Local anesthesia in dentistry provides comfort for the patient, but also as much comfort for the clinician as the planned procedures can be carried out under the best possible conditions. From clinical experience and from the literature, it is clear that dental local anesthesia is not always as successful as anticipated [12345678]. Especially mandibular block anesthesia can be difficult to achieve or challenging in some patients, even in the absence of a tooth with an acute pulpitis. Mandibular block failure rates differ from study to study and teach us that there is no 100% success [1237]. The efficacy of local anesthesia in the maxilla is much higher, based on clinical experience and publications. The main reason is probably the cortical plates of the mandible being thicker and denser and having less porosities that allow for a volume of local anesthetic to be diffused into the cancellous bone in case one attempts a buccal infiltration for instance, explains most of the difference with the maxilla. Another reason is the techniques that are used to achieve local anesthesia. In the maxilla, the most appropriate technique would be a buccal infiltration anesthesia close to the level of the apices of the teeth, while in the mandible, because of the reason mentioned above, local anesthesia is achieved mainly by attempting to deposit a volume of local anesthetic close to the mandibular nerve before it enters the mandible [67910]. Because of anatomical variations in localisation of the second branch of the trigeminal nerve with regard to the ramus of the mandible, the efficacy of local anesthesia is not 100% [1234567891011].

The aim of this current review was to assess the peer-reviewed literature on the topic of dental local anesthetics to see if the efficacy of dental local anesthetics depends on the amide or a combination of amides used.

Fig. 1 shows which search terms were used in the PubMed® database to identify relevant publications, how many publications were found per search term and how publications were finally triaged to be reviewed by both researchers. The inclusion criteria used, were that studies had to be related to human research, performed in the last 10 years, written in English language, and with a focus on dental local anesthetics. After having identified the search terms, the search was conducted between January 2017 and January 2018 by one researcher (NB). As can be derived from Fig. 1, an initial total of 8646 manuscripts were identified. After applying the selection criteria, 79 papers were subsequently read by both researchers, and then categorised in consensus in an Excel spread sheet (Microsoft®, Redmond, Washington, USA) to identify the type of study (e.g. randomised clinical trial), the amides investigated (e.g. articaine), the number of patients included in the study if it was a clinical trial, the country of origin and the year of publication and finally, the conclusion of the study. Both investigators read all 79 publications, and, in consensus, deemed 30 manuscripts eligible for the study's aim.

A total of 30 publications (Fig. 1) were considered relevant for the study: 7 reviews, and 23 clinical trials.

The details of the different studies and their conclusions can be found in Tables 1 and 2. These tables show data regarding the country of origin, the number of subjects involved, which amides were investigated and in the last column the final conclusions as stated in the respective papers. Table 3 tabulates the number of manuscripts that investigated which type of amide and which amide was found to be more or equally in efficacy to achieve local anesthesia. The numbers in the right hand side column refer to the manuscripts reference list.

Of the six amide products used in dental local anesthesia, 13 in vivo studies and 4 reviews found that articaine was the amide with the highest efficacy when compared to either lidocaine, mepivacaine, prilocaine or bupivacaine (see Table 1). Mepivacaine [1213] and bupivacaine [1415] as opposed to lidocaine, appeared to have a higher efficacy in one review [1214] and one in vivo study [1315], each.

Prilocaine, as opposed to lidocaine and bupivacaine, was found to have a higher efficacy in only one in vivo study [16]. Two in vivo studies claimed that ropivacaine had a high efficacy under different concentrations [17], without comparing it to another amide or when comparing it to lignocaine [18].

However, when duration of the local anesthetic effect was taken into account, mepivacaine was shown to work for a shorter duration compared to lidocaine [19].

Eleven studies [2021222324252627282930] either found no significant differences between two types of amides or studied the volume of anesthetic and found its efficacy was significantly greater if higher volumes (more than one cartridge) were administered.

With regard to addition of vasoconstrictors epinephrine and clonidine, one in vivo study concluded that clonidine increased efficacy better than epinephrine, combined with lidocaine [31], while increasing the concentration of epinephrine, with articaine and lidocaine, did not significantly impact the anesthetic efficacy [1415]. Three in vivo studies showed that adding a sodium bicarbonate buffer to lidocaine [3233] and articaine [34], yielded no improvement in efficacy for either. One study [24] investigated the difference between mepivacaine combined with levonordefrin and lidocaine with epinephrine, and concluded that there were no significant differences between them with regard to efficacy.

Other in vivo studies incorporated drugs such as meperidine [3536] and mannitol [37] to lidocaine, and neither appeared to have a significant influence on anesthetic efficacy. Also, liposomal bupivacaine was assessed, but did not improve the efficacy either [38].

The authors noticed that the terms efficiency and efficacy are sometimes incorrectly interchanged. Efficacy is the correct term to be used when assessing the outcome of a product, for instance, or the ability to produce a desired result (e.g. 100% pulpal anesthesia), while efficiency is to be used to assess a process (e.g. how successful is mandibular block anesthesia?) or the state or the quality of being efficient. The mix up is understandable if English is not the native language of the authors, but it should be avoided at all times as it makes the search for papers for a review more complicated.

Based on this review, which covers the past 10 years, the findings suggest that articaine has been researched the most and that it also has the highest efficacy of the amides used in dental local anesthesia. The fact that articaine received so much attention is probably attributable to the fact that before the year 2000, articaine was not available in the USA, whereas in Europe it was already marketed in 1976. As can be derived from tables 1 and 2, 20 of the 31 papers included in our study were conducted in the USA. Although, it was not within the scope of this review paper, nevertheless, the authors are aware of the dubious reputation of articaine with regard to post-operative paresthesia and the discussion about it being manufactured as a 4% solution instead of 2% like lidocaine for dental local anesthesia [163940]. It deserves to be emphasized, however, that in vitro laboratory studies on cell lines have shown that articaine is not the most neurotoxic amide used in dental local anesthesia. One in vitro study, conducted by Mallet et al., tested the toxicity of 6 local anesthetic products on human neuroblastoma cells and found that articaine is the least toxic amide [40], while another in vitro study, by Perez-Castro et al., conducted on a neuronal cell-line, concluded that bupivacaine is the most toxic amide [41]. These findings are in contrast to the reported potential adverse effects, published in two review articles, stating that articaine is harmful in high concentrations, such as 4% [39], and may cause paresthesia [40]. It has to be emphasized that in the latter review, it was found that also prilocaine can potentially cause paresthesia [40]. It is noteworthy that the clinical reports about paresthesia and apparent toxicity almost always involve mandibular block anesthesia. However, it seems strange to us that articaine, for instance, would have a high neurotoxic preference for the second branch of the trigeminal nerve only. Since that was not the aim of the present study, this issue will not be discussed further here, but it definitely deserves further in depth attention.

It is our impression that, after having read the papers regarding efficacy of dental local anesthetics, none of the amides studied and used in dentistry guarantee a 100% success, especially not in the mandible. Therefore, one could conclude that perhaps the technique of administration is inefficient and therefore the efficacy is poor. Intraosseous anesthesia could be the key to increase the efficacy of local anesthetics in the mandible.

From the consulted literature, it is clear that local anesthetics used in dentistry do not show a 100% efficacy, especially not if administered in the mandible or in cases of inflammation (acute irreversible pulpitis). The authors suggest that this opens perspectives to explore more successful ways of administering local anesthesia, in order for the local anesthetic to be more efficacious.