Braz Dent J (1997) 8(2): 85-90 ISSN 0103-6440
| Introduction | Material and Methods | Results and Discussion | Conclusions | References |
We studied possible cardiovascular effects (systolic, diastolic, mean arterial blood pressures, and heart rate) caused by intraoral infiltrative administration of 2% mepivacaine HCl with 1:20,000 levonordefrin in dogs (Canis familiaris), using a Beckman® electrophysiograph. Doses used were 0.514 and 1.542 mg/kg body weight corresponding to one and three 1.8-ml cartridges, respectively, in 70-kg average weight adult men. A statistically significant increase was observed in the systolic and the mean arterial blood pressures.
Key Words: local anesthetics, mepivacaine, levonordefrin, cardiovascular effects.
Mepivacaine belongs to the amide group. It is an odorless crystalline white powder, with a sour taste. It is water-soluble and very stable in solution, resisting acid and alkaline hydrolysis. These chemical characteristics prevent its decomposition during repeated boiling and sterilization. It is difficult to be destroyed by organic esterases and elimination occurs without any structural alteration, due to the molecular chemical stability of the liposoluble and hydrosoluble fraction combination through an amide group (Fiorini, 1961; Rabino and Borio, 1966).
Mepivacaine HCl anesthetic action time without vasoconstrictors is slightly longer than that of lidocaine HCl and procaine HCl, becoming considerably longer with the addition of vasoconstrictor substances (Morelos, 1961). Local infiltration showed excellent tissue compatibility; local reactions began to manifest when an 8% solution was injected which is four times more concentrated than that used in common dental practice (Fiorini, 1961; Rabino and Borio, 1966).
In a comparative study of serum levels in circulating venous blood, 2% mepivacaine HCl without vasoconstrictors reached a peak 30 minutes after intraoral infiltration, in significantly higher concentrations than lidocaine HCl, which reached a maximum peak after 15 minutes (Goebel et al., 1980).
Signs of toxicity in conscious adult patients with 3% mepivacaine HCl without vasoconstrictors were observed when 5 µg/ml venous blood levels were reached (Goebel et al., 1978).
In a study with rabbits, mepivacaine HCl administered intravenously at a 2 mg/kg body weight dosage did not cause either arterial blood pressure or respiratory cycle alterations. However, too high doses may cause a rapid decrease in arterial blood pressure (Brandimarte, 1966).
Fiorini (1961) studied 53 patients undergoing several surgical procedures. Two percent mepivacaine HCl with 1:20,000 levonordefrin was the anesthetic used, with dosages ranging from 1/2 to 3 cartridges. This was well tolerated and did not present any serious side effects, even for patients with cardiovascular disease, diabetes, and arrhythmias. There were no alterations in heart or respiratory rates, and no arterial blood pressure variations.
The addition of vasoconstrictors, besides prolonging the anesthetic action time, also reduces its systemic toxicity by delaying absorption, keeping the anesthetic in contact with the nerve fiber for a longer period of time. Consequently, smaller amounts are necessary for an effective nerve block (Simone et al., 1988; Yagela, 1989; Mackenzie and Young, 1993; Anderson and Reagen, 1993; Brown, 1994). Levonordefrin has a pharmacological effect which is similar to that of epinephrine, showing greater stability, although with less potency when in equivalent concentrations (half the epinephrine potency), with fewer cardiac effects (Ciancio and Bourgault, 1984).
The clinical significance of cardiovascular and hemodynamic changes caused by the release of endogenous catecholamines and administration of exogenous sympathomimetics with local anesthetic agents has long been a controversial subject in dentistry and medicine and remains a subject of continuing study (Campbell and Langston, 1995).
Each animal was then intubated, the left femoral artery was dissected, and a polyethylene cannula was inserted through which we established the connection between the animal and the Beckman® Electrophysiograph (Dynograph, Typerm, Beckman Instruments, USA) to record pressure levels
During these experiments, electrocardiograms (ECG), heart rates and systolic, diastolic and mean arterial blood pressures were recorded.
After the animal was prepared, the electrophysiograph recorded the above-mentioned parameters for 30 minutes to observe the experiment’s stability. A local anesthetic was then applied, and the animals were separated in two groups. Group A: Animals received 2% mepivacaine HCl with 1:20,000 levonordefrin (Carbocain®) in doses corresponding to 0.514 mg/kg body weight (1 cartridge). Group B: Animals received 2% mepivacaine HCl with 1:20,000 levonordefrin (Carbocain®) in doses corresponding to 1.542 mg/kg body weight (3 cartridges).
Administration of local anesthetics was done via intraoral infiltration for 10-20 seconds, using common Luer type syringes, after aspiration to ascertain that the drug was not being injected intravascularly. The experiment was followed up for the next 30 minutes.
The values for heart rate, systolic, diastolic and mean arterial blood pressures recorded before administration of the local anesthetic were considered as control to be 100%. We then calculated changes which occurred in these parameters during the 1st, 2nd, 3rd, 4th, 5th, 10th, 15th, 20th, 25th, and 30th minutes after the beginning of anesthetic administration. These alterations were expressed as percent variations (Table 1). Analysis of variance (2 x 10 factorial model) was used for statistical analysis.
We also observed that diastolic arterial blood pressure was altered, with a tendency towards a continuous increase at doses and time intervals studied (Figure 2). However, these variations were not statistically significant, which seems to preclude an increase in peripheral resistance, making it, therefore, clinically not significant.
Since the mean arterial blood pressure is a consequence of systolic and diastolic blood pressures, we noted an increase (Figure 3), with the difference between average variations, when one or three anesthetic cartridges were applied, being statistically significant.
For the doses used (0.514 mg/kg body weight and 1.542 mg/kg body weight), a slight drop in the heart rate occurred (Figure 4), tending to stabilize and normalize during the time intervals studied for the 1.542 mg/kg body weight dose. A possibility that the heart rate drop might be caused by a vagal reflex may be discarded, since the pressure response was not that intense as to justify this kind of compensatory mechanism.
Conclusions
Considering our experimental conditions, and taking into account the results obtained, we conclude that, even though we observed a statistically significant systolic pressure increase and mean arterial blood pressure increase when the dose was increased from one cartridge to three cartridges, this fact does not pose a significant clinical meaning, as long as patients present arterial blood pressure levels within normal parameters. Heart rate and diastolic arterial blood pressure did not show statistically significant alterations due to variation in the dose.
Brandimarte F: Contributo clinico-statistico sull’uso della Mepivacaine (Carbocaina) nella pratica stomatologica. Minerva Stomat 15: 461-464, 1966
Brown RS: Local anesthetics. Dent Clin North Am 38: 619-632, 1994
Campbell RL, Langston W G: A comparison of cardiac rate-pressure product
and pressure-rate quotient in healthy and medically compromised patients.
Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 80: 145-152, 1995
Ciancio SG, Bourgault PC: Clinical pharmacology for dental professionals. 2nd ed. Littleton, p.112-125, PSG/1984
Fiorini JM: Carbocain: un nuevo agente anestesico local par uso odontologico. Odont Amer 4: 36-41, 1961
Goebel WM, Allen G, Randall F: Circulating serum levels of Mepicaine after dental injection. Anesth Prog 25: 52-56, 1978
Goebel WM, Allen G, Randall F: Comparative circulatory serum levels of 2 per cent Mepivacaine and 2 per cent Lignocaine. Br Dent J 148: 261-264, 1980
Mackenzie TA, Young ER: Local anesthetic update. Anesth Prog 40: 29-34, 1993
Morelos AG: Un nuevo anestesico dental: carbocaina. Rev Cent Med Torreon 7: 1-16, 1961
Rabino G, Borio PS: Un nuovo anestesico locale: Carbocaina. Minerva Stomat 15: 451-458, 1966
Simone JL, Soares MS, Rocha RG, Oliveira MAM, Tortamano N: Anestésicos locais em Odontologia. Odont Mod 15: 7-15, 1988
Yagiela JA: Local anesthetics. In: Pharmacology and therapeutics for dentistry. Neidle EA, Yagiela JA. eds. 3rd ed. Mosby, St. Louis, 230-248, 1989
Yagiela JA: Local anesthetics. Anesth Prog 34: 128-141, 1991
Correspondence: Dr. José Leonardo Simone, Departamento de Stomatologia, Faculdade de Odontologia, Universidade de São Paulo, São Paulo, SP, Brasil.
Accepted April 22, 1997
Electronic publication: March, 1998
