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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 2  |  Page : 50-53

Proposed mechanism of action for twin mix anaesthesia when used as intra-space pterygomandibular injection for inferior alveolar nerve block with emphasis on effects of perineural injection of dexamethasone


1 Department of Oral and Maxillofacial Surgery, People's College of Dental Sciences and Research Center, People's University, Bhopal, Madhya Pradesh, India
2 Department of Oral and Maxillofacial Surgery, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
3 Department of Oral Medicine and Radiology, People's Dental Academy, People's University, Bhopal, Madhya Pradesh, India
4 Department of Periodontics, Karnavati School of Dentistry, Ahmedabad, Gujarat, India
5 Department of Oral and Maxillofacial Surgery, Lenora Institute of Dental Sciences, Rajahmundry, Andhra Pradesh, India

Date of Web Publication8-May-2018

Correspondence Address:
Darpan Bhargava
H-3/2, B.D.A Colony, Nayapura, Lalghati, Airport Road, Bhopal - 462 001, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AIHB.AIHB_33_17

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  Abstract 

There has been recent research on the use of dexamethasone as an adjunct to local anaesthetics to enhance the block characteristics and improve post-operative pain outcomes. Numerous studies have shown that perineural dexamethasone improves post-operative analgesia, along with other clinical benefits. Intra-space pterygomandibular twin mix anaesthesia is a novel technique for inferior alveolar nerve block used for mandibular anaesthesia. Twin mix anaesthesia has its advantages in shortening the latency and prolonging the duration of the soft tissue anaesthesia, along with improving the quality of life in the post-operative period after mandibular oral surgical procedures. The concern regarding the use of perineural dexamethasone has been discussed.

Keywords: Anaesthesia, dental anaesthesia, dexamethasone, inferior alveolar nerve block, lignocaine, local anaesthesia, mandible, twin mix


How to cite this article:
Bhargava D, Koneru G, Deshpande A, Desai K, Dalsingh V. Proposed mechanism of action for twin mix anaesthesia when used as intra-space pterygomandibular injection for inferior alveolar nerve block with emphasis on effects of perineural injection of dexamethasone. Adv Hum Biol 2018;8:50-3

How to cite this URL:
Bhargava D, Koneru G, Deshpande A, Desai K, Dalsingh V. Proposed mechanism of action for twin mix anaesthesia when used as intra-space pterygomandibular injection for inferior alveolar nerve block with emphasis on effects of perineural injection of dexamethasone. Adv Hum Biol [serial online] 2018 [cited 2018 Sep 25];8:50-3. Available from: http://www.aihbonline.com/text.asp?2018/8/2/50/232019


  Introduction Top


Co-administration of steroid and local anaesthetics (LAs) has shown some clinical benefits in the recent research. Perineural dexamethasone injection improves post-operative pain outcomes when given as an adjunct to LA blocks with no clinical evidence of persistent neural damage or functional alteration after perineural administration of the drug.[1] Authors had proposed the co-administration of 2% lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone (twin mix) as intra-space pterygomandibular injection for inferior alveolar nerve blocks for surgical removal of impacted mandibular third molars.[2] Twin mix intra-space pterygomandibular anaesthesia has its advantages in shortening the latency and prolonging the duration of the soft tissue anaesthesia, along with improving the quality of life in the post-operative period after surgical extraction of mandibular third molars. Patients who receive a mixture of 2% lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone show lesser swelling and better mouth opening in the post-operative period when compared to patients who receive lignocaine with epinephrine blocks. This review discusses the possible mechanisms involved in the action of this mixture when used for inferior alveolar nerve block.


  Current Clinical Evidence Top


Evidence-based practice backs the use of twin mix for inferior alveolar nerve blocks specifically in cases where surgical procedure in the mandible is expected to produce post-operative swelling and trismus.

A prospective randomised double-blind study to assess the latency and efficacy of twin mix and 2% lignocaine with 1:200,000 epinephrine in surgical removal of impacted mandibular third molars in 20 patients (40 interventions) ascertained that addition of dexamethasone to lignocaine and its administration as an intra-space injection significantly shortens the latency and prolongs the duration of the soft tissue anaesthesia, with improved quality of life in the post-operative period after surgical extraction of the mandibular third molars.[2]

Through a clinical comparative study on effects of intra-space injection of twin mix versus intraoral-submucosal, intramuscular, intravenous and per-oral administration of dexamethasone on the post-operative sequelae after mandibular impacted third molar surgery, it was concluded that steroid groups had a better clinical outcome with improved quality of life post-operatively when compared to the non-steroid study group. Intra-space injection of dexamethasone in the pterygomandibular space as twin mix was found to have similar clinical effects as conventional methods of administering steroids via intraoral-submucosal, intramuscular, intravenous and per-oral routes.[3]

In a clinical trial for comparative evaluation of efficacy of twin mix versus 2% lignocaine with 1:200000 epinephrine, it was concluded that there was better post-operative outcome with administration of dexamethasone and lignocaine as an intra-space injection in decreasing the post-operative patient discomfort. The anaesthetic efficacy of the twin mix admixture was found to be statistically similar to the control solution of 2% lignocaine with 1:200,000 epinephrine. The ultraviolet spectrometry study for chemical stability of the mixture suggested that there was no change in the active pharmacological compounds (lignocaine or dexamethasone).[4],[5]

A report by Knezevic et al. demonstrated that the addition of dexamethasone to LAs delayed the block onset. This report remains in contradiction to the author's findings in context to the use of twin mix, as the use of the mixture of 2% lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone, as intra-space pterygomandibular injection has shown to reduce the latency period in the clinical trials.[6] The possible reasons for the contradictory finding may be due to the use of different LA drugs in different anatomical space and the use of epinephrine by the authors in the twin mix solution.


  Proposed Mechanisms Involved for the Clinical Effects of Twin Mix Anaesthesia as Pterygomandibular Nerve Block for Surgical Removal of Impacted Mandibular Third Molars Top


The active pharmacological agents that produce the clinical effects of the mixture are 2% lignocaine, 1:200,000 adrenaline and 4 mg dexamethasone. Lignocaine is an amide LA, chemically 2-(diethylamino)-N-(2,6-dimethyl phenyl)-acetamide. The basic mechanism by which lignocaine produces LA is by blocking the voltage-gated sodium channels in the cell membrane of post-synaptic neurons, thereby preventing depolarisation of the neural tissue and inhibiting the generation or propagation of nerve impulses.[7]

Adrenaline in the concentration of 1:200,000 used in the mixture has several beneficial effects that include decrease in the peak plasma concentration of the LA agent, thereby reducing chances of toxicity, increasing duration and quality of anaesthesia, reducing minimum concentration of anaesthetic needed for nerve block and decreasing blood loss during surgical procedures.[8]

Dexamethasone, a corticosteroid, is a potent anti-inflammatory agent and an immunosuppressant. Its anti-inflammatory potency is 20–30 times when compared to cortisol. Dexamethasone exerts potent anti-inflammatory action by inducing the synthesis of endogenous proteins, which block the enzymatic activation of phospholipase A2. This in turn inhibits arachidonic acid release by the cell membrane, with inhibition of the synthesis of prostaglandins, leucotrienes or substances related to thromboxane.[3],[9] Dexamethasone is known to block superoxide production and lysosomal enzyme release in human polymorphonuclear neutrophils inhibiting the functional responses of degranulation. The probable action of dexamethasone on human polymorphonuclear leucocytes is by membrane-bound calcium release.[10]

Usually, addition of vasoconstrictor renders the LA solution more acidic with its pH in the range of 3.5–4.5. This acidic pH of the solution clinically produces a 'sting'-like sensation when injected into the tissue. More basic LA solutions (without vasoconstrictors) do not produce the sting on injection and minimise the tissue injury, otherwise caused by acidic solutions of LA.[11] Addition of dexamethasone to 2% lignocaine with 1:200,000 epinephrine renders the final pH of the mixture more basic (pH=6). LAs in solution exist in equilibrium between the basic uncharged (non-ionised) form, which is lipid soluble, and the charged (ionised) cationic form, which is water soluble. Lipid-soluble, non-ionised form of the LA penetrates the neural sheath and membrane (tissue penetration). The ionised form of the LA binds with the sodium channel and prevents propagating of impulses (clinical action). Altering the pH to a more basic solution, as in case of twin mix, will increase the amount of non-ionised form compared to ionised form which will speed onset. Increasing the pH of lidocaine decreases the pain associated with its infiltration.[2],[12] Dexamethasone solution when mixed with LA solution increases the pH of the LA solution from 4.5 to 6 of the mixture and clinically demonstrated faster onset of anaesthesia and longer duration with reduction of sting-like sensation on injection.[2] Proposition, yet not proved, for steroid-induced shorter onset and prolonged duration, apart from change in pH, may also be due to the vasoconstriction property of dexamethasone or by increase in the activity of the inhibitory potassium channels on nociceptive C-fibres (via glucocorticoid receptors), thus decreasing their activity.[13],[14] On investigation, dexamethasone individually is found to have analgesic effects by increasing the activity of inhibitory potassium channels on nociceptive C-fibres.[15],[16] Yet, another school of thought that holds importance is that glucocorticoids produce vasoconstriction, which might reduce LA absorption, hence prolonging LA nerve contact time.[17],[18]


  Safety Issues with the Use of Perineural Dexamethasone Injections Top


In a systematic review by Knezevic et al. on perineural dexamethasone added to LA for brachial plexus block, it was concluded that perineural dexamethasone in addition to LA solutions significantly improved post-operative pain without increasing complications, and also, smaller doses of dexamethasone (4–5 mg) were as effective as higher doses (8–10 mg).[6] These results are in concurrence of author's proposition of using 4 mg dexamethasone in the twin mix anaesthetic solution.

Concerns remain about the vasoconstrictor effects of dexamethasone, which may cause ischaemic changes in the nerve tissue if injected in nerve proximity. Wang et al. evaluated the effects of topical corticosteroids on the sciatic nerve in adult Wistar rats and suggested that caution is required when using large doses of corticosteroid in nerve proximity as topical dexamethasone adversely affected neural conduction in a dose-dependent manner.[19] Shishido et al. studied the effects of topically applied 0.4% dexamethasone on acute changes in the nerve blood flow and subsequent histologic changes in rat sciatic nerve fibers and concluded that dexamethasone causes statistically significant reductions in normal nerve blood flow at 30 min and 4 h after topical application; however, the reduction is on average below the threshold for causing ischemic changes in the structure of peripheral nerve fibres.[18] Williams et al. opine to execute caution on use of dexamethasone perineurally in doses of 8 mg or greater as this dose does not show any additional clinical benefits over lower doses of dexamethasone.[20]

Choi et al., through their systematic review and meta-analysis of randomised trials on effects of dexamethasone as an LA adjuvant for nerve blocks in the British Journal of Anaesthesia, concluded that to date, dexamethasone appears to be the best method for prolonging analgesia as an adjuvant over clonidine, epinephrine or midazolam. They also highlighted that the clinician should evaluate the risk–benefit ratio with 'off-label' use of perineural dexamethasone.[21] Noss et al., in a systematic review on the use of dexamethasone with LA, have commented that 'while dexamethasone is not approved for perineural use, this application is well described in textbooks and peer-reviewed literature. There has been reported neither an incidence of neurotoxicity nor an increased incidence of complications or side effects associated with perineural use of dexamethasone in humans in the literature.'[22]


  Conclusion Top


Twin mix, a mixture of 2% lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone, as intra-space pterygomandibular injection for inferior alveolar nerve block when used for mandibular surgical procedures, holds promising clinical benefits based on the current clinical evidence. Currently available systematic reviews and meta-analysis of randomised trials have demonstrated the use of perineural dexamethasone, in the doses used, as clinically safe.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
De Oliveira GS Jr., Castro Alves LJ, Nader A, Kendall MC, Rahangdale R, McCarthy RJ, et al. Perineural dexamethasone to improve postoperative analgesia with peripheral nerve blocks: A meta-analysis of randomized controlled trials. Pain Res Treat 2014;2014:179029.  Back to cited text no. 1
    
2.
Bhargava D, Sreekumar K, Rastogi S, Deshpande A, Chakravorty N. A prospective randomized double-blind study to assess the latency and efficacy of twin-mix and 2% lignocaine with 1:200,000 epinephrine in surgical removal of impacted mandibular third molars: A pilot study. Oral Maxillofac Surg 2013;17:275-80.  Back to cited text no. 2
[PUBMED]    
3.
Bhargava D, Sreekumar K, Deshpande A. Effects of intra-space injection of twin mix versus intraoral-submucosal, intramuscular, intravenous and per-oral administration of dexamethasone on post-operative sequelae after mandibular impacted third molar surgery: A preliminary clinical comparative study. Oral Maxillofac Surg 2014;18:293-6.  Back to cited text no. 3
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4.
Bhargava D, Deshpande A, Khare P, Pandey SP, Thakur N. Validation of data on the use of twin mix in minor oral surgery: Comparative evaluation of efficacy of twin mix versus 2 % lignocaine with 1:200000 epinephrine based on power analysis and an UV spectrometry study for chemical stability of the mixture. Oral Maxillofac Surg 2015;19:37-41.  Back to cited text no. 4
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5.
Bhargava D, Deshpande A. Twin-mix anesthesia as pterygomandibular nerve block for surgical removal of impacted mandibular third molars. Int J Stomatol Occlusion Med 2015;8:29-32.  Back to cited text no. 5
    
6.
Knezevic NN, Anantamongkol U, Candido KD. Perineural dexamethasone added to local anesthesia for brachial plexus block improves pain but delays block onset and motor blockade recovery. Pain Physician 2015;18:1-4.  Back to cited text no. 6
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7.
Buck ML. Use of lidocaine for analgesia in children and adolescents. Available from: http://www.medscape.com/viewarticle/820429_2. [Last accessed on 2015 Jun 04].  Back to cited text no. 7
    
8.
Sisk AL. Vasoconstrictors in local anesthesia for dentistry. Anesth Prog 1992;39:187-93.  Back to cited text no. 8
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9.
Ata-Ali J, Ata-Ali F, Peñarrocha-Oltra D, Peñarrocha M. Corticosteroids use in controlling pain, swelling and trismus after lower third molar surgery. J Clin Exp Dent 2011;3:e469-75.  Back to cited text no. 9
    
10.
Coates TD, Wolach B, Tzeng DY, Higgins C, Baehner RL, Boxer LA, et al. The mechanism of action of the antiinflammatory agents dexamethasone and auranofin in human polymorphonuclear leukocytes. Blood 1983;62:1070-7.  Back to cited text no. 10
    
11.
Malamend SF. Buffering local anesthetics in dentistry. Pulse 2011;4:8-9.  Back to cited text no. 11
    
12.
Cepeda MS, Tzortzopoulou A, Thackrey M, Hudcova J, Arora Gandhi P, Schumann R, et al. Adjusting the pH of lidocaine for reducing pain on injection. Cochrane Database Syst Rev. 2010;12:CD006581.  Back to cited text no. 12
    
13.
Cummings KC 3rd, Napierkowski DE, Parra-Sanchez I, Kurz A, Dalton JE, Brems JJ, et al. Effect of dexamethasone on the duration of interscalene nerve blocks with ropivacaine or bupivacaine. Br J Anaesth 2011;107:446-53.  Back to cited text no. 13
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14.
Tandoc MN, Fan L, Kolesnikov S, Kruglov A, Nader ND. Adjuvant dexamethasone with bupivacaine prolongs the duration of interscalene block: A prospective randomized trial. J Anesth 2011;25:704-9.  Back to cited text no. 14
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15.
Johansson A, Hao J, Sjölund B. Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anaesthesiol Scand 1990;34:335-8.  Back to cited text no. 15
    
16.
Attardi B, Takimoto K, Gealy R, Severns C, Levitan ES. Glucocorticoid induced up-regulation of a pituitary K+channel mRNA in vitro and in vivo. Receptors Channels 1993;1:287-93.  Back to cited text no. 16
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17.
Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A. Dexamethasone added to lidocaine prolongs axillary brachial plexus blockade. Anesth Analg 2006;102:263-7.  Back to cited text no. 17
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18.
Shishido H, Kikuchi S, Heckman H, Myers RR. Dexamethasone decreases blood flow in normal nerves and dorsal root ganglia. Spine (Phila Pa 1976) 2002;27:581-6.  Back to cited text no. 18
    
19.
Wang PH, Tsai CL, Lee JS, Wu KC, Cheng KI, Jou IM, et al. Effects of topical corticosteroids on the sciatic nerve: An experimental study to adduce the safety in treating carpal tunnel syndrome. J Hand Surg Eur Vol 2011;36:236-43.  Back to cited text no. 19
    
20.
Williams BA, Schott NJ, Mangione MP, Ibinson JW. Perineural dexamethasone and multimodal perineural analgesia: How much is too much? Anesth Analg 2014;118:912-4.  Back to cited text no. 20
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21.
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;112:427-39.  Back to cited text no. 21
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22.
Noss C, MacKenzie L, Kostash M. Dexamethasone a promising adjuvant in brachial plexus anesthesia? A systematic review. J Anesth Clin Res 2014;5:421.  Back to cited text no. 22
    




 

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