Effectiveness of hyperbaric oxygen therapy in irradiated maxillofacial dental implant patients: A systematic review with meta-analysis.

The significantly higher implant failure rates in maxillofacial patients, undergoing radiotherapy, might be caused by the long-term effects of reduced vascularization compromising the implantation site. An extensive preclinical animal literature and a multitude of clinical reports suggest the use of hyperbaric oxygen (HBO) therapy as it can improve the tissue vascularity. Hence, it may increase the implant survival rate by enhancing osseointegration process in such patients. The objective of this systematic review was to investigate the effectiveness of HBO therapy on dental implant survival rate in irradiated maxillofacial patients who require prosthodontic rehabilitation. An electronic search without time restrictions was undertaken in April 2016 using databases: PubMed, Google Scholar, and the Cochrane Oral Health Group Trials Register. We also tried to contact the manufacturers and researchers in the field for necessary details. Clinical human studies, on irradiated maxillofacial dental implant patients, including randomized controlled trials (RCTs), prospective controlled trials, retrospective studies, and preliminary reports were included in the study. Data collection was carried out by two of the authors' independently. The titles and abstracts of all reports were screened for the study design and type of reported intervention; all the duplicates were removed. The data search yielded 62 titles, out of which 14 articles were selected for the study by the article filtration criteria: Title/abstract/full text. Data which were extracted by two authors with any disagreement were resolved by the third author, and a meta-analysis was done using binary random-effect model. The results show decreased implant failure rate in HBO group (9.21%) compared to non-HBO group (22.44%). The potential limitations of this study are amount of radiation doses used, period lasting from radiotherapy to the placement of the implants, and follow-up period which varies for every subject of the included study, which can affect the treatment outcome. Although there are many sensitive articles published about HBO, including a number of review papers, RCTs are still lacking. According to the statistical analysis, it can be concluded that preventive HBO therapy can reduce the risk of implant failures in irradiated patients by 1.21 (relative risk) with 95% confidence interval (P < 0.001). Hence, HBO can be the effective treatment protocol for the implant treatment in irradiated maxillofacial patients.

INTRODUCTION

Description of the condition

Thorough knowledge and wide field of understanding of the etiologic and risk factors of the implant failure are necessary to decrease the implant failure rates. From the last few years, implants are more commonly used in maxillofacial oral cancer patients, so whether these irradiated patient in the head and neck region are more at risk of losing dental implants or not is still unclear. Reduced tissue healing capacity leads to osteoradionecrosis, necrotic bone exposure, and pathological fracture in response to tissue trauma; thus, with reduced healing ability and osteoradionecrosis in response to injury, the implant survival rate may be reduced for the maxillofacial oral cancer patients who have undergone radiotherapy treatment.[123456]

Description of the intervention

Hyperbaric oxygen (HBO) therapy and its effectiveness is still a controversial topic.[7] There are numerous studies reported for the usefulness of HBO for the treatment of osteoradionecrosis of different bone tissues. In addition to its usefulness in treating osteoradionecrosis, it may also prevent this condition. A randomized/prospective clinical trial using HBO and penicillin was carried out by Marx et al.[8] This trial demonstrated that HBO reduced the development of osteoradionecrosis after tooth removal and this reduction was statistically significant.[9]

HBO therapy can be performed in multiplace or monoplace chambers. Patient is kept in a pure 100% oxygen chamber under pressure of 1.5–3 atmosphere absolute.[10]

How the intervention might work?

HBO therapy increases the oxygen pressure, collagen production, and fibroblastic activity and creates a matrix for neovascularizations.[11] According to Johnsson, it also counteracts the negative effect of irradiation, stimulates the osseointegration, and improves the implant survival rate.[12]

Need to do this systematic review

This systematic review helps maxillofacial surgeon and prosthodontist to understand the evidence, to integrate the valid information, and to provide rational decision-making on the use of the HBO therapy for their patients. It will also help them in improving the dental implant survival rate and quality of life of such patients by providing long-term successful rehabilitation.

OBJECTIVE

The objective of the present review was to compare the implant failure rates for patients being irradiated or previously irradiated in the head and neck region and receiving HBO therapy versus irradiated patients and not receiving such therapy having follow up period of 1-2 years to 26 years.

MATERIALS AND METHODS

Criteria for considering studies for this review

Types of studies

Randomized controlled trials (RCTs), prospective clinical trials, and retrospective studies.

Types of participants

Maxillofacial patients who have had radiotherapy and treated with dental implants for oral rehabilitation.

Types of intervention

HBO therapy compared with no HBO therapy.

Type of comparison

HBO group versus non-HBO group.

Types of outcome measures

Implant failure rates.

SEARCH STRATEGIES

An electronic search without time restrictions was undertaken in April 2016 for clinical studies comparing the implant failure rates (O), in irradiated maxillofacial patients (P), undergoing dental implant treatment either with additional HBO therapy (I) or without HBO therapy (C), using following databases: PubMed, Google Scholar, and the Cochrane Oral Health Group Trials Register. The search strategy used a combination of controlled vocabulary and free text terms.

Following keywords were used in the search box of all three databases either alone or in combination with two or more keywords (i.e., #1, #2, #3, or #1, #2, #3, #5) in an attempt not to miss any related trial, eligible to get included in the study.

Dental implants or oral implants or endosseous implants or osseointegrated implants

Radiation therapy or radiotherapy or irradiation or irradiated tissues

Hyperbaric oxygen or hyperbaric oxygen therapy or HBO therapy or hyperbaric oxygenation

Dental implant failures and/or randomized controlled trials

HBO therapy and experimental trials

Irradiation, dental implants, HBO therapy, randomized controlled trials, experimental trials (Word variations had been used, i.e., radiotherapy for irradiation).

A manual search of dental implant-related journals, reference list of the identified studies, and relevant reviews on the subject was also scanned for possible additional studies. Moreover, online databases providing information about clinical trials in progress were also checked (clinicaltrials.gov; www.centerwatch.com/clinicaltrials; www.clinicalconnection.com; www.cochranelibrary.com).

Data collection and analysis

Selection of studies

The review process consisted of two phases. In the first phase, titles and abstracts of the search were initially screened by two authors for relevance and the full text of relevant abstract was obtained and accessed. Any disagreement was solved by discussion and with the third author's suggestion. The hand search of selected journals as well as search of reference of the selected studies was also done. The articles were obtained after first step of the review process using the following inclusion and exclusion criteria and were screened in the second phase, and relevant and suitable articles were isolated for further processing and data extraction. Duplicates and articles with insufficient necessary data were excluded.

Inclusion criteria's

Clinical human studies, on irradiated maxillofacial dental implant patients, including:

RCTs

Prospective study

Retrospective study

Preliminary reports.

Exclusion criteria's

Case reports

Technical reports

Animal studies

In vitro studies

Review articles

<5 patients treated.

In general, RCTs constitute the highest level of evidence. Although developing recommendations based on the highest level of evidence is desirable, adequate number of RCTs is not always available. Hence, we included some prospective and retrospective clinical studies with a preliminary report (Ali et al., 1997). The purpose of the report was to provide some preliminary data collected from a long-term, prospective investigation on the effects of HBO therapy on implant integration in the irradiated jaw. Data on the effects of various doses of irradiation to the perioral region were collected by regular clinical, radiologic, and histologic examinations.

Data extraction and management

Three review authors independently extracted data from the studies using standardized selection criteria, developed for this review. We tried to contact the authors of primary studies to request further information when data were missing or incomplete. Review authors resolved all differences by discussion. Data were excluded until further clarification became available if agreement could not be reached.

For each trial, the following data were recorded.

Year of publication and country of origin

Details of the participants including demographic characteristics and criteria for inclusion

Details of the type of intervention

Details of the outcomes reported including method of assessment and time intervals.

Assessment of “risk of bias” in the included study

The assessment of the risk bias was conducted using the recommended approach by Cochrane reviews [Table 1 and Graph 1] and was completed independently and in duplicate by two review authors as a part of the data extraction process.

Table 1

Assessment of “risk of bias” in the trials included in the meta-analysis

Graph 1

The assessment of the risk of bias of the included studies

Results of the search for data collection

The database search yielded 62 titles, out of which 22 titles were discarded by title evaluation. Abstracts evaluation was done for the remaining 40 articles, and 6 articles were discarded on the basis of inclusion and exclusion criteria. Full-text data were obtained for the remaining 34 articles, among which 8 articles were discarded due to insufficient data and 12 articles did not match the criteria of the study. Hence, finally, 14 articles were selected for the study [Flowchart 1].

Flowchart 1

Results of the search through various sources

Description of the included studies

The data obtained after the search strategy were tabulated and statistically analyzed. The results were as follows:

Table 2 shows the required details, regarding the 14 selected studies, included in this systematic review

Table 2

Summarized data

Table 3 shows the evidence level of the selected articles according to the study design

Table 3

Evidence level of selected articles

Table 4 shows the characteristics of the each included study.

Table 4

Characteristics of included studies

Description of the excluded studies (with the reason for being excluded)

Table 5 shows the characteristics of the excluded studies.

Table 5

Characteristics of excluded studies

Risk of bias assessment

Table 1 shows the assessment of the risk of bias of the included studies.

Graph 1 shows the assessment of the risk of bias of the included studies.

Effects of intervention and statistical analysis

Effect of intervention was studied for all 14 selected studies, and the implant survival rate for each group was statistically calculated [Tables 2 and 4].

Results of the study

Experimental studies

Table 6 shows estimated values for implant failures in HBO(+) group for an experimental study when the P value is set at P < 0.05, with the confidence interval (CI) of 95%.

Table 6

Estimated values for implant failures in hyperbaric oxygen(+) group for an experimental study when the P value is set at P<0.05, with the confidence interval of 95%

Table 7 shows estimated values for implant failures in non-HBO(+) group for an experimental study when the P value is set at P < 0.05, with the CI of 95%.

Table 7

Estimated values for implant failures in nonhyperbaric oxygen(+) group for an experimental study when the P value is set at P<0.05, with the confidence interval of 95%

Forest Plot 1 shows implant failures in HBO and non-HBO group for experimental studies.

Forest Plot 1

Experimental studies: Implant failures in hyperbaric oxygen versus nonhyperbaric oxygen group

Prospective studies

Table 8 shows estimated values for implant failures in HBO(−) group for three prospective studies when the same P value is set at P < 0.05, with the same CI of 95%.

Table 8

Estimated values for implant failures in hyperbaric oxygen(−) group for prospective studies when the same P value is set at P<0.05, with the same confidence interval of 95%

Table 9 shows estimated values for implant failures in non-HBO(−) group for 3 prospective studies when the P value is set at P < 0.05, with the same CI of 95%.

Table 9

Estimated values for implant failures in nonhyperbaric oxygen(−) group for 3 prospective studies when the P value is set at P<0.05, with the same confidence interval of 95%

Forest Plot 2 shows implant failures in HBO and non-HBO group for prospective studies.

Forest Plot 2

Prospective studies: Implant failures in hyperbaric oxygen versus nonhyperbaric oxygen group

Retrospective studies

Table 10 shows estimated values for implant failures in HBO(−) group for four retrospective studies when the same P value is set at P < 0.05, with the same CI of 95%.

Table 10

Estimated values for implant failures in hyperbaric oxygen(−) group for 4 retrospective studies when the same P value is set at P<0.05, with the same confidence interval of 95%

Table 11 shows estimated values for implant failures in non-HBO(−) group for seven retrospective studies when the same P value is set at P < 0.05, with the same CI of 95%.

Table 11

Estimated values for implant failures in nonhyperbaric oxygen(−) group for 7 retrospective studies when the same P value is set at P<0.05, with the same confidence interval of 95%

Forest Plot 3 shows implant failures in HBO and non-HBO group for retrospective studies.

Forest Plot 3

Retrospective studies: Implant failures in hyperbaric oxygen versus nonhyperbaric oxygen group

Table 12 represents “Pearson's Chi-square test” which shows the total number of implants placed, failed, and survived in both the groups, with P < 0.001, which shows that significant difference exists between both the group regarding the number of implants failed and survived.

Table 12

Represents “Pearson's Chi-square test” which shows the total number of implants placed, failed, and survived in both the groups, with P<0.001, which shows that significant difference exists between both the groups regarding the number of implants failed and survived

Graph 2 shows the significant difference regarding the implant failure rate in both the groups:

Graph 2

The significant difference regarding the implant failure rate in both the groups

Implant failure rate (%) in HBO(+) group: 9.21%

Implant failure rate (%) in non-HBO(−) group: 22.44%

SUMMARY

The present systematic review was undertaken to compare the implant failure rates for patients being irradiated in the head and neck region and receiving HBO therapy versus non-HBO therapy. There are many scientific papers[27] written about this subject including a number of review articles, but only one RCT (Schoen et al. 2007) including a limited number of participants was found for this review.

CONCLUSION

According to above statistical analysis, results show that preventive HBO therapy can reduce the risk of implant failures in irradiated patients, may be due to improved vascularity which leads to reduced risk of radiation-induced damages to tissue, and thus, HBO can be the effective treatment protocol, while planning for the implant treatment in irradiated maxillofacial patients. Still, some important factors, other than irradiation, that affect the implant survival rate in irradiated bone were type of implant, surgical procedures used, time interval between radiotherapy and implant placement, and radiation dose, which were not included in the meta-analysis, due to insufficient data.

Hence, further research work has to be done to specify above-mentioned various reasons of failures and various factors affecting the success and failure rates of dental implants in irradiated maxillofacial patients.

There is a definite need for more RCTs to ascertain the effectiveness of HBO in irradiated maxillofacial dental implant patients. These trials ought to be of a high quality and reported as recommended by the consort statement (www.consort-statement.org/). Each clinical center may have limited numbers of patients and it is likely that multicentered trials will be needed. Only with that clinicians will receive the evidence they need for their study and make the best treatment decisions possible.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.