Abstract
Aim
Articaine and bupivacaine are both amide-type local anesthetic (LA) agents, of almost equal potency. However, lidocaine is considered the gold standard and is the most widely used anesthetic agent because of its potency, safety, and efficiency. Articaine is fast acting and bupivacaine is a long-lasting LA. The aim of this randomized controlled crossover clinical study was to evaluate and compare the clinical anesthetic efficacy of 4% articaine and 0.5% bupivacaine in orthodontic extractions models.
Methods
Forty systemically healthy patients (age range: 10–18 years), requiring premolar extraction for orthodontic reasons (all 4 premolars) were included. Patients were categorized into two groups (4% articaine and 0.5% bupivacaine) in a crossover manner (160 premolars). Parameters recorded included: time of anesthetic onset, duration of postoperative analgesia, time to first rescue analgesic medication, and visual analog scale (VAS). At the first appointment, both upper and lower premolars were extracted on one side of the jaws (right or left). A fixed volume of 1.4 mL of 4% articaine or 0.5% bupivacaine (based on a computer-generated list) was infiltrated in the buccal vestibule (local infiltration) for extraction. At the second appointment, after a washout period of 15 days, the anesthetic agent that was not administered at the first appointment was administered in a crossover manner. Each patient was evaluated using a 100-mm VAS during and after extraction.
Results
The results showed that 4% articaine had significantly faster onset of action and lower VAS scores when compared with bupivacaine. However, the duration of analgesia and time to first rescue analgesic medication was longer in the bupivacaine group.
Conclusion
Articaine seemed to have better potency and efficacy in terms of onset of action and lower pain scores compared to the bupivacaine group. Further studies are required to confirm these results.
Keywords
bupivacaine; carticaine; pain measurement; visual analog pain scale; tooth extraction;
1. Introduction
Local anesthesia and pain management are the most important tenets in any oral surgical procedure. Patient compliance and effective surgical procedure mandates complete pain control in order to gain patient cooperation and manage patient anxiety. Pain perception depends upon the patient's pain threshold and quality of local anesthetics (LAs) used. LAs are believed to be the most frequently used drugs in clinical dentistry. It has been estimated that >300 million cartridges of LA are administered annually by dentists in the United States.1
LAs are chemicals that block nerve conduction in a specific, temporary, and reversible manner, without affecting the patient's consciousness. The molecule consists of two poles: a hydrophilic tertiary or secondary amino group, and a lipophilic aromatic ring. According to the type of intermediate alkyl linkage between them, they are classified under ester-type anesthetics, with an amino-ester bond and whose prototype is procaine, and the amide-type with an amino-amide bond and whose prototype is lidocaine.2
Various LA agents have been studied and reported in the literature, but, because of the long latency period of procaine and allergies to ester anesthetics, lidocaine after its synthesis in 1943 by Nils Löfgren quickly became the gold standard because of its minimal side effects and effective pain control.3 Articaine and bupivacaine are effective and comparable to lidocaine. Articaine (Fig. 1) is a safe anesthetic with a fast onset and an adequate duration with few side effects4 (Table 1). Bupivacaine (Fig. 2) is often chosen for prolonged postoperative pain control and analgesia in extended operations5, 6 (Table 1). Moreover, some authors have attributed its ability to attain longer postoperative analgesic periods, reducing analgesic requirements in the early postoperative hours when the maximum pain intensity is reached.7, 8 However, it has certain side effects with a low therapeutic index.
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This split-mouth design reduces possible research bias by avoiding physiological and psychological differences between tested individuals.9 For orthodontic extractions, both anesthetics can be compared in the same patient, because most orthodontic extractions are bilateral, in the same anatomical positions. They present almost equal difficulty in removal, thereby requiring the same armamentarium, technique, and duration. This makes the comparison between articaine and bupivacaine in the same patient, in two different appointments justified and unbiased.
Numerous studies have been reported in the literature comparing articaine and lidocaine. However, the dearth of studies comparing articaine and bupivacaine makes this study reasonable. The aim of our study was to assess the clinical efficacy of 4% articaine and 0.5% bupivacaine in an orthodontic extraction model in symmetrically positioned maxillary and mandibular premolars.
2. Materials and methods
This prospective, randomized crossover study was carried out from January 2011 to September 2011. The study population consisted of 40 age- and sex-balanced (age range 10–18 years) systemically healthy individuals, attending the Outpatient Section, Department of Oral and Maxillofacial Surgery, Dr. D.Y. Patil Dental College and Hospital, Pune, India. Written informed consent was obtained from those who agreed to participate voluntarily. Ethical clearances were obtained from the Ethical Committee and Review Boards of the institution. Systemically healthy individuals, without reported allergy to LAs, requiring extraction of their premolars for orthodontic reasons, were included. Study parameters included time of anesthetic onset, duration of postoperative analgesia, time to first rescue analgesic medication, and visual analog scale (VAS) score. All extractions were done at 9:00 am. VAS score was recorded intraoperatively 5 minutes after injection, postoperatively every 2 hours at 11.30 am, 1.30 pm, 3.30 pm, 5.30 pm, 7.30 pm, and 9.30 pm.
A computer-generated list was used to allocate each patient into either 4% articaine or 0.5% bupivacaine groups. At the first appointment, a fixed volume of 1.4 mL 4% articaine or 0.5% bupivacaine was infiltrated in the buccal vestibule of maxillary and mandibular premolars (one side of the face). After attaining adequate anesthesia, the extraction procedure was carried out under aseptic conditions. At the second appointment after a washout period of 15 days, the same procedure was repeated in a crossover manner (Fig. 3) on the other side of the face. The parameters were again recorded in a similar manner.
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A previously calibrated examiner (A.T.) performed all the clinical assessments to ensure adequate intra-examiner reproducibility. The examiner was considered calibrated once a statistically significant correlation and statistically nonsignificant difference between duplicate measurements were obtained (r = 0.87 for time of onset; r = 0.90 for duration of postoperative analgesia, r = 0.93 for time of first rescue analgesic medication, and r = 0.81 for VAS score).
2.1. Statistical analysis
Student's t test was used to compare qualitative means. A p value <0.05 was considered statistically significant.
3. Results
3.1. Time of anesthesia onset
The mean time of anesthesia onset for articaine and bupivacaine was 42.53 ± 16.65 seconds and 61 ± 26.63 seconds, respectively. The study showed that the onset period ranged between 35–50 seconds for articaine and 40–90 seconds for bupivacaine. The time of onset of anesthesia with bupivacaine was significantly longer than that with articaine (Table 2).
3.2. Duration of postoperative analgesia
A mean duration of postoperative analgesia was 129.1 ± 45.65 minutes with articaine and 286.92 ± 93.19 minutes with bupivacaine. Hence, we can infer that bupivacaine provides significantly longer duration of postoperative analgesia when compared with articaine (Table 2).
3.3. Time to first rescue analgesic medication
The rescue analgesic medication used was 500 mg paracetamol. The patients took the analgesic medication upon weaning of the anesthetic action and the appearance of the first symptom of pain in the postoperative period. The time to first rescue analgesic medication was 131.38 ± 43.74 minutes for the articaine group and 288.38 ± 91.25 minutes for the bupivacaine group. The time to first rescue analgesic medication was significantly longer with bupivacaine compared with articaine (Table 2), because of its significantly longer duration of action.
3.4. Comparison of VAS score
We included VAS score evaluation for the efficacy analysis. There was a significant difference in pain scores between the groups. The mean value of VAS score was 1.11 ± 1.23 and 3.5 ± 1.48 in the articaine and bupivacaine groups, respectively, maintaining that the pain scores were significantly higher in the bupivacaine group than the articaine group (Table 2).
4. Discussion
It is essential to standardize the procedure for comparing the efficacy of two anesthetic drugs. In this study, we compared the efficacy of 4% articaine hydrochloride with 0.5% bupivacaine hydrochloride during the extraction of bilateral maxillary and mandibular premolars for orthodontic reasons. The study followed a bilateral crossover design, which has the advantage that each patient acts as his/her own control. Thus, the individual characteristics of each patient and their subjective assessment of pain do not influence the results of the study. To avoid differences between surgeons and their subjective assessment influencing the data collected, the same surgeon performed all the extractions. Time of onset, duration of postoperative analgesia, time to first rescue analgesic medication, and VAS score were the parameters discussed in the study. Time of onset was calculated as the interval between injection and the time when anesthesia was achieved. It represents a key factor when choosing different anesthetic solutions.
Articaine, unlike other amide LAs, undergoes biotransformation in both the liver and plasma and is thus cleared quickly from the body10, 11 (Table 1). The available literature indicates that articaine is equally effective when compared with other LAs.12, 13 Articaine is an amide derivative with a thiophene ring in its molecular structure (Fig. 1, Table 1) instead of the usual benzene ring, making it more lipophilic and thus accounting for its faster diffusion properties within tissues and bones, resulting in profound anesthesia and rapid time of anesthetic onset when compared with bupivacaine. This is the reason we could achieve complete anesthesia even on the palatal side, with infiltration of 4% articaine only on the buccal side. However, to standardize the procedure, we infiltrated the palatal side as well. It was observed that on the side where bupivacaine was injected, palatal infiltration was obligatory in order to perform painless extraction. In comparison with other amide-type LAs, articaine contains a carboxylic ester group. Thus, articaine is inactivated in the liver as well as by hydrolyzation in the tissue and blood (Table 1). Articaine is the only LA agent that is inactivated in both ways. Because the Hydrolyzation is fast and starts immediately after injection, 85–90% of the administered articaine is inactivated in this way. The main metabolic product is articainic acid (or more accurately, articainic carboxylic acid), which is nontoxic and inactive as an LA.13 The onset of anesthesia was assessed by the pin prick test. Upon the onset of anesthesia, there was no sensitivity in the associated mucosa after probing it with a Moon probe. The onset was faster with articaine compared to bupivacaine because of the better diffusion of the anesthetic agent. This was in accordance with the study of Gregorio et al.14
In our study, the volume of LA used was fixed, that is, 1.4 mL. In four extractions, the anesthetic volume exceeded 1.4 mL, because of the pain and discomfort experienced by the patient. All these patients belonged to the bupivacaine anesthetic group. In a study done by Gregorio et al,14 additional anesthesia, which the author called reinforcement anesthesia, was necessary in 14% of surgeries performed with bupivacaine and 2% of those performed with articaine. This difference was significant. The authors concluded that bupivacaine was less effective in infiltrative techniques.
Also, the VAS scores were higher in the bupivacaine group when compared with their articaine counterparts. Therefore, we found that the anesthetic efficacy of articaine was significantly better than that of bupivacaine. This is possibly because of the better diffusion of articaine in the tissues rendering more profound anesthesia.15
The duration of postoperative analgesia was longer in the bupivacaine group when compared with the articaine group.16 This could be because of the higher protein binding of bupivacaine and higher pKa of 8.117 (Table 1). Moreover, the rapid metabolism and Hydrolyzation of articaine makes the duration of postoperative analgesia shorter. The longer duration of the anesthesia could be unpleasant for patients and could cause difficulty eating, speaking, and a greater risk of soft tissue trauma.18, 19
Articaine hydrolyzes rapidly, because it occurs both in plasma and liver. It is rapidly eliminated from the body, but the elimination of bupivacaine takes longer. Hence, the duration of postoperative analgesia offered was significantly longer with bupivacaine than articaine. This finding was in accordance with previous studies.14, 20, 21, 22, 23 Because of the longer duration of postoperative analgesia offered by bupivacaine, the time to rescue analgesic medication was also longer.
The patients in the bupivacaine group complained of constant pressure sensation and discomfort, unlike those in the articaine group. In our study of 40 patients, there were no adverse effects, allergic reactions, or complications observed. Keeping the efficacy in mind, articaine is safer and has similar potency as other groups of LAs.24 Because of better diffusion in tissues, articaine offers more profound analgesia with minimal pain or discomfort when compared with bupivacaine.24 Although articaine provided considerably less postoperative analgesia as compared to bupivacaine, the pain experience and the volume of anesthetic required was also less, making it more useful for short intraoral procedures such as extractions, minor surgical procedures, periodontal surgery, growth excision, and biopsies. Although lidocaine is considered the gold standard LA for most dental procedures, articaine is a good substitute.25 Articaine seems to be superior to bupivacaine in spite of its longer postoperative analgesia. Bupivacaine failed to provide profound anesthesia and the patients experienced pain and discomfort, requiring additional volumes of anesthetic agent when compared with articaine. For the efficacy of local anesthesia, multiple variable factors exist, such as technique variability, anatomical variations, pain threshold, complexity of the procedure, and reporting error.20 There are only a handful of studies in the literature20, 21, 22 assessing the efficacy of articaine and bupivacaine. Existing studies are all of third molar disimpaction, which offers large variation in position, anatomy and morphology, surgical procedure, difficulty in extraction, consistency of bone, and technique variability. This crossover study design for orthodontic extractions took adequate control of these variables.
Further controlled clinical trials, with other anesthetic agents in different areas of the oral cavity in various other procedures are necessary to substantiate the safety of articaine.
In conclusion, 4% articaine had significantly faster onset of action and lower pain scores when compared with those of 0.5% bupivacaine. Moreover, the volume of LA required seemed to be lower in the articaine group, demonstrating better anesthetic potency and efficacy. However, further long-term randomized clinical controlled trials are warranted to substantiate our results.
Acknowledgments
We would like to thank all the study participants, junior residents and Post Graduates, assistants, and Nurses for their contributions to this study. We would like to thank Dr. D.Y. Patil Dental College and Hospital for providing the study material. This was a self-funded study; Ethical Clearance number DPU 2011-12/DYPDCH-0013/11.