Comparison of Efficacy of 0.5% Ropivacaine Versus 2% Lignocaine Hydrochloride with Adrenaline (1:80,000) in Surgical Removal of Impacted Mandibular Third Molars with Emphasis on Depth of Anesthesia- Prospective, Randomized, Split Mouth Study

Abstract

Introduction

A good anesthetic and analgesic effect is crucial for any minor surgical treatment to be successful. 2% Lignocaine hydrochloride with Adrenaline (1:80,000) is the most commonly used local anesthetic. However, it is not recommended for long procedures or in patients with cardiovascular diseases, where adrenaline is not desirable. Hence, need arises for a local anesthetic which has longer duration of action and adequate analgesic effect with minimal adverse reaction. 0.5% Ropivacaine is a long-acting amide local anesthetic with vasoconstrictive properties. It is considered to have superior properties compared to lignocaine in terms of duration of action and need for analgesics. This study compared the efficacy of 0.5% Ropivacaine versus 2% Lignocaine Hydrochloride with Adrenaline (1:80,000) in the surgical removal of impacted mandibular third molars.

Materials and Method

A prospective, randomized, split mouth, cross over study was conducted amount 33 patients indicated for surgical extraction of impacted mandibular third molar. Extraction of one side was done using 2% Lignocaine with Adrenaline (1:80,000) and the opposite side was extracted one week later using 0.5% Ropivacaine. Parameters assessed were, pain on injection, time of onset of the local anesthetic, the depth and duration of anesthesia, intensity of pain and need for analgesics postoperatively.

Results

There was no statistically significant difference between the two groups in terms of pain on injection. Time of onset was noted to be faster in the Lignocaine group. Ropivacaine was found to be superior to Lignocaine in terms of depth and duration of anesthesia and the postoperative analgesic effect. No adverse effect were noted in either of the two study groups.

Conclusion

0.5% Ropivacaine can be a suitable alternative to 2% Lignocaine in minor surgical procedures of long duration and in conditions, where the use of vasoconstrictor is contraindicated. It also provides an added benefit of greater depth of penetration into the bone along with a postoperative analgesic effect, thereby increasing the patient comfort. However, further study on a larger sample size is necessary to determine the overall effectiveness and practicality of using Ropivacine as an alternative to lignocaine in minor oral surgical procedures.

Introduction

Impacted third molars are commonly encountered in routine dental practice. Impacted teeth may remain asymptomatic or may be associated with various pathologies such as caries, pericoronitis, cysts, tumors, and also root resorption of the adjacent tooth may be seen. Hence, extraction of the third molars become inevitable and is a very common surgical procedure performed under local anesthesia. [1]

The management of a patient’s postoperative pain after surgical removal of impacted wisdom teeth under local anesthesia is one of the essential factors in the management of patients with impacted teeth apart from intraoperative anesthesia [2]. In third molar surgery, the pain level is sensitive to several factors such as tooth position, patients’ age, surgeons’ clinical competence, and postoperative care. Besides the factors aforementioned, the most important factor in determining the level of intraoperative pain is the anesthetic agent used. [3]

Lignocaine, also known as lidocaine, is the recommended local anesthetic agent for oral procedures. Lignocaine solution has intrinsic vasodilative properties in commercially available concentrations, as a result, a vasoconstrictor is added (usually epinephrine) to counteract the potential vasodilating effects of the local anesthetics, enhance the quality and duration of local anesthesia, assist in hemostasis, and may increase the safety of the local anesthetic [4]. Its quick onset (2–4 min) and a moderate level of soft tissue anesthesia potentiate it as a successful working local anesthetic [5]. However, in conditions such as hyperthyroidism and cardiovascular diseases, local anesthetic containing Adrenaline is not recommended. Moreover, the addition of a vasoconstrictor decreases the pH of the solution, making the local anesthetic injections unpleasant for patients. [6]

One of the most important properties of a long-acting local anesthetic is to reversibly inhibit the nerve impulses, thus causing a prolonged sensory or motor blockade appropriate for anesthesia in different types of surgeries. [7] Ropivacaine is a long-acting regional anesthetic that is structurally related to Bupivacaine. Onset of action of Ropivacaine is approximately between 3–10 min. Median duration of action ranged from 3.7 h (medial brachial cutaneous nerve) to 8.7 h.Ropivacaine can be administered at various concentrations, including 0.5%, 0.75%, and 1%. Thus, Ropivacaine has a greater degree of sensory motor differentiation, which could be useful when the motor blockade is undesirable. The reduced lipophilicity is also associated with decreased potential for central nervous system toxicity and cardiotoxicity. [8]

Despite the better safety profiles, the increased cost of Ropivacaine had limited its use as a local anesthetic of choice for most surgical procedures. However, the cost has been significantly reduced in the past few years. Thus pharmacoeconomic speculations have become a much lesser concern, and there are increased chances that Ropivacaine will be more widely used in the future. [9]

Due to the previously mentioned drawbacks of lignocaine, the need arises for a local anesthetic which has longer duration of action and adequate analgesic effect with minimal adverse reaction. Hence, this study compared the efficacy of 0.5% Ropivacaine versus 2% Lignocaine Hydrochloride with Adrenaline (1:80,000) in patients undergoing surgical removal of bilateral impacted mandibular third molars to determine if Ropivacaine is a suitable alternative to Lignocaine in performing.

Materials and Method

This was a prospective, randomized, split mouth, double blinded study carried out for a period of two years (May 2022- May 2024). The study was conducted at Vydehi Institute of Dental Sciences & Research Center, Bangalore. Patients visiting Department of Oral and Maxillofacial Surgery indicated for bilateral mandibular third molar extraction were chosen for the study.

33 patients underwent surgical extraction of bilateral mandibular third molar, with similar difficulty index using, 0.5% Ropivacaine on one side and 2% Lignocaine with Adrenaline (1:80,000) on the contralateral side. There was an interval of one week between the two extractions. Informed consent was obtained from all individual participants included in the study. The choice of local anesthetic for the first side was randomized using coin flip, and the other local anesthetic was given for the second side. The procedure was performed by the same operator for all the subjects.

All patients above 20 years of age (ASA type I and II), who were symptomatic and indicated for surgical extraction of bilateral mandibular impacted third molars with similar difficulty index were included in the study. Prophylactic extraction of teeth which are asymptomatic as well as teeth with any periapical pathologies were not included in the study. Patients with systemic diseases that contraindicates injection of Lignocaine with Adrenaline or Ropivacaine and patients who were allergic to the local anesthetic, patients with hypersensitivity or contraindications to diclofenac, paracetamol, or any medication given post-surgery, were excluded from the study. Patients, where additional dose of local anesthetic solution was administered during the procedure and patients who were not willing to comply with the study were also excluded.

Intraoperatively, parameters assessed included pain on injection, time of onset of anesthesia, i.e. from the time of injection of local anesthesia till the appearance of tingling sensation and numbness on the ipsilateral side of the tongue and lower lip (subjective symptoms) and the onset of soft tissue anesthesia was recorded. Depth of anesthesia was then recorded by noting the pain scores (10 point Visual Analogue Scale (VAS score) given by the subject during soft tissue incision, flap elevation, bone removal and suturing. A score of zero indicated no pain, while a score of 10 indicates the worst imaginable pain. Mild pain, moderate pain, and severe pain were defined as VAS scores of 1–3, 4–7, and 8–10, respectively. Blood loss was estimated by gravimetric method. Both the patient and the operator were unaware of the local anesthetic being used.

Following the procedure, patients were given a proforma to be filled and returned on the third postoperative day. Duration of anesthesia, Intensity of pain at 4, 6, 8, 12, 24 and 48 h, need for analgesics i.e. the total number of analgesics taken (Tab. Diclofenac 50 mg in combination with Paracetamol 325 mg was given to all the patients to be taken as required) and presence of any adverse effects were noted down by the patient. All the pain scores were recorded using the ten point VAS score. All patients were followed up until postoperative day 7.

Statistical Analysis

Data will be entered in M.S Excel and analyzed using SPSS 19 software. For continuous data, testing of normality is very important, because based on the normality status, measures of central tendency, dispersion, and selection of parametric/ nonparametric test are decided. The Shapiro Wilk test and Mann–Whitney U test was used to evaluate the difference between the two study groups in terms of pain on injection, time of onset and duration of anesthesia and need for analgesics postoperatively.

The Friedman test is a nonparametric statistical test used to detect differences among repeated measures or related samples. If the Friedman test reveals significant differences, posthoc tests (e.g., the Nemenyi test or Dunn's test) were conducted to identify which specific groups differ from each other. This test was used to compare the depth of anesthesia and intensity of pain postoperatively between the 0.5% Ropivacaine and 2% Lignocaine groups. A p value less than 0.05% indicated a statistically significant difference between the two study groups.

Results

This study included 33 patients, of which 18 were males and 15 were females. The average age of the study participants were between 22–45 years (mean age: 32 years). The mean values of the various study variables in both the groups have been shown in Table 1.

Table 1.

Descriptive statistics

			2% Lignocaine			0.5%Ropivaccaine
			Mean	SD	Mean + SD	Mean	SD	Mean + SD
Time of onset of anesthesia (mins)			0.90	0.49	0.89 + 0.49	2.49	0.85	2.48 + 0.85
Intraoperative pain score	Incision		0.45	0.90	0.45 + 0.90	0.27	0.57	0.27 + 0.57
	Flap elevation		0.73	1.53	0.72 + 1.52	0.42	0.94	0.42 + 0.93
	Bone removal		3.61	2.24	3.60 + 2.23	1.45	1.35	1.45 + 1.34
	Suturing		0.67	1.22	0.66 + 1.21	0.52	1.03	0.51 + 1.03
Post-oprative values	Duration of anesthesia(hrs)		1.67	1.05	1.66 + 1.05	3.08	1.14	3.07 + 1.13
	Intensity of pain	4 h	4.56	2.50	4.56 + 2.50	2.36	2.53	2.36 + 2.53
		6 h	4.61	2.15	4.60 + 2.14	2.21	2.38	2.21 + 2.38
		8 h	4.52	2.25	4.51 + 2.25	2.41	2.05	2.40 + 2.04
		12 h	3.52	2.53	3.51 + 2.52	2.15	2.08	2.15 + 2.07
		24 h	2.58	2.57	2.57 + 2.57	1.58	1.80	1.57 + 1.80
		48 h	2.18	2.54	2.18 + 2.54	0.76	1.35	0.75 + 1.34
	Total doses of analgesics taken		5.67	0.69	5.66 + 0.69	4.09	1.55	4.09 + 1.54

The pain on injection scores showed no significant difference between the two groups. The mean time of onset of anesthesia in the 0.5% Ropivacaine group was 2.48 ± 0.85 min when compared to the 2% Lignocaine with Adrenaline group which was 0.89 ± 0.49 min which was found to be statistically significant. (Fig. 1).

Fig. 1.

Comparison between the two groups based on time of onset of anesthesia

The intraoperative pain scores (VAS score) during incision, flap elevation, bone removal and suturing were 0.45 ± 0.90, 0.72 ± 1.52, 3.60 ± 2.23 and 0.66 ± 1.21, respectively in the 2% Lignocaine with Adrenaline group. The intraoperative pain scores in the Ropivacaine group on the other hand were 0.27 ± 0.57, 0.42 ± 0.93, 1.45 ± 1.34 and 0.51 ± 1.03, respectively (Figs. 2 and 3). The intraoperative pain scores were noted to be lesser in the 0.5% Ropivacaine group when compared to the 2% Lignocaine group, which was statistically found to be highly significant. The lower pain score during bone removal indicated that the 0.5% Ropivacaine group had considerably deeper penetration into the bone than the Lignocaine group. There was no significant difference in the amount of blood loss in both the groups suggesting that 0.5% Ropivacaine without adrenaline has efficiency equivalent to that of 2% Lignocaine with 1:80,000 Adrenaline due to the inbuilt vasoconstrictive effect of Ropivacaine.

Fig. 2.

The column chart in the context of the Friedman test for depth of anesthesia. The higher the column, the higher the average rank. Conditions with higher average ranks are considered to have higher central tendencies or, in the context of pain measurements, may suggest higher levels of pain

Fig. 3.

The heatmap is used to visualize the results of the post-hoc test for depth of anesthesia. Each cell in the heatmap is filled with a color representing the adjusted p-value from the post-hoc test. The color intensity or shade usually reflects the level of significance. For example, darker colors may represent smaller p-values, indicating greater significance

The mean duration of anesthesia was higher in the 0.5% Ropivacaine group (3.07 ± 1.13 h) when compared to the Lignocaine group (1.66 ± 1.05 h). (Fig. 4). A significant decrease was noted in the postoperative pain score (VAS score) at 4, 6, 8, 12, 24 and 48 h in the 0.5% Ropivacaine group when compared to the 2% Lignocaine group. Thus Ropivacaine is found to have a longer duration of anesthesia and longer postoperative analgesic effect when compared to the Lignocaine group. The patients in the 2% Lignocaine group comparatively required prolonged dosage of analgesics postoperatively (5.66 ± 0.69) when compared to the 0.5% Ropivacaine group (4.09 ± 1.54). (Figs. 5 and 6).

Fig. 4.

Comparison between the two groups based on duration of anesthesia

Fig. 5.

The column chart in the context of the Friedman test for intensity of pain postoperatively. The higher the column, the higher the average rank suggesting higher levels of pain

Fig. 6.

The heatmap is used to visualize the results of the post-hoc test for intensity of pain postoperatively. Each cell in the heatmap is filled with a color representing the adjusted p-value from the post-hoc test. The color intensity or shade usually reflects the level of significance

There was no statistically significant difference in the intraoperative and postoperative pain scores in terms of gender in both the study groups. Also, none of the patients reported any side effects in both Ropivacaine and Lignocaine group during the study. This shows that both Lignocaine and Ropivacaine have similar safety profile in optimal concentrations.

Discussion

One of the most frequent procedures in Oral and Maxillofacial surgery is the extraction of impacted third molars. Most patients’ primary concern is pain during dental extraction. Pain control is an essential part of dental extraction, and the most common method of pain control is local anesthesia [10]. Surgical extraction of third molars often involves soft tissue flaps and removal of bone tissue. Thus, the postoperative inflammation is often accompanied by severe pain, edema, and limited mouth opening. Hence, these are some of the challenges faced by Oral and Maxillofacial surgeon and especially pain management plays a vital role. [11]

Although Lignocaine with Adrenaline is commonly employed for minor surgical procedures as the local anesthetic of choice, its use is limited in case of patients with underlying cardiovascular diseases or conditions which contraindicate the use of vasoconstrictor rendering it less effective in achieving the desirable effect. Moreover, its intermediate duration of action makes it essential to give multiple injections in procedures of longer duration increasing the patient and operator discomfort. To avoid this, long-acting local anesthetics have been introduced.

Ropivacaine is a long-acting regional anesthetic. It is less lipophilic and therefore is associated with decreased potential for central nervous system toxicity and cardiotoxicity. Thus, Ropivacaine, with its efficacy, lower propensity for motor block, intrinsic vasoconstrictive property and reduced potential for CNS toxicity and cardiotoxicity, making it an ideal option for regional anesthesia and management of postoperative pain. [7]

The time of onset of anesthesia was calculated from the time of injection of local anesthesia till the appearance of tingling sensation and numbness on the ipsilateral side of the tongue and lower lip (subjective symptoms) and the absence of pain on probing the mucosa. In the current study, the time of onset of anesthesia was 2.48 ± 0.85 min on injection of 0.5% Ropivacaine when compared to the 0.89 ± 0.49 min noted in the 2% Lignocaine with Adrenaline group. The reason for longer onset of soft and hard tissue anesthesia with Ropivacaine is due to its poor diffusion through the soft tissue and bone as compared to Lignocaine.

The period from the start of the numbness and tingling following the injection until the return of sensation in the area was used to determine the duration of the anesthesia. The duration of action of Ropivacaine was found to be longer than that of Lignocaine by roughly 1.41 ± 0. 08 h. Ropivacaine also showed superior results in terms of depth of anesthesia and postoperative analgesic effect.

Similar results were obtained in the study conducted by Ram Goyal et.al. on comparing the effectiveness of 0.5% Ropivacaine to 2% Lignocaine with 1:80,000 Adrenaline. The time of onset of Ropivacaine was found to be longer by about 49 s, and the difference was found to be significant. Results also showed that 0.5% Ropivacaine had higher depth of anesthesia, longer duration of action and postoperative analgesic effect than 2% Lignocaine hydrochloride with 1:80,000 Adrenaline with no adverse effects. [12]

Buffering lidocaine with sodium bicarbonate is the commonest method of reducing injection pain. Lidocaine with Adrenaline (epinephrine) has an even lower pH than pure lidocaine. However, the pH of Ropivacaine was found to be less acidic (pH = 7.4) in comparison to Lignocaine without the addition of buffering agent [13]. The verbal rating scale was used to evaluate subjectively the intensity of pain on injection. However, in the current study pain on injection did not show any significant difference between the two groups.

The effectiveness of the two anesthetics was compared based on intraoperative pain and discomfort and the depth of anesthesia. Results from this study showed greater depth of penetration of Ropivacaine when compared to Lignocaine. The pain scores were significantly lower during bone removal in the Ropivacaine group suggesting greater depth of penetration into the hard tissue. The reason why Ropivacaine is more potent than other drugs is because it has a higher dissociation constant (pKa—8.1) and is more lipid soluble. These factors prevent more free base molecules from diffusely passing through the neuronal membrane. [14]

A similar study was conducted by Radha Saodekar for comparative analysis of Lignocaine, Ropivacaine, and Bupivacaine in pain control during extraction of mandibular posterior teeth. Subject response for pain was recorded using the – (a) Visual Analog Scale (VAS) and (b) Verbal Rating scale (VRS). 0.75% Ropivacaine demonstrated better local anesthetic properties when compared with 2% Lignocaine and Bupivacaine. [15]

Studies done by E. Bailey et.al have suggested that maximal pain is felt during the first 3 to 5 h postoperatively after surgical removal of impacted third molars [16]. Our study shows similar results in the Lignocaine group with maximal pain noted in the first 2 to 4 h postoperatively. In contrast, the Ropivacaine group showed maximal pain intensity after 6 to 8 h postoperatively which was statistically significant. The need for rescue medication was noted after 4–6 h in the Ropivacaine group when compared to 2–3 h in the Lignocaine group. The total doses of analgesics taken postoperatively was noted to be four doses in the Ropivacaine group when compared to six doses noted in the Lignocaine group. Similarly, studies done by Ahmed Al-Kahtani [17], Klinger De Souza et.al [18] etc. also showed superior effects of Ropivacaine when compared to Lignocaine in the management of the postoperative pain. These results coincided with our findings which further establishes the benefit of Ropivacaine as an anesthetic of choice with better pain control in postoperative period and also reduced the need for rescue analgesics postoperatively.

When Ropivacaine is used as a local anesthetic, postoperative pain peaks between 6 and 12 h following the treatment. During this period, the effects of the anesthetic may still be noted in some patients. This may be a reason for the lower use of analgesics among some patients in the Ropivacaine group who did not take analgesic tablets during the first 12 h, unlike the Lignocaine group, in which all of the patients took analgesic tablets. [18]

Studies have also demonstrated the anti- inflammatory activity of Ropivacaine. Ropivacaine reduces leukocyte migration and the release of lipoxygenase products, which are important components of the inflammatory response. However, these effects were not found for Lignocaine. [19] The use of dexamethasone to modulate inflammatory effects during the postoperative period does not affect the study outcomes, because it was uniformly applied to both study groups.

Conclusion

From the findings of our investigation, the following conclusions can be made. Ropivacaine at 0.5% concentration demonstrated satisfactory results in terms of intensity of local anesthesia. In comparison to Lignocaine 2% with 1:80,000 Adrenaline, the duration of anesthesia is noticeably longer 0.5% Ropivacaine. 0.5% Ropivacaine is found to be superior to 2% Lignocaine with Adrenaline in terms of reduction of intraoperative and postoperative analgesia. Thus, 0.5% Ropivacaine is a suitable option as a local anesthetic of choice in minor oral surgical procedures such as impactions especially in cases with longer duration of surgery and need for effective pain control is of utmost importance. It provides prolonged duration of anesthesia without the need for an added vasoconstrictor which is an advantage over the use of Lignocaine. It also has the added benefit of minimal CVS effects and hence can be used in patients with underlying cardiac conditions.

Thus, in Oral and Maxillofacial Surgery, 0.5% Ropivacaine can be regarded as a safe, effective, clinically acceptable, and just as potent local anesthetic agent as 2% Lignocaine with 1:80,000 Adrenaline.

Study limitations

Further studies in a larger population may be needed to better determine the efficacy and practicality of using Ropivacaine as an alternative to Lignocaine in minor oral procedures. Additional evaluation of the efficacy of Ropivacaine in patients with systemic conditions which contraindicate the use of a vasoconstrictor should be carried out. Also, comparison needs to be made on the benefit of using Ropivacaine over the other long-acting local anesthetics.

Declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in study were in accordance with the ethical standards of the institutional research committee.

Informed Consent

Informed consent was obtained from all individual participants included in the study.