Risks and Management of Sodium Hypochlorite in Endodontics

Endodontic emergencies are associated with pain and swelling which requires immediate diagnosis and treatment. The main causative factors for these emergencies are pulp and peri-radicular pathosis, traumatic injuries, procedural complications; were sodium hypochlorite accidents can occur. The impetus behind a successful root canal treatment relies on a thorough debridement of tissue remnants, bacteria and toxins from the root canal system. For a proper clean canal, mechanical preparations alone are insufficient, as reviewed by Haapasalo et al. [1]. Several studies shows that instrumentation alone were not 100 % effective to debride and clean the canals but has to be in conjunction with irrigants [2-6]. Uninstrumented areas were reported in 65% of instrumented oval canals, according to Wu and Wesselink [7]. The morphology of the canals makes it difficult for a complete debridement of root canals, as residual pulp tissue and bacteria may persists in the irregularities of the canal. Therefore, irrigants should support and compliment endodontic preparations by flushing out dentinal debris, dissolving organic tissues, disinfecting the canal and providing lubrication during instrumentation without irritating the surrounding tissues. Hydrogen peroxide, chlorhexidine, saline are some of the irrigants used; among which sodium hypochlorite is the commonly used effective antimicrobial and tissue dissolving irrigant. Concentrations of sodium hypochlorite ranges from 0.5%-5.2%, which is applied to the canals during and after mechanical preparation. Effective concentration range of sodium hypochlorite is from 2.6%5.25% [8, 9].


Introduction
Endodontic emergencies are associated with pain and swelling which requires immediate diagnosis and treatment. The main causative factors for these emergencies are pulp and peri-radicular pathosis, traumatic injuries, procedural complications; were sodium hypochlorite accidents can occur. The impetus behind a successful root canal treatment relies on a thorough debridement of tissue remnants, bacteria and toxins from the root canal system. For a proper clean canal, mechanical preparations alone are insufficient, as reviewed by Haapasalo et al. [1]. Several studies shows that instrumentation alone were not 100 % effective to debride and clean the canals but has to be in conjunction with irrigants [2][3][4][5][6]. Uninstrumented areas were reported in 65% of instrumented oval canals, according to Wu and Wesselink [7]. The morphology of the canals makes it difficult for a complete debridement of root canals, as residual pulp tissue and bacteria may persists in the irregularities of the canal. Therefore, irrigants should support and compliment endodontic preparations by flushing out dentinal debris, dissolving organic tissues, disinfecting the canal and providing lubrication during instrumentation without irritating the surrounding tissues. Hydrogen peroxide, chlorhexidine, saline are some of the irrigants used; among which sodium hypochlorite is the commonly used effective antimicrobial and tissue dissolving irrigant. Concentrations of sodium hypochlorite ranges from 0.5%-5.2%, which is applied to the canals during and after mechanical preparation. Effective concentration range of sodium hypochlorite is from 2.6%-5.25% [8,9]. This article reviews the potential complications that occur with sodium hypochlorite in clinical practice, discusses the measures that can be taken to minimize the risks and provides details to appropriate management in rare cases of suspected tissue damage.

Rationale behind using sodium hypochlorite y y
Due to the high pH ,the hydroxyl ions alters the integrity of cytoplasmic membrane of microorganisms, causes irreversible enzymatic inhibition, biosynthetic alterations in cellular metabolism and phospholipid degradation by liquid peroxidation. y y Antifungal activity (Table 1) y y It disrupts or removes biofilms (Table 2). y y Strong dissolving action in the presence of organic tissue and microorganisms, by breaking down of proteins into aminoacids (Table 3). y y Haemostatic property (Table 4).

Drawbacks
The negative property or drawback of sodium hypochlorite is that it can cause soft tissue inflammation if passed outside the confines of root canals [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Acute inflammation followed by necrosis results when sodium hypochlorite comes into contact with vital tissue. It causes severe inflammation and cellular destruction in all tissues except heavily keratinized epithelium [28]. The severity of the complication depends on the concentration of solution, its pH and its duration of exposure. Sodium hypochlorite has a pH of 11-12.5 which causes injury by oxidation of proteins. Higher concentrations have some irritating effects on the periodontal ligament [29].
This article reviews the potential complications that can occur with sodium hypochlorite in clinical practice, discusses the measures that can be taken to minimize the risk and provides details to appropriate management in rare cases of suspected tissue damage.

Toxicity of sodium hypochlorite
Sodium hypochlorite when comes in contact with tissue protiens, forms nitrogen, formaldehyde and acetaldehyde in short time and peptide links are broken resulting in dissolution of proteins. During the process, hydrogen in the amino groups is replaced by chlorine thereby forming chloramines which plays an important role in antimicrobial effectiveness. Necrotic tissues are thus dissolved and microbial agent can reach and clean the infected areas better. Pashley et al. [27] demonstrated the cytotoxicity of Sodium hypochlorite using three independent biological models. They found that a concentration as low as 1:1000 (v/v) Sodium hypochlorite in saline caused complete haemolysis of red blood cells in vitro. As the solution used in this study was isotonic and thus excluded an osmotic pressure gradient, the observed haemolysis and loss of cellular protein was due to the oxidizing effects of Sodium hypochlorite on the cell membrane. Undiluted and 1:10 (v/v) dilutions produced moderate to severe irritation of rabbit eyes whilst intradermal injections of undiluted, 1:2, 1:4 and 1:10 (v/v) dilutions of Sodium hypochlorite caused skin ulcers. Kozol et al. [30] proved Dakin's solution to be detrimental to neutrophil chemotaxis and toxic to fibroblasts and endothelial cells.
Heggers et al. [31] examined wound healing relative to irrigation and bactericidal properties of Sodium hypochlorite in vitro and in vivo models. They concluded that 0.025% sodium hypochlorite was the safest concentration to use because it was bactericidal but not tissuetoxic. Zhang et al. [32] evaluated the cytotoxicity of four concentrations of sodium hypochlorite (5.25%, 2.63%, 1.31%, and 0.66%), eugenol, 3% H 2 O 2 , Ca(OH) 2 paste and MTAD Results showed that toxicity of sodium hypochlorite was dose-dependent. Barnhart et al. [33] measured the cytotoxicity of several endodontic agents on cultured gingival fibroblast using the CyQuant assay. The results showed that IKI and Ca(OH)2 were significantly less cytotoxic than Sodium hypochlorite. Most complications of the use of sodium hypochlorite appear to be the result of its accidental injection beyond the root apex which can cause violent tissue reactions characterized by pain, swelling, hemorrhage, and in some cases the development of secondary infection and paresthesia [34].
A great deal of care should therefore be exercised when using sodium hypochlorite during endodontic irrigation. Ehrich et al. [35] suggested that a clinician should check, both clinically and radiographically for immature apices, root resorption, apical perforations or any other conditions that may result in larger than normal volumes of irrigant being extruded from the root-canal system into the surrounding tissue. Irrigation should be performed slowly with gentle movement of the needle to ensure that it is not binding in the canal. In an in vitro study by Brown et al. [36], the use of a reservoir of irrigation fluid in the coronal access cavity and carried into the root canal during filing resulted in significantly less apical extrusion of irrigation solution than with deep delivery with an irrigation needle.
Complication during irrigation: (review of literature represented in Table 5)

Extrusion beyond the root apex
During root canal irrigation, accidental extrusions can occur. Even minute quantities if extruded causes vaccular probabilities in blood vessels due to the damage to the vessels as well as release of chemical mediators such as histamine for the involved tissue. This causes immediate swelling and often profuse bleeding through the root canal.
In a case report, after wedging the irrigating needle into the root canal, 2.5% sodium hypochlorite was extruded beyond the apex of maxillary left central incisor. The patient experienced severe pain during irrigation of riot canal system so the root canal preparation was

Author
Year Findings Sen et al. [10] 1999 Evaluated antifungal properties of 1% NaOCl, and 5% NaOCl and 0.12 % CHx against candida albicans using cylindrical dentin tubes, and found that in absence of smear layer, candida albicans display antifungal activity after 30 minutes.
Ferguson et al. [11] 2002 Determined in-vitro susceptibility of candida albicans to various irrigants and medicaments, and found out that NaOCl , hydrogen peroxide were effective against candida albicans even when diluted.
Marcia et al. [12] 2009 Evaluated the action of NaOCl associated with an intracanal medicament against candida albicans and E.faecalis and found that 1% NaOCl irrigation were effective in eliminating E.faecalis and candida albicans.
Ruff et al. [13] 2006 Found that 6 % NaOCl was equally effective and statistically superior to Biopure MTAD and 17 % EDTA in antifungal activity Table 1: Antifungal activity.
Clegg et al. [15] 2006 Evaluated effectiveness of three concentrations of NaOCl (6,3,1.5%),2% CHX and biopure MTAD on apical denti film in vitro and found out 6% NaOCl was only capable of both rendering bacteria nonviable and physically remove the biofilm Ozok et al. [16] 2007 Compared growth and susceptibility of different concentrationsof NaOCl of mono and dual species biofilms of fusobacterium nucleatum in-vitro at 24 hrs and found out at 243hrs they were more resistant to NaOCl.
Giardino et al. [17] 2007 Evaluated efficiency of 5.25% NaOCl and MTAD against E.Faecalis biofilm and found that only 5.25% NaOCl can disgregate and biofilm every time.
Moorer et al. [19] 2003 Tissue dissolution was dependent on 3 factors-frequency of agitation,amount of organic matter in relation to amount of irrigant in system and surface area of tissue.
Clarkson et al. [22] 2006 Evaluated tissue dissolution ability of two concentrations of NaOCl on porcine incisor pulp and found greater concentrations provide more dissolution of tissue.

Marcus et al. [23] 2011
Evaluated the tissue dissolving capacity of various concentrations of NaOCl either alone or in combination of 17%EDTA and found that dissolution property was more with NaOCl alone. Showed that concentrations higher than 1mm, suppresses ADP dependent aggregations of blood platelets.

Murina et al. [26] 2006
Showed that anti-aggregant effects of NaOCl are probably due to the oxidation modification of sulphur containing groups in platelet plasmatic membrane. discontinued immediately and temporary dressing given. 3hrs later, the patient came back to clinic with an extended odema and ecchymosis over the left side of face, infraorbital region and upper lip mucosa. After removing the temporary filling, heavy bleeding from the canal was observed. The canal was biomechanically prepared by hand files with sterile saline solution irrigation. Antibiotics were prescribed against secondary infection and analgesics were also administered for pain control. Cold compress, warm mouth rinses was also advised on the first day. On the third day, pain and ecchymosis was reduced. By the 10 th day, no bleeding, pain, or ecchymosis was observed. By the 20 th day root canal obturation was performed.
Reeh and Messer reported on a case of injection of sodium hypochlorite (1%) through a midroot perforation of a maxillary central incisor. The patient experienced the typical symptoms of immediate severe pain and swelling, followed by fistulation and erythema extending to the infraorbital area. Paraesthesia of the floor and ala of the patient's nose persisted for more than 15 months. In a case report presented by Sabala and Powell 5.25% sodium hypochlorite was injected into the Periapical tissues of a left maxillary second premolar. The patient experienced symptoms of sudden, severe pain and a swelling rapidly developed, followed by ecchymosis of the skin. Root canal treatment was completed at the same appointment. To prevent secondary infection, antibiotics were prescribed and a surgical drainage performed. Nine days later the symptoms had resolved.
Management: Gentle irrigation of the affected eye with normal saline or tap water and then refer to the ophthalmologist.

Damage to oral mucosa
Sodium hypochlorite reacts with the protiens and fats of oral mucosa which might lead to secondary infections. The patient must be monitored with immediate treatment if swallowed.
Management: Rinse the oral mucosa with water. Analgesics and antibiotics must be prescribed to reduce secondary infection. Refer to emergency on inhalation or injestion.

Allergic reactions
Sodium hypochlorite allergic reactions results in urticaria, oedema, shortness of breath, bronchospasm and hypotension.
Management: Refer immediately to intensive care unit following first aid management with administration of intravenous steroids and antihistamines [50].

Signs and Symptoms
Prevention of sodium hypochlorite extrusion         Severe tissue damage and neurological deficit following extravasation of sodium hypochlorite solution during routine endodontic treatment.Severe facial edema following root canal treatmentThe chemical reactions of irrigants used for root canal debridement.

Conclusion
To conclude, sodium hypochlorite is an effective antibacterial agent but, when in contact with vital tissues it becomes a potential irritant causing tissue destruction. So, to prevent this, injudicious use should be avoided and by the use of a sealed rubber dam isolation during treatment, use of Leur lock needle for irrigation, maintain a minimum of 2 mm reduction from the working length, and avoiding wedging of needle into the canal and most importantly avoid excessive pressure during irrigation.
Although a safe root canal irrigating solution, its use may also lead to life-threatening complications [51][52][53][54][55]. So, to ensure best safe, long lasting clinical practice, it's essential to recognize and manage these complications. Patient with NaOCl extrusion followed endodontic treatment in maxillary first molar with excruciating pain, with blood stained fluid from left nostril; all managed by first ENT consultant for nasoscopy and then later root canal treatment completed.
Jonathan et al. [53] 2015 A patient with NaOCl extrusion followed perforation during rootcanal treatment in maxillary first premolar with swelling, bruising; pain was managed by i.v antibiotics, analgesics, steroids and then surgical intervention and finally full recovery was observed.
Bernardo et al. [54] 2014 A patient with NaOCl apical extrusion followed rootcanal returned in 24 hours with extreme pain, burning sensation in maxillary region with oedema and was managed by amoxicillin 500mg orally for 7 days then dexamethasone 4mg I.M. for 3days. Symptoms subsided after 8 months.