Infections Up to 76 Days After Stroke Increase Disability and Death

Abstract

Early infection after stroke is associated with a poor outcome. We aimed to determine whether delayed infections (up to 76 days post-stroke) are associated with poor outcome at 90 days. Data came from the international Efficacy of Nitric Oxide Stroke (ENOS, ISRCTN99414122) trial. Post hoc data on infections were obtained from serious adverse events reports between 1 and 76 days following stroke in this large cohort of patients. Regression models accounting for baseline covariates were used to analyse fatalities and functional outcomes (modified Rankin Scale (mRS), Barthel Index, Euro-Qol-5D) at 90 days, in patients with infection compared to those without infection. Of 4011 patients, 242 (6.0%) developed one or more serious infections. Infections were associated with an increased risk of death (p < 0.001) and an increased likelihood of dependency (measured by mRS) compared to those of all other patients (p < 0.001). This remained when only surviving patients were analysed, indicating that the worsening of functional outcome is not due to mortality (p < 0.001). In addition, the timing of the infection after stroke did not alter its detrimental association with fatality (p = 0.14) or functional outcome (p = 0.47). In conclusion, severe post-stroke infections, whether occurring early or late after stroke, are associated with an increased risk of death and poorer functional outcome, independent of differences in baseline characteristics or treatment. Not only are strategies needed for reducing the risk of infection immediately after stroke, but also during the first 3 months following a stroke. This study is registered: ISRCTN registry, number ISRCTN99414122, ClinicalTrials.gov Identifier, NCT00989716.

Keywords: Disability; Glyceryl trinitrate; Infection; Stroke.

Figures

Figure 1

Criteria used for selection of patients for analysis of the effects of infection. Patients were excluded due to lack of defined stroke type, previous stroke or serious adverse events (SAEs) after 76 days. Remaining patients were grouped based on the absence of SAEs or the presence of infections, secondary stroke-related cerebral events (SSRCEs) or other SAEs. Patients with infections were compared to all three of the other patient groups (individually or combined (termed: all other patients)) to assess the effect of infection on case fatality and functional outcome.

Figure 2

Descriptive Kapler-Meier graphs for patients developing infections between 1-76 days post-stroke and other groups of patients. A: Patients with infections (n=212) in comparison to all other patients (after exclusions, n=3,072). B: Patients with infections in comparison to those with secondary stroke-related cerebral events (SSRCEs, n=242) or with other serious adverse events (SAEs, n=306).

Figure 3

Distributions in modified Rankin Scale scores at day 90 for stroke patients with infections and all other patients. A: All patients with serious adverse events (SAEs) between 1-76 days post-stroke and patients without SAEs. B: Patients who survived to 90 days only. C: Surviving patients were split into patients who acquired infections or other SAEs between: 1-7 days post-stroke, 8-28 days post-stroke and 29-76 days post-stroke. The infection group had higher Rankin Scores even when non-surviving patients were removed, indicating more dependency. This was maintained when patients were split into groups based on time of infection occurrence. OR=Odds ratio. CI=Confidence Interval.