Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 695 are immunocompromised. The usual oral dosage for PROPHYLACTIC ANTIBIOTICS amoxicillin with clavulanate is 1,000-mg loading dose FOR MEDICALLY COMPROMISED followed by 500 mg every 8 hours. An alternate dosage PATIENTS is 875 mg every 12 hours. Erythromycin has traditionally been the alternative Prophylactic antibiotic coverage may be indicated choice for patients allergic to penicillin, but it is not for medically compromised patients requiring endo- effective against anaerobes associated with endodontic dontic treatment. The American Heart Association infections. Clarithromycin and azithromycin are (AHA) and the American Academy of Orthopaedic Surgeons have made guidelines for prophylactic anti- macrolides like erythromycin, with some advantages 23,24 over the latter. They have a spectrum of antimicrobial biotic coverage. The guidelines are meant to aid activity that includes facultative bacteria and some practitioners but are not intended as the standard of anaerobic bacteria associated with infections of endo- care or as a substitute for clinical judgment. The dontic origin. They also have less gastrointestinal upset incidence of endocarditis following most procedures than erythromycin. The oral dosage for clarithromycin on patients with underlying cardiac disease is low (see is a 500-mg loading dose followed by 250 mg every 12 Chapter 7 ‘‘Microbiology of Endodontic Disease’’). hours. The oral dosage for azithromycin is a 500-mg A reasonable approach for prescribing prophylactic loading dose followed by 250 mg once a day. antibiotics considers the degree to which the underlying Clindamycin is effective against both facultative disease creates a risk for endocarditis, the apparent risk and strict anaerobic bacteria associated with endo- for producing a bacteremia, adverse reactions to the prophylactic antibiotic, and the cost-benefit aspect of dontic infections. It is well distributed throughout 23 the body, especially to bone, where its concentration the regimen. Antibiotic prophylaxis is employed to approaches that of plasma. Both penicillin and clin- prevent surgical infections or their postoperative seque- lae, to prevent metastatic bacteremias, and to prevent damycin have been shown to produce good results in 25 treating odontogenic infections.4,5,20 Clindamycin is accusation that ‘‘all was not done for the patient.’’ It is suspected that antibiotic prophylaxis is often prescribed rapidly absorbed even in the presence of food in the 25 stomach.21 The oral adult dosage for serious endo- to prevent malpractice claims. dontic infections is a 600-mg loading dose followed How antibiotics quickly kill bacteria in the blood is by 300 mg every 6 hours. difficult to answer when many antibiotics are only Metronidazole is a nitroimidazole that is active effective with actively dividing bacteria. It is speculated against parasites and anaerobic bacteria. However, it that antibiotics may reduce metastatic infections by 4,5,22 preventing adhesion of bacteria to tissues or inhibiting is ineffective against facultative bacteria. It is a 26 valuable antimicrobial agent in combination with growth after attachment. The principles of antibiotic penicillin when penicillin alone has been ineffective.22 prophylaxis state that the antibiotic must be in the The usual oral dosage for metronidazole is a 1,000-mg system prior to an invasive procedure. If a patient has loading dose followed by 500 mg every 6 hours. Con- not taken the prescribed antibiotic, he or she should be sultation with, and referral to other specialists in the rescheduled or wait an hour after administration of the management of facial infections, is indicated for antibiotic for treatment. However, there is data to support the use of an antibiotic up to 2 hours after severe or persistent infections. 25 Cephalosporins are usually not indicated for the the onset of bacteremia. treatment of endodontic infections. First-generation The incidence of bacteremia has been shown to be cephalosporins do not have activity against the anae- low during root canal therapy. A transient bactere- robes usually involved in endodontic infections. mia can result from the extrusion of microorganisms from the root canal to the periapical tissues of the Second-generation cephalosporins have some efficacy 27–31 for anaerobes, however, there is a possibility of cross- tooth. In addition, positioning rubber dam allergenicity of cephalosporins with penicillin. clamps and accomplishing other dental procedures Doxycycline occasionally may be indicated when the may produce bleeding and can lead to a bacteremia. above antibiotics are contraindicated. However, many strains Medically compromised dental patients who are at of bacteria have become resistant to the tetracyclines. risk of infection should receive a regimen of antibio- Ciprofloxacin is a quinilone antibiotic that is not tics that either follows the recommendations of the AHA or an alternate regimen determined in consul- effective against anaerobic bacteria usually found in 23 endodontic infections. With a persistent infection, it tation with the patients’ physicians. Chapter 24 may be indicated if culture and sensitivity tests gives the antibiotic regimens recommended for demonstrated the presence of susceptible organisms. dental procedures. It is believed that amoxicillin, 696 / Endodontics ampicillin, and penicillin V are equally effective tooth with a rubber dam and disinfecting the tooth against alpha-hemolytic streptococci; however, surface and rubber dam with sodium hypochlorite amoxicillin is recommended because it is better or other disinfectant. Sterile burs and instruments absorbed from the gastrointestinal tract and provides must be used to gain access to the root canal system. higher and more sustained serum levels.23 Intracanal irrigation should not be used until after For cardiac conditions associated with endocarditis, the microbial sample has been taken. If there is prophylaxis is recommended for both non-surgical drainage from the canal, it may be sampled with a and surgical endodontic procedures.23 Antibiotic pro- sterile paper point or aspirated into a sterile syringe phylaxis is recommended for cardiac conditions asso- with a sterile 18- to 25-gauge needle, depending on ciated with endocarditis at a high or moderate risk the viscosity of the exudate. The aspirate should category (see Chapter 24). Dental procedures for either be taken immediately to a microbiology which antibiotic prophylaxis is recommended (see laboratory in the syringe or injected into pre- Chapter 24) include endodontic instrumentation reduced transport media. To sample a dry root beyond the apex or surgery, but not intracanal endo- canal, a sterile syringe should be used to place some dontic treatment, post-placement and buildup.23 pre-reduced transport medium into the canal. A From a practical standpoint, it is difficult to deter- sterile endodontic instrument is then used to scrape mine with certainty that endodontic instruments do the walls of the canal to suspend microorganisms not pass beyond the apical foramen. Also included for into the medium. prophylaxis antibiotics is intraligamentary period- To prevent contamination by the normal oral flora, ontal ligament (PDL) local anesthetic injections, but a microbial sample from a soft tissue swelling should not non-intraligamentary ones.23 be obtained before making an I&D. Once profound In 2003, a joint committee of the American Dental anesthesia is achieved, the surface of the mucosa Association and American Academy of Orthopaedic should be dried and disinfected with an iodophor Surgeons published their first advisory statement on swab. A sterile 16- to 20-gauge needle and syringe is antibiotic prophylaxis for patients with prosthetic used to aspirate the exudate. The aspirate should be joints. The dental procedures of concern and the handled as described above. A sample can be collected antibiotic regimens are the same as for endocarditis on a swab after the I&D has been made, but great care Chapter 24. Patients of potential increased risk of must be taken to prevent microbial contamination having a hematogenous total joint infection include with normal oral flora. After collecting the specimen all patients during the first 2 years following joint on a swab, it should be quickly placed in pre-reduced replacement, immunocompromised/immunosuppressed medium for transport to the laboratory. patients, and patients with comorbidities as shown in Good communication with the laboratory personnel Chapter 24.32 is important. The sample should be Gram-stained to demonstrate which types of microorganisms predomi- nate. The culture results should show the prominent COLLECTION OF A MICROBIAL SAMPLE isolated microorganisms and not just be identified as Adjunctive antibiotic therapy for endodontic infec- ‘‘normal oral flora.’’ Antibiotics can usually be chosen tions is most often prescribed empirically based on to treat endodontic infections based on the identifica- knowledge of the bacteria most often associated tion of the prominent microorganisms in the culture. with endodontic infections. At times, culturing With persistent infections, susceptibility testing can be may provide valuable information to better select undertaken to establish which antibiotics are the most theappropriateantibioticregimen.Forexample,an effective against resistant microbial isolates. At present, immunocompromised/immunosuppressed patient it may take 1 to 2 weeks to identify anaerobes using (not immunocompetent) or patients at high risk conventional methods. Some laboratories may have of developing infections (e.g., history of infective molecular methods available to rapidly detect and endocarditis) following a bacteremia require close identify known opportunistic bacteria. monitoring. These patients may have an infection caused by bacteria usually not associated with the oral cavity. Other examples include a seemingly CORTICAL TREPHINATION healthy patient who has persistent or progressive Cortical trephination is defined as the surgical perfora- symptoms following surgical or non-surgical endo- tion of the alveolar cortical plate to release accumulated dontic treatment. An aseptic microbial sample tissue exudates.1 Its use is indicated for patients with from a root canal is collected by first isolating the severe pain of endodontic origin without intraoral or Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 697 extraoral swelling and when drainage cannot be accom- alveolar bone, the use of a surgical high speed round bur plished through the root canal, for example, in the to access the involved root apex and abscessed area, and presence of posts, filling material, or ledging. Cortical the placement of a sutured drain. trephination involves exposing the cortical bone, making Some studies have shown cortical trephination may an opening in the bone, and making a pathway through not be predictable in relieving periapical pain.36–38 A thecancellousbonetotherootend.33–40 Occasionally, prospective randomized blinded clinical trial raised an instrument may be used to penetrate the mucosa and concern about the assumed clinical effectiveness of cortical plate without an incision (Figure 10A,B). Several trephination.38 In that study, pain logs were evaluated studies have demonstrated that a patient with severe after non-surgical endodontic treatment and either real periapical pain without swelling will have significant or simulated trephination. It was found that the rou- relief following trephination.34,41–43 Atechniquefortre- tine use of trephination for the reduction of pain or phination recommended by Henry and Fraser41 involves swelling in symptomatic necrotic pulps in teeth with a submarginal horizontal full thickness flap to access the periapical radiolucencies was not predictable. A sys- tematic review of the literature concerning the emer- gency management of acute apical periodontitis in the permanent dentition also concluded that routine cor- tical trephination did not show significant benefit.44 While there is no higher level of evidence justifying the routine use of surgical trephination, there are lim- ited instances in which it is a reasonable treatment alternative. Patients with severe periapical pain of endodontic origin without swelling may benefit from the procedure.

A DECOMPRESSION: ASPIRATION AND IRRIGATION The terms decompression and marsupialization are often used interchangeably. Decompression is the sur- gical exposure of a cyst wall and insertion of a tube or other type of drain to decompress the lesion during healing.1 It is not uncommon for chronic periapical pathosis to remain clinically asymptomatic and develop a bony defect of significant size. If left undiagnosed and untreated, periapical pathosis may develop into self- perpetuating entities that erode osseous supporting structures and encroach on adjacent teeth, sinus cav- ities, neurovascular bundles, and even the nasal cavity. Bony lesions radiographically exceeding 200 mm2 have a higher statistical chance of being cystic.45 There are radicular cysts that may have progressed to the extent that they are truly independent, and non-surgical endo- dontic treatment may no longer be enough to result in bony healing.46,47 When non-surgical endodontics does not resolve apical pathosis, surgical intervention is an alternative treatment recommendation. Surgical treatment, including the enucleation of extensive bony lesions, may involve unintentional interruption of periapical vascular and neural struc- B tures, development of soft tissue defects, and damage to adjacent anatomic structures. Decompression is a Figure 10 A, Trephination using a #3 spreader. B, Radiograph showing more conservative treatment option that allows the tip of a #3 spreader near root end. Courtesy Dr. Craig Baumgartner. progressive reduction in lesion size and may eliminate 698 / Endodontics the necessity for surgical enucleation. Decompression is sive osseous repair at 3, 6, and 12 months. The use of intended to disrupt the integrity of the lesion wall, decompression to treat odontogenic keratocyst reduce the internal osmotic pressure, and permit oss- (OKC) has been reported by August et al.58 Apedia- eous regeneration (Figure 11). tric nasal airway was modified and placed in 14 In 1982, Suzuki48 suggested treating jaw cysts OKCs for an average of 8.4 months. They were irri- using an irrigational technique. In that study, the gated twice a day with chlorhexidine. At the time of contents of 36 cysts were irrigated weekly for months cystectomy, 9 of 14 no longer showed histological and even years. This irrigation method involved the features of OKCs. The epithelium had dedifferen- use of Ringer’s solution, glucose, and antibiotics. The tiated and lost cytokeratin 10 production in 64% of fluids aspirated from the cysts were quantitatively the patients. analyzed for electrolytes, inorganic substances, pro- Mejia et al.59 reported, in a case series format, teins, and lipids. Irrigation of the lesions eventually the use of a vacuum system within the root canal resulted in the reduction in the volume and size of system. The technique produced a vacuum effect the cysts. The irrigation method is effective for the capable of removing copious amounts of exudate treatment of cysts in jaws.48 Large cysts have been and inflammatory fluids. Perhaps, the removal of decompressed using acrylic stents, obturators, and the rather high osmolarity fluid and disruption of tubing that extends into the lesion.49–53 Acrylic the bony defect lining is the impetus for subse- stents or tubing was often left in for months with quent healing. irrigation of the lesion. Neaverth and Berg52 The combination of aspiration and irrigation as described several cases of large lesion decompression an alternative to surgical endodontic treatment was that lasted from several weeks to more than a year. reported by Hoen et al.60 in 1990. This case series The method used radiopaque tubing in conjunction demonstrated successful outcomes using a single- with water irrigation by the patient. The tube was visit aspiration and saline irrigation of non-healing removed once there was evidence of elimination of bony lesions associated with previously endodonti- the cystic lesion. cally treated teeth. Following profound anesthesia, A surgical technique was described in case series mucosa disinfection and aspiration of the cyst con- format by Wong54 in 1991. After flap reflection, a tents was accomplished using a 16- or 18-gauge surgical fenestration was used to obtain some tissue needle attached to a syringe. Several milliliters of for biopsy, but the majority of bony defect was left viscous aspirate was routinely obtained. The aspi- intact. Copious drainage was accomplished and the rates were submitted for aerobic and anaerobic cul- defect irrigated with saline prior to suturing. This turing, Gram-staining, and immunoglobulin quanti- surgical treatment was effective in producing healing fication. The level of immunoglobulin (Ig) G was while avoiding potential complications.54 Rees55 in significantly elevated in each specimen. Above nor- 1997 reviewed and highlighted the treatment of large mal levels of IgG have been shown to be consistent maxillary cysts by root canal treatment and subse- with cyst fluid.61 It has also been shown there is a quent decompression. The described technique used high level of albumin and globulin in cysts com- a drain made from surgical suction tubing. This seems pared to ‘‘granulomas’’.62 No bacteria were seen or to be the consensus treatment sequence currently in cultured from any of the aspirates. At the 1-year the dental literature. Figure 12 shows the radiographic follow-up appointments, the patients were asympto- and clinical appearance of decompression tube that maticandsignificantbonyhealingwasseenon was left in position for 1 week and the 6-month radiographs. It is important to develop a clear dif- follow-up radiograph after non-surgical root canal ferential diagnosis and to have timely re-evaluations filling. of the patient’s signs and symptoms to determine if A 20-patient cohort study of decompression further treatment is needed.60 results by Enislidis et al.56 is perhaps the best evi- An additional use of aspiration is to obtain a biopsy dence of the technique’s effectiveness. The authors sample. August et al.58 concluded that the use of described the advantages as ease of treatment, con- needle aspiration for biopsy is a useful technique firmed diagnosis with biopsy, low morbidity, and to distinguish between malignant and benign low incidence of complications. The quickest evi- intraosseous jaw lesions. The described technique dence of successful decompression was related by involved the use of a 10-mL syringe containing 1 or Loushine et al.57 in 1991. This case report related 2 mL of air attached to 23- or 25-gauge needles. Once theremovalofthedecompressiontubeafteronly2 within the lesion, suction was applied and several days with follow-up examinations showing progres- quick passes were performed to obtain cellular Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 699

A B

C D

E

Figure 11 A, Surgical window into cyst. B, Healed surgical window. C, Acrylic stint in place for decompression. D, Biopsy from window consistent with radicular cyst. E, Palatal radiographs showing loss of bone on left and bone fill after 3 months of decompression. Courtesy Dr. Craig Baumgartner. 700 / Endodontics

A C

B

Figure 12 A, A 20-mm piece of nasogastric tubing in cyst for decompression. B, Tubing used next to ruler was in place for 1 week. C, Six-month follow- up after non-surgical root canal filling. Courtesy Dr. Craig Baumgartner.

material. The specimens were then placed on glass Endodontic Flare-ups slides for smear preparation. The authors suggested that aspiration may be the diagnostic tool of choice in The American Association of Endodontics’ Glossary of a hospital setting due to its simplicity, suitability as an Endodontic Terms offers the following definition: ‘‘A outpatient procedure, rapidity of interpretation, and flare-up is an acute exacerbation of an asymptomatic 63 pulp/or periapical pathosis after the initiation or con- minimal morbidity. The accuracy of fine-needle 1 aspiration biopsy of head and neck tumors has been tinuation of root canal treatment.’’ Treating similar reviewed in 218 patients.64 The technique was deter- teethinpatientswithcomparablemedicalanddental mined to be a useful modality for the diagnosis of histories is no assurance of a common outcome. While head and neck tumors. The use of such a technique one patient remains asymptomatic, another may have a requires coordination with a pathologist familiar with flare-up. The contrasting clinical outcomes may seem to needle biopsy specimens. occur in a random manner or lead to erroneous Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 701 conclusions about the cause–effect relationship of endo- GENDER AND FLARE-UPS dontic procedures to the flare-up. The development of An extensive review concerning gender variation in moderate to severe inter-appointment pain, with or clinical pain experience reported that women are without swelling, is an infrequent but challenging more likely than men to experience a variety of recur- problem. The severe pain and swelling associated with rent pain.78 In most studies, women have reported flare-ups represent the clinical manifestation of complex more severe levels of pain, more frequent pain, and pathologic changes occurring at a cellular level. There is pain of longer duration than men.79 While a number increasing evidence pointing to multiple complex factors of studies found a significantly higher percentage of involved in producing a flare-up. These factors include females than males had postoperative pain,69,70,75,80 mechanical, microbial, chemical, immunological, gen- others have not found gender to be a significant der, and psychological components. The regulation of factor.66,81 It should be noted that there are consider- periapical inflammation is highly complex and is able variations between different types of clinical anotherfactorinpatients’ response to endodontic 82 22,65–70 pain. Experimental pain, produced under controlled procedures. conditions by brief, noxious stimuli, differs from pro- The reported incidence of inter-appointment 66,69–74 cedural and post-surgical pain. These differences emergenciesrangesfrom1.4to19%. While make the study of pain more complex.79 one study found pain and swelling occurred in as many as 20 to 40% of patients,75 the incidence of severe pain conditions is most frequently reported at SYSTEMIC CONDITIONS less than 5%.65,70,76,77 Variations in the findings are It seems reasonable to assume that host resistance, the result of a number of factors. For example, dif- for example, medical status of the patient, is an ferences exist in the definition of a flare-up. Some important variable in the occurrence of flare-ups. investigators have used swelling as the sole criteria Unfortunately, there is little conclusive evidence for a flare-up after treating asymptomatic teeth with concerning the relationship between host resistance pulp necrosis and chronic apical periodontitis.71 and flare-ups. One study found a highly significant Others have used broader definitions of a flare-up association between flare-ups and the presence of which do not require swelling.65,66,69,70 Some inves- allergies to various substances (sulfa medication, tigators used a retrospective approach in their pollen, dust, and foodstuffs) and the frequency of research,69,73 while others used prospective meth- inter-appointment pain.69 It was suggested that this odologies.65,66,70 Therehavealsobeenvariationsin could have been due to an immediate hypersensitiv- sample size, treatment procedures, number of visits, ity reaction occurring in the periapical tissues in endodontic medications, and other variables that are response to the egress of antigens from the root neither well-defined nor controlled. canal. Although the components of the immediate hypersensitivity reactions (IgE, mast cells, and mast AGE OF PATIENT cell-derived mediators) have been found in periapi- cal lesions, evidence is lacking as to whether these There is a lack of agreement concerning the influence reactions actually occur in the periapical tissues and of age on the incidence of flare-ups. Prospective are responsible for inter-appointment pain.68 An studies assessing the incidence of flare-ups in endo- association between allergy and inter-appointment dontic patients found no correlation between flare- pain has not been confirmed.70 ups and the age of the patient.70 However, a large retrospective study reached a different conclusion. Records of 2,000 patients were examined, and it was ANATOMIC LOCATION determined that when age was evaluated (20–39, Examining the incidence of flare-ups by tooth groups 40–59, over age 60), a significant difference was or between arches (maxillary versus mandibular) has found among age groups (p = 0.0001). Patients in usually shown no significant difference.66,70,80 An the 40- to 59-year range had the most flare-ups and exception was a retrospective study of 2,000 patients those under the age of 20 had the least.69 Conflicting who had received root canal treatment for necrotic conclusions regarding the influence of age on the pulps. Mandibular teeth were associated with more incidence of flare-ups can be attributed to variations inter-appointment emergencies than their maxillary in research methodologies, definitions, sample size, counterparts (p = 0.0247). Mandibular premolars and clinical procedures. followed by mandibular incisors were the most 702 / Endodontics problematic teeth after cleaning and shaping of their treatment of teeth with vital pulps is consistent with root canals.69 findings in other studies.73,74 The periapical diagnosis of acute apical abscess was ANXIETY also related to significantly greater incidence of flare- ups when compared with less symptomatic or less A high incidence of fear and anxiety among patients 70 concerning an endodontic procedure may have a severe apical pathosis. As one might expect, the presence of a sinus tract did not correlate with flare- marked effect on the patient’s intra-operative and 69,70 postoperative response to treatment. It has been ups. Investigators found the presence of a peri- apical radiolucency was significantly related to shown that if a patient expects pain to occur during 65,66,71,74 dental treatment, this increases the likelihood of pain inter-appointment flare-ups. These findings being perceived.83 An anxious patient with a previous are in contrast to others who found a higher incidence of inter-appointment emergencies in teeth without memory of dental pain is more likely to expect pain 69,81,85,86 during subsequent treatment. The slightest pressure apical radiolucencies. The differences in on the tooth can be interpreted as pain and initiate a findings may be attributable to variations in research pain reaction. Anxiety may also lead to increased methodologies, sample size, clinical procedures, sympathetic activity and muscle tension that may patients studied, and definition of flare-ups. cause more pain.79 Patients’ descriptions of their pain can be influenced by their level of anxiety and com- NUMBER OF TREATMENT VISITS plicate the diagnostic process.79 A multivariate analysis of the effectiveness of local A number of studies have determined that less post- anesthesia in pediatric patients indicated anxiety as operative pain results from a single-visit approach to 84 endodontics than a multi-visit course of treat- the strongest predictor of poor pain control. A large 66,87,88 retrospective study noted an association between ment. Other investigators concluded that little or 72 no difference occurred between single- and multiple- apprehension and postoperative pain. The dental 70,89–91 procedures causing the highest levels of stress and visit endodontic therapy. Significant variables anxiety are oral surgery and endodontics. There is a exist among the studies that may account for the high probability that endodontic patients are anxious different conclusions. and expect to experience pain during treatment79 (see Chapter 22). CAUSES OF INTER-APPOINTMENT PAIN Inter-appointment pain is caused by mechanical, PREOPERATIVE HISTORY chemical, and/or microbial injury to the pulp or periapical tissues that are induced or exacerbated OF THE TOOTH during endodontic treatment.68,69,92 The cause of Most studies have found a highly significant relation- injury may vary, but the intensity of the inflammatory ship between the presence of preoperative pain and/ response is usually directly proportional to the inten- or swelling and the incidence of inter-appointment sity of tissue injury.93 Mechanical and chemical emergencies.65,66,69,70 Studies have also shown a injuries are often associated with iatric factors, but statistically significant higher incidence of flare-ups microbial-induced injury is a major cause of inter- in patients taking analgesics and anti-inflammatory appointment pain.68,92,94 Microbial factors may be drugs.66,70 It is reasonable to assume that patients combined with iatric factors to cause inter-appoint- taking those drugs were having preoperative pain. ment pain. Even when endodontic procedures are performed within accepted guidelines, microbes can PULP/PERIAPICAL STATUS cause a flare-up.68 Development of pain precipitated There is no universal agreement concerning the influ- by microbial factors can depend on the interrelation- ence of pulp status and/or the presence of a periapical ship of several factors that are discussed in Chapter 7. lesion on the incidence of inter-appointment emergen- cies. A prospective study found that teeth with vital TREATMENT OF TEETH WITH VITAL AND pulps resulted in relatively few flare-ups, with an over- NON-VITAL PULPS all percentage of 1.3%.66,70 In contrast, pulp necrosis Treatment of teeth with vital (pulpitis) and non-vital correlated to an incidence of flare-ups of 6.5%, a sta- (necrotic) pulps represent pathological conditions that tistically significant increase when compared to vital require different approaches to therapy.95 It has been pulps. A low number of flare-ups following root canal suggested that if the pulp is free of infection, the Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 703 endodontic treatment should be completed in one visit no statistical significance in the relation of re-treatment if other factors permit. Temporization after removal of to flare-ups.70 a vital pulp entails the risk of micro-leakage and con- tamination of the canal.95 A high level of asepsis dur- ing pulpectomy and subsequent obturation is an WORKING LENGTH essential part of treatment. Although asepsis is also The apical portion of the root canal system has been an important part of treating a tooth with a non-vital considered the most critical anatomic area with regard to pulp, the principle concern is the presence of bacteria the need for cleaning, disinfection, and sealing.67,100 in the root canal system. Infected canals may contain Overextension should be avoided as it can result in 95–97 10 to 100 million bacterial cells. Clinicians are postoperative pain.67 Teeth with non-vital (necrotic) faced with the challenge of disinfecting the canal sys- pulps associated with a periapical lesion, as well as tem through instrumentation, irrigation, and medica- root-filled teeth with recalcitrant lesions, represents a tion without pushing debris into the periapical tissues. different biological challenge.67 In these cases, micro- organisms may be at or near the apical foramen and accessory foramina that are in close contact with the RE-TREATMENT CASES periapical tissues.67,101–104 Thus, correct working length Re-treatment cases, in most studies, have had a in infected teeth is essential.67,105 Inaccurate working significantly higher incidence of flare-ups than conven- length or inadvertent over- or under-instrumentation tional cases 69,70 (Figure 13). One study found an extre- can result in negative outcomes for the patient. mely high incidence of flare-ups (13.6%) in re-treatment Over-instrumentation may force infected debris into teeth with apical periodontitis.77 It can be hypothesized the periapical tissues eliciting a severe inflammatory that re-treatment cases are often technically difficult to response and pain. Under-instrumentation will leave treat, and there is a tendency to push remnants of gutta- microorganisms in close proximity to the apical percha, solvents, and other debris into the periapical foramina where they or their virulence factors can gain tissues. Microbes may also be pushed apically during access to the periapical tissues67,106 (see Chapter 7). the re-treatment process. Extrusion of infected debris Incomplete instrumentation can disrupt the balance or solvents into the periapical tissues during preparation within the microbial flora and allow previously inhib- of the canals is allegedly one of the principal causes of ited species to overgrow.107 If those strains of bacteria postoperative pain.92,96,98 Re-treatment cases are usually are virulent and/or reach sufficient numbers, damage associated with a persistent or secondary root canal to the periapical tissues may be intensified and result infection by therapy-resistant microorganisms that in an exacerbation of the lesion. Furthermore, environ- may be more difficult to eradicate when compared to mental changes, induced by incomplete debridement, primary infections.67,98,99 In contrast, others have found have the potential to activate virulence genes.68

Figure 13 Swelling associated with flare-up following revision of previous endodontic treatment. Courtesy Dr. Paul Rosenberg. 704 / Endodontics

A change in host resistance or microbial virulence may before and after surgery, reduces postoperative pain allow a previously asymptomatic situation to become intensity and intake of analgesics improves treatment symptomatic.68 Clinical studies, however, have not compliance, cardiovascular and respiratory indices, linked incomplete canal preparation to flare- and accelerates recovery.113 In a landmark study, it ups.70,91,108,109 was found that preoperative discussion of likely post- surgical treatments and associated discomfort halved OBTURATION the requirement for postoperative morphine and reduced time to discharge. Patients in that study also Overfilling can cause postoperative pain particularly received instructions in a relaxation technique.114 when a substantial amount of filling material extrudes Providing information about the procedure is an through the apical foramen. Gross overfilling involves important step in preparing patients for endodontic the introduction of excess sealer (and its cytotoxic treatment. Information about profound dental components) into the periapical tissues causing tissue 67 anesthesia and preventive pain strategies is an impor- damage and inflammation. A recent study found tant anxiety reduction technique. Perhaps most that overfilling was significantly associated with importantly, the dentist should assure the patient that increased rate of pain and percussion sensitivity in pain prevention is a primary concern. It was deter- 1-week follow-up examinations in comparison with 110 mined that patients given a running commentary teeth not overfilled. Scheduling of the obturation concerning procedures and associated sensations visit in relation to instrumentation may be another rated themselves as less anxious and experiencing less important factor. Obturation in the presence of acute pain than a normal control group.115 Information apical periodontitis can be considered to be a predic- about sensations experienced during treatment as well tor of postoperative pain. In order to avoid increased as a description of procedures appears to have a sig- postoperative pain, patients who present for obtura- nificant impact in reducing patient anxiety.115 tion but have significant acute apical periodontitis Patients should not be allowed to watch surgical pro- should have the procedure postponed until the tooth cedures in a mirror. is more comfortable. Relief of pain can be achieved by treatment directed at reducing tissue levels of factors that stimulate peripheral terminals of nociceptors or OCCLUSAL REDUCTION by reducing mechanical stimulation of sensitized Occlusal reduction is a valuable pain preventive strat- nociceptors (e.g., occlusal adjustment). Thus egy in appropriate cases.116,117 Some earlier studies by deferring obturation of a tooth with pericementitis, raised questions concerning the value of prophylactic further stimulation of sensitized nociceptors is occlusal reduction as a pain preventive mea- avoided.111,112 sure.118,119 The results of a more recent study indi- cated that occlusal reduction should result in less post-treatment pain in patients whose teeth exhibit Strategies to Prevent Flare-ups pulp vitality, preoperative pain, percussion pain, or absence of a periapical radiolucency.120 While the ANXIETY REDUCTION presence of all four conditions is the strongest predictor, the presence of any one or more of the The causes of endodontic flare-ups are varied, and an conditions is enough to indicate the need for occlusal effective preventive strategy must be multifaceted reduction (Figure 14). (see Chapter 23). There is a well-documented rela- Occlusal reduction when performed in appropriate tionship between anxiety, pain threshold, and post- 72,79,83,84 cases is a highly predictable, simple strategy for the operative pain. prevention of postoperative pain and relief of pain due to acute apical periodontitis. There is a biologic rationale for the relief of pain provided by the BEHAVIORAL INTERVENTION occlusal reduction. Mechanical allodynia (i.e., sensi- In preoperative patients, high levels of stress, anxiety, tivity to percussion or biting forces) is due to tissue or pessimism predict poor outcomes in measures that levels of mediators that stimulate peripheral term- range from speed of wound healing to duration of inals of nociceptors. Occlusal adjustment, in either hospital stay. Over 200 studies indicate that preemp- arch, reduces mechanical stimulation of sensitized tive behavioral intervention, to decrease anxiety nociceptors.120,121 Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 705

It is advisable to have endodontic patients take their analgesics ‘‘by the clock’’ rather than on an ‘‘as needed basis’’.121 Patients should take an NSAID or acetaminophen just prior to, or imme- diatelyafter,treatment.Iftheywaittotakemedi- cation until after the onset of pain, there is usually a delay of up to 1 hour before they experience pain relief. It has been suggested that instructing patients to take their analgesics by the clock for thefirstfewdaysprovidesamoreconsistentblood level of the drug and may contribute to more consistent pain relief.121 The combination of ibu- profen and acetaminophen taken together has been shown to produce additive analgesia when treating dental pain.111,121,126–128 Opioids may be added Figure 14 Effect of occlusal reduction on pain. Courtesy Dr. Paul when indicated (see Chapter 22). Rosenberg. LONG-ACTING LOCAL ANESTHETICS Long-acting local anesthetics (e.g., bupivicaine) can Pharmacologic Strategies for Flare-ups provide an increased period of post-treatment analge- sia beyond the usual duration of anesthesia.129,130 By ANTIBIOTICS blocking the activation of unmyelinated C-fiber noci- Antibiotics are frequently prescribed to endodontic ceptors, the anesthetic decreases the potential for 121 patients without a rational biologic basis.122,123 An central sensitization. Long-acting local anesthetics evidence-based review determined that the use of sys- can provide a period of analgesia for up to 8 to 10 temic antibiotics for the prevention of post-treatment hours following block injections and may reduce 121,129 endodontic pain should be discouraged.124 Antibiotic pain even 48 hours later. Use of long-acting treatment is generally not recommended for healthy local anesthetics is a valuable biologically based strat- patients with localized endodontic infections. Systemic egy that provides analgesia during the immediate 121 antibiotics should be considered if there is a spreading postoperative period. Endodontic treatment by infection that indicates failure of local host responses to itself can be expected to provide significant pain relief control bacterial irritants or the patient has a medical (see Chapter 22). condition that compromises defense mechanisms and could expose the patient to higher systemic risks.124 Treatment of Endodontic Flare-ups NSAIDS AND ACETOMINOPHEN Selecting the appropriate treatment after an endodon- tic flare-up is dependent upon understanding its Nonsteroidal anti-inflammatory drugs (NSAIDs) have biological cause. For example, the clinician must been shown to be effective for managing pulpal and determine if a flare-up is primarily iatrogenic in nat- periapical pain.111,125 However, due to the renal ure, as in the case of inaccurate measurement control, effects of NSAIDs as well as interactions with many or microbiologically based, as in an infected necrotic anti-hypertensive drugs, acetaminophen should be situation. considered for post-treatment pain in patients with known sensitivity to NSAIDs or aspirin. Acetamino- phen should also be considered for those with the DIAGNOSIS AND DEFINITIVE following disorders: ulcers, ulcerative colitis, asthma, TREATMENT or hypertension. Pretreatment with NSAIDs or acet- History of the onset of pain is important in deter- aminophen has also been shown to be effective for mining if the pain is spontaneous or provoked by reducing postoperative pain.68,121 Pretreatment with a specific stimulus. For example, if a tooth had a NSAIDs for irreversible pulpitis should have the effect history of acute apical periodontitis and its occlu- of reducing pulpal levels of the inflammatory media- sion had not been reduced, that could be identified tor prostaglandin E2 (PGE2).68,71 as a probable cause of postoperative pain, 706 / Endodontics appropriate treatment should be provided.120 In drainage through the coronal access opening has been contrast, a complaint of swelling, pressure, and advocated as a means of reducing pain following throbbing in the interproximal area might suggest treatment in some necrotic cases.132 Interestingly, a a periodontal component of the problem that retrospective study examined the effect of drainage should be explored. If inaccurate measurement con- upon access on postoperative endodontic pain and trolwasusedorpropermeasurementnotmain- swelling in symptomatic necrotic teeth. It was deter- tained, the clinician must determine if the canal mined that drainage upon access (average of 1.85 was under- or over-instrumented. Working length minutes) did not significantly (p > 0.05) reduce pain, should be reconfirmed, patency to the apical fora- percussion pain, swelling, or the number of analgesic men obtained, and thorough debridement with medications taken, for symptomatic teeth with peria- copious irrigation completed. Remaining tissue, pical radiolucencies.131 It is possible that pre-existent microorganisms and their products, and extrusion apical periodontitis was a factor in the cases studied beyond the apex are major factors responsible for and was not addressed by the establishment of drai- post-treatment symptoms.94 Pain relief in the over- nage. Occlusal relief may also have been required to instrumented case is often dependent on an analge- address that symptom. sic strategy. The under-instrumented case may require further instrumentation to the correct mea- surement,aswellastheuseofanalgesics. I&D The goal of emergency treatment for an endodontic flare-up with a swelling is to achieve drainage.132 The Drainage Through the Coronal Access object of drainage is to evacuate exudate from the periapical spaces (Figure 16). Drainage is best Opening achieved through a combination of canal instrumen- A cardinal principle in the treatment of suppurative tation and I&D. Even in cases where an I&D is to be lesions is the establishment of drainage (Figure 15). implemented, the canal should be accessed, instru- Drainage, upon access to the pulp cavity, releases mented, irrigated, medicated, and closed as soon as purulent or hemorrhagic exudate from the periapical active drainage stops. Systemic antibiotics can be tissues and may reduce periapical pressure in sympto- expected to be more effective once the canal has been matic teeth with radiolucent areas.131 Obtaining debrided, medicated, and closed.133,134

Figure 15 Purulent drainage upon access to the pulp cavity. Courtesy Dr. Craig Baumgartner. Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 707

COMPLEX DIAGNOSES The clinician must be sensitive to the potential of non- odontogenic pain being confused with a flare-up. For example, the words ‘‘tingling’’ or ‘‘burning’’ when used as descriptors of pain are signals of non-odontogenic pain rather than a flare-up. Similarly, although rare, it is possible for a tooth, other than one undergoing endodontic treatment, to suddenly become painful and confuse the diagnosis. A previously undetected periodontal component may also pose a diagnostic problem.

Bacterial Factors Associated Figure 16 Purulent drainage following incision of a fluctuant abscess involving a mandibular anterior tooth (Courtesy Dr. John Ingle). with Flare-ups Bacteria are capable of acting as irritants and induce non-specific innate or specific adaptive immune responses in the host.139,140 The host’s responses to a INSTRUMENTATION bacterial challenge depend largely on virulence factors After considering the biological cause of the flare-up, and the numbers of pathogens, as well as the host’s the clinician may decide to re-enter the symptomatic innate and adaptive immunity. If the host’s defense tooth. Profound local anesthesia is necessary before mechanisms are capable of overcoming a bacterial re-entry. Enhanced magnification and illumination challenge, bacteria will be eliminated. In contrast, if are helpful in reassessing the chamber morphology the bacterial challenge overwhelms the host’s defense for canals that might have been missed at the prior mechanisms, an inflammatory response, as a result 135–137 visit. Working lengths should be reconfirmed, of innate or adaptive immunity, will occur. Micro- patency to the apical foramen obtained, and a thor- organisms have been suggested as the major causative ough debridement with copious irrigation per- agents of flare-ups.68,92,94 Unlike elsewhere in the body, 68 formed. Remaining necrotic tissue, microorganisms, bacteria in the root canal system are well protected and toxic products are important factors responsible from the host’s immune defenses and antimicrobial 94 for flare-ups. Enlarging the apical constriction has agents. The microbes and virulence factors associated 138 been advocated to encourage drainage. Others have with pulpal and periapical infections are discussed in found that instrumenting through the apical foramen Chapter 7 ‘‘Microbiology of Endodontic Disease.’’ 68,138 does not ensure drainage of periapical exudation. The bacterial community in an infected root canal is In some cases, however, drainage may be established closely related to the nutrient supply, bacterial interac- through the root canal system upon instrumentation. tion, and oxidation–reduction potential.107 Endodontic Drainage allows for exudate to be released from the procedures cause changes in the root canal environment, periapical tissues thus reducing localized tissue pressure favoring growth of some pathogens remaining in the 131 and pain. Leaving a tooth open after drainage is incompletely instrumented canals, thus predisposing the complete will result in re-infection from oral patient to a flare-up.94 Some bacterial species may, under 73,94 microbes. certain conditions such as changes in oxidation-reduction potential, bacterial interaction, or environmental stresses, become more virulent and induce higher concentrations TREPHINATION of inflammatory molecules and/or cytokines from As discussed earlier in the chapter, trephination is the damaged periapical tissues, thus intensifying the inflam- surgical perforation of the alveolar cortical plate over matory response.68,94 This is exemplified in some asymp- the root end, to release accumulated tissue exudate tomatic infected teeth with pulpal and/or periapical that is causing pain.1 It may be indicated for patients pathosis,aswellassomeasymptomaticre-treatmentcases with a flare-up when there is exquisite pain, no swel- with periapical pathosis. After initiation or continuation ling, and drainage cannot be accomplished through of root canal treatment, those cases suddenly develop a the tooth. flare-up. Preoperative symptomatic teeth have been 708 / Endodontics shown to produce a higher incidence of flare-ups than 6. Siqueira JF Jr, Roˆc¸as IN, Favieri A, et al. Polymerase chain asymptomatic teeth,69,70 although the mechanism is not reaction detection of Treponema denticola in endodontic clear. It is possible, in teeth that are symptomatic, the infections within root canals. Int Endod J 2001;34:280–4. canals are dominated by pathogens often found asso- 7. Simon JHS, Warden JC, Bascom LK. Needle aspiration: an ciated with pain or an acute periapical abscess. Therefore, alternative to incision and drainage. Gen Dent 1995;1:42–5. these cases are predisposed to flare-up if the canals are not 8. Fouad AF, Rivera EM, Walton RE. Penicillin as a supplement in completely debrided or critical numbers of pathogens are resolving the localized acute apical abscess. Oral Surg Oral Med forced into the apical tissues to overwhelm the host’s Oral Pathol Oral Radiol Endod 1996;81(5):590–5. defenses. A shift in the microbial community in the root 94 9. Henry M, Reader A, Beck M. Effect of penicillin on post- canal may occur before the appearance of a flare-up. operative endodontic pain and swelling in symptomatic Therapeutically, it is easier to reduce the intracanal necrotic teeth. J Endod 2001;27(2):117–23. bacterial count than to control specific pathogens in the infected root canals. Mechanical instrumentation and 10. Lindeboom JAH, Frenken JWH, Valkenburg P, van den antiseptic irrigation have been shown to greatly reduce Akker HP. The role of preoperative prophylactic antibiotic 141 administration in periapical endodontic surgery: a rando- bacterial count in infected root canals. Intracanal mized, prospective double-blind placebo-controlled study. medication between visits with calcium hydroxide may Int Endod J 2005;38:877–81. further reduce the bacterial count.97,142 However, studies have not demonstrated an ability to eliminate all 11.NagleD,ReaderA,BeckM,WeaverJ.Effectofsystemic bacteria in infected root canals using contemporary penicillin on pain in untreated irreversible pulpitis. Oral SurgOralMedOralPatholOralRadiolEndod endodontic procedures. Usually, the pathogenicity of 2000;90:636–40. microorganisms is related to their virulence factors and numbers. Although complete chemo-mechanical pre- 12. Pickenpaugh L, Reader A, Beck M, et al. Effect of Prophy- paration, in combination with intracanal medication, lactic amoxicillin on endodontic flare-up in asymptomatic, maynoteliminatespecificpathogensandtheirvirulence necrotic teeth. J Endod 2001;27(1):53–6. factors, the procedures will significantly reduce the intra- 13. Walton RE, Chiappinelli J. 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I Endod of various medications on postoperative pain following com- J 1989;22:179–83. plete instrumentation J Endod 1994;20:345–54. 91. Eleazer P, Eleazer K. Flare-up rate in pulpally necrotic 73. Barnett F. The incidence of flare-ups following endodontic molars in one visit versus two-visit endodontic treatment. treatment. [Special Issue] J Dent Res 1989;68:1253. J Endod 1998;24:614–16. Chapter 21 / Treatment of Endodontic Infections, Cysts, and Flare-ups / 711

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Egbert A, Bettit G, Welch C, Barttett M. Reducation of effect of 0.5% sodium hypochlorite in endodontic therapy. postoperative pain by encouragement and instruction of Oral Surg Oral Med Oral Pathol Oral Radiol Endod patients. N Engl J Med 1964;270:825–7. 1983;55:307–12. 115. Wardle J. Psychological management of anxiety and pain dur- 97. Sjogren U, Figdor D, Spangberg L, Sunqvist G. The anti- ing dental treatment. J Psychosom Res 1983;27:399–402. microbial effect of calcium hydroxide as a short-term intra- 116. Natkin E. Treatment of endodontic emergencies. Dent Clin canal dressing. Int Endod J 1991;24:119–25. North Am 1974;18:243–55. 98. Siqueira J. Aetiology of the endodontic failure: why well 117. Antrim D, Bakland L, Parker M. Treatment of endodontic treated teeth can fail. Int Endod J 2001;34:1–10. urgent care cases. Dent Clin North Am 1986;30:549–72. 99. Sundqvist G, Figdor D. Life as an endodontic pathogen. 118. Creech J, Walton R, Kaltenbach R. Effect of occlusion relief on Ecological differences between the untreated and root-filled endodontic pain. J Am Dent Assoc 1984;109:64–7. canals. Endod Topics 2003;6:3–28. 119. Jostes J, Holland G. The effect of occlusal reduction 100. Simon J. The apex: how critical is it? Gen Dent 1994;42: after canal preparation on patient comfort. J Endod 330–4. 1984;10:34–7. 101. Nair P, Sjogren U, Krey G, et al. Intraradicular bacteria and fungi 120. Rosenberg P, Babick P, Schertzer L, Leung A. The effect of in root-filled asymptomatic human teeth with therapy-resistant occlusal reduction on pain after endodontic instrumenta- periapical lesions: a long term light and electron microscope tion. J Endod 1998;24:492–6. follow-up study. J Endod 1990;16:580–8. 121. Keiser K, Hargreaves K. Building effective strategies for 102. Nair P. Light and electron microscopic studies of root canal the management of endodontic pain. Endod Topics flora and periapical lesions. J Endod 1987;13:29–39. 2002;3:93–105. 103. Fukushima H, Yamamoto K, Hirohata K, et al. Localization 122. Whitten B, Gardiner D, Jeansonne B, Lemon R. Current and identification of root canal bacteria in clinically asympto- trends in endodontic treatment: report of a national survey. matic periapical pathosis. J Endod 1990;16:534–8. J Am Dent Assoc 1996;127:1333–14. 104. Siqueira J, Lopes H. Bacteria on the apical root surfaces of 123. Yingling N, Byrne B, Hartwell G. Antibiotic use by untreated teeth with periradicular lesions: a scanning elec- members of the American Association of Endodontists in tron microscopy study. Int Endod J 2001;34:216–20. the year 2000: report of a national survey. J Endod 105. Molven O. The apical level of root fillings. Acta Odontol 2002;28:396–404. Scand 1976;34:89–116. 124. Fouad A. Are antibiotics effective for endodontic pain? 106. Siqueira J. Endodontic infections: concepts, paradigms and Endod Topics 2002;3:52–6. perspectives. Oral Surg Oral Med Oral Pathol Oral Radiol 125. Holstein A, Hargreaves K, Niederman R. Evaluation of Endod 2002;94:281–93. NSAIDs for treating post-endodontic pain: a systemic 107. Sundqvist G. Ecology of the root canal flora. J Endod review. Endod Topics 2002;3:3–13. 1992;18:427–30. 126. Wright CI, Antal E, Gillespie W, Albert K. Ibuprofen and 108. Balaban F, Skidmore A, Griffen J. Acute exacerbations follow- acetaminophen kinetics when taken concurrently. Clin Phar- ing initial treatment of necrotic pulps. J Endod 1984;10:78–80. macol Ther 1983;34:707–10. 109. Walton R. Interappointment flare-ups: incidence, related 127. Cooper S. The relative efficacy of ibuprofen in dental pain. factors, prevention and management. Endod Topics Compend Contin Educ Dent 1986;7–11. 2002;3:67–76. 128. Breivik E, Barkvoll P, Skovlund E. Combining diclofinac 110. Gesi A, Hakeberg M, Warfinge J, Bergenholtz G. Incidence with acetaminophen-codeine after oral surgery: a rando- of periapical lesions and clinical symptoms after pulpect- mized, double blind single dose study. Clin Pharmacol Ther omy: a clinical and radiographic evaluation of one- versus 1999;66:625–35. 712 / Endodontics

129. Cout R, Koraido G, Moore P. A clinical trial of long-acting 136. Wolcott J, Ishley D, Kennedy W, et al. Clinical investigation abesthetics for periodontal surgery. Anesth Prog 1990;37:194–9. of second mesiobuccal canals in endodontically treated and 130. Gordon S, Dionne R, Brahim J, et al. Blockage of periapical retreated maxillary molars. J Endod 2002;28:477–9. neuronal barrage reduced post-operative pain. Pain 137. Buhrley L, Barrows M, BeGole E, Wenckus C. Effect of 1997;709:209–15. magnification on location the MB2 canal in maxillary 131. Nusstein J, Reader A, Beck M. Effect of drainage upon access molars. J Endod 2002;28:324–7. on postoperative endodontic pain and swelling in sympto- 138. Weine F. Endodontic therapy. 2nd ed. St. Louis: Mosby; 1976. matic necrosis teeth. J Endod 2002;28:584–8. 139. Mims C, Playfair J, Roitt I, et al. Medical microbiology. 2nd 132. Harrington G, Natkin E. Midtreatment flare-ups. Dent Clin ed. Philadelphia: Mosby; 1999. North Am 1992;36:409–23. 140. Abbas A, Lichtman A, Pober J. Cellular and molecular 133. Baumgartner J, Hutter J. Endodontic microbiology and immunology. 4th ed. Philadelphia: WB Saunders; 2000. treatment of infection. In: Pathways of the pulp. Cohen, S. 141. Bystrom A, Sundqvist G. Bacteriologic evaluation of the and Hargreaves, K. 8th ed. St. Louis: Mosby; 2002. efficacy of mechanical root canal instrumentation in 134. Hutter J. Facial space infections of odontogenic origin. endodontic therapy. Scand J Dent Res 1981;89:321–8. J Endod 1991;17:422. 142. Bystrom A, Claesson R, Sundqvist G. The antibacterial 135. Schwarze T, Baethge C, Stecher T, Guertsen W. Identifica- effect of camphorated paramonochlorophenol, campho- tion of second canals in the mesiobuccal root of maxillary rated phenol and calcium hydroxide in the treatment first and second molars using magnifying loupes or an of infected root canals. Endod Dent Traumatol operating microscope. Aust Endod J 2002;28:57–60. 1985;1:170–5. CHAPTER 22

PHARMACOLOGIC MANAGEMENT OF ENDODONTIC PAIN

KENNETH M. HARGREAVES,AL READER,JOHN M. NUSSTEIN,J.GORDON MARSHALL,JENNIFER L. GIBBS

The management of pain represents both a challenge and anesthetic techniques and pharmacology should be an opportunity for the endodontist. It is a challenge due reviewed as needed by the reader. This section provides to pharmacological (e.g., reduced anesthetic success), an evidence-based rationale of various local anesthetic behavioral (e.g., patient apprehension), and practice agents and primary and supplemental routes of adminis- management (e.g., relationship with referring practi- tration, with an emphasis on clinical implications. tioner) issues. Many of these factors can increase the Before reviewing the clinical trial literature, sev- stress of providing high-quality clinical care to our eral preliminary factors should be considered. First, patients. However, effective pain management also repre- subjective approaches for assessing the depth of sents a unique opportunity to integrate pharmacological, anesthesia (‘‘are you numb?’’) are fraught with a procedural, and behavioral skills in providing outstand- lack of sensitivity and specificity.1–4 Instead, testing ing pain control to grateful patients. A tremendous for pulpal responses in vital teeth, by an application increase in our knowledge of the pain system and its of a cold refrigerant or by using an electric pulp dynamic plasticity in response to tissue inflammation tester (EPT), are effective methods for evaluating occurred over the last decade (Chapter 10, ‘‘Mechanisms anesthesia in pain-free5–9 or symptomatic vital of Odontogenic and Non-Odontogenic Pain’’ and Chap- teeth5,9–11 in nearly5,9,10 all patients. Simply put, ter 11, ‘‘Non-Odontogenic Toothache and Chronic Head the lack of profound anesthesia after an initial and Neck Pains’’). Equally important, a commensurate injection becomes a major indication for supple- increase in analgesic clinical trials provides the clinician mental injection of local anesthetic solutions. Sec- with a unique opportunity to develop biologically and ond, a prior history of incomplete anesthesia often evidence-based strategies for effectively treating endo- predicts subsequent problems with obtaining com- dontic pain patients. This chapter contributes to that plete anesthesia.12 Thisissueshouldbeconsidered skillset by comprehensively reviewing this clinical litera- when reviewing the patient’s dental history. Third, ture and formulating strategies based on the latest results preoperative pain is a risk factor for incomplete from clinical research. To accomplish this goal, the chap- local anesthesia, with up to an eight-fold increase in ter will sequentially review major drug classes available to the prevalence of incomplete anesthesia observed in the practitioner and then usethisinformationtosum- patients with irreversible pulpitis.13 Although the marize evidence-based approaches for pain control. mechanism(s) mediating this clinical problem is incompletely understood, several hypotheses have been advanced including (1) ion trapping of local anesthetic molecules due to lower pH (only possible Local Anesthesia for infiltration injections; block injections are not Profound pain control starts with effective local anesthe- likely to involve acidotic tissue); (2) altered membrane sia. In addition to the obvious ethical and moral obligation excitability of peripheral nociceptors14,15; (3) increased of providing appropriate high-quality care, the technical activity of the tetrodotoxin-resistant (TTXr) class of challenges of endodontic procedures are greatly increased sodium channels that may also be resistant to the without effective anesthesia. Background reviews on local action of local anesthetics16; (4) increased overall

713 714 / Endodontics expression of sodium channels in pulps diagnosed with irreversible pulpitis17; and/or (5) central sensitization that amplifies peripheral input from afferent neurons. Importantly, supplemental techniques such as intraoss- eous9,10,18,19 or periodontal ligament (PDL)11 injec- tions have been demonstrated to increase anesthetic efficacy when an inferior alveolar nerve (IAN) block fails to provide effective anesthesia. Fourth, preopera- tive apprehension, possibly due to previous dental procedures including injections,20–22 may contribute to patient management issues. Topical anesthetics have been reported to be effective in reducing injection discomfort in some,23–26 but not all,27–29 studies, and both pharmacological and psychological components may contribute to the effectiveness of topical anes- 29 thetics. Fifth, a slow rate of injection (60 versus Figure 1 Time–response curve for the development of pulpal anesthesia 30 15 seconds) reduces patient discomfort and can be (defined as no response on Analytical Technologies EPT at setting = 80) of accomplished either manually or by a computer- mandibular first molars following inferior alveolar nerve (IAN) block injection of controlled anesthetic delivery system. Automated anes- 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. Data courtesy of Dr. A. thetic delivery systems have been shown to produce less Reader et al. pain in some studies,31–36 or either no difference or greaterpaininotherstudies37,38; at least some discomfort (EPT) within 15 minutes and continuously demon- has been noted in most studies.32–38 Sixth, epinephrine- strate a lack of responsiveness for 60 minutes. Conver- containing local anesthetics, with their associated low- sely, anesthetic failure is defined as the percentage of ered pH, are thought to be associated with more injection subjects who never achieved two consecutive 80 EPT discomfort in some39,40 but not all41 studies. As noted in readings at any observation time. In general, studies Chapter 10, ‘‘Mechanisms of Odontogenic and Non- performing IAN block injections with one cartridge of Odontogenic Pain,’’ the TRPV1 ‘‘capsaicin receptor’’ is 2% lidocaine with 1:100,000 epinephrine report differ- expressed on pain neurons and is profoundly activated by ent proportions of anesthetic success/failure for the pH solutions of <6.0, which might provide a biological mandibular first molar (53% success/17% failure), first basis for this observation. Seventh, permanent damage to premolar (61%/11%), and the lateral incisor (35%/ thelingualnerveandIANsareveryrare,withacalculated 32%)1–4,45–49 (Figure 1). It is important to note, how- incidence of about 0.0006 to 0.3%.42 Of these reported ever, that 100% of the subjects1–4,45–49 reported pro- injuries, the lingual nerve is affected ~70 to 79%, while the found lip numbness. Therefore, this outcome has no IAN is affected ~21 to 30% of these cases.42,43 In one case predictable value for determining the depth of pulpal series, the lingual nerve was affected in 18 out of 12,104 anesthesia. Although the presence of lip sign does not patients (~0.1%), with 17 of these 18 cases resolved within indicate effective pulpal anesthesia, the absence of a lip 6months.44 Collectively, these general principles of local sign indicates a failed IAN block injection and should anesthesia provide foundation knowledge when using this prompt a second injection of local anesthetic before important class of drugs. treatment begins. Several local anesthetics have been compared in clinical trials using designs similar to that described Mandibular Anesthesia above. As summarized in Table 1, these studies have demonstrated that many local anesthetics produce Numerous studies have evaluated pulpal anesthesia similar levels of anesthesia for IAN block injections. using a standardized testing protocol involving In particular, the equivalency of 3% mepivacaine and repeated application of an EPT using a 0–80 scale of 2% lidocaine with 1:100,000 epinephrine, in patients current.1–4,45–49 This method permits controlled clin- with irreversible pulpitis, is an important finding. It ical trials in which either normal healthy control sub- provides a vasoconstrictor-free alternative when med- jects or odontogenic pain patients using the same ical conditions or drug therapies suggest caution in dependent measure for study outcome. In these stu- administering epinephrine-containing solutions. dies, anesthetic success is defined as the percentage of Mepivacaine is available in a formulation containing subjects who achieve two consecutive 80 readings levonordefrin, an adrenergic agonist with 75% a Chapter 22 / Pharmacologic Management of Endodontic Pain / 715

Table 1 Comparison of Local Anesthetics for Inferior Alveolar Nerve Anesthesia Local Anesthetic I Local Anesthetic II Patient Population Finding Reference

3% Mepivacaine plain 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 2 3% Mepivacaine plain 2% Lidocaine with 1:100,000 epinephrine Irreversible pulpitis I = II 11 2% Mepivacaine with 1:20,000 levonordefrin 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 4 4% Prilocaine plain 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 2 4% Prilocaine with 1:200,000 epinephrine 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 4 4% Articaine with 1:100,000 epinephrine 2% Lidocaine with 1:100,000 epinephrine Healthy volunteer subjects I = II 71 4% Articaine with 1:100,000 epinephrine 2% Lidocaine with 1:100,000 epinephrine Irreversible pulpitis I = II 72 4% Articaine with 1:100,000 epinephrine 4% Articaine with 1:200,000 epinephrine Healthy volunteer subjects I = II 73 activity and only 25% b activity, making it seem more studies have reported that articaine was signifi- attractive than epinephrine (50% a activity and 50% b cantly better than lidocaine for anesthesia after activity).50 However, levonordefrin is marketed as a buccal infiltration of the mandibular first molar, 1:20,000 concentration in dental cartridges.50 Clinically, with articaine producing asuccessrateofabout the higher concentration of levonordefrin makes it 64 to 87%.72,73 equipotent to epinephrine in clinical and systemic Long-acting local anesthetics, including bupiva- effects.4,51 Therefore, 1:20,000 levonordefrin offers no caine and etidocaine, have been advocated for pro- clinical advantage over 1:100,000 epinephrine. longed pain control, with support from several clinical Articaine is available in the United States as a 4% trials.74–79 Recently, etidocaine has been withdrawn solution containing 1:100,000 and 1:200,000 epi- from the market by Dentsply Pharmaceuticals. nephrine.52 Articaine is an amide anesthetic that Although bupivacaine exhibits sustained anesthesia contains a thiophene ring and an ester linkage unlike and pain control, patients should be informed of other amide local anesthetics.52 The extra ester link- prolonged soft tissue anesthesia (lip sign) since this age is susceptible to hydrolysis by plasma esterases.52 may preclude their willingness to use this drug.75 Several studies have reported that articaine is safe Bupivacaine has a somewhat slower onset than 2% when used in appropriate doses.52–60 Although lido- lidocaine but almost twice the duration of pulpal caine and articaine have the same maximum 500 mg anesthesia (approximately 4 hours) in the mandible48 dose for the adult patient,50 the manufacturer’s (Figure 2). recommended maximum dose for a healthy 70 kg Ropivacaine is a structural homologue of bupiva- adult would be 7 cartridges of 4% articaine solution caine that appears to have a lower potential for central compared to 13 cartridges of 2% lidocaine solu- tion.50 Articaine, like prilocaine, has the potential to cause methemoglobinemia and neuropathies.52 While the incidence of methemoglobinemia is rare, dentists should be aware of this complication in patients who are at an increased risk of developing this condition.61 The incidence of neuropathies (involving the lip and/or the tongue), associated with articaine and prilocaine, is approximately five times more than that found with either lidocaine or mepivacaine.62,63 In one retrospective study, the incidence of paresthesia was approximately one in 785,000 injections.62 Therefore, while the paresthe- sia incidence is statistically higher for articaine and prilocaine, it is a clinically rare event that never- theless imposes some medicolegal implications. Figure 2 Time–response curve for the development of pulpal anesthe- Available literature indicates that articaine is sia (defined as no response on Analytical Technologies EPT at setting = equally effective when statistically compared to 80) of mandibular first molars following inferior alveolar nerve (IAN) 60,64–71 other local anesthetics, with relatively few block injection of either 1.8 mL of 2% lidocaine with 1:100,000 epi- studies demonstrating a statistical superiority of nephrine or 1.0 mL of 0.5% bupivacaine with 1:200,000 epinephrine. articaine over lidocaine for nerve blocks. Recent Data courtesy of Dr. A. Reader et al. 716 / Endodontics nervous system (CNS) and cardiovascular toxic increasing the volume of 2% lidocaine with epinephrine effects.80 Anesthesia from injection of 0.5% ropivacaine (from 1.8 to 3.6 mL) does not increase anesthetic with 1:200,000 epinephrine was equivalent to 0.5% success.1,49,84,97,98 Second, increasing epinephrine con- bupivacaine with 1:200,000 epinephrine. One study centration (from 1:100,000 to 1:50,000) does not appear found that 0.5 and 0.75% concentrations of ropivacaine to increase anesthetic success in normal teeth.46,99 without epinephrine were effective for IAN blocks.81 Third, hyaluronidase, an enzyme that reduces tissue IAN block injections are not always successful. As viscosity100 with favorable anesthetic enhancement noted above, patients with preoperative pain are at properties,101,102 was not found to improve the success risk for reduced rates of successful anesthesia. How- of lidocaine anesthesia in a recent double-blind, rando- ever, even in patients without pain, the IAN block mized clinical study.103 Fourth, carbonated solutions are injection is not always successful. Several hypotheses thought to trap the anesthetic within the nerve as well as have been advanced for this lack of complete suc- impose a direct depressant action on nerves.3 Lidocaine cess.69 First, the mylohyoid nerve has been suggested hydrocarbonate, however, was no more effective for to provide accessory innervation that might contri- anesthetic success.3 Fifth, diphenhydramine, an antihis- bute to the clinical failure of IAN block injec- tamine with reported local anesthetic properties,104,105 tions.82,83 However, clinical studies in which IAN did not improve lidocaine anesthesia when injected as a block injections were compared to an IAN block as combined solution.106 Sixth, meperidine, an opioid well as with mylohyoid nerve block failed to demon- analgesic with demonstrated anesthetic properties,107 strate any increase in anesthetic success. This led to did not improve the success of lidocaine anesthesia after the conclusion that the mylohyoid nerve is not a coinjection.107,108 Although these experimental appr- major contributor to failed IAN block injections.84 Sec- oachesusingpharmacological methodswere notsuccess- ond, it is possible that inaccurate positioning of the ful in improving IAN block anesthesia, other studies needle might contribute to IAN block failures; however, evaluating alternative methods of drug delivery proved confirming the needle position with either a medical more successful in addressing this problem. ultrasound device45 or radiographs85,86 failed to Alternative or supplemental injections are indicated increase success rates of IAN injections. Third, it is when IAN block is not successful. One alternative possible that needle deflection might be a cause for approach is to reduce the speed of injection for an IAN IAN block failures.87–89 However, neither a bidirec- block. A slow IAN block injection (60 seconds) signifi- tional rotation method, using the Wand (CompuDent, cantly increases anesthesia success rates (electric pulp Milestone Scientific Inc., Deerfield, IL),89 nor insertion testing), compared to a rapid injection (15 seconds).30 with the needle bevel oriented away from the mandib- There are three supplemental routes of injection that will ular ramus (so the needle would deflect toward the be discussed in the following sections, ‘‘The intraliga- mandibular foramen)90,91 substantially improved anes- mentary injection,’’ ‘‘The intraosseous injection,’’ and thetic success. Fourth, it is possible that the contralateral ‘‘The intrapulpal injection.’’ They are included in the IAN provides an accessory path for innervation. Cross- section under ‘‘Mandibular anesthesia’’ because this is innervation occurs in mandibular incisors92,93 but likely the major, though not exclusive, area for their clinical does not contribute to most cases of IAN block failures. application. Fifth, it is very possible that anesthetic failure of man- dibular anterior teeth might be due to the anatomical organization of the IAN where the ‘‘central core’’ of THE SUPPLEMENTAL axons supplies the distal anterior teeth and the outer INTRALIGAMENTARY INJECTION layer of axons supplies the posterior teeth.94,95 The well- The technique of intraligamentary anesthesia can be described failure of the IAN block to anesthetize ante- reviewed in other published papers or textbooks. Stu- rior teeth1–4,45–49,96 might be simply due to the lack of dies have reported that about 0.2 mL of solution is sufficient drug concentrations to block voltage-gated delivered with each mesial and distal injection using a sodium channels (VGSC) in the central core axons. Of traditional or pressure syringe, that different needle course, this hypothesis does not explain the failure to gauges (25, 27, or 30 gauge) are equally effective,109,110 block posterior mandibular teeth. Collectively, these and that standard syringes are as effective as special findings have prompted much research to increase the ligamental syringes.110–112 Several studies have shown success of IAN nerve block injections. that the intraligamentary injection produces initial suc- Several procedures have been evaluated for increasing cess rates of about 63 to 74% and that, if needed, reinjec- the rate of successful anesthesia of the IAN block. First, tions produce an overall success rate of about 92 to Chapter 22 / Pharmacologic Management of Endodontic Pain / 717

96%.11,110–113 The intraligamentary injection will not be dia.135,136 Sixth, minor damage to the periodontium successful in mandibular anterior teeth.114,115 This route does occur, but only at the site of needle penetration of injection should be considered a type of intraosseous and this subsequently undergoes repair in nearly all injection since the solutions are forced through cases. In very rare instances, periodontal abscesses and the cribriform plate into the marrow spaces around deep pocket formation113,114 or root resorption137,138 the tooth116–120 and not via the PDL. Although back- have occurred after intraligamentary injections. pressure upon injection is the most important factor Seventh, clinical and animal studies have shown no for anesthetic success,116,118 this simply reflects forces effect on the pulp following intraligamentary injec- necessary to penetrate the cribriform plate and does not tions114,121,122,138–140 other than a rapid and prolonged produce pressure anesthesia121,122 like the intrapulpal decrease in pulpal blood flow caused by epinephrine.127 injection.123,124 The presence of a vasoconstrictor signif- No histological induction of pulpal inflammation has icantlyincreasestheefficacyofintraligamentaryinjec- been observed in studies comparing restorative proce- tion,122,125–128 and anesthetic solutions with reduced dures to restorative procedures combined with intrali- vasoconstrictor concentrations (e.g., bupivacaine with gamentary injections.141 Therefore, intraligamentary 1:200,000 epinephrine) are not very effective with this injections are unlikely to cause pulpal necrosis. technique.128,129 The onset of anesthesia is immedi- Eighth, the intraligamentary injection of primary ate110–112,114,121,122 and if anesthesia is still not adequate, teeth may cause enamel hypoplasia of the developing reinjection is indicated. Since the duration of pulpal permanent teeth.142 However, the effect was not due anesthesia in asymptomatic cases following the IAN to the injection itself but due to the anesthetic agents nerve block plus supplemental intraligamentary injec- used. The same effect would seemingly be produced tions is only about 23 minutes,113 the operator must by an infiltration injection next to the developing work fairly quickly and be prepared to reinject if pro- tooth. Ninth, intraligamentary injection has been found anesthesia is lost. Although it has been reported reported to be safe in the presence of mild to mod- that the intraligamentary injection can be used in the erate gingival inflammation or incipient periodonti- differential diagnosis of pulpally involved teeth,130,131 tis.143 Taken together, the intraligamentary route of experimental studies have demonstrated that adjacent injection provides a useful supplemental route for teeth also become anesthetized with the intraligamentary increasing anesthesia success with minimal adverse injection of a single tooth.114,121,122 Therefore, the intra- events reported in the great majority of studies. ligamentary PDL injection should not be used for differ- A recent modification of the intraligamentary sup- ential diagnosis. plemental injection is the computer-assisted local Several studies have evaluated potential adverse anesthetic delivery system such as the Wand or effects that may occur with the intraligamentary route CompuDent (CompuDent, Milestone Scientific of injection. First, intraligamentary injections are more Inc.) that accommodates a standard local anesthetic painful when anesthetizing teeth with irreversible pul- cartridge that is linked by sterile microtubing to a pitis, as compared to normal teeth,5,111,114,122 and this disposable, pen-like handpiece with a Luer-Lok nee- may be due to the mechanical allodynia that often dle attached to the end. The device is activated by a occurs in cases of irreversible pulpitis.132 The patient foot control that automates the infusion of local should be made aware of this possibility. Second, intra- anesthetic solution at a controlled rate. A slow or ligamentary injections typically produce mild postinjec- fast flow rate may be initiated and maintained by a tion pain in the majority of patients for 14 to 72 hours foot pedal control. A 1.4-mL aliquot of solution is after injection,111,114,122 and this would be additive to delivered in 1 minute in the fast mode and in about any postendodontic pain. Third, about 40% of the 4 minutes and 45 seconds in the slow mode. The patients will report that their tooth feels high in occlu- slow rate is used for the intraligamentary injection. sion.114,122 Fourth, although a letter to the editor A recent study,144 using experimental subjects, reported avulsion of a tooth following intraligamentary demonstrated that the Wand method of primary injections,133 no clinical or experimental study has intraligamentary injection of 1.4 mL of 4% articaine reported avulsion or loosening of teeth with this tech- with 1:100,000 epinephrine, versus injection of 1.4 mL nique,114,121,122 and therefore, avulsion should not be of 2% lidocaine with 1:100,000 epinephrine, produced a concern when using the intraligamentary injection similar rates of successful anesthesia of the mandibular technique. Fifth, initial studies in dogs reported cardio- first molar (86 versus 74%, respectively, using EPT). vascular responses to intraligamentary injection of epi- The duration of anesthesia (31–34 minutes) was much nephrine-containing solutions134; however, this has not longer than that reported previously using a pressure been confirmed in clinical studies evaluating tachycar- syringe and 0.4 mL of a lidocaine solution 718 / Endodontics

(10 minutes).114 Another study evaluated patients the Stabident system when apical injections are con- with irreversible pulpitis and a failed IAN block. Suc- sidered. cess of the intraligamentary injection (none or mild As described above, a regular IAN block often pain upon endodontic access or initial instrumenta- provides poor anesthetic success in patients with irre- tion) was obtained in only 56% of the patients.145 The versible pulpitis (i.e., only 19 to 56% of patients results were somewhat disappointing because the report no/mild pain upon access).9–11,19,71,153 Thus, computer-controlled anesthetic delivery system several studies have evaluated whether supplemental should have been capable of delivering approximately intraosseous injections improve anesthetic success 1.4 mL of anesthetic solution via intraligamentary after IAN nerve block in odontogenic pain patients. injection by consistently maintaining a precise flow Several studies have evaluated the Stabident system rate. Thus, other supplemental injection procedures in patients with irreversible pulpitis in mandibular may be indicated in patients with irreversible pulpitis. posterior molars after failed conventional IAN nerve block injections. In general, these trials have demon- strated that a Stabident injection of 2% lidocaine with INTRAOSSEOUS ANESTHESIA 1:100,000 epinephrine produced 79% anesthetic suc- 18 A second route for supplemental injection is the cess at a volume of 0.45 to 0.9mL and 91% success 9 intraosseous injection. There are three intraosseous rate at an intraosseous injection volume of 1.8 mL. systems in the commercial market, including the Sta- The intraosseous injection was more successful than 113 bident system (Fairfax Dental Inc., Miami, FL),the the PDL injection, probably due to the greater X-tip system (Dentsply, Tulsa, OK), the IntraFlow amount of anesthetic solution delivered with the (IntraVantage, Plymouth, MN). However, to date, intraosseous injection. Other studies using a similar most published clinical trials have used either the patient population and experimental design have Stabident or X-tip systems. The Stabident system is demonstrated that supplemental intraosseous injection comprised of a slow-speed handpiece-driven perfora- of 3% mepivacaine produced 80% success after one tor, a solid 27-gauge wire with a beveled end that, cartridge and 98% success following a second intraoss- 10 when activated, drills a small hole through the corti- eous injection. Another study demonstrated that a cal plate. The anesthetic solution is delivered to the supplemental intraosseous injection of 1.8 mL of 4% cancellous bone through the 27-gauge ultra-short articaine with 1:100,000 epinephrine was 87% success- injectorneedleplacedintotheholemadebythe ful after the failure of IAN blocks for posterior teeth 153 perforator; the modified nonbevel needle is recom- diagnosed with irreversible pulpitis. Two conclu- mended for ease of negotiation. The X-tip anesthesia sions are evident from this analysis. First, a supplemen- delivery system consists of a special hollow needle tal intraosseous injection after a failed IAN nerve block that serves as the drill penetrating the cortical plate, significantly improves anesthetic success. Second, it whereupon it is separated and withdrawn. The guide appears that an intraosseous injection of one cartridge sleeve is designed to accept a 27-gauge needle to inject of 3% mepivacaine plain may not be as efficacious as one the anesthetic solution and is removed after injection cartridge of 2% lidocaine with 1:100,000 epinephrine. (Figure 3). However, as noted below, an advantage of mepivacaine Several characteristics are similar among the studied is that 3% mepivacaine does evoke the tachycardia typi- intraosseous delivery systems. First, anesthetic success cally observed with epinephrine-containing anesthetic is improved following injection into a site distal rather solutions. than mesial to the selected tooth.19,51,146–152 The Parallel studies have evaluated the X-Tip system in exception to this rule is the maxillary and mandibular patients with irreversible pulpitis in mandibular pos- second molars where the mesial site should be terior molars after failed conventional IAN nerve selected.19,51,146–152 Second, the onset of anesthesia block injections. In one study evaluating apical posi- is essentially immediate.19,51,146–153 Third, manufac- tioning of the perforator, the X-tip injection site was 3 turer’s instructions locate the perforation site in to 7 mm apical to the mucogingival junction of the attached gingival, where the cortical bone is often mandibular molar or premolar tooth, and 1.8 mL of thinner and one can inject at a site equidistant between 2% lidocaine with 1:100,000 epinephrine was admi- 19 adjacent root structures. However, two studies have nistered. The authors reported that in the absence of successfully used the X-tip system, with its guide sleeve the backflow of anesthetic solution into the oral cav- design, in alveolar mucosa at a more apical loca- ity, the success rate was 82%, but that in the presence 19 tion,19,148 providing a potential clinical advantage over of a backflow, the success rate dropped to 18%. Chapter 22 / Pharmacologic Management of Endodontic Pain / 719

A B

C D

Figure 3 Intraosseous anesthesia delivery system X-tip. A, The X-tip system comes in two parts: the drill and the guide sleeve and special injection needle. First, anesthetize the mucobuccal fold and select a site 2 to 4 mm apical to the alveoli crest and between the roots. B, Place the X-tip drill in a slow-speed handpiece (15,000 to 20,000 rpm) and drill at maximum speed at 90 to the bone. In 2 to 4 seconds the drill will perforate the cortical bone into the cancellous bone. C, Hold the guide sleeve in place and withdraw the drill. D, Insert the special short needle into the hole in the guide sleeve and slowly inject a few drops of anesthetic solution. In the event, additional anesthesia is needed later; the guide sleeve can be left in place until the endof treatment.

Several clinical implications can be derived from backflow occurs, the clinician should consider reper- these studies. First, given the relatively high failure foration at the same or another site. A second intraoss- rate of IAN blocks in patients with irreversible pulpi- eous injection of 1.4 mL of 2% lidocaine with tis, it would be prudent to consider using these 1:100,000 epinephrine 30 minutes after the initial combined methods in all patients with irreversible intraosseous injection provided an additional 15 to pulpitis. Second, anesthetic success requires deposi- 20 minutes of pulpal anesthesia.154 Third, in studies tion of the solution into the cancellous bone. If using either the Stabident or the X-tip system, the 720 / Endodontics duration of anesthesia was sufficient for the entire with a vasoconstrictor-containing anesthetic solutions, debridement appointment.9,19,153 Fourth, no clinical but instead is based on the avoidance of a transient study has reported the anesthetic success rate or tachycardia combined with its reasonably effective adverse events of supplemental intraosseous injection anesthesia.155,158 Fourth, the traditional long-acting in painful teeth with necrotic pulps and periradicular local anesthetic (e.g., bupivacaine) did not demonstrate radiolucencies. Therefore, no evidence-based clinical prolonged anesthesia after intraosseous or maxillary recommendations for necrotic cases can be made due infiltration anesthesia.152,159–161 Given concerns about to this lack of data. This is an area for future research. its potential for cardiotoxicity,162 bupivacaine should Several studies have evaluated potential adverse not be used for intraosseous anesthesia. Fifth, some effects that may occur with intraosseous injections. authors have cautioned that administration of an overly First, pain may occur during perforation and solution large volume of local anesthetic with an intraosseous deposition when using the Stabident system, although injection could lead to overdose reactions.163 However, the incidence of even a moderate transient pain is low venous plasma levels of lidocaine were the same for in asymptomatic patients.146–151 In symptomatic teeth maxillary anterior intraosseous and infiltration injec- with irreversible pulpitis, the incidence of transient tions of 2% lidocaine with 1:100,000 epinephrine.164 moderate–severe pain is about 0 to 16% during Stabi- Therefore, the intraosseous technique should not be dent perforation and about 5 to 31% during injection considered an intravascular injection. Sixth, about 2 of the anesthetic solution.9,10,153 For the X-tip system to 15% of patients receiving Stabident injection have in patients with irreversible pulpitis, there is a 48% reported moderate pain on a postoperative day,51,146, incidence of moderate to severe pain with perforation 149,150,155 although this is less than that reported after and a 27% incidence with injection of anesthetic.19 intraligamentary injection.122 Gallatin et al.165 found Second, it has been estimated that about 1% of per- that significantly more males experienced postoperative forators ‘‘separate’’ during use, requiring removal with pain with the X-tip system than with the Stabident a hemostat.19,146–151 Third, a transient tachycardia (12 system. They felt that this was related to a denser and to 32 bpm) can occur for about 4 minutes in 46 to 93% more mineralized bone in the posterior mandible in of patients after Stabident or X-tip intraosseous injec- males and the fact that the X-tip perforating system tion of epinephrine- and levonordefrin-containing diameter is larger than the Stabident perforator result- solutions.9,19,51,146–150,152,153,155 No significant change ing in the generation of more frictional heat during in diastolic, systolic, or mean arterial blood pressure perforation. Seventh, other postinjection problems has been observed with the intraosseous injection of can occur, including swelling and/or exudate at the site 2% lidocaine with 1:100,000 epinephrine.155,156 In one of perforations in <5% of patients after Stabident and study, a slow intraosseous injection (over 4 minutes possibly a slightly greater prevalence after X-tip injec- 45 seconds using a computer-assisted local anesthetic tions.51,146,149,150,155,165 These slow-healing perforation delivery system) was compared to a ‘‘fast’’ injection sites may be due to overheating of the bone caused by (45 seconds) of 2% lidocaine with 1:100,000 epinephr- pressure during perforation, warranting a slow gentle ine. The slow infusion produced a significantly lowered approach during perforation. To date, all such reported magnitude of tachycardia (12 versus 25 bpm).157 cases have healed without incidence. Although transient tachycardia is noticeable to the patient, it is thought to be not clinically significant in otherwise healthy patients.155 Importantly, there is THE INTRAPULPAL INJECTION no significant increased tachycardia when 3% mepi- In about 5 to 10% of mandibular posterior teeth with vacaine is used for intraosseous anesthesia.155,158 This irreversible pulpitis, supplemental intraosseous injec- represents an alternative approach for patients tions, even when repeated, do not produce profound whose medical condition (moderate-to-severe cardi- anesthesia; pain persists when the pulp is entered. This ovasculardisease)ordrugtherapies (patients taking is an indication for an intrapulpal injection. The tricyclic antidepressants or nonselective b-adrenergic advantage of the intrapulpal injection is that it works blocking agents) suggest caution in administering well for profound anesthesia if given under backpres- epinephrine- or levonordefrin-containing solutions. sure.123,124 Onset will be immediate and no special Based upon these considerations, the intraosseous syringes or needles are required. The major drawback injection of 1.8 mL of 3% mepivacaine without a vaso- of the technique is that needle placement and injection constrictor (e.g., 3% Carbocaine) could be recom- are directly into a vital and very sensitive pulp; the mended as a local anesthetic of first choice. This is not injection may be moderately to severely painful and based on the potential cardiovascular risks associated the patient should be warned of this potentiality.9 Chapter 22 / Pharmacologic Management of Endodontic Pain / 721

Maxillary Anesthesia anterior superior alveolar (P-ASA) injection deposits the anesthetic solution into the incisive canal and Descriptions of conventional techniques for maxillary derives its name from the injection’s ability to suppo- anesthesia are available for review in numerous articles sedly anesthetize both the right and the left anterior and textbooks. Clinically, maxillary anesthesia is more superior alveolar nerves leading to bilateral anesthesia successful than mandibular anesthesia and the infiltration 175 12 of maxillary incisors and canines. However, needle routeisbyfarthedominantapproach. Numerous stu- insertion results in 54 to 58% of the subjects reporting dies have demonstrated that infiltration injection of anes- moderate/severe pain following needle placement.34,176 thetics such as 2% lidocaine with 1:100,000 epinephrine The anterior middle superior alveolar (AMSA) injection results in 90 to 95% successful pulpal anesthesia (obtain- is a new route for anesthetizing the maxillary central ing an 80 reading) in anterior and posterior maxillary 67,68,160,166–169 and lateral incisors, canines, and first and second pre- teeth. Although the onset of infiltration molars.177–179 The AMSA injection site is located pala- anesthesia usually occurs within 5 to 7 minutes, the dura- tally at a point that bisects the premolars and is tion is fairly short in both anterior (20 to 30 minutes) and 160,166–169 approximately halfway between the midpalatine raphe posterior (30 to 45 minutes) maxillary teeth. and the crest of the free gingival margin. However, This may require additional anesthetic injections depend- studies evaluating the AMSA route have reported ing on the length of the procedure. For maxillary infiltra- rather modest to low success rates,180,181 and 32% to tion injections, increasing the volume of 2% lidocaine 38% incidence of moderate injection pain.35 with 1:100,000 epinephrine to 3.6 mL will increase the duration of pulpal anesthesia.167 As with mandibular anesthesia, pulpal anesthesia does not last as long as soft tissue anesthesia.160,166–169 The infiltration injection of 4% Non-Narcotic Analgesics: Nonsteroidal prilocaine (1:200,000 epinephrine) is similar in action to Anti-Inflammatory Analgesics an infiltration injection using 2% lidocaine (1:100,000 epinephrine).169 In most,65–68 but not all,170 studies, max- and Acetaminophen illary infiltration injections of articaine with 1:100,000 The major analgesic drug class for treating endodontic epinephrine were equivalent to both prilocaine and lido- pain is the non-narcotic drugs, consisting of the non- caine with epinephrine. Although bupivacaine provides steroidal anti-inflammatory analgesics (NSAIDs) and long-acting anesthesia in the mandible, it does not pro- acetaminophen. The reader is referred to basic phar- vide prolonged pulpal anesthesia in maxillary infiltration macology texts for an overview of these drugs. The injections.80,159,160 The infiltration injection of anesthetics present review will instead focus on newer evidences without vasoconstrictors, 3% mepivacaine plain and 4% and clinical implications from controlled clinical prilocaine plain, produce a brief duration (15 to 20 min- trials. The NSAID class of drugs are thought to pro- utes) of pulpal anesthesia and accordingly are generally duce their analgesic and anti-inflammatory effects by used only for brief procedures.168,169 the inhibition of cyclooxygenase (COX).182 Other Since many endodontic procedures are done on mechanisms such as inhibition of cell signaling mole- one tooth at a time, the infiltration route is most cules (e.g., NFkB) have also been proposed.183 Two commonly employed. However, for the sake of com- major isotypes of COX have been described,184,185 and pleteness, major maxillary block injections that are NSAID drugs can be classified based upon their pre- effective for anesthetizing multiple teeth will be briefly ference for blocking COX1 or COX2. NSAIDs such as reviewed. The posterior superior alveolar (PSA) nerve ibuprofen should be considered ‘‘mixed COX’’ inhibi- block anesthetizes some first molars, and all second tors since they can inhibit both enzymes at clinical and third molars.7 Generally, to ensure patient com- dosages. Moreover, a recent study has reported that fort for the first molar, an additional buccal infiltration the analgesic efficacy of ibuprofen depends upon the injection after the PSA block may be needed. The genetic mutation of COX1, with patients having certain infraorbital nerve block injection will anesthetize polymorphisms of COX1 displaying significantly better the first and second premolars and the lip, but not analgesic responses than patients having other poly- the central or lateral incisors.171,172 The second division morphisms.186 If confirmed, then variations in patient nerve block will successfully anesthetize the pulps of responses to NSAIDs might be due to variations in the molar teeth and about 50% of the second premo- mutations on the gene encoding the COX1 enzyme. lars.173,174 The high tuberosity approach is preferred Blockade of COX1 is associated with increased risk for over the greater palatine approach because the success gastrointestinal side effects such as ulcers, whereas rate is similar and it is less painful.173 The palatal- blockade of COX2 is associated with increased 722 / Endodontics

Table 2 Meta-Analysis of Non-Narcotic Analgesics for Relief of Postoperative Pain Percentage of Patients N (No. of Drug with ‡50% pain relief patients)

Ibuprofen 200 mg 46 1,194 Ibuprofen 400 mg 56 3,402 Ibuprofen 600 mg 79 203 Diclofenac 50 mg 50 367 Diclofenac 100 mg 70 204 Acetaminophen 600–650 mg 36 1,265 Acetaminophen 600–650 mg 48 911 plus codeine 60 mg Placebo ~13 6,497

Data adapted from Barden J et al.192

important, only the acetaminophen/codeine combina- tion was associated with any significant increase in adverse effects.192 Fortunately, these findings mirror the responses of endodontists published in a recent Figure 4 Schematic illustration of the relationship between risk for survey196 where non-narcotics, especially ibuprofen adverse side effect profile of non-narcotic analgesics based on the relative 187 600 mg, were dominantly selected for pain control over inhibition of COX1 versus COX2. Adapted from FitzGerald GA. the acetaminophen/opiate combination drugs. Other studies have evaluated the analgesic benefit of NSAIDs for treating pain after nonsurgical endodontic cardiovascular risk such as thrombotic events.187 procedures.197–215 In general, the randomized placebo- Instead of a bimodal classification, the NSAIDs should controlled endodontic studies have demonstrated be viewed as having an inhibitory continuum,187 where significant analgesic benefits for patients treated with drugs can have varying efficacy for inhibiting COX1 flurbiprofen,202 flurbiprofen/tramadol,197 intracanal versus COX2, and accordingly would be expected to ketorolac,198 IM ketorolac,208 intraoral ketorolac vary in their clinical side effect profile (Figure 4). Based (in some,201,207 but not all216 studies), piroxicam,210 upon findings demonstrating rapid upregulation of mefanamic acid,211 aspirin,211 diclofenac,209 ketoprofen prothrombic enzymes188 and cardiac events,189,190 it (in some,199,209 but not all200 studies), ibuprofen,199,204 has been suggested that most patients would be best and ibuprofen/acetaminophen.204 managed with the non-COX2-selective NSAIDs such as Interestingly, ibuprofen 600 mg produced only a ibuprofen.191 modest/moderate analgesic effect in several postendo- Several systematic reviews have been published dontic studies.217–220 It is not clear if this modest analge- describing the efficacy and adverse effect profile of sic effect reflects a non-COX pain mechanism in NSAIDs for treating both postsurgical pain192–194 and endodontic pain patients reflective of chronic inflamma- postendodontic pain.195 In general, these studies have tory conditions (e.g., cytokines), or whether it represents demonstrated that NSAIDs produce excellent analgesic a ‘‘floor effect’’ where nonsurgical root canal treatment responses in patients who can tolerate this class of by itself reduces pain to the extent that it is difficult to drugs. For example, in a meta-analysis of >14,000 third detect further reduction by the addition of an analgesic. molar patients,192 several NSAIDs were shown to This latter point has been observed in many endodontic produce a dose-related analgesic effect (defined as trials where non-surgical root canal treatment (NS- >50% pain relief). These data are summarized in RCT) plus a placebo pill resulted in a 50 to 80% pain Table 2. Since many clinicians were originally taught reduction, 24 to 48 hours after treatment.197,199 How- that acetaminophen/codeine combinations provide ever, the overall interpretation of these data provide superior pain control, it is worth carefully reviewing strong support for the use of NSAIDs as a primary class these data. The lowest studied dose of ibuprofen of analgesics for treating acute inflammatory pain due to (200 mg) actually has about the same analgesic response either surgical or nonsurgical procedures. as acetaminophen 600 to 650 mg/codeine 60 mg. More- As noted in Chapter 10, ‘‘Mechanisms of Odonto- over, the 400 mg and 600 mg doses of ibuprofen pro- genic and Non-Odontogenic Pain,’’ the VGSC play duce substantially greater levels of analgesia. Equally the dominant role in the signaling of nociceptor Chapter 22 / Pharmacologic Management of Endodontic Pain / 723 activity from the periphery to the CNS. In particular, Steroids the TTX-resistant class of VGSCs expressed on noci- Various classes of drugs have been studied for the ceptors is relatively resistant to lidocaine and is sensi- 197 tized by prostaglandins.16,221,222 One interpretation of management of endodontic posttreatment pain. these basic science findings is that NSAIDs would be These include non-narcotic analgesics comprising expected to increase the effectiveness of local anes- NSAIDs and acetaminophen, opioids and glucocorti- thetics by virtue of their ability to reduce prostaglan- coids (steroids). This section will consider the use of din levels in inflamed tissue. A preemptive approach glucocorticoids for the management of endodontic to improve anesthesia in patients with irreversible pain. For an in-depth description of the pharmacology, pulpitis is to give ibuprofen 1 hour before anesthetic pharmacodynamics, mechanisms and sites of action, as 223 well as their anti-inflammatory actions, the reader is administration. A recent study evaluated ibuprofen 198,199,234–238 given before local anesthetic injection in patients with directed to review articles. irreversible pulpitis. It concluded that it significantly The potent anti-inflammatory properties of glucocor- improved the depth of anesthesia using an EPT testing ticoids were first appreciated and utilized as an adjunct to endodontic therapy more than 50 years ago.239–241 paradigm. Another study pretreated patients with 242 either a placebo or with acetaminophen 650 mg or Steroids have been used as a pulp-capping agent, as the combination of ibuprofen 600 mg with acetami- an intracanal medicament either alone or in combina- tion with antibiotics/antihistamines,198,240,241,243–247 nophen 650 mg. They concluded that the odds ratio 199,248,234–236,239,249–253 for the combination group tended to favor successful and systemically as a means to anesthesia in the active groups as compared to the decrease pain and inflammation in endodontic patients. placebo.224 However, both of the studies have fairly In critically evaluating the literature, it must be kept small sample sizes, and further research is needed on in mind that the most powerful conclusions are gen- this potentially important clinical finding. erated from studies that are prospective, randomized, Acetaminophen represents the second major mem- double-blind, and placebo-controlled. However, none ber of the non-narcotic class of analgesics. Its utility is of the endodontic reports on the use of corticoster- largely based on the finding that its side effect profile oids published prior to 1984 meets these criteria, and is less adverse than the NSAIDs, and that the drug can the results therefore should be considered as lower be used in patients for whom NSAIDs are contra- levels of evidence. Results from studies that used indicated.225 Although acetaminophen has been used corticosteroids in combination with other agents for nearly 100 years, its mechanism of action remains (antibiotics and/or antihistamines) are also difficult mostly unknown. Acetaminophen does inhibit per- to interpret, as results ascribed to one of the agents 199,200 ipheral COX activity in inflamed tissues but only at may reflect the activity of the combination. doses of about 1,000 mg.226 Recent studies have sug- Equally difficult to interpret are results from studies 198,240,241,243–247 gested additional mechanisms by which acetamino- using intracanal steroid delivery. The phen may act by metabolic conversion to a compound methodology in these studies cannot account for previously called AM404, which is a cannabinoid-like either the dosage or the delivery period of the intra- analgesic.227 Indeed, acetaminophen antinociception is canal medicament to reach the site of action (peria- reversed in mice by pretreatment with a cannabinoid pical tissues). In these studies, very small dosages of receptor antagonist.228 However, other potential the steroid are placed into the canal(s). Even assuming mechanisms have been proposed including modulation apical patency of unknown size, the steroid must pass of the serotonin receptor 5HT1A.229 through the apical foramen via passive diffusion along In humans, acetaminophen inhibits central sensitiza- a concentration gradient, and this may be opposed by tion under conditions that exclude a potential periph- a potential backpressure from periapical transudate or eral site of action,230 suggesting that this drug also has a exudate. For a critical assessment of these studies, the CNS site of action. Interestingly, animal studies demon- reader is directed to review an article by Marshall.238 strate that acetaminophen produces synergistic effects Studies evaluating the systemic administration of cor- with a variety of NSAIDs (i.e., ibuprofen, diclofenac, ticosteroid as the sole agent, in a known dose, are the ketoprofen, meloxicam, metamizol, naproxen, nimesu- critical ones in evaluating the efficacy of the steroid’s lide, parecoxib, and piroxicam) using a mouse model of ability to decrease endodontic posttreatment pain. tissue hyperalgesia.231 This finding appears to have clin- In a randomized, prospective, double-blind, placebo- ical implications since acetaminophen/NSAID combi- controlled study, Marshall and Walton235 evaluated nations appear to be very effective for pain control the effect of the intramuscular injection of dexametha- following surgical232,233 or endodontic204 procedures. sone on posttreatment endodontic pain when compared 724 / Endodontics to a placebo. After endodontic instrumentation and/ saline) or dexamethasone (2, 4, 6, 8 mg/mL). The injec- or obturation, patients received an IM injection of tion was given into the masseter, internal ptyergoid, or 1.0 mL of either dexamethasone (4 mg/mL) or sterile buccinator muscle; preference was given to introoral saline. Pain levels of none, mild, moderate, or severe muscles anesthetized for treatment. Patients recorded were recorded preoperatively at 4, 24, and 48 hours their pain levels on a 0 to 9 scale. Pretreatment and posttreatment.Teethwithvitalandnecroticpulpsas posttreatment (4, 8, 24, 48, and 72 hours) pain levels well as retreatment cases were included. No antibio- were recorded. The type and the amount of posttreat- tics were taken by the patients and no postoperative ment analgesics taken were also recorded. No antibiotics infections were reported. The amount of additional were given at any time. Results showed patients receiv- postoperative pain medication required was not ing dexamethasone had significantly less severe pain at 4 recorded. Results indicated that dexamethasone sig- and 8 hours postoperatively (p<0.05) and took signifi- nificantly reduced both pain incidence and severity at cantly less pain medication compared to the placebo 4 hours posttreatment. At 24 hours posttreatment, (dexamethasone mean, 1.98 tablets; placebo mean, patients in the corticosteroid group showed a trend 4.64 tablets). When evaluated on a milligram per kilo- toward less pain. gram dosage basis, patients who received 0.07 to Another double-blind study evaluated the effect of 0.09 mg/kg of IM dexamethasone had significantly less oral dexamethasone on posttreatment pain.252 Fifty pain at 8 hours and required significantly less post- patients presenting for endodontic treatment were operative pain medication when compared to the IM studied. Retreatment cases and patients presenting placebo. with purulent drainage or cellulitis were excluded. Kaufman et al.254 were the first to evaluate the Teeth were instrumented and closed with no intraca- effect of the intraligamentary delivery of dexametha- nal medication. Pretreatment, 8, and 24 hours post- sone on endodontic posttreatment pain. Forty-five treatment pain levels were recorded on a visual analog patients were randomly assigned to one of three scale (0–100). Patients randomly received dexametha- experimental groups. Endodontic treatment was com- sone (0.75-mg tablet) or a placebo, with instructions pleted in one appointment on both vital and necrotic to take three tablets immediately and then one tablet pulps, with and without periapical radiolucencies. every 3 hours until bedtime for a total of seven tablets. After the administration of local anesthesia, but prior Results showed that patients receiving dexamethasone to endodontic treatment, patients in Group 1 received had significantly less pain at 8 and 24 hours when 4 to 8 mg of slow-release methylprednisolone (Depo- compared to those receiving the placebo (p<0.01) Medrol) via an intraligamentary syringe. Single- A third study250 evaluated the effect of oral dexa- rooted teeth received 4 mg, and multirooted teeth methasone on endodontic interappointment pain, but received 8 mg. Group 2 received a PDL injection of at a much higher dosage than the preceding study.252 3% mepivacaine in a similar fashion to Group 1. Forty patients with ‘‘asymptomatic vital inflamed’’ Patients in Group 3 received no PDL injection. pulps were evaluated. After endodontic instrumenta- Pretreatment pain levels were not recorded. Patients tion and temporization, alternate patients were given were telephoned at 24 hours posttreatment and either dexamethasone (4 mg per tablet) or a placebo. reported their pain intensity on a 1–10 scale. The Instructions were to take one tablet immediately and results showed a significant decrease in postoperative then one tablet at 4 and 8 hours posttreatment for a pain in the methylprednisolone group compared to total dose of 12 mg in the dexamethasone group. Pain the active and passive placebo groups (p<0.05). was recorded on a visual analog scale at 8, 24, and Gallatin et al.248 evaluated pain reduction in patients 48 hours posttreatment. Patients receiving dexametha- with untreated irreversible pulpitis using an intraoss- sone had a statistically significant reduction in pain at eous injection of methylprednisolone. Forty patients all post treatment periods. with a clinical diagnosis of irreversible pulpitis actively Liesinger et al.234 in a double-blind, randomized, associated with moderate–severe pain participated in prospective, placebo-controlled study evaluated the this prospective double-blind study. The involved effect of four different dosages of dexamethasone on tooth was anesthetized followed by an intraosseous posttreatment endodontic pain. All patients (N=106) injection of 1 mL of either methylprednisolone presented with pretreatment pain. Pulp status was (Depo-Medrol 40 mg/mL) or saline. The blinded solu- recorded (vital and necrotic cases were included). tions were administered using the Stabident system Endodontic instrumentation and/or obturation was (Fairfax Dental Inc.). No endodontic treatment was performed after which patients randomly received a performed at this time. Patients were given a 7-day pain 1.0-mL intraoral injection of either a placebo (sterile diary as well as analgesic medication. Over the 7-day Chapter 22 / Pharmacologic Management of Endodontic Pain / 725 observation period, patients who received Depo-Medrol Results indicated that the patients in the dexa- reported significantly less pain (p<0.05) compared to a methasone group had a statistically significant placebo while taking significantly fewer analgesics decreased incidence and severity of endodontic (p<0.05). interappointment pain. Bramy et al.236 evaluated the intraosseous admin- Prior to interpreting these studies,248,234–236,249– istration of corticosteroid for pain reduction in 251,253 it is critical to remember that endodontic symptomatic necrotic teeth. Thirty-eight patients treatment has a major effect in reducing posttreat- with a clinical diagnosis of pulpal necrosis with ment pain regardless of pharmacologic intervention. associated periapical radiolucency participated in As stated by Hargreaves,255 ‘‘ This reduction in post- the study. All patients experienced moderate–severe treatment pain, combined with variable levels of pain at the time of presentation with mild or no preoperative pain, reduces the statistical power of clinical swelling. After complete canal debridement, endodontic clinical trials for detecting active analge- patients in a double-blind fashion randomly sics over time in all patient groups (the so-called received an intraosseous injection of 1 mL of either floor effect). This limitation is a problem in inter- methylprednisolone (Depo-Medrol 40 mg/mL) or preting clinical studies in general and may explain sterile saline. All subjects received ibuprofen and why some endodontic clinical trials fail to detect Tylenol #3 (with codeine) and were instructed to analgesic treatment or only detect it in those patients take the medication as needed for pain. Patients with moderate/severe pain.’’ This has been shown by recorded their pain levels and the type and amount Torabinejad et al.199 and Rogers et al.198 where var- of pain medications taken for 7 days postopera- ious agents including corticosteroid significantly tively. The results showed that the steroid group reduced posttreatment pain but only in those had significantly less postoperative pain and took patients who presented for treatment with at least significantly less pain medication over the 7 days moderate/severe pretreatment pain. It would seem when compared to the placebo group (p<0.05). No that the systemic administration of a corticosteroid antibiotics were taken by patients at any time. to ameliorate endodontic posttreatment pain would In a follow-up study, Claffey et al.249 evaluated pain be appropriate only for those patients who present reductioninsymptomaticteethwithnecroticpulps with at least moderate levels of preoperative pain. using an oral dose regimen of methylprednisolone. The Three independent studies234,236,249 meet the criteria materials and methods were nearly identical to Bramy of being prospective, randomized, double-blind, pla- et al.236 except that no patient had clinical swelling, and cebo-controlled with no drug combinations, and after canal debridement, patients randomly received including patients who presented with the required either oral methylprednisolone (48 mg/day for 3 days) level of pretreatment pain. Importantly, these studies or an oral placebo (lactose 48 mg/day for 3 days) in a showed that the systemic administration of corticos- double-blind fashion. All patients received ibuprofen teroid not only significantly reduces posttreatment and Tylenol #3 and a diary to record pain, percussion pain at various times but also significantly reduces pain, swelling, and number and type of pain medication the amount of additional pain medication required. taken. Clinical success was defined as any patient who Interestingly, the reports by Bramy et al.236 and experienced only none–mild pain, none–mild percus- Claffey et al.249 show significant pain relief with the sion pain, none–mild swelling, and did not take any administration of a steroid for up to 7 days posttreat- Tylenol #3. No antibiotics were prescribed or taken. ment, in contrast to Liesinger et al.234who found sig- The results showed that patients who received methyl- nificant differences in pain reduction only in the first prednisolone had a significantly higher level of clinical 8 hours. It is possible that these findings are due to success when compared to the placebo (p<0.05). differences in dosages of different corticosteroids or Ouyang et al.253 evaluated the effect of submuco- due to the routes of administration. This is probably sally injected dexamethasone on both the incidence not the case, as dexamethasone is approximately five and the severity of endodontic interappointment times as potent as methylprednisolone. The 6 to 8 mg pain. Teeth with a diagnosis of asymptomatic pulpal intramuscular dosage used by Liesinger et al.234 would necrosis were endodontically treated in one appoint- be equivalent to 30 to 40 mg of methylprednisolone. ment. Eighty patients received a submucosal injec- Intraosseous 40 mg of methylprednisolone was the tion of 5 mg dexamethasone; the control group of dosage used by Bramy et al.236 It may be speculated 80 patients had endodontic treatment performed that these differences in the duration of action might but no submucosal injection. Pain incidence and be related to differences in the preoperative pulpal and severity was evaluated for 3 days postoperatively. periapical status of the patient populations of these 726 / Endodontics studies. All of the patients in the studies by Bramy pathogenic microorganisms. None of the studies et al.236 and Claffey et al.249 presented for treatment published since 1984 supports this premise, includ- with necrotic pulps, associated periapical radiolucen- ing those cases with a diagnosis of pulpal necrosis cies, and either mild or no swelling. The majority of with periapical radiolucency where the potential for patients in the study by Liesinger et al.234 had a pre- dissemination of an infectious process might be operative diagnosis of irreversible pulpitis and acute expected.236,249 Antibiotics were not given or needed apical periodontitis. Those patients with necrotic at any time during these studies nor were the steroids pulps had no associated periapical radiolucencies. It associated with any increase in infection rate compared is plausible that corticosteroids may be more effica- to the control groups. It can be concluded that anti- cious in attenuating the pain associated with pulpal biotics are not routinely required or recommended in necrosis and an associated radiolucency compared to conjunction with corticosteroids for the management pain associated with irreversible pulpitis. Necrosis/radi- of endodontic posttreatment pain in the otherwise olucency is associated with a more complex chronic healthy patient. inflammatory process. Thus the efficacy of corticoster- oids, in endodontic pain patients, may be related to variations in the periapical immunological/inflamma- Opioid Analgesics tory dynamics of teeth with irreversibly inflamed pulps compared to necrotic pulps. Because opioids are not anti-inflammatory, nonopioids OnthebasisoftheworkofBramyetal.236 and with anti-inflammatory efficacy (e.g., aspirin, ibupro- Claffey et al.,249 it is plausible that corticosteroids fen) are the analgesics of first choice for endodontic would have efficacy in cases of endodontic flare-up pain.260 It has been shown that codeine in a 30 mg that result after treatment of previously asympto- dose provides no more analgesia than a placebo.261,262 matic teeth with necrotic pulps with or without However, a 60 mg dose of codeine produces signifi- associated periapical radiolucencies. This premise cantly more analgesia than a placebo. Thus, opioids in has not been investigated. The low incidence of this the appropriate dosage may be of benefit when addi- type of flare-up256 would require a multicenter tional pain control in needed. For example, if an study over a period of years to achieve an adequate NSAIDisnotcontrollingapatient’sdiscomfort,an sample size. opioid combination such as acetaminophen/hydroco- It appears that the route of systemic administration done may be prescribed in addition to the NSAID. of a steroid is not a determinant in the efficacy of Opioids in combination with an NSAID produce addi- action.234,236,249 When given in equivalent dosages, tional analgesia beyond the ceiling effect of the NSAID. agents such as dexamethasone and methylprednisolone Opioid analgesics activate mu receptors that inhibit the appear to be interchangeable. If a systemic steroid is to transmission of nociceptive signals from the trigeminal be administered, an intraoral IM injection or an nucleus to the higher brain centers and activate periph- intraosseous injection would seem to be preferable over eral receptors to reduce pain.263,264 Although opioid an extraoral IM injection. Clinicians are familiar with analgesics may be effective for the relief of moderate to intraoral and intraosseous injections, and the site of severe pain, their use is limited by adverse side effects injection is already anesthetized. Intraoral injection of that include nausea, vomiting, drowsiness, dizziness, steroid would be preferable to a written prescription constipation, and respiratory depression. In addition, for glucocorticoid as no assumption to patient com- chronic use is associated with tolerance and depen- pliance is required. An injection dosage of 6 to 8 mg of dence. Because of the numerous side effects, opioids dexamethasone or 40 mg of methylprednisolone are usually used in combination with other analgesics appears to be appropriate for the adult patient. If an to manage endodontic pain. Table 3 has a list of opioids oral route is chosen, 48 mg of methylprednisolone per day for 3 days and by extrapolation 10 to 12 mg of dexamethasone per day for 3 days should provide sig- Table 3 Opioid Analgesic Combinations nificant posttreatment pain relief. Opioid Combination Usual Dose It has been stated that antibiotics must be given in Acetaminophen (300 mg) and codeine (30 mg) 2 tablets q4h conjunction with steroids to prevent an infection Aspirin (325 mg) and codeine (30 mg) 2 tablets q4h secondary to a decrease in the inflammatory Acetaminophen (500 mg) and hydrocodone (5 mg) 1-2 tablets q6h response.239,257–259 The implication is that suppres- Acetaminophen (325/500 mg) and oxycodone (5 mg) 1 tablet q6h sion of inflammation also means a decrease in local Aspirin (325 mg) and oxycodone (5 mg) 1 tablet q6h Ibuprofen (200 mg) and hydrocodone (7.5 mg) 1 tablet q6h defenses permitting unchecked proliferation of Chapter 22 / Pharmacologic Management of Endodontic Pain / 727 in combination with aspirin, acetaminophen, and ibu- 1,000 mg, four times a day for no more than 2 to profen that may be used to alleviate pain of endodontic 3 days after the procedure. This combination of origin. Clinicians must be aware of drug-seeking analgesics provides a useful alternative to the classi- patients who request a specific opioid. cal use of narcotic-containing analgesic drugs. • It is our belief that the integration of high-quality clinical research findings together with the clini- cian’s own skills, the patient’s desires and the par- Conclusions ticulars of each case, represents the highest level of clinical care. From this perspective, this chapter A thorough knowledge of the biological (Chapter 10, represents an important contribution, but is only ‘‘Mechanisms of Odontogenic and Non-Odontogenic one source of information on the pharmacology of Pain’’) and pharmacological aspects of odontogenic pain control. Clinicians must supplement this pain reveals several important conclusions that are information and evaluate its application to any summarized as follows: particular clinical case. • There is no single magic bullet for treating pain. Clinicians need to develop skills for differential diagnoses of pain disorders, delivering positive behavioral management strategies, identifying risk References factors for postprocedural pain, effective intraoss- 1. Vreeland DL, Reader A, Beck M, et al. An evaluation of eous injection of local anesthetics (particularly in volumes and concentrations of lidocaine in human inferior cases of painful mandibular teeth, especially irre- alveolar nerve block. J Endod 1989;15(1):6–12. versible pulpitis), using combinations of an NSAID 2. McLean C, Reader A, Beck M, et al. An evaluation of 4% with acetaminophen (in patients who can tolerate prilocaine and 3% mepivacaine compared with 2% lidocaine these drugs), delivering effective and appropriate (1:100,000 epinephrine) for inferior alveolar nerve block. dental treatment, and following up all patients to J Endod 1993;19(3):146–50. ensure their appropriate response. 3. Chaney MA, Kerby R, Reader A, et al. An evaluation of • The intensity of preoperative pain is a useful predic- lidocaine hydrocarbonate compared with lidocaine hydro- 199,202,265 tor of post-endodontic pain, and this risk chloride for inferior alveolar nerve block. Anesth Prog factor should be considered when developing the 1991;38(6):212–16. pain treatment plan before treatment commences. 4. Hinkley SA, Reader A, Beck M, Meyers WJ. An evaluation of • Preoperative pain in a mandibular tooth is a risk 4% prilocaine with 1:200,000 epinephrine and 2% mepiva- factor for anesthetic failure of IAN block injections. caine with 1:20,000 levonordefrin compared with 2% lido- The best evidence to date, which balances efficacy caine with 1:100,000 epinephrine for inferior alveolar nerve with minimal adverse effects, would support treat- block. Anesth Prog 1991;38(3):84–9. ing patients with an irreversible pulpitis of a man- 5. Dreven LJ, Reader A, Beck M, et al. An evaluation of an dibular tooth first with an IAN block injection, electric pulp tester as a measure of analgesia in human vital followed immediately by an intraosseous injection teeth. J Endod 1987;13(5):233–8. of 3% mepivacaine. Little is known about benefits/ risks of an intraosseous injection of symptomatic 6. Certosimo A, Archer R. A clinical evaluation of the electric pulp tester as an indicator of local anesthesia. Oper Dent mandibular teeth with pulpal necrosis and periapi- 1996;21:25–30. cal radiolucencies. • Emerging clinical evidence provides qualitative sup- 7. Loetscher C, Melton D, Walton R. Injection regimen for port that a preoperative NSAID would be expected anesthesia of the maxillary first molar. J Am Dent Assoc to enhance the magnitude of anesthesia, although 1988;117:337–40. additional research is needed. 8. Jones VR, Rivera EM, Walton RE. Comparison of carbon • In patients who can tolerate the drug classes, there dioxide versus refrigerant spray to determine pulpal respon- is strong preclinical and clinical trial data demon- siveness. J Endod 2002;28(7):531–3. strating that the combination of an NSAID with 9. Nusstein J, Reader A, Nist R, et al. Anesthetic efficacy of the acetaminophen provides effective pain control in supplemental intraosseous injection of 2% lidocaine with both postsurgical and postendodontic patients. One 1:100,000 epinephrine in irreversible pulpitis. J Endod possible strategy to treat patients in moderate-to- 1998;24(7):487–91. severe pain would be to consider combinations 10. Reisman D, Reader A, Nist R, et al. Anesthetic efficacy of the of up to ibuprofen 600 mg and acetaminophen supplemental intraosseous injection of 3% mepivacaine in 728 / Endodontics

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undergoing two-visit root canal treatment. Int Endod antibiotics for pain relief in irreversible pulpitis. J Endod J 2004;37(1):29–37. 2006;32:87–92. 266. Oguntebi B, et al. Postoperative pain incidence related to the type 269. Isett J, Reader A, Gallatin E, et al. Effect of an intraosseous of emergency treatment of symptomatic pulpitis. Oral Surg Oral injection of Depo-Medrol on pulpal concentrations of PGE2 Med Oral Pathol Oral Radiol Endod 1992;73:479–83. and IL-8 in untreated irreversible pulpitis. J Endod 267. Nagle, D, Reader A, Beck M, Weaver J. Effect of systemic 2003;29(4):268–71. penicillin on pain in untreated irreversible pulpitis. Oral Surg 270. Agarwala V, Reader A, Nusstein J, Beck M. Anesthetic Oral Med Oral Pathol Oral Radiol Endod 2000;90(5):636–40. efficacy of a preemptive intraosseous injection of Depo- 268. Keenan JV, Farman AG, Fedorowicz Z, Newton JT. A Cochrane Medrol in untreated irreversible pulpitis [abstract]. J systematic review finds no evidence to support the use of Endod 2006;32:238. CHAPTER 23

ANXIETY AND FEAR IN THE ENDODONTIC PATIENT

STANLEY F. MALAMED

Fear and anxiety is far from being a uniquely endo- endodontist, confronted with a patient who is in dontic problem; it is, however, a more significant pain and having possibly been in pain for several problem within because of the commonplace nature months, and who is fearful not just of the local of the patients’ underlying problem: pain. Dentistry anesthetic injection but of ‘‘root canal work’’ itself. consistently appears in lists of our most common fears Other chapters have information on the management along with fear of heights, flying, mice, and public of endodontic infection (Chapter 20, ‘‘Treatment of speaking.1 Common dental fears include fear of the Endodontic Infections, Cysts, and Flare-Ups’’) and endo- unknown, fear of pain, and, perhaps most commonly, dontic pain (Chapter 10, ‘‘Mechanisms of Odontogenic fear of the ‘‘shot.’’ and Nonodontogenic Pain’’) and pain of nonendodontic Studies over the years have evaluated the incidence origin (Chapter 11, ‘‘Nonodontogenic Toothache and of dental phobia (odontophobia) in the general popu- Chronic Head and Neck Pains’’). lation.2–4 They indicate that between 10 and 30% of Fear and pain are a potent combination capable of the adult population suffer from moderately severe to provoking some of the most catastrophic situations extreme odontophobia. Chanpong et al.4 in a survey imaginable in the dental office, such as cardiac arrest. (n = 1101) of Canadian adults found 7.6% stating Surveying the incidence of medical emergencies in the they had ‘‘missed, cancelled or avoided a dental dental environment, Malamed6 found that 54.9% appointment because of fear or anxiety.’’ In response occurred during the administration of the local anes- to the question ‘‘How would you assess your feelings thetic with an additional 22.0% occurring during towards having dental treatment done?’’, 5.5% dental treatment. When a medical emergency arose assessed themselves as either ‘‘very afraid’’ (2.0%) or during dental treatment, 65.8% occurred either during ‘‘terrified’’ (3.5%). In this ‘‘high fear’’ group, 49.2% extirpation of the pulp (26.9%) or extraction of the had missed, cancelled, or avoided a dental appoint- tooth (38.9%).7 Over three-quarters of medical emer- ment because of fear or anxiety compared with only gencies seen in dentistry are stress-related. Potentially 5.2% of the ‘‘low or no fear’’ group. stress-related medical emergencies include syncope, Enkling et al.5 reported that in 67% of odontopho- angina pectoris, bronchospasm, seizures, hyperventi- bic patients a prior painful dental or medical experi- lation, and the so-called ‘‘epinephrine reaction.’’ ence was the primary cause of their fear, followed by fear of needles (33%). Dental fear is real and it hurts. For the patient, it is Recognition of Fear and Anxiety palpable. For the doctor and office staff, it stands as a barrier to the delivery of quality dental care. Within Recognition of dental fear should not be left until the the realm of endodontics, many patients requiring patient is seated in the dental chair. Quite often the treatment do so as a result of their extreme odonto- receptionist is asked revealing questions by patients, phobia. The first endodontic appointment, during such as ‘‘Is the doctor gentle?’’, ‘‘Does the doctor give which access will be gained and pulpal tissues good shots?’’ Patients in the reception area may con- removed, provides the greatest challenge to the verse amongst themselves, discussing their upcoming

737 738 / Endodontics treatment, perhaps in lurid ways. This invaluable infor- Management of Fear and Anxiety mation must be relayed to chair-side personnel who can now act to prevent a ‘‘problem’’ from developing. The concept behind the successful use of sedation is that Once seated in the dental chair, the patient’s fears fearful patients are overly focused on everything that usually become more obvious. Fearful patients simply happens around them, and to them, in the dental envir- do not ‘‘look’’ comfortable. Legs remain crossed and onment. Administration of a central nervous system fingers clutch the armrest of the dental chair, the (CNS)-depressant drug lessens the patients’ awareness, so-called ‘‘white-knuckle syndrome.’’ The patient clo- moving their minds away from the dental chair. They no sely watches everything, not wanting to be ‘‘snuck up longer over-respond to stimulation. They no longer care on’’ by the doctor. Responses to questions are unu- about the procedure and, in effect, become more ‘‘nor- sually prompt; speech is rapid. Perspiration may be mal’’ patients. Stated even more simply, sedation is about observed on the patient’s forehead, upper lip, and distraction. perhaps underarms. If any of the above is noted, it is important for the DEFINITIONS doctor to confront the patient, asking them ‘‘if any- Sedation occurs as a result of depression of the CNS. thing about the upcoming procedure bothers them.’’ Although various levels of CNS depression will be dis- Once the patient admits to having fears and once the cussed, one is in fact dealing with a continuum, from the fears are out in the open, the ‘‘problem’’ should be earliest manifestations of a drug’s action, anxiolysis, manageable. through the controlled loss of consciousness, general Management problems occurring during the local anesthesia. As most jurisdictions require a licensed den- anesthetic administration can be almost entirely pre- tist to obtain a permit before being allowed to administer vented by taking a patient’s ‘‘feelings’’ about receiving CNS-depressant drugs via various routes and to varying ‘‘shots’’ into consideration. Most people do not relish levels of CNS depression, a number of dental (and med- the thought of receiving intraoral local anesthetic injec- ical) organizations have published guidelines for the safe tions as demonstrated by the high incidence of adverse and effective use of these drugs.9–11 reactions occurring at this time. Fifty-five percent of all When describing, and defining, the various levels of medical emergencies reported by Malamed6 were faint- CNS depression, the precise wording of the definition ing, and over 54% of all emergencies occurred during may vary slightly from state to state and organization to administration of the local anesthetic. Syncope organization, but the essence of the definitions is the accounted for 61.1% of dental office medical emergen- same. The reader is strongly advised to adhere to those cies reported during a 1-year period in New Zealand.8 definitions that have been established in the jurisdiction Fainting during injection is preventable by following a in which he/she is licensed. Until recently, the terms few simple steps aimed at making all local anesthetic used to describe the levels of CNS depression were (in injections as comfortable (atraumatic) as possible: (1) order of increasing levels of depression): anxiolysis ! placing the patient about to receive an intraoral injec- conscious sedation ! deep sedation ! general anesthe- tion into a supine position prior to injection, (2) slow sia. New definitions, first proposed by the American administration of the local anesthetic solution, and Society of Anesthesiologists, describe the degree of (3) use of sedation, if warranted, prior to the adminis- CNS depression ultimately achieved (Table 1).12 The tration of the local anesthetic. definitions that follow are taken from the American

Table 1 Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia Minimal Sedation Moderate Sedation/Analgesia (Anxiolysis) (Conscious Sedation) Deep Sedation/Analgesia General Anesthesia

Responsiveness Normal response to Purposeful* response Purposeful* response Unarousable, even verbal stimulation to verbal or tactile stimulation after repeated or painful with painful stimulus stimulation Airway Unaffected No intervention required Intervention may be required Intervention often required Spontaneous ventilation Unaffected Adequate May be inadequate Frequently inadequate Cardiovascular function Unaffected Usually maintained Usually maintained May be impaired

*Source: American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists.12 Chapter 23 / Anxiety and Fear in the Endodontic Patient / 739

Dental Association’s (ADA’s) Guidelines for the Use of maintained.11,12 In accord with this particular defini- Sedation and General Anesthesia by Dentists.11 tion, the drugs and/or techniques used should carry a margin of safety wide enough to render unintended Minimal Sedation loss of consciousness unlikely. Repeated dosing of an Minimal sedation was previously associated with agent before the effects of previous dosing can be fully anxiolysis—a minimally depressed level of conscious- appreciated may result in a greater alteration of the ness that retains the patient’s ability to independently state of consciousness than is the intent of the dentist. and continuously maintain an airway and respond Furthermore, a patient whose only response is a reflex- appropriately to physical stimulation or verbal com- ive withdrawal from a painful stimulus is not consid- mand, and that is produced by a pharmacologic or ered to be in a state of moderate sedation. nonpharmacologic method or a combination thereof. Deep Sedation Although cognitive function and coordination may be modestly impaired, ventilatory and cardiovascular This is a drug-induced depression of consciousness functions are unaffected.11–12 In accord with this par- during which patients cannot be easily aroused but ticular definition, the drug(s) and/or techniques used respond purposefully following repeated or painful should carry a margin of safety wide enough to render stimulation. The ability to independently maintain unintended loss of consciousness unlikely. Further- ventilatory function may be impaired. Patients may more, patients whose only response is a reflexive with- require assistance in maintaining a patent airway, and spontaneous ventilation may be inadequate. Cardio- drawal from repeated painful stimuli would not be 11,12 considered to be in a state of minimal sedation. vascular function is usually maintained. When the intent is minimal sedation for adults, the General Anesthesia appropriate dosing of enteral drugs is no more than This is a drug-induced loss of consciousness during the maximum recommended dose of a single drug which patients are not arousable, even by painful that can be prescribed for unmonitored home use. stimulation. The ability to independently maintain Nitrous oxide/oxygen (N O–O ) when used in 2 2 ventilatory function is often impaired. Patients often combination with sedative agents may produce mini- require assistance in maintaining a patent airway, and mal, moderate, or deep sedation or general anesthesia. positive pressure ventilation may be required because The following definitions apply to administration of depressed spontaneous ventilation or drug-induced of minimal sedation: depression of neuromuscular function. Cardiovascu- Maximum recommended therapeutic dose (MRTD): lar function may be impaired.11,12 Because sedation maximum FDA-recommended dose of a drug and general anesthesia are a continuum, it is not approved for unmonitored home use. Incremental always possible to predict how an individual patient dosing: administration of multiple doses of a drug will respond. Hence, practitioners intending to pro- until a desired effect is reached, but not to exceed duce a given level of sedation should be able to the MRTD. Titration: administration of incremental diagnose and manage the physiologic consequences doses of a drug until a desired effect is reached. (rescue) for patients whose level of sedation becomes Knowledgeofeachdrug’stimeofonset,peak deeper than initially intended.12 response, and duration of action is essential. For all levels of sedation, the practitioner must have Although the concept of titration of a drug to the training, skills, and equipment to identify and effect is critical, when the intent is minimal manage such an occurrence until either assistance sedation, one must know whether the previous arrives (emergency medical service) or the patient dose has taken full effect before administering an returns to the intended level of sedation without air- additional drug dose. way or cardiovascular complications. Moderate Sedation REGULATION This was previously associated with conscious seda- Through the 1960s, upon receiving a dental degree tion—a drug-induced depression of consciousness and a license to practice dentistry, the dentists were during which patients respond purposefully to verbal allowed to administer any form of anesthesia (from commands, either alone or accompanied by light local anesthesia to sedation to general anesthesia). tactile stimulation. No interventions are required to No prohibitions, except for common sense, existed. maintain a patent airway, and spontaneous ventilat- As no formal training had been received in these ion is adequate. Cardiovascular function is usually techniques (aside from local anesthesia) in dental 740 / Endodontics school, most new doctors prudently avoided their Orally administered drugs had always been an use, managing fearful patients as best they could. important management technique within the specialty Some, however, felt that they could easily administer practice of pediatric dentistry, with chloral hydrate, anesthesia (in the broad sense) to their patients. hydroxyzine, and promethazine forming a triad of Although some were successful, a large enough oft-used drugs. In 1985 the American Academy of number became involved in serious untoward Pediatric Dentistry developed guidelines for the use events, leading to death or severe neurologic of sedation by pediatric dentists who received ade- damage, that governmental agencies (state dental quate clinical and didactic experience in this techni- boards and/or legislatures) began to seriously ques- que during their residencies. These guidelines have tion whether dentists should be allowed to perform been reevaluated several times with the most recent these techniques. version accepted and published in 2006.16 In the early 1970s, an Alaskan dentist had several Unfortunately, some untrained nonpediatric den- deaths occur under halothane general anesthesia. As tists (e.g., general dentists), now unable to administer this dentist had little or no formal training in general drugs parenterally, began using oral sedative drugs to anesthesia, Alaska became the first state to ban the achieve more profound levels of CNS depression, with administration of general anesthesia in the dental predictable results: death and severe morbidity (e.g., office. In 1974, in response to four patient deaths brain damage). Legislation to require permits for oral under general anesthesia in a short span of time in conscious sedation (OCS) in children appeared in the office of an untrained dentist, Ohio became the the late 1990s. Enacted in 2000, California’s legisla- first state to limit the use of general anesthesia to tion requires a permit for OCS in patients less than dentists who could prove adequate training, either 13 years of age.17 At present, 11 states require advanced through an oral surgery program or a 1-year anesthe- education and awarding of a permit for a licensed siology residency13 (J. Weaver, personal communica- dentist to administer OCS to a pediatric patent.15 tion, January 2006). OCS for adult dental patients had an increase in As of 21 December 2006, all 50 states have enacted popularity in the mid-1990s, which continues today. regulation governing the administration of general Although many oral drugs are available, one, triazo- anesthesia and deep sedation in dental offices.14 Deep lam, has proven the most popular.18,19 sedation, by virtue of the fact that the patient’s venti- And now, for the first time, state dental boards have latory status and ability to maintain an airway may be acted proactively rather than reactively, as in the past, impaired, requires a level of training equal to that of enacting legislation mandating continuing dental educa- general anesthesia. Education and training in general tion (CDE) and a permit to administer OCS to the adult anesthesia requires a minimum of a 1-year or 2-year, dental patient. As of December 2006, 19 states have full-time residency in anesthesiology. requirements for CDE and a permit for adult OCS.15 Some dentists, untrained and now unable to admin- One route of drug administration has yet to be dis- ister general anesthesia, began administering CNS- cussed: inhalation. In contrast to the oral route, the depressant drugs parenterally, either intramuscularly or inhalation route represents the most controllable tech- intravenously, as these techniques had not yet been regu- nique of drug administration. In dentistry in the United lated. Not surprisingly, a number of deaths occurred, States, the combination of N2OandO2 is available and as well as other serious morbidities over the ensuing used, with varying frequency, in approximately 35% of years. And also, not surprisingly, legislative bodies dental offices.20 The ADA, in concert with manufac- began to regulate parenteral sedation. All 50 states turers of inhalation sedation units, mandated the inclu- now regulate the administration of parenteral con- sion of safety features into these machines. The goal of scious sedation.15 (Intranasal [IN] sedation, a relatively these safety features is to make it close to impossible the new approach to CNS-depressant drug administration administration of levels of O2 less than 21% (ambient in dentistry, is classified as a parenteral route of drug air) to a patient.21 Deaths and serious morbidity asso- administration.) ciated with N2O–O2 inhalation sedation in dentistry The oral route, the least effective and least control- have not occurred in recent years due primarily to the lable common mode of drug delivery, had always addition of these safety features and the requirement of enjoyed a somewhat limited use in dentistry. As other the ADA’s Commission on Dental Accreditation that all routes of drug delivery and levels of sedation encoun- graduating dental students be trained to proficiency tered increased scrutiny and regulation, interest bur- in inhalation sedation.22 As of December 2006, only geoned in this, as yet, unregulated mode of drug a handful of states require a permit for the use of administration. inhalation sedation. Chapter 23 / Anxiety and Fear in the Endodontic Patient / 741

SEDATION: NONDRUG TECHNIQUES Table 2 Efficacy of Sedation by Routes of (IATROSEDATION) Drug Administration Management of a patient’s dental fear begins as soon Expected as the patient enters the office. The environment, the Technique Titrate Rapid Success ambiance of the office, establishes a mood either of Route to Effect Reversal Rate(%) quiet relaxation or of a hurried, frenetic pace. The dental staff should be alert to any tell-tale signs of Intravenous Yes Yes* 90 dental fear and, if noted, report it to the dentist Inhalation Yes Yes 80 immediately. ‘‘Forewarned is forearmed.’’ Relaxation Intramuscular No No 67 of a patient by the doctor’s behavior has been termed Intranasal iatrosedation, a term formulated by Dr. Nathan Fried- Oral (adult) No No 50–60 man, for many years chairman of the Section of Oral (child) No No Older: 50–60 Younger: 35–40 Human Behavior at the University of Southern Cali- # fornia, School of Dentistry.23 The word is derived General anesthesia† Yes Yes 0 from the Greek prefix iatro, ‘‘pertaining to the doc- *Opioids, benzodiazepines. tor,’’ and sedation, ‘‘the relief of anxiety.’’ †General anesthesia is not a sedation technique. It is included for The concept on which iatrosedation is based is rather comparative purposes only. basic: that the behavior of the doctor and staff has a #Dependent on route of administration and drug. profound influence on the behavior of the patient. Other terms applied to this concept include sugges- SEDATION: DRUG TECHNIQUES tion, chairside/bedside manner, and the laying on of (PHARMACOSEDATION) hands. The underlying premise of all these techniques In dentistry, CNS-depressant drugs are administered issimilar:thatonecanusenonchemicalmeanstoaid by four routes: commonly by oral and inhalation, and in relaxing the patient. For a more in-depth discus- less commonly by intravenous (IV) and intramuscular sion of nondrug techniques of sedation, the reader is (IM). IN drug administration is a relatively recent referred to Sedation: a guide to patient management.24 addition to this armamentarium, primarily employed Examples of iatrosedative techniques include hypno- to provide moderate sedation in children.25 sis, acupuncture, audioanalgesia, and biofeedback. The following is a brief overview of these routes of Iatrosedation forms the building block for all seda- CNS-depressant drug administration in dentistry. It is tion techniques requiring drug administration. Simply not meant to substitute for a complete course in pharma- put, a patient who remains fearful, perhaps with dis- cology or in the safe and effective technique of drug trust of the doctor, is less likely to ‘‘allow’’ their CNS- administration. The doctor wishing to administer drugs depressant drug to work. Although true for all routes by any of these routes should check with their state Board of drug administration, it is especially relevant with the of Dental Examiners for specific education and permit oral and inhalation routes. requirements for each technique or level of sedation. Consider the patients’ frame of mind in the dental office: afraid that something/everything is going to be painful. Their dentist is telling them, nonverbally, to INHALATION SEDATION (N2O–O2) ‘‘trust me.’’ ‘‘Allow me, a stranger, to give you a drug Inhalation sedation with N2O–O2 represents the most that will decrease your level of consciousness so that controllable technique of sedation available. Inhala- you are less aware of what is happening around you.’’ ‘‘I tion sedation possesses a number of compelling clin- will take good care of you.’’ The doctor who establishes ical properties that serve to increase its success rate a bond of trust with their patients will have them sit and its safety, including (1) rapid onset of action back in the dental chair and ‘‘let the drug work.’’ Con- (~20–30 seconds); (2) a level of CNS depression that versely, where the doctor–patient relationship is can rapidly be increased, if necessary; (3) the level of strained or uncomfortable, patients are much less likely CNS depression that can be rapidly decreased, if to surrender to the clinical effects of the drug, not needed—a significant factor in increasing the safety wanting to ‘‘lose control’’ of the situation. The level of inhalation sedation; (4) complete recovery follow- defined as minimal sedation is highly unlikely to suc- ing the delivery of 100% O2 at the conclusion of the ceed in this situation. Moderate sedation would have a procedure, permitting almost all N2O–O2 patients to somewhat greater success rate but still with a signifi- be discharged from the dental office unescorted, and cant, perhaps unacceptably high, failure rate (Table 2). with no prohibitions on their postinhalation sedation 742 / Endodontics activities. No other route of drug administration Table 3 Technique of Administration of Inhalation Sedation offers this significant advantage. Because of its rapid with N2O–O2 onset, inhalation sedation with N2O–O2 may be 1. Prior to placing nasal hood, start a flow of 5 to 6 LPM (liters per titrated. The ability to titrate increases both the suc- minute) of O2. cess and safety of the technique. 2. Have patient assist in proper placement and securing of the nasal hood. In order for a drug to be titrated, it must enter into 3. Determine if patient can ‘‘breathe comfortably’’ with 100% oxygen (‘‘Is the cardiovascular system rapidly. When possible, the flow volume adequate?’’). Increase the flow, if necessary. titration allows the doctor to individualize the dosage 4. Start titration of N2O by increasing its flow to 1 LPM, decreasing the of the drug for each patient, negating the so-called O2 flow by 1 LPM. ‘‘bell-shaped’’ or ‘‘normal distribution’’ curve. 5. After 1 minute determine what, if any, signs and symptoms the patient may be experiencing. The technique of inhalation sedation with N2O–O2 6. If needed, increase N2O by 0.5 LPM, decreasing O2 0.5 LPM. possesses very few significant disadvantages. One fac- 7. Repeat steps 5 and 6 until the patient reaches the desired level of tor, common to it and several other techniques, is that sedation. of patient cooperation. The patient breathes the gasses 8. Administer local anesthesia as would be done if the patient were not through a small mask placed on the nose, the nasal receiving N2O–O2. hood. Uncooperative patients, usually odontophobic 9. At the conclusion of the procedure, increase the O2 flow to the level determined in step 3 and return the N2O to 0 LPM. younger children, or any patient who is claustropho- 10. Permit the patient to breathe 100% O2 for not less than 3 to 5 bic, might not allow the nasal hood to be placed, minutes before considering removal of the nasal hood. condemning the inhalation route to failure. Persons 11. Assess recovery from sedation. If considered recovered, remove nasal unable to breathe through their nose, for whatever hood before terminating the flow of O2. 12. Permit the patient to leave dental chair. Have a staff person close to reason, will be unable to receive inhalation sedation the patient so as to prevent any possible injury when standing, due in a dental office. A recommended technique of to postural hypotension. administration of N2O–O2 is outlined in Table 3. 13. Document treatment in the patient’s chart. Inhalation sedation with N2O–O2 may be employed to provide minimum to moderate sedation. It may also be used, in conjunction with drugs administered by other routes, to supplement the CNS depression they provide. N2O–O2 when used in combination with seda- tive agents may produce minimal, moderate, or deep sedation or general anesthesia.11 The use of N2O–O2 inhalation sedation in endodontics should become more common given the positive attri- butes of the technique. A common complaint from endo- dontists is that the nasal hood is in the way (Figure 1). Once experience is gained in the technique, this ceases to be a concern. Inhalation sedation with N2O–O2 has a success rate of approximately 80% in adult patients.

ORAL CONSCIOUS SEDATION The oral route of drug administration is the least con- trollable route of drug administration. A number of factors work against an orally administered drug being effective, including a slow onset of action (~1 hour for most drugs); erratic absorption of the drug from the gastrointestinal (GI) tract; and, for some drugs, a signif- Figure 1 N2O–O2 nasal hood. icant hepatic first-pass effect. For these reasons, titration of the drug to clinical effect is not possible, eliminating the most important safety factor in drug administration. The duration of CNS depression from orally admi- Once administered, the level of CNS depression nistered drugs greatly exceeds the typical length of the reached by oral drugs is not easily increased (providing dental visit so these patients will always require an deeper sedation) or decreased (lighter sedation). escort on being discharged from the office. This escort Chapter 23 / Anxiety and Fear in the Endodontic Patient / 743 should be a responsible adult who has a vested interest Many excellent oral preparations are currently avail- in the health and safety of the patient. able for administration. Table 4 presents some com- The only advantages associated with the oral route monly used drugs and their recommended dosages.26,27 of drug administration are that it is easier for both the When used alone, and in recommended dosages, doctor and the patient. orally administered drugs will have only an approxi- Having just described a technique that seems quite mately 50 to 60% success rate with adult patients. This mediocre compared with other routes of administra- success rate is even lower in younger children. tion,itmustbestatedthatthereisalegitimateplace for orally administered CNS depressants in dentistry. Odontophobic patients, especially when faced with INTRAVENOUS CONSCIOUS SEDATION the fear of root canal treatment, frequently require CNS-depressant drugs administered intravenously in management with CNS depressants (1) the night prior the dorsum of the hand reach the brain in approxi- to the planned appointment, in order for the patient to mately 20 seconds. With this rapid onset, IV drug experience a restful night’s sleep, and (2) in the morn- administration allows patients to be titrated to a ing, 1 hour prior to the scheduled dental visit, to assist desired level of CNS depression, thereby increasing them in overcoming any last minute increase in their control over the effect of the administered drug and, anxiety. ultimately, the safety of the technique. Other advan- In the absence of other sedation techniques in a tages of IV drug administration include the ability to dental office, the oral route may also be used for intra- rapidly increase the level of sedation, if needed, and the operative sedation. However, owing to the lack of con- reversibility of many intravenously administered drugs trol maintained over this technique by the doctor, the (benzodiazepines and opioids). goal in administering oral CNS depressants should be Disadvantages associated with intravenously admi- limited to minimal to moderate CNS depression. nistered CNS depressants include the requirement of

Table 4 Common Orally Administered CNS Depressants Usual Dental Generic Name Proprietary Name Availability (mg) Dosage

Benzodiazepines

Alprazolam Niravam, Xanax Tab: 0.25, 0.5, 1.0, 2.0 0.25–0.5 (max 4 mg/day) Diazepam Valium Tab: 2, 5, 10 2–10 mg bid-qid Flurazepam Dalmane Cap: 15, 30 15–30 mg at bedtime Lorazepam Ativan 0.5, 1.0, 2.0 2–3 mg/day given bid-tid Midazaolam Versed Syr: 2 mg/mL Pediatrics: 0.25–1.0 mg/kg single dose Oxazepam Serax Cap: 10, 15, 30 Adults (Anxiety): mild to moderate: Tab: 15 severe: 15–30 tid-qid Triazolam Halcion Tab: 0.125, 0.25 0.25 qhs, max 0.5

Miscellaneous, non-benzodiazepine anxiolytics, sedatives

Eszopiclone Lunesta Tab: 1.0, 2.0, 3.0 Initial: 2mg qhs Zaleplon Sonata Cap: 5, 10 Insomnia: 10 qhs Zolpidem Ambien Tab: 5, 10 Adult: usual 10 mg qhs

Miscellaneous sedative-hypnotic

Chloral hydrate n/a Syr: 500 mg/5ml Adults: 500 mg – 1gr 15–30 mg hs; max 2 g/day Hydroxyzine HCl Atarax Syr: 10 mg/5mL Tab: 25, 50, 100 Adults (Sedation): 50–100 mg

Hydroxyzine pamoate Vistaril Cap: 25, 50, 100 Sus: 25 mg/5mL

Tab = Tablet; Syr = Syrup; Cap = Capsule; Sus = Suspension. Sources: (1) ADA/PDR Guide to Accepted Dental Therapeutics26. (2) www.ePocrates.com27 744 / Endodontics fasting prior to the procedure (NPO status); an inabil- unlike diazepam, is water soluble, thus capable of ity to quickly lessen the level of CNS depression; an being administered intramuscularly and intranasally inability to reverse the clinical actions of some drugs (see following discussions of these techniques). The (e.g., barbiturates); and prolonged clinical recovery amnestic properties of midazolam are considerably with an attendant need for an adult escort for the greater than diazepam’s, providing lack of recall for patient when discharged from the dental office. most, if not all, of the dental appointment. Clinical Venipuncture is a learned skill and, though nor- sedation, however, from the dentist’s perspective, is mally quite easy to achieve, represents the most diffi- not quite as good with midazolam compared with cult part of the entire IV sedation procedure. Once diazepam. Both drugs, with one titrating dose, provide venous access is obtained, titration to the desired level the doctor with approximately 1 hour of working time. of CNS depression is normally accomplished easily. Direct injection of a drug into a vein, followed by Many CNS-depressant drugs are available for IV removal of the syringe at the start of the dental pro- administration, but those most often employed are cedure, gave way to the continuous IV infusion, in the benzodiazepines, midazolam (Versed), and diaze- which venous access is maintained for the duration of pam (Valium). the procedure. Initially, winged needles, also known State requirements for a permit to employ IV con- as ‘‘scalp vein’’ and ‘‘butterfly needles,’’ were used scious sedation (also termed ‘‘parenteral sedation’’ or (Figure 2). Easy to insert, the winged needle has the ‘‘moderate sedation’’) most often mandate 60 hours of disturbing propensity to perforate the vein during the didactics and either 10 or 20 cases of IV sedation admi- dental procedure, leading to loss of venous access nistered by the doctor in a supervised environment.15 and formation of a hematoma. In recent years, the Variation may exist from jurisdiction to jurisdiction, so indwelling catheter has become increasing popular. it is strongly advised that specific state dental board regulations be consulted. Basic IV sedation techniques have evolved over the past three decades. The combination of pentobarbital (Nem- butal), meperidine (Demerol), and scopolamine repre- sented the original IV technique introduced in the 1950s by Dr. Neils Bjo¨rn Jo¨rgensen at Loma Linda University.28 As described by Jo¨rgensen, the drugs were injected directly into the vein via the syringe that was then removed.29 The Jo¨rgensen technique provided a duration of CNS depres- sion of approximately 2 hours, a function of the barbitu- rate, a pentobarbital. With the introduction in the early 1960s of the benzodiazepine diazepam, a shorter duration of CNS depression became possible.30 An additional ben- efit of diazepam was a brief period (approximately 10 minutes) of retrograde amnesia, permitting potentially traumaticprocedurestobedonewithalikelihoodofthe patient not having any recall. For the patient this meant, in essence, that the fearful event (e.g., local anesthetic injec- tion) never happened. IV conscious sedation with a benzodiazepine has become the most popular technique in dentistry. IV benzodiazepine sedation meets the needs of contem- porary dental practice, that is, sedation for approxi- mately 1 hour. Introduced in the United States in 1986, midazolam (Versed) has now supplanted diaze- pam (Valium) as the most used IV benzodiazepine in the area of 1-hour IV conscious sedation. Midazolam, Figure 2 IV needles. Chapter 23 / Anxiety and Fear in the Endodontic Patient / 745

major safety benefit and thereby limiting its indica- tions for use in sedation in dentistry. Doses of IM drugs are primarily determined on a weight (e.g., mg/kg) basis. Given the appropriate dosage, approximately 70% of patients should be CNS depressed to the desired level of sedation. However, another 15% will likely be undersedated with that same dose, whereas the remaining 15% are CNS depressed to a level beyond that which is being sought. This latter group, hyperresponders to the drug, may be CNS depressed to a level beyond which the doctor is able to safely manage them. For example, an IM drug is administered to a patient to achieve a level of moderate sedation (formerly termed ‘‘conscious sedation’’). However, the resultant level of CNS depression is deep sedation.Atthislevel,patientsareunabletoadequately maintain their airway without assistance (e.g., head-tilt, chin-lift). Dental care would, of course, need to be postponed as the doctor is required to ‘‘rescue’’ patients from this unintended level of CNS depression. Airway management and, possibly, ventilatory assis- Figure 3 Indwelling catheter. tance are continued until the level of CNS depression lightens, a process that could require several hours. Along with the inability to titrate IM drugs, it is also Once inserted and secured in a vein, the 300 plastic not possible to rapidly lessen or deepen the level of catheter is unlikely to accidentally become dislodged sedation. Reversal of intramuscularly administered (Figure 3). drugs, if possible, by intravenously administered fluma- Opioids, specifically the short-acting fentanyl, have zenil or naloxone, would be somewhat successful for a also been used in IV conscious sedation with increased period of time. However, as a reservoir of the IM drug frequency. When the primary goal of IV drug admin- exists within the muscle into which it was injected istration is management of fear, there is usually little or previously, the drug will continue to be absorbed over no need for opioid administration. Indeed, in the vast several hours leading to the likelihood of a rebound majority of successful IV sedation cases, the only sedation effect occurring as the action of the intrave- drug(s) administered are either midazolam and/or dia- nously administered reversal agent diminishes. IM zepam. However, in situations in which surgery or administration of the reversal agent is generally not other dental procedures that may prove painful are recommended as its onset, 10 to 20 minutes, is too slow planned, or in which successful pain control may not to provide any immediate relief in the event of over- be easily achieved with local anesthesia alone, opioid sedation. Additionally, the degree of the intramuscularly administration may be justified. administered reversal agent’s effectiveness would be less When administered carefully via titration, success than that seen following its administration IV. rates of 90% may be achieved with IV sedation. The IM drugs are not as controllable as intravenously IV route can be used to achieve moderate and deep administered drugs. Sedation should therefore be lim- sedation, as well as general anesthesia. ited to a moderate level, with the doctor trained to recognize and manage (e.g., rescue) the patients INTRAMUSCULAR should they inadvertently enter deep sedation. IM, like IV, is a parenteral route of administration, in Patients receiving IM drugs for sedation must also which the drug by-passes the GI tract, being absorbed maintain NPO status prior to sedation. directly into the systemic (venous) circulation. The Recovery from IM drugs is prolonged; thus, the hepatic first-pass effect is negated, leading to more patient must have an adult escort when being dis- reliable absorption and more rapid onset of action charged from the office. This being said, it would seem (~10–20 minutes) than with enterally administered that IM drugs have few indications in dentistry. How- drugs. However, titration is not possible, as the onset ever, used judiciously by the doctor trained in parent- is not rapid enough, thus denying the IM route a eral conscious sedation (IV, IM, IN), the technique 746 / Endodontics can be employed with a likelihood of success of about cue) the patients should they enter into deep sedation. 67%. Midazolam is the most commonly employed IM Patients receiving IN drugs for sedation must also CNS-depressant drug in conscious sedation. maintain NPO status prior to sedation. Recovery from IN drugs is prolonged, thus the INTRANASAL requirement for an adult escort for the patient when The IN administration of CNS-depressant drugs is rela- discharged from the office. tively new within medicine and dentistry, though it has Techniques of conscious sedation will enable the been used for many years by drug abusers (e.g., cocaine) endodontist to manage the dental fears of the over- and for the administration of nasal decongestants. whelming majority of odontophobic patients. Table 6 Nasal mucosa is highly vascular; therefore, absorp- illustrates the possible uses of the techniques of con- tion of drugs instilled into the nares is more rapid scious sedation in endodontic practice. Unfortunately, than for other routes of administration. Lam et al.25 not all fears can be successfully managed with con- compared the efficacy, in children, of IN midazolam scious sedation techniques. For these few patients, with that of its IM administration, finding the level general anesthesia is required. of sedation to be comparable. IN midazolam has also been adopted in emergency medicine in the GENERAL ANESTHESIA management of acute seizures in pediatric patients.31 General anesthesia is the controlled loss of consciousness, Primosch32 compared nasal drops versus nasal spray the final step in our continuum of CNS depression that as a technique of IN drug administration and found startedwithminimalsedation. The success rates of the that although the effectiveness of conscious sedation sedation techniques described above, along with the was not influenced by the method of nasal adminis- amnestic properties of some of the drugs employed, tration, spray administration produced significantly specifically the benzodiazepines midazolam and triazo- less aversive behavior than administering drops in lam, has decreased the need for general anesthesia as a 2- to 3-year-old dental patients of similar behavioral method of managing significant numbers of odontopho- characteristics. bic patients. Most studies and clinical usage of the IN route of All 50 states regulate the use of general anesthesia in drug administration appear in pediatrics, there being dentistry.14 A residency in anesthesiology of either 1- or few reports of the use of this technique, and of its 2-year duration usually represents the educational effectiveness, in adults, thereby limiting its utility in requirement. As of November 2007, seven residencies most endodontic cases. in anesthesiology for dentists were accredited by the The advantages of IN drug administration include its American Dental Board of Anesthesiology.33 more rapid onset of action (compared with enteral Doctors who have completed accredited residen- routes) and the lack of need for injection and the cies, dentist anesthesiologists, provide anesthesia ser- accompanying trauma, both psychological and physical, vices for other dentists either (1) by establishing a associated with it. free-standing outpatient surgical center, in which the Disadvantages of IN drug administration are simi- endodontist (or any other dentist) brings the odonto- lar to those of IM. IN drugs cannot be titrated. phobic patient to the surgical center to carry out the Dosages are based on weight (mg/kg). Along with scheduled procedures while the patient receives gen- the inability to titrate IN drugs, it is also not possible eral anesthesia provided by the dentist anesthesiolo- to rapidly lessen or deepen the level of the resultant gist, or (2) by traveling to the office of the dentist who CNS depression. Reversal of intranasally administered will be managing the dental needs of the fearful drugs, if possible, by intravenously administered flu- patient, wherein dentist anesthesiologists bring along mazenil or naloxone, would be somewhat successful. all of their anesthesia drugs, equipment, and expertise. IM or IN administration of a reversal agent is gener- Once general anesthesia has been induced by the ally not recommended as its onset, 10 to 20 minutes, dentist anesthesiologist, the dentist can then proceed is too slow to provide any immediate relief in the with the endodontic procedure on a now more nearly event of oversedation. Additionally, the efficacy of ‘‘ideal’’ patient. an IM or IN reversal agent would be less than that seen with its IV administration. IN drugs are not as controllable as intravenously SUMMARY administered drugs. The level of CNS depression Dental fears exist and are a fact of life, especially in the sought should, therefore, be limited to moderate, with specialty of endodontics. The primary obstacles to suc- the doctor trained to recognize and manage (e.g., res- cessful endodontic treatment are the presence of dual Chapter 23 / Anxiety and Fear in the Endodontic Patient / 747

Table 5 Comparison of Routes of Drug Administration Titrate Route of Drug Yes– Administration Onset of Action No Advantages Disadvantages

Inhalation Rapid (~20 seconds) Yes Patient need not be NPO; rapid onset; Patient cooperation required; ineffective titration; rapidly increase if unable to breathe through nose or decrease level of CNS depression; full recovery in most patients; no prohibitions of postoperative functions Oral Slow (~ 1 hour for No Easy for patient; easy for doctor Patient cooperation needed; slow onset; maximal inability to titrate; erratic absorption from clinical effect) GI tract; significant hepatic 1st-pass effect for some drugs; no control over ultimate level of CNS depression; inability to quickly increase or decrease level of CNS depression; inability to reverse CNS depression; prolonged recovery; requirement for escort for patient on leaving dental office Parenteral: Intermediate No More reliable absorption than Patient must be NPO; potential needle injury; Intramuscular (10–20 minutes) oral; minimal patient cooperation relatively slow onset; inability to titrate; no required control over ultimate level of CNS depression; inability to quickly increase or decrease level of CNS depression; inability to reverse CNS depression; prolonged recovery; requirement for escort for patient on leaving dental office Parenteral: Rapid (~20 seconds) Yes Rapid onset; titration; rapidly Venipuncture is learned technique; patient Intravenous increase level of CNS depression; must be NPO; inability to quickly decrease level of most drugs reversible CNS depression; prolonged recovery; requirement for escort for patient on leaving dental office Parenteral: Intermediate No More reliable absorption than Unpleasant (bitter) taste if liquid enters oral cavity; Intranasal (10–20 minutes) oral; minimal patient cooperation may irritate nasal mucosa; inability to titrate; no required control over ultimate level of CNS depression; inability to quickly increase or decrease level of CNS depression; inability to reverse CNS depression; prolonged recovery; requirement for escort for patient on leaving dental office

Table 6 Techniques of Conscious Sedation—Summary CNS Depression CNS Depression Ability to Level When Level Used in Preoperative Perioperative Titrate Used Alone Combination Night prior Morning of to treatment treatment Oral sedation Yes Yes Yes No Min, mod Min, mod, deep, GA Inhalation Yes Yes Mod Mod, deep, GA IV Yes Yes Mod, deep, GA Mod, deep, GA IM/IN Yes No Mod, deep, GA Mod, deep, GA

Min = minimal sedation; Mod = moderate sedation; Deep = deep sedation; GA = general anesthesia. problems: pain and fear. To ignore fear, in the best of unable to sit still during their treatment, adding to the circumstances, will complicate dental treatment unne- frustration of the treating doctor. Fear increases cate- cessarily, as the patient remains an unwilling partici- cholamine release into the cardiovascular system with a pant throughout the procedure. Fear lowers the pain resultant rise in the incidence and severity of medical reaction threshold, with odontophobic patients being emergency situations. 748 / Endodontics

The recognition of fear, and its management, 16. American Academy of Pediatrics. American Academy of Pediatric removes the primary obstacle to the delivery of health Dentistry. Cote CJ, Wilson S. Work Group on Sedation. Guide- care. Once fear is eliminated, clinically adequate pain lines for monitoring and management of pediatric patients during control is normally accomplished quite readily. As and after sedation for diagnostic and therapeutic procedures: an Peter Milgrom wrote, ‘‘Deal with the fear first, then update. Pediatrics 2006;118(6):2587–602. pain will be a minor problem.’’5,34 17. Dental Board of California, Chapter 2, Article 5.5. Oral con- scious sedation. Dental Board of California, Sacramento, CA. [email protected] 2000 accessed 9 Febuary 2007. 18. Feck AS. Goodchild JH. The use of anxiolytic medications to References supplement local anesthesia in the anxious patient. Compend Contin Educ Dent 2005;26(3):183–6, 188, 190. 1. Our most common fears. Dental Health Advisor, Spring 1987. 19. Dionne RA, Yagiela JA, Cote CJ, et al. Balancing efficacy and 2. Dionne DA, Gordon SM, McCullagh LM, Phero JC. Assessing safety in the use of oral sedation in dental outpatients. J Am the need for anesthesia and sedation in the general popula- Dent Assoc 2006;137(4):502–13. tion. J Am Dent Assoc 1998;129(2):167–73. 20. Clark M, Brunick A. Handbook of nitrous oxide and oxygen 3. Gatchel RJ, Ingersoll BD, Bowman L, et al. The prevalence of sedation. 2nd ed. St. Louis: C.V. Mosby; 2003. dental fear and avoidance: a recent survey study. J Am Dent Assoc 1983;107(4):609–10. 21. American Dental Association Seal of Acceptance Program. www.ada.org/ada/seal/index.asp accessed 9 Febuary 2007. 4. Chanpong B, Haas DA, Locker D. Need and demand for seda- tion or general anesthesia in dentistry: a national survey of the 22. Commission on Dental Accreditation, Accreditation standard Canadian population. Anesth Prog 2005;52(1):3–11. 23, American Dental Association, Chicago, IL 2006. 23. Friedman N. Iatrosedation. In: McCarthy FM, editor. Emer- 5. Enkling N, Martwinski G, Johren P. Dental anxiety in a gencies in dental practice. 3rd ed. Philadelphia: WB Saunders; representative sample of residents of a large German city. Clin 1979. Oral Investig 2006;10(1):84–91. 24. Malamed SF. Iatrosedation. In: Malamed SF, editor. Sedation: 6. Malamed SF. Beyond the basics: emergency medicine in den- a guide to patient management. 4th ed. St. Louis: CV Mosby; tistry, J Am Dent Assoc 1997;128(7):843–54. 2002. 7. Matsuura H. Analysis of systemic complications and deaths 25. Lam C, Udin RD, Malamed SF, et al. Midazolam premedica- during dental treatment in Japan. Anesth Prog 1990;36:219–28. tion in children: a pilot study comparing intramuscular and 8. Broadbent JM, Thomson WM. The readiness of New Zealand intranasal administration. Anesth Prog 2005;52(2):56–61. general dental practitioners for medical emergencies. NZ 26. Byrne BE, Tibbetts LS, editors. Conscious sedation and agents Dent J 2001;97:82–6. for the control of anxiety. In: ADA/PDR guide to accepted 9. American Association of Oral and Maxillofacial Surgeons. dental therapeutics, 4th ed. Chicago, IL: ADA Publishing Parameters of care for oral and maxillofacial surgery: a guide Division; 2006, pp. 23–51. for practice, monitoring and evaluation, Rosemont, Ill: The 27. www.ePocrates.com Association of Oral and Maxillofacial Surgeons; 1995. 28. Jorgensen NB, Leffingwell FE. Premedication in dentistry. J 10. Academy Report: The use of conscious sedation by period- South Calif Dent Assoc 1953;21:25. ontists. J Periodontol 2003;74:933. 29. Jorgensen NB, Hayden J Jr. Premedication, local and general 11. American Dental Association. Guidelines for the use of sedation anesthesia in dentistry. Philadelphia: Lea amp; Febiger; 1967. and general anesthesia by dentists. Draft 11 November 2006. 30. O’Neill R, Verrill PJ, Aellig WH, et al. Intravenous diazepam 12. American Society of Anesthesiologists Task Force on Sedation in minor oral surgery. Br Dent J 1970;128:15. and Analgesia by Non-Anesthesiologists. Practice guidelines 31. Harbord MG, Kyrkou NE, Kyrkou MR, et al. Use of intranasal for sedation and analgesia by non-anesthesiologists. Anesthe- midazolam to treat acute seizures in paediatric community set- siology 2002;96(4):1004–17. tings. J Paediatr Child Health 2004;40(9–10):556–8. 13. Ohio State Dental Board, Ohio State Dental Board Law and 32. Primosch RE, Guelmann M. Comparison of drops versus Rules, Columbus, Ohio, 1974. spray administration of intranasal midazolam in two- and 14. Department of State Government Affairs, 30a Statutory Require- three-year-old children for dental sedation. Pediatr Dent ments for general anesthesia/deep sedation, American Dental 2005;27(5):401–8. Association,December21,2006,Chicago,IL. 33. www.asdahq.org/training.html accessed 23 November 2007. 15. Department of State Government Affairs, 30b Conscious 34. Milgrom P, Weinstein P, Getz T. Treating fearful dental patients: Sedation Permit Requirement, American Dental Association, a patient management handbook. 2nd ed. Seattle, WA: Univer- December 21, 2006, Chicago, IL. sity of Washington Continuing Dental Education; 1995.12 CHAPTER 24

THE MEDICALLY COMPLEX ENDODONTIC PATIENT

BRADFORD R. JOHNSON,DENA J. FISCHER,JOEL B. EPSTEIN

One of the challenges faced by dental specialists today is MEDICAL HISTORY AND PATIENT in the assessment and management of patients with INTERVIEW increasingly complex medical conditions. Not only has the average life expectancy increased dramatically over the past 50 years, but our geriatric patients are much ‘‘Never Treat a Stranger’’ (Attributed to Sir more likely to be at least partially dentulous and have a William Osler) complex medical history with multiple medical problems The value of a thorough medical history and patient and the use of multiple medications.1 Approximately interview cannot be overemphasized. Recognition of a 25% of patients aged 65 to 74 and 35% of patients aged medical condition that requires treatment modifica- 75 and older have a medical condition that would tion prior to treatment can avert significant treatment place them in the ASA (American Society of Anesthesiol- complications. Approximately 25 to 30% of patients ogists’ Health Classification System) category III or IV seeking treatment in a dental office can be expected to (Figure 1).2 An aging population with both the desire report at least one medical condition that has poten- and resources to preserve their natural dentition will tial relevance to dental treatment, although not all of drive the demand for root canal therapy for patients with these conditions will require treatment modifica- complex medical conditions. Even in a typical popula- tion.6,7 An adverse outcome, due to failure to recog- tion of younger and presumably healthier patients, nize a known risk factor and modify treatment approximately 50% of patients referred to a dental speci- accordingly, is a major predictor of a successful liabi- alty practice can be expected to report at least one posi- lity claim.8 Cardiovascular disease, drug allergies, dia- tive finding on their health history questionnaire.1,3 Since betes, and concerns about the safety of vasoconstrictor medical complexity is often an indication for referral to a use are some of the most common medical reasons dental specialist,4,5 endodontists should be prepared to for referral to a specialist.1,9,10 This is consistent with accurately evaluate medically complex patients and iden- an analysis of the most common medical emergencies tify situations that require a modification of normal in the dental office: angina, hypoglycemia, adverse treatment procedures and identify oral and systemic reaction to local anesthetics, and seizures.11 conditions requiring diagnosis and management. A standard health history questionnaire should cover The purpose of this chapter is to serve as a brief all common medical conditions (both treated and overview of common medical conditions that require untreated), surgeries, hospitalizations, medications, and some modification of the treatment protocol to allergies. Although many standard forms are readily avail- ensure safe endodontic treatment in an ambulatory able and are usually convenient and easy to complete, dental setting. It is not intended as a substitute for most of these forms do not clearly lead to a specific case-specific clinical judgment or consultation with determination of risk for dental treatment. More useful medical experts. For the purposes of this chapter, a medical risk assessment models are under development medically complex patient will be defined as any and will be briefly discussed later in this section. The patient requiring modification of the usual treatment written health history questionnaire should always be procedure. supplemented with a patient interview to help decrease

749 750 / Endodontics

ASA physical Therapy modifications (McCarthy and classification Description Malamed, 1979)

ASA 1 A normal healthy patient None (stress reduction as indicated)

ASA 2 A patient with mild Possible stress reduction and other systemic disease modifications as needed

ASA 3 A patient with a severe Possible strict modifications; stress systemic disease that reduction and medical consultation are limits activity, but is not priorities incapacitating

ASA 4 A patient with an Minimal emergency care in office (may incapacitating systemic consist of pharmacologic management disease that is a constant only); hospitalize for stressful elective threat to life treatment; medical consultation urged

ASA 5 A moribund patient who Treatment in the hospital is limited to life is not expected to survive support only; for example, airway and without the operation hemorrhage management

ASA 6 A declared brain-dead Not applicable patient whose organs are being removed for donor purposes

Figure 1 American Society of Anesthesiologists’ (ASA) health classification system and suggested treatment modifications. Adapted from Tables 1 and 2, Goodchild J and Glick M.27 false-positive and false-negative findings and to further alert the clinician to unlisted medical conditions as explore positive findings.12 The clinician should review well as potential drug interactions. Relevant medical any positive findings with the patient and determine the conditions and severity of systemic disease can often patient’s level of compliance with medical treatment be determined by a careful analysis of the patient’s recommendations. For example, a compliant patient with list of medications.15 Allergies to materials used in well-managed hypertension presents a relatively low risk endodontic treatment are covered later in this chap- compared to a patient who refuses to take prescribed ter and drug interactions are covered in Chapter 25, medications or does so erratically. Unfortunately, for a ‘‘Drug Interactions and Laboratory Tests.’’ variety of reasons, the reliability of self-reported informa- Herbs, dietary supplements, vitamins, and other tioninthehealthhistorymaybelessthanideal.Patients over the counter medications can contribute to com- may simply forget to report important medical informa- plications in the dental setting, although patients tion, but it has also been shown that some patients will often fail to report the use of these substances in the intentionally omit relevant information due to concerns initial evaluation.16 In a recent survey of surgical over privacy or failure to understand how the information patients, approximately one-third reported the use could be relevant to dental practice.13,14 of a nonprescription medication that could poten- tially inhibit coagulation or interact with anes- thetics.17 In particular, Ginkgo biloba, ginger, garlic, MEDICATIONS AND ALLERGIES ginseng, feverfew, and vitamin E all inhibit platelet The list of medications and allergies should be con- aggregation and can increase the risk of bleeding.18 sistent with the disclosed medical conditions and can Ingredients in over-the-counter (OTC) weight loss Chapter 24 / The Medically Complex Endodontic Patient / 751 products can potentiate the effect of epinephrine and and endogenous secretion of epinephrine in otherwise increase cardiac stress, although the most obvious healthy adults.19,20 In fact, even anticipation of a example of this phenomenon, ephedra, has been routine dental checkup can result in increased blood removed from the US market by FDA order. pressure in some patients.21 Most changes in heart rate and blood pressure are within the normal phy- siological range, although more significant changes PREVIOUS DENTAL TREATMENT have been observed before administration of local A standard screening question for all patients should anesthetic, during subgingival scaling and during enquire about any problems with previous dental treat- extractions.22 Since there are no specific guidelines ment. This line of questioning serves several important for assigning stress levels to various dental procedures, functions. First, it allows the patient to discuss any clinical judgment is essential in determining whether previous negative dental experiences as well as express or not stress-reducing treatment modifications should possible anxiety related to the proposed treatment. A be employed. Dental specialists, by virtue of addi- report of difficulty in achieving profound local anesthe- tional training and experience, should be expected to sia is a common finding, especially for root canal provide treatment in a shorter time period and should therapy. This provides an opportunity to demonstrate be better prepared to manage perioperative complica- concern for your patient and discuss how you plan to tions than a general practitioner. avoid a repeat of the previous experience. Second, Endodontic treatment in general is often consid- potential adverse reactions to dental materials or drugs ered a high-stress dental visit, especially among may emerge in response to this question. Finally, since patients with no prior endodontic treatment experi- this question is designed at least in part to help develop ence or patients who have had a previous negative rapport with your patient, it can serve as a good lead experience with endodontic treatment. For many, into other important but potentially more sensitive the perception of the treatment often differs from questions (e.g., use of oral contraceptives, history of the reality that most current endodontic treatment is human immunodeficiency virus (HIV)) minimally invasive, relatively comfortable, efficient and very well tolerated by the majority of patients when skillfully performed. In a study that measured PHYSICAL EXAM: VITAL SIGNS salivary cortisol levels in patients undergoing a vari- In addition to the mandatory health history ques- ety of dental procedures, root canal treatment was no tionnaire and patient interview, vital signs (blood different than a routine dental exam, prophylaxis, or pressure, heart rate, respiratory rate, temperature, restorative treatment, and only tooth extraction height, and weight) should be recorded prior to resulted in a significant increase in salivary corti- dental treatment whenever possible. In particular, sol.23 Surgical root canal procedures, the presence blood pressure, heart rate, and respiratory rate pro- of acute pain, self-reported dental anxiety, or diffi- vide the essential risk assessment baseline informa- culty with previous treatment, and lengthy proce- tion for all patients. Temperature may be routinely dures would all be expected to increase the level of recorded but is specifically indicated in the presence stress.22,24 If any of these conditions are present in of infection or signs of generalized malaise or toxi- addition to significant systemic disease, treatment city. Height and weight can usually be obtained from modification including a stress reduction protocol the patient or the guardian, and this information is should be considered (see Chapter 23, ‘‘Anxiety particularly important in determining appropriate and Fear in Endodontics’’). drug dosages in pediatric and geriatric patients and in assessing unexplained changes in weight. PHYSICAL HEALTH STATUS RELATIVE STRESS OF THE PLANNED The American Society of Anesthesiologists’ (ASA) Health Classification System is the most widely used PROCEDURE AND BEHAVIORAL system for assessing physical health status and helps CONSIDERATIONS to determine the potential need for medical consul- A patient’s ability to tolerate the stress of dental treat- tation and treatment modifications prior to dental ment depends on the procedure planned, time and medical procedures (see Figure 1). In general, required to complete the procedure, physical health ASA I status represents a healthy patient who does status, and psychological factors. Anticipation of a not require any treatment modification. An ASA II stressful dental procedure can increase the heart rate patient presents with well-controlled systemic 752 / Endodontics disease and usually will not require significant treat- requires any modification in the usual treatment pro- ment modification, although stress reduction may be tocol and, if so, what modifications are recommended. indicated. Patients in the ASA III category or above Since the ultimate responsibility for providing safe will almost always require medical consultation and treatment rests with the dentist, any concerns about possible treatment modifications. However, the ASA recommended treatment modifications should be classification system has several significant limita- resolved with the physician prior to treatment. tions and should be used only as a general guide for determining peri- and postoperative risk. Even experienced anesthesiologists exhibit differences of opinionintheclassificationofcases.25,26 In addition, Assessing the Need for Treatment when used alone, the ASA system is not a good Modifications predictor of operative risk.27 Various authors have proposed a medical risk assessment process that focuses more clearly on medical conditions specifi- MULTIDIMENSIONAL RISK ASSESSMENT cally relevant to dental practice.2,6,27,28 Clinicians MODEL (MD-RAM) may want to consider health history questionnaires Systemic disease can result in the loss of reserve capa- and verbal questions that focus primarily on medical city to handle stress.15 A patient’s ability to handle conditions that would, when present, elevate the stress decreases in direct relation to the extent of sys- patient to ASA II status or above. That is, any posi- temic disease. The three primary components of risk tive response to one of the health history questions assessment for dental treatment are physical health would automatically classify the patient as at least status (reserve capacity), emotional or psychological ASAIIandfurtherexplorationwouldbenecessaryto status, and type of dental procedure planned.30 determine the extent of systemic disease. de Jong Lapointe et al.15 proposed a two-dimensional risk et al.12,28,29 have developed and validated a patient assessment model that correlated the severity of disease questionnaire consisting of approximately 30 questions and procedural stress. However, this model presented for use in assessing the risk for dental treatment. only two specific medical conditions as examples (ischemic heart disease and chronic obstructive pul- monary disease (COPD)) and did not explicitly con- MEDICAL CONSULTATIONS sider patient anxiety as a variable. Dental anxiety can Approximately one-third of patients referred for a med- increase sympathetic activity and for some patients can ical consultation result in recommendations for some potentially precipitate a medical emergency.31 modification of treatment procedures.9 A request for We propose a new model, the Multidimensional consultation may occur by phone or letter and each Risk Assessment Model (MD-RAM; Figures 2 and 3), approach has certain advantages and disadvantages. A that incorporates the three primary aspects of risk phone conversation is immediate and may allow for the assessment into a unified approach for evaluating discovery of additional useful information. However, perioperative risk related to treatment for the ambu- the lack of a written letter from the physician increases latory dental patient. In this model, the dental patient the risk for potential misunderstanding and provides a is assigned a score ranging from 1 to 4 in each of the lower level of documentation from a medicolegal stand- three domains: physical health status (using the ASA point. The substance of all medical consultation con- classification system); procedural stress (type of versations should be documented in the patient’s record procedure, length of time to complete the procedure, and, whenever possible, a letter detailing the physician’s and clinician expertise—Figure 4); and psychological recommendations should be requested. A letter pro- status (self-reported dental anxiety—Figure 5). As vides more formal documentation of the communica- with any model, the output is only as good as the tion between health care providers. information input. When requesting a medical consultation, the clini- This model may provide a general guide for patient cian should be specific and concise. The medical con- assessment and is not intended to be all inclusive or a dition in question should be identified and the nature substitute for case-specific clinical judgment. The of dental procedure planned should be described (e.g., primary purpose of this model is to assist clinicians a brief description of the procedure, the type of anes- in determining if treatment modification, often a thetic planned, the potential for bleeding, the expected stress reduction protocol, may be indicated prior to length of procedure). The clinician should specifically dental treatment. Disease-specific recommendations ask the physician if the patient’s medical condition will be discussed later in the chapter. Chapter 24 / The Medically Complex Endodontic Patient / 753

Figure 2 Multidimensional Risk Assessment Model (MD-RAM).

MD-RAM score Interpretation

3-5 No treatment modification usually indicated

6-7 Possible medical consultation and treatment modification

8-9 Medical consultation often indicated and probable treatment modification

10-12 Medical consultation strongly advised; may require treatment in a hospital or specially equipped out-patient facility

Figure 3 Interpretation of MD-RAM score. 754 / Endodontics

Procedural stress scale Examples*

1 Denture adjustment; non-invasive oral exam; radiographs

2 Procedures requiring local anesthesia; prophylaxis with sub-gingival scaling; simple restorative procedures; uncomplicated non-surgical root canal treatment

3 Patients with acute pain and/or significant infection; extractions; surgical root canal; periodontal surgery

4 Bony impactions; trauma surgery

* = The clinician should consider possible upgrading if procedure is lengthy and move either up or down depending on clinician’s experience.

Figure 4 Estimating procedural stress. Adapted in part from Lapointe HJ et al.15

Dental anxiety scale Verbal descriptor

1 No anxiety

2 Mild anxiety

3 Moderate anxiety

4 Severe anxiety

Figure 5 Behavioral scale—patient’s self-reported dental anxiety.

Cardiovascular Disease quarter receiving successful treatment for hyperten- sion.32 The goal for patients with diabetes or renal HYPERTENSION disease is to maintain blood pressure below SBP of 130 and DBP of 80. Since hypertension is typically Hypertension is one of the most common medical asymptomatic, approximately one-third of patients conditions likely to be encountered in a dental office. with high blood pressure are unaware of their condi- Hypertensive patients are defined as those receiving tion.33 Even patients with normal blood pressure at the treatment for hypertension or those with a mean systo- age of 55 to 65 years have an almost 90% risk of devel- lic blood pressure (SBP) of 140 mg Hg or greater and/or oping hypertension by the age of 80 to 85 years.34 a mean diastolic blood pressure (DBP) of 90 mg Hg or Patients with untreated or inadequately treated hyper- greater. By this definition, approximately 24% of the tension are at significantly increased risk for acute com- adult population of the United States is hypertensive plications such as myocardial infarction (MI) and with about half of this group untreated and only one- stroke and chronic complications of hypertension. Chapter 24 / The Medically Complex Endodontic Patient / 755

Systolic Blood Pressure Diastolic Blood Pressure Classification (SBP) in mm Hg (DBP) in mm Hg Normal < 120 and < 80

Prehypertension 120-139 or 80-89

Stage 1 Hypertension* 140-159 or 90-99

Stage 2 Hypertension ≥ 160 or ≤ 100

* For patients with diabetes or renal disease, the goal is to maintain blood pressure less than 130/80 mm Hg.

Figure 6 Blood pressure classification for adult patients. Adapted from Herman WW et al.36

The clinical significance to the dental practitioner is tion strategies prior to treatment.36 Although clear clear—since at least 15% of all adult dental patients have guidelines for establishing a cutoff point for dental either untreated or inadequately treated hypertension, treatment (emergency or routine) are lacking, it is initial blood pressure measurement is an essential screen- generally accepted that patients with SBP greater than ing tool prior to dental treatment. In addition, it is 180 and/or DBP greater than 110 should be referred appropriate to measure blood pressure at least annually for medical consultation and treatment prior to den- during recall visits for all patients and at every visit for tal treatment and only emergency management of patients when an invasive dental procedure is planned. pain or acute infection should be considered.36 Guidelines for the classification of blood pressure Patients with SBP above 210 and/or DBP above 120 were recently revised in the seventh report of the Joint should be referred for emergent medical evaluation. National Committee on Prevention, Detection, Eva- luation, and Treatment of High Blood Pressure (JNC 7, 2003) (Figure 6). The JNC 7 report added a new VASOCONSTRICTOR USE IN PATIENTS category, prehypertension, for patients with SBP of WITH CARDIOVASCULAR DISEASE 120 to 139 and/or DBP of 80 to 89 in recognition of Vasoconstrictors are used routinely in endodontic the fact that this group was at greater risk for devel- therapy as a component of local anesthetics and often oping hypertension and should receive lifestyle mod- as a hemostatic agent during periapical surgery. Local ification advice and subsequent monitoring. The anesthetic with a vasoconstrictor, most commonly report also combined the previous Stage 2 and Stage lidocaine with 1:100,000 epinephrine, is the usual 3 categories into a new Stage 2 category for patients anesthetic of choice for root canal therapy, although with SBP greater than or equal to 160 and/or DBP many nonsurgical procedures can be performed using greater than or equal to 100. From a practical stand- local anesthetics without vasoconstrictor.37 When a point, patients with well-controlled hypertension or vasoconstrictor is indicated, epinephrine is preferred SBP below 160 and DBP below 100 should tolerate all over norepinephrine or levonordefrin due to a routine dental procedures,35 although referral for eva- decreased potential for alpha-1 receptor stimulation. luation by the patient’s physician is appropriate due Surgical procedures typically require greater quanti- to the well-documented benefits of maintaining blood ties of local anesthetic with a vasoconstrictor than pressure in the normal range. Patients with SBP nonsurgical root canal treatment. In particular, between 160 and 180 or DBP between 100 and 110 patients with advanced cardiovascular disease, geria- should also be able to tolerate most dental procedures tric patients, and patients taking certain medications without significantly increased risk of perioperative (e.g., MAO inhibitors and nonselective beta blockers) cardiovascular complications; however, complexity may have a reduced tolerance for vasoconstrictor- and stress of the planned treatment should be care- containing local anesthetics. Since local anesthetics fully considered with attention given to stress reduc- with vasoconstrictors are very helpful in obtaining 756 / Endodontics adequate hemostasis and visibility during periapical in patients receiving an IO injection with a 3% mepi- surgery, it may be difficult to perform the procedure vacaine solution. Although in this study no signifi- using anesthetics without vasoconstrictors.38 cant change in blood pressure was found in either The use of local anesthetics with vasoconstrictors in group, the authors recommended 3% mepivacaine patients with cardiovascular disease has been some- without vasoconstrictor for patients with any medical what controversial and was addressed by the JNC 7 condition that could reduce their tolerance for report. While the general goal should be to minimize epinephrine. the use of vasoconstrictors in patients with cardiovas- Although most experts agree that the use of gingival cular disease, the benefit of greater depth and dura- retraction cord containing epinephrine should be tion of anesthesia when local anesthetics with a avoided in patients with significant cardiovascular dis- vasoconstrictor are used is a significant argument in ease,36,40 some uncertainty exists over the use of racemic favor of their use. Adequate pain control is an essen- epinephrine-impregnated pellets as recently advocated tial component of endodontic therapy since pain- for improved hemostasis during periapical surgery.38,43 related stress could stimulate the release of significant In two clinical studies, no significant changes were quantities of endogenous catecholamines. Different observed in blood pressure or heart rate when epinephr- kinds of stress can increase the release of endogenous ine pellets (either cotton or collagen) were placed in the epinephrine by as much as 20 to 40 times over base- bony crypt to improve hemostasis during periapical line values.39 Pooled results from six studies of surgery.44,45 It is unlikely that a patient healthy enough patients undergoing extraction or other minor oral to tolerate two or three cartridges of local anesthetic surgery procedure demonstrated an average increase with 1:100,000 epinephrine would experience any in SBP and DBP of 11.7 and 3.3 mm Hg, respectively, untoward effects from the proper use of epinephrine- as well as an increase in heart rate of 4.7 beats per impregnated pellets during periapical surgery. Regard- minute (bpm). The use of local anesthetics containing less, other alternative topical hemostatic agents are epinephrine for these procedures resulted in an addi- available and should be considered for patients with tional relatively minor increase in SBP of 4 mm Hg significant cardiovascular disease. and 6 bpm.32 Careful aspiration and use of adequate gauge needle to facilitate aspiration during injection is required to minimize the chance of intravascular ISCHEMIC HEART DISEASE injection. Most authors feel that 0.036 to 0.054 mg When coronary atherosclerotic heart disease becomes of epinephrine (approximately two to three cartridges sufficiently advanced to produce symptoms, it is of local anesthetic with 1:100,000 epinephrine) should referred to as ischemic heart disease. Ischemic heart be safe for all patients except those with severe cardi- disease is relatively common in the general popula- ovascular disease or other specific risk factors, and tion, especially with increasing age, and typically those with SBP requiring urgent medical atten- presents as angina or heart failure.46 In most cases, tion.36,40,41 Local anesthetics with vasoconstrictors diminished blood perfusion of the myocardium due should be avoided or used with extreme caution in to coronary artery disease (atherosclerosis) is the patients with the following cardiovascular conditions: underlying cause with hypertension as a common severe or poorly controlled hypertension, arrhythmias contributing factor in heart failure. CHF and enlarge- that are refractory to treatment, MI within the past ment of the heart result from weakening of the month, stroke within the past 6 months, coronary damaged heart muscle. artery bypass graft within the past 3 months, and Chest pain secondary to ischemic heart disease results uncontrolled congestive heart failure (CHF).30 when the oxygen demand of the myocardium exceeds An important exception to this general rule regard- the oxygen supply. Transient pain is referred to as ing vasoconstrictors is the choice of local anesthetic angina pectoris and is often described as an aching, for intraosseous (IO) injections in patients with car- squeezing sensation or tightness in the middle of the diovascular disease. IO injections are most commonly chest. Angina is often precipitated by physical activity or used as a supplemental anesthetic technique for teeth stress and may radiate to the arm or jaw and may that are otherwise difficult to anesthetize. A transient present as facial or dental pain. Fear and anxiety asso- increase in heart rate can be expected in about two- ciated with dental treatment may be a precipitating thirds of patients receiving an IO injection using factor for angina in some patients.46 Sublingual or other lidocaine with 1:100,000 epinephrine, although heart forms of nitrates are the standard treatment for angina rate returns to near baseline within 4 minutes after and should result in rapid reversal of symptoms. injection.42 No increase in heart rate was found Patients should always be instructed to bring their usual Chapter 24 / The Medically Complex Endodontic Patient / 757 antianginal medicine with them for dental appoint- ing oral benzodiazepine (e.g., triazolam or ativan) ments. If symptoms are not relieved with oral nitrates and/or nitrous oxide can reduce the stress of a dental and suspension of stress-inducing activity, then MI procedure and increase the effectiveness of local should be suspected and immediate emergency treat- anesthesia.31 Clinicians must be aware of the medical ment should be initiated. Since angina is usually a need and legal requirements that include special train- transient event, patients with progressive pain or pain ing, permits, and monitoring when anxiolysis crosses at rest are considered to have unstable angina and pre- over into conscious sedation. If conscious sedation is sent a significant perioperative risk for MI.30 These required, it is best performed by a trained provider of patients are usually categorized as ASA IV. Chest pain anesthesia/sedation and with another operator pro- that is manageable with rest or medication and rela- viding the dental care. tively unchanged in duration, frequency, or severity over time is termed stable angina and represents a better prognosis and somewhat lower risk level than unstable HEART MURMURS AND VALVULAR angina. Typically, patients with stable angina would be DISEASE classified as ASA II or ASA III. Patients with valvular disease present two primary Compared to other surgical procedures, most dental considerations for dental treatment: potential risk for and oral surgery procedures are considered relatively infective endocarditis and risk of excessive bleeding low risk.47,48 However, a history of significant cardiac in patients on anticoagulant therapy.46 Management disease can be a major predictor of perioperative risk, considerations for patients on anticoagulant therapy are even for procedures with relatively low procedural stress. discussed later in this chapter. Most heart valve abnorm- Recent MI (less than 1 month), unstable angina, past MI alities affect either the aortic or the mitral valve and with significant residual damage, decompensated CHF, represent partial obstruction of blood flow (stenosis) or significant arrhythmias, and severe valvular disease are valve incompetence (regurgitation). Heart murmurs are all considered major predictors of increased periopera- common and may be benign or signify major underlying tive cardiovascular risk, and these patients would usually diseases such as degenerative valve disorders (e.g., aortic be classified as ASA IV. Patients with stable angina, past stenosis), rheumatic heart disease, congenital valve history of MI (greater than 1 month) with minimal lesions, prosthetic valves, atrial fibrillation, or CHF.51 residual myocardial damage, compensated CHF, or Two other conditions that place patients at increased risk diabetes mellitus (DM) should be considered at inter- for infective endocarditis are systemic lupus erythemato- mediate risk and would usually be classified as ASA II or sus and certain medications used for weight reduction ASA III.30,47 The presence of multiple risk factors creates (dexfenfluramine and fenfluramine–phentermine).51,52 an additive increase in the overall perioperative risk.49 Dental management requires evaluation of the type of Even patients with a history of recent MI or unstable heart condition and the risk of bacteremia from the angina should be able to tolerate routine dental proce- planned dental procedure. New guidelines for the pre- dures with local anesthesia, although medical consulta- vention of infective endocarditis were published in 2007 tion is required and conscious sedation with monitoring and represent a significant change from previous Amer- is often recommended.48,50 ican Heart Association guidelines.53 For example, anti- Treatment modification considerations for patients bioticprophylaxisisnolongerrecommendedforpatients with ischemic heart disease should include morning with a history of mitral valve prolapse (with or without appointments, short appointments, oral premedica- regurgitation), rheumatic heart disease, bicuspid valve tion with an anxiolytic drug and/or nitrous oxide/ disease, aortic stenosis, and certain congenital heart oxygen sedation, limited use of vasocontrictors (as conditions. Antibiotic prophylaxisisnowrecommended previously discussed), adequate pain management only for patients with valvular disease associated with the (during and after the dental appointment), and pos- highest risk of adverse outcomes from infective endocar- sible cardiac monitoring.30 Sedation with a short act- ditis. For patients in the highest risk category, antibiotic 758 / Endodontics

Antibiotic prophylaxis recommended

Highest risk of adverse outcome from infective endocarditis:

Prosthetic heart valve

Previous infective endocarditis

Congenital heart disease (CHD)*

Unrepaired cyanotic CHD, including palliative shunts and conduits

Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or catheter, during the first six months after the procedure

Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device

Cardiac transplantation recipients who develop cardiac valvulopathy

* antibiotic prophylaxis is not recommended for other forms of CHD

Figure 7 Recommendations for antibiotic prophylaxis based on risk stratification for infective endocarditis. Adapted from Wilson W et al.53

Antibiotic prophylaxis recommended only for patients at highest risk for adverse

outcome from infective endocarditis (Figure 24-7):

All dental procedures that involve manipulation of gingival tissue or the periapical

region of teeth or perforation of the oral mucosa (does not include routine local

anesthetic injections through noninfected tissue)

Figure 8 Risk of dental procedures. Adapted from Wilson W et al.53 prophylaxis is recommended for dental procedures that risk for infective endocarditis.54 The incidence and involve manipulation of gingival tissues or the periapical magnitude of bacteremia when canal instrumentation region of teeth or perforation of the oral mucosa. For all does not extend into the periapical tissues is very low, other patients with valvular disease, the risks associated and almost all bacteria are eliminated from the blood with routine antibiotic prophylaxis are greater than within 10 minutes.55,56 Canal instrumentation beyond potential benefits.53 Figures7and8listthespecificheart the apex, intraligamentary and IO injections, and peria- valve abnormalities and dental procedures that are con- pical surgery can all be expected to result in a higher risk sidered highest risk for infective endocarditis. In general, for transient bacteremia. In these situations, antibiotic procedures associated with nonsurgical root canal treat- premedication is recommended for patients in the ment such as local anesthetic injection, placement of the highest risk disease categories. Infective endocarditis is rubber dam, and instrumentation when contained within only rarely directly linked to dental procedures and the the canal system do not place the patient at significant efficacy of the recommended antibiotic regimen is Chapter 24 / The Medically Complex Endodontic Patient / 759

Standard oral regimen Adults: 2.0g Amoxicillin

Children: 50mg/kg

Alternative oral regimen for Adults: patients allergic to penicillin or 2.0g Cephalexin or other 1st or 2nd generation cephalosporin in patients who are currently taking equivalent dosage* a penicillin class antibiotic OR 600mg Clindamycin OR 500mg Azithromycin or clarithromycin

Children: 50mg/kg Cephalexin or other 1st or 2nd generation cephalosporin in equivalent dosage* OR 20mg/kg Clindamycin OR 15mg/kg Azithromycin or clarithromycin

Patients unable to take oral Adults: medications 2.0g IM or IV Ampicillin OR 1.0g IM or IV Cefazolin or ceftriaxone*

Children: 50mg/kg IM or IV Ampicillin OR 50mg/kg IM or IV Cefazolin or ceftriaxone* Alternative IM/IV regimen for Adults: patients allergic to penicillin and 1.0g IM or IV Cefazolin or ceftriaxone* unable to take oral medications OR 600mg IM or IV Clindamycin

Children: 50mg/kg IM or IV Cefazolin or ceftriaxone* OR 20mg/kg IM or IV Clindamycin within 30 minutes before the procedure

* = Cephalosporins should be used with caution in patients reporting an allergy to penicillin since approximately 5%–15% of patients who are allergic to penicillin will demonstrate cross reactivity with cephalosporins, especially first and second generation cephalosporins.

Figure 9 Antibiotic prophylaxis for dental procedures—all regimens are a single dose given 30 to 60 minutes before the procedure. Adapted from Wilson W et al.53 questionable.53,57–61 The current regimen and drugs of to be performed with the chair in a more upright choice for antibiotic prophylaxis are presented in Figure 9. position. They also suggest that the use of a rubber According to Lessard et al., some patients with sig- dam may be contraindicated for some of these patients nificant heart murmurs may have dyspnea, fatigue and due to restriction of air flow; however, this may be difficulty in breathing when reclined in the dental overcome with careful application of the rubber dam. chair51 and therefore the dental procedure may need Failure to use the rubber dam is considered below the 760 / Endodontics standard of care for root canal therapy and extraction control bleeding should be adequate.66,67 Jeske and may be the only option for these patients if a rubber Suchko,68 in a review prepared for the American Dental dam cannot be used. Association Council on Scientific Affairs and Division of Science, recommend against routine discontinuation of anticoagulant therapy prior to dental procedures, ANTICOAGULANT THERAPY including surgical procedures. Regardless of the man- AND BLEEDING DISORDERS agement approach selected, consultation with the Management of patients on anticoagulant therapy patient’s physician and an INR test on the day of surgery depends on the type of anticoagulant, the reason for antic- are strongly recommended. Hospitalization and conver- oagulant therapy, and the type of procedure planned. sion to heparin therapy may be considered in special Warfarin (Coumadin—DuPont Pharmaceuticals, cases, but the patient, physician, and surgeon must Wilmington, DE) anticoagulants are commonly pre- carefully weigh the potential risks against the expected scribed for the treatment or the prevention of thromboem- outcome and benefits. A new category of heparin antic- bolic events. This category of anticoagulant works by oagulant, low molecular weight heparins (LMWHs), blocking the formation of prothrombin and other clotting allows for patient self-administration and may present factors. The international normalized ratio (INR) value is a viable alternative for some patients who need to the accepted standard for measuring prothrombin time remain at a high level of anticoagulation but wish to (PT). The desired therapeutic range for INR is usually reduce the cost and time associated with traditional between 2 and 3.5, depending on the underlying medical heparin conversion therapy. indication for anticoagulant therapy. Low-dose aspirin therapy is known to increase Limited oral surgery procedures, defined as simple bleeding time by irreversibly inhibiting platelet aggre- forceps extraction of one to three teeth, may be safely gation. No treatment modifications should be neces- performed on patients with INR values within the sary for nonsurgical root canal procedures. However, normal therapeutic range.62–64 Nonsurgical root canal surgical procedures require evaluation of the reason treatment does not usually require modification of for and the necessity of aspirin therapy. It has been a anticoagulant therapy, although it is important to common practice to advise patients to discontinue ascertain that the patient’s INR is within the thera- aspirin therapy for 7 to 10 days prior to an oral peutic range, especially if a nerve block injection is surgical procedure.69 At low-dose therapeutic levels required. Periapical surgery may present a greater (<100 mg/day), aspirin may increase bleeding time challenge for hemostasis even for patients well main- and potentially complicate surgical procedures. How- tained within the therapeutic range. The clear field ever, Ardekian et al.69 concluded that low-dose visibility normally required for proper surgical man- aspirin therapy (<100 mg/day) should not be discon- agement of the root end may not be possible in tinued prior to oral surgery procedures and that patients on anticoagulant therapy. Consultation with bleeding could be controlled by local measures. the patient’s physician is required to assist in devel- Higher dose therapy may present a greater risk for oping an appropriate treatment plan. Some patients bleeding either during or after surgery. Even though a may be able to tolerate discontinuation of warfarin patient on aspirin therapy may not be at high risk for therapy 2 days prior to a planned surgical procedure significant intra- or postoperative bleeding, a concern to allow for the INR to ‘‘drift’’ downward. In a pro- for periapical surgery is the visibility problems spective cohort study, Russo et al.65 report that sus- created by oozing blood. Consultation with the pension of warfarin 2 days prior to a surgical proce- patient’s physician is advised to determine the med- dure resulted in no bleeding problems and no ical reason for aspirin therapy and to weigh the risks thromboembolic events. They found that the average and benefits of discontinuing aspirin prior to the time spent at an INR less than 2.0 (critical value) was proposed surgery. It should be possible to perform 28 hours and that 90% of the patients returned to the periapical surgery without discontinuing aspirin ther- desired therapeutic INR value within 7 days. How- apy if necessary, but the visibility during the proce- ever, this strategy may place certain patients at greater dure may be compromised and the prognosis may risk for a thromboembolic event and in these cases decrease accordingly.38 discontinuation of anticoagulant therapy would not Nonsteroidal anti-inflammatory drugs (NSAIDs) be recommended. also have an antiplatelet effect but, unlike aspirin, In general, patients on warfarin anticoagulant ther- the effect is reversible when discontinued and platelet apy should present minimal risk for significant bleeding activity should be expected to return to normal within during or after oral surgery and local measures to approximately three half-lives of the drug. Other Chapter 24 / The Medically Complex Endodontic Patient / 761 commonly prescribed antiplatelet drugs include Medications are usually the first line of treatment dipyridamole, ticlopidine, clopidogrel, abciximab, for cardiac arrhythmias, although many of these have integrelin, tyrafiban, and lamifiban. Heavy alcohol a narrow therapeutic safety range (e.g., digoxin) and consumption, liver disease, and certain medications must be carefully monitored. Surgery, cardioversion, can increase the risk of perioperative bleeding in and pacemakers are also used to treat arrhythmias. It patients taking antiplatelet medications. Medical is common for patients with atrial fibrillation to be consultation is advised prior to surgical procedures treated with an anticoagulant (typically warfarin and lab tests to determine platelet count and function sodium—management considerations discussed pre- (PFA-100 and Ivy BT) may be indicated. Some herbs viously in this chapter). A history of cardiac arrhyth- and dietary supplements may also affect bleeding risk. mia is often disclosed in the medical history. In Patients with inherited or acquired bleeding disorders addition to the medical history, patients with an are also at risk for excessive bleeding during and after irregular pulse, unusually rapid or slow pulse, periapical surgery procedures and may be at risk from reports of syncope, palpitations, dizziness, angina, local anesthetic injections particularly when using nerve or dyspnea should be referred to a physician for block injections. Impaired liver function secondary to evaluation prior to dental treatment. Once the nat- past or current alcohol or drug abuse may also predis- ure of arrhythmia and the stability of the condition pose a patient to excessive bleeding during surgery. A have been determined, most dental treatment can be medical consultation, usually with a hematologist, is safely performed using the same stress reduction required prior to dental treatment for patients with treatment modifications listed in the discussion of serious bleeding disorders such as thrombocytopenia, ischemic heart disease. As always, the clinician and hemophilia, and von Willebrand’s disease. Replacement staffshouldbepreparedtomanageamedicalemer- of deficient coagulation factors or platelet transfusion gency if necessary. may be required prior to dental treatment,70 particularly Electrical interference from certain dental devices is a if an inferior alveolar nerve block is required or a surgi- potential concern for patients with implanted cardiac cal treatment is planned. If non-surgical root canal pacemakers or cardioverter/defibrillators. In particular, treatment can be performed with only infiltration local electronic apex locators (EAL) and electric pulp testers anesthesia, replacement may not be necessary.71 How- (EPT) are commonly used in root canal therapy. Man- ever, this decision must be reached in consultation with ufacturers of EAL and EPT devices warn against the use the patient’s hematologist. of these devices in patients with cardiac pacemakers. However, current cardiac pacemakers are very well shielded from external electrical fields and the possibi- ARRHYTHMIAS AND CARDIAC lity for electrical interference seems to be very low. PACEMAKERS A recent clinical study supports previous in vitro Cardiac arrhythmias are a heterogeneous group of research and a case report in concluding that EAL and conditions defined as any disturbance in the normal EPT devices should be safe to use in patients with rate or rhythm of the heartbeat. Arrhythmias are the cardiac pacemakers and cardioverter/defibrillators.74–76 result of abnormal impulse generation, impulse con- One caveat from this study is that a mucosal lip clip was duction, or both and can range from harmless to life used to complete the circuit with the EPT device instead threatening.46 The overall prevalence of cardiac of the common clinical practice of having the patient arrhythmias in the general dental patient population hold the EPT wand in their hand. This lip clip technique is 15% to 17% with approximately 2 to 4% represent- is recommended if one elects to use an EPT device on a ing serious, potentially life-threatening arrhythmias.30 patient with a cardiac pacemaker, since the practice of Although arrhythmias are not uncommon in normal, using the patient’s hand to complete the circuit may healthy adults, the possibility of underlying cardiovas- allow for electrical current to pass through an area of the cular disease, systemic disease, or medication-induced body in closer proximity to the pacemaker. The safety of arrhythmia should be carefully evaluated prior to this variation of the EPT technique has not yet been dental treatment. Anxiety associated with dental treat- tested. ment may induce arrhythmias in susceptible patients. In addition, patients with cardiovascular disease are more prone to arrhythmias during oral surgery pro- CONGESTIVE HEART FAILURE cedures with local anesthesia.72 Patients taking CHF is the fourth most common medical diagnosis in digoxin for atrial fibrillation or CHF are especially at all age groups and represents the end-stage of other risk for arrhythmias during oral surgery procedures.73 common cardiovascular diseases such as coronary 762 / Endodontics

New York Heart Association CHF Dental management classification Signs and symptoms considerations

Class I No limitations on physical activity; Should be able to tolerate routine no dyspnea, fatigue, or palpitations dental treatment; stress reduction with ordinary physical activity protocol as needed

Class II Slight limitation on physical Should be able to tolerate routine activity; comfortable at rest but dental treatment; stress reduction may experience fatigue, protocol as needed; possible palpitations, and dyspnea with medical consultation ordinary physical activity

Class III Significant limitation of activity; Medical consultation; consider comfortable at rest but even minor treatment in hospital dental clinic activity results in symptoms or similar facility; avoid vasoconstrictors

Class IV Symptoms present at rest; Medical consultation; conservative symptoms exacerbated by any treatment only; treatment in physical activity hospital dental clinic; avoid vasoconstrictors

Figure 10 New York Heart Association’s classification system for patients with congestive heart failure (CHF) and dental management considerations. Adapted from Little JW et al.30 artery disease, hypertension, cardiomyopathy, and treatment in special care facilities or hospital-based valvular heart disease.30 CHF results in an inability clinics. The New York Heart Association (NYHA) has of the heart to efficiently pump blood that can involve developed a classification system for CHF that can be one or both ventricles. Patients with CHF typically adapted to assist in assessing risk for dental treatment present with significantly diminished reserve capacity (Figure 10). for handling stress (including dental treatment) and are often taking multiple medications with the poten- tial for drug interactions. Diabetes Patients with well-managed CHF should tolerate routine dental treatment with possible minor treatment Diabetes mellitus (DM) is a complex metabolic dis- modifications, similar to those recommended for order characterized by abnormalities in carbohydrate, patients with ischemic heart disease. In addition, the fat, and protein metabolism resulting either from a underlying causes (coronary artery disease, hyperten- deficiency of insulin (type 1) or from target tissue sion, valve disease, etc.) and medications should be resistance to its cellular metabolic effects (type 2). considered and managed appropriately. Patients with Hyperglycemia is the most clinically important meta- moderate to advanced CHF may require a more bolic aberration in DM and the basis for its diagnosis. upright chair position due to the presence of pulmon- Chronic hyperglycemia is associated with ophthalmic, ary edema. The clinician should be alert for orthostatic renal, cardiovascular, cerebrovascular, and peripheral hypotension when making adjustments in chair posi- neurological complications. DM is defined as a fasting tion. Uncompensated, advanced CHF requires medical blood glucose level greater than 125 mg/dL and the consultation prior to dental treatment and vasocon- normal fasting blood glucose level is considered to be strictors should be avoided. These patients may require less than 110 mg/dL. Patients with fasting plasma Chapter 24 / The Medically Complex Endodontic Patient / 763 glucose levels greater than 110 mg/dL but less than which should be taken into account prior to dental 126 mg/dL represent a transitional condition between procedures. normal and DM and are considered to have impaired glucose tolerance.77 Identification of patients at this stage can allow for earlier preventive interventions and possibly delay or prevent progression to DM. Pulmonary Disorders: Asthma, COPD, There are 20.8 million children and adults in the and Tuberculosis United States, or 7% of the population, who have DM. While an estimated 14.6 million have been diag- Asthma is a chronic inflammatory respiratory disease nosed with DM, 6.2 million people (or nearly one- with recurrent episodes of chest tightness, coughing, third) are unaware that they have the disease.78 The dyspnea, and wheezing resulting from hyperrespon- epidemic of obesity in the United States is anticipated siveness and inflammation of bronchiole tissue. Overt to result in an increase in the prevalence of diabetes. attacks may be provoked by allergens, upper respira- When reviewing medical histories, the clinician tory tract infections, genetic and environmental fac- should be aware of cardinal symptoms of DM, such tors, certain medications, and highly emotional states as polydipsia, polyuria, polyphagia, weight loss, and such as anxiety, stress, and nervousness. weakness, and should be referred to a physician for The endodontist should obtain a good history to diagnosis and treatment.30 In diabetic patients, the determine the severity and stability of disease. Patients clinician should ascertain how well controlled the should be instructed to bring their inhalers (broncho- condition may be. Dental appointment scheduling dilators) to each appointment and inform the endo- should take into account the importance of nutri- dontist of the earliest sign or symptom of an asthma tional consistency and the avoidance of appointments attack. During dental treatment, the most likely times that will overlap with or prevent scheduled meals. for an acute exacerbation of asthma are during and Symptoms of hypoglycemia may range from mild, immediately after local anesthetic administration and such as anxiety, sweating, tachycardia, to severe, such with stimulating procedures such as pulp extirpa- as mental status changes, seizure, and coma. Severe tion.83 Because stress is implicated as a precipitating hypoglycemic episodes are a medical emergency and factor in asthma attacks, sedation may be beneficial. should promptly be treated with 15 g of oral carbo- While nitrous oxide may be used in patients with hydrate, such as 6 oz orange juice, three to four teas- mild-to-moderate asthma, its use is contraindicated poons of table sugar, five Life Savers, or three glucose in patients with severe asthma due to its potential to or dextrose tablets. If a patient is unable to cooperate cause airway irritation.84 Alternatively, oral premedi- or swallow, 1 mg glucagon may be administered by cation may be accomplished with small doses of a subcutaneous or intramuscular injection. Side effects short-acting benzodiazepine. In patients taking theo- of glucagon include nausea, vomiting, and headache. phylline, macrolide antibiotics should be avoided, as It has been well established that hyposalivation, they have the potential to develop toxic levels of gingivitis, periodontitis, and periodontal bone loss theophylline. In addition, it is important to note that are associated with DM, especially when poorly con- aspirin and other NSAIDs may trigger asthma attacks trolled.79,80 The well-controlled diabetic is at no in a proportion of patients.85 greater risk of postoperative infection than is the COPD is a term for pulmonary disorders character- nondiabetic.81 Therefore, surgical procedures in well- ized by chronic irreversible obstruction of airflow from controlled diabetics do not require prophylactic the lungs and represents the fourth most common cause antibiotics. However, when surgery is necessary in of death in the United States.86 The three most common the poorly controlled diabetic, prophylactic antibiotics forms of COPD are chronic bronchitis, emphysema, and should be considered due to the altered function of bronchial asthma. Patients with pulmonary diseases typi- neutrophils in diabetics. Surgery may also increase cally present with one or more of the following symp- insulin resistance such that a diabetic may become toms:cough,dyspnea,sputum,hemoptysis,wheezing,or hyperglycemic in the postoperative period. Preopera- chest pain.87 Patients should be placed in a semisupine tive antibiotics should be administered in these position. Since the use of a rubber dam may induce a instances.82 Furthermore, delayed alveolar healing feeling of airway constriction, careful application of the following dentoalveolar surgery should raise the suspi- rubber dam and administration of humidified low-flow cion of osteomyelitis, for which prompt surgical oxygen, generally between 2 and 3 L/min, may be con- consultation should be arranged. Finally, patients with sidered. Nitrous oxide should not be used in patients DM may present with systemic complications, each of with severe COPD. 764 / Endodontics

Tuberculosis (TB) is an infectious disease that is and glucose in a localized area of the brain. The endo- spread by way of bacilli-containing airborne droplets, dontist should be aware of how to identify the patient typically by coughing, sneezing, or talking. The signature having a stroke in his/her office. Regardless of the pro- lesion of TB is the tubercle, a granuloma formed by the cedure, a patient’s blood pressure should be checked continuing ingress of macrophages and lymphocytes to before treatment to identify a patient whose blood thesiteofinfection.88 In the lung, tuberculous granulo- pressure is elevated and who might be at risk for a stroke mas are frequently associated with regions of tissue if subjected to stress. Slurred speech, loss of motor necrosis, termed caseous necrosis due to its gross appear- control over a portion of the body, unilateral facial ance. After the infection is established, symptomatic droop, unilateral visual changes, and unilateral severe individuals will show pulmonary manifestations of the headache are all potential signs of a stroke or a transient disease, often limited to the periphery of the middle and ischemic attack. Should any of these events occur, the lower regions of the lung,88 though reactivated disease is patient should have his/her vital signs checked, be most commonly found in the lung apices.89 Oral tuber- placed in a supine position, have vital signs monitored, cular infections are rare, occurring in 0.05 to 5% of and be transported to an emergency facility immedi- patients with TB, though when lesions are present, they ately, as treatment must be activated in a timely manner. typically consist of ulcers, fissures, or swellings on the Patients with a history of stroke may be at risk for dorsum of the tongue.90 Despite the declining incidence aspiration due to swallowing abnormalities, so they of TB in the United States, health care workers including should be positioned in a semisupine position, and endodontists and their staffremainathighriskforcon- rubber dams should be carefully applied and should tracting the disease. It is imperative for the endodontist always be used. Poststroke patients may be on oral to educate office staff about TB prevention and recogni- anticoagulants; so if surgical intervention is planned, tion of symptoms and oral manifestations of the disease the endodontist should contact the physician to deter- to protect the staff and other patients from becoming mine whether or not the risk of a thromboembolic event infected. A thorough medical history should be obtained, outweighs the benefits of postoperative hemostasis and any elective dental procedures on a patient with (please refer to section ‘‘Anticoagulant therapy and established or suspected active TB should be delayed bleeding disorders’’). The endodontist should also be until the individual can be treated and subsequently aware that the poststroke patient may experience emo- proved noninfectious. Routine dental treatment is tional problems, including depression and behavior appropriate after it has been established that the patient inappropriate to the situation. has been adequately treated and there are no signs or Seizures are one of the most commonly encoun- symptoms of active disease. The clinician should be tered neurological disorders and can manifest as an aware of potential drug interactions when managing isolated incident with unknown etiology or as a symp- dental patients undergoing antitubercular treatment. In tom of a condition that requires long-term treatment. patients taking medications such as rifampin and isonia- A seizure is a temporary involuntary disturbance of zid, acetominophen should be avoided due to the poten- brain function that results in synchronous, excessive, tial for liver damage. The use of aspirin and muscle abnormal electrical discharges of the neurons in the relaxantsisdiscouragedinthose individuals taking strep- central nervous system.92 This manifestation can take tomycin due to a heightened risk of ototoxicity and the form of motor disturbances, altered feelings, or respiratory paralysis, respectively.91 Streptomycin is also changes in the patient’s level of consciousness. The known to cause facial paresthesia and pancytopenia. two main categories of seizure classification are partial and generalized. Most people who have seizures have good control and are capable of receiving routine Central Nervous System: Stroke, dental care. The endodontist should be aware of the patient’s seizure medications, since many antibiotics Seizure Disorders, and Hydrocephalic are contraindicated. Should a seizure occur in the Shunts dental office, the procedure should be stopped imme- diately and all instruments should be removed from Cerebrovascular accident or stroke is defined as the the oral cavity. The patient should be placed in a acute onset of neurologic deficits persisting for at least supine position and low to the ground. Basic life 24 hours. Strokes are subclassified into ischemic insults, support should begin immediately, including opening occurring secondary to thrombosis or embolization, or the airway, obtaining vital signs such as heart rate and hemorrhagic, which usually indicate an arterial process. blood pressure, and contacting emergency medical The lack of blood flow leads to deprivation of oxygen services. Chapter 24 / The Medically Complex Endodontic Patient / 765

The risk of shunt infection following invasive dental dures,96–98 and other authors have recommended treatment for patients with hydrocephalic shunts (ven- antibiotic prophylaxis for all hemodialysis patients triculoperitoneal and ventriculoatrial) is believed to be undergoing procedures that cause mucosal bleeding about 3.0 to 5.0% and because of this there is a lack of to prevent vascular access infections, bacteremia, and consensus regarding the need for antibiotic prophy- infective endocarditis.97 Renal osteodystrophy and laxis.93 The authors of this study found that pediatric secondary hyperparathyroidism may occur in late- dentists were more likely to be concerned about strep- stage disease due to disorders in calcium, phosphor- tococcal microorganisms and neurosurgeons were ous, and abnormal vitamin D metabolism. Such a more concerned about staphylococcal microorganisms manifestation may predispose renal patients to jaw in shunt infection. The majority of both groups recom- fracture during surgical procedures. mended penicillin prophylaxis, although there are Because many drugs are metabolized via the kidney, more appropriate antibiotics if staphylococcal micro- renal dosing should account for the drug’s extended organisms are presumed to be responsible for most half-life by lengthening the interval between medication shunt infections (please refer to the discussion in sec- doses. In particular, antibiotic medications should be tion ‘‘Prosthetic joints and other prosthetic devices’’). adjusted for renal dosing. NSAIDs should be avoided Consultation with the patient’s neurosurgeon is in patients with renal insufficiency due to their nephro- advised and close attention to any changes in prophy- toxic effects, but no longer need to be avoided when the laxis guidelines is important. patient has ESRD.

Renal Disease and Dialysis Cancer Chemotherapy and Radiation Chronic renal failure is a slowly progressive condition characterized by an irreversible reduction in the glo- Therapy merular filtration rate. The progression of this disease Oropharyngeal cancer encompasses a variety of malig- begins with an asymptomatic decrease in the kidney nant diseases. More than 90% of oral cancers are function and eventually results in end-stage renal dis- squamous cell cancers, 9% are salivary gland tumors, ease (ESRD). Throughout the decline in function, sarcomas and lymphomas, and the remaining 1% are multiple systems are affected, directly related to the metastatic cancers originating in other parts of the kidney dysfunction. ESRD is potentially fatal unless body.99 In the year 2006, the American Cancer Society the patient undergoes dialysis or kidney transplanta- reported 31,000 people with newly diagnosed orophar- tion (please see section ‘‘Solid Organ Transplanta- yngeal cancers and 7800 deaths from this disease.100 tion’’ regarding kidney transplantation). Dialysis Numerous risk factors have been implicated in the may take the form of hemodialysis, which represents etiology of oropharyngeal cancer, including tobacco, 90% of dialysis treatment,94 or peritoneal dialysis. excessive alcohol, ultraviolet light exposure, immuno- This treatment removes fluid and wastes and equili- suppression, and viruses. Oral cancer has a variable brates electrolytes and acid–bases via diffusion and appearance, including white or red patches, an exophy- osmosis across a semipermeable membrane. tic mass, an ulceration, a granular raised lesion, a The clinician should be aware of the ESRD patient’s submucosal mass, or a combination thereof. Treatment type and days of dialysis treatment as well as comor- of oropharyngeal cancer is composed of surgical inter- bid conditions such as hypertension and/or diabetes. vention, radiation treatment, and chemotherapy and Mechanical trauma to platelets and anticoagulants for systemic cancers possibly hematopoietic stem cell such as heparin used during hemodialysis may transplantation (HSCT). Multimodality therapy is now increase the renal patient’s tendency for bleeding. more commonly used for oropharyngeal cancer in While it is recommended that dental procedures be order to obtain increased survival rates. performed on nondialysis days, typically the day after Cancers that are amenable to surgery and do not dialysis,95 the endodontist should be aware that affect the oral cavity require few treatment plan mod- abnormal platelet function may cause a greater risk ifications. However, oropharyngeal cancer treatments of bleeding during surgical procedures. In addition, and complications may cause significant changes in patients with ESRD require aggressive treatment of the oral cavity. Preceding cancer treatment, all sources odontogenic infections. Antibiotic premedication has of inflammation and potential infection should be also been recommended for hemodialysis patients eliminated. Whenever possible, nonrestorable teeth with shunts who undergo invasive dental proce- and teeth with a poor long-term periodontal 766 / Endodontics prognosis (i.e., not expected to be retained for the BON, though minimally invasive procedures have been patient’s lifetime) within the field of high-dose radia- recommended.106 Before initiation of bisphosphonate tion should be extracted more than 2 weeks prior to therapy, aggressive preventive treatment should be per- radiation therapy. Symptomatic nonvital teeth can be formed including oral hygiene, caries control, and endodontically treated at least 1 week before initiation extraction of teeth with a poor long-term prognosis. of head and neck radiation or chemotherapy although For patients who have been taking bisphosphonate dental treatment of asymptomatic teeth even with medication, preventive care for high-risk patients is periapical involvement can be delayed, particularly if important to reduce the risk of developing BON. Non- treatment can be limited to intracanal therapy. Many surgical endodontic treatment of teeth that would cancer patients have indwelling catheters that may be otherwise be extracted should be considered. Teeth with susceptible to infection and, while controversial, the extensive carious lesions might be treated by nonsurgi- American Heart Association (AHA) regimen for anti- cal endodontic therapy possibly followed by crown biotic prophylaxis (see Figure 9) has been recom- resection and restoration similar to preparing an over- mended before invasive dental procedures.101 If an denture abutment.109 For patients at higher risk of individual is receiving chemotherapy, the endodontist developing BON, surgical procedures including surgical should be familiar with the patient’s white blood endodontic procedures should be avoided if possible. count (WBC) count and platelet status. Endodontic Informed consent for endodontic procedures should procedures can be performed if the neutrophil count involve a discussion of risks, benefits, and alternative is greater than 2000 cells per cubic millimeter and treatments with the patient. platelets are greater than 50,000 cells per cubic milli- meter. Postradiation osteonecrosis (PRON) results from radiation-induced changes in the jaws, may arise in bones exposed to high-dose radiation, and is char- Bone Marrow and Solid Organ acterized by asymptomatic or painful bone exposure. Transplantation Protocols to reduce the risk of osteonecrosis include selection of endodontic therapy over extraction, expert atraumatic surgical procedures, considering HEMATOPOIETIC STEM CELL the use of nonlidocaine local anesthetics that contain TRANSPLANTATION no or low concentration of epinephrine, and prophy- HSCT may be indicated in patients with hematologi- lactic antibiotics plus antibiotics during the week of cal malignancy, nonhematological malignancy, and healing.102 some nonmalignant disorders. Patients may undergo an autologous (self) or an allogeneic (nonself) trans- plantation, each of which has its own pros and cons. BISPHOSPHONATE-ASSOCIATED The goal is to treat bone marrow disease or to inten- OSTEONECROSIS OF THE JAWS sify therapy that would destroy the bone marrow, Bisphosphonates are bone resorption inhibitor medica- following which the patient is ‘‘rescued’’ by the infu- tions that are commonly used in conjunction with can- sion of previously stored autologous hematopoietic cer chemotherapy and the prevention or treatment of stem cells or hematopoietic stem cells from a matched osteoporosis. Recent reports have suggested that donor. Prior to transplantation, patients should bisphosphonates (e.g., pamidronate, zoledronic acid) undergo a thorough dental examination and treat- may cause osteonecrosis of the maxillary and mandib- ment to permit adequate healing before the HSCT. ular bones, either spontaneously or following dental Pretreatment endodontic therapy should be com- surgical procedures or oral trauma.103–107 Although pleted at least 10 days prior to initiation of cancer the mechanism of action is unknown, it is suggested therapy. Teeth with poor prognoses should be that a decrease in bone cellularity and antiangiogenic extracted, utilizing the 10-day window as a guide. effects and decreased blood flow resulting from bispho- The current AHA protocol for antibiotic prophylaxis sphonate therapy could lead to a generalized impair- prior to invasive oral procedures may be warranted in ment in bone remodeling.105 There appears to be a patients who have indwelling catheters (e.g., Hickman dose–response relationship in that patients taking IV catheter). Prophylactic antibiotics are also recom- formulations appear to be at greater risk for bispho- mended in patients who are neutropenic (<1,000 sphonate-associated osteonecrosis (BON).108 There are neutrophils per cubic millimeter). currently no scientific data to support any specific treat- During and following high-dose chemotherapy/ ment protocol for the management of patients with HSCT, aggressive oral hygiene measures should be Chapter 24 / The Medically Complex Endodontic Patient / 767 instituted. Numerous oral complications may develop, antibiotics may be recommended for invasive proce- including mucositis, graft-versus-host disease, infec- dures. Further, patients may have indwelling catheters tion, taste changes, and bleeding. Patients should not that may lead to a recommendation for antibiotic resume routine dental treatment, including dental scal- prophylaxis. Should a patient experiences transplant ing and polishing, until adequate immunological rejection, dental care provided should be limited reconstitution has taken place; this typically occurs no to emergency care only until stabilization is again less than 1 year posttransplant. The aerosolization of achieved. After the posttransplantation patient has debris and bacteria during the use of high-speed rotary stabilized, indicated dental procedures may be per- cutting instruments can put the patient at risk for formed after consultation with the patient’s transplant aspiration pneumonia; additionally, bacteremias occur team. Postoperative guidelines regarding prophylactic as a result of dental treatment and can cause serious antibiotics have not been established but, if recom- outcomes. Should treatment be deemed necessary mended, AHA guidelines may be used.110 Finally, the within 1 year posttransplant, the endodontist must endodontist should be aware that posttransplant reci- consult with the oncologist to determine appropriate pients will likely be on immunosuppressant therapy, treatment. regardless of the length of time posttransplant.

SOLID ORGAN TRANSPLANTATION Prosthetic Joints and Other It is important to reduce the risk of infection in the immunosuppressed recipient of a transplant.110 Pre- Prosthetic Devices transplant patients should undergo eradication of Patients with prosthetic joints may be at increased dental disease, including endodontic procedures as risk for developing a hematogenous joint infection warranted to remove any potential sources of infec- following dental procedures. Since the necessity of tion, and deferral of any elective treatments. Of prophylactic antibiotics in this group of patients is course, the endodontist should take into account controversial, consultation with the patient’s ortho- the underlying condition for which the transplant is pedic surgeon is advised. Current recommendations required. In the immediate posttransplant period, include antibiotic coverage with higher risk dental emergency dental procedures may be necessary. At procedures (see Figure 8) within 2 years following this stage, patients are highly immunosuppressed prosthetic joint surgery, for those who have had pre- to prevent organ rejection, so the AHA regimen of vious hematogenous prosthetic joint infections and antibiotic prophylaxis with possible postoperative for those with some medical conditions (Figure 11).111

All patients during first two years following total joint replacement

Immunocompromised/immunosuppressed patients Inflammatory arthropathies such as rheumatoid arthritis, systemic lupus erythematosus Drug- or radiation-induced immunosuppression

Patients with medical comorbidities Previous prosthetic joint infections Malnourishment Hemophilia HIV infection Type 1 diabetes Malignancy

Figure 11 Patients at potential increased risk of experiencing hematogenous total joint infection. Adapted from ADA, AAOS Advisory statement.111 768 / Endodontics

Patient Type Suggested Drug Regimen

Patients not allergic to Cephalexin, cephradine or 2 grams orally 1 hour prior penicillin amoxicillin to dental procedure

Patients not allergic to Cefazolin or ampicillin Cefazolin 1g or ampicillin penicillin and unable to take 2g intramuscularly or oral medications intravenously 1 hour prior to the dental procedure

Patients allergic to Clindamycin Clindamycin 600 mg orally penicillin 1 hour prior to the dental procedure

Patients allergic to Clindamycin 600mg intravenously 1 hour penicillin and unable to take prior to the dental procedure oral medications

Figure 12 Suggested antibiotic prophylaxis regimens for patients with total joint replacement. Adapted from ADA, AAOS Advisory statement.111

The selection of antibiotic and dosage regimen differs less of the patient’s phase of pregnancy.112 Elective den- slightly from the commonly accepted regimen for tal procedures may often be performed in the second prevention of bacterial endocarditis since different trimester, when the pregnancy is mostly devoted to microorganisms are more commonly associated with maturation. While some medications may be harmful late joint infections (Figure 12). These guidelines sug- to the fetus, safe alternatives are often available. Lido- gest prophylaxis for recently placed large joint pros- caine and prilocaine local anesthetics have an FDA theses even though there is little evidence that oral category B rating and consequently should be first-line flora account for many infections in joint prostheses. choices for use with pregnant women. A common These guidelines will be continually reviewed and misconception is concern over the use of local anes- current guidelines must be followed for medicolegal thetics containing epinephrine. Local anesthetics con- purpose. taining epinephrine should be relatively safe for use Antibiotic prophylaxis is not indicated for dental during pregnancy113 and allow for greater depth and patients with pins, plates, screws, and penile or breast duration of anesthesia as well as reduction of any poten- implants, nor is it routinely indicated for dental tial systemic effect of lidocaine. In addition, the only patients 2 years after total joint replacements. A commonly available alternative to local anesthetics with patient with a total joint replacement or other surgi- a vasoconstrictor is 3% mepivicaine, an FDA category C cally placed prosthesis with acute orofacial infection drug. If antibiotics are warranted, many first-line should be aggressively treated as any other patient to choices are rated by the FDA as category B for pregnancy eliminate the source of infection, and appropriate risk. Pregnant women may be more susceptible to infec- antibiotics should be administered as warranted. tion,114 which may be partly due to physiological changes as well as alterations in pharmacokinetics.

Pregnancy Few procedures are contraindicated during pregnancy. Human Immunodeficiency Virus There is no contraindication to using necessary diag- HIV is a blood-borne retrovirus infection transmitted nostic procedures, such as appropriate radiographs, as primarily by blood and bodily fluids by intimate sexual long as normal safety precautions are followed. If dental contact and parenteral means. Upon infection, a viral caries is the source of pain or infection, invasive care enzyme reverse transcriptase allows the virus to inte- such as endodontic therapy should be provided regard- grate its own DNA into the genome of an infected cell Chapter 24 / The Medically Complex Endodontic Patient / 769 and replicate using the infected cell’s ribosomes and antibiotics for patients with SCA, although the major- protein synthesis. Initially, immune seroconversion ity of pediatric dentistry program directors and pedia- with antiviral antibody production occurs followed by tric hematologists recommend antibiotic coverage for a significant decrease in CD4+ lymphocytes over a per- invasive procedures such as extraction or other surgical iod of up to years. The most effective management in procedures.119 The use of a local anesthetic with no the progression of HIV infection and AIDS is a combi- vasoconstrictor (or minimal vasoconstrictor) may be nation of antiviral agents known as highly active anti- advisable for nonsurgical procedures since the micro- retroviral therapies (HAART), which has significantly vasculature is often already compromised by SCA. increased the lifespan and the quality of life of indivi- Osteomyelitis is much more common in patients with duals infected with HIV. Upon initial assessment of an SCA117 and the risk/benefit ratio for surgical endodon- HIV-infected individual, the patient’s physician should tic procedures should be carefully considered for be contacted to determine CD4+ counts as well as base- patients with SCA. line kidney and liver function. It is safe and desirable to assure that comprehensive dental care is available to HIV-positive patients. No modification of irreversible Liver Disease procedures or surgical treatment is recommended unless patients have reduced platelet count (<50,000 End-stage chronic liver disease (cirrhosis) is the result of cells per milliliter) or neutrophil counts <1,000 cells hepatocellular injury and necrosis that leads to fibrosis per milliliter, at which time a patient may require anti- and nodular regeneration. Cirrhosis may be asympto- biotic prophylaxis. Routine antibiotic use is contraindi- maticforlongperiodsoftimeandmaybeundiagnosed cated. The prognosis for successful healing of necrotic untilsystemicsignsareapparent. Ultimately, chronic teeth with chronic apical periodontitis following root liver disease affects multiple body systems. For more canal treatment is essentially the same for HIV-positive information on the preliver transplant patient, please patients as for noninfected patients.115,116 The endo- see section ‘‘Solid organ transplantation’’ earlier in this dontist should examine oral tissues, as oral conditions chapter. associated with HIV may identify a person who is Performing any surgery in the preliver transplant unknowingly infected with HIV, may be used in staging patient involves the risk of severe hemorrhage due to and classification, and/or may denote progression to thrombocytopenia or reduced hepatic synthesis of AIDS. Surgically treated teeth do not show delayed coagulation factors. Preoperative evaluation should healing. Antibiotics are used only if warranted by the include a complete blood count with platelet count, clinical infection, and in a neutropenic patient. PT or INR, and partial thromboplastin time to ensure an intact coagulation system. Patients with cirrhosis have an increased susceptibility to infection. Odonto- genic infections should be treated aggressively with Sickle Cell Anemia appropriate antibiotic treatment. Antibiotic prophy- Sickle cell anemia (SCA) affects approximately 1 in laxis prior to dental procedures is recommended only 400 African-Americans and as much as 30% of the if the patient has a history of spontaneous bacterial population of some Central and West African coun- peritonitis (SBP), ascites (accumulation of excess fluid tries. Clinical concerns in endodontic practice include in the abdomen), another medical indication for anti- the propensity for painful vasoocclusive episodes and biotic prophylaxis, or whose medical condition would bacterial infections.117 Since patients with SCA may be drastically deteriorate should SBP develop. When considered immunocompromised and infections can antibiotic prophylaxis is indicated in the patient with trigger a sickle cell crisis, these patients usually require end-stage liver disease, a recommended oral regimen aggressive treatment of infections, including the use of is 2.0 g of amoxicillin plus 500 mg of metronidazole systemic antibiotics.117 The vasoocclusive aspects of the 1 hour before the dental procedure, or patients may disease can result in tissue and bone necrosis and be given 2.0 g of ampicillin plus 500 mg of metroni- pulpal necrosis in an otherwise intact and healthy dazole intravenously 1 hour before the procedure.120 tooth.118 Since teeth with asymptomatic necrotic pulps Finally, the pharmacokinetics of drugs commonly can become infected, patients with SCA require careful used in dentistry can be altered in patients with end- pulpal evaluation. Nonsurgical root canal treatment of stage liver disease. Alteration of medication dosage asymptomatic necrotic teeth prior to the development based upon hepatic compromise, additional medica- of acute symptoms and infection is indicated. There is tions, and site of metabolism of the medication may a lack of consensus regarding the value of prophylactic require consultation with the patient’s physician. 770 / Endodontics

Adrenal Suppression and Long-Term with direct patient questioning about the history of allergic reactions to any drugs or substances. True Steroid Use allergic reactions are characterized by one or more of The adrenal cortex produces mineralocorticoids, such the following signs and symptoms: skin rash, swelling, as aldosterone, and glucocorticoids, such as cortisol, urticaria, chest tightness, shortness of breath, rhinor- 123 which are important in maintaining fluid volume. Adre- rhea, and conjunctivitis. nocortical insufficiency may result primarily from Addi- Type I (immediate or anaphylactic, IgE-mediated) son’s disease, an autoimmune condition, or secondarily and Type IV (delayed, cell-mediated) are the two types from hypothalamic or pituitary disease or from the of allergic reactions most likely to be encountered as a administration of exogenous corticosteroids (30 mg result of exposure to a substance used in endodontic per day or more of cortisol equivalent [about 5 mg treatment. Type I hypersensitivity requires previous prednisone]). Supplemental steroids are often recom- exposure to the antigen and can occur after a single mended before and possibly following surgery to pre- prior exposure or multiple prior exposures to the aller- vent adrenal crisis in patients who receive chronic daily gen. The reaction occurs shortly after exposure and can steroid therapy.121 In these patients, for minor surgical rapidly progress to life-threatening anaphylaxis. Type procedures such as routine endodontic surgeries, the IV hypersensitivity typically appears 48 to 72 hours after glucocorticoid target is about 25 mg of hydrocortisone exposure and is mediated by T lymphocytes in contrast equivalent (5 mg of prednisone) on the day of surgery. If to the humoral immune system (antibody)-mediated a moderate risk surgery is to be performed, the gluco- Type I reaction. Contact dermatitis is a classic Type IV corticoid target is about 50 to 75 mg per day of hydro- reaction. When materials used in endodontic treatment cortisone equivalent on the day of surgery and for one come in contact with the periapical tissues (either postoperative day. Nonsurgical dental procedures, intentionally or inadvertently), there is the potential including nonsurgical root canal treatment, generally for a delayed Type IV hypersensitivity reaction. The require no supplementation; however, this should be allergic potential of various materials commonly used reviewed on a case-by-case basis and consideration in endodontic treatment is summarized in Figure 13. given to the anticipated procedural stress and patient tolerance for dental treatment.121 As a rule of thumb, a patient who recently discontinued the use of exogenous LOCAL ANESTHETICS corticosteroids should wait 2 weeks before undergoing True Type I allergy to an amide local anesthetic is surgical procedures. Patients on alternate day steroids extremely rare. Nevertheless, patients reporting a his- do not likely require steroid supplementation. Efforts to tory of allergic reaction to a local anesthetic require control pain and infection can decrease the risk of an thorough evaluation prior to proceeding with treat- adrenal crisis. ment (assuming that a local anesthetic is needed for root canal treatment) since true allergic reactions have been reported.124–133 Perhaps the most common response elicited upon exploration of the presumed Allergy to Materials Used in allergic reaction is a report of tachycardia, syncope or general uneasiness following local anesthetic injection. Endodontic Therapy Such a response almost certainly represents a psycho- The prevalence of allergies and allergy-related diseases genic reaction rather than true allergy.132,134 Careful has increased significantly in recent years.122 Approxi- aspiration during injection can help prevent an inad- mately 15 to 20% of dental patients report some form vertent intravascular injection and subsequent of allergy on their medical history questionnaire and increased toxicity and potential for adverse reaction. approximately 5% report allergy to one or more In a recent prospective study of 5,018 dental patients drugs.123 In fact, allergy is the single most common who received a local anesthetic, 25 (0.5%) adverse reac- positive finding on the medical history questionnaire.2 tions were recorded.124 Twenty-two of the reactions Fortunately, with the exceptions of latex and certain were mild, quickly reversible, and considered to be psy- antibiotics, the majority of reported allergies are to chogenic in nature. Only two of the reactions were substances not typically used in dental treatment. Even initially viewed as possible allergic reactions and both so, many materials used in root canal therapy have the of these were excluded as true allergic reactions after potential for eliciting an allergic reaction. The medical provocative challenge tests. In another study of 236 history questionnaire serves as the first stage in screen- patients who experienced an adverse reaction after injec- ing for allergies but should always be supplemented tion of local anesthetic, all tested negative following Chapter 24 / The Medically Complex Endodontic Patient / 771

Category Material Allergic potential Barriers Natural rubber latex + Vinyl (polyvinyl chloride) –* Nitrile (acrylonitrile and –* butadiene) Polychloroprene (Neoprene) –* Irrigating solutions and Sodium hypochlorite + disinfectants (0.5%–6%) Hydrogen peroxide – (3%–30%) Chlorhexidine + (0.2%–2%) Iodine Potassium iodide + (2%–5%) Ethylenediamine tetraacetic acid – (EDTA) (10%–17%) Citric acid – (10%–50%) MTAD ? (mixture of tetracycline, citric acid and detergent) Intracanal medications Phenols + Aldehydes + Calcium hydroxide – Iodine containing pastes + Sealers and filling materials ZnOE materials (various sealers + and temporary filling materials) Epoxy resins + Glass ionomers – Composite resins ? Mineral trioxide aggregate – (MTA) Calcium chelate/polyvinyl resin – Gutta percha (trans 1,4-isoprene ? polymer)

* = Type I allergic reactions are generally not seen with use of these synthetic materials; however, chemicals used in processing and powders in gloves may still cause Type IV reactions in sensitive individuals ? = allergic potential is uncertain or unknown but probably low; allergy to one of the components is possible.

Figure 13 Allergic potential of materials commonly used in endodontic treatment. Adapted in part from Hensten A and Jacobsen N,158 and Zehnder M.151 intradermal injection of local anesthetic containing tial causes of allergic reactions. Although reaction to the epinephrine and preservative.135 sulfite preservative is also believed to be rare,135 allergic Both sulfite preservatives used in local anesthetics reactions to preservatives used in local anesthetics have containing epinephrine and latex allergen released into been reported.136–138 Since preservatives are used only the anesthetic solution from the vial stopper are poten- in local anesthetics containing a vasoconstrictor, the risk 772 / Endodontics of allergic reaction from this potential source can be NRL and this number increases to as much as 17% for eliminated by using an anesthetic without vasoconstric- health care workers.146 Urticaria is the most common tor and preservative (e.g., 3% mepivicaine). Local anes- initial finding in Type I sensitivity reaction to NRL.144 thetic cartridges contain two potential sources of latex Patients with a history of multiple surgeries (especially allergen that could possibly leach into the anesthetic spina bifida) or atopy (multiple allergies) and health solution—the rubber stopper and the diaphragm. A care workers all have an increased risk of sensitivity to recent review of the literature found no case reports or NRL. Some food allergies (e.g., avocado and banana) are controlled studies demonstrating that the latex present associated with an increased risk of latex allergy. Con- in a dental local anesthetic cartridge could cause an sidering the multiple potential sources of exposure to allergic reaction.139 However, the same review found NRL in the dental office (e.g., rubber dam material, several case reports of allergic reactions attributed to gloves, local anesthetic cartridges, rubber mouth props, trace amounts of latex found in other medication vial rubber tubing, and even some blood pressure cuffs), stoppers and intravenous tubing. Even though there is history of allergy to NRL requires special treatment no strong evidence to support the avoidance of local modifications. In addition, clinicians who treat patients anesthetic cartridges in patients with a known latex with known or suspected sensitivity to NRL should be allergy, experts in the area have recommended using prepared to provide initial management of an acute local anesthetic from glass-enclosed vials to avoid any allergic reaction if necessary. potential risk of exposure to latex allergens.140,141 If it Consultation with the patient’sprimarycarephysician can be determined that the local anesthetic cartridge or allergist is advised to help assess the degree of risk, contains non-latex materials for the diaphragm and previous reactions and treatment, and possible premedi- stopper, then there is no need for concern. cation with a corticosteroid. All potential sources of NRL It should also be noted that a documented allergy to exposure in the dental office should be considered. Non- one type of amide local anesthetic does not necessarily latex gloves and rubber dam materials are now readily imply allergy to all amide local anesthetics and often a available from commercial sources, and these items may readily available alternative can be found after test- be easily substituted for NRL-containing products. Since ing.128,132 As a practical matter, patients referred for latex allergens can be transferred by contact with powder allergy testing should be given sample cartridges of at from latex gloves and other sources, it may be prudent to least two different local anesthetics so that the allergist schedule the patient as the first of the day to decrease the can test with the same solution that will be used for chance of contact with residual latex allergens on envir- dental treatment. Options for patients with a docu- onmental surfaces, clothing, and room air.147 The poten- mented allergy to all commonly used local anesthetics tial for cross-reaction with gutta-percha in NRL-sensitive include sedation, general anesthesia, electronic anesthe- patients has not been demonstrated although caution sia,132,142 and injectable diphenhydramine. A solution should be exercised to avoid extrusion of any filling of 1% diphenhydramine with 1:100,000 epinephine can material beyond the confines of the root canal space be compounded by a local pharmacist and used for (for more on this subject, please refer to section ‘‘Intra- infiltration or mandibular block injections. The dosage canal medications, cements, and filling materials’’). Also, should be limited to a maximum of 50 mg at each as previously discussed, the potential for reaction to latex appointment.123 allergens present in the local anesthetic cartridge stopper or diaphragm should be considered. LATEX Ofthemanymaterialsusedinthedentalofficewiththe ANTIBIOTICS AND ANALGESICS potential for initiating an allergic reaction, natural rub- Allergy to penicillin is one of the most common drug ber latex (NRL) is the most common.143 Reports of allergies and affects approximately 2.5 million people allergic reactions to NRL beganin1987coincidentwith in the United States.123 Although many reported the widespread adoption of universal precautions, allergic reactions cannot be confirmed unless the including the use of latex gloves for practically all med- patient is willing to undergo testing to rule out ical and dental procedures.144,145 Type IV sensitivity is allergy to penicillin, it is safest to assume the allergy themostcommontypeandisrelatedtothevarious is real and select an alternative antibiotic. In the case chemicals used in processing NRL. The potentially much of allergy to penicillin, it should be presumed that more serious Type I sensitivity to NRL is a reaction to the patient is also allergic to the synthetic penicillins. proteins found in NRL. Approximately 6% of the gen- In addition, cephalosporins show cross-reactivity in eral population is believed to have Type I sensitivity to approximately 5% to 10% of penicillin allergic Chapter 24 / The Medically Complex Endodontic Patient / 773 patients.123 Clindamycin is an appropriate alterna- used in current endodontic therapy. Calcium hydro- tive to penicillin for treatment of endodontic infec- xide paste, a commonly used intra-appointment med- tions and bacterial endocarditis prophylaxis.54,148 ication, is not allergenic. Temporary filling materials Clarithromycin is another medication that can be containing zinc oxide and eugenol (ZnOE) have the considered. More information about antibiotic selec- potential for allergic reactions and, unlike materials tion and dosage is found in Chapter 21, ‘‘Treatment contained exclusively within the confines of the root of Endodontic Infections, Cysts, and Flare-Ups.’’ canal space, are likely to have contact with mucosal NSAIDs are the usual drugs of first choice for tissues.160 management of endodontic-related pain and are tol- Zinc oxide and eugenol, a potential allergen, is a com- erated well by most patients. However, caution should mon component of many root canal sealers and two be used in prescribing NSAIDs in patients with common root-end filling materials (IRM and Super asthma and/or known allergy or sensitivity to aspirin. EBA). Sealers containing formaldehyde or paraformal- Reports of allergy to codeine are most commonly dehyde (such as N2 paste and Endometazone), especially related to gastrointestinal side effects rather than true when extruded beyond the apex, have been demon- allergy, although allergy to opioid analgesics does strated to stimulate often severe allergic reactions.161–164 occur. If the patient’s history suggests an adverse Resin-based sealers such as AH26 and AHPlus also have reaction related to gastrointestinal distress (including the potential to stimulate an allergic response,158 nausea, emesis, or constipation), an alternative syn- although this is believed to be rare. Calcium hydroxide- thetic narcotic or a combination pain medicine may based sealers such as Sealapex or glass ionomer sealers be considered. Analgesics are discussed in more detail such as Ketac-Endo could be reasonable alternatives for in Chapter 22, ‘‘Management of Endodontic Pain.’’ patients with known allergy to any of the components of ZnOE or resin-based sealers. As always, one should care- IRRIGATING SOLUTIONS fully read the list of ingredients since at least one sealer marketed as a calcium hydroxide-based sealer contains a Sodium hypochlorite, in concentrations varying from significant ZnOE component. 0.5% to 6%, is currently the most commonly used Dentin-bonded resin-type root-end filling materials canal disinfectant and irrigating solution in endodon- 149–151 have demonstrated excellent biocompatibility in long- tics. Sodium hypochlorite not only possesses term clinical studies with no evidence of allergic reac- excellent tissue solvent and antimicrobial properties tions in treatment failures.165–167 However, the choice of but also demonstrates concentration-related tissue resin filling material is important since some resins are toxicity. Although an allergic reaction and/or hyper- known to release formaldehyde when setting. Mineral sensitivity to sodium hypochlorite when used as an trioxide aggregate (MTA), a relatively new material used endodontic irrigating solution is rare, several cases have 150,152,153 for root-end fillings, apexification, perforation repair, been reported. It has been suggested that some and pulp capping, has demonstrated excellent biocom- patients may be sensitized by exposure to household 168–170 150 patibility and no suspected allergic potential. bleaching products. Alternatives to sodium hypo- Althoughtherehavebeencasereportsofsuspected chlorite include sterile saline or water, chlorhexidine allergic reactions to gutta-percha in patients who were (0.2% to 2%), iodine potassium iodide (2% to 5%), allergic to NRL,171,172 the possibility that the reactions hydrogen peroxide (3%), ethylenediamine tetraacetic were due to another material used in root canal treat- acid (EDTA, 10% to 17%), citric acid (10%), and a 151,154–157 ment could not be ruled out. In fact, cross-reactivity recently introduced material, MTAD. Of between commercially available gutta-percha and NRL these alternatives, iodine potassium iodide and chlor- has not been demonstrated.173,174 In addition, gutta- hexidine possess the potential for stimulating an percha is normally well contained within the confines allergic reaction. A recent review article provides an oftherootcanalspaceandthereforeshouldnothavethe excellent overview of the relative advantages and dis- 151 potential to elicit an immune response. Gutta-percha advantages of these selected irrigating solutions. manufactured for root canal treatment contains other ingredients such as barium sulfate,zincoxide,waxes,and INTRACANAL MEDICATIONS, CEMENTS, coloring agents; so potential allergy to any of these mate- AND FILLING MATERIALS rials should be considered, especially if there is a potential Intracanal medications such as formocresol, formal- for extrusion of filling material. Newer non-gutta-percha dehyde, eugenol, camphorated phenols, and cresatin filling materials (e.g., Resilon) show promise but could are all known to be potential allergens.158,159 Fortu- be expected to contain many of the same added ingre- nately, these canal medications are not frequently dients as commercially available gutta-percha. 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Tate AR, Norris CK, Minniti CP. Antibiotic prophylaxis for 104. Migliorati CA. Bisphosphanates and oral cavity avascular children with sickle cell disease: a survey of pediatric den- bone necrosis. J Clin Oncol 2003;21(22):4253–4. tistry residency program directors and pediatric hematolo- gists. Pediatr Dent 2006;28(4):332–5. 105. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular 120. Douglas LR, Douglass JB, Sieck JO, Smith PJ. Oral manage- and maxillary bone: an emerging oral complication of sup- ment of the patient with end-stage liver disease and the liver portive cancer therapy. Cancer 2005;104(1):83–93. transplant patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86(1):55–64. 106. Migliorati CA, Casiglia J, Epstein J, et al. Managing the care of patients with bisphosphonate-associated osteonecrosis: an 121. Miller CS, Little JW, Falace DA. Supplemental corticoster- American Academy of Oral Medicine position paper. J Am oids for dental patients with adrenal insufficiency: reconsi- Dent Assoc 2005;136(12):1658–68. deration of the problem. J Am Dent Assoc 2001;132(11):1570–9; quiz 1596–7. 107. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteo- necrosis of the jaws associated with the use of bisphospho- 122. Kay AB. Allergy and allergic diseases. First of two parts. nates: a review of 63 cases. J Oral Maxillofac Surg N Engl J Med 2001;344(1):30–7. 2004;62(5):527–34. 123. Little JA, Falace DA, Miller CS, Rhodus NL. Dental manage- 108. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] ment of the medically compromised patient. St. Louis, MO: review: bisphosphonates and osteonecrosis of the jaws. Ann Mosby; 2002. pp. 314–27. Intern Med 2006;144(10):753–61. 124. Baluga JC, Casamayou R, Carozzi E, et al. Allergy to local 109. American Association of Endodontists. Endodontic implica- anaesthetics in dentistry. Myth or reality? Allergol Immuno- tions of bisphosphonate associated osteonecrosis of the jaws. pathol (Madr) 2002;30(1):14–19. AAE Position Paper; 2006. 125. El-Qutob D, Morales C, Pelaez A. Allergic reaction caused by 110. Guggenheimer J, Eghtesad B, Stock DJ. Dental management articaine. Allergol Immunopathol (Madr) 2005;33(2):115–16. of the (solid) organ transplant patient. Oral Surg Oral Med 126. Finder RL, Moore PA. Adverse drug reactions to local Oral Pathol Oral Radiol Endod 2003;95(4):383–9. anesthesia. Dent Clin North Am 2002;46(4):747–57, x. 778 / Endodontics

127. Brown RS, Paluvoi S, Choksi S, et al. Evaluating a dental 146. Clarke A. The provision of dental care for patients with patient for local anesthesia allergy. Compend Contin Educ natural rubber latex allergy: are patients able to obtain safe Dent 2002;23(2):125–8, 131–2, 134 passim; quiz 140. care? Br Dent J 2004;197(12):749–52; discussion 746. 128. Malanin K, Kalimo K. Hypersensitivity to the local 147. Kosti E, Lambrianidis T. Endodontic treatment in cases of anesthetic articaine hydrochloride. Anesth Prog 1995;42(3– allergic reaction to rubber dam. J Endod 2002;28(11):787–9. 4):144–5. 148. Baumgartner JC, Xia T. Antibiotic susceptibility of bacteria 129. Bosco DA, Haas DA, Young ER, Harrop KL. An anaphylac- associated with endodontic abscesses. J Endod toid reaction following local anesthesia: a case report. Anesth 2003;29(1):44–7. Pain Control Dent 1993;2(2):87–93. 149. Johnson BR, Remeikis NA. Effective shelf-life of prepared 130. MacColl S, Young ER. An allergic reaction following injec- sodium hypochlorite solution. J Endod 1993;19(1):40–3. tion of local anesthetic: a case report. J Can Dent Assoc 150. Kaufman AY, Keila S. Hypersensitivity to sodium hypo- 1989;55(12):981–4. chlorite. J Endod 1989;15(5):224–6. 131. Ravindranathan N. Allergic reaction to lignocaine. A case 151. Zehnder M. Root canal irrigants. J Endod 2006;32 (5):389– report. Br Dent J 1975;138(3):101–2. 98. 132. Ball IA. Allergic reactions to lignocaine. Br Dent J 152. Caliskan MK, Turkun M, Alper S. Allergy to sodium hypo- 1999;186(5):224–6. chlorite during root canal therapy: a case report. Int Endod J 133. Seng GF, Kraus K, Cartwright G, et al. Confirmed allergic 1994;27(3):163–7. reactions to amide local anesthetics. Gen Dent 1996;44(1):52–4. 153. Dandakis C, Lambrianidis T, Boura P. Immunologic evalua- 134. Rood JP. Adverse reaction to dental local anaesthetic tion of dental patient with history of hypersensitivity reac- injection—‘allergy’ is not the cause. Br Dent J 2000; tion to sodium hypochlorite. Endod Dent Traumatol 189(7):380–4. 2000;16(4):184–7. 135. Berkun Y, Ben-Zvi A, Levy Y, et al. Evaluation of adverse 154. Torabinejad M, Khademi AA, Babagoli J, et al. A new solu- reactions to local anesthetics: experience with 236 patients. tion for the removal of the smear layer. J Endod Ann Allergy Asthma Immunol 2003;91(4):342–5. 2003;29(3):170–5. 136. Campbell JR, Maestrello CL, Campbell RL. Allergic response 155. Shabahang S, Pouresmail M, Torabinejad M. In vitro anti- to metabisulfite in lidocaine anesthetic solution. Anesth Prog microbial efficacy of MTAD and sodium hypochlorite. J 2001;48(1):21–6. Endod 2003;29(7):450–2. 137. Schwartz HJ, Sher TH. Bisulfite sensitivity manifesting as 156. Beltz RE, Torabinejad M, Pouresmail M. Quantitative ana- allergy to local dental anesthesia. J Allergy Clin Immunol lysis of the solubilizing action of MTAD, sodium hypochlor- 1985;75(4):525–7. ite, and EDTA on bovine pulp and dentin. J Endod 138. Seng GF, Gay BJ. Dangers of sulfites in dental local anes- 2003;29(5):334–7. thetic solutions: warning and recommendations. J Am Dent 157. Vianna ME, Gomes BP, Berber VB, et al. In vitro evaluation Assoc 1986;113(5):769–70. of the antimicrobial activity of chlorhexidine and sodium 139. Shojaei AR, Haas DA. Local anesthetic cartridges and hypochlorite. Oral Oral Surg Oral Med Oral Pathol Oral latex allergy: a literature review. J Can Dent Assoc Radiol Endod 2004;97(1):79–84. 2002;68(10):622–6. 158. Hensten A, Jacobsen N. Allergic reactions in endodontic 140. Malamed SF. Medical emergencies in the dental office. 5th practice. Endod Top 2005;12:44–51. ed. St. Louis, MO: Mosby; 2000. p. 394. 159. Gawkrodger DJ. Investigation of reactions to dental materi- 141. Roy A, Epstein J, Onno E. Latex allergies in dentistry: als. Br J Dermatol 2005;153(3):479–85. recognition and recommendations. J Can Dent Assoc 160. Hensten-Pettersen A, Jacobsen N. Perceived side effects of 1997;63(4):297–300. biomaterials in prosthetic dentistry. J Prosthet Dent 142. Malamed SF, Quinn CL. Electronic dental anesthesia in a 1991;65(1):138–44. patient with suspected allergy to local anesthetics: report of 161. Forman GH, Ord RA. Allergic endodontic angio-oedema in case. J Am Dent Assoc 1988;116(1):53–5. response to periapical endomethasone. Br Dent J 1986; 143. Scully C, Ng Y-L, Gulabivala K. Systemic complications due to 160(10):348–50. endodontic manipulations. Endod Top 2003;4:60–8. 162. Kunisada M, Adachi A, Asano H, Horikawa T. Anaphylaxis 144. Huber MA, Terezhalmy GT. Adverse reactions to latex pro- due to formaldehyde released from root-canal disinfectant. ducts: preventive and therapeutic strategies. J Contemp Dent Contact Dermititis 2002;47(4):215–18. Pract 2006;7(1):97–106. 163. Haikel Y, Braun JJ, Zana H, et al. Anaphylactic shock during 145. Hamann CP, DePaola LG, Rodgers PA. Occupation-related endodontic treatment due to allergy to formaldehyde in a root allergies in dentistry. J Am Dent Assoc 2005;136(4):500–10. canal sealant. J Endod 2000;26(9):529–31. Chapter 24 / The Medically Complex Endodontic Patient / 779

164. Braun JJ, Zana H, Purohit A, et al. Anaphylactic reactions aggregate in the mandible of guinea pigs: a preliminary report. to formaldehyde in root canal sealant after endodontic J Endod 1995;21(11):569–71. treatment: four cases of anaphylactic shock and three of 170. Koh ET, McDonald F, Pitt Ford TR, Torabinejad generalized urticaria. Allergy 2003;58(11):1210–15. M. Cellular response to mineral trioxide aggregate. J Endod 165. Rud J, Rud V, Munksgaard EC. Long-term evaluation of 1998;24(8):543–7. retrograde root filling with dentin-bonded resin composite. 171. Gazelius B, Olgart L, Wrangsjo K. Unexpected symptoms to J Endod 1996;22(2):90–3. root filling with gutta-percha. A case report. Int Endod J 166. Rud J, Rud V, Munksgaard EC. Periapical healing of man- 1986;19(4):202–4. dibular molars after root-end sealing with dentine-bonded 172. Boxer MB, Grammer LC, Orfan N. Gutta-percha allergy in a composite. Int Endod J 2001;34(4):285–92. health care worker with latex allergy. J Allergy Clin Immunol 167. Andreasen JO, Munksgaard EC, Fredebo L, Rud J. Period- 1994;93(5):943–4. ontal tissue regeneration including cementogenesis adjacent 173. Costa GE, Johnson JD, Hamilton RG. Cross-Reactivity stu- to dentin-bonded retrograde composite fillings in humans. dies of gutta-percha, gutta-balata, and natural rubber latex J Endod 1993;19(3):151–3. (Hevea brasiliensis). J Endod 2001;27(9):584–7. 168. Torabinejad M, Chivian N. Clinical applications of mineral 174. Hamann C, Rodgers PA, Alenius H, et al. Cross-reactivity trioxide aggregate. J Endod 1999;25(3):197–205. between gutta-percha and natural rubber latex: 169. Torabinejad M, Hong CU, Pitt Ford TR, Kaiyawasam SP. assumptions vs. reality. J Am Dent Assoc 2002;133(10): Tissue reaction to implanted super-EBA and mineral trioxide 1357–67. CHAPTER 25

DRUG INTERACTIONS AND LABORATORY TESTS

PAUL D. ELEAZER

Drug Interactions tion of distribution is epinephrine and b-blocker drugs competing for the same binding site on Drug interaction discussions are often exhaustive, albumin. Metabolism-type pharmacokinetic inter- but may not be directed to probabilities of interac- actions include the macrolide family of antimicro- tions clinicians are more likely to experience. bials competing for the breakdown liver enzyme Drug–drug interactions as well as some food–drug pathway with drugs such as Tagamet (cimetidine). and herbal medicine–drug interactions that are Elimination drug reactions include the competi- likely to occur will be considered in this chapter. tion of methotrexate and nonsteroidal anti- While dentists are not obliged to treat every inflammatory drugs (NSAIDs) for removal by the patient, they cannot deny treatment based on a kidney. patient’s disability, such as a medical condition. An example of pharmacodynamic reaction is Therefore, it is important to be prepared to treat ethanol and a benzodiazepine combining to increase patients taking multiple drugs by becoming aware central nervous system (CNS) sedation without a of dangerous drug interactions. detectable difference in plasma levels in either of The drug interaction information in this chapter the drugs from their levels if administered alone. is derived from the work of a panel of pharmacolo- Interviewing the patient may provide valuable gists who factor likelihood of an interaction with clues about possible drug reactions or interactions. severity of the possible reaction to arrive at a level of When drug action is plotted against response in a clinical significance.1 Some less likely reactions with large patient population, the graph is almost always serious potential adverse results are also included. a bell-shaped curve, meaning that a few patients Certainly new reactions, some serious, will be dis- develop an exaggerated response and some show covered as more knowledge accumulates. On-line very little effect. Most people have the expected resources are available for updated information.2,3 response. If a patient has a history of over- or Principles of pharmacology and history taking can under-response to a drug, the clinician should be help the clinician determine probable risk for indivi- alert to a similar response. Drug interactions for dual patients. Drug interactions can be classed as members of the same drug class are likely to pharmacokinetic or pharmacodynamic. Pharmacoki- be analogous, but there are exceptions. A second netic reactions include changes of rate or extent of major consideration in history taking is the absorption, distribution, metabolism, or excretion. possibility of inaccurate reporting by the patient. Pharmacodynamic drug interactions involve a Such may be the case with a patient who denies change in the patient’s response without a change in a medical problem based on a sense of bravado or drug plasma level. one who vainly wants to postpone admission of An example of a pharmacokinetic absorption is the encroachment of age. Furthermore, patients the anti-diarrheal Kao-Pectate (kaolin and pectin) may simply forget important details of their drugs which decreases absorption of tetracycline antibio- or dosages. Also, many lay persons who are not tics. An example of pharmacokinetic drug interac- well versed in medical conditions may not grasp

780 Chapter 25 / Drug Interactions and Laboratory Tests / 781 the importance of reporting all their specific con- icines and those on atypical diets also may be more ditions or chronic medications. likely to have an unexpected drug reaction. Some authors have suggested that generic medi- Some patients may not be greatly affected by a cations may not be as effective as brand name drug interaction and might not report it to their drugs, especially for certain categories of drugs. An prescribing doctor. Even among observant patients, example of this is illustrated by the discovery of the number of dramatic drug interactions that imperfections with enteric coatings that would not affect every patient every time is probably very protect the medication from adverse effects of low. This inconsistency of effect may allow the acidic stomach contents.4 practitioner to gain confidence in prescribing drugs The prudent practitioner should observe drug if they see their patients having no problems. Even interaction reports for newly introduced drugs and for a specific individual, past experience with com- be cautions about prescribing these drugs until suffi- bining drugs is no guarantee of safety. cient time has elapsed to elucidate all reactions. The most serious reactions of concern to den- Often, drug interactions are discovered after a drug is tists are listed in Tables 1–12. With theophylline, introduced to the market, even though many lab tests, the margin between therapeutic dose and toxic animal tests, and human trials were performed before level is narrow. With international travel now com- release of the drug for sale. An example of such a monplace, drugs removed from the market in one situation is the drug ketorolac (Toradol). It was found country may be brought in from another, making very effective in controlling postoperative dental pain the need to know overseas trade names as well and was widely prescribed before being associated with as the generic labels. Such is the case with non- stomach and kidney problems that eventually lead to sedating antihistamines astemizole (Hismanal) and withdrawal of the oral form from the market, except terfenadine (Seldane), which can cause life-threa- for brief follow-up to parenteral use.5 tening torsades de pointes cardiac arrhythmias if Dentists are fortunate in that they seldom need to combined with macrolide antibiotics. prescribe drugs for chronic use. Brief exposure limits Systemic epinephrine can adversely affect a drug interactions and side effects compared to long- patient without drug interaction by increasing term use. Even so, some important drug interactions anxiety and causing frightening tachycardia. occur rapidly. Keeping the local anesthetic in the local area mini- For many drug interactions, the net result is mizes the possibility of drug interaction. However, simply a change in reaction to one or both drugs. Lipp et al.7 experimented with labeled epinephrine The change can be an increased response or a and found a 22% incidence of intravascular injec- decreased effect. Sometimes, a combination of tion without positive aspiration, meaning that the drugs results in an unexpected interaction. An clinician should not derive a false sense of security example of a surprising increased drug effect occurs from a lack of aspiration of blood during an when administering benzodiazepine drugs to anesthetic injection. Avoidance of systemic inter- patients taking the calcium channel blocker diltia- action can best be assured by slow injection with zem (Cardizem). The combination causes little observation of the patient for signs of systemic change to diltiazem action, but results in a rapid injection of epinephrine, such as pallor, tachycar- increase in benzodiazepine sedation, apparently dia, and anxiety. because the calcium channel blocker decreases The concept of decreased drug effect of oral con- metabolic breakdown of the benzodiazepine. In traceptives by orally administered antibiotics has one study, the area under the curve of drug con- received attention in the lay press. Careful research centration over time for a benzodiazepine was has led to the belief that antibacterial drugs com- nearly tripled.6 monly used by dentists are very unlikely to cause Individual variation plays an important role in a failure in oral contraception. Research suggests much of what we know about drug interactions. that the antifungal drug ketoconazole and the anti- Generally, those affected more are the elderly, tuberculosis drug rifampin may have an effect whose metabolic systems are less robust. Often, on oral contraceptives. It is prudent for clinicians to those with chronic systemic disease, and those tak- suggest alternative methods of contraception to ing multiple medicines, are more likely to have female patients of childbearing age because birth drug interactions, perhaps because unknown reac- control pills are not 100% effective and because of tions may be at work. Patients taking herbal med- the misinformation in the lay press. 782 / Endodontics

Over-the-counter drugs can cause drug interac- take a few days to appear. Damaged muscle leads to tions of concern to the dentist. Herbals can also increased creatine phosphokinase enzyme levels, cause drug interaction problems. One problem with which are typically used to confirm a clinician’s herbals is that many patients consider them to be suspicion of this potentially very serious drug inter- dietary supplements and fail to report that they are action. Early reports question whether rosuvastatin taking an herbal. Recent study has elucidated many (Crestor) is subject to this interaction.8 drug interactions with herbals. Ergot derivatives, which mitigate vascular head- Dentists commonly use antimicrobial drugs, aches, may interact with macrolide antibiotics, pain relievers, and local anesthetics. Antimicrobial inducing peripheral ischemia secondary to vasos- drugs have eliminated many risks of life. The first pasm. Not all patients respond to reversal therapy true antibiotic, penicillin, came into common use for this drug interaction, making this a very serious among dentists following World War II. Because potential problem. so many patients have taken antibiotics, it is a little Yet another category of classic interaction with wonder that many drug interactions have been drugs slowing metabolic pathways occurs with identified. macrolides. To reach therapeutic levels, theophyl- Tetracyclines were developed after penicillin. As line is often administered in doses close to the toxic they were gaining in popular usage, penicillin drugs threshold. When paired with erythromycin, the were undergoing structural changes to offer differ- decreased elimination may push the concentration ent forms to counter antimicrobial resistance. Ery- of the bronchodilator into the danger zone. thromycin, the original macrolide antibiotic, was Obviously, the higher the patient’s therapeutic introduced after tetracyclines. For a time, erythro- dose, the greater the risk. Early studies indicate mycin was widely popular among dentists, who azithromycin probably acts similarly, while clari- chose it because there was no risk of anaphylactic thromycin may not.9,10 reaction and because antibiotic resistance to this Table 1 contains more serious and more prob- drug originally seemed to be a limited problem. able reactions of drugs with macrolide antibiotics. While severe allergic problems have not arisen, Dentists who prescribe macrolides should maintain bacterial resistance and serious drug interactions vigilance for signs of any interaction. have limited use of erythromycin and its congeners, Table 2 ranks potential reactions to metronida- clarithromycin (Biaxin) and azithromycin (Zithro- zole (Flagyl), a drug many dentists prescribe. This max). The many drugs now known to interact with drug’s antibacterial spectrum is for obligate anae- macrolides do so because of shared metabolic path- robes, but some obligate anaerobes are resistant. ways that delay metabolism. Higher levels of one or Clinicians often use this DNA impeding agent with both drugs commonly result in severe cardiac a penicillin or cephalosporin bactericidal drug. rhythm problems, some life-threatening. Surpris- Research has shown that most endodontic infec- ingly, even anti-arrhythmic drugs may cause such tions contain multiple organisms, characteristically arrhythmias when administered with macrolides. with many facultative microbes.11 Outcome analy- One should note that combinations do not always sis of microbial susceptibilities of cultures from cause a predictable reaction, meaning that prescrib- endodontic infections shows that metronidazole ing a certain dose for a particular individual with- alone is not effective for these infections.12 out untoward reaction does not guarantee a similar Metronidazole shares the adverse interaction of result for subsequent prescriptions. anticoagulant drugs with all antibiotics. By killing Severe muscle wasting serious reactions may normal gut flora, the production of vitamin K occur with macrolides when combined with ‘‘sta- decreases, thus altering the balance between the tin’’ drugs, very commonly used for lowering cho- normal clotting enhancing vitamin and the clot- lesterol. These drugs inhibit HMG-CoA reductase, preventing anticoagulant. The result is that a clin- a key enzyme in the production pathway of the ical bleeding problem is more likely. Metronidazole ‘‘bad’’ or low density cholesterol. Muscle aches has an additional interaction of importance to the are among the first symptoms that can occur with clotting balance. It further increases bleeding pro- the drug alone, but occur much more often when clivity by a direct inhibition of metabolism of the macrolide antibiotic effectively increases its warfarin (Coumadin).13 concentration by impeding metabolism through Also of note, metronidazole shows interaction their common liver pathway. The symptoms may with ethanol, just like with disulfram (Antabuse), Chapter 25 / Drug Interactions and Laboratory Tests / 783

Table 1 Potential Reactions between Macrolide* Antibiotics and All Drugs Rapid Reactions Delayed Reactions

Very significant Established reaction Established reactions s Carbamazepine (Tegretol) (! toxicity) (76b) s Cisapride (Propulcid) (! arrhythmia) (192) s Digoxin (! toxicity) (285a) Probable reaction Probable reactions Ergot derivatives (! peripheral ischemia) (315a) s Anticoagulants (! bleed) (79) s Statins (! myopathy) (rhabdomyolysis) (368hb) s Primozide (Orap) antipsychotic (! cardiotoxicity) (575d) Suspected reactions s Antiarrhythmics (! arrhythmia) (36a) s Eplerenone (hyperkalemia) (! arrhythmia) (312c) Grapefruit = s absorption (! toxicity) (479f) Some quinolones = (! arrhythmia) (479h) Verapamil, s macrolide (! cardiotoxicity (759) Somewhat less significant Established reactions s Theophylline (! toxicity) (714a) s Corticosteroid (! possible toxicity) (221) s Cyclosporine = (! nephrotoxicity amp; neurotoxicity) (236a) Probable reaction Rifampin (! t antibacterial/s gut effects) (479i) Suspected reaction Suspected reactions s Benzodiazepines (! sedation) (131a) Tacrolimus (Prograf) (! s tacrolimus toxicity) (685d) Repag. (Prandin) (! s Repag = t blood glucose) (613b)

Numbers indicate page number in Facts and Comparisons, Drug Interactions.1 *Macrolides share liver metabolic pathways with many other drugs, generally resulting in delayed metabolism of both drugs, which increases drug levels. t Drug action is probably diminished. s Drug action is probably increased. resulting in nausea and vomiting in many patients. Except for potentially fatal allergic reactions The clinician should caution patients to avoid etha- (anaphylaxis), the penicillin family of antibiotics, nol while taking metronidazole and for 1 full day and the cephalosporins, have remained relatively thereafter to ensure no untoward drug interaction. free of serious drug interactions (Table 3). The Another drug interaction of metronidazole is, when penicillins are very effective against common endo- combined with Antabuse, patients taking metroni- dontic pathogens.12 Most cephalosporins are not dazole have experienced acute psychotic reactions.

Table 3 Penicillins/Cephalosporins and All Drugs Table 2 Metronidazole* (Flagyl) and All Drugs Delayed Reactions

Rapid Reactions Delayed Reactions Suspected reactions Tetracyclines (! cidal drug) (560) Very significant s Anticoagulants (bleed) (82) Methotrexate (! toxicity) (496c) Somewhat less significant Suspected reactions Somewhat less significant Suspected reaction Barbiturates speed metabolism of Suspected reactions Ethanol (! disulfram metronidazole (! t antibacterial) Allopurinol (Zyloprim) (! rash) (555) reaction) (335) (512), Disulfram (! acute psychosis) Food decreases ! absorption (559) (304) Beta-blockers (t antihypertensive + antianginal) (155) Numbers in brackets indicate page number in Facts and Comparisons, Warfarin, s bleeding (51) Drug Interactions.1 Aminoglycosides, inactivated by parenteral Penicillin (PCN) (22) *This antibiotic decreases metabolism of warfarin. It also may cause Aminoglycosides + cephalosporin (! nephrotoxicity) (18) nausea if combined with ethanol or disulfram (Antabuse), but reaction Numbers in brackets indicate page number in Facts and Comparisons is inconsistent. Drug Interactions.1 t Drug action is probably diminished. t Drug action is probably diminished. s Drug action is probably increased. s Drug action is probably increased. 784 / Endodontics effective against the strict anaerobes found in endo- cisapride (Propulcid) may interrupt normal dontic infections. There may be cross-allergenicity nerve impulse conduction within the heart that between penicillins and cephalosporins. may threaten life. Yet another problem that qui- Methotrexate, a powerful anti-metabolite for noloneshaveisthedruginteraction with theo- some types of cancer and for refractory arthritis phylline. The shared metabolic pathway similarly patients, combined with penicillin has caused causes theophylline concentrations to increase to severe toxicity, including renal failure, myelosup- toxic levels. These similarities occur even though pression, neutropenia, thrombocytopenia, and skin the molecular structures of the two drug classes ulcers. Cephalosporins have not been reported to are quite different. cause this drug interaction. Coumadin plus a quinolone may produce a car- Quinolone antibiotics have potential to cause diac rhythm problem.14 All antibiotics can cause severe interactions with several drugs (Table 4). bleeding problems for patients taking anticoagu- As with macrolides, quinolones cause serious car- lants because the antibiotic kills gut flora that pro- diac rhythm problems in the presence of many duce vitamin K, a natural substance that enhances other drugs. The macrolide–quinolone combina- clotting. Lack of this balance means patient takes tion is one of the drug interactions that can cause longer to clot. When healthy patients take an anti- fatal arrhythmias. Macrolides or quinolones plus biotic, the reduction in vitamin K causes no clini- cally apparent change in clotting parameters. The well-informed dentist should be able to evaluate blood clotting tests such as bleeding time and Table 4 Quinolone* Antibiotics and All Drugs International Normalized Ratio (INR) with the Rapid Reactions Delayed Reactions patient’s physician. Tetracyclines have seen resurgence in popularity Very significant Probable reaction Anticoagulants s bleed (92) among dentists because of their actions against Suspected reactions collagenase and their effectiveness against period- Serious arrhythmias with: ontal pathogens, many shared with endodontic phenothiazines (573); diseases. Both of these advantages carry over into Cisapride (Propulsid) (610b); endodontics. While there is a long list of drugs that Macrolide antibiotics (479h); Tricyclic antidepressants (750a); interact with tetracyclines, the reactions tend Ziprasidone (Geodon) (773e); to be inconsistent and are rarely life-threatening Antiarrhythmics (36b) (Table 5). The digoxin–tetracycline interaction Somewhat less significant arguably has the most serious potential. In a small Antacids, t Quinolone absorption Suspected reactions portion of the population, the gut flora metabol- (610) Cyclosporine, nephrotoxicity (238j) izes a significant percentage of their digoxin Theophylline s Theo ! toxicity dose, meaning that they need a fairly high dose (716) to achieve the proper steady-state digoxin level. Probable reactions Sulcralfate (Carafate) = t Quinolone absorption (610j) Heavy metal salts = t Quinolone absorption (610f) Table 5 Tetracycline and All Drugs Suspected reactions Delayed Reactions Sevelamer (Ranagel) = t Quinolone absorption (610i) Suspected reactions Tizanidine (Zanaflex) = t Pens/Cephs, cidal/ static (560) Tizanidine metabolism ! t Digoxin, s dig. (295) oxicity (735 ab) Somewhat less significant Food = t Quinolone absorption Suspected reactions (610d) Activated charcoal, absorbs (182) Heavy metal salts = chelation (686) (687) (688) (693) (696) Numbers in brackets indicate page number in Facts and Comparisons Drug Retinoids (Accutane) risk of (614) benign intracranial hypertension Interactions.1 *Note that serious psychotic reactions can occur with these drugs. Such Numbers in brackets indicate page number in Facts and Comparisons reactions may persist long after the drug is discontinued. Drug Interactions.1 t Drug action is probably diminished. t Drug action is probably diminished. s Drug action is probably increased. s Drug action is probably increased. Chapter 25 / Drug Interactions and Laboratory Tests / 785

Tetracyclines can induce significant microflora NSAID reaction is with methotrexate, resulting in changes, such that greater digoxin absorption leads kidney failure. This reaction is more likely with to toxic levels. As noted above, macrolides interact high-dose methotrexate, typically used for anti- with digoxin in a different way, inhibiting renal neoplastic therapy, as opposed to the lower doses excretion of digoxin, also reaching potentially toxic used for rheumatoid arthritis refractory to less levels, and this change can last for many days after powerful drugs. macrolide is stopped. Patients taking b-blockers may experience While it may be nice to contemplate treating hypertension breakthrough when taking NSAIDs. endodontic patients without antibiotics, such is Sulindac (Clinoril) apparently does not have the an unrealistic dream. No antibiotic is without propensity to cause this reaction.15 potential interaction with other drugs. The rapid Lithium toxicity induced by adding NSAIDs has discovery of new interactions mandates that those occurred. The decrease of lithium metabolism has who treat infected patients keep abreast of contem- not resulted in clinical problems in healthy porary information. patients.16 Pain control drugs fall into a similar situation. NSAIDs and the very popular antidepressants Certainly, modern endodontic techniques and bet- that work by selective serotonin re-uptake inhibi- ter appreciation of the value of ‘‘not’’ harming tion (SSRI) drugs within brain synapses can interact tissues adjacent to root canals have helped reduce adversely. Increased gastrointestinal (GI) bleeding the need for pain-relieving drugs. Yet, postopera- has been reported, although the problem has also tive pain will remain a factor in treating some occurred when an SSRI drug was used alone.17 endodontic maladies. Clinical experience of many Narcotic pain relievers will continue to play a dentists reinforces the experimental observations useful role for dentists, albeit less necessary because that NSAIDs are effective pain relievers. Most prac- of improved understanding and better instruments titioners find NSAIDs as effective as codeine or and techniques. Demerol (meperidine) is the most hydrocodone for most patients. Chronic NSAID troublesome for potential interactions. The most use has revealed stomach and kidney problems, serious, sometimes resulting in death, is less likely especially among the elderly, but only a few pro- now because oxidase inhibitors are rarely pre- blems have been associated with short-term use. scribed. Other reactions are listed in Table 7. Serious drug interactions with NSAIDs are rela- Control of intra-operative pain is a standard by tively rare (Table 6). The effect of Coumadin is which patients judge their endodontic caregiver. potentiated by NSAIDs. The prescription of Pilots are judged by how smoothly they can land NSAIDs for only a few doses limits the clinical a plane even though this is a small part of a pilot’s appearance of this interaction. But a very serious skill. Similarly, patients judge us by our skill at giving an ‘‘easy shot.’’ There are two separate drug interaction consid- Table 6 Nonsteroidal Anti-inflammatory Drugs and All erations with local anesthetics, the anesthetic itself Drugs Delayed Reactions

Very significant Table 7 Narcotics* and All Drugs Probable reaction Rapid Reactions Delayed Reactions Anticoagulants s bleed (86a, 86b) Suspected reaction Very significant Methotrexate s Methotrexate (! toxicity) (496) Demerol and Mao inhibitors (488) Somewhat less significant Somewhat less significant Probable reaction Probable reaction Suspected reaction Beta-blockers = t antihypertensive (154) Demetrol + Phenothiazines (488a) Demetrol + Ritonavir Suspected reactions (Norvir) (488b) Aminoglycosides, s antibiotic (21) Suspected reaction s Lithium (! Li toxicity) (464) Barbiturates (112) SSRI, s gut bleed (548) Numbers in brackets indicate page number in Facts and Comparisons SSRI, selective serotonin re-uptake inhibition. Numbers in brackets Drug Interactions.1 indicate page number in Facts and Comparisons Drug Interactions.1 Note that death has been reported from giving Demerol to Manomine t Drug action is probably diminished. oxidase (MAO) inhibitor patients. s Drug action is probably increased. *Most reactions are due to additive central nervous system effects. 786 / Endodontics and the vasoconstrictor. Epinephrine is very rapidly Table 9 Local Anesthetics and All Drugs metabolized, so any drug interaction is rapidly Rapid Reaction apparent (Table 8). Tolerance of the vasoconstric- tor in one dose means that an additional dose after Somewhat less significant about 5 minutes can be given with similar result, Established reactions Beta blockers [! (Lido. toxicity)] (450a) given that neither is injected systemically. Histamine H2 Antagonists (Tagamet) (! Lido. toxicity) (451) Hypertensive events have been documented in Suspected reaction patients taking b-blockers, Furazolidone (Furox- Succinylcholine, s succinylcholine half-life (636) one) tricyclic antidepressants, methyl dopa, and Numbers in brackets indicate page number in Facts and Comparisons the anti-hypertensive drugs guanethedine (Ismelin) Drug Interactions.1 and Rauwolfia alkaloids. Beta-blocker interact- t Drug action is probably diminished. ions are potentially the most serious. It is advisable s Drug action is probably increased. to take a preoperative blood pressure reading to establish a baseline for that patient. Furthermore, intravascular injection occurs without a positive aspiration of blood.7 enzymes. Yet, the reaction does not occur every The anesthetic itself does not cause any known time the drugs are combined.19 Research on other very serious drug interactions (Table 9). The pro- histamine H2 antagonists failed to show this inter- blem with the anesthetic is that repeated injec- action. tions build to overdose levels because, unlike the Benzodiazepine reactions are typically one of the very rapidly metabolized vasoconstrictor, the increased drug effects and can be accounted for by anesthetic agent is metabolized over hours. This beginning with a lower dose, perhaps a half pill, is especially important for pediatric patients until the patient’s own reaction is defined. The whose body mass cannot tolerate as much anes- protease inhibitor reactions however have been thetic as an adult. reported to induce severe sedation and respiratory Beta-blockers may interact with lidocaine, low- depression. As noted in Table 10, no drug interac- ering the number of doses to reach the toxic range. tions with benzodiazepines have been ranked in the This drug interaction is believed to be via inhibi- very significant category. tion of hepatic metabolic enzymes.18 Table 11 lists drugs that may be used by dentists Cimetidine (Tagamet) increases lidocaine levels that interact with Coumadin (warfarin). This too, probably by the same general effect on liver extensive list calls for careful consideration by the

Table 10 Benzodiazepine* and All Drugs Rapid Reaction Delayed Reaction Table 8 Epinephrine*-Containing Local Anesthetics and All Drugs Somewhat less significant Rapid Reactions Established reactions Suspected reactions Ethanol (325) Carbamazepine (Tegretol) (123a) Very significant Azole antifungals (122b) Hydantoins (Dilantin) (375) Established reaction Modafinil (Provigil) (131b) Beta Blockers ! hypertension then bradycardia (312) Non-nucleoside reverse Suspected reaction transcriptase (131d) Furazolidone (Furozone) antibiotic ! hypertension (674a) Inhibitors Somewhat less significant Protease inhibitors (133) Established reaction St. John’s Wort (136a) Tricyclic antidepressants ! hypertension (683) Macrolide antibiotics (131a) Suspected reactions Rifampin (136) Rauwolfia alkaloids ! hypertension (682) Probable reactions Methyldopa ! hypertension (680) Diltiazem (Cardizem) (128) Guanethidine ! hypertension (354) Food (129b)

Numbers in brackets indicate page number in Facts and Comparisons Numbers in brackets indicate page number in Facts and Comparisons Drug Interactions.1Epinephrine is rapidly metabolized, so delayed Drug Interactions.1 reactions do not occur. *In most reactions, benzodiazepine effect is increased, but decreased *Minimize risk by injecting slowly and watching patient reaction. with Rifampin. Generally, titration of dosage is indicated. Chapter 25 / Drug Interactions and Laboratory Tests / 787

Table 11 Drugs Prescribed by Dentists That May Table 12 Drugs Prescribed by Dentist That May Interact Interact with Warfarin Anticoagulant with Herbal Medicines Delayed Reactions Significance levels Very significant Established reactions 1 Amoxicillin + Khat ! t amoxicillin (85, 86) Sulfonamides, bleed (98) 1 ASA or NSAIDs + Ginkgo biloba ! bleed by platelet Metronidazole, bleed (82) aggregation) (19, 20) Vitamin E, bleed *(197a) 1 Benzodiazepines + Kava ! s benzo levels (sedation) Aspirin (ASA), bleed (94) (84) Probable reaction Benzodiazepine + St. John’s Wort ! NSAIDs/(86a) CoX2 inhibitors (86b) = bleed t Benzodiazepine (sedation) Quinolones = bleed (92) 2 Corticosteroids + Licorice ! s corticosteroid (87) Macrolides = bleed (79) 1 Ciprofloxacin + Calcium-supplemented orange juice ! Somewhat less significant s Cipro (95a) # antibiotic absorption Established reaction 1 Cipro + Zinc ! s Cipro (154ba) # antibiotic Suspected reactions absorption Acetaminophen = s vitamin K, thus t bleed (39) 1 Acetaminophen + Ethyl Alcohol ! Hepatotoxic Carbamazepine (Tegretol), t bleed (50) Metabolite (14e) Vitamin K = t bleed (109) 1 Macrolide antibiotics + Grapefruit ! s absorption of Most antibiotics kill vitamin K bacteria = bleed (51, 89, 92, 47, macrolide (toxicity) (44a) 82, 93, 98) 2 Tetracycline + Zinc ! s tetracycline # antibiotic absorption NSAIDs, nonsteroidal anti-inflammatory drugs. Numbers in brackets 1 Tetracycline + dairy products !#Tetracycline due to 1 indicate page number in Facts and Comparisons Drug Interactions. Most chelation (12a–12d) drug interactions result in increased bleeding. Tylenol, Tegretol, rifampin, Levofloxacin + orange juice (plain or with ca++) !# and vitamin K increase bleeding. The Tylenol reaction is apparently not Levoflox (95f) consistent and, if reported, exceeded six doses/week. Vitamin K reverses the action of warfarin. However, there is currently no antidote for Plavix. Numbers in brackets indicate page number in Facts and Comparisons t Drug action is probably diminished. Drug Interactions.1 s Drug action is probably increased. Significance level 1 = herbal drug should not be combined. Significance level 2 = herbal drug may be continuously allowed. t Drug action is probably diminished. dentist and alerting the patient to watch for signs of s Drug action is probably increased. bleeding. Notably, the rapid reaction category is empty, indicating that short-term use carries less harmful potential. Apparently, this citrus fruit speeds absorption far more than other similar fruits. The result can be damagingly high levels of drug, even in the absence of other drugs. This action contradicts the typical Drug Interactions with Food finding that food binds with drugs to decrease absorption, or at least slows drug absorption. and Herbals Khat is a stimulant plant from East Africa that is Many patients are now taking herbal medicines, yet usually chewed. It has been imported into the consider them asharmless foodsupplements.Table 12 United States and other counties as a recreational lists more serious interactions with prescription euphoric agent. It sometimes is smoked to achieve drugs that should be reviewed (the table is derived higher concentrations, which may induce hallucina- from the panel of experts described in the beginning tions. Khat has been shown to decrease absorption of this chapter). Facts and comparisons herbal sup- of amoxicillin and its close congener, ampicillin. plements and food publication ranks potential inter- This may lead to persistence of an infection. A small actions into only three categories, of which the more study demonstrated the maximum decrease to occur serious two are included.20 However, many new drug 2 hours after chewing khat.21 Other potential drug interactions with herbals and food are currently interactions with khat have not been investigated under study and the fact that more people are now thoroughly. taking herbals means that more interactions will be Ginkgo biloba, which is commonly used as a elucidated. memory enhancer, interacts with salicylates and Grapefruit–drug absorption interactions account NSAIDs to increase bleeding. The apparent for many newly discovered drug level changes. mechanism is by lowered platelet aggregation. 788 / Endodontics

Kava, an herbal drug from the South Pacific plant phen, resulting in the rapid metabolism of acetami- of the same name, is drunk as a tea or now available in nophen with consequent high levels of a toxic pill form to relieve stress and produce a sense of well- acetaminophen metabolite, known as NAPQI, being. A single, but serious drug interaction-induced N-acetyl-p-benzoquinone. coma has been reported. While the reaction occurred when combined with alprazolam (Xanax), experts anticipate that the danger likely extends to the entire benzodiazepam family.22 Lab Tests of Potential Importance Another herbal anxiolytic–benzodiazepine interac- in Endodontics tion has been anticipated, but not yet reported, between a benzodiazepine and the weed-derived Dentists may be uncomfortable in ordering St. John’s Wort. Experimental evidence demonstrated laboratory tests. Referral to a physician is always that the combination of the herbal and clonazepam appropriate, but there is no reason for a dentist (Klonapin) decreased the benzodiazepine levels.23 to be intimidated by the process. Dentists are often Licorice has been shown to alter levels of corticos- the first healthcare provider to identify systemic teroids, either increasing or decreasing the drug.24 disease. Frequently, this is the case because oral The interaction would be more serious in patients on tissues are the first to be affected. Also, many high-dose steroid. No evidence exists yet as to exact patients do not regularly visit their physician, or mechanism of the interaction or about any potential many receive only cursory information on subtleties problems with natural steroid drugs or overall action of oral changes from disease. Leukemia, bacterial on inflammation or healing. endocarditis-induced oral petechiae, bleeding disor- Orange juice, particularly when calcium-fortified, ders, various cancers, and many other diseases are lowers the levels of the fluoroquinones Cipro first suspected in the dental office. Ordering a (ciprofloxacin) and Levaquin (levofloxacin). While laboratory test to confirm or rule-out suspicions the exact mechanism is unknown, the suspicion is is perfectly appropriate for any dentist. Culture that the orange juice and the drug compete for and sensitivity testing for identification of the transportation across the intestinal membrane.25 cause of an infection and the most likely effective Cipro absorption is also diminished in the pre- antimicrobial should be in every dentist’s arma- sence of zinc, as are tetracycline concentrations. mentarium. This essential heavy metal additive is common in Laboratory tests are commonly helpful to dentists. multivitamin preparations. The net result of the The list of lab tests commonly helpful to dentists is interactions is lowering of antibiotic levels in the not exhaustive, and dentists should not be limited to 25 to 40% range.26,27 those tests listed below. Disorders of inflammation, Tetracycline absorption is also hindered by dairy perhaps related to a chronic dental infection, may products, which all contain the heavy metal ion cause an increased erythrocyte sedimentation rate. calcium. Doxycycline is the least affected of the tetra- Blood tests can be helpful in identifying blood cycline family to bind with heavy metal ions, a pro- dyscrasias from cellular imbalances to inflammatory cess called chelation.28 system evaluation and to clotting factors. Most clas- Ethyl alcohol is discussed in ‘‘Drug Interactions’’, sic hemophiliacs are diagnosed early in life and can but there is a brief review in here.20 Perhaps, because provide the dentist with important information by it is so often used or abused among patients, alcohol history. Every dentist should be aware of the risks is sometimes considered a food. Generally, its inter- associated with altered blood clotting profiles of their actions are to increase action of drugs that act on the patients. Newly identified risk assessment studies CNS. It delays gastric emptying, so can delay absorp- have shown the mortality and morbidity of decreas- tion of almost any drug taken by mouth. It specifi- ing anti-clotting parameters. The dentist should be cally interacts with metronidazole in a disulfram class comfortable in interpreting these tests to determine if reaction, inducing nausea and vomiting. All the a patient is a candidate for a surgical procedure. above reactions are dose related, so the astute The prothrombin time test has been largely clinician should caution patients accordingly. The replaced by the INR, which uses a standardized interaction with Tylenol (acetaminophen) is different control and expresses the result in a percent of and potentially lethal. Chronic use of ethyl alcohol normal clotting time. This test evaluates the extrinsic increases the enzyme that metabolizes acetamino- clotting mechanism. With an INR of 1 being the Chapter 25 / Drug Interactions and Laboratory Tests / 789 normal level, minor dental-alveolar surgery can be outcome. The dentist who suspects such a problem carried out to an INR level <3.5 with local methods will probably refer the patient to an allergist for of hemostasis sufficing. For other than minor sur- skin or other tests and then help manage the dental gery, consultation should be obtained with consid- aspects of the patient’s care. eration for modification of the anticoagulation or hospitalization. The partial thromboplastin time test remains valuable to determine the intrinsic clotting path- Summary way, which is the clotting factors in blood plasma. There is a limited understanding of drug interaction Bleeding time, the number of minutes required incidence because of under-reporting. Also, animal for a standard wound to clot, may help diagnose studies may not transfer directly to the human. later onset problems of importance to the dentist Animals cannot express mood changes effectively such as von Willebrand’s disease, where the intrin- and there are some metabolic differences between sic factor VIII is diminished by this hereditary animals and man. defect. Also, bleeding time identifies disorders of The astute clinician should explain possible the platelet system, including those induced by adverse or undesirable reactions with patients so salicylates or NSAIDs. that they may watch for an adverse outcome. This Complete blood counts enumerate platelets, chapter emphasizes drug reactions that are poten- different white blood cells, and red blood cells tially very serious and/or very likely to occur. Some and can confirm or rule out many suspicious practitioners will see interactions of drugs beyond findings. An increased number of red cells, poly- those covered here. It is important to report sus- cythemia vera, can reveal itself as darker gingival, pected drug interactions to the Food and Drug because of the engorgement of the vascular sys- Administration (FDA) for evaluation. The FDA tem. Bleeding gingival can be seen in many forms periodically sends information about newly discov- of leukemia. Petechiae due to sickle cell anemia ered serious drug interactions to practitioners can be diagnosed by the occasional characteristic registered by state license to practice dentistry. shaped red blood cells. Furthermore, the reader should remember that While it is easier to direct patients and staff who are information about drug interactions is constantly accidentally exposed to blood-borne pathogens to changing, mostly with newly discovered interaction someone trained in counseling for such risks, tests reports. for such infectious agents may be ordered by the dentist who suspects a disease. Patients with unexplained radiolucencies of their jaws may need testing for certain disorders. For References example, a multiple myeloma patient will have the abnormal Bence Jones protein in their urine. A 1. Tatro DS, editor. Facts and comparisons, drug interactions facts. St. Louis: Wolters Klewer Health; 2006. patient with hyperparathyroidism-caused bone radiolucencies will have elevated blood calcium 2. Lexi-Comp, Inc. http://www.lexi.com. and decreased blood phosphorus. Urine levels of 3. Epocrates, Inc. http://www.epocrates.com. calcium may be lower, with increased urine phos- 4. Agyilirah GA, Banker GS. Polymers for enteric coating phorus. Serum alkaline phosphatase is elevated in applications. In: Tarcha PJ, editor. Polymers for controlled hyperparathyroidism, although not as markedly as drug delivery. Cleveland, OH: CRC Press; 1990. with Paget’s disease. Diabetes mellitus has broad implications in heal- 5. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers ing. Blood or urine glucose elevations can be the criteria for potentially inappropriate medication use in older adults. Arch Intern Med 2003;163:2716–24. impetus needed to send a patient for medical care. Allergies can make life unpleasant for many. 6. Bachman JT, Olkkola KT, Aranko K, et al. Dose of mid- They may stem from food allergies which can cause azolam should be reduced during diltiazem and verapamil nutritional imbalances which may be suggested by treatments. Br J Clin Pharmacol 1994;37:221–5. changes in oral tissues. They may include dental 7. Lipp M, Dick W, Daublander M, et al. Exogenous and endo- materials, such as nickel or eugenol, making the genous plasma levels of epinephrine during dental treatment patient less likely to have a favorable treatment under local anesthesia. Reg Anesth 1993;18(1):6–12. 790 / Endodontics

8. Cooper KJ, Martin PD, Dane AL, et al. The effect of 19. Jackson JE, Bentley JB, Glass SJ, et al. Effects of histamine- erythromycin on the pharmacokinetics of rosuvastatin. 2 receptor blockade on lidocaine kinetics. Clin Pharmacol Eur J Clin Pharmacol 2003;59:51–6. Ther 1985;37:544–8. 9. Gillum GJ, Israel DS, Scott RB, et al. Effect of combination 20. Tatro DS, editor. Facts and comparisons, drug interactions therapy with ciprofloxacin and clarithromycin on theo- facts, Herbal supplements and food. St. Louis: Wolters phylline pharmacokinetics in healthy volunteers. Antimi- Klewer Health; 2006. crob Agents Chemother 1996;40:1715–16. 21. Attef OA, Ali AA, Ali HM Effect of khat chewing on the 10. Pollak TP, Slayter KL. Reduced serum theophylline concen- bioavailability of ampicillin and amoxicillin. J Antimicrob trations after discontinuation of azithromycin: evidence for Chemother 1997;39:523–5. an unusual interaction. Pharmacotherapy 1997;17(4):827–9. 22. Almeida JC, Grimsley EW. Coma from the health food 11. Munson MA, Pitt-Ford T, Chong B, et al. Molecular and store: interaction between kava and alprazolam. Ann cultural analysis of the microflora associated with endo- Intern Med 1996;125:940–1. dontic infections. J Dent Res 2002;81(11):761–6. 23. Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, 12. Baumgartner JC, Xia T. Antibiotic susceptibility of bacteria Hall SD. The effects of St. John’s Wort (Hypericum perfor- associated with endodontic abscesses. J Endod 2002:29:44–7. atum) on human Cytochrome P450 activity. Clin Pharma- col Ther 2001;70:317–26. 13. Yacobi A, Lai C, Levy G. Pharmacokinetic and pharmaco- dynamic studies of acute interaction between warfarin 24. Homma M, Oka K, Ikeshima K, Takahashi N, Nitsuma T, enantiomers and metronidazole in rats. J Pharmacol Exp Fukudu T, Itah H. Different effects of traditional Chinese Ther 1984;231:72–9. medicines containing similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol 14. Linville T, Matani D. Norfloxacin and warfarin. Ann 1995;47:687–92. Intern Med 1989;110:751–2. 25. Wallace AW, Victory JM, Amsden GW. Lack of bioequiva- 15. Pope JE, Anderson JJ, Felson DT. A meta-analysis of the lence when levofloxacin and calcium-fortified orange juice effects of nonsteroidal anti-inflammatory drugs on blood are coadministered to healthy volunteers. J Clin Pharmacol pressure. Arch Intern Med 1993;153:477–84. 2003;43:539–44. 16. Levin GM, Grum C, Eisele G. Effect of over-the-counter 26. Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of dosages of naproxen sodium and acetaminophen on ferrous sulfate and multivitamins with zinc on absorption plasma lithium concentrations in normal volunteers. of ciprofloxacin in normal volunteers. Antimicrob Agents J Clin Psychopharmacol 1998;18:237–40. Chemother 1989;33:1841–4. 17. Dalton SO, Johansen C, Mellemkjaer L, et al. Use of 27. Penttila¨ O, Hurme H, Neuvonen PJ. Effect of zinc sulfate selective serotonin reuptake inhibitors and risk of up- on the absorption of tetracycline and doxycycline in man. per gastrointestinal tract bleeding. Arch Intern Med Eur J Clin Pharmacol 1975;9:131–4. 2003;163:59–64. 28. Matilla MJ, et al. Interference of iron preparations and 18. Bax NDS, Al-Asady LD, Deacon CS, et al. Inhibition of milk with the absorption of tetracyclines. Excerpta Medica drug metabolism by b -adrenoceptor antagonists. Drugs International Congress Series No. 254. Toxicological Pro- 1983;26(Suppl 2):121–6. blems of Drug Combinations. 1927:128–33. CHAPTER 26 ENDODONTICS INSTRUMENTS AND ARMAMENTARIUM

A. DENTAL DAM AND ITS APPLICATION

WILLIAM G. SCHINDLER

Itmaybedifficult,ifnotimpossible,toachieveasterile made prior to the placement of the dental dam. field in endodontics; however, every effort should be made Examples of this situation may include severe tipping to work as much as possible in a bacteria-free field. That of teeth, extreme calcification of the canal system, and being said, the use of dental dam is absolutely essential orientation difficulties related to coronal restoration. during nonsurgical endodontic therapy. For root canal However, once the chamber or canals have been located treatment, rapid, simple, and effective methods of dam and before instruments or irrigating solutions have applications have been developed. In all but the most been used, the dental dam must be placed. unusual circumstances, the dental dam can be placed on the tooth being treated in less than a minute. Its routine usewillenhanceeveryaspectofendodontictherapy. Although the modern nonsurgical endodontic Equipment approach to the use of dental dam has changed, the importance and purposes of the dam remain the same: DAM MATERIAL 1. It provides a dry, clean, and disinfected operating Dental dam is available in a variety of thicknesses, field removed from saliva and blood. colors, sizes, and material. The medium-weight thick- 2. It protects the patient from possible aspiration or ness is highly recommended for general all-around swallowing of tooth debris, restorative materials, use. It has the advantage of nicely adapting to the bacteria, necrotic pulp tissue, and instruments1–3 cervical area of the tooth, providing a fluid seal with- (Figure 1). out the use of floss or ligature ties around each tooth. 3. It protects the adjacent soft tissues (tongue, lips, Also, it does not tear easily and provides more protec- cheek) by retracting them out of the way. tion from injury to the adjacent soft tissues and 4. It protects the patient’s soft tissues from irritating increased visibility than does the thinner material. irrigating solutions and drugs that may be used There are, however, some advantages in the use of during treatment. thin-weight dam material on mandibular anterior 5. Visibility and efficiency are improved. teeth and partially erupted posterior teeth. These teeth 6. Its routine use protects the clinician from litiga- have very little bulk of contour and the thinner mate- tion related to instrument aspiration or swallow- rial will exert less dislodging force on the clamp. The ing. Even swallowing diluted sodium hypochlorite disadvantage is that it is easily torn. can be dangerous in addition to it having an Dam materials may be purchased in precut 5˝  5˝ unpleasant taste.4 Use of dental dam for nonsurgi- (127 mm  127 mm) or 6˝  6˝ (152 mm  152 cal endodontics is the standard of care.5 mm) sheets. The choice of light- or dark-colored material is largely up to the practitioner. Darker mate- The clinician should be aware that there may be rare rial provides a contrasting color as a background for instances when coronal access to root canals might be the light-colored tooth.

791 792 / Endodontics

B

A

Figure 1 A, Swallowed endodontic file ended up in the appendix resulting in acute appendicitis. B, Specimen shows file in the appendix removed by appendectomy. Use of dental dam would have prevented this complication. C, Dental burs can sometimes disengage from hand pieces and be swallowed, as shown here. This is also preventable with dental dam. (A and B, Reproduced with permission from Thomsen LC, Appleton SS, Engstrom HI. Appendicitis induced by an endodontic file. Gen Dent 1989;37:50.)

Dental dam is available in latex or non-latex mate- not been correctly centered over the hole, and a rial. With the apparent increasing incidence of ‘‘nick’’ on the cutting margin results, producing an patients allergic to latex, non-latex dental dam must incomplete jagged cut in the dam material. This be available in all offices.6,7 Latex-free dams are avail- results in a poor seal at the time of placement and able (Coltene Whaledent, Inc., Cuyahoga Falls, OH) may make the dam susceptible to tearing. and supplied in a powder-free, 6˝ Â 6˝, medium thickness. In an emergency, non-latex glove material FRAMES can also be used (Figure 2). In addition to supporting the dam, frames should be radiolucent to prevent obstruction of an important PUNCH area on radiographs that are taken during treatment. Any dental dam punch that is convenient for the There are a variety of dental dam frames that meet operator and creates a sharp, clean hole in the dam this requirement. The U-shaped Young’s frame is material is satisfactory. All too often the punch has made of radiolucent plastic for endodontic Chapter 26 / Endodontics Instruments and Armamentarium / 793

Figure 2 Latex-free barrier dams must be used for patients sensitive to latex; in this case a latex-free glove was cut up and used as a barrier.

Figure 3 The U-shaped Young’s dental dam frame is an example of commonly used frames. applications. It is easily manipulated and is used fit the face, is made of radiolucent nylon, and may be in widely (Figure 3). The Nygaard-Østby (N-Ø) dental placewhileatoothissubjectedtoX-rayswithoutinterfer- dam frame (Coltene Whaledent, Inc.) is shield-shaped to ing with the radiographic image. 794 / Endodontics

An articulated frame developed to facilitate endo- patient’s face. The frame retains its configuration dontic radiography (Figure 4) is also curved to fit the but may then be reshaped after use. face. It is hinged in the middle to fold back, allowing Recently, several dental companies have introduced easier access for film and sensor placement. Derma- disposable, single-use, pre-framed dental dams. The Frame (Ultradent Products, Inc., South Jordan, UT) is HandiDam (Figure 5) and the InstaDam (Zirc Co., a soft metal frame that may be formed to fit the Buffalo, NY) allow the clinician to quickly apply the

A B

Figure 4 Hinged dental dam frame. A, In closed position, frame is curved to fit face. B, Open position, from either side, allows passage of radiographic film holder.

Figure 5 Frame and dam combinations such as the HandiDam (Aseptico, Inc., Woodinville, WA) allow convenient placement of a dental dam barrier for single teeth; the material is available both in latex and latex-free. Chapter 26 / Endodontics Instruments and Armamentarium / 795

Figure 6 There are a variety of clamps available for all situations, including plastic clamps.

dam without the addition of a conventional frame. Both Plastic clamps (Moyco/Union Broach, York, PA) of these innovative devices are available in latex and are also available in two sizes, large and small, and latex-free versions. are used in selected cases. When metal clamp obstruc- tion is a problem, radiolucent plastic clamps allow for CLAMPS an unobstructed film-view of the tooth. The dental dam clamp secures the dam to the tooth and helps in soft-tissue retraction. Although the selec- FORCEPS tion of five to seven clamps will permit the clinician to Either the Ash- or Ivory-style clamp forceps is accep- isolate the majority of teeth treated, the experienced table. One advantage of the Ivory forceps, however, is operator will expand that number. Teeth that are rotated, partially erupted, fractured, unusual in crown form, or with severe carious involvement all present Table 1 Dental Dam Clamp Selection problems requiring special clamps or clamping techni- Clamps ques. There are a variety of clamps available to meet any clinical situation that may arise (Figure 6). Table 1 Maxillary teeth lists a suggested assortment of metal clamps for various Central incisor 6, 9, 210, 212 teeth. Lateral incisor 6, 9, 210, 00 For endodontic treatment particularly, the use of Canine 6, 9, 210 clamps with wings allows a more rapid, efficient Premolars 0, 2, 2A, W2A means of applying the dental dam. The wings allow Molars 3, W3, W8A, 14, 14A the dentist to place the clamp, dam, and frame in one operation (Figure 7). In addition, the wings cause a Mandibular teeth broader buccal–lingual deflection of the dam from the Incisors 6, 9, 210, 212 isolated tooth, thus allowing increased access. One Canine 6, 9, 210 disadvantage of the use of winged clamps is that the Premolars 0, 00, 2, W2A wings may occasionally interfere with radiographic Molars 3, W3, W8A, 14, 14A interpretation of file or master cone positioning. 796 / Endodontics

Figure 7 Winged clamp, dental dam, and frame ready for placement on Figure 8 Wedjets cord (Coltene Whaledent, Inc.) can help stabilize the tooth. Bow of clamp is oriented to the distal. interproximal area of the dental dam. the projections from the engaging beaks. These allow can be wedged into the interproximal space over the the clinician the opportunity to exert a gingivally dam to fix the dam in place. directed force, which is often necessary to direct the Even with proper techniques of placement of the clamp beyond the bulk of contour and into proximal dental dam, there will still be clinical situations in undercuts. The Ash-style forceps beaks, however, which some small amount of leakage of fluids can be afford a fulcrum point for posterior or anterior rota- anticipated. Adjustments can be made including repo- tion of the clamp. sitioning of the clamp and closer attention to inver- sion of the dam material around the tooth. When those techniques are ineffective, leakage can usually ADJUNCTS TO DENTAL DAM PLACEMENT be effectively controlled by the placement of a ‘‘patch- In addition to the previously mentioned materials, ing’’ material at the interface of the tooth and the dam several other items will be of benefit for the efficient material. Orabase, rubber base adhesive, Cavit, a mix- application of the dental dam. ture of Super Poly-Grip Denture Adhesive with zinc A plastic or cement instrument can be used to shed oxide powder, and periodontal packing have been the dental dam off the wings of the clamp once the used in the past with limited success.8 Currently, the clamp has been positioned. It is also used, along with application of OraSeal Caulking (Ultradent Products, a stream of air, to invert or ‘‘tuck’’ the edges of the Inc.) seems to provide a quick, easy-to-apply solution dam into the gingival sulcus, thus ensuring a fluid- to the problem of seepage of fluids around the dental proof seal. This is particularly necessary in multi- dam (Figure 9). tooth applications. Dental floss is an essential adjunct to dam place- ment, even for endodontic therapy. Floss can be used for testing of contacts prior to dam application and Techniques of Application for passing the dam material through the contacts after placement. It is recommended that the operator ROUTINE TECHNIQUES release the lingual grasp of the floss after passing it Two techniques of dental dam application that can be through the contact and pulling it out to the buccal, used routinely are next described, followed by examples rather than back through the contact. Another pro- of special situations that may complicate the process. duct that may help with the stabilization of the inter- Prior to application of the dental dam, it is sug- proximal dam is the Wedjets stabilizing cord (Coltene gested that the patient should rinse for 30 seconds Whaledent, Inc.) (Figure 8). Small strips of the cord with an effective antibacterial agent. A mouth rinse of Chapter 26 / Endodontics Instruments and Armamentarium / 797

A B

Figure 9 A, Partially erupted first molar clamped with a W8A with leakage toward the lingual and distal. B, Leakage controlled with Oraseal (Ultradent Products, Inc.).

0.12% chlorhexidine gluconate, such as Peridex 1. Select the clamp to be used. (Proctor & Gamble, Cincinnati, OH), will reduce the 2. Punch one appropriate-sized hole just off center number of microorganisms in the mouth prior to of a 6˝ Â 6˝ piece of dam material. dam placement.9 3. Loosely attach the dam material to the four cor- ners of the frame. 4. Place the clamp over the bulk of contour of the SINGLE MOTION TECHNIQUE tooth to be isolated and ensure the clamp is This is the most efficient endodontic dam application secure. technique through the use of winged clamps resulting 5. Stretch the dam over the clamp so the dam mate- in the dam, clamp, and frame being taken to the tooth rial is seated under the clamp and hugging the to be isolated in a single motion (see Figure 7). cervical area of the tooth. 1. Select the clamp to be used. 6. Completely stretch the dental dam onto all 2. Punch one appropriate-sized hole just off center prongs of the frame. of a 6˝ Â 6˝ piece of dam material. 7. Use floss to aid in passing the dam through con- 3. Stretch the dam over the frame and fit the clamp tacts. through the punched hole so that the wings retain Regardless of the technique used, the surface of the the clamp. tooth and dental dam should be disinfected with an 4. Place the clamp over the tooth with the accom- appropriate disinfectant (i.e., 2.5% sodium hypo- panying frame and dam attached so the clamp is chlorite, 10% iodine tincture, 2% chlorhexidine) prior seated over the bulk of contour of the tooth. to access of the root canal system.10 5. Use a plastic or cementing instrument to flick the dam off of the wings of the clamp. The dam material should be positioned on the tooth below REMOVAL OF DAM the clamp. 6. Use floss to aid in passing the dam through con- 1. For single-tooth applications, simply remove the tacts. clamp with the forceps and remove the dam. 2. For multiple-tooth applications, first remove the clamp, then place a finger under the dam in the DOUBLE MOTION TECHNIQUE vestibule, and stretch the dam to the facial, away This technique is still very efficient, requires the use of from the teeth. Cut the stretched interproximal a winged or wingless clamp, and involves a seven- dam with scissors and then remove the dam. steps procedure. After removal, it is essential that the dam be 798 / Endodontics

inspected to ensure that no interproximal dam has been left between the teeth.

Techniques for Special Situations

MULTIPLE ADJACENT TEETH REQUIRING TREATMENT OR EXTREME MOBILITY OF THE TOOTH BEING TREATED The posterior tooth is clamped normally whereas a second clamp is reversed (with the bow pointing mesially) on the most anterior tooth (Figure 10). Or, the most posterior tooth is clamped normally, whereas the anterior portion of the dam is retained without a clamp. A strip of dental dam, a piece of Figure 10 The posterior tooth is clamped normally whereas a second clamp is reversed (with the bow pointing mesially) on the more anterior floss, or a Wedjets cord can be placed interproximally tooth. to hold the anterior portion of the dam in place.

INSUFFICIENT TOOTH STRUCTURE OR PORCELAIN CROWNS OF VENEERS for the clamped tooth and one for the tooth anterior to the tooth to be treated. The dam between the two WHERE AN INTACT POSTERIOR TOOTH IS holes can be cut with iris scissors. Once the clamp is IN PLACE placed on the posterior tooth, the dam can be placed The split-dam technique can be effectively used utiliz- on the clamped tooth and stretched mesially to ante- ing a clamped tooth posterior to the tooth to be rior tooth and held in place with a Wedjets cord, floss, treated (Figure 11). Two holes can be punched, one or a cut piece of dental dam. A cotton role can be

Figure 11 The split-dam technique can be effectively used by clamping a tooth posterior to the one to be treated and stretching over a tooth anteriorly. Chapter 26 / Endodontics Instruments and Armamentarium / 799 placed under the lip or cheek in the mucobuccal fold Summary over the tooth to be treated. Clinicians will find endodontic procedures more rewarding and less frustrating as their mastery of dental dam applications increases. The use of simpli- BRIDGE ABUTMENTS, SPLINTS, fied techniques, improved materials, and organized AND ORTHODONTICS WITH WIRES procedures, as well as patience and practice, will has- Punch a larger-than-normal hole in the dam. Place ten this mastery. Endodontists have long recognized OraSeal around the punched hole on the underside of that the use of dental dam is imperative in the practice the dam. Clamp the tooth in the normal manner. If of endodontics. leakage is a problem, add more Oraseal around the abutment at the site of leakage. References TOOTH WITH CALCIFIED PULP CHAMBER 1. Goultschin J, Heling B. Accidental swallowing of an endo- dontic instrument. Oral Surg Oral Med Oral Pathol Oral AND CANAL(S) Radiol Endod 1971;32:621–2. Use the three-tooth dental dam isolation technique 2. Govila CP. Accidental swallowing of an endodontic instru- previously described in the multiple adjacent teeth ment. A report of two cases. Oral Surg Oral Med Oral Pathol requiring treatment technique. The involved tooth is Oral Radiol Endod 1979;48:269–71. without a clamp, allowing the clinician to better visualize the Cemento Enamel Junction (CEJ) region 3. Lambrianidis T, Beltes P. Accidental swallowing of endodontic of the tooth. A periodontal probe can be traced along instruments. Endod Dent Traumatol 1996;12:301–4. the root surface to orientate oneself to the crown–root 4. The Dentist Insurance Company, California Dental Associa- angulations during difficult access cavity preparations. tion. Rubber dam it. Liability Lifeline 2004;80:1–7. 5. Cohen S, Schwartz, S. Endodontic complications and the law. J Endod 1987;13:191–7. TERMINAL TOOTH WITH INSUFFICIENT 6. de Andrade ED, Ranali J, Volpato MC, de Oliveira MM. TOOTH STRUCTURE Allergic reaction after rubber dam placement. J Endod If insufficient tooth structure is present to allow a 2000;26:182–3. clamp from being placed on the tooth and the tooth 7. Kosti E, Lambrianidis T. Endodontic treatment in cases of is the terminal tooth in an arch, the clinician must first allergic reaction to rubber dam. J Endod 2002;28:787–9. determine whether the tooth is sufficiently periodon- 8. Weisman MI. Remedy for dental dam leakage problems. tally sound and restorable. If the tooth is determined J Endod 1991;17:88–9. to be retainable, perhaps a clamp with prongs extend- ing apically can be used to effectively engage and hold 9. Miller CH. Infection control. Dent Clin North Am on the tooth, followed by dam placement. If that is 1996;40:437–56. unsuccessful, the tooth may require coronal build-up 10. Ng Y, Spratt D, Sriskantharajah S, Gulabivala K. Evaluation of restoration with pin-retained restorative materials so protocols for field decontamination before bacterial sampling the retainer can be properly placed. Additionally, the of root canals for contemporary microbiology techniques. J terminally positioned tooth can undergo periodontal Endod 2006;29:317–20. crown lengthening to expose more tooth structure to 11. Lovdahl PE, Gutmann JL. Periodontal and restorative con- allow for clamp placement11 (see Chapter 18, ‘‘Endo- siderations prior to endodontic therapy. Gen Dent dontic–Periodontic Differentiation’’). 1980;28:38–45. B. INTRODUCTION OF NICKEL–TITANIUM ALLOY TO ENDODONTICS

WILLIAM A. BRANTLEY

Prior to the prescient review article by Civjan et al.1 torsional ductility, which was superior to that for on the potential uses of nickel–titanium alloys for machined stainless steel instruments,5,6 and cutting dentistry, pioneering feasibility studies for orthodon- ability of the NiTi hand files, was reported by Walia tics were performed by George Andreasen et al.2,3 et al.7 at the 1989 annual meeting of the American This work led to the commercial development of Association for Endodontists. the first NiTi alloy for orthodontics (Nitinol) by Based on these promising research results, innova- the Unitek Corporation (now 3M Unitek, Monrovia, tive dental manufacturers began to market NiTi CA). The mechanical properties of this alloy, along endodontic instruments in the 1990s. A major imp- with its notable clinical applications, were presented etus was the merger of Quality Dental Products with in a classic article by Andreasen and Morrow.4 Par- Tulsa Dental Products (now Dentsply Tulsa Dental, ticularly important were the very low elastic modulus Tulsa, OK), and this latter company introduced Pro- and very wide elastic working range of the NiTi alloy, File NiTi rotary files in 1993. Subsequently, many compared with stainless steel, which was the major other manufacturers introduced NiTi rotary instru- orthodontic wire alloy for clinical use at that time. ments for endodontics, and studies of the properties Subsequently, Harmeet Walia thought that this and performance of these instruments became an nickel–titanium (NiTi: see next section) alloy might intensive area for endodontics research. In January have enormous potential for endodontic files, because 2007,PubMedlistedover350articlesdealingwith its very low elastic modulus would permit the nego- various aspects of the NiTi endodontic instruments tiation of curved root canals with much greater facil- since their inception. ity than stainless steel instruments available at the time. Using special large-diameter orthodontic wires contributed by the Unitek Corporation, Quality Den- Mechanical Behavior and NiTi Phases for tal Products (Johnson City, TN) fabricated the first Nickel–Titanium Alloys prototype NiTi hand files by machining rather than the conventional manner of twisting the tapered The NiTi alloy used in orthodontics and endodontics stainless steel wire blanks. The properties of these first was developed by Buehler and associates. This alloy NiTi files in bending and torsion were compared with was termed ‘‘Nitinol’’ from nickel, titanium, and the those for stainless steel hand files of the same size Naval Ordnance Laboratory, the site of this develop- manufactured by a similar machining process. The ment work that is described in a classic review article highly promising initial results of these pioneering by Buehler and Wang.8 The alloy is based on the NiTi laboratory studies were first presented by Walia intermetallic compound and can exhibit superelastic et al.5 at the annual meeting of the International behavior (termed ‘‘pseudoelastic’’ in materials science) Association for Dental Research in 1987, and a more and shape memory with appropriate processing condi- complete description of this work was published tions.9 Because of the difference in atomic weights of the next year in a seminal article in the Journal of nickel and titanium, the equiatomic NiTi alloy compo- Endodontics.6 Subsequently, more information about sition is 55 wt% Ni and 45 wt% Ti.

800 Chapter 26 / Endodontics Instruments and Armamentarium / 801

When a superelastic NiTi wire is loaded in tension, normal elastic behavior initially occurs. With further tensile loading, the elastic stress reaches a certain level at which there is an extended horizontal region of elastic strain (upper superelastic plateau). Up to about 10% elastic strain can occur in a superelastic NiTi orthodontic wire at this constant stress.10 During subsequent tensile unloading, the alloy will exhibit a horizontal region of elastic strain at a lower stress (lower superelastic plateau) on the stress–strain plot. With further unloading, the strain reaches the end of the lower superelastic plateau, and the final portion on the stress–strain plot again corresponds to the linear elastic unloading. Khier et al.11 compared the bending properties of superelastic and nonsuperelastic NiTi orthodontic wires. For elastic bending of superelastic NiTi ortho- dontic wires having clinically relevant test spans, the upper and lower superelastic plateaus are less well defined (Figure 1), because stress varies linearly over the cross-section. The regions on the bending plots that correspond to these plateaus have greater slopes for nonsuperelastic NiTi wires, such as the original 3M Unitek Nitinol orthodontic wire (Figure 2). If the

Figure 2 Cantilever bending plots for 6 mm test spans of four different sizes of the nonsuperelastic NiTi alloy Nitinol (3M Unitek). Reprinted from Khier et al.11 with permission from the American Association of Orthodontists.

superelastic alloy is loaded in tension to a value of strain beyond the upper plateau region, there will be some permanent strain after unloading. This permanent strain will be greater for a nonsuperelastic NiTi wire having the same dimensions and loaded to the same overall strain as the superelastic wire. By contrast, a NiTi wire alloy that exhibits shape memory behavior in the oral environment will have no residual permanent strain after unloading from beyond the upper plateau region; the wire will completely return to its initial dimensions before loading.9 The mechanical behavior of the superelastic, non- superelastic, and shape memory NiTi alloys arises from the nature and proportions of their microstruc- tural phases, which has been discussed by Brantley12 Figure 1 Cantilever bending plots for 6 mm test spans of four different for orthodontic NiTi wires. There are three NiTi 9 sizes of the superelastic NiTi alloy Nitinol SE (3M Unitek). Reprinted phases in these alloys. Austenitic NiTi (austenite) from Khier et al.11 with permission from the American Association of has a complex body-centered cubic structure, and Orthodontists. exists at higher temperatures and lower stresses. 802 / Endodontics

Martensitic NiTi (martensite) has a complex structure Several phase transformation temperatures are described as monoclinic, and exists at lower tempera- important: As, the starting temperature for transfor- tures and higher stresses. Transformation between aus- mation to austenite; Af,thetemperatureatwhich tenite and martensite occurs by a twinning process at transformation to austenite is finished; Ms,thestart- the atomic level, and the reversibility of this twinning ing temperature for transformation to martensite; 9,12 is the origin of shape memory. During tensile load- and Mf, the temperature at which transformation to ing, the upper superelastic plateau corresponds to the martensite is finished. The Rs and Rf temperatures stress-induced transformation from the initial austeni- for transformations involving the R-phase are tic structure to martensite, and the lower superelastic defined in a similar manner. plateau corresponds to reverse transformation from If a NiTi orthodontic wire or endodontic instrument martensite to austenite. is cooled to a sufficiently low temperature (shown in The R-phase is an intermediate phase with a rhom- later differential scanning calorimetry [DSC] plots), it bohedral structure that can form during forward trans- will consist entirely of martensite. Upon heating, mar- formation from martensite to austenite on heating and tensite will start transforming to R-phase at the Rs tem- reverse transformation from austenite to martensite on perature, and this transformation will be finished at the 9 cooling. Formation of R-phase is favored by the pre- Rf temperature. With further heating, R-phase starts sence of dislocations and precipitates in the NiTi transforming to austenite at the As temperature, and 13 alloy. A substantial density of dislocations is expected transformation is finished at the Af temperature. Alter- in NiTi orthodontic wires and endodontic instruments, natively, if the NiTi orthodontic wire or endodontic because the alloy experiences considerable permanent instrument is heated above the Af temperature, it will deformation during the manufacturing processes. be converted entirely to austenite. Then, upon cooling to Because of the relatively narrow range of the equia- sufficiently lower temperature, the alloy starts transform- tomic NiTi phase field in the nickel–titanium phase ing from austenite to R-phase at the Rs temperature, and diagram at low temperatures, Ti2Ni and Ni3Ti precipi- this transformation will be finished at the Rf tempera- tates are expected in Ti-rich and Ni-rich alloys, respec- ture. With further cooling, R-phase starts transforming 14 tively. Oxide particles also form during processing of to martensite at the Ms temperature, and transformation 9 the NiTi alloy by manufacturers. Such nickel–titanium is finished at the Mf temperature. These transformation oxide precipitates have been observed by Alapati et al.15 processes are summarized in Figure 4. on the cutting tip of a rotary instrument (Figure 3) and were presumably elongated during the manufac- turing process for the starting wire blank. Use of Differential Scanning Calorimetry to Study Nickel–Titanium Alloys DSC can be used to easily determine the transforma- tion temperature ranges (TTRs) for NiTi phases and

Forward transformation sequence M → R → A (Heating)

Reverse transformation sequence A →→R M (Cooling)

Figure 4 Structural transformations in NiTi alloys for orthodontic wires and endodontic instruments: M, martensite; R, R-phase; A, austenite. Beginning with martensite at low temperatures, starting temperatures are Rs and As for forward transformations on heating, which are finished Figure 3 SEM photograph of the cutting tip for a LightSpeed instrument at Rf and Af temperatures. Beginning with austenite at high tempera- after one simulated clinical use, showing elongated nickel-titanium oxide tures, starting temperatures are Rs and Ms for reverse transformations precipitates and flattening of the rollover. Scale bar length is 5 mm. on cooling, which are finished at Rf and Mf temperatures. Starting and Reprinted from Alapati et al.15 with permission from the American finishing temperatures for the same transformation can be different for Association of Endodontists. heating and cooling. Chapter 26 / Endodontics Instruments and Armamentarium / 803

16,17 20 enthalpy changes in NiTi alloys. A test sample is ufacturers. (Some investigators determine the Af tem- heated or cooled at the same rate (typically 10C/min) perature from the intersection of a tangent line to the as an inert control material. The difference in thermal right side of the peak with an extension of the adjacent energy to heat both materials at this rate is plotted as baseline, which gives a lower value.) A single exothermic heat flow per unit sample weight (W/g) as a function peak is observed on the cooling curve, because the peaks of temperature. Bradley et al.18 used DSC to compare associated with the reverse transformations of A fi R superelastic, nonsuperelastic, and shape memory NiTi followed by R fi M could not be resolved. orthodontic wires. Figure 6 presents DSC plots for the tip segment from In their first published article on the use of DSC to another as-received ProFile instrument (Dentsply investigate NiTi rotary instruments, Brantley et al.19 Tulsa Dental) in a subsequent study by Brantley compared ProFile (Dentsply Tulsa Dental) and Light- et al.,21 investigating instruments subjected to simu- Speed (LightSpeed Technology, San Antonio, TX) lated clinical use. This test sample was also in the instruments in the as-received condition. Figure 5 pre- superelastic condition, but the Af temperature on the sents heating and cooling DSC plots for a test sample heating curve was less than 0C. The endothermic peak consisting of several segments from an as-received Pro- on the heating curve corresponds to the M fi R trans- File instrument. The temperature range from –75Cto formation, followed by R fi A, which could not be 75C is shown. The lower curve is for the initial heating resolved as two separate peaks. The weaker broad cycle and the upper curve is for the subsequent cooling exothermic peak over the same temperature range on cycle. Exothermic reactions are represented by peaks in the cooling curve corresponds to the reverse transfor- the upward direction. The two endothermic peaks on mations of A fi R, followed by R fi M. The broad the heating curve correspond to initial transformation low-temperature peak has been reported by Brantley from martensite to R-phase (M fi R), followed by et al.22 to arise from twinning within martensite, and transformation from R-phase to austenite (R fi A). similar low-temperature peaks have been observed by 23,24 This latter transformation is completed at an Af tem- Brantley et al. in NiTi orthodontic wires, using perature of approximately 25C, so the as-received temperature-modulated DSC. instrument will be in the superelastic condition at Figure 7 presents DSC plots for the tip segment of a 37C, which Thompson reported to be desired by man- ProFile instrument, from the same batch as the

Figure 5 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for a test sample of several segments from one as-received ProFile NiTi instrument. Reprinted from Brantley et al.19 with permission from the American Association of Endodontists. 804 / Endodontics

Figure 6 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for the tip segment from another as-received ProFile instrument. Reprinted from Brantley et al.21 with permission from the American Association of Endodontists.

Figure 7 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for the tip segment from a ProFile instrument subjected to one simulated clinical use. Reprinted from Brantley et al.21 with permission from the American Association of Endodontists. Chapter 26 / Endodontics Instruments and Armamentarium / 805

Figure 8 Differential scanning calorimetry (DSC) heating (lower) and cooling (upper) curves for the tip segment from a LightSpeed instrument subjected to one simulated clinical use. Reprinted from Brantley et al.21 with permission from the American Association of Endodontists.

instrument for Figure 6, which had been subjected to These two DSC studies by Brantley et al.19,21 one simulated clinical use.21 Similar DSC plots were showed that there are substantial differences in the obtained for tip segments from other ProFile instru- character of the NiTi phases for segments taken from ments in this batch, which had been subjected to three different portions of the same rotary NiTi instru- and five simulated clinical uses. After one, three, and ment. Moreover, evident batch effects were observed five simulated clinical uses, the tip segments still intheDSCplotsforinstrumentsfromthesame remained in the superelastic condition, with the Af manufacturer. The DSC results also indicated that temperature on the heating curve less than 0C. Thus, the stresses experienced by a rotary instrument dur- DSC was unable to detect effects from up to five ing manufacturing vary with position along its axis simulated clinical uses on the tip segments of these andthattheremaybedifferencesinthemanufactur- instruments. ing procedure and starting NiTi alloy. Nevertheless, Figure 8 shows DSC plots for the tip segment from regardless of the considerably different character of a LightSpeed NiTi rotary instrument that had been the various DSC plots,19,21 test samples from the subjected to one simulated clinical use.21 This tip ProFile and LightSpeed instruments, in either the segment is also in the superelastic condition, because as-received condition or after simulated clinical use,  the Af temperature on the heating DSC curve is less always displayed superelastic behavior at 37 C, than 25C. There were minimal differences compared although there were relatively large differences in with Figure 8 for the DSC plots from tip segments of the Af values for test samples. other LightSpeed instruments from the same batch From these DSC studies,19,21 it is tempting to that were subjected to three and five simulated clinical assume that the optimum microstructure for super- uses, as well as with DSC plots from the tip segment elastic NiTi rotary instruments would have the max- of an as-received LightSpeed instrument.21 Interest- imum amount of austenite that could reversibly ingly, the DSC plots for a test sample consisting of transform to martensite, with a large enthalpy change several segments for a LightSpeed instrument from a (peak area). When there is substantial stable work- different batch were similar to Figure 5 for an as- hardened martensite in the microstructure, the enth- received ProFile instrument.19 alpy change for reversible transformation to austenite is 806 / Endodontics much smaller.18,23 However, further research is needed and it should be extensively employed for future to test this hypothesis and its relevance to the clinical investigations on NiTi instruments. Future research performance of NiTi instruments. should also include the use of X-ray diffraction and In a contemporary DSC study, Kuhn and Jordan25 transmission electron microscopy, along with scan- analyzed ProFile (Dentsply Maillefer, Baillagues, ning electron microscopy and measurements of Switzerland) and Hero NiTi rotary instruments hav- mechanical properties, to determine the NiTi phases ing different ISO (International Organization for and their characteristics in as-received, heat-treated, Standardization) sizes and tapers. Both as-received and clinically-used instruments. and clinically used instruments were selected, and X-ray diffraction provides information about the test samples were obtained from portions of the NiTi phases in a test sample, and Iijima et al.27 have instruments that would be active or inactive during reported the use of a new micro-X-ray diffraction cutting. Their observations were in good agreement technique to determine the NiTi phases at different with the results by Brantley et al.19,21. The DSC plots locations on a NiTi instrument. Although preparation for as-received Hero instruments with different of the very thin foil specimens is challenging, trans- tapers were similar to Figure 5, and plots for active mission electron microscopy can be used to obtain and inactive portions of the same instrument were insight at the nanometer to submicron level into  different. The Af temperature of 20 Conheatingfor causes of fatigue behavior and provide information Hero instruments was lower than the Af temperature about the NiTi phases and dislocation configurations of 35C for ProFile instruments. Transformation due to manufacturer processing or clinical use of the temperatures were decreased after clinical use of the instruments.28–30 Scanning electron microscopic instruments. (SEM) observations of polished and etched test sam- Kuhn and Jordan25 also studied the effects of heat ples can show whether the rotary instrument has a treatments at six temperatures from 350 to 700C. conventional wrought microstructure or provide evi- Whereas only single peaks were observed on the heat- dence of heat treatment that caused recrystallization ing and cooling DSC plots for as-received instruments to yield equiaxed grains.12 Vickers hardness measure- (interpreted as direct transformations of M fi A and ments can be used to verify whether the NiTi instru- A fi M, respectively), the DSC plots were altered for ment is in the superelastic condition and to investi- annealed test samples. Heat treatments below 510C gate the extent of work hardening.12,31 resulted in two DSC peaks during heating (M fi R As another example of combining experimental followed by R fi A) and two peaks during cooling techniques, Miyai et al.32 recently investigated tor- (A fi R followed by R fi M). After heat treatments sional and bending properties of EndoWave, Hero above 510C, one peak was observed during heating 642, K3, ProFile .06, and ProTaper instruments and (interpreted as M fi A) and one peak during cooling found that their functional properties (particularly (interpreted as A fi M). Heat treatment shifted the flexible bending load level) were related to phase martensite transformation to lower temperatures. transformation behavior determined by DSC. When heat treatment was performed at 600C, recrys- Transformation temperatures for Hero and K3 tallization of the NiTi microstructure occurred in the instruments were significantly lower than for Endo- instruments, as previously found for NiTi orthodontic Wave, ProFile, and ProTaper instruments. How- wires.12 Kuhn and Jordan25 observed that heat treat- ever, the clinical significance and predictability ments below 600C caused test samples to have from such DSC results for performance of the NiTi increased bending flexibility, whereas flexibility was instruments remain to be established in future decreased by heat treatments above 600C. They research. recommended that heat treatment at 400C, corre- sponding to the recovery annealing stage before recrystallization,12 be utilized by manufacturers prior to machining the NiTi instruments to decrease the Effects of Heat Sterilization on Properties work hardening of the alloy. of Nickel–Titanium Instruments Alapati et al.26 have recently reported the first use of temperature-modulated DSC to investigate heat- There have been numerous laboratory studies of treated NiTi rotary instruments. This technique pro- NiTi instruments subjected to multiple heat steriliza- vides much greater resolution about the complex tion cycles. Repeated sterilization has been found by structural transformations in the NiTi orthodontic Silvaggio and Hicks33 and Canalda-Sahli et al.34 to wires than is possible with conventional DSC,23,24 cause changes in torsion and bending properties, and Chapter 26 / Endodontics Instruments and Armamentarium / 807 by Rapisarda et al.35 and Scha¨fer36 to affect cutting Recent extensive clinical studies by Knowles et al.46 efficiency. However, Hilt et al.37 found no effects on for LightSpeed instruments and by Di Fiore et al.47 for the torsional properties, hardness, and microstructure ProFile, ProTaper, ProFile GT, and K3 Endo instru- of NiTi files from the number of sterilization cycles ments reported separation (fracture) rates of less than and the type of autoclave sterilization. 1.5% and much less than 1%, respectively. No statis- Whereas Mize et al.38 found that repeated heat tically significant difference in incidence of fracture sterilization did not affect the number of cycles for was found for the ProFile, ProTaper, ProFile GT, and fatigue failure, Chaves Craveiro de Melo et al.39 and K3 Endo instruments.47 Although these rates are very Viana et al.40 reported that repeated heat sterilization low and justify the widespread use of rotary NiTi instru- caused substantial increases in the number of cycles ments, clinical failures are sources of anguish for both for failure. These observations indicate the necessity the patient and endodontist. Accordingly, there have of having a standard technique for evaluation of the been substantial research efforts to characterize the fatigue behavior of NiTi instruments. instrument failures and determine their origins and Recent DSC studies by Alexandrou et al.41 have to develop new instruments that would minimize the shown that after 11 sterilization cycles, ProFile and occurrence of failures. Flexmaster instruments had the completely austenitic One contributing mechanism for clinical failure of structure needed for superelastic behavior in the oral NiTi instruments, reported by Alapati et al.,48 may be environment. Alexandrou et al.42 also found that after the widening of surface machining grooves by tena- 11 sterilization cycles, the Mani NRT instruments cious dentin debris deposits. The SEM photograph in were either austenite or a mixture of austenite and Figure 9 shows an example of this phenomenon for a R-phase at 37C and concluded that these instruments clinically fractured ProTaper instrument. The poten- are also capable of superelastic behavior under clinical tial role of dentin debris for failure of rotary NiTi conditions. instruments requires further study. In future studies, it would be worthwhile to com- Alapati et al.49 have also performed an extensive pare etched microstructures of the NiTi alloy for SEM study of clinically failed NiTi rotary instruments instruments subjected to multiple heat sterilization to characterize the major aspects of their fracture cycles with etched microstructures for as-received processes. Instruments generally appeared to exhibit instruments to determine whether changes occurred in the original wrought structure due to the steriliza- tion cycles. Comparison of the X-ray diffraction pat- terns and Vickers hardness for sterilized and as- received instruments would reveal12,27,31 whether ster- ilization caused relief of the residual stresses present in the as-received instruments from the manufacturing process. Such residual stresses may contribute to the clinical failure of the NiTi instruments.

Failure of Nickel–Titanium Instruments and Failure Mechanisms The manufacturing process of machining the NiTi rotary instruments from starting wire blanks20 results in rollover at the edges of the flutes6 and a variety of 6,43–45 surface defects. Machining grooves, microcracks, Figure 9 SEM photograph of a clinically fractured ProTaper instrument and surface debris are evident when as-received instru- showing a widened machining groove containing dentin debris that was ments are examined with a scanning electron micro- close to the area in which the fracture occurred. Scale bar length is scope, and instrument fracture generally occurs at 22 mm. Reprinted from Alapati et al.48 with permission from the Amer- surface defects. ican Association of Endodontists. 808 / Endodontics

Figure 10 Secondary electron image of the fracture surface of a ProTaper rotary instrument that failed during clinical use, showing Figure 11 SEM photograph of the fracture surface of a ProFile GT elongated dimples indicative of ductile fracture and secondary phase instrument that failed during clinical use, showing transgranular (clea- particles that may be nickel-titanium oxides. Scale bar length is 6 mm. vage) fracture and intergranular fracture along grain boundaries. Scale Reprinted from Alapati et al.49 with permission from the American bar length is 3 mm. Reprinted from Alapati et al.49 with permission from Association of Endodontists. the American Association of Endodontists. ductile fracture, rather than brittle fracture, as shown in Figure 10 of a clinically fractured ProTaper instru- torsional deformation, giving an ‘‘unfluted appear- ment,49 where the surface has the characteristic ance,’’ and permanent bending deformation without dimpled appearance for ductile fracture.50,51 SEM instrument separation, as well as instruments that observations at high magnification show that these fractured in these modes, under clinical conditions, dimples are nucleated at secondary phase particles in have been observed by other investigators.44,52–56 The the microstructure, such as nickel–titanium oxides.9 axial fracture mode for clinically retrieved instru- The volume fraction of such particles may indicate ments49 involved crack propagation in a direction the quality of the starting NiTi wire alloy used for approximately parallel to the flutes that connected manufacturing the instruments. pitted regions on the surface. These pits may have An example of a more complex fracture surface been former sites of secondary phase particles. is shown for a clinically failed ProFile GT instru- Alapati et al.49 did not observe the characteristic ment in Figure 11.49 Transgranular fracture striations50,51 for cyclic fatigue on the fracture sur- occurred across the fine grains in this microstruc- faces of clinically failed NiTi instruments, presum- ture, as well as intergranular fracture along some ably because the instrumentation time before frac- grain boundaries. Voids or regions of separation ture of the retrieved instruments was insufficiently between some grains can also be seen in Figure 11 long. These investigators concluded that separation and suggest the loss of small grains, subgrains, or of the used instruments, retrieved for their study, secondary phase particles during the fracture pro- was generally caused by a single overload event that cess.49 Although this rotary instrument may have resulted in ductile fracture. By contrast, Cheung experienced overall ductile fracture during clinical et al.55 observed striations indicative of fatigue fail- failure, the features in Figure 11 do not resemble ure for numerous ProTaper instruments that had thoseforductilefractureinFigure10. fractured during clinical use, and these authors con- Two other major failure processes, excessive tor- cluded that fatigue failure is an important mode of sional deformation without separation and axial frac- separation during clinical instrumentation. An ture, were observed by Alapati et al.49 for these clini- example of the fine-scale striations is shown in Fig- cally retrieved NiTi rotary instruments. Permanent ure 12 from a laboratory study by Luebke et al.57 of Chapter 26 / Endodontics Instruments and Armamentarium / 809

treatment of these instruments may yield beneficial results. Tripi et al.58 recently compared the effects of instru- ment design and surface treatment on the cyclic fati- gue of ProFile, RaCe, K3, Hero, and Mtwo instru- ments. While the best fatigue resistance was found for the ProFile instruments, the electropolishing sur- face treatment for RaCe instruments increased their fatigue resistance by reducing the presence of micro- cracks, surface debris, and other machining damage. Lee et al.59 first proposed the application of ion implantation to NiTi instruments. They reported that boron-ion implantation more than doubled the surface hardness of Nitinol at the nanoindentation depth of 0.05 mm, yielding a hardness value greater than that of stainless steel. Figure 12 SEM photomicrograph of the in vitro fracture surface of a 60 NiTi Gates Glidden drill tested to failure in bending fatigue, showing fine Rapisarda et al. subsequently employed both a striations that form during fatigue crack propagation. Scale bar length is thermal nitriding technique and nitrogen-ion implan- 0.7 mm. Reprinted from Luebke et al.57 with permission from the Amer- tation to increase the wear resistance of NiTi instru- ican Association of Endodontists. ments. The ion-implanted samples had a higher N:Ti ratio, which suggested the presence of a titanium nitride layer. Both the thermal-nitrided and nitro- gen-ion-implanted instruments had higher wear resis- NiTi Gates Glidden drills subjected to cyclic cantile- tance and increased cutting ability in acrylic blocks ver bending. compared with control instruments without surface In summary, numerous studies have shown that modifications. An SEM study of nitrogen-ion- NiTi alloys for rotary instruments can possess implanted instruments by these investigators61 significant ductility in bending and torsion, without revealed the absence of surface wear and morphology experiencing separation in certain clinical cases, where changes that occurred in control instruments after the the canals have substantial curvature or where rota- same period of simulated clinical use. tion of the tip is hindered. Fracture initiation often Scha¨fer36 used a physical vapor deposition (PVD) appears to occur at machining grooves, with a possi- process to create a TiN surface coating on NiTi instru- ble role from retained dentin debris in these grooves. ments. Surface-coated instruments had greater cutting Retrieved instruments, which failed during clinical efficiency (penetration into plastic samples with use, may fracture from cyclic fatigue after longer cylindrical canals) compared with control instruments, periods of use or from single overload events after and their cutting efficiency was not altered by repeated relatively brief periods of use. Clearly, the manufac- autoclave or sodium hypochlorite sterilization. turing process for NiTi rotary instruments and the Lastly, use of heat treatments for the NiTi instru- need for a starting NiTi wire alloy of high metallurgi- ments, or general modifications in proprietary ther- cal quality are major factors for reducing the inci- momechanical processing procedures for the starting dence of clinical failure of these instruments. wire blanks, may provide other strategies.62 It has been noted that Kuhn and Jordan25 explored the use of heat treatments at temperatures ranging from 350 to 700C. They concluded that annealing around Strategies for Improved Nickel–Titanium 400C yields a suitable proportion of NiTi micro- structural phases and a beneficial effect (limiting Instruments brittleness) on the mechanical properties of these Several strategies have been employed to develop instruments. Previous research on NiTi orthodontic NiTi instruments that should have improved clinical wires has shown that heat treatment at 400Cdoes performance. These strategies have included electro- not affect the bending properties of superelastic wires, polishing the machined surfaces, ion implantation whereas heat treatment at 600C causes loss of super- to create harder surfaces, and use of special sur- elastic behavior.10,11 Heat treatment for 10 minutes at face coatings. Research has also suggested that heat 500C had minimal effect on the cantilever bending 810 / Endodontics plots, but 2 hours of heat treatment at this tempera- 11. Khier SE, Brantley WA, Fournelle RA. Bending properties of ture decreased the average superelastic bending superelastic and nonsuperelastic nickel-titanium orthodontic moment during unloading of the wire test span. wires. Am J Orthod Dentofacial Orthop 1991;99:310–128. Heat treatment can alter the phase transformation 12. Brantley WA. Orthodontic wires. In: Brantley WA, Eliades T, temperatures for the NiTi alloy, such as reduction of editors. Orthodontic materials: scientific and clinical aspects. Stuttgart: Thieme; 2001. pp. 15–21, 84–97. the Ms temperature to subambient levels to yield a 12 completely austenitic structure at room temperature. 13. Miyazaki S, Otsuka K. Development of shape memory alloys. Heat treatment within only the recovery annealing Iron Steel Inst Jpn Int 1989;29:353–77. stage for the NiTi alloy would reduce residual stresses 14. Goldstein D, Kabacoff L, Tydings J. Stress effects on nitinol of potential importance for fracture behavior without phase transformations. J Metals 1987;39:19–26. altering the microstructure. Presumably, heat treat- 15. Alapati SB, Brantley WA, Svec TA, et al. Scanning electron ment at temperatures of 600C and higher, causing 12,25 microscope observations of new and used nickel-titanium recrystallization of the wrought microstructure, rotary files. J Endod 2003;29:667–9. should be avoided for the rotary instruments. Given 16. Todoroki T, Tamura H. Effect of heat treatment after cold the special nature of the NiTi alloy phases and their 9 working on the phase transformation in TiNi alloy. Trans Jpn transformations, one can envision the future devel- Inst Metals 1987;28:83–94. opment of complex thermomechanical processing cycles to optimize the starting NiTi wire blanks or 17. Yoneyama T, Doi H, Hamanaka H, et al. Super-elasticity and thermal behavior of Ni-Ti alloy orthodontic arch wires. Dent new heat treatments to improve the cutting efficiency Mater J 1992;11:1–10. and fatigue resistance of the instruments after machin- ing from these blanks. 18. Bradley TG, Brantley WA, Culbertson BM. Differential scan- ning calorimetry (DSC) analyses of superelastic and nonsu- perelastic nickel-titanium orthodontic wires. Am J Orthod Dentofacial Orthop 1996;109:589–97. References 19. Brantley WA, Svec TA, Iijima M, et al. Differential scanning 1. Civjan S, Huget EF, DeSimon LB. Potential applications of cer- calorimetric studies of nickel titanium rotary endodontic tain nickel-titanium (Nitinol) alloys. J Dent Res 1975;54:89–96. instruments. J Endod 2002;28:567–72. 2. Andreasen GF, Brady PR. A use hypothesis for 55 nitinol wire 20. Thompson SA. An overview of nickel-titanium alloys used in for orthodontics. Angle Orthod 1972;42:172–7. dentistry. Int Endod J 2000;33:297–310. 3. Andreasen GF, Hilleman TB. An evaluation of 55 cobalt 21. Brantley WA, Svec TA, Iijima M, et al. Differential scanning substituted nitinol wire for use in orthodontics. J Am Dent calorimetric studies of nickel-titanium rotary endodontic Assoc 1971;82:1373–5. instruments after simulated clinical use. J Endod 2002;28:774–8. 4. Andreasen GF, Morrow RE. Laboratory and clinical analyses of nitinol wire. Am J Orthod 1978;73:142–51. 22. Brantley WA, Guo WH, Clark WAT, Iijima M. TEM confir- mation of low-temperature martensite transformation in 5. Walia H, Brantley W, Gerstein H, Arpaio J. New metallurgy nickel-titanium orthodontic wire. J Dent Res 2003;82(Special root canal files. J Dent Res 1987;66(Special Issue):349, Issue A): Abstract No. 1535. Abstract No. 1943. 23. Brantley WA, Iijima M, Grentzer TH. Temperature- 6. Walia H, Brantley WA, Gerstein H. An initial investigation of modulated DSC study of phase transformations in nickel- the bending and torsional properties of Nitinol root canal titanium orthodontic wires. Thermochimica Acta files. J Endod 1988;14:346–51. 2002;392–3:329–37. 7. Walia H, Costas J, Brantley W, Gerstein H. Torsional ductility 24. Brantley WA, Iijima M, Grentzer TH. Temperature- and cutting efficiency of the Nitinol file. J Endod 1989;15:174 modulated DSC provides new insight about nickel-titanium [Abstract 22]. wire transformations. Am J Orthod Dentofacial Orthop 8. Buehler WJ, Wang FE. A summary of recent research on the 2003;124:387–94. nitinol alloys and their potential application in ocean engi- 25. Kuhn G, Jordan L. Fatigue and mechanical properties of nickel- neering. Ocean Eng 1968;1:105–20. titanium endodontic instruments. J Endod 2002;28:716–20. 9. Duerig TW, Melton KN, Sto¨ckel D, Wayman CM, editors. 26. Alapati SB, Brantley WA, Schricker SR, et al. Investigation of Engineering aspects of shape memory alloys. London: Butter- transformations in used and heat-treated nickel-titanium worth-Heinemann; 1990. pp. 3–45, 369–93. endodontic instruments. J Dent Res 2006;85(Special Issue 10. Miura F, Mogi M, Ohura Y, Hamanaka H. The super-elastic A): Abstract No. 38. property of the Japanese NiTi alloy wire for use in orthodontics. 27. Iijima M, Brantley WA, Alapati SB, Nusstein JM. Micro-XRD Am J Orthod Dentofacial Orthop 1986;90:1–10. study of nickel-titanium rotary endodontic instruments after Chapter 26 / Endodontics Instruments and Armamentarium / 811

clinical use. J Dent Res 2005;84(Special Issue A): Abstract No. 42. Alexandrou G, Chrissafis K, Vasiliadis L, et al. Effect of heat 1479. sterilization on surface characteristics and microstructure of Mani NRT rotary nickel-titanium instruments. Int Endod J 28. Guo WH, Brantley WA, Li D, et al. Fatigue studies of high- 2006;39:770–8. palladium dental casting alloys: Part II. Transmission electron microscopic observations. J Mater Sci: Mater Med 43. Eggert C, Peters O, Barbakow F. Wear of nickel-titanium 2002;13:369–74. Lightspeed instruments evaluated by scanning electron micro- scopy. J Endod 1999;25:494–7. 29. Guo WH, Brantley WA, Clark WAT, et al. Transmission electron microscopic investigation of a Pd-Ag-In-Sn dental 44. Sattapan B, Nervo GJ, Palamara JEA, Messer HH. Defects in alloy. Biomaterials 2003;24:1705–12. rotary nickel-titanium files after clinical use. J Endod 2000;26:161–5. 30. Guo WH, Brantley WA, Clark WAT, et al. Transmission electron microscopic studies of deformed high-palladium 45. Tripi TR, Bonaccorso A, Tripi V, et al. Defects in GT rotary dental alloys. Dent Mater 2003;19:334–40. instruments after use: an SEM study. J Endod 2001;27:782–5. 31. Alapati SB, Brantley WA, Nusstein JM, et al. Vickers hardness 46. Knowles KI, Hammond NB, Biggs SG, Ibarrola JL. Incidence investigation of work-hardening in used NiTi rotary instru- of instrument separation using LightSpeed rotary instru- ments. J Endod 2006;32:1191–3. ments. J Endod 2006;32:14–16. 32. Miyai K, Ebihara A, Hayashi Y, et al. Influence of phase 47. Di Fiore PM, Genov KA, Komaroff E, et al. Nickel-titanium transformation on the torsional and bending properties of rotary instrument fracture: a clinical practice assessment. Int nickel-titanium rotary endodontic instruments. Int Endod J Endod J 2006;39:700–8. 2006;39:119–26. 48. Alapati SB, Brantley WA, Svec TA, et al. Proposed role of 33. Silvaggio J, Hicks ML. Effect of heat sterilization on the embedded dentin chips for the clinical failure of nickel- torsional properties of rotary nickel-titanium endodontic titanium rotary instruments. J Endod 2004;30:339–41. files. J Endod 1997;23:731–4. 49. Alapati SB, Brantley WA, Svec TA, et al. SEM observations 34. Canalda-Sahli C, Brau-Aguade E, Sentis-Vilalta J. The effect of nickel-titanium rotary endodontic instruments that frac- of sterilization on bending and torsional properties of K-files tured during clinical use. J Endod 2005;31:40–3. manufactured with different metallic alloys. Int Endod J 50. Dieter GE. Mechanical metallurgy. 3rd ed. New York: 1998;31:48–52. McGraw-Hill; 1986. pp. 254–6, 262–4, 394–8. 35. Rapisarda E, Bonaccorso A, Tripi TR, Condorelli GG. Effect of 51. Kerlins V, Phillips A. Modes of fracture. In: Metals handbook. sterilization on the cutting efficiency of rotary nickel-titanium Vol 12. 9th ed. Fractography. Metals Park, OH: ASM Inter- endodontic files. Oral Surg Oral Med Oral Pathol Oral Radiol national; 1987. pp. 12–71. Endod 1999;88:343–7. 52. Tygesen YA, Steiman HR, Ciavarro C. Comparison of distor- 36. Scha¨fer E. Effect of sterilization on the cutting efficiency of tion and separation utilizing ProFile and Pow-R nickel-tita- PVD-coated nickel-titanium endodontic instruments. Int nium rotary files. J Endod 2001;27:762–4. Endod J 2002;35:867–72. 53. Arens FC, Hoen MM, Steiman HR, Dietz GC Jr. Evaluation of 37. Hilt BR, Cunningham CJ, Shen C, Richards N. Torsional single-use rotary nickel-titanium instruments. J Endod properties of stainless-steel and nickel-titanium files 2003;29:664–6. after multiple autoclave sterilizations. J Endod 2000;26:76–80. 54. Parashos P, Gordon I, Messer HH. Factors influencing defects 38. Mize SB, Clement DJ, Pruett JP, Carnes DL Jr. Effect of of rotary nickel-titanium endodontic instruments after clin- sterilization on cyclic fatigue of rotary nickel-titanium endo- ical use. J Endod 2004;30:722–5. dontic instruments. J Endod 1998;24:843–7. 55. Cheung GSP, Peng B, Bian Z, et al. Defects in ProTaper S1 39. Chaves Craveiro de Melo M, Guiomar de Azevedo Bahia M, instruments after clinical use: fractographic examination. Int Lopes Buono VT. Fatigue resistance of engine-driven rotary Endod J 2005;38:802–9. nickel-titanium endodontic instruments. J Endod 2002;28:765–9. 56. Shen Y, Cheung GSP, Bian Z, Peng B. Comparison of defects in ProFile and ProTaper systems after clinical use. J Endod 40. Viana ACD, Gonzalez BM, Buono VTL, Bahia MGA. Influ- 2006;32:61–5. ence of sterilization on mechanical properties and fatigue resistance of nickel-titanium rotary endodontic instruments. 57. Luebke NH, Brantley WA, Alapati SB, et al. Bending fatigue Int Endod J 2006;39:709–15. study of nickel-titanium Gates Glidden drills. J Endod 2005;31:523–5. 41. Alexandrou GB, Chrissafis K, Vasiliadis LP, et al. SEM obser- vations and differential scanning calorimetric studies of new 58. Tripi TR, Bonaccorso A, Condorelli GG. Cyclic fatigue of differ- and sterilized nickel-titanium rotary endodontic instruments. ent nickel-titanium endodontic rotary instruments. Oral Surg J Endod 2006;32:675–9. Oral Med Oral Pathol Oral Radiol Endod 2006;102:E106–14. 812 / Endodontics

59. Lee DH, Park B, Saxena A, Serene TP. Enhanced surface 61. Rapisarda E, Bonaccorso A, Tripi TR, et al. Wear of nickel- hardness by boron implantation in Nitinol alloy. J Endod titanium endodontic instruments evaluated by scanning electron 1996;22:543–6. microscopy: effect of ion implantation. J Endod 2001;27:588–92. 60. Rapisarda E, Bonaccorso A, Tripi TR, et al. The effect of 62. Alapati SB. An investigation of phase transformation mechan- surface treatments of nickel-titanium files on wear and cut- isms for nickel-titanium rotary endodontic instruments (PhD ting efficiency. Oral Surg Oral Med Oral Pathol Oral Radiol dissertation). Columbus, OH: The Ohio State University, Endod 2000;89:363–8. 2006. C. INSTRUMENTS FOR CLEANING AND SHAPING

TIMOTHY A. SVEC

Instrumentation of the root canal system requires both hand and rotary files. No canal system can or should be instrumented with rotary files alone. The development of hand and engine-driven files will be discussed with an emphasis on nickel–titanium rotary files.

Basic Endodontic Instruments After the introduction of standardized instruments,1 about the only changes made were the universal use of stainless rather than carbon steel and the addition of smaller (Nos. 6 and 8) and larger (Nos. 110–150) sizes as well as color coding. It was not until 1976 that the first approved specification for root canal instruments was published (ADA Specification No. 28).

ENDODONTIC INSTRUMENT STANDARDIZATION In 1959, a new line of standardized instruments and 2 filling material was introduced to the profession: Figure 1 Original recommendation for standardized instruments. Cutting 1. A formula for the diameter and taper in each size blades 16 mm in length are of the same size and numbers as standar- of instrument and filling material was agreed on. dized filling points. The number of the instrument is determined by diameter size at D1 in hundredths of millimeters. Diameter 2 (D2) is 2. A formula for a graduated increment in size from uniformly 0.32 mm greater than D1, a gain of 0.02 mm/1 mm of cutting one instrument to the next was developed. blades. Reproduced with permission from Ingle JI. In Grossman, LI, 3. A new instrument numbering system based on editor. Transactions of the Second International Conference on Endo- instrument metric diameter was established. dontics. Philadelphia: University of Pennsylvania; 1958. p. 123. This numbering system, last revised in 2002,3 using numbers from 6 to 140, is based on the diameter of Instruments with a taper greater than the ISO (Inter- the instruments in hundredths of a millimeter at the national Standards Organization) standard of 0.02 mm/ beginning of the tip of the blades, a point called D0 mm have become popular: 0.04, 0.06, 0.08, 0.10, and (diameter 1 mm) (Figure 1), and extending up the 0.12. This means that for every millimeter gain in the blades to the most coronal part of the cutting edge at length of the cutting blade, the width (taper) of the D16 (diameter 2–16 mm in length). Additional revi- instrument increases in size by 0.04, 0.06, 0.08, 0.10, or sions are under way to cover instruments constructed 0.12 of a millimeter rather than the ISO standard of with new materials, designs, and tapers greater than 0.02 mm/mm. These new instruments allow for greater 0.02 mm/mm. coronal flaring than the 0.02 instruments.

813 814 / Endodontics

The full extent of the shaft, up to the handle, comes in Spa˚ngberg10 noted that few brands are within accep- three lengths: standard, 25 mm; long, 31 mm; and short, table dimensional standards. 21 mm. The long instruments are often necessary when Cormier et al.6 have warned of the importance of treating canines over 25 mm long. Shorter instruments using only one brand of instruments because of dis- are helpful in second and third molars or in the patient crepancies in instrument size among manufacturers. who cannot open widely. Other special lengths are Seto et al.7 noted that grinding the flutes in files rather available. than twisting them ‘‘does not improve the strength or Ultimately, to maintain these standards, the Amer- ductility of the instrument . . . (and) may also create ican Association of Endodontists (AAE) urged the more undesirable fluting defects.’’ Since then, however, American Dental Association (ADA) and the United grinding has improved and gained importance because States Bureau of Standards to appoint a committee for most nickel–titanium instruments must be machined, endodontic instrument standardization. A committee not twisted. Several recent studies have indicated that was formed and produced a specification package that this type of manufacturing does not weaken instru- slightly modified Ingle’s original standardization.1 ments. In fact, most studies indicate that both manu- Then a worldwide committee was formed: ISO, con- facturing processes produce files that meet or exceed sisting of the Fe´de´ration Dentaire International, the ISO standards.11–13 World Health Organization, and the ADA Instrument It has also been found that autoclaving has no Committee. The ISO has now formulated interna- significant deleterious effects on stainless steel or tional specifications using the ADA proposal as a nickel–titanium endodontic instruments.14,15 Now model. made universally of nickel–titanium and stainless steel ANSI (American National Standards Institute)/ rather than carbon steel, K-type instruments are pro- ADA standards have also been set for other instru- duced using one of two techniques. The more tradi- ments and filling materials: No. 58, Hedstroem files; tional is produced by grinding graduated sizes of No. 63, rasps and barbed broaches; No. 71, spreaders round wire into various shapes such as square, trian- and condensers; No. 95, root canal enlargers; as well gular, or rhomboid. A second grinding operation as No. 57, filling materials; No. 73, absorbent points; properly tapers these pieces. To give the instruments and No. 78, obturating points. Committee work is the spirals that provide the cutting edges, the square continuing to make these standards comparable with or triangular stock is then grasped by a machine that ISO standards. twists it counterclockwise a programed number of The relevant standards have tolerances for size times—tight spirals for files, loose spirals for reamers. maintenance (both diameter and taper), surface deb- The cutting blades that are produced are the sharp ris, cutting flute character, torsional properties, stiff- edges of either the square or the triangle. In any ness, cross-sectional shape, cutting tip design, and instrument, these edges are known as the ‘‘rake’’ of type of metal. Variations from these tolerances have the blade. The more acute the angle of the rake, the been noted4–9 (Figure 2). More recently, Stenman and sharper the blade. There is approximately twice the