Statin use and risk of delirium in the critically ill

Abstract

Rationale: Delirium is common in intensive care unit (ICU) patients and is a predictor of worse outcomes and neuroinflammation is a possible mechanism. The antiinflammatory actions of statins may reduce delirium.

Objectives: To determine whether critically ill patients receiving statin therapy had a reduced risk of delirium than those not on statins.

Methods: A prospective cohort analysis of data from consecutive ICU patients admitted to a UK mixed medical and surgical critical care unit between August 2011 and February 2012; the Confusion Assessment Method for ICU was used to determine the days each patient was assessed as being free of delirium during ICU admission.

Measurements and main results: Delirium-free days, daily administration of statins, and serum C-reactive protein (CRP) were recorded. Four hundred and seventy consecutive critical care patients were followed, of whom 151 patients received statins. Using random-effects multivariable logistic regression, statin administration the previous evening was associated with the patient being assessed as free of delirium (odds ratio, 2.28; confidence interval, 1.01-5.13; P < 0.05) and with lower CRP (β = -0.52; P < 0.01) the following day. When the association between statin and being assessed as free of delirium was controlled for CRP, the effect size became nonsignificant (odds ratio, 1.56; confidence interval, 0.64-3.79; P = 0.32).

Conclusions: Ongoing statin therapy is associated with a lower daily risk of delirium in critically ill patients. An ongoing clinical trial, informed by this study, is investigating if statins are a potential therapy for delirium in the critically ill.

Figure 1.

(a) The relationship between levels of C-reactive protein (CRP) according to statin use the previous evening. Each point shows the average CRP after adjustments for covariates in each group along with 95% confidence intervals (whiskers above and below the point estimate). There is little overlap in the width of the confidence intervals in each group, suggesting that statin use significantly influences CRP (P < 0.01). (b) The relationship between adjusted CRP and probability of being delirium-free, adjusting by statin use. Each point shows the probability of being free of delirium along with 95% confidence intervals (whiskers above and below point estimate). The higher the CRP, the lower the probability of being free of delirium. For example, if CRP is 20 mg/L the probability of being delirium-free on a given day is 65%; if CRP is 100 mg/L, the probability is 42%. Together, these figures show that statin use is associated with lower CRP, and this in turn is associated with a higher probability of being free of delirium.