<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<article article-type="review-article" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">
  <front>
    <journal-meta>
      <journal-id journal-id-type="pmc">DRJ</journal-id>
      <journal-id journal-id-type="pubmed">Dent Res J</journal-id>
      <journal-id journal-id-type="publisher-id">Dental Research Journal</journal-id>
      <journal-title>Dental Research Journal</journal-title>
      <issn pub-type="ppub">1735-3327</issn>
	<issn pub-type="epub">2008-0255</issn>
      <publisher>
        <publisher-name>Medknow Publications Pvt Ltd</publisher-name>
	<publisher-loc>India</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">DRJ-11-423</article-id>
      
<article-id pub-id-type="doi">10.4103/1735-3327.139414</article-id>
      <article-categories>
	<subj-group subj-group-type="headings">
		<subject>Review Article</subject>
	</subj-group>
      </article-categories>
      <title-group>
        <article-title>A review on common chemical hemostatic agents in restorative dentistry</article-title>
      </title-group>
	<contrib-group>
<contrib contrib-type="author">
<name><surname>Tarighi</surname>
<given-names>Pardis</given-names></name>
<xref ref-type="aff" rid="aff1"/></contrib>
<contrib contrib-type="author">
<name><surname>Khoroushi</surname>
<given-names>Maryam</given-names></name>
<xref ref-type="aff" rid="aff2"/><xref ref-type="corresp" rid="cor1"/></contrib>
</contrib-group>
<aff id="aff1">Torabinejad Dental Research Center and Department of Operative Dentistry, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran</aff><aff id="aff2">Dental Materials Research Center and Department of Operative Dentistry, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran</aff>

      <author-notes>
	<corresp id="cor1"><bold>Address for correspondence:</bold>Maryam Khoroushi, Dental Materials Research Center and Department of Operative Dentistry, School of Dentistry, Isfahan University of Medical Sciences, Hezar Jerib Street, Post Code: 81746-73461, Isfahan, Iran <email xlink:href="khoroushi@dnt.mui.ac.ir">khoroushi@dnt.mui.ac.ir</email></corresp>

      </author-notes>
      <pub-date pub-type="ppub">
        <season>Jul&#x2013;Aug</season>
        <year>2014</year>
      </pub-date>
      <volume>11</volume>
      <issue>4</issue>
      <fpage>423</fpage>
      <lpage>428</lpage>   
      
      <permissions>
        <copyright-statement>Copyright: &#x000a9; Dental Research Journal</copyright-statement>
        <copyright-year>2014</copyright-year>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
</license>
      </permissions>
      <abstract><p>Control of hemorrhage is one of the challenging situations dentists confront during deep cavity preparation and before impressions or cementation of restorations. For the best bond and least contamination it is necessary to be familiar with the hemostatic agents available on the market and to be able to choose the appropriate one for specific situations. This review tries to introduce the commercially available hemostatic agents, discusses their components and their specific features. The most common chemical agents that are widely used in restorative and prosthodontic dentistry according to their components and mechanism of action as well as their special uses are introduced. PubMed and Google Scholar were searched for studies involving gingival retraction and hemostatic agents from 1970 to 2013. Key search words including: "gingival retraction techniques, impression technique, hemostasis and astringent" were searched. Based on the information available in the literature, in order to achieve better results with impression taking and using resin bonding techniques, common hemostatic agents might be recommended before or during acid etching; they should be rinsed off properly and it is recommended that they be used with etch-and-rinse adhesive systems.</p>
</abstract>
      <kwd-group><kwd>Adhesive restorations</kwd>
<kwd>bleeding</kwd>
<kwd>hemostatic agents</kwd>
<kwd>restorative dentistry</kwd>
</kwd-group>	
      
    </article-meta>
  </front>
  <body>
	<sec><title/>
</sec><sec><title>Introduction</title><p> </p>

<p>The oral cavity poses many challenges for operative dentistry from the constraining effect of tongue and cheeks to other obstacles of visualization and isolation, such as sulcular fluid, saliva and gingival bleeding while preparing teeth for restorative procedures. <sup><xref ref-type="bibr" rid="ref1">1</xref></sup>,<sup><xref ref-type="bibr" rid="ref2">2</xref></sup> The so-called "moisture control" is an essential part of any restorative dentistry procedure, direct or indirect. <sup><xref ref-type="bibr" rid="ref3">3</xref></sup> It has been reported that contamination of a prepared cavity has a detrimental effect on the durability of direct resin composite bond to tooth structure, <sup><xref ref-type="bibr" rid="ref4">4</xref></sup>,<sup><xref ref-type="bibr" rid="ref5">5</xref></sup>,<sup><xref ref-type="bibr" rid="ref6">6</xref></sup> especially when subgingival finish lines exists. <sup><xref ref-type="bibr" rid="ref7">7</xref></sup> Although use of dental dam provides good control of the restoration area and access to the preparation, in many situations its use is precluded. <sup><xref ref-type="bibr" rid="ref8">8</xref></sup> Therefore, alternative methods of controlling moisture and blood might be considered.</p>

<p>Historically, techniques for soft-tissue management and moisture control are categorized into three main methods: Mechanical, chemical or surgical. <sup><xref ref-type="bibr" rid="ref9">9</xref></sup> Mechanical methods were the first methods introduced for moisture control, especially for fixed restorations during impression taking. <sup><xref ref-type="bibr" rid="ref8">8</xref></sup>,<sup><xref ref-type="bibr" rid="ref10">10</xref></sup>,<sup><xref ref-type="bibr" rid="ref11">11</xref></sup> Among them, gingival retraction cord is the most popular. <sup><xref ref-type="bibr" rid="ref11">11</xref></sup>,<sup><xref ref-type="bibr" rid="ref12">12</xref></sup> However, plain cords not moistened with suitable medicaments generally are not able to control hemorrhage effectively <sup><xref ref-type="bibr" rid="ref2">2</xref></sup> and greater sulcular displacement happens when mechanical and chemical methods are combined, like retraction cords impregnated with hemostatic agents. <sup><xref ref-type="bibr" rid="ref1">1</xref></sup>,<sup><xref ref-type="bibr" rid="ref8">8</xref></sup>,<sup><xref ref-type="bibr" rid="ref11">11</xref></sup></p>

<p> There have been improvements in mechanical retraction with the introduction of cordless retraction techniques like GingiTrac (centrix), which uses a heavy viscosity matrix combined with a light body retraction paste and Magic Foam Cord (Colten-Whaledent), a polyvinyl siloxane material, expanding the sulcus before impression taking. The latter also provides some hemostasis. <sup><xref ref-type="bibr" rid="ref8">8</xref></sup>,<sup><xref ref-type="bibr" rid="ref13">13</xref></sup></p>

<p> Chemical methods include a variety of chemical solutions and gels acting as astringents or hemostatic agents. <sup><xref ref-type="bibr" rid="ref11">11</xref></sup>,<sup><xref ref-type="bibr" rid="ref14">14</xref></sup> Moreover, surgical methods such as electrosurgery and laser are alternative methods when hemorrhage is more serious or when soft-tissue removal and displacement are also required. <sup><xref ref-type="bibr" rid="ref11">11</xref></sup>,<sup><xref ref-type="bibr" rid="ref15">15</xref></sup>,<sup><xref ref-type="bibr" rid="ref16">16</xref></sup> The combination of chemical and mechanical methods or chemomechanical methods is the most popular retraction technique today and although it is used by 80&#x0025; of dentists, <sup><xref ref-type="bibr" rid="ref7">7</xref></sup>,<sup><xref ref-type="bibr" rid="ref9">9</xref></sup>,<sup><xref ref-type="bibr" rid="ref17">17</xref></sup> few reviews exist on the subject.</p>

<p>Some recent cordless retraction techniques combine chemical and mechanical methods and provide a non-invasive tissue management, like Expasyl (Kerr), a paste-like material containing aluminum chloride (AlCl <sub>3</sub> ) syringed into the sulcus, acting both as a chemical hemostatic agent and retraction material (chemomechanical method). <sup><xref ref-type="bibr" rid="ref8">8</xref></sup>,<sup><xref ref-type="bibr" rid="ref11">11</xref></sup> Although it provides excellent hemostasis, the retraction is minimal. <sup><xref ref-type="bibr" rid="ref8">8</xref></sup> Promising results, like effective bleeding control and less histologic damage than retraction cords, have been shown with Expasyl and Magic Foam Cord. <sup><xref ref-type="bibr" rid="ref13">13</xref></sup>,<sup><xref ref-type="bibr" rid="ref18">18</xref></sup>,<sup><xref ref-type="bibr" rid="ref19">19</xref></sup> Retraction cords impregnated with hemostatic agents like AlCl <sub>3</sub> or ferric sulfate (Fe <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> ) are other examples of chemomechanical method.</p>


</sec><sec><title>Chemical Agents Commonly Used in Restorative Dentistry</title><p> </p>

<p>Chemically, active gingival retraction agents are categorized as Class I (vasoconstrictors, adrenergics) or Class II (hemostatic agents, astringents). <sup><xref ref-type="bibr" rid="ref7">7</xref></sup> The difference between vasoconstrictors, hemostatic agents and astringents are as follows, as described by the British Journal of Pharmaceutical Research. <sup><xref ref-type="bibr" rid="ref20">20</xref></sup></p>

<p> Vasoconstrictors like epinephrine do not coagulate, but act by constricting blood vessels and decreasing their size. There have been concerns, however, over the use of racemic epinephrine-impregnated cords due to elevation of blood pressure and increase in heart rate <sup><xref ref-type="bibr" rid="ref1">1</xref></sup>,<sup><xref ref-type="bibr" rid="ref11">11</xref></sup>,<sup><xref ref-type="bibr" rid="ref14">14</xref></sup>,<sup><xref ref-type="bibr" rid="ref21">21</xref></sup> and no benefits have been recognized over other non-impregnated cords. <sup><xref ref-type="bibr" rid="ref22">22</xref></sup> Astringents, such as alum or aluminum potassium sulfate (KAl (SO <sub>4</sub> ) <sub>2</sub> ), AlCl <sub>3</sub> and zinc chloride (ZnCl <sub>2</sub> ), are substances that act by precipitating proteins on the superficial layer of mucosa and make it mechanically stronger. Styptics like ferric chloride and Fe <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> are concentrated forms of astringents, which cause superficial and local coagulation. <sup><xref ref-type="bibr" rid="ref20">20</xref></sup></p>

<p> Hemostatic agents arrest more serious hemorrhage from cut capillaries and arterioles. AlCl <sub>3</sub> and ferrous sulfate are preferred astringents among dentists because of minimum tissue damage <sup><xref ref-type="bibr" rid="ref11">11</xref></sup>,<sup><xref ref-type="bibr" rid="ref20">20</xref></sup> and also ease of use and effective results. <sup><xref ref-type="bibr" rid="ref8">8</xref></sup> There is a wide range of products based on these two components from different manufacturers to choose from <xref ref-type="table" rid="T1">Table 1</xref> lists the most recent well-known hemostatic products available with their active ingredients and concentrations.{Table 1}</p>

<p>Trichloroacetic acid has also been a subject of research due to its hemostatic and decalcifying effect. <sup><xref ref-type="bibr" rid="ref5">5</xref></sup>,<sup><xref ref-type="bibr" rid="ref23">23</xref></sup>,<sup><xref ref-type="bibr" rid="ref24">24</xref></sup>,<sup><xref ref-type="bibr" rid="ref25">25</xref></sup>,<sup><xref ref-type="bibr" rid="ref26">26</xref></sup> It is used in medicine as a cauterizing agent <sup><xref ref-type="bibr" rid="ref25">25</xref></sup> and in dentistry as a means to eliminate gingival hyperplasia. <sup><xref ref-type="bibr" rid="ref23">23</xref></sup> It causes coagulation necrosis in the adjacent soft-tissue <sup><xref ref-type="bibr" rid="ref26">26</xref></sup> and due to its very low pH of 1, is not a common hemostatic agent, but may be used as both hemostatic and etchant in cervical restorative lesions. <sup><xref ref-type="bibr" rid="ref5">5</xref></sup>,<sup><xref ref-type="bibr" rid="ref24">24</xref></sup></p>

<p> In general, common hemostatic agents used in restorative dentistry include ferric (ferrous) sulfate and AlCl <sub>3</sub> . However, there are other reagents such as KAl (SO <sub>4</sub> ) <sub>2</sub> and aluminum sulfate (Al <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> ) and ZnCl <sub>2</sub> , which have slight differences in their mechanisms of action and efficiency and will be explained here briefly.</p>

<p>Al <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> compounds (KAl(SO <sub>4</sub> ) <sub>2</sub> [Alum] and Al <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> )</p>

<p><list list-type="bullet"><list-item><p>Alum: In a 100&#x0025; concentration is only slightly less effective in shrinking the gingival tissues than epinephrine and it shows good tissue recovery. Although its tissue retraction and hemostatic abilities are limited, <sup><xref ref-type="bibr" rid="ref27">27</xref></sup> alum has been recommended for use as a hemostatic agent as a substitute for epinephrine because it is safer and has fewer systemic effects. <sup><xref ref-type="bibr" rid="ref28">28</xref></sup></p>
</list-item><list-item><p>Al <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> : It is effective in controlling hemorrhage and is biologically acceptable. A practical concern is that sulfate compounds can inhibit/retard the setting reaction of additional-reaction impression materials. <sup><xref ref-type="bibr" rid="ref28">28</xref></sup></p>
</list-item></list></p>

<p>AlCl <sub>3</sub></p>

<p>It is one of the most commonly used astringents. <sup><xref ref-type="bibr" rid="ref27">27</xref></sup>,<sup><xref ref-type="bibr" rid="ref29">29</xref></sup> It acts by constricting blood vessels and extracting fluid from tissues. The material is used in concentrations of 5-25&#x0025; and has minimal systemic side-effects. <sup><xref ref-type="bibr" rid="ref28">28</xref></sup> AlCl <sub>3</sub> is the least irritating among hemostatic agents used with cords, but it disrupts the setting of polyvinyl siloxane impression materials. However, rinsing thoroughly with water resolves its inhibitory effect. <sup><xref ref-type="bibr" rid="ref30">30</xref></sup></p>

<p>Ferric subsulfate (Fe <sub>4</sub> (OH) <sub>2</sub> (SO <sub>4</sub> ) <sub>5</sub> )</p>

<p>Furthermore, known as Monsel&#x2032;s solution, it has been used in gingival displacement. <sup><xref ref-type="bibr" rid="ref27">27</xref></sup>,<sup><xref ref-type="bibr" rid="ref30">30</xref></sup> It is slightly more effective than epinephrine in gingival displacement. Tissue recovery is good and the recommended time of use is 3 min. The literature suggests that ferric or ferrous salts are corrosive and injurious to soft-tissues and enamel and they stain the teeth. These properties are attributed to the high acidity (72&#x0025;, pH &lt;1) of the solution. <sup><xref ref-type="bibr" rid="ref30">30</xref></sup></p>

<p>Fe<sub>2</sub> (SO <sub>4</sub>) <sub>3</p>

<p></sub>It does not traumatize the tissue noticeably and healing is more rapid than with AlCl <sub>3</sub> . Solutions of Fe <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> above 15&#x0025; are very acidic and can cause significant tissue irritation and post-operative root sensitivity. It coagulates blood so quickly that it must be placed directly against the cut tissue. The recommended application time is 1-3 min. <sup><xref ref-type="bibr" rid="ref31">31</xref></sup></p>

<p> The resulting tissue displacement is maintained for at least 30 min. <sup><xref ref-type="bibr" rid="ref20">20</xref></sup> The tissue is temporarily discolored for 1 or 2 days. It disrupts the setting reaction of polyvinyl siloxanes. Therefore, all traces of the medicament should be rinsed off thoroughly from the tissue before taking an impression. <sup><xref ref-type="bibr" rid="ref27">27</xref></sup> Due to its iron content, Fe <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> stains gingival tissues a yellow-brown to black for several days. <sup><xref ref-type="bibr" rid="ref30">30</xref></sup></p>

<p>ZnCl <sub>2</sub> (bitartrate)</p>

<p>This material has been used in 8&#x0025; and 40&#x0025; concentrations. Because both of these concentrations are escharotic and result in permanent injury to the soft-tissue and probably to the bone, their use has not been recommended. <sup><xref ref-type="bibr" rid="ref30">30</xref></sup></p>

<p>Tannic acid (20&#x0025; and 100&#x0025;)</p>

<p>Although this material is less effective than epinephrine, it shows very good tissue recovery. The recommended time of application is 10 min. <sup><xref ref-type="bibr" rid="ref32">32</xref></sup> The hemostatic efficacy of tannic acid is minimal. <sup><xref ref-type="bibr" rid="ref14">14</xref></sup></p>

<p>Negatol solution</p>

<p>It is a 45&#x0025; condensation product of metacresol sulfonic acid and formaldehyde. It provides better retraction than epinephrine. However, its tissue recovery is poor. It is highly acidic and decalcifies teeth in both 10&#x0025; and 100&#x0025; concentrations. <sup><xref ref-type="bibr" rid="ref14">14</xref></sup></p>

<p> As seen in <xref ref-type="table" rid="T1">Table 1</xref>, popular reagents have concentrations of 20-25&#x0025; AlCl <sub>3</sub> and 15.5-20&#x0025; Fe <sub>2</sub> (SO <sub>4</sub> )3 <sup><xref ref-type="bibr" rid="ref8">8</xref></sup> usually never crosses these borders because higher amounts (60&#x0025; or more) can induce severe inflammation and necrosis. <sup><xref ref-type="bibr" rid="ref21">21</xref></sup> Moreover, there are several studies reporting the least viability of fibroblasts in higher concentrations <sup><xref ref-type="bibr" rid="ref33">33</xref></sup> and increased cell viability by decreasing the concentration of astringents. <sup><xref ref-type="bibr" rid="ref7">7</xref></sup></p>

<p> A relatively high level of acidity is also attributed to hemostatic agents, ranging from one to three in both gel and solution forms. <sup><xref ref-type="bibr" rid="ref34">34</xref></sup>,<sup><xref ref-type="bibr" rid="ref35">35</xref></sup> Not only this acidic behavior raises inflammatory responses in gingival tissues, <sup><xref ref-type="bibr" rid="ref33">33</xref></sup>,<sup><xref ref-type="bibr" rid="ref36">36</xref></sup> but also it interferes with some bonding processes by removing the smear layer, <sup><xref ref-type="bibr" rid="ref37">37</xref></sup>,<sup><xref ref-type="bibr" rid="ref38">38</xref></sup> thus interfering with self-etch adhesive systems. In addition, exposed root surfaces to this high acidity can cause post-operative sensitivity, which is said to be best controlled clinically with desensitizing agents. <sup><xref ref-type="bibr" rid="ref8">8</xref></sup> However, an acidic pH is needed for hemostatic agent&#x2032;s stability and effectiveness. <sup><xref ref-type="bibr" rid="ref39">39</xref></sup></p>

<p> There have also been investigations on the negative effects of these materials on surface details of additional silicone and polyether impression materials, but it has been reported that they do not interfere with the polymerization and setting reaction of impression materials. <sup><xref ref-type="bibr" rid="ref40">40</xref></sup>,<sup><xref ref-type="bibr" rid="ref41">41</xref></sup>,<sup><xref ref-type="bibr" rid="ref42">42</xref></sup> Moreover, when residues are carefully washed away these negative effects are reversed. <sup><xref ref-type="bibr" rid="ref39">39</xref></sup></p>


</sec><sec><title>Application of Haemostatic Agents in Clinical Dental Practice</title><p> </p>

<p>Hemostatic agents are increasingly used as a method of easier fluid control in dental procedures. Although some side-effects have been investigated during bonding and impression taking, including tissue inflammation and cell viability, it is established that proper use of these handy materials can minimize the negative effects, maximizing their advantages. Some adverse effects, such as inflammation and tissue necrosis, are already solved by lower concentrations and gel-type formulations marketed by manufacturers <xref ref-type="table" rid="T1">Table 1</xref>.</p>

<p>In addition, based on previous studies the most negative effects of astringents on bond strength and marginal seal occur when all-in-one adhesives are used, the bonding effectiveness, of which depends on the smear layer; however, quality of bonding for etch-and-rinse adhesives are least affected in this regard. <sup><xref ref-type="bibr" rid="ref37">37</xref></sup>,<sup><xref ref-type="bibr" rid="ref43">43</xref></sup>,<sup><xref ref-type="bibr" rid="ref44">44</xref></sup> Surface changes in enamel and dentin do not happen when lower concentrations and shorter application times of astringents are used due to their low pH; <sup><xref ref-type="bibr" rid="ref5">5</xref></sup>,<sup><xref ref-type="bibr" rid="ref24">24</xref></sup> however, a minimum amount of 0.3-0.5 mL is enough for a single tooth to stop bleeding. <sup><xref ref-type="bibr" rid="ref39">39</xref></sup> The least hard and soft-tissue damage is recorded in the normal 3-10 min application time <sup><xref ref-type="bibr" rid="ref11">11</xref></sup>,<sup><xref ref-type="bibr" rid="ref36">36</xref></sup> and if any inflammation occurs it would subside within 7-10 days after application. <sup><xref ref-type="bibr" rid="ref7">7</xref></sup></p>

<p> Since concerns still exist on hemostatic agents&#x2032; interference with bonding <sup><xref ref-type="bibr" rid="ref45">45</xref></sup>,<sup><xref ref-type="bibr" rid="ref46">46</xref></sup>,<sup><xref ref-type="bibr" rid="ref47">47</xref></sup> and impression taking, it is wise to remove the residues by water spray or surfactant-containing mouthwashes, such as Plax (Colgate), Consepsis Scrub (a chlorhexidine slurry; Ultradent products) or cleansing agents such as prep-quick (2&#x0025; glycolic acid; Ultradent). Water irrigation for at least 10 s <sup><xref ref-type="bibr" rid="ref45">45</xref></sup> also eliminates the staining and discoloration effect of ferric (iron) compounds on gingival and esthetic restorations <sup><xref ref-type="bibr" rid="ref2">2</xref></sup>,<sup><xref ref-type="bibr" rid="ref24">24</xref></sup> and it has been reported that chlorhexidine gluconate helps hemostasis happen in a shorter time due to its surfactant effect. <sup><xref ref-type="bibr" rid="ref46">46</xref></sup></p>


</sec><sec><title>Conclusion</title><p> </p>

<p>Based on the existing information in the literature, among the widely used chemical agents for control of hemorrhage in restorative dentistry, the most common hemostatic agents are AlCl <sub>3</sub> and Fe <sub>2</sub> (SO <sub>4</sub> ) <sub>3</sub> in 15-25&#x0025; concentrations and 3-10 min application times. In order to achieve better outcomes during taking impression or using bonding agents, common hemostatic agents recommended before or during etching, should be rinsed off properly and it is more recommended that they be used with etch-and-rinse adhesive systems.</p>
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