: 378-384. doi: 10.1097/AAP.0000000000000745.
31. Mousa SA, Zhang Q, Sitte N, Ji R, Stein C. beta-Endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue. J Neuroimmunol 2001; 115: 71-78. doi: 10.1016/s0165-5728(01)00271-5.
32. Picard PR, Tramèr MR, McQuay HJ, Moore RA. Analgesic efficacy of peripheral opioids (all except intra-articular): a qualitative systematic review of randomised controlled trials. Pain 1997; 72: 309-318. doi: 10.1016/s0304-3959(97)00040-7.
33. Murphy DB, McCartney CJ, Chan VW. Novel analgesic adjuncts for brachial plexus block: a systematic review. Anesth Analg 2000; 90: 1122-1128. doi: 10.1097/00000539-200005000-00023.
34. Schnabel A, Reichl SU, Zahn PK, Pogatzki-Zahn EM, Meyer-Frießem CH. Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials. Eur J Anaesthesiol 2017; 34: 576-586. doi: 10.1097/EJA.0000000000000628.
35. Candido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD. Buprenorphine added to the local anesthetic for axillary brachial plexus block prolongs postoperative analgesia. Reg Anesth Pain Med 2002; 27: 162-167. doi: 10.1053/rapm.2002.30671.
36. Johansson A, Hao J, Sjolund B. Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anesthesiol Scand 1990; 34: 335-338. doi: 10.1111/j.1399-6576.1990.tb03097.x.
37. Knight JB, Schott NJ, Kentor ML, Williams BA. Neurotoxicity of common peripheral nerve block adjuvants. Curr Opin in Anaesthesiol 2015; 28: 598-604. doi: 10.1097/ACO.0000000000000222.
38. Heesen M, Klimek M, Imberger G, Hoeks SE, Rossaint R, Straube S. Co-administration of dexamethasone with peripheral nerve block: intravenous vs perineural application: systematic review, meta-analysis, meta-regression and trial-sequential analysis. Br J Anaesth 2018; 120: 212-227. doi: 10.1016/j.bja.2017.11.062.
39. Kirkham KR, Jacot-Guillarmod A, Albrecht E. Optimal dose of perineural dexamethasone to prolong analgesia after brachial plexus blockade: a systematic review and meta-analysis. Anesth Analg 2018; 126: 270-279. doi: 10.1213/ANE.0000000000002488.
40. Ma R, Wang X, Lu C, et al. Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine-serine protein kinase B-dependent mechanism. Neuroscience 2010; 5: 67: 329-342. doi: 10.1016/j.neuroscience.2009.12.049.
41. Watkins TW, Dupre S, Coucher JR. Ropivacaine and dexamethasone: a potentially dangerous combination for therapeutic pain injections. J Med Imaging Radiat Oncol 2015; 59: 571-577. doi: 10.1111/1754-9485.12333.
42. Desmet M, Braems H, Reynvoet M, et al. I.V. and perineural dexamethasone are equivalent in increasing the analgesic duration of a single-shot interscalene block with ropivacaine for shoulder surgery: a prospective, randomized, placebo-controlled study. Br J Anaesth 2013; 111: 445-452. doi: 10.1093/bja/aet109.
43. Ho CM, Wu HL, Ho ST, Wang JJ. Dexamethasone prevents postoperative nausea and vomiting: benefit versus risk. Acta Anaesthesiol Taiwan 2011; 49: 100-104. doi: 10.1016/j.aat.2011.06.002.
44. De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology 2011; 115: 575-588. doi: 10.1097/ALN.0b013e31822a24c2.
45. Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS. Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis. Br J Anaesth 2013; 110: 191-200. doi: 10.1093/bja/aes431.
46. Wilder-Smith CH, Wilder-Smith OH, Farschtschian M, Naji P. Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing. Acta Anaesthesiol Scand 1998; 42: 299-305. doi: 10.1111/j.1399-6576.1998.tb04920.x.
47. Mannion S, O’Callaghan S, Murphy DB, Shorten GD. Tramadol as adjunct to psoas compartment block with levobupivacaine 0.5%: a randomized double-blinded study. Br J Anaesth 2005; 94: 352-356. doi: 10.1093/bja/aei057.
48. Baraka A, Jabbour S, Ghabash M, et al. A comparison of epidural tramadol and epidural morphine for postoperative analgesia. Can J Anaesth 1993; 40: 308-313. doi: 10.1007/BF03009627.
49. Sarsu S, Mizrak A, Karakurum GJ. Tramadol use for axillary brachial plexus blockade. Surg Res 2011; 165: e23-27. doi: 10.1016/j.jss. 2010.09.032.
50. 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. doi: 10.12998/wjcc.v5.i8.307.
51. Lee IO, Kim WK, Kong MH, et al. No enhancement of sensory and motor blockade by ketamine added to ropivacaine interscalene brachial plexus blockade. Acta Anaesthesiol Scand 2002; 46: 821-826. doi: 10.1034/j.1399-6576.2002.460711.x.
52. Kirksey MA, Haskins SC, Cheng J, Liu SS. Local anesthetic peripheral nerve block adjuvants for prolongation of analgesia: a systematic qualitative review. PLoS One 2015; 10: e0137312. doi: 10.1371/journal.pone.0137312.
53. Bier A. Übereinen neun weg localanaesthesia an den gliedmassen zu erzeugen. Arch Klin Chir 1908; 86: 1007-1016.
54. Lee F, Shoemaker JK, McQuillan PM, et al. Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip. Am J Physiol Heart Circ Physiol 2000; 279: 586-593. doi: 10.1152/ajpheart.2000.279.2.H586.
55. Reuben SS, Steinberg RB, Kreitzer JM, Duprat KM. Intravenous regional anesthesia using lidocaine and ketorolac. Anesth Analg 1995; 81: 110-113. doi: 10.1097/00000539-199507000-00022.
56. Seyfi S, Banihashem N, Bijani A, Hajian-Taliki K, Daghmehchi M, Caspian J. Analgesic effects of lidocaine-ketorolac compared to lidocaine alone for intravenous regional anesthesia. Intern Med 2018; 9: 32-37. doi: 10.22088/cjim.9.1.32.
57. Armstrong P, Power I, Wildsmith JA. Addition of fentanyl to prilocaine for intravenous regional anaesthesia. Anaesthesia 1991; 46: 278-280. doi: 10.1111/j.1365-2044.1991.tb11496.x.
58. Acalovschi I, Cristea T, Margarit S, Gavrus R. Tramadol added to lidocaine for intravenous regional anesthesia. Anesth Analg 2001; 92: 209-214. doi: 10.1097/00000539-200101000-00040.
59. Memiş D, Turan A, Karamanlioğlu B, Pamukçu Z, Kurt I. Adding dexmedetomidine to lidocaine for intravenous regional anesthesia. Anesth Analg 2004; 98: 835-840. doi: 10.1213/01.ane.0000100680. 77978.66.
60. Kleinschmidt S Stöckl W, Wilhelm W, Larsen R. The addition of clonidine to prilocaine for intravenous regional anaesthesia. Eur J Anaesthesiol 1997; 14: 40-46. doi: 10.1046/j.1365-2346.1997.00063.x.
61. Kurt, N, Kurt I, Aygünes B, Oral H, Tulunay M. Effects of adding alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia. Eur J of Anaesthesiol 2002; 19: 522-525. doi: 10.1017/s0265021502000856.
62. Elhakim M, Sadek RA. Addition of atracurium to lidocaine for intravenous regional anaesthesia. Acta Anaesthesiol Scand 1994; 38: 542-544. doi: 10.1111/j.1399-6576.1994.tb03948.x.
63. Ramamurthy S, Hoffman J. Intravenous regional guanethidine in the treatment of reflex sympathetic dystrophy/causalgia: a randomized, double-blind study. Guanethidine Study Group. Anesth Analg 1995; 81: 718-723. doi: 10.1097/00000539-199510000-00011.
This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2020 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe