Treatment Delay Impact on Open Reduction Internal Fixation of Mandibular Fractures: A Systematic Review.

BACKGROUND: The impact of mandible fracture treatment delay has been contested in the literature for decades, with conventional wisdom favoring earlier surgical treatment to prevent postoperative complications, primarily infection. Through a systematic review of all available evidence, this study aims to determine whether delay to open reduction and internal fixation of traumatic mandibular fractures influences outcomes.
METHODS: MEDLINE, EMBASE, CINAHL, and Web of Science were systematically searched for English language literature pertaining to the above research question and screened in duplicate. Methodological quality scoring was performed using MINORS criteria. Qualitative and quantitative findings from relevant studies are presented.
RESULTS: Twenty eligible studies including 2,671 patients had open reduction internal fixation, with or without adjunct mandibulomaxillary fixation. All studies were observational cohort or case-control studies of low methodological quality with a mean MINORS score of 6.5 of 16 (40.6%) for noncomparative studies and 11.2 of 24 (46.7%) for comparative studies. Only 5 of 20 (25%) studies recommended earlier treatment. Due to insufficient reporting of data and study heterogeneity, the impact of treatment delay on complications could not be quantitatively analyzed.
CONCLUSIONS: There is substantial heterogeneity and no consensus on the definition of "early" versus "delayed" surgical treatment for patients with traumatic mandibular fractures. The majority of included studies do not make a recommendation for earlier treatment. Future, well-designed prospective studies are essential to determine if there is an optimal surgical treatment delay of mandibular fractures that mitigates the risk of infectious and noninfectious complications.

INTRODUCTION

Although closed reduction of mandible fractures via mandibulomaxillary fixation (MMF) has therapeutic value, open reduction internal fixation (ORIF) has become the standard of care for achieving anatomic reduction for a wide variety of mandibular fractures, including condylar head fractures.[1] However, mandible ORIF is considered to have a higher risk of postoperative infectious complications, as compared with MMF,[2-5] given the introduction of hardware in a grossly contaminated oral cavity. Intuitively, earlier ORIF should reduce the open fracture contamination exposure, though delayed ORIF allows for soft-tissue edema to subside and wound closure under reduced tension, which may theoretically decrease the risk of subsequent wound dehiscence and hardware exposure.

Early expert opinion suggested that ORIF for mandibular fractures should be performed within 6 hours of injury to reduce complication rates.[6] This time threshold was later extended to 24 hours,[7] and by the 1990s to within 48–72 hours.[8] To date, there remains no consensus on the optimal ORIF treatment delay or whether delayed treatment increases complication rates. At our center, this poses a scheduling challenge for booking mandible ORIF cases as a “Priority 2” (to be completed within 24 hours), or a “Priority 3” (to be completed within 72 hours).

Previous reviews have addressed, at least in part, the topic of mandible fracture ORIF treatment delay.[9-11] However, earlier reviews analyzed heterogeneous populations of patients with various facial fractures,[9-11] included patients treated exclusively with closed surgical techniques,[9-11] and were either outdated,[9] or not truly systematic in nature.[10,11] This study is the first systematic review to focus specifically on patients with mandible fractures receiving ORIF and includes several studies not analyzed in the aforementioned reviews.

The primary research question of this systematic review is: in patients with traumatic mandible fractures, does “early” compared with “delayed” ORIF impact postoperative complications, primarily infection?

METHODS

Search Strategy and Study Screening

The search strategy was designed based on our research question that was formulated a priori using a “Population, Intervention, Comparison, Outcome, Timing” (PICOT)[12] format (Table 1). The inclusion/exclusion criteria were also determined a priori (Table 2).

Table 1.

PICOT Research Question

Table 2.

Inclusion and Exclusion Criteria

The online databases Medline, Embase, CINAHL, and Web of Science were searched from inception until December 22, 2016. All database searches utilized wildcard truncation, synonyms, and MeSH terms for the following search terms: “mandible,” “fracture,” “complications,” “time factors,” and “surgery.” The Cochrane Central Register of Controlled Trials[13] and clinicaltrials.gov[14] were searched for any relevant published or unpublished studies. References of relevant studies and previously published reviews were also searched. This systematic review was registered in PROSPERO.[15]

Titles, abstracts, and full text studies were screened in duplicate by 2 reviewers (N.S., A.C.). Discussion took place to address any disagreements about study inclusion or exclusion, and if needed, the senior author (M.J.C.) resolved any uncertainties.

Data Abstraction

Data were extracted into a Microsoft Excel spreadsheet (2011 release; Microsoft, Redmond, WA) and included study characteristics, patient demographics, time factors, fracture location, mechanism of injury, and postoperative complications. Studies that grouped patients as cases (presence of postoperative complication) and controls (absence of postoperative complications) and reported treatment delay data (ie, time from injury to mandible ORIF) in each group were classified as case-control studies,[16] whereas studies that grouped the patients by treatment delay and reported postoperative complication data in each group were classified as cohort studies.

ORIF-specific patient data were extracted wherever possible if stratification allowed to maximize data inclusion.[8] Studies that did not stratify for patients receiving MMF without ORIF were excluded from this systematic review to maintain population homogeneity.[4,17-24] Mandible fracture location and complication data were recorded based on number of patients (n) with a fracture in a given region of the mandible, or if not reported, then the number of fractures (N) reported for a given mandibular region.

Data Analysis

Due to study heterogeneity and inadequate reporting of data, quantitative synthesis of the data into a meta-analysis was not feasible. Instead, descriptive statistics such as weighted means and proportions were calculated for the baseline characteristics data if reported by an acceptable number of studies. Data reported in terms of number of fractures were not used in our quantitative analysis to avoid overrepresentation of outcomes such as complications, which were not necessarily independent for each mandible fracture (eg, a patient with a trifocal mandibular fracture reporting malocclusion is recorded as 1 case of malocclusion rather than 3).

Assessing Methodological Quality

The validated criteria from Methodological Index for Non-Randomized Studies (MINORS)[25] were used for assessing the quality of all included studies in duplicate (N.S. and A.S.). A 50% score was set as an arbitrary methodological quality threshold. A 12-week average follow-up period was agreed upon a priori to sufficiently allow for manifestation of most relevant postoperative complications. The raw scores were recorded and were converted into calculated percentages.

RESULTS

Literature Search, Eligibility Assessment, and Article Selection

After initially retrieving 11,233 studies, 2,670 (23.8%) duplicates were removed. The remaining 8,563 studies were searched systematically yielding 19 full-text, primary research studies.[8,16,26-42] One additional study was sourced from the subsequent reference search.[43] A total of 20 articles were included in the study and are depicted in a flow diagram (Fig. 1) using a modified “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA)[44] template.

Fig. 1.

Adapted PRISMA flow diagram depicting systematic review of literature relating to impact of treatment delay on outcomes in traumatic mandible fracture ORIF.

Methodological Quality Assessment of Included Studies

The 20 included studies were assigned a MINORS score ranging from 4 to 8 out of 16 for noncomparative studies, and ranging from 6 to 15 out of 24 for comparative studies (Tables 3, 4). The average MINORS score for case–control studies was 10.9 of 24 (45.4%), and all were comparative. The average MINORS score for cohort studies was 6.5 of 16 (40.6%) for noncomparative studies, and 12.0 of 24 (50.0%) for comparative studies. The average MINORS score for all studies included in this systematic review was 6.5 of 16 (40.6%) for noncomparative studies and 11.2 of 24 (46.7%) for comparative studies. Only 9 of 20 included studies had a calculated MINORS score greater than or equal to 50%, of which only 2 studies made a recommendation for earlier ORIF treatment.

Table 3.

Methodological Quality Scoring of Included Case–control Studies Using MINORS Criteria[25]

A low MINORS score was primarily assigned due to a lack of: prospective data collection, assessor blinding, and sample size calculations (Tables 3, 4). Additional factors contributing to low scoring included a lack of adequate control groups, and several studies having greater than 5% loss to follow-up and inadequate follow-up periods.

Baseline Characteristics of Included Studies

There were a total of 2,671 patients from the 20 included studies published between 1979 and 2016 (Table 5), and only 1 study was prospective in nature.[16] All studies were observational, with more case–control studies (11/20) than cohort studies (9/20). Five of 20 studies made an overall recommendation for earlier treatment, whereas 14 studies did not make a recommendation for earlier treatment. Among these 14 studies, only 1 found a “loose trend toward better outcomes with delayed fixation” but overall did not suggest an association between timing of surgical repair and postoperative complications.[29] One study did not have a clear recommendation for or against earlier treatment.[39]

Table 5.

Summary of Key Information for Included Case–control and Cohort Studies

With respect to patient demographics (Table 6), 77.84% of patients were male (16/20 studies reporting), and the average age of patients was 31.3 years old (14/20 studies reporting). The mean time delay from injury to ORIF surgery was approximately 116 hours or 4.8 days (8/20 studies reporting). The follow-up time averaged 13.0 weeks (7/20 studies reporting) and ranged from 0.7 to 100 weeks (11/20 studies reporting). Table 7 demonstrates that the most commonly fractured anatomic region of the mandible was the angle, with 679 patients affected (6/20 studies reporting), followed by the mandibular body, with 190 patients affected (5/20 studies reporting). Table 8 demonstrates that assault was the most common mechanism causing mandibular fractures, with 870 patients affected (10/20 studies reporting), followed by 532 cases of blunt trauma (9/20 studies reporting), and 373 cases of road traffic accidents (13/20 studies reporting).

Table 6.

Patient Demographics and Time-related Data

Table 7.

Anatomic Distribution of Mandible Fractures

Table 8.

Mechanism of Injury Contributing to Traumatic Mandible Fractures

Four hundred fifty-five patients (18.5%) had at least 1 postoperative complication following ORIF, based on 19 of 20 studies reporting the total number of patients with complications (Table 9). Two hundred thirteen patients (8.2%) had infectious complications of any type (19/20 studies reporting). Infection was the most commonly reported complication, followed by 128 patients (7.1%) with malocclusion (11/20 studies reporting), and 52 patients (3.5%) with wound dehiscence (9/20 studies reporting).

Table 9.

Postoperative Complications following ORIF of Traumatic Mandibular Fractures

Attempted Meta-analysis

Treatment delay time thresholds were too variable to pool cohort study data, with only 2 studies sharing time intervals among cohort groups (Fig. 2). There was inadequate reporting of mean treatment delay times to pool data for 7 of 11 case–control studies. Four of the 20 included studies reported sufficient treatment delay data to facilitate depiction in a Forest plot (Fig. 3). The data from 2 studies suggested that treatment delay was longer for patients with complications,[28,30] whereas 2 studies suggested a longer treatment delay for patients without complications.[27,29] The heterogeneity score was 83%, and therefore it was unreliable to pool mean treatment time by postoperative complications.

Fig. 2.

Time-relevant group classification for included cohort and case–control studies detailing barriers to representing data in meta-analysis using a Forest plot. Treatment delay thresholds for cohort studies are highly variable prohibiting data pooling, while case–control studies had inadequate reporting of mean time delay data.

Fig. 3.

Forest plot for included case–control studies with sufficient reporting of mean time delay from injury to surgery (hours) demonstrating duration of treatment delay for “complication” and “no complication” groups. Treatment delay was longer on average by 69.32 hours for the pooled groups with “complications.”

DISCUSSION

There is insufficient data to reliably determine the importance of treatment delay as an independent predictor of postoperative complications following ORIF of traumatic mandible fracture(s). Only 5 of the 20 studies included in this systematic review concluded that prolonged treatment delay increased the risk of postoperative complications for traumatic mandible fractures. There was significant variation in the time thresholds proposed delineating “early” versus “delayed” ORIF, ranging from 6 hours to 7 days (Fig. 2). Significant time threshold heterogeneity for cohort studies, incomplete data reporting of mean treatment delay times for case–control studies, and overall insufficient stratification of reported data prevented synthesis of the collected data into a formal meta-analysis. The optimal treatment delay for minimizing complications in patients requiring mandible fracture ORIF remains unknown.

Alternative Risk Factors for Postoperative Complications

Alternative risk factors, other than treatment delay, have been posited as contributors to the development of postoperative complications in patients with mandible fractures (Table 10). It has been suggested that these factors may be confounders resulting in prolonged treatment delay, such as noncompliance and comorbid substance use.[19,20]

Table 10.

Factors Implicated to be Associated with Postoperative Complications following Surgical Treatment of Mandible Fractures

With respect to patient factors increasing complication rates, Malanchuk and Kopchak[22] demonstrated that age was a significant predictor of infection for tooth-bearing mandible fractures treated with open or closed reduction, with patients less than 20 years old and greater than 60 years old having infection rates of 9.4% and 55%, respectively. Periodontal disease has been linked to delayed healing of mandibular body fractures.[45] Luz et al.[28] found that 75% of patients with complications following ORIF for mandible fractures were partially edentulous, whereas 76.2% of patients without complications were fully dentate. One of the most significant contributors for developing complications in patients with traumatic mandible fractures is substance use, including alcohol abuse.[4,19-21,23,32,45] Domingo et al.[5] found that as many as 53.6% of drug users with mandible fractures developed surgical-site infection and suggested this may be due to their relatively poor nutrition, wound healing, and compliance with postoperative oral care. Smoking has also been reported to increase post-ORIF complication rates 4-fold and infection rates 6-fold, as compared with nonsmokers receiving ORIF.[5,26,27]

With regard to mandible fracture factors influencing postoperative complications, higher risk anatomic regions include the mandibular angle[22,34] and the body; Luz et al.[28] reported that 43.8% of body fractures had complications requiring reoperation. Patients with comminuted[21,22,28] and multifocal[26] mandible fractures were found to be at higher risk of developing complications, including infection. Czerwinski et al.[21] reported that the rate of comminution in patients with complications was 32% compared with 22% in patients without complications. Compared with closed fractures, open fractures have been reported to have as high as a 14-fold increased complication rate (14% versus 1%),[5] and another study found that 80% of patients with postoperative complications had open mandibular fractures.[28] Similarly, Anderson and Alpert[31] reported that 100% of patients with complications (predominantly infectious) had teeth in the line of their mandible fracture, which are considered open fractures by definition,[8] and theoretically create a conduit for bacterial seeding. In keeping with this hypothesis, Wagner et al.[34] reported that 69% of patients (9 of 13) receiving mandible fracture treatment involving tooth extraction had post-ORIF complications.

Lastly, there is evidence to suggest that ORIF surgical technique is a factor in predicting increased complication rates. An included study[31] reported a 46% infection rate (6/13 mandible fractures) associated with improper ORIF technique. Odom and Snyder-Warwick[26] reported that ORIF utilizing intraoral incision was associated with a 16.8% complication rate, compared with 0% with extraoral incision, and 27% with combined intraoral and extraoral incisions. However, these data may have been confounded by the fact that more complex and comminuted mandible fractures tend to require a combined approach.[28]

Strengths

To date, this is the first systematic review on mandible fracture treatment delay that focuses specifically on ORIF intervention timing. Ensuring the best possible methodological quality was of high importance, and this systematic review was designed in adherence with PRISMA guidelines.[44] The search strategy was constructed in collaboration with our health sciences librarian using a PICOT question formulated a priori and was also registered a priori in the PROSPERO database. The literature search was conducted in duplicate and the included studies were also scored in duplicate using MINORS, a validated tool for assessing the methodological quality of nonrandomized studies.

Limitations

Incomplete data reporting and insufficient data stratification were frequently encountered, as the majority of included studies were retrospective in nature. Six of 20 included studies did not report mean patient age making exclusion of irrelevant studies more difficult.[8,31,33,37,40,41] Reported follow-up times were regularly shorter than 12 weeks, and 9 of 20 included studies did not report any follow-up data (Table 6). Inadequate follow-up periods were, however, penalized as part of the MINORS scoring criteria (Tables 3, 4).

There was variation among the types of mandible fracture included across studies with Spinelli et al.[35] focusing on angle fractures only, Barker et al.[29] excluding condylar and alveolar fractures, and 5 of 20 included studies not reporting mandible fracture location.[8,29,30,36,43] It is therefore difficult to compare complication rates between such studies, given that mandible fracture location is considered an important factor influencing the development of complications.[16]

ORIF hardware has also changed over the decades, with the earlier studies in the 1970s to 1980s utilizing interosseous wiring in as many as 93.8–96.0% of cases,[17,34] whereas recent studies have tended toward mini-plate use exclusively.[35,36] Early adopters of mini-plate hardware may have encountered more complications related to operator learning before the popularization and refinement of this modern ORIF technique.[31]

The definition of treatment delay in the literature was highly variable. Unfortunately, some studies needed to be excluded during the full-text review, as they did not report time from injury to ORIF treatment, but rather used intervals such as injury to admission[2] or diagnosis to treatment,[3] or did not specify a time interval at all.[46]

Among the 20 included studies, there was still heterogeneity with respect to whether MMF was used as an adjunct to ORIF (Table 5). The utilization of MMF in addition to ORIF was deemed acceptable for inclusion, as MMF did not contribute to the development of mutually exclusive reported complications during review of the included studies.

There was heterogeneous reporting of parameters such as fracture location and complication data (Tables 7, 9), either in terms of number of patients affected (n),[16,26,28,31,32,35] or number of fracture cases (N).[27,33,34,38-42] This prevented pooling of data as it could not be assumed that each fracture case was attributed to an individual patient, such as in patients with multifocal fractures. A paucity of data reporting and stratification was also problematic for reporting substance abuse data, with only 1 study individually stratifying by number of patients using tobacco, alcohol, and illicit drugs.[38] No useful data could be extracted from studies like Luz et al.[28] that reported all forms of substance abuse (ie, smoking, alcohol, and illicit drug use) in a single category, and many studies did not report substance use data at all (Table 6). Therefore, sample sizes were too small to determine if complications were correlated with any particular type of substance abuse.

Formal statistical analysis in the form of P values or confidence intervals was lacking among included studies to substantiate recommendations supporting shorter treatment delay.[8,31,37] In general, there was a lack of stratified time delay data for cohort study subgroups and case–control subgroups, thereby preventing meaningful statistical calculations that could determine quantitatively if in fact treatment delay was associated with an increased risk of complications. Even in the best-case scenario (Fig. 3), small sample sizes, large confidence intervals, and a heterogeneity score > 50% led our statistician to recommend against pooling of data in a formal meta-analysis.

Future Directions

A well-designed prospective cohort study is the next logical step to answer the question of whether treatment delay is an independent factor impacting postoperative mandible fracture complications and accurately estimate an optimal time threshold for treatment delay. A priori sample size calculations will be necessary to ensure adequate study power for patients and operative characteristics adjustments.[47] A prospective design will ensure complete and consistent data collection and reporting for the primary and secondary outcomes, but also ensure appropriate stratification for other factors such as fracture location, fracture etiology, substance abuse, and especially treatment delay data. Based on the most commonly reported complications in this systematic review, we propose that all future studies include the following outcomes: infection (all cause), osteomyelitis, hardware infection, malocclusion, malunion, nonunion, wound dehiscence, and hardware failure (Table 11). Lastly, confounding factors such as substance abuse (ie, tobacco, alcohol, and illicit drugs), noncompliance, fracture complexity, and comorbid injury severity must be collected and controlled for to ensure that treatment delay is the only independent variable in the study design.

Table 11.

Recommended Outcome Set for Future Studies Investigating Surgical Treatment Delay for Traumatic Mandible Fractures

CONCLUSIONS

There is no consensus on whether ORIF treatment delay is an independent risk factor for the development of postoperative complications in patients with traumatic mandible fractures. There is no consistently utilized time threshold distinguishing “early” versus “delayed” treatment, and 14 of 20 included studies did not conclude that treatment delay was a predictor of postoperative complications. Future well-designed prospective studies of higher methodological quality are essential to determine if there exists an optimal treatment delay threshold that mitigates complication risks.

Table 4.

Methodological Quality Scoring of Included Cohort Studies Using MINORS Criteria[25]