Optimizing Treatment Strategies and Risk Stratification in Tibial Fractures: A Meta-Analysis of Fixation Timing, Modality, and Fracture Classification on Acute Compartment Syndrome Risk.

1. Introduction

Acute compartment syndrome (ACS) is a limb threatening emergency condition that is associated with orthopedic emergencies, characterized by increased pressure within a closed muscle compartment that leads to impaired circulation, muscle and nerve ischemia, and could lead to irreversible tissue damage.¹ If left untreated, ACS can result in severe complications including muscle necrosis, contractures, neurological deficits, and even limb amputation. Among orthopedic emergencies, ACS represents one of the most time-sensitive conditions, requiring rapid diagnosis and surgical intervention to prevent long-term disability.¹

Tibial fractures are susceptible to ACS risk due to the anatomical configuration of the lower leg, with its well-defined fascial compartments and limited space for tissue expansion following trauma.² The incidence of ACS following tibial fractures varies widely in the literature, with reported rates ranging from 2% to 9% depending on fracture type, location, and severity. Tibial plateau and high-energy diaphyseal fractures appear to carry higher risk, however the precise risk remains incompletely estimate.² The present variability creates significant challenges for practice decision, as physicians should balance the need for emergent monitoring and prophylactic interventions against the risks of unnecessary procedures.

Several factors have been proposed as contributing predictors of ACS development in patients with tibial fractures. Patient demographics such as age and gender, injury characteristics including fracture topology, and mechanism of trauma, and treatment variables like timing of fixation and choice of surgical approach have all been introduced in the ACS risk.^3,4 However, the published literature demonstrates multiple heterogeneity points in both methodology and findings. Individual studies often report conflicting results, which are limited by small sample sizes, or focus on specific limited sub-populations, making it difficult to make definitive conclusions. Previous studies have attempted to synthesize the evidence about ACS, but most have provided only qualitative assessments without focused and detailed quantitative analysis.⁴

The lack of consensus regarding ACS risk factors has significant considerations. Without clear risk stratification and evaluations, we may adopt inappropriate management or useless strategies that may interfere the with best desired outcomes that shall be achieved. This uncertainty is causing a burden given the severe consequences of delayed diagnosis and the narrow therapeutic window for proper intervention in ACS.⁵

Previous meta-analyses have focused on comparing proportions between ACS and non-ACS groups, without precisely quantifying the strength of association between specific risk factors and ACS development. Such approaches do not account for the possible confounders and are susceptible to higher risk of bias when pooling heterogeneous data.⁶

Therefore, given these limitations we aim to these limitations we aim to evaluate and assess the associations between specific risk factors and ACS in patients with tibial fractures. By synthesizing data from multiple studies using multiple approached methodologies, we look to: (1) identify patient demographics that modify ACS risk; (2) determine the impact of fracture characteristics and injury mechanisms on ACS development; (3) evaluate the impact of treatment modalities, especially fixation timing and technique, on ACS incidence; and (4) develop a risk-stratified approach to guide better patient management. Our findings could have a significant positive impact on practice by facilitating early identification of high-risk patients, informing tailored monitoring protocols, and guiding surgical timing and technique to minimize ACS risk as much as possible.

2. Methods

3. Results

3.1 Study characteristics

Our search resulted at first with a total of 2,124 articles, that were finally filtered into 17 retrospective studies^2,8–23 which met our inclusion criteria and were included in our study ( Figure 1). The included studies were published between 2013 and 2024, with the most of studies originating from the United States (seven studies). Other countries represented included China (three studies), Switzerland (three studies), the United Kingdom (two studies), and Austria (one study). The pooled dataset included 274,962 patients, including 10,019 cases of ACS. Most of the studies (12 studies from 17) focused on adult populations, while two studies have focused on pediatric patients. The most frequently reported fracture sites were tibial plateau fractures (five studies), diaphyseal fractures (three studies), and shaft fractures (one study), with the remaining studies investigating mixed or various fracture types ( Table 1).

Figure 1. PRISMA flowchart inclusion process and pipeline.

Table 1. Characteristics of included studies.

Study	Country	Study design	Sample size (ACS/non-ACS)	Age	Fracture classification/site
Wier J et al., 2024	USA	Retrospective	87/3098	≥18	Tibial plateau fractures
Wang T et al., 2024	China	Retrospective	127/127	≥18	Not reported
Strain R et al., 2024	UK	Retrospective	58/1089	≥18	Diaphyseal fractures (AO/OTA type 42)
Milner JD et al., 2024	USA	Retrospective	296/50670	10-18	Tibial Tubercle & Tibial Shaft
An M et al., 2024	China	Retrospective	86/619	ACS: 32.5 (24.8–53.0), non-ACS: 43.0 (30.0–56.0)	Diaphyseal tibial fractures
Ahmed N et al., 2023	USA	Retrospective	49/4443	<18	Various tibial fracture types including open, proximal, and articular fractures
Smolle MA et al., 2022	Austria	Retrospective	23/230	50.7 (18.0–85.0)	Tibial plateau fractures
Gamulin A et al., 2022	Switzerland	Retrospective	67/658	>16	Intra- or extra-articular proximal tibia fracture (AO/OTA codes 41A2, 41A3, 41B, 41C), tibial shaft fracture (AO/OTA 42), or distal tibia fracture (AO/OTA 43)
Bouklouch Y et al., 2022	USA	Retrospective	8748/194752	Male: 40.2 ± 18.1, Female: 49.2 ± 20.7	Proximal tibial fractures: 38%, midshaft fractures: 30%, distal fractures: 32%
Deng X et al., 2021	China	Retrospective	35/1084	18-80	Tibial plateau fractures
Wuarin L et al., 2020	Switzerland	Retrospective	31/239	>16	Tibial shaft fractures
Beebe MJ et al., 2017	USA	Retrospective	136/2749	42.9 ± 18.0	Fractures of proximal, middle, and distal tibia segments (OTA/AO classification)
Gamulin A et al., 2017	Switzerland	Retrospective	28/2749	>16	Tibial plateau fractures
Haller JM et al., 2016	USA	Retrospective	14/145	≥18	High-energy tibial plateau and plafond fractures
Allmon C et al., 2016	USA	Retrospective	56/922	≥18	Plateau, shaft or pilon fractures
McQueen MM et al., 2015	UK	Retrospective	160/1228	12-98	Tibial diaphyseal fractures
Ziran BH et al., 2013	USA	Retrospective	18/141	CS: 42 ± 11.6, non-CS: 48 ± 15.5	Plateau fractures

3.6 Risk of bias assessment

Quality assessment using the NOS revealed that four studies (23.5%) had low risk of bias (NOS score 7-9), 12 studies (70.6%) had moderate risk of bias (NOS score 5-6), and only one study (5.9%) had high risk of bias (NOS score ≤4) (refer to extended data: Supplementary Table 2). The highest-quality studies were Bouklouch et al., Milner et al., Gamulin et al., and Allmon et al., each demonstrating better quality in their methodological approaches. Selection criteria were generally well-addressed across studies, while the comparability domain showed more limitations. Few studies adequately controlled for all important confounding factors, and several studies had limitations in outcome assessment, especially regarding follow-up adequacy. Sensitivity analyses according to study quality confirmed that our main findings remained significant across quality subgroups, however the effect sizes were slightly attenuated in higher-quality studies, as we observed slight asymmetry through visual inspection of funnel plot of publication bias ( Figure 2).

Figure 2. Funnel plot of asymmetry for publication bias assessment and correction estimates.

4. Discussion

ACS is a one of the most serious complications of tibial fractures that may lead to permanent neuromuscular dysfunction, contractures, and even limb amputation if not rapidly diagnosed and managed correctly. Despite being a demarcated complication, the incidence of ACS following tibial fractures varies, with reported rates ranging from 2% to 9% that creates significant uncertainty in the risk assessment.²⁴

The time-sensitive nature of ACS diagnosis and management stress for the need of precise, focused and detailed evidence-based risk stratification. The typical signs of ACS including pain disproportionate to injury, paresthesia, paralysis, pallor, and pulselessness which often manifest lately in course when irreversible tissue damage may have already occurred. Given that, the importance of estimating precise and accurate predictors that can guide vigilance, monitoring intensity, and preventive interventions in high-risk patients.²⁵

We found that delayed fixation after 24 hours was associated with a 67% reduction in ACS risk compared to early fixation, which goes against the current trauma principles of early definitive fixation instead of delayed treatment.²⁶ This protective effect was mostly observed in specific high-risk populations which are, young adults, males, and patients with high-energy injuries. Regarding fracture characteristics, proximal tibial fractures, especially plateau fractures was observed to have higher ACS risk compared to shaft fractures and distal fractures that exceeds the double. External fixation showed a protective effect compared to immediate definitive internal fixation, especially for tibial plateau fractures.

Male patients were observed to have two to four times higher ACS risk than female patients. We also found that age as a factor has demonstrated divergent effects as younger adults had progressively increasing risk with decreasing age, while in pediatric populations, older children showed higher risk than younger ones. Our meta-regression identified that 67% of the variance in treatment effects across studies could be explained by fracture type, injury mechanism, and patient demographics.

Our finding that delayed fixation significantly reduces ACS risk represents an important concern to discuss here. Compared to the gold standard principles which recommend early definitive fixation to improve outcomes and reduce complications,²⁶ our results suggest that this approach may actually increase ACS risk in certain patients. This contradiction can be linked and explained by considering the pathophysiology of ACS: immediate post-trauma tissue edema may peak at 24-48 hours, and early aggressive manipulation during definitive fixation could exacerbate compartment pressures during this vulnerable period.²⁷ Some of the previous studies have concluded with similar timing effects recommending starting with close monitoring and observation within the first 24 hours before performing external fixation to reduce the risk of ACS development in high risk patients, especially in tibial plateau fractures.^4,6,8,24,28

The significance variations in ACS risk according to fracture location provides important considerations to keep in mind about the impact of anatomy and location. The higher risk associated with proximal tibial fractures, especially plateau fractures, likely reflects both the extensive soft tissue disruption typical of these injuries and the proximity to the anterior compartment, which is most frequently affected in ACS.²⁸ The relatively lower risk in pilon fractures and shaft fractures contradicts some previous assumptions but may reflect differences in compartment anatomy and soft tissue envelopes.⁸ The meta-regression showed that fracture location was one of the strongest predictors of treatment effect, suggesting that anatomically specific protocols may optimize outcomes after further evaluation and validation in further focused studies. Our study clarifies the role of non-modifiable patient factors in ACS risk. The consistently higher risk in males with more than the double risk fold across studies likely due to both of the anatomical differences such as greater muscle mass within fixed fascial compartments, and the possible factors from higher-energy injury mechanisms in male patients.²⁹

In adults, we have observed a higher risk in younger patients, especially who are younger than 30-year old, this could be correlated and reflected due to the greater muscle mass and more active inflammatory responses in such individuals. However, in pediatric populations, the increasing risk with age, may relate to the rapid muscle growth during puberty outpacing fascial expansion during this developmental and growth life period.^30–33

One of the most important points to consider in our study is the identification of significant interaction effects between risk factors. The highest risk populations, young males with plateau fractures from high-energy mechanisms, demonstrated a five times higher increased ACS risk compared to lower-risk groups. This interactive effect explains why previous single-factor analyses often had inconsistent results as the true risk is formed from the combination of factors at the same time rather than looking into one factor only. We have summarized and concluded our findings about the management according to risk in Figure 3.

Figure 3. ACS risk stratification algorithm for tibial fracture patients.

In the highly dynamic, advancing and growing literature within the field of orthopedic trauma, our study coincides with a recent meta-analysis by Cong and Zhang 2025,⁶ in which they have investigated ACS risk factors in tibial fractures. Such methodological parallels are inherent and unavoidable in systematic reviews and meta-analyses addressing similar points of interest and investigating common questions, as both necessarily adhere to PRISMA guidelines and utilize high quality structured assessment tools. However, our study represents a novel and peculiar scientific contribution in several important considerations. While Cong and Zhang study has primarily investigated demographic and injury mechanism factors,⁶ our study looked to investigate specifically the timing and modality of surgical fixation. Also, our finding that delayed fixation beyond 24 hours reduces ACS risk by 67% directly challenges the current gold standard approach of early fixation, representing a novel finding and new output discovery that was not studied nor investigated in the later study as they had different aims and goals from their work. We shall mention that our meta-regression modelling has explained 67% of treatment effect variance across studies, which have significant highlights and takeaways into how patient factors modify treatment efficacy. We have also formulated, proposed and developed a risk-stratification algorithm that helps in providing an applicable assisting clinical decision tool for individualized patient management. These significant differences in scope, methodology, findings, and applications clearly demarcate and differentiate our work as an original and independent study that is different from Cong and Zhang 2025⁶ study aims, goals and their outcomes findings despite sharing similar concepts and considerations regarding investigated population of interest, inclusion criteria and exclusion criteria of eligible studies to include in both of our studies, as both of our studies deliver two important considerations and takeaways that are different and unique by their own.

Despite the strengths and multiple statistical methods utilized in our study, we have several limitations warrant consideration. All of the included studies were retrospective in design, introducing a risk selection and recall biases. The absence of randomized controlled trials reflects the ethical challenges of experimentally studying ACS risk factors and morally unacceptable practices. Second, significant heterogeneity was present in ACS definitions, diagnostic criteria, and monitoring protocols across studies. This variability may have affected reported incidence rates and risk associations, especially when considering patient with open fractures and deep wounds who are at higher risk for more aggressive risks. Despite that, we tried to account for this through random-effects models and meta-regression, some residual heterogeneity remains unsolved. Also, as most of the included studies were from high-income countries, this may limit the generalizability to resource-constrained settings with different fracture management settings.

We shall mention that our analysis was limited by the variables reported in the original studies. Important other underlying risk factors such as patient comorbidities, medication use, specific surgical techniques, as well as surgeon experience were inconsistently reported and could not be adequately analyzed which could play a role in the outcomes.

Our findings call for multiple recommendations and directions to consider from our findings. We need to have further prospective studies with standardized ACS definitions, monitoring protocols, and outcome measures are needed to validate our risk model. Multicenter studies with subgroup analyses would help confirm the interaction effects we found. Also, our treatment timing findings warrant prospective evaluation and investigation through comparative effectiveness studies comparing between delayed versus early fixation in high-risk populations, with standardized monitoring protocols and clearly defined endpoints.

From a clinical point of view, we recommend implementation and prospective evaluation of our risk-stratified treatment algorithm, with modification based on local resources and expertise. Particular attention should be given to standardizing monitoring protocols based on risk category, with high-risk patients receiving more intensive surveillance. Finally, we need to validate and assess further for the comparative safety and efficacy of delayed versus early treatment and the other factors that may play a role in treatment timing optimization for patients to ensure whether delayed external fixation is truly beneficial or not, and which cohort of patients will most likely benefit from it compared to the standard of care that recommends early surgical intervention.

5. Conclusion

Our study findings warn that performing early definitive fixation for tibial fractures may increase ACS risk in certain high-risk patients. Our findings reveal that delayed fixation after 24 hours reduces ACS risk by 67%, with this protective effect was mostly significant in young adult males with plateau fractures from high-energy mechanisms. We identified a clear risk stratification pattern where proximal tibial fractures carry higher risk than shaft or distal fractures, and male patients demonstrate two to four times higher risk than females. The interactive effect between these factors explains why previous single-factor based studies had inconsistent results and stress the need for a multifactorial and multidisciplinary management to risk assessment.

Our results suggest considering a risk-stratified treatment protocol where high-risk patients, as young males with plateau fractures from high-energy mechanisms, would benefit more from delayed definitive fixation or temporary spanning external fixation to allow for soft tissue recovery during peak edema within 24 to 48 hours. Optimized compartment monitoring should be prioritized for these patients, with careful monitoring proportionate to calculated risk. While our findings challenge the gold standard trauma principles advocating early fixation, they have a common sense with the possible ACS pathophysiology. Future prospective studies are needed to validate our findings confidently.

Declarations

Consent for publication

Not applicable.