ALLERGY TO LOCAL ANESTHETICS IN DENTAL PRACTICE

                

Dr Caterina Detoraki MD, Ph.D.

                                                                   

Introduction

Local anesthetics (LAs) are drugs widely used in clinical practice having revolutionized modern medicine from both the diagnostic and therapeutic point of view. In the first case, these drugs are used for patients’ preparation for different procedures (endoscopic, radiologic etc.) whereas in the second case they provide anesthesia for surgical interventions. As such, these agents are commonly administered in dental practice.

LAs were discovered in 1884, by a young Viennese ophthalmologist, Carl Koller that instilled cocaine, a natural agent, in his conjunctiva obtaining an anesthetic effect. A few years later, the first synthetic anesthetic Procaine, was produced (Einhorn, 1904) (1).

As LAs have been widely and increasingly used since last century, different LA agents have been synthesized. LAs can induce adverse reactions following their administration. In particular, allergic (hypersensitivity) reactions to local anesthetics have been reported; although these reactions are rare, in some cases the problem seems over-estimated being responsible for frequent therapeutic abstaining.

Therefore, this communication aims to point up the pathogenic and clinical aspects of hypersensitivity reactions to local anesthetics in order to offer a “model of behavior” for dentists who may face different adverse reactions induced by LAs in the daily clinical practice.

                                                                        

Pharmacology

LAs have similar molecular configuration with a lipophilic aromatic ring connected to a hydrophilic amine group (1). The type of linking bond is used to classify these drugs into ester and amide groups (Table 1). Ester are all derivatives of para-aminobenzoic acid (PABA) and include cocaine, procaine, tetracaine, benzocaine e chloroprocaine. The amide group, actually the most frequently used in clinical practice, includes lidocaine, mepivacaine, etidocaine, prilocaine, bupivacaine and dibucaine.

Table 1

ESTERS	AMIDES(two letters “i” in their name)
Procaine	Lidocaine
Tetracaine	Mepivacaine
Benzocaine	Articaine
Chloroprocaine	Prilocaine
	Bupivacaine
	Dibucaine
	Etidocaine

   

Mechanism of action

LAs induce an anesthetic effect by blocking nerve conduction, thus blocking afferent nerve signals to the brain (1). Nerve conduction blockade is obtained by a reversible binding of the anesthetic drug to the voltage gated sodium channels present in the nerve cell membrane, blocking therefore the formation of action potentials. The lipophilic nature of the LA facilitates diffusion across cell membrane and binding inside the cell (2).

     

Metabolism

Ester LAs are rapidly hydrolyzed by plasma cholinesterases, except cocaine which is metabolized by the liver. PABA is an intermediate metabolite, unable to induce anesthesia but it is a known allergen (1). It must be mentioned that parabens are widely used as additives in several lotions, cosmetics and foods. Thus, patients with hypersensitivity reactions to parabens can cross-react to PABA, if they are injected by LAs of the ester group. These phenomena can be at the basis of the higher prevalence of allergic reactions to ester compared to amid anesthetics. In fact, the incidence of hypersensitivity reactions to LAs has been drastically decreased since 1950, when the amide group has been introduced.

Amides undergo liver metabolism and renal excretion. In patients affected by liver failure it is therefore prudent to pay attention in order to reduce the total dosage of LA administered (3). Similarly to esters, some amides may also contain preservatives, such as sulphites and methyl-parabens, both chemically similar to PABA and therefore can cause allergies in sensitized individuals (2) (4).

In conclusion, the ester group is more frequently implicated in allergic reactions compared to the amid group. In addition, different esters can cross-react within the ester group. The cross-reactivity is not reported between esters and amides.

   

Adverse reactions to LAs

Drugs used for local anesthesia may provoke adverse reactions caused by different pathogenic mechanisms, that in most cases can be only suspected but rarely demonstrated.

These reactions can be distinguished in two groups: toxic reactions and hypersensitivity reactions.

      

Toxic reactions may be observed depending on the way of administration of the compound, the site of injection (accidental intravascular injection) and the clinical conditions of the patient (kidney or liver failure). Thus, the risk of toxic reactions could be significantly minimized staying within safe dosage parameters and using safe injection techniques (5). The symptoms of toxicity can be important and include agitation, tremors-convulsion, bradycardia and eventually cardiovascular collapse and respiratory depression.

It should be noted that vasoconstrictors such as adrenaline are frequently associated to the LA injection in order to lengthen anesthesia duration and make the site of surgical intervention ischemic. The administration of adrenaline can induce different signs and symptoms: tachycardia, hypertension, convulsions, loss of consciousness. More often, these events rely on an exaggerated individual response or on a rapid intravascular passage as in case of an accidental intravascular injection. (6).

More frequently, hyperventilation, nausea, vomit, sweating, dizziness or light bradycardia following LA injection may be reported . These reactions -often mimicking allergic reactions- are autonomic reactions (5).

 

Hypersensitivity reactions to LAs

Mook described the first report of allergic type reaction to LA in 1920 in a dentist who developed eczema on his hand after handling apothesin, a congener of procaine (1).Hypersensitivity reactions to LAs make no more than 1% of LA reactions. However, these reactions may be clinically important as they are unexpected and potentially serious (7). Based on Gell & Coombs classification, hypersensitivity reactions can be distinguished in: immediate (type I) or delayed (type IV).

    

Type I reactions are mediated by the interaction between specific antibodies of the IgE class, produced following exposure of a sensitized subject to various antigens/allergens (drugs, pollens, foods etc.). The following exposure of the patient to the same allergen induces interaction between two IgE specific molecules and the high affinity receptors for IgE (FcεRI) present on the cell membrane of mast cells and basophils. Mast cells and basophils are namely the primary effector cells of allergic reactions. Activation of these cells is characterized by a series of enzymatic and structural intracellular changes inducing histamine release and production of vaso-active mediators (leukotrienes, prostaglandines, PAF, tryptase, chymase ecc.), cytokines and chemokines responsible for the clinical manifestations of allergic reactions (8).

From the clinical point of view, signs and symptoms may vary and different organs and systems may be involved. Skin manifestations such as urticaria with pruritic rush, often associated to angioedema (lips, tongue, eyelid etc.) may be present. Respiratory symptoms may vary from rhinorrea to bronchospasm whereas cardiovascular symptoms such as severe hypotension may dominate the signs. In this context, systemic anaphylaxis represents without doubts, the most critical and dramatic clinical event within the scenario of hypersensitivity reactions. Anaphylactic reactions may be characterized by clinical symptoms of different grading of severity (Table 2)

 

Table 2 Grading of severity of anaphylactic reactions

Grade of severity	Skin	Gastrointestinal System	Respiratory System	Cardiovascular System
I	Pruritus Urticaria Angioedema
II	Pruritus Urticaria Angioedema	Nausea Cramping	Rhinorrea Dyspnoea Hoarseness	Tachycardia Arrythmia Blood pressure change
III	Pruritus Urticaria Angioedema			Shock
IV	Pruritus Urticaria Angioedema		Respiratory arrest	Shock Cardiac arrest

Although principal targets of anaphylaxis are cardiovascular, respiratory and gastrointestinal systems and the skin, these may be involved separately or in combination. Thus, it is important to understand that signs and symptoms considered “minor” may not be always present before the involvement of the respiratory and cardiovascular systems. In some cases, typical signs such as tachycardia, often considered a characteristic sign of systemic anaphylaxis, may not be present.

Allergic reactions mostly elapse like a unique event within minutes or a few hours from drug administration, but in some cases clinical manifestations may be present even after many hours from the initial event or they may have a prolonged duration (> 24 hours).

In some cases, a pseudo-allergic mechanism may be involved, induced by the activation of complement components following exposure to exogenous antigens (drugs, radiographic contrast media) or endogenous antigens (tryptase) with formation of anaphylatoxins. The later can directly induce degranulation of the primary effector cells (mast cells and basophils) of allergic reactions. From the clinical point of view these manifestations can’t be distinguished from anaphylactic reactions.

                                   

 

Type IV hypersensitivity reactions to LAs are basically induced by contact through the skin with subsequent manifestation of eczema lesions often involving the hands. These reactions appear after a prolonged period of exposure to the drug and may be secondary to the release of histamine by non IgE- mediated mechanisms.

Parallel to hypersensitivity reactions to LAs, reactions induced by preservatives -metabisulphites and parabens- contained in commercially available LA preparations have been reported. Metabisulphites are present as anti-oxidants, in different concentrations, in preparations containing adrenaline. These compounds are widely used in food industry, being contained as additives in different foods (wine, beer, etc.) and are marked as E221-E227. Metabisulphites may cause non IgE-mediated hypersensitivity reactions, characterized by rhinitis, rush, headache, dyspnoea, cramping (10).

Parabens, are rarely used as preservatives in different preparations of local anesthetics and can induce hypersensitivity reactions of type I and IV. Methylparabens and propylparabens are metabolized in chemical components structurally similar to PABA (4).

     

Patients’ evaluation

A correct evaluation of patients at risk of hypersensitivity reactions to LAs is necessary for their prevention and/or management.

Subjects at risk of hypersensitivity reactions to LAs are considered those who experience one or more of the previously described clinical manifestations during or following injection of a LA agent. Thus, a detailed history is an essential first step towards an accurate diagnosis. In some cases, in the base of symptoms reported by the patient (agitation, sweating, nausea, bradycardia), it may be possible to suspect an adverse autonomic reaction excluding an allergic sensitization.

It is important to underline that atopy is not a risk factor for the majority of allergic drug reactions (11). This means that patients affected by allergic diseases such as bronchial asthma, allergic rhinitis, food allergy etc., are not at higher risk for hypersensitivity reactions to drugs, compared to non atopic individuals. However, patients affected by chronic diseases (bronchial asthma, cardiovascular diseases etc.), may have a more severe course of allergic reactions due to the diseases’ nature and to the therapy administered (β-blockers or ACE-inhibitors ) for their treatment. Therefore, patients affected by chronic diseases must be adequately controlled and β-blockers or ACE-inhibitors therapy should be suspended before surgery.

In differential diagnosis of hypersensitivity reactions to LAs, allergy to various agents used during anesthesia in dental practice (chlorexidine, latex etc.) should be considered. Similarly, drug allergy induced by antibiotics and/or FANS, administered to patients before or during dental interventions should be examined.

In case of previous hypersensitivity reactions to LAs the patient should be referred to a specialist (allergist) to perform specific challenge tests in order to identify which LA should be used for future surgery.

When evaluating a patient for LA allergy, it is essential to obtain a detailed history including the LA used previously and a description of the reaction. The Joint Council of Allergy, Asthma, and Immunology (JCAAI) recommends that if the LA that caused the reaction in a patient is known, the specialist should consider for skin testing a LA of another class: for example if an ester caused the reaction, than an amide LA should be used for testing. If an amide is involved, then another amid may be tested, as there has not been reported cross-reactivity between amid groups (1). LAs used for testing should not contain preservatives and adrenaline that may alter skin reactivity.

Testing should be performed in the hospital where in case of severe hypersensitivity reactions therapeutic interventions can be immediate (12).

The incremental dose challenge test protocol is the following:

1. Prick test with undiluted LA

2. Intra-dermal injection with diluted LA in increasing concentrations (1:100, 1:10, 1:1)

3. Subcutaneous injection with undiluted LA in increasing concentrations (0,1 ml, 0,3 ml, 0,5 ml).

Injections are repeated every 15 minutes.

After the last injection, patients remain under clinical observation for approximately 2 hours.

The performance of alternative skin tests or in vitro tests without the for mentioned incremental dose challenge test are not safe and efficacious.

It should be mentioned that even in case of a negative challenge test, it is not possible to exclude the possibility of non IgE-mediated reactions. Thus, in case of patients with documented adverse reactions to LAs and negative challenge tests, it is necessary to prescribe a preventive therapy to administer prior to the LA injection .

In the clinical practice, the use of the following pharmacologic protocol, has demonstrated efficacy in reducing the incidence and severity of hypersensitivity reactions to local anesthetics:

 

 

48, 24 and 2 hours before dental surgery:

CETIRIZINE 10 mg

RANITIDINE 300 mg

13, 7 and 1 hours before dental surgery :

PREDNISONE 25 mg

1 hour after dental surgery:

CETIRIZINE 10 mg

RANITIDINE 300 mg

 

 

Concluding remarks

LA agents, have revolutionized our ability to provide surgical interventions in a pain-free manner .

The classification of LAs in two groups, esters and amids, is based on their structural and metabolic characteristics. Esters can more frequently induce allergic hypersensitivity reactions. Amids, are less allergenic and not significantly cross-reactive. They are widely used in clinical- surgical practice.

As 1% or less of the reactions to LAs are truly immune system mediated (type I or type IV), the problem of allergic reactions to LA appears often over estimated in dental practice and frequently induces to therapeutic abstaining.

Challenge skin tests with incremental doses of LA, preservative and adrenaline-free, performed by the specialist, are currently considered the gold standard, shown to be efficacious and safe in the evaluation of LA allergy. Challenge tests should be performed in patients with documented previous adverse reactions to LAs.

The best therapy for allergic, hypersensitivity reactions including anaphylaxis is prevention. Thus, patients at risk should be rapidly recognized in order to prevent or possibly attenuate severity of allergic reactions.

 

 

References

1. Boren E, Teuber SS, Naguwa M, and Gershwin ME. A critical review of local anesthetic sensitivity. Clinical Reviews in Allergy & Immunology. 32; 119-127, 2007.

2. McLure HA, and Rubin AP. Review of local anesthetic agents. Minerva Anesthesiol. 71; 59-74, 2005.

3. Haas DA. Un update on local anesthetics in dentistry. JADA. 134; 888-893, 2003.

4. Eggleston ST and Lush LW . Understanding allergic reactions to local anesthetics. Ann Pharmacother. 30; 851-857, 1996.

5. Thyssen JP, Mennè T, Elberling J, Plaschke P, and Johansen JD. Hypersensitivity to local anesthetics-update and proposal of evaluation algorithm. Contact Dermatitis. 59; 69-78, 2008.

6. Moneret Vautrin A, Widmer S, Cromer A, Pupil P, Grilliat GP. Anestetici locali. in MC Laxenaire, Moneret Vautrin DA. Il rischio allergico in anestesia e rianimazione, Masson, Milano, /Parigi/Barcellona/ Bonn, 1992.

7. Finucane BT. Allergies to local anesthetics- the real truth. Can J Anesth. 50; 869-874, 2006.

8. Marone G, Granata F, Spadaro G, Genovese A, Triggiani. The histamine-cytokine network in allergic inflammation. J Allergy Clin Immunol.112; (4 Suppl):S83-8, 2003.

9. Marone G. Reazioni anafilattiche ed anafilattoidi. Patogenesi, prevenzione, diagnosi e terapia. Ed. Sprinter, 1997.

10. Simon RA, Stevenson DD. Adverse reactions to food and drug additives. In Elliot Middleton, JR Charles ER, Elliot FE 1 Franklin Adkinson N, Yunginger JW. Allergy. Principles and practice. 4th Ed, Mosby, St. Louis, 1993.

11. R Mirakian, P W Ewan, S R Durhamw, L J F Youltenz, P Dugue´, P S Friedmannz, J S Englishk, P A J Huber and S M Nasser. BSACI guidelines for the management of drug allergy. Clinical and Experimental Allergy. 39; 43–61, 2009.

12. Società Italiana di Allergologia ed Immunologia Clinica. Memorandum: Diagnostica di allergia a Farmaci. Folia Allergol Immunol Clin 36: 437-56, 1989.

 

 

For information, contact:

   

Dr Caterina Detoraki (Aikaterini Detoraki)

Email: caterinadetoraki@hotmail.com

Brief profile

Dr Detoraki graduated in 1999 from the School of Medicine of the University of Naples Federico II where she also followed her residency in Allergy and Clinical Immunology. She attended the Asthma and Allergy Center of the Johns Hopkins University, Baltimore (USA) and after her residency, the Division of Allergic and Respiratory Diseases in the Department of Pediatrics -University of Naples Federico II, obtaining additional experience in the diagnosis and management of allergic diseases in children.

She attended various National and International Congresses and is co-author of scientific papers published by Italian and international journals.

In 2008 she received her Ph.D. degree in Clinical Physiology and Experimental Medicine from the University of Naples Federico II.

Since 2006 she works as a specialist in Allergy and Clinical Immunology, in the University Hospital Federico II of Naples.

TETRACLEAN: A contribution to root canal cleaning

Dr. Luciano Giardino

The aim of endodontic therapy is to remove the infection and root out the bacteria from the root canal system (Sjogren U, Fidgor D, Persson S, Sundqvist G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with periapical periodontitits Int. End. J 1997; 30(5): 297-306).

The instrumentation is unable to root out the bacterial load by itself (Bystrom A, Sundqvist G. Bacteriologic evaluation of the efficacy of mechanical root canal instrumentation in endodontic therapy. Scan J Dent Res 1981; 89(4): 321-8).

These findings have been confirmed by subsequent works, as well, such as Dalton et Al.’s (Dalton BC et Al. bacterial reduction with nickel-titanium rotary instrumentation. J Endod 1998; 24(11): 763-7), which pointed out that there is no noticeable difference in root canal cleaning when rotary or manual instruments are used.

During the instrumentation phase the main function of the irrigants is to remove the debris from the root canal: thanks to the synergy between instrumentation and irrigation the number of bacteria inside the root canal is significantly reduced (Siqueira JF, et al. Mechanical reduction of the bacterial population in the root canal by three instrumentation techniques. J Endod 1999; 25(5): 332-5).

As Radcliffe pointed out (Radcliffe CE et Al: Antimicrobial activity of varying concentrations of sodium hypochlorite on the endodontic microrganisms Actinomices Israelii, A. naeslundii Candida Albicans and Enterococcus Faecalis Int. Endod. J 2004; 37: 438-46) the action of sodium hypochlorite is made difficult by the anatomical complexity of the endodontium (pic 1), by the polymicrobial nature of the bacterial flora (pic 2), by the presence of the biofilm (pic 3) and by the presence of the smear layer (pic 4) produced by our instruments.

Moreover the endodontic environment proves to be very hostile to the irrigants.

Haapasalo and colleagues (Haapasalo M, Qian W, Portenier I, Waltimo T. Effects of Dentin on the antimicrobial properties of endodontic medicaments. J Endodon 2007; 33(8): 917-925) indicated the interactions between irrigants and intermediate medications used in vivo.

Collagen, hydroxyapatite, serum proteins and dentin can strongly inhibit the action of various substances used in the cleaning of the root canal system. Dentin, for example, acts as a buffer both with acid and basic substances.

Sodium hypochlorite is unable to remove any bacterial load, after a one-hour incubation, if the irrigant has been preincubated with dentin powder 24 hours before use.

Other substances, such as the organic ones, can interfere with the action of the irrigants. 20% of the dentin biomass is made up of Type I Collagen; remaining necrotic pulp tissue and inflammatory secretion, which can accumulate in the root canal from the various foramina, are to be added.

Another aspect, connected to the decrease in the action of the disinfectants, is linked to their very mechanism of action. In order to remove the bacterial load there must be contact between the bacterial wall and the irrigant.

The dynamics of the action contemplates on the one hand a reduction of the bacterial load but, at the same time, a progressive inactivation of the used substances. Moreover, a decrease in the results is always observed when switching from in vitro to in vivo experimentations. There are several possible reasons that may explain this (Haapasalo M. et Al. 2007): in addition to the already mentioned inactivation mechanisms of the drugs inside the canals, the irrigants have a short exposition time and a reduced total volume: this means that only a very limited amount of irrigant comes into contact with the bacteria and for a time that is always too limited.

Inside our canals most of the bacteria are linked together in a highly organized structure, the biofilm (pics 5,6), able to resist the removal action in various ways.

The bacteria in the biofilm are immersed in a matrix, called glycocalyx, that acts as a mechanical barrier against antibacterial agents. During its evolution, the biofilm releases bacteria that infect, in planktonic form, the surrounding space.

The biofilm is more resistant to the action of antibiotics like doxycycline, amoxycycline and metronidazole. The final result of all these actions is that the biofilm turns out to be 1000 times more resistant than the bacteria in planktonic form (Svensater G, Bergenholtz G. Biofilms in endodontics infections. Endodontic Topics 2004; 9: 27-36).

In 2003 Torabinejad suggested to use a universal irrigant which, used with 1.3% Sodium Hypochlorite, would be able to remove the smear layer from the root canal walls (Torabinejad M et Al A new solution for the removal of smear layer. J Endod 2003; 29: 170-5) and make it easier to get rid of the Enterococcus Faecalis from the infected dentin (Shabahang S, Torabinejad M. Effects of MTAD on Enterococcus Faecalis –contaminated root canals of extracted human teeth. J Endod 2003; 29: 576-9).

This irrigant is a mixture of Doxycycline (an antibiotic of the tetracycline group), Citric Acid and a surfactant (Tweed 80). Citric acid acts as a chelating agent, assisted by a weak action of the antibiotic, while the surfactant should make its penetration in the root canal system easier.

Despite a long series of articles promoted by Torabinejad’s team stressed its efficiency, other articles showed important limitations.

Tay and colleagues (Tay et Al Ultrastructure of smear layer – covered intraradicular dentin after irrigation with BioPure MTAD J. Endod 2006; 32(3): 218-21) showed that the composite is too aggressive on the intertubular dentin, resulting in a marked reduction of the exposed collagen matrix .

Ruff and colleagues underlined its complete inefficiency against fungi (Ruff ML, McClanahan SB, Babel BS. In vitro antifungal efficacy of four irrigants as a final rinse. J Endod 2006; 32(4): 331-3) while Dunavant (Dunavant TR et Al. Comparative evaluation of endodontic irrigants against Enterococcus Faecalis biofilms. J Endodon 2006; 32(6): 527-31) noticed that Sodium Hypochlorite was more efficient in eliminating the biofilm while Clegg and colleagues (Clegg MS et Al. The effects of exposure to irrigants solution on apical dentin biofilm in vitro. J Endodon 2006; 32(5): 434-7) underlined the inability of this product to remove the biofilm from the third apical.

A study carried out on a biofilm model published by Giardino and colleagues (Giardino L, Ambu E, Rimondini R, Savoldi E, Cassanelli C, Debbia EA Comparative evaluation of antimicrobial efficacy of Sodium Hypochlorite, MTAD and Tetraclean against Enterococcus faecalis biofilm. J Endodon 2007; 33(7): 852-5) confirmed the very poor action of MTAD on this structure (pic 7) .

In 2004 Luciano Giardino patented an irrigant prototype, always antibiotic-based, called Tetraclean. It is similar to MTAD, although showing important differences:

· the amount of doxycycline is reduced to a third (50mg/5ml vs. 150mg/5ml of MTAD)

· Polypropylene glycol

· Citric acid and cetrimide

The researches to validate the effectiveness of the product were conducted in cooperation with the University of Genoa, with the team from the University of Modena-Reggio Emilia, with Dr. Emanuele Ambu, holding the Chair of Endodontics at the same University and his team, with Professors Mario and Renato Leonardo and Dr. Fernanda Pappen from Araraquara University of Sao Paulo, Brazil , Prof. M. Haapasalo Dean of British Columbia University, Professors Sandro Rengo, P. Ausiello, A. Valletta, F. Riccitiello, M. Amato, M. Simeone, Dr. F.A. D’Apolito, Dr. G. Spagnuolo, Dr. V. D’Antò, Dr. C. D’Ambrosio, Dr. P. Carratù of the Department of Odontostomatologic and Maxillofacial Sciences, Department of Endodontics, University of Naples “Federico II”.

The base research made it possible to verify that Tetraclean is active, in agar, on the bacteria responsible of primary endodontic infections, such as Prevotella Intermedia and the Porphyiromonas Gingivalis (pics 8,9) (L. Giardino, E. Ambu, R. Rimondini, E.A. Debbia Antimicrobial effect of MTAD, Tetraclean, Cloreximid and Sodium Hypochlorite on three common endodontic pathogens. IJDR 2009 in press) and on the Enterococcus Faecalis causing an inhibition area larger than the one determined by Sodium Hypochlorite (Giardino L, Ambu E, Generali L, Savoldi E. Effetto antimicrobico di due nuovi irriganti nei confronti dell’Enterococcus faecalis: studio comparativo in vitro. G It Endo 2006; 20(2); 91-94).

The trials were also performed in “dirty” conditions (Tab 1) and also in these cases Tetraclean passed the European validation tests (Test for the Evaluation of Bactericidal Activity Dilution-Neutralization Method EN 1276 – 1997) (Neglia R, et Al. Comparative in vitro and ex vivo studies on the bactericidal activity of Tetraclean, a new generation endodontic irrigant, and sodium hypochlorite. New Microbiologica: 2008; 31, 57-65).

The advanced research made it possible to find out that Tetraclean is able to eliminate the biofilm in 60 minutes and that after 5 minutes (pic 10) there is a 90% reduction (Giardino L, Ambu E, Rimondini R, Savoldi E, Cassanelli C, Debbia EA Comparative evaluation of antimicrobial efficacy of Sodium Hypochlorite, MTAD and Tetraclean against Enterococcus faecalis biofilm. J Endodon 2007; 33(7): 852-5).

These results were also confirmed by the Haapasalo team (Pappen FG, Shen Y, Qian W, Leonardo MR,Giardino L, Haapasalo M . In vitro Antibacterial Action of Tetraclean, MTAD and formula modifications: direct exposure test and effect on the biofilm. Submitted to Int Endod J 2009). Samples of dental biofilm were incubated in anaerobic conditions on hydroxyapatite discs. After a 14 day incubation, the biofilms were exposed to the irrigant solutions for 30 seconds, 1 minute and 3 minutes. The Live/Dead Baclight staining was used (Molecular Probes, Europe BV) to distinguish live (green) from dead (red) cells (pics 11,12).

The samples were observed using the Confocal Laser Microscope. The 3D biofilm pictures were transferred to the Imaris 5.0 software for a quantitative analysis to assess the green live cells percentage. After 3 minutes the percentage of live bacterial cells exposed to Tetraclean was 0.44 lower than MTAD (Tab 2).

The subsequent step was to observe the behaviour in time of the irrigant against the Enterococcus Faecalis in an “ex vivo” model, i.e. on an extracted tooth. Also in this case the action of Tetraclean was compared to that of Sodium Hypochlorite and that of the nutrient broth (Neglia R, et Al. Comparative in vitro and ex vivo studies on the bactericidal activity of Tetraclean, a new generation endodontic irrigant, and sodium hypochlorite. New Microbiologica: 2008; 31, 57-65).

The samples were contaminated with E. Faecalis using the “overnight” method and then irrigated. Samplings and seedings at fixed time spans made it possible to evaluate the behaviour of the irrigants in the 144 subsequent hours.

As one can see in Tab 3, the mere mechanical action of irrigating using the nutrient broth is able to reduce the bacterial load of nearly 4 logarithms: obviously, the bacterial load will go back to its peak levels after 24 hours due to the total absence of any antibacterial action of this “irrigant”.

Sodium hypochlorite, on the other hand, reduces the bacterial load to zero immediately after the irrigation. This supports what was previously noticed, that is to say that this irrigant is the only one which is able to completely get rid of the surface load, arranged in the biofilm.

Unfortunately, however, in the subsequent 96 hours the load starts to rise again, until it gets back to the pre-treatment infection levels in at least 70% of the examined samples. These data were also confirmed in vivo as proved by this clinical case (pic 13 - 13bis).

Tetraclean, vice versa, seems to have no action at all after the irrigation (its behaviour being similar to the nutrient broth), but exerts its action progressively during the subsequent 72 hours until it completely eradicates the bacterial loads in all the examined samples.

The hypotheses on this behaviour are partially linked to the bacteriostatic action of the doxycycline and partially to its substantivity, i.e. it quickly binds to the dentin and is subsequently released without losing its antibacterial activity; this property creates a reserve of active antibacterial agent which is slowly and steadily released from the dentinal surface.

However the problem seems to be more complex. During the speculative phase, the authors have conjectured that the behaviour of Sodium Hypochlorite is quite linear: its antibacterial action is very strong because it completely eliminates the bacterial load from the root canal surface.

However, due to the difficulties to penetrate into dentinal tubules, as showed by Elio Berutti and colleagues (Berutti E, Marini R, Angeretti A. Penetration ability of different irrigants into dentinal tubules. J Endodon 1997, 23(12), 725-7), Sodium Hypochlorite is not able to reach the deepest areas of the root canal system: for this reason these areas represent reservoirs of infection for the recontamination of the root canal system.

Tetraclean is probably able to penetrate these structures and exert its action over the time, thus eliminating the bacterial strains under development.

In order to confirm this hypothesis another study was carried out – its preliminary findings were presented by Ambu and Giardino at the 2007 SIE Congress held in Naples while the final results, in publishing, were presented for the first time at the SIE National Congress held in Turin in November 2008. In this research the authors investigated the tubular penetration of 5.25% Sodium Hypochlorite and Tetraclean, marking the irrigants and observing the samples with a polarized optical microscope and a confocal laser microscope. The findings of this experience confirm that Tetraclean is able to penetrate deep into dentinal tubules (6-700µ) (pics 14,15) while the action of Sodium Hypochlorite is usually confined to the root canal surface (pic 16).

The better tubular penetration is also due to a low surface tension of Tetraclean compared to the other tested irrigants (Giardino L, Ambu E, Becce C, Rimondini L, Morra S. Surface tension comparison of four common root canal irrigants and two new irrigants containing antibiotics. J Endodo 2006; 32(11): 1091-3) (Tab 4).

In an in vitro study, 10 single rooted teeth were instrumented at the apex using manual Protaper files till file F2, the canals were irrigated with 2ccs of Sodium Hypochlorite when switching instruments and at the end of the preparation the canals were irrigated with Tetraclean for 4 minutes.

The teeth were subsequently fractured in 2 and examined using SEM in order to verify the degree of cleanliness in the medium and apical coronal third. The results confirm a good degree of cleanliness at all the examined levels (pics 17-21).

The cleaning action of Tetraclean was also evaluated using SEM (pics 22-24) and histologically (pics 25,26) in the necks of the mandibular molars by means of a 30 second final passive ultrasonic activation of the irrigant in the root canals.

The passive ultrasonic activation makes it possible to effectively clean anatomical areas otherwise difficult to reach using just root canal instruments (pics 27,28).

The effectiveness and clinical safety of Tetraclean was evaluated in two microbiological and clinical studies.

In the Department of Endodontics – University of Modena-Reggio Emilia – headed by Dr. Ambu, 10 patients suffering from chronic apical periodontitis and periapical radiotransparency were selected. After isolating with a dam and opening the pulp chamber a first microbiological sampling was carried out using a paper cone. After the shaping each root canal was irrigated with 5ccs of Thiosulfate to neutralize the action of Sodium Hypochlorite and finally irrigated with Tetraclean. After drying each root canal a second microbiological sampling was carried out.

The microbiological exams carried out at the Department of Microbiology of the same University, headed by Prof. Blasi, showed a 90% decrease of the total microbial load on all the treated root canals (pic 29 ).

The clinical results of the pilot study on 200 patients treated with periodical checkups for a year by Prof Rengo’s team on behalf of the Ministry of Health suggest that Tetraclean is clinically efficient and safe and confirm that the risks associated with the use of this irrigant are almost absent.

Endodontic therapy is solely a microbiological treatment. From what has been discussed so far the difficulty of providing a scientific rationale to our root canal cleaning clearly emerges.

Sodium Hypochlorite does not always work on Enterococcus Faecalis, but it always works on Gram-negative bacteria and on the ones responsible for primary infections. Intermediate medications, such as Calcium Hydroxide and Iodoformic paste, are often useless in the therapy of the post treatment endodontic pathology since the Enterococcus Faecalis, true protagonist in 70% of these occurrences, can easily survive despite their presence.

It is however common knowledge, as Nair demonstrated, that a one-visit therapy leaves many areas that cannot be reached by irrigants and instruments infected. For sure, nowadays there is no “magic liquid” or “magic device” able to sort all our problems out. There are protocols that can be used and proposed.

We are suggesting one, to be considered as a summary of what has been discussed so far:

- Generously irrigate using 5.25% NaOCl during instrumentation in order to remove the smear layer while it is building up

- Widen the root canal to a preparation with at least a .06 conicity and 25 apical diameter (or shape at greater conicity)

- Use devices (e.g. ultrasonic or sonic systems) to make the break-up of the biofilm and the deepest possible penetration of the irrigants easier

- Use EDTA for a minute at the end of the instrumentation to get rid of the organic part of the smear layer

- Replace the last step with the use, for 5 minutes, of antibiotic-based irrigants, as soon as they are available

As Gary Doern, Professor of Microbiology – University of Iowa – wrote: Gram-negative bacteria appeared on Earth 3.5 billion years ago, Gram-positive 3.4 billion years ago, fungi 2.7 billion years ago and Homo Sapiens Sapiens just 250,000 years ago. We have been in the antibiotic era for just 70 years. If we were to compare the time from the appearance of bacteria up to now to a year, the bacteria would have appeared the first second of January 1^st while men at 11:56 pm of December 31^st. We would have had antibiotics since 23:59:59.5 pm of New Year’s Eve. Having established who will win the war, let’s try and win some battles!

I sincerely thank Dr Ambu and all his team for the highly scientific and brotherly contribution lavished during these 5 years.

Many thanks also to Dr L. Generali and Prof Cavani for the pictures on the study on penetration using fluorescence and confocal microscopes and Dr. C. Rimoldi for the valuable contribution in the microbiological part, object of her degree thesis.

For information:

Dr. Luciano Giardino

Surgeon, Dentist

12, Via Marinella

88900 Crotone

Phone/fax 0962 21249

e-mail: lucianogiardino@libero.it

Author of over 70 articles on national and international magazines.

CLOPD Confirmed Contract Professor – Chair in Periodontology – University of Brescia – AY 2002-2007, confirmed AY 2007-08

He holds the Chair of Histopathological Aspects of Periodontal Disease – Additional Periodontal I MED/28

CLOPD Contract Professor - Chair in Endodontics - University of Turin AY 2000-2004

Speaker in National and International Congresses dealing with Endodontic and Periodontal Histology and Microbiology

Visiting Scientist Researcher Dept of Endodontology UConn University 1988

Visiting Researcher Dept. Microbiology and Virology “Cotugno” Hospital, Naples 1992

Winner of Garberoglio Prize, 2002 and SPE Turin, 2002

Ordinary Member SIE, ESE, Active Member IADR and New York Academy of Sciences

Editorial Board “Giornale Italiano di Endodonzia”

Revisor “Indian Journal of Dental Research”

Composites in dentistry

 

Dr. Davide Apicella

 

Composite materials used in dentistry are made up of a fluid resin and a solid filler. The resin is made up of monomers (monomers are molecules). The solid filler is made up of glass, quartz and silicon particles. Taken alone the filler is like a fine-grained powder (silicon, quartz, glass particles powder) to the touch. Defining a composite material as macro-, micro- or nano- filled refers to the particle dimension (granulometry).

How much powder is mixed with how much resin?

The amount of filler in respect to the amount of resin is defined filler percentage. The “amount” referred to is the volume of filler and of resin. A filler percentage of 80% means that the amount of filler mixed with resin accounts for the 80% of the volume of resin alone.

PICTURE 1-2

The filler percentage varies on the different dental composites on the market.

However we can distinguish two main categories of composite materials according to their filler percentage: high filler percentage composites (about 70% in volume) and low filler percentage composites (about 50% in volume).

If every glass or quartz particle had the size of a stone, a high filler percentage composite material would look like a dry-stone wall, where the stones it is made up of are very close to each other.

Every stone has got an irregular shape: this means that it cannot fit perfectly with the adjacent stones having irregular shapes themselves. A wall only made up of “big” stones, having a given volume (Vg) but whose shape is irregular and varies from stone to stone, would have wide gaps between the stones it is made up of.

(PICTURE 3-4).

The whole wall takes up a given volume Vm: 50-60% of this is taken up by big stones all having a volume Vg. The remaining volume percentage equals the sum of all the gaps between the stones: this hollow volume is defined Vv.

In order to fill the hollow volume, that is to “fill” the hollow spaces, smaller stones (PICTURE 5) can be added among the bigger stones: adding the smaller stones will result in the creation of smaller gaps which will be filled with even smaller stones.

In the above mentioned dry-stone wall, we can figure the resin as a thin layer of glue spread on the interfaces between all the stones.

A high filler percentage composite material appears as a solid array of quartz and/or glass particles of different sizes, closely in contact to each other and with a thin layer of resin spread on the interfaces between the particles.

The definitions of macro-, micro, micro-hybrid- and nano- composite are referred to the sizes of the particles and how differently shaped particles are combined together to “fill the gaps” of the dry-stone wall.

If every glass or quartz particle had the size of a stone, a low filler percentage composite material would look like a wall whose stones are separated by a thick layer of cement.

The result of this mixture is a viscous paste. Viscosity is defined as the ability of the molecular particles a fluid is made up of to flow one upon the other. In a dental composite material viscosity depends on the friction between the molecules (monomers) flowing one upon the other, on the friction between quartz and/or glass particles flowing one upon the other and on the friction between quartz and/or glass particles flowing on the monomers. The higher the friction between particles and/or molecules, the higher the viscosity of the paste; the lower the friction between molecules and/or particles, the lower its viscosity.

A possible example can be a tube of cavit and saliva. Cavit has a higher viscosity than saliva. This is due to the higher friction between the molecules/particles of cavit and the molecules/particles of saliva.

The viscosity of a composite material in paste form (not hardened yet) depends on:

• Filler (powder)-resin volume ratio
• Resin viscosity

 

BIS-GMA is the resin employed as matrix in dental composites. Its high viscosity dramatically reduces its workability at room temperature. For this reason BIS-GMA is diluted adding low viscosity resins like TEGDMA.

The filler is constituted by lithium silicate, aluminum silicate, quartz and barium glasses particles.

Composites are classified according to the granulometry of the filler, that is the size of the particles.

In macro-filled composites the average dimensions of the particles range from 1 to 30 mm.

In homogeneous micro-filled composites the average dimensions of the particles range from 0.04 to 0.06 mm.

In hybrid composites the filler is made up of both 1-30 mm particles and 0.04-0.06 mm particles.

In these classes of composites the filler is simply added to the matrix.

In other kinds of composites, the very particles are made up of a composite material. This is the case with Inhomogeneous Micro-Filled Composites, which can be subdivided into:

• Micro-filled complexes reinserted into the mass, where some micro-particles are put into BIS-GMA resin; the resulting mixture is polymerized and, when hardened, ground and shred till the composite granules reach a size ranging from 1 to 200 mm; at this point the granules are put back into BIS-GMA resin to get the final composite;
• Composites micro-filled with pre-polymerized spherical particles: these micro-particles are put into spheres of partially polymerized resin, then the polymeric spheres which also contain the micro-particles are added as filler in the BIS-GMA resin to get the final composite. The composite spheres range from 20 to 30 mm;
• Microparticles agglomerate complexes: the micro-particles are aggregated in resin-free agglomerates sized 1-25 mm; then the agglomerates are put into BIS-GMA resin to get the final composite.

The microparticles are then present as granules or pre-polymerized spheres or agglomerated granules rather than individual particles. This allows to incorporate higher amounts of filler without noticeably increasing the viscosity of the material.

The adhesion of the matrix to the filler particles has improved using an organic silicon glue called silane.

Dr Davide Apicella,

was born in Naples on December 19^th, 1980.

He obtained his degree in Dentistry and Prosthodontics at the Faculty of Medicine and Surgery, Second University, Naples on September 29^th, 2008 with a mark of 110/110.

In the 2006/2007 Academic Year he worked as contract orthognathodontics tutor in the Master Degree in Dentistry and Prosthodontics, Faculty of Medicine and Surgery, Second University, Naples.

On November 1^st, 2008 he started to attend his first year of a Ph.D. in Biomaterials in Odontostomatology and Ophthalmology – 24^th cycle, Second University, Naples.

Scientific works published on journals indexed in the National Library of Medicine and having an Impact Factor:

2009: Aversa R, Apicella D, Perillo L, Sorrentino R, Zarone F, Ferrari M, Apicella A.

Non-linear vischoelastic three dimensional finite element analysis on the effect of endocrown material rigidity on alveolar bone modeling process. Dental Materials. 2009 Jan 15. (Epub ahead of print).

2008: Ferrari M, Sorrentino R, Zarone F, Apicella D, Aversa R, Apicella A. Non-Linear Visco-Elastic Finite Element Analysis of The Effect of The Length of Glass Fiber Posts on The Biomechanical Behaviour of Directly Restored Incisors and Surrounding Alveolar Bone. Dental Materials Journal. 2008 Jul;(4):485-98.

2007: Sorrentino Roberto; Salameh Ziad; Apicella Davide; Auriemma Tommaso; Zarone Fernando; Apicella Antonio; Ferrari Marco. Three-dimensional finite element analysis of stress and strain distributions in post-and-core treated maxillary central incisors. The journal of adhesive dentistry 2007;9(6):527-36. Department of Dental Materials and Restorative Dentistry, University of Siena, Policlinico Le Scotte, Siena, Italy.

2006: Annunziata Marco; Aversa Raffaella; Apicella Antonio; Annunziata Antonio; Apicella Davide; Buonaiuto Curzio; Guida Luigi. In vitro biological response to a light-cured composite when used for cementation of composite inlays. Dental materials : official publication of the Academy of Dental Materials 2006;22(12):1081-5. Department of Odontostomatological, Orthodontic and Surgical Disciplines, Second University of Naples S.U.N., Naples, Italy.

2006: Zarone Fernando; Sorrentino Roberto; Apicella Davide; Valentino Bartolomeo; Ferrari Marco; Aversa Raffaella; Apicella Antonio. Evaluation of the biomechanical behavior of maxillary central incisors restored by means of endocrowns compared to a natural tooth: a 3D static linear finite elements analysis. Dental materials : official publication of the Academy of Dental Materials 2006;22(11):1035-44. Second University of Naples, DISPAMA, Material Division, Aversa, Italy.

2005: Zarone Fernando; Apicella Davide; Sorrentino Roberto; Ferro Valeria; Aversa Raffaella; Apicella Antonio. Influence of tooth preparation design on the stress distribution in maxillary central incisors restored by means of alumina porcelain veneers: a 3D-finite element analysis. Dental materials : official publication of the Academy of Dental Materials 2005;21(12):1178-88.

2005: Apicella Antonio; Simeone Michele; Aversa Raffaella; Lanza Alessandro; Apicella Davide. Light shielding effect of overlaying resin composite on the photopolymerization cure kinetics of a resin composite and a dentin adhesive. Dental materials : official publication of the Academy of Dental Materials 2005;21(10):954-61.

2005: Lanza Alessandro; Aversa Raffaella; Rengo Sandro; Apicella Davide; Apicella Antonio. 3D FEA of cemented steel, glass and carbon posts in a maxillary incisor. Dental materials : official publication of the Academy of Dental Materials 2005;21(8):709-15.

2005: Simeone Michele; Lanza Alessandro; Rengo Sandro; Aversa Raffaella; Apicella Davide; Apicella Antonio. Inlay shading effect on the photopolymerization kinetic of a dental composite material used as bonding system in an indirect restoration technique. Dental materials : official publication of the Academy of Dental Materials 2005;21(8):689-94.

 

For information

Davide Apicella:

davidsail@msn.com