Pain during dental caries treatment is a major problem in dentistry [1]. Traditional caries removal methods using a rotating device cause heat, pressure, and vibration to the dental pulp, eliciting discomfort and pain to the patient and requiring local anesthesia. Moore et al. [2] reported severe dental phobia in about 10% of the adult population, especially for drilling. A related study among Korean children and adolescents found the main causes of phobia to be pain, local anesthesia, and noise from rotating instruments during dental treatment. Such phobia was responsible for the avoidance of dental visits [3]. In addition, the drilling method has a disadvantage in the large amount of tooth removal due to elimination of the sound dentin [45].

Therefore, alternative methods of conventional caries therapy were introduced for the purpose of minimal invasion without causing pain. These include sonoabrasion, air abrasion, ultrasonics, chemo-mechanical systems, and lasers [6]. Among these, the Chemomechanical system is reported to be the most effective alternative to the conventional dental removal method [789].

Chemo-mechanical caries removal (CMCR) is a method of softening carious dentin by using a chemical agent that selectively removes infected dentin while allowing for remineralization. Unlike the traditional rotary method, CMCR does not cause heat, pressure, and vibration. Consequently, there is no pain and local anesthesia is not required. Therefore, it is effective for children and adolescents, especially those with dental phobia [1011]. Some CMCR agents that are currently commercialized include Carisolv™ (Medi Team Dental AB, Savedalen, Sweden), Papacarie® (Formula e Acao, Sao Paulo, Sao Paulo, Brazil), and Carie-care™ (Uni Biotech, Pharmaceuticals Pvt., India) [1213].

In the meantime, systematic reviews and meta-analyses of the efficacy of Carisolv™ and Papacarie® have been done [71213141516]. However, these have not been done on the efficacy of Carie-care™. It is therefore, necessary to conduct these reviews and meta-analyses in order to assess the efficacy of Carie-care™ for caries removal in children and adolescents. The aim of this study was to investigate if the application of Carie-care™ can affect the outcomes of dental caries in children and adolescents. The primary outcome is pain, while the secondary outcomes include complete caries removal (CCR), time, local anesthetic need, and behavioral response changes.

This study was performed with reference to the PRISMA guidelines for systematic reviews. PICO was used to formulate the research question as follows: “Is Carie-care™, a CMCR agent, effective in reducing pain when compared to conventional drilling methods for dental caries in children and adolescents?”

A Comprehensive literature search was performed in PubMed, EMBASE, and the Cochrane Library up to 30 September 2018. The following keywords were used in the literature search: ‘chemo-mechanical caries removal agent’, ‘dental caries’, ‘Carie-care’, ‘chemo-mechanical caries removal’, ‘chemo-mechanical caries excavation’, other related keywords, and their combinations. The search was limited to publications in English. Duplicate articles were excluded from the search process along with articles not meeting the purpose of this study, using title and abstract screening. We also conducted a handwriting search on Google scholar. Afterwards, two reviewers examined the full text according to the inclusion and exclusion criteria of this study and evaluated and selected the appropriate papers.

The literature search and selection process is displayed in Fig. 1. Finally, 4 studies met the inclusion criteria of this review and included 260 teeth in 120 children and adolescents (Table 1). The summary of the features of included studies is shown in Table 2.

The CMCR method is appropriate for younger patients, especially those with dental phobia, because it preserves maximal tooth structure, is less irritating to the dental pulp and reduces patient discomfort [1718]. Carisolv™ was first introduced in 1998 as a gel-type CMCR agent with sodium hypochlorite as the active ingredient and containing 3 amino acids [19]. It had some disadvantages which included that it had to be applied with specially designed instruments, was expensive, and children disliked the taste and smell of chlorine [20]. In 2003, Papacarie® was introduced and its active ingredient is papain enzyme and chloramine. Papain is antibacterial and anti-inflammatory, and chloramine is effective in removing denatured tissue. There is no need for a special device, and it is cheaper than Carisolv™. It also has the advantage of being biocompatible because it is composed of a natural material [421]. Carie-care™ is an enzyme-based gel formulation developed in 2010 and the active ingredient, endoprotein, acts as an antibacterial agent and a disinfectant. In addition, in Carie-care™, papain gel (natural anti-inflammatory property) and clove oil (analgesic and anesthetic action) compounds have additional advantages over Carisolv™ or Papacarie® [19]. In addition, Carie-care™ is less expensive than Papacarie® and has a longer shelf life [2223].

There have been attempts to conduct systematic reviews and meta-analyses on the clinical efficacy of Carisolv™ and Papacarie®. Both materials showed no significant differences in terms of CCR ability compared with traditional caries removal methods. In terms of duration, the CMCR method required more time than the conventional method. Carisolv™ was reported to require more time than Papacarie® [13]. In the CMCR method, pain was reduced compared to the conventional method, and the need for local anesthesia was reduced. Maru et al. [7] compared pain experienced by patients with visual analog scale (VAS) and found that the rotary group experienced more pain compared to the Carisolv™ group. In Deng et al.'s study [15], the pain perception assessment was performed with Wong-Baker faces pain scale (WBF), and it was found that patients treated with the traditional drill method felt significantly more pain during treatment than with Papacarie®. In addition, it was reported that patients using Papacarie® experienced less anxiety than the traditional method group. Li et al. [14] reported a significant difference in the need for local anesthesia between the Carisolv™ and conventional groups. Patients treated with Carisolv™ neither felt any discomfort nor required local anesthesia.

The results of this study showed that pain was reduced in all 4 studies [19222425] compared with the traditional method. In Rajakumar et al.'s study [19], pain was assessed by WBF and verbal pain scale (VPS). On comparing the two assessment methods, the Carie-care™ group showed lower pain scores than the conventional rotary group. In Hegde and Chaudhari's study [24], the pain threshold was evaluated during the caries removal by VAS. In comparison with the Carie-care™ group, the traditional group felt the greatest pain. In Pathivada et al.'s study [25], the degree of pain was measured by WBF: while the traditional method group felt pain, the Carie-care™ group did not feel any pain at all. Similarly, in Nagaveni et al.'s [22] study, the pain response between the two groups was assessed by the Sound, eye, and motor (SEM) scale, and the Carie-care™ group did not feel any pain compared to the traditional pain group.

In this review, CCR was reported in 3 studies [192425], with no significant difference from the traditional method except for one study [24]. In terms of time, 4 studies [19222425] showed that CMCR method took more time. One study [25] reported that more than a quarter of the traditional group subjects required local anesthesia, whereas the Carie-care™ group did not require any anesthesia.

In this study, assessment of behavioral responses was reported in 2 studies [2425]. In the Carie-care™ group, dental phobia was significantly lower than the control group [24]. In Pathivada et al.'s study [25], co-operation was measured by Frankl behavior rating scale (FBS). A more positive co-operation was also observed in the Carie-care™ group. In this study [25], Carisolv™ was also compared with traditional methods and Carie-care™ in terms of co-operation. Both CMCR groups showed significantly positive co-operation compared to the traditional group, but there was no significant difference between Carisolv™ and Carie-care™.

The studies included in this review were not suitable for meta-analysis for the following reasons: different outcome measurement scales, study design and dentition. However, this study is significant because it is the first review article to evaluate the clinical efficacy of Carie-care™ over the conventional method, with a relatively small heterogeneity in the age range of 3–15 years.

However, there were some limitations in this review. Firstly, all of the included studies were conducted in India and therefore limited general application of outcomes. Therefore, future reviews should include studies from several countries. Secondly, two of the papers were randomized controlled trials (RCTs), while the other two were LOE 3 as clinical control studies. Thirdly, the sample size was small due to the number of papers reviewed. Therefore, additional large-scale, high-quality and well-designed RCTs are required.

In conclusion, this systematic review showed that Carie-care™ as a CMCR agent reduces pain but requires more time than the conventional method during caries treatment. There was no significant difference in CCR between the two methods. Local anesthesia was not required in the CMCR group. In addition, dental phobia decreased compared to the control group, and cooperation was better. Therefore, it is a useful alternative to the conventional methods in children and adolescents, but additional studies are needed for further verification.