Use of Silver Diamine Fluoride for Dental Caries Management in Children and Adolescents, Including Those with Special Health Care Needs

Abstract

Background:  This manuscript presents evidence-based guidance on the use of 38 percent silver diamine fluoride (SDF) for dental caries management in children and adolescents, including those with special health care needs. A guideline workgroup formed by the American Academy of Pediatric Dentistry developed guidance and an evidence-based recommendation regarding the application of 38 percent SDF to arrest cavitated caries lesions in primary teeth.
Types of studies reviewed:  The basis of the guideline’s recommendation is evidence from an existing systematic review "Clinical trials of silver diamine fluoride in arresting caries among children: A systematic review." (JDR Clin Transl Res 2016;1[3]:201-10). A systematic search was conducted in PubMed®/MEDLINE, Embase®, Cochrane Central Register of Controlled Trials, and gray literature databases to identify randomized con- trolled trials and systematic reviews reporting on the effect of silver diamine fluoride and address peripheral issues such as adverse effects and cost. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of the evidence and the evidence-to-decision framework was employed to formulate a recommendation.
Results:  The panel made a conditional recommendation regarding the use of 38 percent SDF for the arrest of cavitated caries lesions in primary teeth as part of a comprehensive caries management program. After taking into consideration the low cost of the treatment and the disease burden of caries, panel members were confident that the benefits of SDF application in the target populations outweigh its possible undesirable effects. Per GRADE, this is a conditional recommendation based on low-quality evidence.
Conclusions and practical implications:  The guideline intends to inform the clinical practices involving the application of 38 percent SDF to enhance dental caries management outcomes in children and adolescents, including those with special health care needs. These recommended practices are based upon the best available evidence to-date. A 38 percent SDF protocol is included in Appendix II. (Pediatr Dent 2017;39(5):E135-E145)

^{KEYWORDS:   SILVER DIAMINE FLUORIDE, CLINICAL RECOMMENDATIONS, GUIDELINE, ANTI-INFECTIVE AGENTS, CARIOSTATIC AGENTS, SILVER COMPOUNDS, CARIES, TOPICAL FLUORIDES}

Scope and purpose

The guideline intends to inform the clinical practices involving the application of silver diamine fluoride (SDF) to enhance dental caries management outcomes in children and adolescents, including those with special health care needs. Silver diamine fluoride in this guideline’s recommendation refers to 38 percent SDF, the only formula available in the United States. These recommended practices are based upon the best available evidence to-date. However, the ultimate decisions regarding disease management and specific treatment modalities are to be made by the dental professional and the patient or his/her representative, acknowledging individuals’ differences in disease propensity, lifestyle, and environment. The guideline provides practitioners with easy to understand evidence-based recommendations. The American Academy of Pediatric Dentistry's (AAPD) evidence-based guidelines are being produced in accordance with standards created by the National Academy of Medicine (formerly known as the Institute of Medicine) and mandated by the National Guideline Clearinghouse™ (^NGC), a database of evidence-based clinical practice guidelines  and related documents maintained as a public resource by the Agency for Healthcare Research and Quality (AHRQ) of the U.S. Department of Health and Human Services (USDHHS).

Health intents and expected benefits or outcomes. The guideline is based on analysis of data included in a recent systematic review and meta-analysis¹ and summarizes evidence of the benefits and safety of SDF application in the context of dental caries management, mainly its effectiveness in arresting cavitated caries lesions ² in the primary dentition. Its intent is to provide the best available information for practitioners and patients or their representatives to determine the risks, benefits, and alternatives of SDF application as part of a caries management program. Prevention of new caries lesion development and outcomes in permanent teeth, such as root caries lesion arrest, were not the focus of this guideline; however, because they are of interest and relevant to caries management within the scope of pediatric dentistry, they are mentioned and will be included in future iterations of the guideline as the supporting evidence base increases.

Clinical questions addressed. The panel members used the Population, Intervention, Control, and Outcome (PICO)³ formulation to develop the clinical questions that will aid practitioners in the use of SDF in primary teeth with caries lesions. Does the application of SDF arrest cavitated caries lesions as effectively as other treatment modalities in primary teeth?

Methods

This guideline adheres to the National Academy of Medicine's guideline standards⁴ and the recommendations of the Appraisal of Guidelines Research and Evaluation (AGREE) instrument.⁵ The guidance presented is based on an evaluation of the evidence presented in a 2016 systematic review published by Gao and colleagues.¹  

Search strategy. Literature searches were used to identify systematic reviews that would serve as the basis of the guideline. Secondly, the results of the searches served as sources of evidence or information on issues related to, but outside the context of, the PICO, such as cost, adverse effects, and patient preferences. Literature searches were conducted in PubMed®/MEDLINE, Embase®, Cochrane Central Register of Controlled Trials, gray literature, and trial databases to identify systematic reviews and randomized controlled trials of SDF. Search results were reviewed in duplicate at both the title and abstract and the full-text level when warranted. Disagreements were resolved by consensus; if agreement could not be reached, the AAPD Evidence-Based Dentistry Committee (EBDC) overseeing the workgroup was consulted to settle the question. A detailed description of the search strategies is presented in Appendix I.

Inclusion and exclusion criteria. The criteria used to identify publications for use in the guideline were determined by the clinical PICO question. See Appendix I for search strategies. Publications which addressed the use of SDF to arrest caries lesions in primary teeth, regardless of language, merited full-text review; in vitro studies and studies of the use of SDF outside of the guideline’s stated outcomes were excluded. No new randomized controlled trials were identified that warranted updating the meta-analysis found in the systematic review¹ selected as the basis for this guideline.

Assessment of the evidence. The main strength of this guideline is that it is based on a systematic review of prospective randomized and controlled trials of SDF¹ . Evidence was assessed via the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach⁶ , a widely adopted and peer reviewed system of evaluating study quality (Table 1). The guideline recommendation is based on the meta-analysis of four controlled trials (three randomized), extracted in duplicate, from a systematic review of SDF¹ . Randomized (RCTs) and controlled clinical trials (CCTs) offer the highest level of clinical evidence; therefore, a recommendation based on a systematic review and meta-analysis of graded RCTs/CCTs provides more reliable and accurate conclusions that can be applied towards patient care.

This guideline is limited by the small number of RCTs evaluating SDF, the heterogeneity of the included trials, and selection bias that may have been introduced by possibly poor sequence generation^7,8 and selective reporting by one study⁷ . Weaknesses of this guideline are inherent to the limitations found in the systematic review1 upon which this guideline is based. Major limitations of the supporting literature include lack of calibration and/or evidence of agreement for examiners assessing clinical outcomes and unclear definitions or inconsistent criteria for caries lesion activity.^9,10 Arguably, without a valid and reliable method to determine lesion activity at baseline and follow-up, misclassification bias is possible, especially because clinicians cannot be blinded with regard to SDF application (due to the dark staining).^9,10 The absence of rigorous caries detection and activity measurement criteria in the reviewed literature can decrease the validity of the reported results.^9,10 Other reviewers of the systematic review1 noted similar and additional limitations.^9,10

Formulation of the recommendations. The panel formulated this guideline collectively via surveys, teleconferences, and electronic communications from January 2017–August 2017. The panel used the evidence-to-decision framework in an iterative manner to formulate the recommendations. Specifically, the main methods used were discussion, debate, and consensus seeking.¹¹ To reach consensus, the panel voted anonymously on all contentious issues and on the final recommendation. GRADE was used to determine the strength of the evidence.¹²

Understanding the recommendations. GRADE rates the strength of a recommendation as either strong or conditional. A strong recommendation “is one for which guideline panel is confident that the desirable effects of an intervention outweigh its undesirable effects (strong recommendation for an intervention) or that the undesirable effects of an intervention outweigh its desirable effects (strong recommendation against an intervention).”⁶ A strong recommendation implies most patients would benefit from the suggested course of action (i.e., either for or against the intervention). A conditional recommendation “is one for which the desirable effects probably outweigh the undesirable effects (conditional recommendation for an intervention) or undesirable effects probably outweigh the desirable effects (conditional recommendation against an intervention), but appreciable uncertainty exists.”⁶ A conditional recommendation implies that not all patients would benefit from the intervention. The individual patient’s circumstances, preferences, and values need to be assessed more than usual. Practitioners need to allocate more time for consultation along with explanation of the potential benefits and harms to the patients and their caregivers when recommendations are rated as conditional. Practitioners’ expertise and judgment as well as patients’ and their caregivers’ needs and preferences establish the suitability of the recommendation to individual patients. The strength of a recommendation presents different implications for patients, clinicians, and policy makers (Table 2).

Recommendations

The SDF panel supports the use of 38 percent SDF for the arrest of cavitated caries lesions in primary teeth as part of a comprehensive caries management program. (Conditional recommendation, low-quality evidence) 

Summary of findings

The recommendation is based on data from a meta-analysis of data extracted from RCTs and CCTs of SDF efficacy with various follow-up times and controls (Table 3). Based on the pooled estimates of SDF group, approximately 68 percent (95 percent confidence interval [95% CI]=9.7 to 97.7) of cavitated caries lesions in primary teeth would be expected to be arrested two years after SDF application (with once or twice a year application). Using data with longest follow-up time (at least 30 months follow-up; n=2,567 surfaces from one RCT7 and one CCT8 ), SDF had 48 percent higher (95% CI=32 to 66) success rate in caries lesion arrest compared to the controls (76 percent versus 51 percent arrested lesions, in absolute terms). In other words, 248 more cavitated caries lesions would be expected to arrest by treatment with SDF compared to control treatments, per 1000 surfaces after at least 30 months followup. Considering the stratum with most data (n=3,313 surfaces from three RCTs and one CCT, with follow-up of 24 months or more), similar estimates of relative and absolute efficacy were produced (i.e., RR 1.42 [95% CI=1.17 to 1.72]) and 72 percent versus 50 percent arrested lesions, in absolute terms. Other follow-up and application frequency strata are listed in the summary of findings (Table 3). The range of estimates of SDF efficacy between the included trials was categorically wide. Rates of arrest on untreated groups may seem unusually high, and this may be due to background fluoride exposure. In one of the trials⁷ , all participants (i.e., both the SDF-treated and control children) received 0.2 percent sodium fluoride (NaF) rinse every other week in school, while in other trials, children were either given fluoride toothpaste¹³ or reported use of fluoride toothpaste⁸ . The panel determined the overall quality of the evidence for this comparison was low or very low, owing to serious issues of risk of bias (unclear method for randomization, selective reporting, and high heterogeneity) in the included studies. No studies were identified regarding the arresting effect of SDF on cavitated caries lesions in adult patients. The panel suggests that similar treatment effects may be expected for other age groups, but the lack of evidence informing this recommendation restrained the panel from providing an evidence-based recommendation.

The panel made a conditional recommendation regarding the use of SDF for the arrest of cavitated caries lesions in primary teeth as part of a comprehensive caries management program. After taking in consideration the low cost of the treatment and the disease burden of caries, panel members were confident that the benefits of SDF application in the target populations outweigh its possible undesirable effects. Specifically:

1. Untreated decay in young children remains a challenge, from clinical and public health standpoints, in the U.S. and worldwide.¹⁴ It confers significant health and quality of life impacts to children and their families, and it is marked by pronounced disparities.¹⁵
2. Surgical-restorative work in young children and those with special management considerations (e.g., individuals with special health care needs) often requires advanced pharmacologic behavior guidance modalities (e.g., sedation, general anesthesia). These pathways of care have additional health risks and limitations (e.g., possible effects on brain development in young children, mortality risks¹⁶), and often are not accessible, at all or in a timely manner.^17-19 The U.S. Food and Drug Administration has issued a warning “that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than three may affect the development of children’s brains.”²⁰
3. The cost of managing severe early childhood caries is disproportionally high, especially when hospitalization is necessary. The need to treat children in a hospital setting with general anesthesia is a common scenario in the U.S. and other countries.²¹ Studies report that children from the less-affluent regions have higher dental surgery rates than those from more-affluent communities (25.7 vs. 6.9 per 1,000)¹⁷, which results in an economic burden for communities already impacted by the effects of poverty-related health problems.^19,22
4. With caries lesion arrest rates upwards of 70 percent (i.e., higher than other comparable interventions), SDF presents as an advantageous modality. Besides its efficacy, SDF is favored by its less invasive (clinically and in terms of behavior guidance requirements) nature and its inexpensiveness.
5. The undesirable effects of SDF (mainly esthetic concerns due to dark discoloration of carious SDF-treated dentin) are outweighed by its desirable properties in most cases, while no toxicity or adverse events associated with its use have been reported.

In sum, the panel felt confident that a conditional recommendation was merited because, although a majority of patients would benefit from the intervention, individual circumstances, preferences, and values need to be assessed by the practitioner after explanation and consultation with the caregiver.

Research considerations. Research is needed on the use of SDF to arrest caries lesions in both primary and permanent teeth. The panel urges researchers to conduct well-designed randomized clinical trials comparing the outcomes of SDF to other treatments for the arrest of caries lesions in primary and permanent teeth.

Potential adverse effects. Silver diamine fluoride contains approximately 24-28 percent (weight/volume) silver and 5-6 percent fluoride (weight/volume).²³ Exposure to one drop of SDF orally would result in less fluoride ion content than is present in a 0.25 mL topical treatment of fluoride varnish. The exact amount of silver and fluoride present in one drop of SDF is determined by the specific gravity of the liquid and the dropper used. More studies are required to determine that amount, given the stability of the product manufactured and packaged in the U.S.

In published clinical trials encompassing over 4,000 young children worldwide, exposure to manufacturer’s recommended amounts of SDF has not resulted in any reported deaths or systemic adverse effects.

Oral absorption can include absorption in mucous membranes in the mouth and the nasal cavity. The short-term health effects in humans as a result of exposure to water or food containing specific levels of silver are unknown. The Environmental Protection Agency (EPA) suggests levels of silver in drinking water not to exceed 1.142 mg/L (1.42 ppm). Silver diamine fluoride should not be used in patients with an allergy to silver compounds.²⁴ The main disadvantage of SDF is its esthetic result (i.e., permanently blackens enamel and dentinal caries lesions and creates a temporary henna-appearing tattoo if allowed to come in contact with skin). Skin pigmentation is temporary since the silver does not penetrate the dermis. Desquamation of the skin with pigmentation occurs when keratinocytes are shed over a period of 14 days.²⁵ Silver diamine fluoride also permanently stains most surfaces (e.g., counters, clothing) with which it comes into contact.

Guideline implementation. This guideline will be published in the AAPD’s Reference Manual and the journal, Pediatric Dentistry. Social media, news items, and presentations will be used to notify AAPD members about the new guideline. This guideline will be available as an open access publication on the AAPD’s website. Patient education materials are being developed and will be offered in the AAPD’s online bookstore. See Appendix II for practical SDF guidance and the Resource Section of the AAPD Reference Manual for a SDF chairside guide.²⁶

Cost considerations. Silver diamine fluoride is an effective and inexpensive means of arresting cavitated caries lesions in primary teeth.²⁷ It is inexpensive due to the low cost of materials and supplies and relatively short chair time required for application. Nevertheless, an empirical cost analysis discussion for SDF would need to address the several additional considerations and parameters. First, given the wide array of surgical and non-surgical management approaches for cavitated caries lesions in the primary dentition, agreement on consensus endpoints and, therefore, total cost is challenging and controversial. Second, cost should include patient/family and practitioner time, health care services utilized, and cost of non-health impacts, if any. Third, SDF economic analyses are likely best approached via a cost-utility framework, wherein expenditures are juxtaposed to quality-adjusted or disease-free years. To illustrate the importance of defining a consensus treatment endpoint, in this scenario disease-free years can be interpreted as caries inactive, no surgical intervention needed, or pain-free years. Finally, the economic benefits of SDF application must be considered in the context of pathways of clinical care (i.e., disease management) and account, among other factors, for the risks and costs associated with advanced behavior management techniques (e.g., indicated surgical-restorative work may require sedation or general anesthesia in some cases), families’ preferences, and opportunity costs (e.g., time investment beyond the direct costs).

Recommendation adherence criteria

Guidelines are used by insurers, patients, and health care practitioners to determine quality of care. In principle, following best practices and guidelines is believed to improve outcomes and reduce inappropriate care.²⁸ Therefore, measuring adherence to oral health-related guidelines is key and can serve as manifestation of the dental community’s role as a “responsible steward of oral health.”²⁹ Though measurement of oral health outcomes is in its early days at both system and practice levels, system-level performance measures for some oral health areas have been developed by the Dental Quality Alliance of the American Dental Association in partnership with the AAPD and other dental organizations. The goals of professional accountability, transparency, and oral health care quality can be furthered through these measures.

Workgroup. In December 2016, the AAPD’s Board of Trustees approved a panel nominated by the EBDC to develop a new evidence-based clinical practice guideline on SDF. The panel consisted of general and pediatric dentists in public and private practice involved in research and education; the stakeholders consisted of representatives from general dentistry, dental hygiene, governmental and non-governmental agencies, and international and specialty dental organizations.

Stakeholders and external review. This guideline was reviewed by external and internal stakeholders continuously from the beginning of the process until the formulation of the guideline. Stakeholders were invited to take part in anonymous surveys to determine the scope and outcomes of the guideline, bringing in points of view from different geographical regions, dental specialties, and patient advocates. Comments also were sought on the draft of the guideline. All stakeholder comments were taken into consideration, addressed, and acted upon as appropriate per group deliberation. Additional feedback from stakeholders is expected after publication and dissemination of the guideline.

Intended users. The target audience for this guideline is general dentists, pediatric dentists, pediatricians, and family practice physicians. Public and private payors will benefit from reviewing the evidence for coverage decisions regarding SDF use, and patients and patient advocates may find it useful as a reference for current available treatments for caries management. The target populations include children and adolescents, including those with special health care needs.

Guideline updating process. The AAPD’s EBDC will monitor the biomedical literature to identify new evidence that may impact the current recommendations. These recommendations will be updated five years from the time the last systematic search, unless the EBDC determines that an earlier revision or update is warranted.

Funding. The preparation of this guideline was funded by the American Academy of Pediatric Dentistry, a dental specialty organization with over 10,000 members.

Author contributions. All authors contributed to the formation and drafting of the guideline recommendations and the manuscript. Dr. Crystal served as chair of the workgroup and provided expert oversight. Dr. Marghalani provided statistical support and created the GRADE tables. Ms. Graham provided methodical support for the development of the guideline, including search strategy development. All authors contributed to the critical revision of the manuscript and approved the guideline.

Declaration of interest. Dr. Crystal is a member of the AAPD Editorial Board. Dr. Divaris is a member of the AAPD Editorial Board. Dr. Marghalani is an ad hoc reviewer for Pediatric Dentistry. Dr. Sulyanto is an ad hoc reviewer for Pediatric Dentistry. Dr. Wright is a member of the AAPD Editorial Board. No other conflicts of interested were reported.