|DENTAL SCIENCE - ORIGINAL ARTICLE
|Year : 2012 | Volume
| Issue : 6 | Page : 390-393
Pharmacodynamic responses of exogenous epinephrine during mandibular third molar surgery
Sivaraj Sivanmalai1, Sivakumar Annamalai1, Santhosh Kumar1, Christo Naveen Prince2, Chandrakala2, Vinod Thangaswamy1
1 Department of Oral and Maxillofacial Surgery, JKK Nattraja Dental College and Hospitals, Komarapalayam, Namakkal, Tamil Nadu, India
2 Department of Oral Medicine and Radiology, JKK Nattraja Dental College and Hospitals, Komarapalayam, Namakkal, Tamil Nadu, India
|Date of Submission||01-Dec-2011|
|Date of Decision||02-Jan-2012|
|Date of Acceptance||26-Jan-2012|
|Date of Web Publication||28-Aug-2012|
Department of Oral and Maxillofacial Surgery, JKK Nattraja Dental College and Hospitals, Komarapalayam, Namakkal, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The systemic effects attributable to the injection of dental local anesthetic solutions have been the subject of discussion for many years. Aim and Objective: The aim of the present study was to investigate the biochemical and hemodynamic effects of adrenaline in lignocaine local anesthetic solutions when used in clinical doses in patients undergoing third molar surgery under general anesthesia. Materials and Methods: Of the total 30 patients, 15 were given local anesthetic solution containing adrenaline and the other 15 were given the same without adrenaline. Hemodynamic and biochemical parameters were recorded at considerable intervals. The changes from the pre-local anesthetic (baseline) values with each treatment were compared by analysis of variance and Student's t-test. The changes within each treatment were compared by the paired t-test. Results and Conclusion: This study shows that exogenous adrenaline administration in clinical doses produces systemic effects even in conditions where the endogenous release of the catecholamines would be expected to be considerable.
Keywords: Epinephrine, general anesthesia, pharmacodynamics, third molar surgery
|How to cite this article:|
Sivanmalai S, Annamalai S, Kumar S, Prince CN, Chandrakala, Thangaswamy V. Pharmacodynamic responses of exogenous epinephrine during mandibular third molar surgery. J Pharm Bioall Sci 2012;4, Suppl S2:390-3
|How to cite this URL:|
Sivanmalai S, Annamalai S, Kumar S, Prince CN, Chandrakala, Thangaswamy V. Pharmacodynamic responses of exogenous epinephrine during mandibular third molar surgery. J Pharm Bioall Sci [serial online] 2012 [cited 2021 Jul 29];4, Suppl S2:390-3. Available from: https://www.jpbsonline.org/text.asp?2012/4/6/390/100296
Techniques to control bleeding during maxillofacial surgeries include using moist pressure packs, electrocautery, electrically heated scalpel blade, and other hemostatic agents, and positioning the patients so that their head area is elevated above the remainder of the body. But the most effective means of controlling bleeding is the use of local vasoconstrictors and hypotensive anesthesia.
Epinephrine is employed most commonly as the vasoconstrictor. It is typically infiltrated into the area of surgery 7-10 min prior to beginning of the dissection. Epinephrine concentration of 1:200,000 is sufficient to produce the hemostasis needed. It is usually administered in combination with local anesthetic (LA) which thereby lessens the pain provoked by the surgery and helps to decrease the depth of general anesthesia.
Because the effect of the anxiety and pain during dental injection can be reduced to a minimum by anxiety reduction methods such as premedication, sedation, and topical anesthesia, a study of hemodynamic response to exogenous epinephrine is meaningful.
Cunningham et al.  noted a slight transient increase in plasma potassium after infiltration of lignocaine with adrenaline during cone biopsies under general anesthesia. Cunningham et al.  also noted increase in blood glucose 5 min following infiltration of 0.5% lignocaine with 1:200,000 adrenaline, while a control group that received plain lignocaine showed no significant increase in blood glucose level.
The aim of the present study was to investigate the biochemical and hemodynamic effects of adrenaline in lignocaine LA solutions, when used in clinical doses in patients undergoing third molar surgery under general anesthesia.
| Materials and Methods|| |
This study was conducted at Department of Oral and Maxillofacial Surgery, JKK Nattraja Dental College and Hospitals, Komarapalayam. A total of 30 patients undergoing third molar surgery were included in this prospective, randomized, clinical study. The fact that all subjects were free of any medical complication meant that a uniform general anesthetic technique could be employed for all the patients.
These patients underwent standard mandibular third molar surgical procedures between January 2010 and March 2010. Patients with respiratory, cardiovascular diseases, renal or hepatic disorders were excluded. All the patients were premedicated with 10 mg diazepam orally and 0.2 mg glycopyrrolate intramuscularly 1 h preoperatively. Venous access for induction was established with 22-gauge plastic cannula in a suitable vein in the dorsum of the left hand.
Anesthesia was induced by thiopentone and vecuronium bromide given intravenously, nasotracheal intubation maintained with intermittent positive pressure ventilation using a mixture of nitrous oxide, oxygen, and halothane. The same consultant anesthetist administered the general anesthetics for all the patients.
Before the surgery commenced, the subject received 4 ml of a LA solution. This was administered as infiltration at each site of the incision. Fifteen patients received 2% lignocaine (Group I) and 15 were given 2% lignocaine with 1:200,000 adrenaline (Group II) (i.e. total of 20 μg adrenaline). The LA allocation was random. All injections and surgery were performed by the same surgeon who was aware of the identity of the LA used. However, the anesthetist who made the hemodynamic recordings and removed the blood samples was blind in this respect.
The following recordings and blood samplings were made for each subject. Prior to induction, separate 22-gauge plastic cannula was inserted in a suitable vein in the dorsum of left hand for measurement of serum potassium and blood glucose concentrations. 2.5 ml of blood was collected in a glass test tube for estimation of serum potassium and another 2.5 ml of blood was collected in a glass test tube containing sodium fluoride and potassium oxalate.
Serum potassium was determined using a photocolorimetric method, and blood glucose was determined with o-toluidine test using colorimetric method. After induction and 1 min before LA injection, blood pressure and heart rate were recorded with a non-invasive blood pressure monitor and pulse oxymeter, respectively, and 5 ml of blood was collected for potassium and glucose assay.
These recordings and samplings were repeated immediately following and at 1, 10, and 20 min after the LA administration. Surgery began following the immediate post-injection recordings and was still in progress for all patients when the 20-min recordings were taken. This meant that the 10- and 20-min readings were taken at times when the patients were subjected to surgical stress. The patient's electrocardiograms were monitored throughout the general anesthesia.
The changes from the pre-LA (baseline) values with each treatment were compared by analysis of variance and Student's t-test. The changes within each treatment were compared by the paired t-test.
| Results|| |
The age of the patients in this investigation was 20 ± 3 years for those in whom the adrenaline containing local anesthesia was used (Group II) and 22 ± 2 years for those who received the vasoconstrictor-free solution (Group I). The body weights of both groups were similar, being 45 ± 3 kg and 47 ± 2 kg, respectively. The surgical stress experienced by both groups of patients as measured by the operating time did not differ significantly. The results of the study and statistical data are presented in [Table 1], [Table 2], [Table 3], [Table 4], [Table 5] and [Table 6]. In the analysis of the results, the readings performed 1 min before the administration of the LA were taken as baseline values and the changes at 0, 10, and 20 min from this baseline were analyzed. In the analysis, the P values less than 0.05 were considered as significant.
|Table 1: Changes from baseline values (pre-LA): Systolic blood pressure (P value)|
Click here to view
|Table 2: Changes from baseline values (pre-LA): Diastolic blood pressure (P value)|
Click here to view
|Table 3: Changes from baseline values (pre-LA): Mean arterial blood pressure (MABP) (P value)|
Click here to view
|Table 6: Changes from baseline values (pre-LA): Plasma potassium (P value)|
Click here to view
There were no significant differences in the changes in blood pressure and heart rate between treatments at any of the times recorded. There was no significant change in the plasma potassium concentration between the immediate pre-induction concentration (pre-GA) and that recorded immediately before the injection of the LA (pre-LA).
There were significant changes in plasma potassium concentration between treatments immediately following and 20 min after the LA injection [Table 6]. Immediately following the injection, there was a significant rise in plasma potassium from the baseline concentration in Group II patients. The increase in plasma potassium concentration from baseline after LA injection was significant at 10 min in Group I patients [Table 6].
There was significant rise in blood glucose concentration between the immediate pre-induction concentration (pre- GA) and that recorded immediately before the injection of the LA (pre-LA). There was no difference in this respect between Group I and Group II. The changes in blood glucose concentration were significantly different between treatments at 10 and 20 min and the glucose levels were significantly greater than the baseline values at 10 and 20 min within each treatment group [Table 5].
| Discussion|| |
This investigation was designed to isolate intraoperative systemic effects of adrenaline administered during LA injections in patients undergoing mandibular third molar surgery under general anesthesia. Any influences on postoperative pain control that might be attributable to the regimes were not considered. The results obtained were similar to those reported earlier in patients having orthognathic surgery under general anesthesia.
Meechan and Rawlins in 1987 found no significant changes in heart rate or systolic blood pressure attributable to the injection of 50 μg adrenaline.  In 1988, they also demonstrated a reduction in diastolic blood pressure following the use of adrenaline containing LAs,  but this did not occur in the present study.
The effect of adrenaline on potassium homeostasis was demonstrated by D'Silva.  He showed that the intravenous injection of adrenaline in anesthetized cats produced an early transient increase in potassium concentration which was superseded by a longer lasting hypokalemia. Similar effects on dogs have been reported by Todd and Vick, and Lim et al. , The hypokalemic effect of adrenaline is well recognized and has been demonstrated in human volunteers after intravenous injection of adrenaline , and also following extravascular intraoral injection of adrenaline containing LAs. ,
The early hyperkalemic phase which is not maintained by the presence of the catecholamine  and is thought to occur in one circulation time  has not received much attention in humans, although Cunningham et al.  noted a slight transient increase in plasma potassium after infiltration of lignocaine with adrenaline during cone biopsies under general anesthesia. The detection of the early transient increase in potassium concentration following the administration of the adrenaline containing solution in the present study supports the findings of other researchers who have reported a rapid uptake of adrenaline into the circulation following intraoral injection.  This hyperkalemic phase was not detected in patients having third molar surgery under local anesthesia although similar quantities of LA solutions were employed.
The faster rate of injection might result in higher peak concentrations of adrenaline and certainly meant that the immediate post-injection blood sample was removed closer to the time at which anesthetic administration began. Both of these factors are important as the hyperkalemic effect is highly dose dependent  and its detection is governed by the time lapse between adrenaline injection and the time of sampling.  The difference in potassium concentration between treatments in the 20 min following LA administration noted in the present study is similar to the findings of the investigations done by Meechan and Rawlins in 1988. 
Those who received the adrenaline containing solution had lower plasma potassium levels than those who received plain lignocaine. The reduction from the pre-injection potassium concentration produced by the adrenaline containing solution reported by Meechan et al. , in 1987 did not occur in the present investigation or was reported in Rawlins et al.'s  study in 1988. The slow rise in potassium with plain lignocaine has occurred consistently.
The results of this investigation confirm the findings that the amount of adrenaline contained in dental LA solution does affect plasma potassium levels in the early post-injection ,, period and that this effect still occurs in patients where other kalemotropic influences are present. The shifts in potassium recorded were small and unlikely to be a hazard in most individuals, although the patients in this study were young and fit. There are patients, for example, those with severe potassium depletion and those receiving digitalis, in whom even small decreases in potassium may be dangerous. 
In addition, the hypokalemic effect of adrenaline is exacerbated in individuals treated with kaliuretic diuretics, a phenomenon that has been demonstrated in patients undergoing such therapy and receiving adrenaline containing LAs for minor oral surgery. 
It has been claimed that the quantity of adrenaline injected during dental LA is unlikely to have much effect on glucose metabolism. On the other hand, it has been recognized for some time that general anesthesia may be associated with a rise in blood sugar.  Clarke et al.  focused on blood glucose levels in women having minor gynecological procedure under general anesthesia and found that with all agents, the blood sugar rose significantly, with a peak at 15 min. These researchers suggested that it was unlikely that the effect was pharmacological, being more likely due to the stress of surgery. ,
In the present study, there was a change in blood sugar in the early stage of the general anesthesia. The glucose concentration was significantly greater at 10 and 20 min in both treatment groups from the levels recorded immediately before the administration of the LA. , In addition, there were significant differences in the changes in blood glucose levels between treatments at 10 and 20 min following the injection of the LA solution.
Thus, even in the presence of other factors which change blood sugar concentration, there is sufficient adrenaline contained in clinical doses of dental LAs to affect the glucose concentration. Cunningham et al.  observed similar increases in blood glucose 5 min following cervical infiltration of 0.5% lignocaine with 1:200,000 adrenaline, while a control group that received plain lignocaine showed no significant increase.
| Conclusions|| |
It can be concluded that though there were no significant changes in the hemodynamic parameters in both the treatment groups, there were significant changes in the biochemical parameters.
There were significant changes in plasma potassium concentration between treatments immediately and 20 min after the LA injection. Immediately following the injection of the adrenaline containing solution, there was a significant rise in plasma potassium from the baseline concentration. The increase in plasma potassium concentration from baseline with the injection of plain lignocaine was significant at 10 min.
The changes in blood glucose concentration were significantly different between treatments at 10 and 20 min and the glucose levels were significantly greater than the baseline values at 10 and 20 min within each treatment group.
In conclusion, this investigation showed that although no hemodynamic effects were detected following the injection of 20 μg adrenaline contained in dental LAs in stressed patients, there were significant metabolic effects.
The use of adrenaline containing solutions produced higher plasma potassium concentration and higher blood glucose levels than the injection of plain lignocaine. It is obvious that the effects recorded are unlikely to be hazardous in most patients because the use of LAs is such a safe technique.
Nevertheless, the results show that exogenous adrenaline administration in clinical doses produces systemic effects even in conditions where the endogenous release of the catecholamines would be expected to be considerable.
The results suggest that when considering the systemic effects of LA injections, metabolic as well as hemodynamic changes should be investigated, and this study needs to be undertaken with a larger sample.
| References|| |
|1.||Cunningham AJ, Donnelly M, Bourke A, Murphy JF. Cardiovascular and metabolic effects of cervical epinephrine infiltration. Obstet Gynecol 1985;66:93-8. |
|2.||Meechan JG, Rawlins MD. The effects of adrenaline in lignocaine anaesthetic solutions on plasma potassium in healthy volunteers. Eur J Clin Pharmacol 1987;32:81-4. |
|3.||Meechan JG, Rawlins MD. The effects of two different local anaesthetic solutions on plasma potassium levels during third molar surgery. J Am Dent Assoc 1988;302:150-4. |
|4.||D' Silva JL. The action of adrenaline on serum potassium. J physiol 1934;82:393-5. |
|5.||Todd EP, Vick RL. Kalemotropic effect of epinephrine: Analysis with adrenergic agonists and antagonists. Am J Physiol 1971;220:1964-9. |
|6.||Lim M, Linton RA, Band DM. Continuous intravascular monitoring of epinephrine induced changes in plasma potassium. Anesthesiology 1982;57:272-4. |
|7.||Brown MJ, Brown DC, Murphy MB. Hyperkalemia from Beta 2 -receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:1414-9. |
|8.||Struthers AD, Reid JL, White Smith R, Rodger JC. Effect of intravenous adrenaline on electrocardiogram, blood pressure, and serum potassium. Br Heart J 1983;49:90-3. |
|9.||Meechan JG, Rawlins MD. The effect of adrenaline in lignocaine anaesthetic solutions on plasma potassium in patients receiving kaliuretic diuretics. J physiol 1987;209:60-9. |
|10.||Craig AB Jr, Honig CR. Hepatic metabolic and vascular responses to epinephrine: A unifying hypothesis. Am. J. Physiol 1963;205:1132-8. |
|11.||Tolas AG, Pflug AE, Halter JB. Arterial plasma epinephrine concentrations and haemodynamic responses after dental injection of local anaesthetic with epinephrine. J Am Dent Assoc 1982;104:41-3. |
|12.||Brewer G, Larson PS, Schroeder AR. On the effect of epinephrine on blood potassium. J physiol 1939;708-12. |
|13.||Meechan JG, Rawlins MD. A comparison of the effect of two different dental local anaesthetic solutions on plasma potassium concentration. Br Dent J 1987;163:191-3. |
|14.||Kunin AS, Surawicz B, Sims EA. Decrease in serum potassium concentrations and appearance of cardiac arrhythmias during infusion of potassium with glucose in potassium-depleted patients. N Engl J Med 1961;266:228-32. |
|15.||Meechan JG, Rawlins,MD. Kalemotropic effects of local anaesthetics in patients receiving Kaliuretic diuretics. J Dent Res 1990;69:250-3. |
|16.||Clarke RS. The influence of anaesthesia with Thiopentone on blood sugar level. Br J Anaesth 1968;40:46-52. |
|17.||Clarke RSJ, Bali IM, Issac M, Dundee JW, Sheridan B. Plasma cortisol and blood sugar following minor surgery under intravenous anaesthetics. Anaesthesia 1974;29:545-50. |
|18.||Dionne RA, Goldstein DS, Wirdzek PR. Effects of diazepam premedication and epinephrine containing local anaesthetics on cardiovascular and plasma catecholamine responses to oral surgery. Anesth Analg 1984;63:640-2. |
|19.||Knoll-Kohler E, Frie A, Becker J, Ohlendor D. Changes in plasma epinephrine concentrations after dental infiltration anaesthesia with different doses of epinephrine. J Dent Res 1989;68:1098-101. |
|20.||Jastak JT, Yagiela JA. Vasoconstrictors and local anaesthesia - a review and rationale for use. J Am Dent Assoc 1983;107:623-30. |
|21.||Troullos ES, Goldstein DS, Hargreaves KM. Plasma epinephrine levels and cardiovascular response to the high administered doses of epinephrine contained in local anaesthesia. Anesth Prog 1987;34:10-4. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]