Early mobilisation after hip fracture surgery reduces the risk of infection: an inverse probability of treatment weighted analysis

Abstract

Background

Mobilisation within the first day following hip fracture surgery is recommended. However, an in-depth analysis of the association between early mobilisation and the risk of infection is lacking.

Objective

To examine the association between early mobilisation and the subsequent risk of hospital-treated infections following hip fracture surgery.

Methods

Using nationwide registries, we included 36 229 patients aged ≥65 who underwent surgery for hip fracture (2016–21). Exposure was time from surgery to first mobilisation in hours. Outcomes were any hospital-treated infection, pneumonia, urinary tract infection and sepsis within 2–30 days and reoperation due to surgical-site infection within 2–365 days of surgery. We calculated cumulative incidences (risks), risk differences (RD) and hazard ratios (HR) with 95% confidence intervals (CIs) using the inverse probability of treatment (IPT) weighted method to account for confounding.

Results

Overall, 27 174 (75%) patients were mobilised ≤24 h, 2890 (8%) between 24 and 36 h, and 6165 (17%) were mobilised >36 h of surgery or had no registration of mobilisation time.

In the weighted analysis, the risk of any infection was 12.9% (CI 11.7%–14.2%) in patients mobilised 24–36 h of surgery and 10.9% (CI 10.5%–11.7%) in those mobilised ≤24 h, corresponding to RD of 2.0% (CI 0.7–3.3) and HR of 1.2 (CI 1.1–1.3). Similar associations were observed for pneumonia and urinary tract infection but not for sepsis and reoperation.

Conclusions

Infection is a common complication after hip fracture surgery. Mobilisation within 24 h is clearly associated with reduced infection risk. Our results emphasise the importance of early mobilisation and suggest a possible pathway for reducing complications and mortality after hip fracture.

Key Points

• Early mobilisation reduces infection risk by 2%-points within 30 postoperative days compared to mobilisation at 24–36 h.

• Early mobilisation primarily reduces pneumonia and urinary tract infection risk—by 1.3% points and 0.5% points, respectively.

• Mobilisation within 12 h postsurgery yields the lowest infection risk, indicating further benefits of earlier mobilisation.

• The study underscores the significance of early mobilisation in postoperative care to minimise complications.

Introduction

Hip fractures represent a significant health burden among older people. Mortality is almost 10% in the first 30 postoperative days [1], and patients suffer a high risk of postoperative complications [2–5] and permanent disability [6]. The recommended optimal treatment of patients with hip fracture involves a multidisciplinary setup addressing not only the surgical but also the complex analgesic, medical, cognitive, nutritional, social and rehabilitation needs of these patients. Still, postoperative infections, such as pneumonia, urinary tract infections and sepsis, are observed in 14% of cases [2] and are considered a serious postoperative complication that can substantially impact mortality, prolong hospital stays, increase health care costs and adversely affect nonfatal outcomes [7, 8]. Indeed, respiratory tract infections are highlighted as the most common cause of early postoperative death in patients with hip fractures [7, 8].

Early mobilisation following hip fracture surgery is widely endorsed as a gold standard practice to mitigate postoperative complications and enhance recovery outcomes [9–11]. While the benefits of early mobilisation in reducing mortality and improving functional recovery are well documented [12, 13], its specific impact on postoperative infections remains underexplored [13–15]. The link between immobilisation and increased infection risk is rooted in several pathophysiological processes that take place early in the pre-, peri- and postoperative period: Immobility can lead to decreased ventilation of specific regions of the respiratory tissue, impaired clearance of mucus and, consequently, a higher risk of pneumonia [16]. Additionally, aspiration is more likely if the patients are not sufficiently mobilised during meals. Urinary stasis, increasing the likelihood of urinary tract infections [17], is also more frequent if the patient is immobilised. Bed-ridden patients are also at higher risk of cognitive deterioration, potentially masking symptoms of infection, resulting in increased severity, due to later recognition. Based on these processes, optimising the timing of mobilisation seems highly relevant. However, recommendations for early mobilisation vary from 12 to 24 h in Italy [18], <24 h in Denmark [19] to ‘the first postoperative days’—possibly leaving patients in bed for 36 h in several other countries including the UK [9].

Consequently, an in-depth understanding of the relationship between the timing of mobilisation after hip fracture surgery and infection risk is crucial for enhancing comprehensive, multidisciplinary postoperative care protocols that minimise these adverse events.

This study aims to fill the gap in current knowledge by providing a detailed analysis of the association between time to early mobilisation and the subsequent risk of hospital-treated infections including pneumonia, urinary tract infections, sepsis and reoperation due to surgical site infections following hip fracture surgery.

Methods

Data sources

This study is based on Danish medical databases that collect nationwide, routinely registered data on all hospital contacts [20]. The Danish government provides tax-supported health care to all residents and no private hospitals are involved in the emergency treatment of patients, making the public hospital databases complete regarding emergency contacts. Databases are linked through the unique civil registration number that is generated from the Civil Registration System, which contains information on civil and vital status and migration [21].

The ‘Danish Multidisciplinary Hip Fracture Registry’ (DMHFR) [22] is a clinical quality database on all patients >65 years operated for a hip fracture at a Danish hospital since 2004. Patients with pathological fractures due to malignancy as well as those with periprosthetic fractures are not included in the database. Thus, the population consists of patients with traumatic fractures, the majority due to low-energy trauma.

The ‘Danish National Patient Registry’ (DNPR) [23] records all hospital contacts in Denmark. For each contact, dates of admission and discharge, along with primary and secondary discharge diagnoses, are registered, using the International Classification of Diseases, 10th edition (ICD-10).

Study variables

Exposure

Date-timestamp (date, hour, minute) of operation start and first postoperative mobilisation are routinely recorded in the DMHFR. As these variables are used in national and local clinical audits to benchmark hospitals on their performance and to facilitate quality improvements in the care given to hip fracture patients in Denmark, they are expected to have high validity. If the date timestamp of mobilisation was not registered after an operation, the DMHFR assumes the worst-case scenario that the patient had not been mobilised.

Time from operation until the time of first postoperative mobilisation was computed in hours. The exposure was subsequently dichotomized into ≤24 h vs 24–36 h for the main analysis. Further, we categorised the exposure in 12 h intervals: <12, 12–24, 24–36, >36 or missing for the supplementary analyses.

Outcome

Within 2–30 days after surgery, we studied the outcome of any hospital-treated infection (ICD-10 codes as previously reported [24]). Furthermore, we studied pneumonia, urinary tract infection and sepsis as individual outcomes. Reoperation due to surgical-site infection was studied within 2–365 days after surgery. Follow-up started on the second postoperative day to ensure time for the exposure to occur before the outcome was counted.

Covariates

We measured the following covariates as potential confounders:

• Patient demographics: age, sex, residence type, geographical area.

• Patient characteristics: body mass index, prefracture mobility (from the cumulated ambulation score [25]), marital status and education level.

• Patient comorbidities—based on a previously reported study identifying 27 comorbidities (Supplementary Table 1) with a prevalence above 1% in patients with hip fracture [24].

• Fracture characteristics: fracture type, operation type.

• Structural characteristics: year of surgery, surgery delay.

Statistical analysis

Patients were followed from the second postoperative day to the date of outcome of interest, death, emigration or end of follow-up (31 December 2021).

Baseline characteristics were summarised both overall and across exposure groups using counts and percentages and medians with inner-quartile ranges were appropriate.

Main analysis

In the crude and weighted analyses, we computed cumulative incidences (risks), cumulative incidence differences (risk differences) and hazard ratios (HRs) with 95% confidence intervals (Cis) for infection to compare patients mobilised within 24–36 with patients mobilised ≤24 h as a reference.

Risks were calculated using the Aalen–Johanson estimator, treating death as a competing risk—as recommended in previous literature [26, 27]. To calculate the HRs, we chose the Cox regression over the Fine–Grey competing risk regression [28], as the answer to our clinical question is better addressed by the Cox model since this estimates the cause-specific hazard of infection among patients who are event-free and alive at that given time [29]. The proportionality assumption of the Cox model was found satisfactory.

In the weighted analysis, we used the stabilised inverse probability of treatment (sIPT) weighting method to balance the measured confounders. The IPT weights were derived from propensity scores [30], which were computed using logistic regression to predict the probability of being mobilised ≤24 h or 24–36 h post-surgery as a function of the covariates described above. Weights were then stabilised by multiplying the weights in the group mobilised ≤24 h by the proportion of patients mobilised ≤24 h in the total study population and by multiplying the weights in the group mobilised within 24–36 h by the proportion of patients mobilised within 24–36 h in the total study population. For each covariate, standardised mean differences below 0.1 between the exposure groups were used as criteria for a well-balanced analysis.

Supplementary analysis

Instead of a dichotomised exposure, we calculated crude risks by time to first mobilisation in 12-h intervals.

Sensitivity analysis

We also tested the robustness of the findings in a sensitivity analysis.

Since a notable number of patients were mobilised in the hours around the 24-h cut-off, we excluded patients mobilised between 18 and 24 h to ensure a distinct difference between the patients mobilised early vs late. Thus, we calculated weighted risks, risk differences and HRs for patients mobilised between 24 and 36 h compared with patients mobilised ≤18 h.

The study is reported according to the REporting of Studies Conducted Using Observational Routinely-collected Data guidelines [31]. All statistical analyses were conducted using ‘SAS’ (version 9.4, SAS Institute Inc., Cary, NC).

Results

Patient characteristics

A total of 36 229 patients aged 65 years or older undergoing hip fracture surgery between 2016 and 2021 were included in the study. Among these, 27 174 (75%) were mobilised ≤24 h, 2890 (8%) were mobilised between 24 and 36 h and 6165 (17%) were either mobilised after 36 h or had no recorded mobilisation time. Patients mobilised ≤24 h were more likely to have a surgery delay below 12 h, were more likely to have higher prefracture baseline mobility, had fewer comorbidities and experienced longer lengths of stay than patients mobilised between 24 and 36 h, as detailed in Table 1. These differences were slightly more pronounced when comparing patients mobilised ≤24 h with those mobilised after 36 h or with no record of mobilisation time. Any difference in baseline characteristics between patients mobilised ≤24 h and those mobilised between 24 and 36 h were well balanced after the sIPT weighting (Supplementary Figure 1A and B).

Main analysis

Any infection

In the sIPT weighted analysis, the risk of any hospital-treated infection within 30 days postsurgery was 12.9% (95% CI, 11.7%–14.2%) for patients mobilised between 24 and 36 h, compared to 10.9% (95% CI, 10.5%–11.3%) for those mobilised ≤24 h (Figures 1 and 2). This corresponds to a risk difference of 2.0% (95% CI, 0.7%–3.3%) and an HR of 1.2 (95% CI, 1.1–1.3).

Pneumonia

In the sIPT weighted analysis, the risk of pneumonia within 30 days postsurgery was 5.7% (95% CI, 4.9%–6.6%) for patients mobilised between 24 and 36 h, compared to 4.4% (95% CI, 4.2%–4.6%) for those mobilised within 24 h in the weighted analysis (Figures 1 and 2). This corresponds to a risk difference (RD) of 1.3% (95% CI, 0.4%–2.2%) and a hazard ratio (HR) of 1.3 (95% CI, 1.1–1.6).

Urinary tract infection

In the sIPT weighted analysis, the risk of urinary tract infection within 30 days was 4.1% (95% CI, 3.4%–4.8%) for patients mobilised between 24 and 36 h, compared to 3.6% (95% CI, 3.4%–3.8%) for those mobilised within 24 h (Figures 1 and 2). This corresponds to a risk difference (RD) of 0.5% (95% CI, −0.3% to 1.3%) and a hazard ratio (HR) of 1.2 (95% CI, 0.9–1.4).

Sepsis and surgical-site infection

For the outcomes of sepsis and surgical-site infection, the estimates were imprecise due to the low number of events. However, we observed no difference in the risk of sustaining these outcomes based on time to mobilisation.

Results from the crude analysis for all outcomes of infection can be seen in Supplementary Table 2.

Supplementary analysis

The crude risk of any infection was observed to be lowest among patients mobilised <12 h after surgery, 8.8% (95% CI, 8.1%–9.6%) and gradually increases as the time of first mobilisation was delayed to a maximum of 16.7% (95% CI, 15.0%–18.6%) for patients mobilised later than 36 h after surgery (Table 2 and Figure 3).

Patients mobilised before 12 h following surgery had a crude risk of pneumonia reaching 3.5% (95% CI, 3.0%–3.9%), whereas patients mobilised later than 36 h following surgery had an 8.5% (95% CI, 7.3%–9.9%) 30-day risk of pneumonia (Table 2 and Figure 3).

Patients mobilised before 12 h following surgery had a crude risk of urinary tract infection of 2.9% (95% CI, 2.5%–3.3%), whereas patients mobilised later than 36 h following surgery had a 4.9% (95% CI, 3.9%–6.0%) 30-day risk of urinary tract infection (Table 2 and Figure 3).

Sensitivity analysis

After excluding patients mobilised within 18–24 h, the difference in infection risk was slightly augmented in early vs late mobilisation: any infection RD of 2.7% (95% CI, 1.4–4.1) and HR of 1.3 (95% CI, 1.2–1.5), pneumonia RD of 1.5% (95% CI, 0.6–2.4) and HR of 1.4 (95% CI, 1.2–1.7) (see Supplementary Table 3).

Discussion

Main findings

This study demonstrated a clear association between early mobilisation ≤24 h posthip fracture surgery and a reduced risk of hospital-treated infections. By early mobilisation, a 2%-point reduction in risk of any hospital-treated infection in the first 30 postoperative days could be achieved, mainly because of reduced risk of pneumonia (1.3% points) and urinary tract infection (0.5%-points). Furthermore, our supplementary analysis suggests an additional reduction in risk of infection can be obtained by mobilising patients as soon as possible—those mobilised <12 h following surgery had the lowest crude risk of infection. These findings reinforce the widely accepted importance of timely postoperative mobilisation to mitigate complications.

Comparison with previous literature

Several studies have described the risk of postoperative medical complications among patients with hip fracture mobilised early (first postoperative day) vs late [14, 15, 32, 33] and the topic has recently been compiled in a narrative review [17]. To our knowledge, only one study provides quantitative estimates of infection risk by early weight-bearing (first postoperative day) hip fracture management. Even though the exposure in this North American cohort is not directly comparable, the absolute estimates for pneumonia and urinary tract infection are within the same range as the estimates from this study.

Aprisunadi et al. [17] conducted a review on the effects of early mobilisation on postoperative outcomes for hip and lower extremity surgeries. They emphasised that early mobilisation significantly reduces postoperative complications, including deep vein thrombosis, pulmonary embolism, pneumonia, urinary tract infection and overall mortality, which corroborates our findings on the reduction of infection rates. While both the original investigations [14, 15, 32, 33] and the review [17] agree on the critical role of early postoperative interventions, our study extends the findings by providing specific risk reductions for various types of infections in a much larger sample size, and a more robust statistical analysis using the sIPT weighting method as well as accounting for competing risk of death. Our study is the first to provide a detailed qualitative risk assessment for different types of infections at varying times of mobilisation. Our results specifically highlight the critical role of early mobilisation in preventing respiratory and urinary tract infections, which are particularly prevalent and detrimental in older patients undergoing hip fracture surgery. Additionally, Aprisunadi et al. emphasised the importance of multidisciplinary and orthogeriatric-led approaches and the need for personalised mobilisation plans also including analgesic considerations to optimise outcomes, which is further supported by our findings.

The physiological mechanisms underpinning these findings are well documented [16, 17]. Early mobilisation enhances cardiovascular function, improves pulmonary mechanics and facilitates gastrointestinal and urinary system function. These physiological benefits collectively contribute to a lower infection risk. Additionally, our research has previously demonstrated that regaining prefracture mobility levels, which is more likely achieved when patients are mobilised early [34], is associated with a lower infection risk [35].

Implications

Quality indicators are essential in maintaining consistent care standards and minimising the risk of complications and mortality in hip fracture patients [36, 37]. Implementing standardised protocols for early mobilisation, monitoring adherence to these protocols, and regularly assessing patient outcomes can help ensure high-quality care. An increasing body of evidence underlines the importance of timely mobilisation postsurgery in patients with hip fracture; however, a discrepancy consistently prevails in the identification of the most relevant time window for early mobilisation. Some of the most influential guidelines, including the British National Centre for Health and Care Excellence recommend ‘mobilization on the day after surgery’ [9], which potentially leaves room for patients being immobilised for 36 h or maybe even more. In Denmark, the steering committee for the DMHFR is responsible for issuing the recommendations and has since its implementation in 2003 had both 24 and 36 h benchmarks. The latter was removed around 2020, and, from 2017, the timestamps were implemented to allow for more dynamic monitoring. Interestingly, the results from our supplementary analysis, although these are only crude estimates, indicate an additional benefit by lowering the time limit for mobilisation even further, although defining a cut-off value seems somewhat arbitrary considering that the earlier patient are mobilised the lower their risk of infection appear. Considering the dynamic pathophysiological mechanisms, a more relevant approach may be to aim for early mobilisation as soon as possible, not as before or after 24 h postsurgery, for all patients with hip fracture.

Thus, early mobilisation is a cost-effective intervention to reduce postoperative complications, keeping length-of-stay and health care costs at a minimum.

Methodological considerations

This large, population-based, cohort study uses routinely collected health care data from a nationwide registry. As access to hospital treatment is universal and free in Denmark, and all hip fracture treatment is performed in public hospitals, selection bias is expected to be minimal. The hip fracture diagnosis codes have been validated in the DNPR and found to have satisfactory positive predictive values above 80% [38] and similarly, the ICD-10 codes for infection in the DNPR has been validated with a good result [39].

When investigating a nonfatal outcome in a cohort with high mortality, competing risk of death is an important issue to consider. The Kaplan–Meier method has been shown to overestimate the cumulative incidences in this situation [27]. Consequently, we use the cumulative incidence method with death as a competing risk.

The chosen categories of early mobilisation reflect the current DMHFR clinical recommendations and facilitate emulation of a randomized clinical trial approach to address confounding. Finally, residual confounding can potentially occur if patients with a high risk of the outcome for some reason are not mobilised early, e.g. due to clinical deterioration in the pre- or perioperative period. To account for this, we used the sIPT weighted method in our main analysis [30], and, by including all common comorbidities as potential confounders, the risk of medical instability will be, by large, adjusted for. However, despite this robust method, a potential for residual confounding still exists due to factors that are not covered by adjusting for the chronic comorbidities. We are, however, confident that the impact of this on our results is minimal. Furthermore, unmeasured confounding may also potentially be present.

In conclusion, early mobilisation within 24 h posthip fracture surgery is associated with a 2% reduction in infections, including pneumonia and urinary tract infections, within 30 days. A further reduction in the risk of infection may be achievable by mobilising patients even earlier. These findings underscore the importance of early mobilisation in postoperative care protocols to enhance recovery and minimise complications. Implementing standardised early mobilisation protocols may lead to better patient outcomes and lower health care costs.

Acknowledgements:

The authors wish to thank the surgeons, physicians and other health care professionals for their cooperation in submitting high-quality clinical data to the national registries.

Declaration of Conflicts of Interest:

None declared.

Declaration of Sources of Funding:

None.

Research Data Transparency and Availability:

To protect the privacy of patients, individual-level data are not allowed to be publicly disclosed. The statistical code can be made available upon reasonable request.

References