Comparative Evaluation Of The Effectiveness Of Dexamethasone And Adrenaline With 2% Lignocaine For Pterygomandibular Nerve Blocks: A Randomized Controlled Clinical Study

: Background and Aim: Dexamethasone, a glucocorticoid, has been used in local anesthetics as an additive for various locoregional nerve blocks. Although, its use in the dental field has not been unexplored and concealed. The current study was conducted to evaluate and compare the calibre of anesthesia, their hemodynamic response, vasoconstrictive effects, and control of pain while administering pterygomandibular nerve blocks using 2% Lignocaine hydrochloride solution with Dexamethasone(4mg/ml) with that of the standard 2% Lignocaine hydrochloride solution and Adrenaline


Introduction:
Pain and inflammation are inevitable responses of living tissues to any surgical trauma as it results in the release of inflammatory mediators that enervates the peripheral nociceptors, eventually resulting in hyperalgesia and patient discomfort 1 .Pain control is an important aspect of patient management and involves the usage of individual drugs, and multimodal analgesics singly or in combinations, with or without LA agents.
Corticosteroids are important adjuncts to surgery since they suppress inflammatory mediators, thereby reducing post-surgical oedema.Conventionally, systemic corticosteroids are administered (pre/intra/post operatively) post the evulsion of impacted mandibular wisdom teeth surgically aimed to reduce the post-operative outcome such as swelling, trismus, and pain.Thoren H et al. determined through a retrospective study correlating the ramification of perioperative glucocorticosteroids on surgical wound healing that there was no higher risk of interference in the healing of bone with doses equivalent to 30 mg or less of dexamethasone 2 .Grossi GB et al. comparatively assessed the effects of dexamethasone injected submucosally in the doses of 4mg and 8 mg on the postoperative distress following wisdom tooth surgery and ascertained that the difference between the two dosage regimens was statistically not significant 3 .Dexamethasone, a synthetic glucocorticoid has a halflife of 36-54 hours as they have 20-30 times more potent anti-inflammatory action in contrast to cortisol.It has been recommended as a single-dose therapy for controlling post-surgical inflammatory sequelae in the maxillofacial region 4 .Bhargava et al have demonstrated the effectiveness of Twin Mix (1.8 ml of 2 % lignocaine with 1:200,000 epinephrine + 1 ml of 4 mg dexamethasone inj.) injected into pterygomandibular space (intra-space administration), reducing the postoperative outcome following mandibular wisdom tooth removal.It was also determined that the admixture reduced the latency and prolonged the duration of anesthesia 5 .Administration of intra-space twin mix has been proven to be efficient to the conventional methods of steroid administration 4 Based on the above, the current study was intended to comparatively assess the efficacy of 2% Lignocaine with Dexamethasone sodium phosphate (4mg) and 2% Lignocaine with Adrenaline bitartrate (1:80000 ie 12.5 μgm/ml) for pterygomandibular nerve blocks in the surgical removal of impacted mandibular wisdom teeth.In accordance with the null hypothesis of the study tested, the efficacy of Dexamethasone with 2% Lignocaine when compared with Adrenaline with 2% Lignocaine in the surgical evulsion of impacted mandibular wisdom teeth, showed no difference in their outcome variables-the quality of anaesthesia, vasoconstriction effects, hemodynamic response and pain control.

Materials and Method:
This randomized controlled triple-blind (operator, subject, and observer) study was performed in the Dept. of Oral and Maxillofacial Surgery at a recognized dental college.The formula used to calculate the sample size (n) is: n= 2 (Zα +Zβ) 2 [s] 2 /d 2 Wherein: Zα: z variate of α error i.e. a constant with a value 1.96, Zβ: having a value of 0.84.
Hence, from the literature, the mean and standard deviation was contemplated, and almost 40 subjects per group were determined.The ethical clearance was obtained from the Institutional Ethics Committee.
Patients in the age range of 18 to 45 years, reporting to the maxillofacial surgery OPD for surgical extraction of impacted mandibular wisdom teeth and consenting to be a part of this study, were enrolled for the study.A complete medical history was taken and routine hematological and radiological investigations were prescribed.After ascertaining that the patient belonged to ASA-I, had no history of drug allergy were used in this research, or any active infection currently, the molar to be extracted was moderately difficult (5-7, as per Pederson's Difficulty Index 6 ) and consented to be a part of this study, he/she was randomly allocated to one of the 2 groups by computer generated sequence.Childbearing mothers, nursing mothers, patients with a past history of cardiovascular or other medical ailments, or any contraindication and/or drug interaction with Dexamethasone/ Adrenaline, apprehensive patients, any illness or medication in the past week were excluded.
For the test group/ Group 1: 1ml of Dexamethasone sodium phosphate (4mg/ml) was mixed with 2ml of plain 2% lignocaine just prior to the surgical procedure.
The control group (Group 2) was administered with standard solution of 2% Lignocaine with Adrenaline 1:80,000.The surgical procedure was conducted by a single standardized operator and the variables were noted and measured by a single observer, both blinded.All surgical procedures were carried out using Pterygomandibular nerve blocks after ascertaining negative aspiration of blood.
The outcome variables assessed were, i) calibre of anesthesia (onset, duration, and depth) ii) vasoconstrictive effects/ blood loss, iii) hemodynamic variables i.e., SBP, DBP, MABP, and HR, and iv) postoperative pain control.The onset of anesthesia, determined in seconds, is defined as the time interval from the time of administration of local anesthetic to the first tingling sensation experienced by the subject on the labium inferious oris.Duration, determined in minutes, was recorded from the time of the first sensation of paraesthesia on the labium inferious oris until the first prescriptive rescue analgesic was consumed by the subject.Depth of anesthesia was a measure of intra-operative pain control assessed using a visual analogue scale (VAS).The vasoconstrictive effects were estimated from the loss of blood volume which was calculated as the difference in weights of the gauze pieces used preoperatively and postoperatively and the difference in the volume of used saline and suction jar collection.SBP, DBP, MABP, and HR were determined until LA injection and periodical at intervals of 5mins, 10mins, 15mins, 30mins, and 45mins using a multiparameter monitor (Intellivue MX 400, Philips, with more than 95% accuracy).

Statistical Procedures:
MS For all the statistical tests, the power to study was given as 80%, by keeping α error (false positive) at 5% and β error (false negative) at 20%, and P<0.05 was considered to be statistically significant.
On inter-group comparison, the mean age of the subjects was considered to be statistically nonsignificant (P>0.05), while ruling out any confounding effect of age.Similarly, for prevalence of sex of the subjects obtained was not statistically significant (P >0.05).
Table 1 shows the inter-group comparison of amount of solution injected, number of injections, Onset, duration, depth, vasoconstrictive effects and post-op pain control Table 2 shows the inter group comparison of hemodynamic variables

Discussion:
From the systematic review and meta-analysis conducted by Markiewicz MR et al, it is evident that the administration of steroids clinically reduces postoperative edema and improves the range of motion after the surgical evulsion of the wisdom tooth, thereby reducing postoperative morbidity 7 .Bhargava et al conducted a pilot study to analyze the effectiveness of intra-space administration (pterygomandibular) of Twin Mix (1.8 ml 2 % lignocaine with 1:200,000 epinephrine + 1 ml of 4 mg dexamethasone) along with 2 % lignocaine with 1:200,000 epinephrine for surgical extraction of mandibular third molars 5 .The study deduced that the inclusion of Dexamethasone improved both the comfort postoperatively, and also shortened the inception and the period of the soft tissue anesthesia.Further, it was shown that the postoperative comfort with Twin mix was comparable to other routes of steroid administration 4 .UV Spectrometry confirmed the chemical stability of Twin mix 8 .The study on absorption of dexamethasone systemically after intra-space vs intra muscular administration showed statistically no significant difference in plasma concentration of venous blood using high performance liquid chromatography 9,10 .Noss C et al through their systematic review, affirmed the safety of perineural usage of dexamethasone 11 .
In the present study, a freshly prepared mixture of 1ml Dexamethasone sodium phosphate (4mg) and 2% lignocaine was comparatively evaluated with the standard Adrenaline (12.5gm/ml) and 2% lignocaine 1:80000 for pterygomandibular nerve blocks to examine the quality of anesthesia, its hemodynamic alterations, surgical blood loss and intra and postoperative pain control.
Onset of LA action showed a highly significant difference(p=0.000)with a Mean of 196.50 sec for grp1, and 283.88 sec for grp2; (Table 1).This was consistent with the results from other studies 4,5,12 .The decreased onset of action with Dexamethasone as an additive has been explained on the basis of vasoconstrictive action, alkalinization of LA solution (rendering more unionised entities, RN) and increasing the inhibitory activity of potassium channels on Cfibres 5 .
Duration of action showed a highly significant difference (p=0.000) with a Mean of 183.75min for grp 1, and 109.95min for grp2; (Table 1).This was also consistent with previously reported studies for pterygomandibular blocks as well as upper and lower extremity nerve blocks 1,4,5,12,13 .The mechanism of prolonged action has been described on the basis of multi-modal anti-inflammatory effects of dexamethasone thereby leading to minimal release of inflammatory mediators like leukotrienes and prostaglandins 15 .
Similarly, the number of post-operative analgesics consumed in 3 days by the subjects in Group 1 mean (2.75) was less than group 2 (5.40) (Table 1) thereby, the variation obtained was statistically significant (p=0.000).Similar inference was drawn by Chong et al 13 in the systematic review and meta-analysis stating the superiority of perineural administration in comparison with iv administration for post-operative pain control.
The intra-operative VAS score showed statistically no significant difference (mean 2.15 for grp 1, 2.23for grp 2), amount of solution used and number of injections between the 2groups; suggesting that 4mg/ml of dexamethasone might be equally effective as an additive to lignocaine as 12.5 gm/ml of Adr in terms of depth of anesthesia with similar quantities of solution being used in 2 groups.
The amount of blood loss as assessed indirectly by 2 methods, showed statistically no significant difference, affirming the vasoconstrictive effect of Dexamethasone.M.E.Ullian reviewed the function of steroids in the management of vascular tone and concluded that "corticosteroids enhance the actions of vasoconstrictor hormones thereby augmenting the vascular tone and have direct effect on vascular smooth muscle cells that are unconventional of vasoconstrictor hormones" 16 .Thus, vasoconstrictive effects of dexamethasone are comparable to Adr.
There was statistically no significant difference in SBP, DBP, MABP and HR amongst the 2groups at all intervals (Table 2).There is evidence of sodium and water retention on prolonged usage of glucocorticoids, there by leading to hypertension.However, a single dose of 4mg does not lead to hemodynamic changes. 17ne of the study subjects reported with any drug related local and/or systemic adverse effects.
Thus, it can be concluded that dexamethasone as an additive may be safely administered with lignocaine for maxillofacial nerve blocks because it alkalinizes the solution, leads to early onset, prolongs analgesia thereby reducing consumption of systemic post-op analgesics.Administration is easy in a single prick with LA, so no separate injections/ oral administration is required.Due to its anti-inflammatory properties and added local effect, post-operative Quality of life is better.

Limitations and Future Scope:
Based on the approval from IEC, this study had to be restricted to the subjects from ASA-I category.However, more studies may be designed including medically compromised patients in whom adrenaline is contraindicated or only limited amounts are permissible.Effectiveness of Dexamethasone may be studied with other anaesthetics.The effect of this combination may also be studied with other nerve blocks.