- Email: [email protected]
In Patients With Symptomatic Irreversible Pulpitis, Articaine is 3.6 Times More Efficacious Than Lidocaine in Achieving Anesthetic Success When Used for Supplementary Infiltration After Mandibular Block Anesthesia
Accepted Manuscript DECLARATIVE TITLE: In patients with symptomatic irreversible pulpitis, articaine is 3.5 times more efficacious than lidocaine in achieving anesthetic success when used for supplementary infiltration after mandibular block anesthesia Mathilde C. Peters, DMD, PhD, Professor Emerita, Clinical Professor, Consultant for Clinical Research, Tatiana M. Botero, D. DDS, MS, Clinical Associate Professor, Diplomate American Board of Endodontics PII:
S1532-3382(17)30076-3
DOI:
10.1016/j.jebdp.2017.03.003
Reference:
YMED 1178
To appear in:
The Journal of Evidence-Based Dental Practice
Please cite this article as: Peters MC, Botero TM, DECLARATIVE TITLE: In patients with symptomatic irreversible pulpitis, articaine is 3.5 times more efficacious than lidocaine in achieving anesthetic success when used for supplementary infiltration after mandibular block anesthesia, The Journal of EvidenceBased Dental Practice (2017), doi: 10.1016/j.jebdp.2017.03.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Kung_spl_RAE - Peters JEBD_V1.docx
Review Analysis and Evaluation
RI PT
DECLARATIVE TITLE: In patients with symptomatic irreversible pulpitis, articaine is 3.5 times more efficacious than lidocaine in achieving anesthetic success when used for supplementary infiltration after mandibular block anesthesia. ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Does articaine provide an advantage over lidocaine in patients with symptomatic irreversible pulpitis? A systematic review and meta-analysis. Kung J, McDonagh M, Sedgley CM. J Endod 2015;41(11):1784-94.
SC
PURPOSE/QUESTION: The authors studied the comparative efficacy and adverse event incidence of articaine versus lidocaine in reducing pain when used in endodontic treatment of a “hot” tooth in adults.
TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.
M AN U
SOURCE OF FUNDING: This study was supported by the OHSU Department of Endodontology Les Morgan Endowment Fund and a resident research grant from the American Association of Endodontists Foundation.
REVIEWER NAME and CONTACT INFORMATION:
TE D
Mathilde C. Peters, DMD, PhD Professor Emerita – U of Michigan Clinical Professor, Consultant for Clinical Research – LSUHSC 612 Jefferson Ave, New Orleans LA 70115 [email protected]
AC C
EP
Tatiana M. Botero D. DDS, MS Clinical Associate Professor – U of Michigan Diplomate American Board of Endodontics Cariology, Restorative Sciences and Endodontics University of Michigan, School of Dentistry, 1011 N University, Room 2309 Ann Arbor, MI 48109-1078 [email protected]
ACCEPTED MANUSCRIPT 2
Kung_spl_RAE - Peters JEBD_V1.docx
Summary
RI PT
Selection Criteria: Only double-blind, randomized controlled clinical trials (RCTs) published in a peer-reviewed journal were considered. Based on a PROSPERO protocol, a comprehensive search from 1976 (when articaine was first introduced) up to February 2015 was conducted on four electronic databases (MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov) to identify eligible studies by using strict inclusion and exclusion criteria. NonEnglish language articles without English abstracts were excluded. Hand searches of reference lists from identified clinical trials, review articles, and major textbooks completed the search.
SC
Studies were included that evaluated the pulpal anesthetic solutions of 4% articaine compared with 2% lidocaine, delivered as a similar volume dose of at least 1.0 mL per injection in combination with a vasoconstrictor, in adult patients with symptomatic irreversible pulpitis. Studies that used anesthetic delivery via any route were included. Studies were excluded if they offered insufficient information about the diagnosis of symptomatic irreversible pulpitis or the definition of anesthetic success. Studies were also excluded when dichotomous data for anesthesia outcome were unavailable.
M AN U
A total of 275 records were initially identified. Two investigators independently assessed eligibility of the studies by title and abstract. Seventeen potentially eligible studies were then assessed for inclusion and quality by reading the full text, resulting in the final inclusion of 10 studies in the meta-analysis. Discrepancies between reviewers were resolved by consensus with a third person. The “Risk of Bias” assessment was done independently by the two reviewers following the Cochrane collaboration tool, and disagreements were resolved by consensus. Key Study Factor: The primary study factor was the comparative efficacy of articaine and lidocaine in pain reduction when used in endodontic treatment of a “hot” tooth in adults. Reporting on comparative adverse event incidence was the secondary study focus.
TE D
Main Outcome Measure: The primary outcome measure was the reduction of pulpal pain leading to ‘‘successful anesthesia’’ of teeth with symptomatic irreversible pulpitis.
EP
Main Results: The 10 included studies were single-site clinical trials, involving 746 patients, published between 2004 and 2014 (origin: India (5), USA (3), UK (1), Brazil (1)). Success rates for articaine and lidocaine ranged from 24% and 23%, respectively, for inferior alveolar nerve block delivery to 100% and 89%, respectively, for maxillary infiltration.
AC C
For combined studies (all 10 trials), articaine was 2.21 times more likely than lidocaine to achieve successful 2 anesthesia (odds ratio [OR] = 2.21; 95% confidence interval [CI] = 1.41–3.47; P = .0006; heterogeneity [I ] = 40%). Subgroup analyses showed: • No significant difference between articaine and lidocaine in either maxillary infiltration (3 trials; P = .19) or in mandibular block anesthesia alone (5 trials; P = .16). • Taking all mandibular anesthesia studies using any delivery route into account (8 trials), articaine was 2 superior to lidocaine (OR = 2.20; 95% CI = 1.40–3.44; P = .0006; I = 30%). • When used for supplemental infiltration after successful mandibular block anesthesia (3 trials), articaine was significantly more effective than lidocaine (OR = 3.55; 95% CI = 1.97–6.39; P < .0001; I2 = 19%). No adverse event incidences were reported in combined studies (involving 746 cases).
Conclusions:
In patients with symptomatic irreversible pulpitis, articaine is as effective as lidocaine for mandibular block and
ACCEPTED MANUSCRIPT 3
Kung_spl_RAE - Peters JEBD_V1.docx
maxillary infiltration anesthesia. In cases of persistent pulpal pain despite successful mandibular block anesthesia, supplementary infiltration with articaine instead of lidocaine showed a 3.55 times greater likelihood of achieving successful anesthesia. No adverse event incidences were reported in these studies.
RI PT
Commentary and Analysis This research presents a timely update and critical appraisal of our current knowledge evaluating the anesthetic efficacy of articaine versus lidocaine in symptomatic patients. Importantly, it is the first English language systematic review that included only parallel-designed RCTs (evaluating independent samples) with participants diagnosed with symptomatic irreversible pulpitis, while 2 earlier English language systematic reviews (1, 2) included both RCTs and cross-over studies evaluating both patients with pain and volunteers without pain.
SC
The current review is focused on one of the most difficult situations a dentist encounters in daily practice: anesthesizing a tooth with symptomatic irreversible pulpitis.(3) Relief of the often excruciating pain is the first and foremost action a patient expects and the dentist wants to deliver.(4, 5) Achieving fast and reliable profound anesthesia in an acutely painful tooth is a challenge.(6, 7)
M AN U
This well-conducted study provides a thorough review of recently published RCTs, presenting important outcomes and a detailed discussion that contributes to the evidence base supporting daily clinical practice. The review’s evidence supports the use of articaine for patients with symptomatic irreversible pulpitis, in particular as used as supplementary infiltration when pulpal pain persists despite a successful mandibular block anesthesia (defined as lip numbness). Data extraction included risk of bias judgments to inform about heterogeneity of the studies.(8) The random-effects statistical model used allowed the meta-analysis to account for inherent heterogeneity issues. In addition, sensitivity analyses (e.g., excluding 1 study identified as a potential outlier with unclear reporting) confirmed that the overall results of the meta-analysis were not affected.
TE D
This article makes a key contribution to evidence-based dentistry and as such should guide the way readers conduct their clinical practice. Despite the heterogeneity of the studies included, it provides level 1 evidence for the superiority of articaine over lidocaine for specific delivery paths when treating symptomatic irreversible pulpitis teeth.
EP
When used for mandibular block anesthesia alone or for maxillary infiltration, articaine was as effective as lidocaine. Confronted with the continued sensitivity of a mandibular ‘hot’ tooth after a successful mandibular block, dentists are 3.6 times more likely to achieve anesthetic success when using supplementary infiltration with articaine compared to lidocaine. To achieve effective mandibular anesthesia via any route of administration other than inferior alveolar nerve block, the use of articaine is significantly superior to using lidocaine.
AC C
Many general practitioners may not be aware that reports of a low level of safety regarding articaine neurotoxicity were based on retrospective studies with biased data recruitment that showed no scientific evidence demonstrating that 4% articaine solution was neurotoxic or unsafe to use in any aspect of clinical dentistry.(9) The outcomes of this systematic review add to earlier reports on safety data.(1, 2) The additional absence of adverse event incidences in this systematic review of 746 patients confirms that dentists can have confidence in the safe use of articaine for successful dental anesthesia in adults with irreversible pulpitis.
ACCEPTED MANUSCRIPT 4
Kung_spl_RAE - Peters JEBD_V1.docx
Strength of Recommendation Taxonomy (SORT) Grading Level 1
– Good-quality, patient-oriented evidence
STRENGTH OF RECOMMENDATION GRADE:
RI PT
LEVEL OF EVIDENCE:
Grade A – Consistent, good-quality patient-oriented evidence
7. 8. 9.
M AN U
5. 6.
TE D
4.
EP
3.
Katyal V. The efficacy and safety of articaine versus lignocaine in dental treatments: a meta-analysis. J Dent 2010;38:307–17. Brandt RG, Anderson PF, McDonald NJ, et al. The pulpal anesthetic efficacy of articaine versus lidocaine in dentistry: a metaanalysis. J Am Dent Assoc 2011;142:493–504. Wallace JA, Michanowicz AE, Mundell RD, Wilson EG. A pilot study of the clinical problem of regionally anesthetizing the pulp of an acutely inflamed mandibular molar. Oral Surg Oral Med Oral Pathol 1985;59:517–21. Segura-Egea JJ, Cisneros-Cabello R, Llamas-Carreras JM, Velasco-Ortega E. Pain associated with root canal treatment. Int Endod J 2009;42:614–20. Malamed SF. Local anesthetics: dentistry’s most important drugs, clinical update 2006. J Calif Dent Assoc 2006;34:971–6. Fleury AA. Local anesthesia failure in endodontic therapy: the acute inflammation factor. Compendium 1990;11:210. 212, 214 passim. Quint JH. The failure of local anesthesia in acute inflammation. Br Dent J 1981;151:214. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available at: www.cochrane-handbook.org. Accessed August 11, 2015. Yapp KE, Hopcraft MS, Parashos P. Articaine: a review of the literature. Br Dent J 2011;210:323–9.
AC C
1. 2.
SC
References
S1532-3382(17)30076-3
DOI:
10.1016/j.jebdp.2017.03.003
Reference:
YMED 1178
To appear in:
The Journal of Evidence-Based Dental Practice
Please cite this article as: Peters MC, Botero TM, DECLARATIVE TITLE: In patients with symptomatic irreversible pulpitis, articaine is 3.5 times more efficacious than lidocaine in achieving anesthetic success when used for supplementary infiltration after mandibular block anesthesia, The Journal of EvidenceBased Dental Practice (2017), doi: 10.1016/j.jebdp.2017.03.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Kung_spl_RAE - Peters JEBD_V1.docx
Review Analysis and Evaluation
RI PT
DECLARATIVE TITLE: In patients with symptomatic irreversible pulpitis, articaine is 3.5 times more efficacious than lidocaine in achieving anesthetic success when used for supplementary infiltration after mandibular block anesthesia. ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Does articaine provide an advantage over lidocaine in patients with symptomatic irreversible pulpitis? A systematic review and meta-analysis. Kung J, McDonagh M, Sedgley CM. J Endod 2015;41(11):1784-94.
SC
PURPOSE/QUESTION: The authors studied the comparative efficacy and adverse event incidence of articaine versus lidocaine in reducing pain when used in endodontic treatment of a “hot” tooth in adults.
TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.
M AN U
SOURCE OF FUNDING: This study was supported by the OHSU Department of Endodontology Les Morgan Endowment Fund and a resident research grant from the American Association of Endodontists Foundation.
REVIEWER NAME and CONTACT INFORMATION:
TE D
Mathilde C. Peters, DMD, PhD Professor Emerita – U of Michigan Clinical Professor, Consultant for Clinical Research – LSUHSC 612 Jefferson Ave, New Orleans LA 70115 [email protected]
AC C
EP
Tatiana M. Botero D. DDS, MS Clinical Associate Professor – U of Michigan Diplomate American Board of Endodontics Cariology, Restorative Sciences and Endodontics University of Michigan, School of Dentistry, 1011 N University, Room 2309 Ann Arbor, MI 48109-1078 [email protected]
ACCEPTED MANUSCRIPT 2
Kung_spl_RAE - Peters JEBD_V1.docx
Summary
RI PT
Selection Criteria: Only double-blind, randomized controlled clinical trials (RCTs) published in a peer-reviewed journal were considered. Based on a PROSPERO protocol, a comprehensive search from 1976 (when articaine was first introduced) up to February 2015 was conducted on four electronic databases (MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov) to identify eligible studies by using strict inclusion and exclusion criteria. NonEnglish language articles without English abstracts were excluded. Hand searches of reference lists from identified clinical trials, review articles, and major textbooks completed the search.
SC
Studies were included that evaluated the pulpal anesthetic solutions of 4% articaine compared with 2% lidocaine, delivered as a similar volume dose of at least 1.0 mL per injection in combination with a vasoconstrictor, in adult patients with symptomatic irreversible pulpitis. Studies that used anesthetic delivery via any route were included. Studies were excluded if they offered insufficient information about the diagnosis of symptomatic irreversible pulpitis or the definition of anesthetic success. Studies were also excluded when dichotomous data for anesthesia outcome were unavailable.
M AN U
A total of 275 records were initially identified. Two investigators independently assessed eligibility of the studies by title and abstract. Seventeen potentially eligible studies were then assessed for inclusion and quality by reading the full text, resulting in the final inclusion of 10 studies in the meta-analysis. Discrepancies between reviewers were resolved by consensus with a third person. The “Risk of Bias” assessment was done independently by the two reviewers following the Cochrane collaboration tool, and disagreements were resolved by consensus. Key Study Factor: The primary study factor was the comparative efficacy of articaine and lidocaine in pain reduction when used in endodontic treatment of a “hot” tooth in adults. Reporting on comparative adverse event incidence was the secondary study focus.
TE D
Main Outcome Measure: The primary outcome measure was the reduction of pulpal pain leading to ‘‘successful anesthesia’’ of teeth with symptomatic irreversible pulpitis.
EP
Main Results: The 10 included studies were single-site clinical trials, involving 746 patients, published between 2004 and 2014 (origin: India (5), USA (3), UK (1), Brazil (1)). Success rates for articaine and lidocaine ranged from 24% and 23%, respectively, for inferior alveolar nerve block delivery to 100% and 89%, respectively, for maxillary infiltration.
AC C
For combined studies (all 10 trials), articaine was 2.21 times more likely than lidocaine to achieve successful 2 anesthesia (odds ratio [OR] = 2.21; 95% confidence interval [CI] = 1.41–3.47; P = .0006; heterogeneity [I ] = 40%). Subgroup analyses showed: • No significant difference between articaine and lidocaine in either maxillary infiltration (3 trials; P = .19) or in mandibular block anesthesia alone (5 trials; P = .16). • Taking all mandibular anesthesia studies using any delivery route into account (8 trials), articaine was 2 superior to lidocaine (OR = 2.20; 95% CI = 1.40–3.44; P = .0006; I = 30%). • When used for supplemental infiltration after successful mandibular block anesthesia (3 trials), articaine was significantly more effective than lidocaine (OR = 3.55; 95% CI = 1.97–6.39; P < .0001; I2 = 19%). No adverse event incidences were reported in combined studies (involving 746 cases).
Conclusions:
In patients with symptomatic irreversible pulpitis, articaine is as effective as lidocaine for mandibular block and
ACCEPTED MANUSCRIPT 3
Kung_spl_RAE - Peters JEBD_V1.docx
maxillary infiltration anesthesia. In cases of persistent pulpal pain despite successful mandibular block anesthesia, supplementary infiltration with articaine instead of lidocaine showed a 3.55 times greater likelihood of achieving successful anesthesia. No adverse event incidences were reported in these studies.
RI PT
Commentary and Analysis This research presents a timely update and critical appraisal of our current knowledge evaluating the anesthetic efficacy of articaine versus lidocaine in symptomatic patients. Importantly, it is the first English language systematic review that included only parallel-designed RCTs (evaluating independent samples) with participants diagnosed with symptomatic irreversible pulpitis, while 2 earlier English language systematic reviews (1, 2) included both RCTs and cross-over studies evaluating both patients with pain and volunteers without pain.
SC
The current review is focused on one of the most difficult situations a dentist encounters in daily practice: anesthesizing a tooth with symptomatic irreversible pulpitis.(3) Relief of the often excruciating pain is the first and foremost action a patient expects and the dentist wants to deliver.(4, 5) Achieving fast and reliable profound anesthesia in an acutely painful tooth is a challenge.(6, 7)
M AN U
This well-conducted study provides a thorough review of recently published RCTs, presenting important outcomes and a detailed discussion that contributes to the evidence base supporting daily clinical practice. The review’s evidence supports the use of articaine for patients with symptomatic irreversible pulpitis, in particular as used as supplementary infiltration when pulpal pain persists despite a successful mandibular block anesthesia (defined as lip numbness). Data extraction included risk of bias judgments to inform about heterogeneity of the studies.(8) The random-effects statistical model used allowed the meta-analysis to account for inherent heterogeneity issues. In addition, sensitivity analyses (e.g., excluding 1 study identified as a potential outlier with unclear reporting) confirmed that the overall results of the meta-analysis were not affected.
TE D
This article makes a key contribution to evidence-based dentistry and as such should guide the way readers conduct their clinical practice. Despite the heterogeneity of the studies included, it provides level 1 evidence for the superiority of articaine over lidocaine for specific delivery paths when treating symptomatic irreversible pulpitis teeth.
EP
When used for mandibular block anesthesia alone or for maxillary infiltration, articaine was as effective as lidocaine. Confronted with the continued sensitivity of a mandibular ‘hot’ tooth after a successful mandibular block, dentists are 3.6 times more likely to achieve anesthetic success when using supplementary infiltration with articaine compared to lidocaine. To achieve effective mandibular anesthesia via any route of administration other than inferior alveolar nerve block, the use of articaine is significantly superior to using lidocaine.
AC C
Many general practitioners may not be aware that reports of a low level of safety regarding articaine neurotoxicity were based on retrospective studies with biased data recruitment that showed no scientific evidence demonstrating that 4% articaine solution was neurotoxic or unsafe to use in any aspect of clinical dentistry.(9) The outcomes of this systematic review add to earlier reports on safety data.(1, 2) The additional absence of adverse event incidences in this systematic review of 746 patients confirms that dentists can have confidence in the safe use of articaine for successful dental anesthesia in adults with irreversible pulpitis.
ACCEPTED MANUSCRIPT 4
Kung_spl_RAE - Peters JEBD_V1.docx
Strength of Recommendation Taxonomy (SORT) Grading Level 1
– Good-quality, patient-oriented evidence
STRENGTH OF RECOMMENDATION GRADE:
RI PT
LEVEL OF EVIDENCE:
Grade A – Consistent, good-quality patient-oriented evidence
7. 8. 9.
M AN U
5. 6.
TE D
4.
EP
3.
Katyal V. The efficacy and safety of articaine versus lignocaine in dental treatments: a meta-analysis. J Dent 2010;38:307–17. Brandt RG, Anderson PF, McDonald NJ, et al. The pulpal anesthetic efficacy of articaine versus lidocaine in dentistry: a metaanalysis. J Am Dent Assoc 2011;142:493–504. Wallace JA, Michanowicz AE, Mundell RD, Wilson EG. A pilot study of the clinical problem of regionally anesthetizing the pulp of an acutely inflamed mandibular molar. Oral Surg Oral Med Oral Pathol 1985;59:517–21. Segura-Egea JJ, Cisneros-Cabello R, Llamas-Carreras JM, Velasco-Ortega E. Pain associated with root canal treatment. Int Endod J 2009;42:614–20. Malamed SF. Local anesthetics: dentistry’s most important drugs, clinical update 2006. J Calif Dent Assoc 2006;34:971–6. Fleury AA. Local anesthesia failure in endodontic therapy: the acute inflammation factor. Compendium 1990;11:210. 212, 214 passim. Quint JH. The failure of local anesthesia in acute inflammation. Br Dent J 1981;151:214. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available at: www.cochrane-handbook.org. Accessed August 11, 2015. Yapp KE, Hopcraft MS, Parashos P. Articaine: a review of the literature. Br Dent J 2011;210:323–9.
AC C
1. 2.
SC
References