Comparison of Formocresol and Ferric Sulfate Pulpotomy in Primary Molars: A Systematic Review and Meta-analysis
M. Fallahinejad Ghajari 1~, N. Memar Kermani 2, MJ. Kharazi Fard 3, M. Vatanpour 4, 5
1Associate Professor, Department of Pediatric Dentistry, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Postgraduate Student, Department of Pediatric Dentistry, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Statistical Consultant, Dental Research Center, Tehran University of Medical Science, Tehran, Iran
4Assistant Professor, Department of Endodontics, School of Dentistry, Islamic Azad University, Tehran, Iran
5Assistant Professor, Center for Endodontic Research, Tehran, Iran
~ Corresponding author:
M. Fallahinejad Ghajari, De- partment of Pediatric Dentistry, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Received: 6 March 2008 Accepted: 13 August 2008
Abstract:
Objective: Several studies have compared ferric sulfate and formocresol pulpotomy in primary molars. The results of these studies, however, could not be compared due to dif- ferences in evaluated outcomes (clinical, radiographic, or histologic) and follow up dura- tion. The aim of the present study was a systematic review of similar studies and a meta- analysis of their results to provide the latest evidence on the issue.
Materials and Methods: Web-based search was done in EMBASE, Cochrane, Pubmed, Google Scholar, IranMedex, Scientific Citation Index (SCI), and Scopus index databases.
A hand search also was conducted in scientific and research dental journals approved by the Ministry of Health and Medical Education of Iran. Eight randomized clinical trial arti- cles were selected. Clinical success, clinical and radiographic success (total success) rate were assessed as outcome variables. Peto test served for data analysis.
Results: The clinical success of formocresol pulpotomy was comparable to that of ferric sulfate (P=0.574). In addition, the difference between total success rate of the two methods in different studies was insignificant (P=0.42).
Conclusion: No significant difference existed between the total success rate of formocre- sol and ferric sulfate pulpotomy, and ferric sulfate can be an appropriate alternative for formocresol.
Key Words: Tooth, Deciduous; Pulpotomy, formocresol, ferric sulfate; Review [Publica- tion Type]; Meta-Analysis [Publication Type]
Journal of Dentistry, Tehran University of Medical Sciences, Tehran, Iran (2009; Vol. 6, No.1)
INTRODUCTION
The routine treatment for primary molars is pulpotomy [1]. The first material used for pulpotomy contained formaldehyde [2]. Since the introduction of formocresol many studies have been performed on its application and success rate [1,2]. With a reported clinical and radiographic success rate of 70% to 100%, this material still is a gold standard in pulpotomy
[3]. In spite of the high success rate of for- mocresol pulpotomy, probable side effect of this materials have raised some concerns lead- ing to controversial discussions during the re- cent twenty years [4-6]. These concerns are about cytotoxic, carcinogenic and mutagenic effects, as well as sensitivity of immunization system, systemic disorders and changes in the liver and the kidney [3,4,6-9], Radioisotopes
of have been detected even in lungs, skeletal muscles and brain-spinal fluid of animals [9].
Thus, various materials such as corticoster- oids, collagen, glutaraldehyde, ferric sulfate, freeze dried-bone, bone morphogenic protein, osteogenic protein, MTA, and bioactive glass have been suggested as alternatives to for- mocresol [1,9,10]. Some methods such as elec- tro surgery and laser radiation also have been introduced as substitute to pulpotomy [1,9,10].
Several studies have compared ferric sulfate and formocresol pulpotomy in primary molars [3,5,7,10]. The results of these studies, how- ever, could not be compared due to differences in evaluated outcomes (clinical, radiographic, or histologic) and follow up duration. Meta- analysis, which is a systematic and quantita- tive review of similar studies, can be used to draw total conclusions with high statistical power [11].
The aim of the present study was a systematic review of similar studies and a meta-analysis of their results to provide the latest evidence on the issue.
MATERIALS AND METHODS
In this systematic review following web based
data banks were searched: Pubmed (1966- 2007), EMBASE (1984-2007), Scopus (1996- 2007), SCI (1995-2007), IranMedex (2004- 2007), Google Scholar (1996-2007), and Cochrane Library (1999-2007). The keywords have been shown in Table 1. In these searches, no language restriction was applied. A hand search with the same keywords was also con- ducted in scientific and research dental jour- nals approved by Ministry of Health and Medical Education of Iran.
All randomized controlled trials containing keywords shown in Table1, in which the clini- cal and radiographic success rates of for- mocresol and ferric sulfate in primary molars pulpotomy had been compared were selected.
The search was ended on 25 June 2007.
Inclusion and exclusion criteria: Table 2 shows the inclusion and exclusion criteria .Two inde- pendent reviewers assessed all of the selected studies in order to meet the eligibility criteria.
Nine randomized controlled clinical trials met the criteria. Quality assessment of each article was carried out using standard CONSORT form. Name of the first author, year of the publication, mean age of the subjects, clinical and radiographic success criteria (rate), and
Table 1. Search Strategy in Databases.
No Keywords Results
1 Pulpotomy 1674
2 Dental pulp exposure 571
3 Formocresol 340
4 Formocresols 329
5 Ferric Sulfate 261
6 Ferric Sulphate 429
7 3*1 224
8 4*1 201
9 3*2 21
10 4*2 20
11 5*1 29
12 6*1 12
13 5*2 9
14 6*2 1
15 (7 or 9) and (11or 13) 22
16 (7 or 9) and (12 or14) 11
17 (8 or10) and (11 or 13) 20
18 (8 or 10) and (12 or 14) 3
the method of recruitment of each study were inserted in separated sheets. Then the meth- odological soundness of each study was evalu- ated by two independent reviewers based on the Jadad's Scale [12,13]. These two reviewers were blinded to journal and author names.
Then three major questions were asked: were the participants of each study groups random- ized; was the investigation a blind study; and was there a description of withdrawals and dropouts? The first two questions were scored from zero to two and the third question from zero to one. The grades were summed up and considered as the methodological scale of each study.
The result of each study was considered as failure if one or more of the following signs existed: radiolusency of forca, destruction of
periapical bone, pain, inflammation, sinus tract, or fistula, sensitivity to percussion, and external or internal root resorption.
Statistical Analysis: The heterogeneity of re- sults of the studies was assessed using stan- dard chi-square test. The odds ratios and 95%
confidence intervals for each study were calcu- lated. The results were analyzed using Peto Mantel-Haenszel (Peto) method. Classic fail- safe N test and funnel plot served for assess- ment of publication bias.
RESULTS
Based on the defined criteria, eight studies were selected (Table 3).
Clinical Success Rate
The heterogeneity test revealed no heterogene-
Table 2. Inclusion and exclusion criteria in meta-analysis comparing formocresol and ferric sulfate pulpotomy.
Inclusion Criteria
1- All of teeth be primary molar with vital pulp and exposure by trauma or caries 2- At least 6 month follow up
3- Presence of no bone destruction between roots and periapical, no periodontium involvement, no inflation or sinus tract, no widening periodontal ligament, no calcific pulp degeneration, no internal and external resorption, no pathologic sub-luxation, and no night pain.
4- Tooth should be restorable with amalgam or SCC.
5- Evaluation of results by clinical and radiographic observation
6- Comparison of results on the base of a standard definition of success or failure.
Exclusion criteria
1- Non randomized sample for formocresol or sulfate ferric treatment.
2- In vitro studies or retreatment.
3- Studies without comparison of formocresol and ferric sulfate pulpotomy.
4- Studies comparing formocresol or sulfate ferric pulpotomy with other methods.
5- Different method of treatment 6- Unavailability of relative article.
Table 3. Summery of include studies in meta analysis study comparing formocresol and ferric sulfate pulpotomy.
Study Sample Size Follow up Points Jaddad's Scale
Huth et al 2005 100 6,12,18,24 months 5
Fei et al 1991 56 3,6,12 months 3
Haghgou et al 2005 60 3,6,12 months 3
Bahrololoumi et al 2005 69 3,6,9 months 2
Marcovic etal 2005 71 18 months 2
Fuks et al 1997 92 6-34 months 2
Nakhjavani et al 2004 43 3,6,9,12 months 2
Ibricevic et al 2000 70 3-20 months 2
ity among the studies (P=0.9). Then Peto test (fixed effect model) was used to aggregate the results of different comparisons. This test showed no significant differences between formocresol and ferric sulfate pulpotomy (OR=0.82, P=0.62) (Fig 1). Classic fail-safe N
test and funnel plot showed that no publication bias existed among these studies (P=0.73) (Fig 2).
Radiographic Success Rate
Since no heterogeneity regarding radiographic
Fig 1. Funnel plot of included studies in meta analysis study comparing formocresol and ferric sulfate pulpotomy for assessment of publication bias (clinical success rate)
Fig 2. Forest plot of different comparisons between Formocresol and Ferric sulfate (clinical success rate) in meta
-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0
0
1
2
3
4
5
6
Standard Error
Log odds ratio
Study name Subgroup within study Statistics for each study Odds ratio and 95% CI
Odds Lower Upper
ratio limit limit Z-Value p-Value Bahrololoumi etal 2005 clinical 3 months 1.000 0.000 38706.731 -0.000 1.000 Bahrololoumi etal 2005 clinical 6 months 1.000 0.000 38706.731 -0.000 1.000 Bahrololoumi etal 2005 clinical 9 months 1.000 0.000 38706.731 -0.000 1.000 Fei etal 1991 clinical 12 months 0.929 0.055 15.621 0.051- 0.959 Fei etal 1991 clinical 3 months 0.663 0.134 3.282 0.503- 0.615 Fei etal 1991 clinical 6 months 0.593 0.091 3.852 0.548- 0.584 Huth etal 2005 clinical 12 months 1.000 0.000 6464.001 0.000 1.000 Huth etal 2005 clinical 18 months 0.548 0.048 6.262 0.484- 0.628 Iricevic etal 2000 clinical 3-20 months 1.000 0.000 35844.319 0.000 1.000 Marcovic etal 2005 clinical 18 months 1.209 0.253 5.774 0.238 0.812 Haghgou etal 2005 clinical 3 months 0.322 0.013 8.235 0.685- 0.494 Haghgou etal 2005 clinical 6 months 2.077 0.177 24.313 0.582 0.560 Haghgou etal 2005 clinical12 months 1.000 0.000 123593.812 0.000 1.000 0.823 0.382 1.774 0.496- 0.620
0.01 0.1 1 10 100
Favours A Favours B
success rate existed between included studies (P=0.83), Peto fixed effect model was used to pool the data from different studies. This test showed no significant differences between ra- diographic success rate of the two comparison groups (OR=1.48, P=0.11) (Fig 3). Classic
fail-safe N test showed no publication bias (P=0.17), and funnel plot confirmed this find- ing graphically (Fig 4).
Total Success Rate
To aggregate different data from included
Fig 3. Funnel plot of included studies in meta analysis study comparing formocresol and ferric sulfate pulpotomy, for assessment of publication bias (radiographic success rate).
-5 -4 -3 -2 -1 0 1 2 3 4 5
0
2
4
6
8
10
Standard Error
Log odds ratio
Study name Subgroup within study Statistics for each study Odds ratio and 95% CI Odds Lower Upper
ratio limit limit Z-Value p-Value Fei et al 1991 total 3 months 0.267 0.026 2.764 1.108- 0.268 Fei etal 1991 total 12 months 0.125 0.014 1.118 1.860- 0.063 Fei etal 1991 total 6 months 0.192 0.020 1.857 1.425- 0.154 Huth etal 2005 total 12 months 3.907 0.770 19.831 1.644 0.100 Huth etal 2005 total 24 months 0.089 0.005 1.657 1.622- 0.105 Huth etal 2005 total 6 months 1.000 0.000 6464.001 0.000 1.000 Nakhjavani etal 2004 total 12 months 1.156 0.300 4.450 0.210 0.833 Nakhjavani etal 2004 total 3 months 3.582 0.368 34.872 1.099 0.272 Nakhjavani etal 2004 total 6 months 1.254 0.297 5.290 0.308 0.758 Nakhjavani etal 2004 total 9 months 1.156 0.300 4.450 0.210 0.833 0.918 0.509 1.656 0.286- 0.775
0.01 0.1 1 10 100
Favours A Favours B
studies Peto fixed effect model was used due to absence of heterogeneity among these stud- ies (P=0.6). This test revealed no significant differences between the two comparison groups (P=0.77, OR=0.98) (Fig 5). There was
no publication bias among different studies (P value of classic fail-safe N test=0.28) (Fig 6).
DISCUSSION
Ferric Sulfate generates plug by agglutination
Fig 5. Forest plot of different comparisons between Formocresol and Ferric sulfate (total success rate) in meta- Fig 6. Funnel plot of included studies in meta-analysis study comparing formocresol and ferric sulfate pulpotomy, for assessment of publication bias (total success rate).
-3 -2 -1 0 1 2 3
0
1
2
3
4
5
Standard Error
Log odds ratio
Study name Subgroup within study Statistics for each study Odds ratio and 95% CI
Odds Lower Upper
ratio limit limit Z-Value p-Value Bahrololoumi etal 2005 radiographic 3 months 2.951 0.288 30.245 0.911 0.362 Bahrololoumi etal 2005 radiographic 6 months 7.476 0.922 60.600 1.884 0.060 Bahrololoumi etal 2005 radiographic 9 months 7.563 0.963 59.419 1.924 0.054
Fei etal 1991 radiographic 12 months 0.157 0.017 1.445 1.635- 0.102
Fei etal 1991 radiographic 3 months 0.114 0.013 1.007 1.954- 0.051
Fei etal 1991 radiographic 6 months 0.192 0.020 1.857 1.425- 0.154
Fuks etal 1997 radiographic 6-34 months 0.893 0.188 4.243 0.142- 0.887
Huth etal 2005 radiographic 12 months 3.907 0.770 19.831 1.644 0.100
Huth etal 2005 radiographic 6 months 1.000 0.000 6464.001 0.000 1.000
Iricevic etal 2000 radiographic 3-20 months 1.000 0.058 17.116 0.000 1.000 Marcovic etal 2005 radiographic 18 months 1.300 0.374 4.522 0.413 0.680 Nakhjavani etal 2004 radiographic 12 months 2.198 0.483 9.995 1.019 0.308 Nakhjavani etal 2004 radiographic 3 months 3.582 0.368 34.872 1.099 0.272 Nakhjavani etal 2004 radiographic 6 months 1.776 0.381 8.291 0.731 0.465 Nakhjavani etal 2004 radiographic 9 months 1.776 0.381 8.291 0.731 0.465 Haghgou etal 2005 radiographic 3 months 0.028 0.000 2786.270 0.607- 0.544 Haghgou etal 2005 radiographic 6 months 77.509 0.001 10392112.715 0.722 0.470 Haghgou etal 2005 radiographic 9 months 1.000 0.000 15760345.787 0.000 1.000
1.482 0.916 2.397 1.601 0.109
0.01 0.1 1 10 100
Favours A Favours B
of blood protein that seals blood Capillary and it is applied in primary molars pulpotomy [1,7]. In this meta-analysis study, comparison of clinical and radiographic success of primary molars pulpotomy with Formocresol and Fer- ric Sulfate was done.
Some controversies on considering internal root resorption as pulpotomy failure existed in different studies. For example, in Fuks et al [14] study internal root resorption was consid- ered as normal because no change appeared after 34 months. Bahrololoomi et al [15] sug- gested that internal root resorption have no effect on other teeth development and it should not be considered as radiographic failure. In other studies, however, the internal root re- sorption has been considered as failure [1].
Thus, it was defined as failure in this meta- analysis. In Markovic et al study [16] dentine bridge formation on pulp was observed in 40.5% of ferric sulfate pulpotomies but not in formocresol pulpotomies.
In Baradaran Nakhjavani et al study [17] on ferric sulfate pulpotomy in previously resorbed areas there was 12.5% hard tissue formation indicating pulp vitality. In Fuks et al study [14], pulp canal obliteration with dentine ap- position by odontoblast-like cells considered as success because it is an indicator of protec- tion of pulp vitality. Fei et al [18] suggested 18% and 44% success rates for ferric sulfate and formocresol pulpotomy respectively.
The method of sample size calculation was not pointed out in studies except in Huth et al [19]
using PS method (power and sample size cal- culation program, version 2.1.31, Dupont and Plummer). While a small sample size offers low statistical power, the high number of sam- ples leads to some difficulties in follow up.
The other important point is randomization and its method.
Fei et al [18] has used random numeric table and Huth et al [19] has used block randomiza- tion. In other studies, however, the randomiza- tion method has not been reported clearly
[18,19]. Another problem is the blindness of pulpotomy assessors in follow up. Fei et al [18], Huth et al [19] and Haghgoo [20] have reported blinding but in Fuks et al [14], Bara- daran Nakhjavani et al [17], and Ibricevic and al-Jame [1] blinding has not been mentioned.
In Bahrololoomi et al study [15] also it was not obvious that assessors are those perform- ing pulpotomies or not.
To assure validity and reliability of study, the rate of dropout must be less than 10% of total sample. Dropout can happen because of vari- ous reasons but for children, it is mostly exfo- liation of primary teeth. Usually longer terms of follow up causes lower rates of success.
This may explain 100% clinical success rate in Probably for this reason in Fei et al [18] study (12 months follow up) and Bahrololoomi et al study [15] (9 months follow up). In none of the studies with long-term follow up 100% clinical success was observed except for Ibricevic and al-Jame study [1] in which after 20 months follow up, clinical success was 100% but ra- diographic success was 97.2% [1]. Thus, long term follow up such as study by Huth et al [19]
(24 months) and Fuks et al [14] (34 months) provide more validity and reliability [14,19].
Due to various follow up durations in different studies, only the first time of follow up was used for analysis, which led to elimination of the data of some samples.
CONCLUSION
Clinical success rate of vital primary molar pulpotomy with formocresol was significantly lower than ferric sulfate but no significant dif- ference existed between the total success rate (clinical and radiographic) of formocresol and ferric sulfate pulpotomy, and ferric sulfate can be an appropriate alternative for formocresol.
ACKNOWLEDGMENTS
The authors are extremely grateful for the sup- port of Dr.SJ Ghazi Mirsaeid in the preparing of full text of some articles.
REFERENCES
1- Ibricevic H, al-Jame Q. Ferric sulfate as pulpo- tomy agent in primary teeth: twenty month clinical follow-up. J Clin Pediatr Dent 2000 Summer;
24(4):269-72.
2- Antar F, Bacho R, Abi Hatem G, Ghosn Z. Is formocresol still the medication of choice for pulpotomies in primary teeth? A literature review.
Lebanon Journal of Dental Medicine 2004;3:53.
3- Cotes O, Boj JR, Canalda C, Carreras M. Pulpal tissue reaction to formocresol vs. ferric sulfate in pulpotomized rat teeth. J Clin Pediatr Dent 1997 Spring;21(3):247-53.
4- Casas MJ, Layug MA, Kenny DJ, Johnston DH, Judd PL. Two-year outcomes of primary molar ferric sulfate pulpotomy and root canal therapy.
Pediatr Dent 2003 Mar-Apr;25(2):97-102.
5- Vargas KG, Packham B. Radiographic success of ferric sulfate and formocresol pulpotomies in relation to early exfoliation. Pediatr Dent 2005 May-Jun;27(3):233-7.
6- Casas MJ, Kenny DJ, Judd PL, Johnston DH. Do we still need formocresol in pediatric dentistry? J Can Dent Assoc 2005 Nov;71(10):749-51.
7- Fuks AB, Eidelman E, Cleaton-Jones P, Micha- eli Y. Pulp response to ferric sulfate, diluted for- mocresol and IRM in pulpotomized primary ba- boon teeth. ASDC J Dent Child 1997 Jul-Aug;
64(4):254-9.
8- Smith NL, Seale NS, Nunn ME. Ferric sulfate pulpotomy in primary molars: a retrospective study. Pediatr Dent 2000 May-Jun;22(3):192-9.
9- Hunter ML, Hunter B. Vital pulpotomy in the primary dentition: attitudes and practices of Spe- cialists in Paediatric Dentistry practising in the United Kingdom. Int J Paediatr Dent 2003 Jul;
13(4):246-50.
10- Salako N, Joseph B, Ritwik P, Salonen J, John P, Junaid TA. Comparison of bioactive glass, min- eral trioxide aggregate, ferric sulfate, and for- mocresol as pulpotomy agents in rat molar. Dent Traumatol 2003 Dec;19(6):314-20.
11- Fallahzadeh H, MoeintaghaviA, Foruzanmehr
M. Clinical comparison of Persica and Chlorhexi- dine mouthrinses using meta-analysis technique.
Journal of Islamic Dental Association of Iran 2006 spring;18(1):62-72.
12- Torabinejad M, Bahjri K. Essential elements of evidenced-based endodontics: steps involved in conducting clinical research. J Endod 2005 Aug;
31(8):563-9.
13- Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996 Feb;
17(1):1-12.
14- Fuks AB, Holan G, Davis JM, Eidelman E. Fer- ric sulfate versus dilute formocresol in pulpoto- mized primary molars: long-term follow up. Pedi- atr Dent 1997 Jul-Aug;19(5):327-30.
15- Bahrololoomi Z, Ghodrati AR, Ghane G. Clini- cal and radiographic comparison of primary molars after pulpotomy with formocresol and ferric- sulfate. Journal of Shahid Sadoughi University of Medical Sciences 2005 Spring;13(2):81-5.
16- Markovic D, Zivojinovic V, Vucetic M.
Evaluation of three pulpotomy medicaments in primary teeth. Eur J Paediatr Dent 2005 Sep;6(3):
133-8.
17- Baradaran Nakhjavani Y, Mighani Gh, Akha- van M. A survey on clinical and radiographic changes of pulpotomy using ferosulfate and for- mocresol in primary molars. Journal of Dental Medicine Summer;2004:17(2):53-61.
18- Fei AL, Udin RD, Johnson R. A clinical study of ferric sulfate as a pulpotomy agent in primary teeth. Pediatr Dent 1991 Nov-Dec;13(6):327-32.
19- Huth KC, Paschos E, Hajek-Al-Khatar N, Hollweck R, Crispin A, Hickel R, et al. Effective- ness of 4 pulpotomy techniques--randomized con- trolled trial. J Dent Res 2005 Dec;84(12):1144-8.
20- Haghgoo R. Clinical and radiographic Com- parison of ferric sulfate and formocresol pulpo- tomy technique in teeth. Dental Journal of Shahid Beheshti University of Medical Science 2005 Summer;23(2):249-55.
