Long-term functional outcome in patients with acquired infections after acute spinal cord injury

Abstract

Objective: To investigate whether prevalent hospital-acquired pneumonia and wound infection affect the clinical long-term outcome after acute traumatic spinal cord injury (SCI).

Methods: This was a longitudinal cohort study within the prospective multicenter National Spinal Cord Injury Database (Birmingham, Alabama). We screened datasets of 3,834 patients enrolled in 20 trial centers from 1995 to 2005 followed up until 2016. Eligibility criteria were cervical SCI and American Spinal Cord Injury Association impairment scale A, B, and C. Pneumonia or postoperative wound infections (Pn/Wi) acquired during acute medical care/inpatient rehabilitation were analyzed for their association with changes in the motor items of the Functional Independence Measure (FIM_motor) using regression models (primary endpoint 5-year follow-up). Pn/Wi-related mortality was assessed as a secondary endpoint (10-year follow-up).

Results: A total of 1,203 patients met the eligibility criteria. During hospitalization, 564 patients (47%) developed Pn/Wi (pneumonia n = 540; postoperative wound infection n = 11; pneumonia and postoperative wound infection n = 13). Adjusted linear mixed models after multiple imputation revealed that Pn/Wi are significantly associated with lower gain in FIM_motor up to 5 years after SCI (-7.4 points, 95% confidence interval [CI] -11.5 to -3.3). Adjusted Cox regression identified Pn/Wi as a highly significant risk factor for death up to 10 years after SCI (hazard ratio 1.65, 95% CI 1.26 to 2.16).

Conclusion: Hospital-acquired Pn/Wi are predictive of propagated disability and mortality after SCI. Pn/Wi qualify as a potent and targetable outcome-modifying factor. Pn/Wi prevention constitutes a viable strategy to protect functional recovery and reduce mortality. Pn/Wi can be considered as rehabilitation confounders in clinical trials.

Figure 1. Dataset selection and analysis chart

(A) Patients enrolled into the National Spinal Cord Injury Database (NSCID) within 1 day after spinal cord injury (SCI) were assigned to long-term follow-up. Datasets from the NSCID collected between 1995 and 2005 comprise data on pneumonia or postoperative wound infection (Pn/Wi) and motor items of the Functional Independence Measure (FIM) long-term outcome. Thus, those datasets were screened for eligibility. The data for statistical analysis were selected stepwise with respect to quality aspects of the particular assessment tools, possible confounding factors, and the availability of key baseline data. The linear mixed regression models were performed as a complete case analysis and—in order to control for attrition bias—after multiple imputation. *Total numbers may differ from subgroup numbers because some items applied multiple times. (B) Assessment points following SCI are indicated representing medians and interquartile range. AIS = American Spinal Cord Injury Association impairment scale; ISNCSCI = International Standards for Neurologic Classification of Spinal Cord Injury.

Figure 2. Differential recovery of motor items of the Functional Independence Measure (FIM_motor) total score up to 5 years in the total sample and stratified for lesion severity (American Spinal Cord Injury Association impairment scale [AIS])

Differences from FIM_motor baseline (median) at admission were compared between patients with and without documented pneumonia or postoperative wound infection (Pn/Wi) at discharge, 1 year after spinal cord injury (SCI), and 5 years after SCI. FIM_motor was significantly reduced in the Pn/Wi group in the total sample and in AIS A at all time points up to 5 years, whereas in AIS B and C, statistical significance was only transiently present. Sample size: FIM_motor score at discharge (d), 1 year, and 5 years: (d) n = 619 without Pn/Wi, n = 553 with Pn/Wi; (1 y) n = 398, n = 322; (5 y) n = 217, n = 176. AIS A: (d) n = 251, n = 363; (1 y) n = 163, n = 205; (5 y) n = 91, n = 118. AIS B: (d) n = 149, n = 104; (1 y) n = 103, n = 61; (5 y) n = 55, n = 35. AIS C: (d) n = 219, n = 86; (1 y) n = 132, n = 56; (5 y) n = 71, n = 23. Boxes are plotted as median and interquartile range; whiskers are defined according to Tukey and outliers are indicated by dots. Mann-Whitney test statistical significances are corrected using the Bonferroni method: *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 3. Infection-associated mortality

Kaplan-Meier curves indicate an increased cumulative mortality for patients with pneumonia or postoperative wound infection (Pn/Wi) in the overall population (A) and subsequent stratification for injury severity (B–D) during the 5-year follow-up. Sample size: number of events of death, number of patients. (A) Total sample (American Spinal Cord Injury Association impairment scale [AIS] A–C): n = 294, n = 1,203; (B) AIS A: n = 182, n = 631; (C) AIS B: n = 56, n = 263; (D) AIS C: n = 56, n = 309. SCI = spinal cord injury.