Review Article Sodium Hypochlorite Accident: A Systematic Review Maud Guivarc’h, DDS, MSc,*† Ugo Ordioni, DDS,*‡ Hany Mohamed Aly Ahmed, BDS, HDD (Endo), PhD,§ Stephen Cohen, MA, DDS, FICD, FACD,k Jean-Hugues Catherine, DDS, MSc,*¶ and Frederic Bukiet, DDS, MSc, PhD*# Abstract Introduction: Sodium hypochlorite (NaOCl) extrusion beyond the apex, also known as ‘‘a hypochlorite accident,’’ is a well-known complication that seldom occurs during root canal therapy. These ‘‘accidents’’ have been the subject of several case reports published over the years. Until now, no publication has addressed the global synthesis of the general and clinical data related to NaOCl extrusion. The main purpose of this article was to conduct a systematic review of previously published case reports to identify, synthesize, and present a critical analysis of the available data. A second purpose was to propose a standardized presentation of reporting data concerning NaOCl extrusions to refine and develop guidelines that should be used in further case report series. Methods: A review of clinical cases reporting NaOCl accidents was conducted in June 2016 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist; it combined an electronic search of the PubMed database and an extensive manual search. Results: Forty full-text articles corresponding to 52 case reports published between 1974 and 2015 were selected. Four main categories of data were highlighted: general and clinical information, clinical signs and symptoms of NaOCl extrusions, management of NaOCl extrusions, and healing and prognosis. Overall, up to now, clinical cases were reported in a very unsystematic manner, and some relevant information was missing. Conclusions: A better understanding of the potential causes, management, and prognosis of NaOCl accidents requires a standardization of reported data; this study proposes a template that can fulfill this objective. (J Endod 2017;43:16–24) Key Words Apical extrusion, endodontics, irrigant, review, sodium hypochlorite S odium hypochlorite Significance (NaOCl), because of Knowledge on hypochlorite extrusions during endits antimicrobial properodontic treatment is primarily based on previously ties and tissue-dissolving published case reports. A new proposal is introcapabilities, has been duced to provide better standardization of data reused as the irrigant of porting, which can pave the way for more choice for cleaning root systematic identification of etiology and prevention canals in endodontic theror, if necessary, management and prognosis of apy (1). When confined to NaOCl accidents. the root canal system, these properties enable thorough disinfection. Until now, no other solution has matched the efficacy of NaOCl. However, cytotoxic activity is a well-known shortcoming of NaOCl that may cause acute injuring effects if it reaches the periapical area. In contact with vital tissues, NaOCl quickly oxidizes surrounding tissues leading to rapid hemolysis and ulceration, inhibition of neutrophil migration, and destruction of endothelial and fibroblast cells (2). NaOCl extrusion during root canal therapy (RCT) is commonly referred to as ‘‘the hypochlorite accident’’; it causes acute immediate symptoms and potentially serious sequelae (3). The frequency of such events remains unknown because it is not systematically reported to insurance companies and cannot be diagnosed retrospectively. Considering the millions of RCTs performed all over the world, it is believed to be a relatively rare occurrence. However, 1 study showed that almost half of endodontic practitioners described the occurrence of at least 1 NaOCl accident in their career (4). In a study reviewing the factors affecting NaOCl extrusion during RCT, the authors concluded that the literature did not allow establishing reliable conclusions but rather led to speculation regarding the risk factors (5). To the best of our knowledge, and up to this date, no publication has provided a global synthesis of the general and clinical data related to NaOCl extrusions. The main aim of this study was to conduct a systematic review focused on previously published case reports to identify, synthesize, and present a critical analysis of available data on hypochlorite accidents. A second purpose was to propose a standard presentation of reported data concerning NaOCl extrusions that could be used in case report series. Developing systematic documentation that can be adapted universally may pave the way to a better understanding of the factors related to NaOCl extrusion and its consequences as well as proper guidelines for optimizing subsequent management strategies. From the *UFR Odontologie de Marseille, Aix-Marseille Universite, Assistance Publique des H^opitaux de Marseille, France; †UMR 7268-ADES Aix-Marseille Universite-EFS-CNRS, Faculte de Medecine de Marseille, France; ‡Centre Massilien de la Face, Marseille, France; §School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; kArthur A Dugoni School of Dentistry, University of the Pacific, San Francisco, California; ¶UMR 7268-ADES Aix-Marseille Universite-EFS-CNRS, Faculte de Medecine de Marseille, France; and #Giboc, ISM UMR 7287 CNRS, Aix Marseille Universite, Marseille, France Address requests for reprints to Dr Maud Guivarc’h, 19 rue Henri Ch^eneaux, 13008, Marseille, France. E-mail address: maud.guivarch@gmail.com 0099-2399/$ - see front matter Copyright ª 2016 American Association of Endodontists. http://dx.doi.org/10.1016/j.joen.2016.09.023 16 Guivarc’h et al. JOE — Volume 43, Number 1, January 2017 Review Article Results surrounding the buccal roots of maxillary teeth could be 2 contributing factors enabling the spread of NaOCl into the surrounding soft tissues (4, 5). Half of the retrieved data did not provide information on the patients’ health status or the initial pulpal and periapical status. It is worth noting that these parameters may constitute additional risk factors and may impact the severity of the complications (4). The toxicity of NaOCl is mainly caused by its chemical composition, but other factors such as the concentration, volume, and pressure of extrusion could exacerbate the consequences of these accidents (47). The volume of NaOCl extruded was provided in only 5 reports. However, the reliability of this information remains unclear. Unfortunately, the NaOCl concentration was mentioned in only half of the cases (30/52) even though this is essential information. From what we could glean from the articles that did mention the concentration of NaOCl, it ranged from 1%–5.25%. No information on how the solution was obtained (ie, pharmaceutical preparation or over-the-counter purchase) was provided. A few reports (10/52) provided information about the irrigation method, needle design, and syringe capacity, which play a significant role in the strength of the irrigant flow (48, 49). Information related to rubber dam usage, which does not directly influence NaOCl extrusions, was present in 20 of 52 cases. The hypothesis of potential factors having favored the occurrence of irrigant extrusion was present in only 29 of the 52 cases. Factors such as open apices, either iatrogenic or anatomic (7, 15, 21, 23, 32, 33, 37, 39); undiagnosed perforation (8, 10, 13, 15, 18, 28–30, 35, 46); needle wedging (17, 44); and close approximation with surrounding structures such as an antral tooth (10, 12, 24, 41) may have facilitated NaOCl extrusion. General and Clinical Information The patients’ sex and tooth scheduled for treatment were always specified (Table 1). The occurrence of NaOCl extrusions was mainly reported in females (44/52) and maxillary teeth (41/52). The predominance of these 2 categories in cases reports was consistent with previously experienced NaOCl extrusions by endodontists (4). Despite the lack of scientific evidence, it seems that the decrease of bone density in women compared with men and the thinness of cortical bone Manifestations of NaOCl Extrusion The description of the symptoms after NaOCl extrusion was shown to be acute and of sudden onset (Fig. 2). Severe pain was almost systematic (45/52) even though the patients were anesthetized (36). Profuse hemorrhaging through the root canal was reported in one third of the cases (17/52). Swelling occurred in almost every case (49/52), Materials and Methods In June 2016, a literature search was performed on clinical cases reported on hypochlorite accidents according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist (6) (Fig. 1). An electronic search of the PubMed database (1950-present) was conducted using 5 combinations of the following key words: [SODIUM HYPOCHLORITE], [IRRIGANT], [EXTRUSION], [ACCIDENT], [COMPLICATIONS], and [ENDODONTICS]. A manual search of the Journal of Endodontics (1975-); International Endodontic Journal (1980-); Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics (1995-2011); Australian Endodontic Journal (1982-); British Dental Journal (1970-); and Journal of the American Dental Association (1910-) was performed. Furthermore, the references listed in the retrieved full-text articles were reviewed to identify additional publications. After the removal of duplicate publications, title review, and abstract selection, 57 articles were screened to fulfill the inclusion criteria as follows: 1. Indexed case reports from peer-reviewed journals written in English and 2. A hypochlorite accident occurring during canal irrigation with the full text available. Records identified through PubMed database searching (n=228) Screening Identification Finally, 40 full-text articles corresponding to 52 cases reports published between 1974 and 2015 were selected and reviewed by the authors. Two different reviewers (M.G. and U.O.) independently identified and categorized the available information in the publications. Additional records identified through other sources (n=28) Records after duplicates removed (n=231) Eligibility Full-text articles assessed for eligibility (n=57) Included Records screened (n = 231) Studies included (n=40) Records excluded (n=174) Full-text articles excluded according to exclusion criteria (n=17) Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of the systematic review process (meta-analysis was not performed). JOE — Volume 43, Number 1, January 2017 Sodium Hypochlorite Accident 17 General and clinical information Guivarc’h et al. Author(s), y JOE — Volume 43, Number 1, January 2017 Becker et al, 1974 (7) Reeh and Messer, 1989 (8) Sabala and Powell, 1989 (9) Becking, 1991 (10) Becking, 1991 (10) Becking, 1991 (10) Gatot et al, 1991 (11) Ehrich et al, 1993 (12) Linn and Messer, 1993 (13) Tosti et al, 1996 (14) Tosti et al, 1996 (14) € lsmann et al, 2000 (15) Hu € lsmann et al, 2000 (15) Hu Mehra et al, 2000 (16) Balto et Al-Nazhan, 2002 (17) Gernhardt et al, 2004 (18) Witton et al, 2005 (19) Witton et al, 2005 (19) Bowden et al, 2006 (20) Keçeci et al, 2006 (21) Keçeci et al, 2006 (21) Crincoli et al, 2008 (22) Pelka et Petschelt, 2008 (23) Zairi and Lambrianidis, 2008 (24) ~ o et al, 2009 (25) de Sermen Markose et al, 2009 (26) Lam et al, 2010 (27) Wang et al, 2010 (28) Wang et al, 2010 (28) Chaudhry et al, 2011 (29) Chaudhry et al, 2011 (29) Chaudhry et al, 2011 (29) Chaudhry et al, 2011 (29) Lee et al, 2011 (30) Tegginmani et al, 2011 (31) Behrents et al, 2012 (32) Bosh-Aranda et al, 2012 (33) Bosh-Aranda et al, 2012 (33) Paschoalino et al, 2012 (34) Bither and Bither, 2013 (35) Kandian et al, 2013 (36) Klein and Kleier, 2013 (37) Zhu et al, 2013 (38) Aguiar et al, 2014 (39) Goswami et al, 2014 (40) Goswami et al, 2014 (40) Information on Sex Age medical context F F M F F M F M F F F M M F F F F F F F F F F F F F F F F F F F F F F F F F F M F M F F F M 23 44 58 42 31 29 32 22 33 49 46 55 — 55 17 49 43 44 45 35 41 32 58 32 69 46 37 59 69 59 63 26 38 25 31 32 43 53 24 65 62 2 52 28 14 13 A A A — — — — A A — — — — A A — A — — — A A A A A — A — — — — — — A A A A — — A A A A — A — Tooth 13 11 25 37 27 35 11 16 13 14 12 or 22 23 43 63 11 34 12 15 37 22 21 13 22 15 13 16 13 23 47 34 23 21 34 21 21 25 26 24 16 15 13 51/61 14 24 36 36 NaOCl Information on concentration NaOCl Information on Pulp Periapical favoring factor (%) quantity equipment suspected Dam Practitioner status Lesion V NV NV — — — NV NV — — — — — — NV V NV — — NV NV NV NV NV — — V NV V — — — — NV NV — — — V V NV V V V — — No Yes Yes — — — — No — — — — — — Yes No Yes — — Yes No No Yes No — — No Yes No — — — — Yes Yes No — — No No Yes No No No — No A A — A A — — A A — — A A — A A — — — A A — A A — — — A — A — — — A — A A A A A — A — A A — Yes Yes Yes No — — — Yes — — — — — — Yes Yes Yes — — No No — Yes Yes Yes — — Yes Yes — — — No — — — — — — — — No Yes — No — DS DS EC GP — — — EC GP — — — — — DS DS GP — — DS DS — GP GP GP GP GP GP GP GP GP GP GP — DS GP GP — EC GP GP — EC GP GP GP 5.25 1 5.25 — — — — 5.25 — — — 3 3 — 1 5.25 UKN — — 2.5 2.5 — 3 2.5 5 5.5 — 2.5 2.5 5.25 2 2 — — 3 3 — — 1 — 2 2.5 5.25 2.5 — — 0.5 mL 1–2 mL — — — — — — — — — — 1 mL — 1.5 mL — — — — — — — — — — — — — — 1 mL — — — — — — — — — — — — — — — — A — — — — — — A — — — — — — — A — — — — — — — A — — — A A — — — — — — — — — — — — A A A — — Review Article 18 TABLE 1. A Summary of Reports for General Health, Clinical Information, and Irrigation Procedures JOE — Volume 43, Number 1, January 2017 appearing within a few minutes up to a few hours after the accident. Swelling was usually large and diffuse (similar to cellulitis), extending intra- and extraorally well beyond the site of the affected tooth; it sometimes resulted in difficulties opening the ipsilateral eye (17, 25, 31). When these extrusions involved the maxillary sinus, the immediate effect indicated a different clinical picture (12, 24, 41). Rather than acute pain, the first signs were irrigant flowing from the nostrils along with the taste of NaOCl in the throat. A burning sensation in the maxillary sinus rather than severe pain was usually present, with little or no bleeding from the canal and no evidence of immediate swelling. NaOCl extrusion within the sinus might also lead to epistaxis and sinus congestion. These less severe symptoms might be because NaOCl was not extruded in an enclosed space, which allowed its evacuation, thus limiting the time of contact (12). The subsequent symptoms in the hours and days after extrusion were generally well-documented. Hemolysis was responsible for profuse interstitial bleeding, probably causing immediate or secondary facial hematomas (30/52), although the latter were not systematic (32). Mucosal and bone necrosis were reported as a result of the chemical burn caused by NaOCl (15/52), sometimes accompanied by a purulent discharge (35). Three cases of apical secondary infection involving purulent discharge were described (10, 11, 25). Contact with NaOCl is highly toxic to vital tissues, including nerves (2). Consequently, neurologic signs such as sensory and/or motor defects after extrusion can be expected and were present in 17 of 52 patients. Residual anesthesia and/or paresthesia occurred when the trigeminal nerve was affected (8–11, 13, 15, 19, 23, 25, 27, 29, 33, 44). Cases of facial nerve damage involving paralysis of the mimic musculature were also described (19, 23). Trismus was reported and frequently associated with NaOCl extrusion on maxillary teeth (5/ 7 cases). Air emphysema-like symptoms after NaOCl extrusion also occurred, with patients showing crepitus (25, 45). Cone-beam computed tomographic imaging was used to explore radiographic manifestations of NaOCl extrusion on 1 maxillary premolar tooth whose apex was close to the soft tissues (32). Air bubble appearance areas were noted throughout the soft tissues, but the authors concluded that it was not possible to determine if these radiolucent structures were full of air or fluid. Ophthalmologic symptoms may be present including eye pain, blurring of vision, diplopia, and right corneal patchy coloration. These constellations of signs/symptoms were described emanating from a maxillary central incisor (11) and canine (36). Moreover, 2 patients presented with life-threatening airway obstruction caused by massive swelling in the submental and sublingual spaces with elevation of the floor of the mouth after extrusion through the mandibular teeth (20, 42). Indicators of the severity of these extrusions included difficulties in swallowing followed by respiratory distress. 60 50 Number of cases —, unavailable information; A, available information; DS, dental school; EC, endodontic clinic; F, female; GP, general practitioner; M, male; NaOCl, sodium hypochlorite; NV, nonvital; V, vital. Laverty, 2014 (41) Al-Sebaei et al, 2015 (42) Başer Can et al, 2015 (43) Bramante et al, 2015 (44) Chaugule et al, 2015 (45) Hatton et al, 2015 (46) F F F F F F 37 42 56 56 4 66 — A — A — A 26 41 24 11 64/65 14 NV — NV NV V — Yes — Yes Yes No No A — A A — A — Yes — — — — GP DS GP DS DS GP 2 3 — 1 3 — — — — — — — — — — A — — Review Article 40 30 20 10 0 Yes No/US Figure 2. Clinical manifestations of NaOCl extrusions. US, unspecified. Sodium Hypochlorite Accident 19 Management and follow-up Guivarc’h et al. Immediate local gesture Author(s), y JOE — Volume 43, Number 1, January 2017 Becker et al, 1974 (7) Reeh and Messer, 1989 (8) Sabala and Powell, 1989 (9) Becking, 1991 (10) Becking, 1991 (10) Becking, 1991 (10) Gatot et al, 1991 (11) Ehrich et al, 1993 (12) Linn and Messer, 1993 (13) Tosti et al, 1996 (14) Tosti et al, 1996 (14) € lsmann et al, 2000 (15) Hu € lsmann et al, 2000 (15) Hu Mehra et al, 2000 (16) Balto and Al-Nazhan, 2002 (17) Gernhardt et al, 2004 (18) Witton et al, 2005 (19) Witton et al, 2005 (19) Bowden et al, 2006 (20) Keçeci et al, 2006 (21) Keçeci et al, 2006 (21) Crincoli et al, 2008 (22) Pelka and Petschelt, 2008 (23) Zairi and Lambrianidis, 2008 (24) ~ o et al, 2009 (25) de Sermen Markose et al, 2009 (26) Lam et al, 2010 (27) Wang et al, 2010 (28) Wang et al, 2010 (28) Chaudhry et al, 2011 (29) Chaudhry et al, 2011 (29) Chaudhry et al, 2011 (29) Chaudhry et al, 2011 (29) Lee et al, 2011 (30) Tegginmani et al, 2011 (31) Behrents et al, 2012 (32) Bosh-Aranda et al, 2012 (33) Bosh-Aranda et al, 2012 (33) Paschoali et al, 2012 (34) Bither and Bither, 2013 (35) Kandian et al, 2013 (36) Klein and Kleier, 2013 (37) Zhu et al, 2013 (38) Aguiar et al, 2014 (39) Goswami et al, 2014 (40) Goswami et al, 2014 (40) Canal Tooth Anesthesia irrigation closed U U U U U U U U U U U U U U U U U U U U U U U U U Postextrusion medical and local treatment Other Surgical drain ICM ICM Surgical drain U U U U Surgical drain U UT UP UC UP/M U U U U U UP/M UP Sinus irrigation UP U ICM UP U U U U U U U ATB Time for Cold Warm Mouth Surgical signs of PK AIS AH packs packs rinses treatment Hospitalization regression Sequelae UP UM UT UP UP UP/M UP UP U U UM U U UP UP UP U U U U UP UP/M UM UP UP UP U UP UP UP UP UP U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U 21 d 21 d 9d 60 d 14 d >30 d 14 d 28 d <21 d 7d 21 d 7d 60 d 42 d 4d 14 d 30 d 90 d 30 d 15 d 10 d 15 d 30 d 4d 15 d 30 d 30 d 14 d 21 d NA 90 d 90 d 90 d 7d 90 d 6d 14 d 14 d 14 d 14 d >14 d 42 d 21 d 21 d 21 d 28 d UN UF UN + F UN UN UF UN + F UN + F UN UN UN Review Article 20 TABLE 2. A Summary of Reports for Management and Follow-up Review Article U U, yes; AH, antihistamines; AIS, anti-inflammatory steroids; ATB, antibiotics; C, cyclin; F, tissue fibrosis; ICM, intracanal medication; M, macrolide; N, neurologic; NA, not applicable; P, penicillin; PK, painkillers; T, tetracycline. U U U U U U U U Laverty, 2014 (41) Al-Sebaei et al, 2015 (42) Başer Can et al, 2015 (43) Bramante et al, 2015 (44) Chaugule et al, 2015 (45) Hatton et al, 2015 (46) U U U U UP UC UM UP UP UP U U U U U U U U U U U U U U U 7d 21 d 10 d 28 d 7d NA UN Emergency hospitalization in an intensive care unit was required in these situations. JOE — Volume 43, Number 1, January 2017 Management of NaOCl Extrusions In the first reported case on NaOCl extrusions, it was stated that the treatment should be palliative and protective (7). This article also described early management, which included minimizing the exquisite pain and hemorrhage control as well as patient’s reassurance, and close follow-up in the hours and days after the accident (Table 2). In order to gain rapid pain relief, anesthetic infiltration had been attempted (9, 15, 23). However, local anesthesia usually will cause additional pressure in the soft tissues with little benefit. In the presence of diffuse swelling, infiltration anesthesia is contraindicated to avoid spreading of any existing infection (17); a nerve block should be used instead (47). Very little information was provided regarding the use of vasoconstrictors and the location of the injection attempted for pain relief. Theoretically, vasoconstrictors might limit the diffusion of NaOCl, but this would likely increase the risk of promoting tissue necrosis, especially with highly concentrated solutions promoting local ischemia (50). One third of the cases (18/52) indicated immediate canal irrigation after extrusion, mostly using a saline solution. The use of chlorhexidine (CHX) instead of saline was also reported (23). However, this should be avoided to prevent the formation of a potential toxic precipitate, which can occur upon combination with NaOCl (51). In a NaOCl extrusion related to deciduous incisors, the use of lidocaine with 1:100,000 epinephrine as a rinse solution was described to stop bleeding from the canals, but the procedure was unsuccessful (37). It has been postulated that continuous canal irrigation would reduce the severity of acute tissue responses by diluting the NaOCl (3, 14, 35, 47); however, this speculation is questionable. Indeed, it is clear that unless solution is forced into periapical tissues (as the NaOCl had been), this procedure would fail. Moreover, introducing more liquids into the canal may prevent the primary phase of NaOCl drainage. Bleeding should not be prevented, and aspiration with a high-volume aspirator would help to evacuate NaOCl. Because the bleeding is usually profuse, paper point usage and microtips placed over the access opening would clearly be ineffective. Information indicating whether a tooth was closed or left open after the extrusion was missing in more than half of the cases (34/52). However, some articles reported worsening of the clinical situation after what seemed to be untimely tooth closing with root canal dressing (17, 21, 28, 32) or even filling with gutta-percha (9, 15, 16, 30). These situations were mostly associated with an initial misdiagnosis of the extrusion. Reports showed that post-treatment instructions included frequently applying extraoral cold packs on the day of the extrusion to minimize edema (19/52). Some authors recommended that it could be followed by the application of warm compresses (8/52) and warm saline rinses (5/52). The latter intended to stimulate microcirculation in order to prevent tissue necrosis and accelerate healing. In a few cases, incision and drainage were performed on the day of the extrusion or soon afterward (9, 17, 32) and were sometimes combined with a rubber drain insertion (9), a decompression of the hematoma (16, 20), or a surgical debridement of necrotic tissues (11, 16, 29, 30, 35). Apical surgery was also performed in 3 cases with no real justification (8, 9, 30). As an adjunct to conventional treatment, low-intensity laser therapy over the necrotic area was performed in 1 case. The authors observed favorable repair although no scientific evidence exists to support this assumption (44). Sodium Hypochlorite Accident 21 Review Article Figure 3. A Proposed Template for Recording Data after Sodium Hypochlorite Extrusion. Prescriptions were mostly analgesics, antibiotics, and steroids. Drugs containing paracetamol (ie, acetaminophen) appeared to be the most commonly used analgesic and were sometimes combined with codeine. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was also reported (18, 32, 34, 36, 41, 43, 45). The association between paracetamol and NSAIDs (acetaminophen + ibuprofen) has been shown to be very effective in pain control (52). NSAIDs should be prescribed in an analgesic dosage (ie, no more than 1200 mg a day for a maximum of 5 days) in the presence of a hemorrhagic condition associated with an increased risk of infection (40). Antibiotics were almost systematic (45/52); however, the active ingredients were not always specified. Penicillin was the drug of choice when there was no history of allergy, but it was sometimes combined with clavulanic acid (25/52) or macrolide (4/52). Macrolides alone (17, 24, 32, 43), tetracycline (7, 18), and cephalosporin (9, 42) were prescribed anecdotally. The risk of spreading infection or an impaired immune system should be the criterion for prescribing antibiotics (3, 15). Steroids were prescribed in many of the reports after the NaOCl injury (28/52). Antihistamines were prescribed in some reports with the expectation that they would limit the extension of edema (22, 31, 45). It was theorized that the acute inflammatory response involves the release of chemical mediators such as histamine, which increases vascular permeability (53). Additionally, a nasal decongestant was prescribed when the maxillary sinus was involved (12, 24, 41). Most of the time, postextrusion management was ambulatory using only oral medications. However, about one third of patients (18/52) were hospitalized for monitoring and intravenous administration of drugs. Healing and Prognosis The literature shows considerable variations in the healing process and duration of this undesirable event; it generally took a few weeks for patients to recover from the initial signs and lingering symptoms (pain, edema, hematoma, and tissue necrosis). The shortest healing time was for a case that had involved the sinus; the tooth and surrounding tissues 22 Guivarc’h et al. were asymptomatic with normal contours and color only 4 days after the NaOCl extrusion (24). However, the pain and swelling could last up to 30 days (10, 19, 23) and possibly longer; 1 report documented that it took up to 4 months for the swelling to resolve (26). Mucosal healing could take up to 60 days (15). In some cases, it resulted in fibrosis and scar tissue (10, 11), possibly leading to a disfiguring scar (27, 29). The use of an alternative nonirritating solution (saline or CHX) for future irrigation was sometimes recommended when completing endodontic treatment (3, 23, 33, 39, 40). However, this step does not seem clinically pertinent for several reasons: the reason for the extrusion should always be determined to prevent a recurrence, CHX lacks the tissue dissolving effect, and the concentration of CHX recommended for endodontic use is cytotoxic (54) and may cause similar effects to NaOCl if extruded (55). Extraction of the affected tooth was performed in 7 cases for unspecified reasons (16, 26), a nonretainable tooth (35–37), persistent pain (33), and the patient refusing to complete the endodontic treatment that had been started (41). Of the 17 cases describing initial nerve damage, 8 patients presented with altered sensitivity and/or motor impairment at or after the 1-year follow-up (8, 11, 15, 23, 27, 29, 33). One patient was diagnosed with residual neuropathic pain (29). In some reports, the follow-up period was too short to assess the degree of recovery (11, 27, 46). Discussion This systematic review aimed to identify and classify the data presented in numerous case reports and to provide a critical assessment of all the extant literature. By analyzing 52 case reports, 4 main categories were highlighted: general and clinical information, clinical signs and symptoms resulting from NaOCl extrusion, management of NaOCl extrusions, and healing and prognosis. Reports, up to this date, provide an uneven overview of the symptoms, management strategies, possible complications, and prognosis. Overall, the literature shows that clinical cases were reported in an unsystematic manner, and some relevant information was missing. JOE — Volume 43, Number 1, January 2017 Review Article Sudden pain, profuse bleeding, and almost immediate swelling constitute a triad of signs/symptoms pathognomonic of NaOCl extrusion. Ignorance of an accurate diagnosis and proper patient management when a NaOCl accident occurs could lead to an unnecessary delay and sometimes even panic. Indeed, some practitioners chose to perform the endodontic treatment subsequent to the NaOCl extrusion despite patient suffering (21, 28, 42) or even to complete the root canal filling (9, 15, 16, 30, 41) when all signs and symptoms converged to deduce it was an NaOCl accident. Some articles reported no or improper and untimely immediate management and monitoring after extrusion, leading to emergency consultations with colleagues or physicians contacted by patients feeling in dire straits (9, 13, 19, 29, 46). The management of NaOCl extrusions appeared to be very empirical. All or most of the signs and symptoms resolved within a few weeks. Permanent sequelae could be divided into nerve lesions and scar tissues. Neurologic examination of the trigeminal and facial nerves should systematically be performed once anesthesia has dissipated. Tooth loss has not been reported as a direct result of NaOCl extrusion, but it may be involved. The latter is a real trauma for the patient, and it can lead to subsequent refusal to achieve the endodontic treatment. Exploring the factors enabling NaOCl extrusions and/or influencing the severity of complications would require more clinical data (pre-, peri-, and postoperative) as well as general and medical information on the patient. However, the latter was scarce. This conclusion is in accordance with the work of Boutsioukis et al (48), which only considered factors suspected to enable irrigant extrusion. Incomplete information could be explained by the fact that most cases were reported by a secondary team whose essential role was postaccident management rather than by the treating practitioner. Considering all these elements, we propose that future case reports should require the following: information about the patient and the affected tooth, the irrigation method, the immediate extrusion signs/symptoms, the management and etiology of the accident, and the postextrusion monitoring and prognosis. Standardization of these data would avoid incomplete information because of omission. Moreover, it would facilitate comparison among different case reports and enable universal guidelines for avoiding or managing NaOCl emergencies. The present study proposes a template that can fulfill this objective and paves the way for better understanding of the factors, management, and prognosis of hypochlorite accidents (Fig. 3). Conclusions The NaOCl accident is a serious complication that requires prompt attention by dental practitioners. 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