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Statin Use and Risk of Delirium in the Critically Ill
Study Question: Is statin use associated with a reduction in systemic inflammation and subsequently less delirium?
Study Description: This single center, prospective cohort study included all consecutive patients admitted to a 19 bed mixed medical and surgical adult ICU. There were no exclusion criteria.
Patients were allocated to the “never statin” group if they did not receive statins throughout ICU admission regardless of pre-admission use. Statins were only prescribed for patients who had been on a statin pre-admission. On an individual day, patients in the “statin” group were allocated to the ”never statin” group if they did not receive the statin for any reason. Statins were administered in the evening and blood for serum C-reactive protein (CRP) measurement was drawn the next morning. If any CAM-ICU assessment on a given day was recorded as positive or the patient was unable to be assessed, that day was counted as not delirium- or coma-free.
Results: The study analysis included 470 consecutive patients with 2,927 person-days of follow up. One hundred sixty-seven patients were assessed as having delirium at least once; of these patients, 44 had delirium throughout the admission. The median duration of delirium was 2 days (IQR 1-5).
Results were analyzed using regression models. An association between statin use and being delirium-free was observed (OR 2.28, 95% CI 1.01-5.13, p < 0.05). Statin use was also associated with lower CRP levels (b=-0.52, 95% CI -0.7 to -0.33, p < 0.01). When accounting for CRP, the observed effect size of statin administration on the probability of being free of delirium was reduced and became non-significant (p = 0.32), however a significant relationship between CRP and being free of delirium remained (OR 0.68, 95% CI 0.51-0.90). For each additional day the statin was received, the odds of being coma- and delirium-free increased (OR 1.39, 95% CI 1.18-1.63, p < 0.001).
Conclusion(s): Ongoing statin therapy was associated with a lower daily risk for delirium and concomitant reduction in serum CRP.
Perspective: A causal relationship between statin use and prevention of delirium cannot be concluded due to the study methodology. Statin administration was omitted for 46% of total admission days for patients who had been receiving statins pre-admission. Data regarding known confounders (type of sedative agents used, concomitant delirium treatment) was not collected. Also, patients in the “statin” group received the same statin that they were on prior to admission, so only three statins were prescribed (simvastatin, pravastatin and atorvastatin) and dosing information was lacking. Given these results, it would be acceptable to continue statin therapy in patients receiving them pre-admission with appropriate safety monitoring, however, clinicians should not recommend starting statin therapy for the prevention of delirium until results of randomized clinical trials are available.