Statins and Delirium During Critical Illness

Abstract

Objective Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness whereas discontinuation of statin therapy is associated with increased delirium. Design Multicenter, prospective cohort study. Setting Medical and surgical intensive care units (ICUs) in two large tertiary care hospitals in the United States. Patients Patients with acute respiratory failure or shock. Measurements and Main Results We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median [interquartile range] age was 61 [51–70] years and APACHE II was 25 [19–31], 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, 588 (77%) developed delirium. After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; e.g., statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10–0.49) but not among patients without sepsis on day 1 (OR, 0.92; 95% CI, 0.46–1.84) or among those with sepsis later, e.g., on day 13 (OR, 0.70; 95% CI, 0.35–1.41). Prehospital statin use was not associated with delirium (OR, 0.86; 95% CI, 0.44–1.66; p = 0.18), yet the longer a prehospital statin user’s statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the OR depending on sepsis status and study day due to significant interactions). Conclusions In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.

Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial

“…The findings that rosuvastatin did not improve delirium in intensive care conflicts with two rigorous observational studies, 19,20 which showed strong and consistent associations between statin use and reduced daily delirium in intensive care, particularly for patients with sepsis early in their stay in intensive care. 19 The high overall prevalence of delirium in our study or heterogeneity in baseline risk for delirium within our study cohort might have affected our results.…”

“…19 The high overall prevalence of delirium in our study or heterogeneity in baseline risk for delirium within our study cohort might have affected our results. Additionally, the differences between our findings and those of observational studies might be a result of unmeasured confounders biasing the observational studies—a limitation minimised in a randomised, double-blind trial.…”

“…19 Not surprisingly, the prevalence was lower (36%) in the other observational study of statins for delirium, 20 which assessed all consecutive patients admitted to a single intensive care unit in which only 42% of patients were mechanically ventilated, and lower than the pooled prevalence in a meta-analyses of critically ill patients (31·8%). 52 The prevalence of cognitive impairment at 6 months and 12 months in this report was very similar to a separate patient cohort from ARDSNet’s EDEN trial (36% at 6 months, 25% at 12 months), which used an identical battery of cognitive tests and definition of cognitive impairment.…”

“…Studies of patients having cardiac or vascular surgery 17,18 suggest that statins might protect against delirium. Moreover, two large, well-designed, observational studies 19,20 of critically ill patients provide data showing strong and consistent associations between statin use and reduced odds of daily delirium in intensive care, particularly in patients with sepsis early in their intensive care unit stay. This potential benefit is hypothesised to be mediated through a reduction in systemic inflammation.…”

“…20 Consequently, there is great interest in further evaluating the effect of statins on delirium in intensive care and subsequent cognitive function in randomised trials. 8,19–22 …”