Impact of agitation status during intensive care on functional outcomes and mortality in patients with cardiovascular disease

Abstract Background Agitation in patients during intensive care is a frequent complication. Several studies have reported that restlessness and agitation are risk factors for prolonged intensive care unit (ICU) stay and poor prognosis. Since patients with cardiovascular disease (CVD) requiring intensive care are ageing and thereby easily affected by responses, including changes in mental status, optimal management of sedation and agitation statuses during ICU stay is considered crucial. However, the influence of different agitation levels during CVD treatment in the ICU on clinical outcomes after ICU discharge is still unclear. Purpose To investigate the associations of the agitation level during ICU stay with mortality after ICU admission and functional outcomes at hospital discharge. Methods We studied 2236 patients (mean age 67.8±0.3 years) who were admitted to the ICU of a university hospital for CVD treatment and whose highest Richmond Agitation-Sedation Scale (RASS) ≥0, measured daily during ICU stay. In addition to clinical characteristics, we investigated the incidence of all-cause mortality during hospitalization and after hospital discharge. We also measured functional outcomes at discharge among 1625 patients, including 6 minutes walk distance (6MWD), Mini-Cog test, and Patient Health Questionnaire-2 (PHQ-2) as physical, cognitive, and mental functions, respectively. In statistical analysis, patients were divided into three groups based on the highest RASS levels during ICU stay in each patient (Calm: RASS=0, Restless: RASS=1, Agitation: RASS≥2). Kaplan-Meier analysis with a log-rank test and the multivariate Cox proportional hazard model were used to clarify whether higher agitation levels were associated with all-cause mortality. Moreover, the differences between the agitation levels and functional outcomes at hospital discharge were compared using the analysis of covariance. Results During the median follow-up of 1.9 years, all-cause death occurred in 280 patients (12.5%), with an incidence rate of 5.57/100 person-years. The Restless and Agitation groups showed higher mortality than the Calm group (P<0.001), and higher agitation levels in the ICU were significantly associated with a higher rate of all-cause mortality (adjusted hazard ratio: 1.37, 95% confidence interval: 1.19–1.57, P<0.001). Furthermore, as compared with the Calm group, the Restless and Agitation groups showed significantly lower levels of 6MWD (all P<0.001) and Mini-cog (P=0.004 and P<0.001, respectively) and a higher PHQ-2 (all P<0.001), even after adjusting for clinical confounders. Conclusions Agitation during ICU stay in CVD patients was associated with low functional outcomes at hospital discharge and high mortality rate after discharge, irrespective of agitation level. Detailed information on the agitation status during intensive care may be an important indicator in developing management and treatment strategies for patients with CVD admitted to ICU.