Marginal structural models demonstrate treatment time effect on mortality in multi-system trauma patients with femoral shaft fracture

Abstract

Context. Fractures of the femoral shaft are common and have potentially serious consequences in patients with multiple traumatic injuries. The appropriate timing of fracture repair is controversial.

Objective. To assess the effect of timing of internal fixation on mortality in multi-system trauma patients

Design. Retrospective cohort.

Setting. Data from public and private Trauma Centers throughout the United States reported to the National Trauma Data Bank (version 5.0 for 2000–2005).

Patients. 3069 multi-system trauma patients (Injury Severity Score ≥15) who underwent internal fixation of femoral shaft fractures.

Intervention. Time to treatment was defined in categories as the time from admission to internal fixation: t₀≤12 hours; 12<t₁≤24; 24<t₂≤48; 48<t ₃≤120; 120<t₄.

Main outcome measure. The relative risk of in-hospital mortality comparing the four later periods to the earliest one was estimated using logistic regression, multivariate standardized risk ratios, and Inverse Probability of Treatment Weighting (IPTW). Subgroups with serious head, chest, abdominal and additional extremity injury were investigated.

Results. The mortality risk estimated by IPTW was significantly lower in several time categories: t₁ (RR=0.45, 95%CI: 0.15–0.98, p=0.03), t₂ (RR=0.83, 95%CI: 0.43–1.44, p=0.49), t₃ (RR=0.58, 95%CI: 0.28–0.93, p=0.03) and t₄ (RR=0.43, 95%CI: 0.097–0.94, p=0.03). Those with serious abdominal trauma (Abbreviated Injury Score, AIS≥3) experienced the greatest benefit from delay of internal fixation beyond 12 hours (RR=0.82 for AIS<3, 95%CI: 0.54–1.35; versus RR=0.36 for AIS≥3, 95%CI: 0.13–0.87; p-value for interaction =0.09). The results of the logistic regression and multivariate standardized risk ratios agreed with IPTW estimates. Qualitative and quantitative testing of modeling assumptions supported the validity of the marginal IPTW estimates.

Conclusion. Delayed repair of femoral shaft fractures beyond 12 hours in multi-system trauma patients significantly reduced mortality for three of the four treatment periods studied. Patients with serious abdominal injury benefit most from delayed treatment. This work applies causal inference methodology and assumption testing that is well suited to orthopaedic therapeutic studies when randomization is not possible or ethical.