Ongoing Statin Therapy Lowers Risk for Delirium in ICU

Steven Fox

January 17, 2014

Ongoing use of statin therapy in critically ill patients may be associated with reduced risk for dementia, and this effect may be mediated by the anti-inflammatory properties of statins, according to a study published online January 17 in the American Journal of Respiratory and Critical Care Medicine.

"Neuro-inflammation is believed to be a significant factor in delirium pathophysiology," write Valerie J. Page, MB, ChB, from the Intensive Care Unit, Watford General Hospital, United Kingdom, and coauthors. In addition, they note, statins have a number of anti-inflammatory properties and have been the focus of potential therapies for a number of clinical conditions thought to be linked to systemic inflammation.

Delirium, one such condition, occurs in up to 65% of critically ill patients on mechanical ventilation in the United Kingdom and is a predictor of significantly worse clinical outcomes. "Delirium is independently associated with a 3-fold increased risk of mortality at 6 months, and for survivors, a 10-fold increased risk of cognitive impairment at 12 months," the authors write. "Long-term cognitive impairment after critical illness reduces quality of life, increases health care costs and leads to institutionalization."

The researchers designed a prospective cohort study of 470 consecutive intensive care unit patients who were treated at the hospital from August 2011 to February 2012 to find out what effect statin administration might have on patients in intensive care units who are at risk for delirium, No patients were excluded, and the study population included patients who had been admitted to hospital for a variety of problems, including elective emergencies, as well as for medical and surgical reasons.

The researchers collected comprehensive data on the patients, including age, sex, presence of hypercholesterolemia, ischemic heart disease, diabetes, peripheral and cerebrovascular disease, and whether they had undergone surgery for aortic aneurysms.

In addition to documenting the reason for admission and whether it had been an elective or emergency admission, the researchers also assessed daily severity of illness scores, presence of sepsis, number of days patients had required use of a ventilator, and whether they had been taking statins before admission.

Attending nurses regularly scored levels of patient sedation by means of the Richmond Agitation Sedation Scale and then assessed delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). They also monitored levels of C-reactive protein (CRP), an established marker of systemic inflammation.

"In this population of patients admitted to critical care, after adjusting for age, sex, [and] daily illness severity, ongoing statin therapy was associated with a lower daily risk of delirium as well as a concomitant reduction in serum CRP," the researchers report.

More specifically, they say, administration of statins the previous night was significantly associated with patients being free of delirium the following day (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.01 - 5.13; P < .05). Patients who received statins the previous night had lower levels of CRP the following day (β, −0.52; P < .01).

When the link between statins and lack of delirium was controlled for CRP, the effects size did not reach statistical significance (OR, 1.56; 95% CI, 0.64 - 3.79; P = .32).

"These findings are the first to suggest that ongoing statin use reduces brain dysfunction as assessed using the CAM-ICU in consecutive critical care admissions," the researchers write.

They add that the data imply that the anti-inflammatory effects of statins may help stave off systemic inflammation and associated delirium. However, they emphasize that additional studies are needed to confirm the findings.

This study was funded by the UK's National Institute for Health Research, Biotechnology and Biological Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and Medical Research Council.

Am J Respir Crit Care Med. Published online January 17, 2014.

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