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Systematic Reviews and Meta-analysis
ARTICLE IN PRESS
doi:
10.25259/JGOH_15_2021

Impact of platelet-rich fibrin on pain after mandibular third molar extraction: A systematic review and meta-analysis

Department of Public Health Dentistry, Tagore Dental College and Hospital, Chennai, Tamil Nadu, India
Department of Oral and Maxillofacial Surgery, Private Practitioner, Chennai, Tamil Nadu, India
Corresponding author: Kumara Raja, Department of Public Health Dentistry, Tagore Dental College and Hospital, Chennai, Tamil Nadu, India. drkumararaja87@gmail.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Raja K, Devi K. Impact of platelet-rich fibrin on pain after mandibular third molar extraction: A systematic review and meta-analysis. J Global Oral Health, doi: 10.25259/JGOH_15_2021

Abstract

Platelet rich fibrin (PRF) is an autologous biomaterial and has many clinical applications. It is produced without the addition of anticoagulant and with no gelling agent, through the immediate centrifugation of blood after collection. The effect of PRF on post-surgical pain is unclear. Thus the aim of this systematic review was to assess whether PRF was effective in controlling pain after the extraction of bilateral mandibular third molars. A comprehensive literature search was performed for articles published from January 2000 to January 2021 in the PubMed, PubMed Central, Directory of Open Access Journals (DOAJ), Campbell systematic review, Scopus, Cochrane review, Embase and Google scholar. Randomized clinical trials with PRF used as one of the comparison groups PRF after extraction and articles assessing pain as an outcomes measure were included for the systematic review. Results should a total of 160 records were found by preliminary screening through database search and 30 records were retrieved by additional sources, of which eleven were selected for qualitative analysis and four for quantitative analysis. A meta-analysis was performed only for pain, due to the considerable heterogeneity among studies for the other outcome variables. The overall quality of evidence was low for all outcomes of included studies. In these studies pain was assessed using a visual analog scale ranging from 0 (no pain) to 10 (most severe pain) point scale. Post-operative pain on day 1, 3 and 7 showed statistically significant difference between the PRF and non - PRF groups. In conclusion PRF administered after third molar extraction significantly reduced pain. But, further randomized control trails with a larger cases and well-designed models are essential to validate the current findings.

Keywords

Mandibular third molar
Pain
Platelet-rich fibrin

INTRODUCTION

Third molar extraction is one of the most common operations in oral and maxillofacial surgery (M3). The literature on M3 removal consequences is vast.[1]

After the third tooth is removed, pain, edema, inflammation, alveolar osteitis (dry socket), and bleeding are all possible post-operative consequences. To prevent post-operative problems, oral and maxillofacial surgeons are continuously working to enhance their surgical technique.[2]

Inflammatory pain is caused by tissue damage and inflammation, neuropathic pain is caused by damage to the central nervous system, and changes in the nervous system’s normal function is caused by changes in the nervous system’s normal function (functional pain).[3] Pain is a key issue that might discourage patients from obtaining dental treatment in clinical settings.[4,5]

The excision of an impacted molar may cause severe agony to the patient. It begins when the anesthetic wears off and peaks on the 1st day following surgery. If a dry socket or infection arises, inflammation can make it more difficult to alleviate postoperative discomfort.[6,7]

This is classified as being of short to moderate duration, with the peak severity occurring during the first 12 h after surgery.[8,9] As a result, oral and maxillofacial surgeons are continuously refining their surgical techniques to reduce post-operative problems.

Using a centrifuge to produce a platelet-rich fibrin (PRF) clot from autogenous whole blood, Dr. Joseph Choukroun of France was the first to discuss the use of PRF in oral and maxillofacial surgery.[10] To accelerate socket repair and reduce post-operative discomfort, he suggested utilizing a platelet concentrate autogenous substance (PRF) in tooth extraction sites.[11] PRF is part of a new class of platelet concentrates that are simple to prepare and do not need biological blood processing. PRF is a kind of autologous tissue that may be employed in a number of therapeutic applications. It is created without anticoagulants or gelling chemicals, and it is made by centrifuging blood just after it is been processed.[11] One of the main benefits of PRF over first-generation platelet concentrate platelet-rich plasma (PRP) is the complex and resilient structure of the fibrin matrix, which stores a considerable number of cytokines inside its structure and releases them slowly during healing (PRP).[12] The fibrin matrix’s particular design, in combination with the leukocyte material it contains, may have a healing impact, lowering surgery-related morbidity. PRF had demonstrated good outcomes in the treatment of bony deformities, maxillary sinus augmentation, dental implant surgery, periodontal tissue engineering, post-extraction socket repair, and third molar surgery.[13] Some researchers have discovered that PRF can help reduce discomfort following mandibular third molar surgery in particular.[14]

The real impact of PRF on post-operative problems, however, is unclear. The goal of this systematic study was to see if PRF was effective in controlling pain after bilateral mandibular third molar extractions. The hypothesis for this review was that applying PRF locally to the extraction site of the lower third molars would minimize post-operative pain.

MATERIALS AND METHODS

The parameters for this systematic review were based on the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis declaration.[15] A detailed protocol was developed prior and was registered in the PROSPERO database (Registration number CRD42020187688).

Multiple electronic databases such as PubMed, PubMed Central, Directory of Open Access Journals (DOAJ), Campbell systematic review, Scopus, Cochrane review, Embase, and Google Scholar were used to conduct a conventional literature search. This review covered all English-language articles that were published between January 2000 and January 2021.

The articles with following criteria were included for the review

  • Randomized and control trails assessing bilateral mandibular third molars impaction requiring surgical extraction

  • Randomized and control trails with at least two comparison groups: One group receiving PRF after extraction and the other group receiving control treatment without PRF after extraction

  • Articles published in the English language

  • Articles assessing pain as an outcomes measure.

The exclusion criteria were as follows

  • Randomized and control trails were PRF placed on maxillary third molars

  • Randomized and control trails without comparison group

  • Letter to editor, case report, personnel proceedings, personal communications, and any types of reviews were excluded from the study

  • Systematic reviews and meta-analysis

  • Studies published in language other than English.

Search strategy

PubMed, PubMed Central, EMBASE, Google Scholar, DOAJ, Scopus, Campbell systematic review, and Cochrane were used to conduct a complete electronic search. The search was conducted using medical subject heading phrases as well as free text words. To identify the relevant papers, researchers used keywords such as platelet-rich plasma, PRF, pain, tooth extraction, mandibular third molar, impaction, and postoperative problems. This evaluation covered studies that were published up through January 2021. The reference lists of the eligible paper as well as review articles were manually searched.

The search for suitable research was conducted until January 30, 2021. During the search process, if any relevant publications were discovered without full text, the respective authors were contacted through email to obtain the article. Duplicate articles were initially eliminated. The study’s titles and abstracts were then evaluated separately by two writers using the eligibility criteria.

Finally, the inclusion and exclusion criteria were applied to the entire text of the articles that were initially included in the study. If the two author’s options differed during the process, they came to an agreement through conversation. The inter examiner reliability was measured using Cohen’s kappa.

Extraction of data

The first author used a data extraction form to obtain data from the included studies, which was then confirmed by consensus with the second author. The following information was gathered from each article: For PRF sample collection, volume of blood drawn and centrifugation parameters such as speed and time were gathered from included studies [Table 1]. For description of included studies: The first author’s surname, the year, the article was published, the location of the study, the mean age or range, the number of participants in the test and control groups, the number of follow-up visits, and the outcome measured. Two authors independently derived these results. Any disagreements were handled between them, and in the end, they came to an agreement [Table 2].

Table 1:: Method of PRF preparation in the included studies.
Author, Year Volume of blood drawn, in ml Centrifugation parameters speed and time
Sybil et al.,[17] 2020 10 ml 3000 rpm for 10 min
Bhujbal et al.,[18] 2020 6 ml 3000 rpm for 10 min
Surekha et al.,[19] 2019 10 ml 3000 rpm for 10 min
Kapse et al.,[20] 2019 10 ml 2700 rpm for 12 min
Singha et al.,[21] 2019 10 ml 3000 rpm for 15 min
Dar et al.,[22] 2018 10 ml 3000 rpm for 12 min
Unakalkar et al.,[23] 2018 NR NR
Gulsen et al,[24] 2017 10 ml 3000 rpm for 10 min
Asutay et al.,[25] 2017 12 ml 2700 rpm for 12 min
Kumar et al.,[26] 2015 5 ml 3000 rpm for 10 min
Ozgul et al.,[27] 2015 10 ml 3000 rpm for 10 min

NR: Not reported, PRF: Platelet-rich fibrin

Table 2:: Characteristics of included studies.
Author, Year Place of study Mean age, (Range) Number of participants Follow-up visits
(Post-operative visits)
Outcome assessed
Test Control
Sybil et al.,[17] 2020 India 32.3 (18–55) 25 25 Pain, tenderness, and edema – 1st, 3rd day, 1 week, and 1 month.
Sensitivity – 1 week, 1, 3, and 6 months.
Area-specific SBI and Plaque Index – 1 week and 1, 3, and 6 months.
Area-specific CAL, probing depth, and radiographic bone height – 3 and 6 months.
Pain, edema, tenderness, sensitivity, SBI, Plaque Index, CAL, probing depth, and bone height
Bhujbal
et al.,[18] 2020
Mean age : 22 20 20 Soft-tissue healing, pain, and swelling – 1st day, 3rd day, and 7th day.
Radiological bone density – 3rd and 6th month.
Soft-tissue healing, pain, and swelling
Surekha
et al.,[19] 2019
15 15 Pain, facial swelling, soft-tissue healing, – 1st, 3rd, and 7th day.
Bone density – 1st and 3rd month.
Pain, facial swelling, soft-tissue healing, and bone density
Kapse
et al.,[20] 2019
India 25.47±0.90 years
18–40
30 30 Pain and swelling – 1, 3, 7, and 14 day.
Bone healing – 8th and 16th post-operative week.
Pain, swelling and bone healing.
Singha
et al.,[21] 2019
Madhya Pradesh, India. 18–30 years 100 100 Pain, Facial measurements, mouth opening, dry socket, and infection – 1st, 3rd, and 7th day.
Wound Dehiscence – 3rd and 7th day
Soft tissue healing – 7th day
Pain, facial measurements, mouth opening, dry socket, infection and wound dehiscence, and soft-tissue healing.
Dar et al.,[22] 2018 Srinagar, Jammu and Kashmir, India. 18–50 60 60 Pain – 1st, 3rd, 7th, and 14th day.
Swelling – 1st, 3rd, 7th, and 14th day
Bone healing – 4th and 12th week
Pain, swelling, periodontal health, and bone healing.
Unakalkar
et al.,[23] 2018
India 18–40 25 25 Pain – 1st, 3rd, 7th, and 14th day.
Trismus – 1st, 3rd, 7th, and 14th day.
Swelling – 1st, 3rd, 7th, and 14th day.
Periodontal health– 8th and 16th week.
Bone healing – 8th and 16th week.
Pain, swelling, trismus, periodontal health, and bone healing.
Gulsen
et al.,[24] 2017
Turkey 17–27 30 30 Edema – 2nd and 7th day.
Pain – 6 h, 12 h. 1st, 2nd, 3rd, and 7th day.
Edema and pain
Asutay
et al.,[25] 2017
Turkey 20.32 years (18–29 years) 30 30 Pain – 6 h, 12 h, and 1, 2, 3, 4, 5, 6, and 7 days after surgery.
Trismus and mouth opening 2nd and 7th Post-operative days.
Pain, trismus, and mouth opening
Kumar
et al.,[26] 2015
India 19–35 years 16 15 Pain, Swelling, and mouth opening – 1st, 1, and 3 month.
Periodontal pocket depth and bone formation – 1 and 3 month.
Pain, swelling, maximum mouth opening, periodontal pocket depth and bone formation.
Ozgul
et al.,[27] 2015
Turkey 18–28 years 56 56 Pain and facial swelling – 1, 3, and 7 day. Pain and facial swelling

CAL: Clinical attachment level, SBI: Sulcus bleeding index

Quality assessment

The studies included in the review were analyzed using the Cochrane collaboration method driven by the Cochrane Handbook for Systematic Intervention Reviews (RevMan, version 5.3 The Cochrane Collaboration, Copenhagen, Denmark).[16] The risk of bias in the studies that were included was rated as “low,” “unclear,” or “high.” Method of sequence creation, allocation sequence concealment, blinding of care providers and participants, blinding of outcome assessors, inadequate outcome data, selective outcome reporting, and other forms of bias were all examined to determine the risk of bias in each research. Any discrepancies between the writers were worked out through communication.

Data analysis

Review manager version 5.3 software was used for performing the analysis.

RESULTS

A first database search yielded 160 entries and further sources yielded 30 more records. Out of the 190 papers, 111 were evaluated for eligibility, with 96 articles failing to fulfill the inclusion criteria and just 11 being included in the review. The flow diagram for the selection of articles included in this study is shown in [Figure 1]. [Table 1] shows method of PRF Preparation for all included studies.[17-27]

Figure 1:: Search strategy.

The overall quality of evidence was low for all outcomes. The risk of bias was evaluated as unclear in most studies, except for selective reporting, because of lack of detail in the reports. The assessments of risk of bias for included studies are given in [Figures 2 and 3]. Only two studies (5/14) described the random sequence generation and allocation concealment while detailed information was deficient in the other nine trials. None of the trials (0/11) described blinding of participants and personnel clearly being judged to be “High” in this domain. The majority of trials (5/11) provided no details related to blinding of outcome assessment and for five (5/11) judged to be “unclear” due to lack of details. Only five trials (5/11) showed low risk of bias for incomplete outcome data according to the reports of the drop-outs or intention-to-treat analysis. Majority of the studies (11/12) had low risk of bias for selective reporting and other bias.

Figure 2:: Review author’s judgment’s about each risk of bias item presented as percentages across all included studies.
Figure 3:: Risk of bias overview for evaluating the judgments of the author on each risk of bias items for each study included. Green stands for a low bias risk, yellow reflects an unknown bias risk, and red suggests a high bias risk.

A total of 260 cases from four RCTs were included in the meta-analysis of pain. In these studies, pain was assessed using a visual analog scale ranging from 0 (no pain) to 10 (most severe pain) point scale. For day-1 post-operative pain, there was statistically significant differences (WMD, −1.05; 95% CI, −1.33 to −0.77; P = 0.00001) between the PRF and non-PRF groups [Figure 4]. Similarly, significant difference was observed for day-3 post-operative pain between the PRF and non-PRF groups (WMD, −1.00; 95% CI, −1.28 to −0.72; P = 0.00001) [Figure 5]. Day-7 also showed significant difference between the PRF and non-PRF groups. (WMD, −0.67; 95% CI, −1.01 to −0.33; P = 0.0001) [Figure 6].

Figure 4:: Forest plot and meta-analysis comparing day-1 post-operative pain for 10 point VAS scale. SD: Standard deviation
Figure 5:: Forest plot and meta-analysis comparing day-3 post-operative pain for 10 point VAS scale. SD: Standard deviation
Figure 6:: Forest plot and meta-analysis comparing day-7 post-operative pain for 10 point VAS scale. SD: Standard deviation

DISCUSSION

PRF stands for platelet concentrates of the second generation. Slow polymerization occurs throughout preparation, resulting in a fibrous protein network that promotes cell motility and proliferation, similar to that observed in natural cells. PRF is widely utilized as a direct graft or in combination with allograft or xenograft in the oral and maxillofacial areas.[28] In addition, without the use of a flap, PRF clots are utilized to repair acute sinus perforations.[29] Socket retention, infrabony flaws, and periodontal issues are among the other indications for PRF usage.[11] The present meta-analysis looked at the influence of PRF on a mandibular third molar in 260 cases from four studies, with the goal of evaluating the effect of PRF on postoperative pain following mandibular third molar surgery.

This might aid the oral and maxillofacial surgeon in giving a better post-operative outcome for his or her patients. Only pain was used as an outcome measure in this meta-analysis. The meta-analysis for these additional factors was not possible due to methodological heterogeneity across the included studies.

The findings of this meta-analysis revealed that when PRF was used, pain was reduced on the 1st, 3rd, and 7th days following surgery, with a statistically significant difference between the PRF and non-PRF groups. These findings point to PRF having a therapeutically positive effect on post-operative pain, as well as confirming the notion that applying PRF following lower third molar extraction reduces post-operative discomfort. Although these findings are encouraging, due to the significant possibility of bias in the studies included, care is advised to avoid misunderstanding of the real data.

Our findings matched those of Xiang et al.,[30] who found that applying PRF locally during the extraction of the lower third molar considerably reduced discomfort on the 3rd post-operative day. Canellas et al.[13] and Al-Hamed et al.[14] both show that PRF has a clinically positive impact on post-operative pain.

A meta-analysis could be performed only for pain. The lack of a meta-analysis for various additional variables, such as edema, trismus, soft-tissue healing, and bone density, was due to the high methodological heterogeneity across the included studies. The randomized procedure and allocation concealment are the most essential components of a clinical trial in terms of risk of bias analysis. Only two of the 11 publications included in this study explained the process for generating the allocation sequence in sufficient depth, as well as the strategy for concealing the allocation sequence. Inadequate allocation concealment can lead to incorrect treatment effect estimates. The current meta-analysis has the following drawbacks: To begin with, the number of research included was limited, potentially reducing statistical power. Second, only studies that used the same measuring scale were considered. Third, only papers published in English were considered. Finally, the length of follow-up in the four trials differed significantly, making it difficult to determine the long-term clinical effects of PRF on the mandibular third molar.

CONCLUSION

Despite the limitations, this study shows that PRF given after third molar extraction considerably reduces discomfort. To corroborate the current findings, more study with larger instances and well-designed models is required.

Declaration of patient consent

Patient’s consent not required as there are no patients in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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