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of delirium assessments after ICU discharge could have ledto underestimation of its occurrence. Finally, we did notperform a baseline assessment of inflammatory markers,although inflammation is a possible mechanism associatedwith delirium development [1, 7, 15].

In conclusion, we did not find an association betweenpreoperative statin treatment and postoperative deliriumin a large cohort of patients undergoing isolated orcombined surgical revascularization.

We thank Marialisa Nesta for assistance with data collection.

References

1. Katznelson R, Djaiani GN, Borger MA, et al. Preoperativeuse of statins is associated with reduced early delirium ratesafter cardiac operations. Anesthesiology 2009;110:67–73.

2. Norkiene I, Ringaitiene D, Misiuriene I, et al. Incidence andprecipitating factors of delirium after coronary artery bypassgrafting. Scand Cardiovasc J 2007;41:180–5.

3. Kazmierski J, Kowman M, Banach M, et al. Incidence andpredictors of delirium after cardiac surgery: Results fromThe IPDACS Study. J Psychosom Res 2010;69:179.–85

4. Loponen P, Luther M, Wistbacka JO, et al. Postoperativedelirium and health related quality of life after coronaryartery bypass grafting. Scand Cardiovasc J 2008;42:337–44.

5. Ely EW, Gautam S, Margolin R, et al. The impact of deliriumin the intensive care unit on hospital length of stay. IntensiveCare Med 2001;27:1892–900.

6. Rudolph JL, Jones RN, Levkoff SE, et al. Derivation andvalidation of a preoperative prediction rule for delirium aftercardiac surgery. Circulation 2009;119:229–36.

7. Redelmeier DA, Thiruchelvam D, Daneman N. Deliriumafter elective surgery among elderly patients taking statins.CMAJ 2008;179:645–52.

8. Kazmierski J, Kowman M, Banach M, et al. Preoperativepredictors of delirium after cardiac surgery: a preliminarystudy. Gen Hosp Psychiatry 2006;28:536–8.

9. Koster S, Hensens AG, Schuurmans MJ, van der Palen J.Risk factors of delirium after cardiac surgery A systematicreview. Eur J Cardiovasc Nurs 2011; 10:197–204.

10. Koster S, Hensens AG, van der Palen J. The long-termcognitive and functional outcomes of postoperative deliriumafter cardiac surgery. Ann Thorac Surg 2009;87:1469–74.

11. Sironi L, Cimino M, Guerrini U, et al. Treatment withstatins after induction of focal ischemia in rats reduces theextent of brain damage. Arterioscler Thromb Vasc Biol2003;23:322–7.

12. Stepien K, Tomaszewski M, Czuczwar SJ. Neuroprotectiveproperties of statins. Pharmacol Rep 2005;57:561–9.

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neurologic morbidity after coronary artery bypass grafting.Neurology 2009;73:2099–106.

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17. Mariscalco G, Klersy C, Zanobini M, et al. Atrial fibrillationafter isolated coronary surgery affects late survival. Circula-tion 2008;118:1612–8.

18. First MB. Diagnostic and statistical manual of mental disor-ders. 4th edition. Washington, DC: American PsychiatricAssociation Press, 2000:136–9.

19. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP,Horwitz RI. Clarifying confusion: the confusion assessmentmethod. A new method for detection of delirium. Ann InternMed 1990;113:941–8.

20. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium incritically ill patients: Validation of the confusion assessmentmethod for the intensive care unit (CAM-ICU). Crit CareMed 2001;29:1370–9.

21. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure–definition, outcome measures, animal models, fluid ther-apy and information technology needs: the Second Inter-national Consensus Conference of the Acute DialysisQuality Initiative (ADQI) Group. Crit Care 2004;8:R 2 0 4 – 1 2 .

22. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D.A more accurate method to estimate glomerular filtrationrate from serum creatinine: a new prediction equation.Modification of Diet in Renal Disease Study Group. AnnIntern Med 1999;130:461–70.

23. Rosenbaum PR. Optimal matching for observational studies.J Am Stat Assoc 1989;84:1024–32.

24. Austin PC. Goodness of fit diagnostics fort the propensityscore model when estimating treatment effects using cova-riate adjustment with the propensity score. Pharmacoepide-miol Drug Saf 2008;17:1202–17.

25. Bucerius J, Gummert JF, Borger MA, et al. Predictors of deliriumafter cardiac surgery delirium: effect of beating-heart (off-pump)surgery. J Thorac Cardiovasc Surg 2004;127:57–64.

26. Banach M, Kazmierski J, Kowman M, et al. Atrial fibrilla-tion as a nonpsychiatric predictor of delirium after cardiacsurgery: a pilot study. Med Sci Monit 2008;14:CR286 –291.

27. Inouye SK, Bogardus ST, Jr., Charpentier PA, et al. Amulticomponent intervention to prevent delirium in hospi-talized older patients. N Engl J Med 1999;340:669–76.

28. Gertz K, Laufs U, Lindauer U, et al. Withdrawal of statintreatment abrogates stroke protection in mice. Stroke 2003;34:551–7.

29. Flacker JM, Cummings V, Mach JR, Bettin K, Kiely DK, WeiJ. The association of serum anticholinergic activity withdelirium in elderly medical patients. Am J Geriatr Psychiatry1998;6:31–41.

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31. Xu M, Yuan G, Wei F. Effect of atorvastatin in patients withchronic heart failure–insights from randomized clinical tri-als. Arch Med Sci 2010;6:866–73.

32. Gertz K, Laufs U, Lindauer U, et al. Withdrawal of statin treatmentabrogates stroke protection in mice. Stroke 2003;34:551–7.

33. Le Manach Y, Godet G, Coriat P, et al. The impact ofpostoperative discontinuation or continuation of chronic

statin therapy on cardiac outcome after major vascularsurgery. Anesth Anlg 2007;104:1326–33.

INVITED COMMENTARY

Mariscalco and colleagues [1] studied statin therapy forthe prevention of delirium after cardiac procedures in alarge prospective controlled study that used propensity

atins to match the treatment and control groups. Nobenefit from statin therapy was apparent. The studyappeared adequately powered even though the inci-

dence of delirium in the total study population was lower

0003-4975/$36.00doi:10.1016/j.athoracsur.2012.02.060

1448 MARISCALCO ET AL Ann Thorac SurgPREOP STATINS DO NOT DECREASE POSTOP DELIRIUM 2012;93:1439–48A

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than predicted. In particular, there was no trend towardbenefit from statins that might have become significant in alarger study. In the context of the nonrandomized design itshould be noted that several important mechanisms ofdirect injury to the brain during cardiopulmonary bypass(including hypoperfusion and embolism) were not mea-sured or controlled for in this study, a point that the authorsappropriately acknowledge in the study limitations.

Delirium remains a troublesome complication aftercardiac procedures. It is distressing for patients and theirrelatives and complicates postoperative care. Its occur-rence is also associated with other adverse postoperativeoutcomes (including death), although whether prevent-ing delirium per se would also reduce these associatedcomplications (as the authors of this study imply) re-mains uncertain. Nevertheless, pursuit of a strategy toreduce the incidence of both delirium and the relatedproblem of postoperative cognitive dysfunction remainsa worthy goal. Unfortunately the evidence is mountingthat statins are ineffective in this regard.

Mariscalco and colleagues are among a large group of

researchers worldwide who have investigated pharma-

cologic neuroprotection in cardiac procedures only tofind inconsistent or negative results. This general line ofinvestigation should, however, continue to be encour-aged. The ongoing absence of editorial bias againstpublishing well-conducted negative studies in The Annalsof Thoracic Surgery is an important contribution to clarityabout the issue and to a research effort that may one day“strike gold.”

Simon Mitchell, MB ChB, FANZCA

Department of AnaesthesiologyUniversity of AucklandPrivate Bag 92019Auckland, New Zealand 1142e-mail: sj.mitchell@auckland.ac.nz

Reference

1. Mariscalco G, Cottini M, Zanobini M, et al. Preoperativestatin therapy is not associated with a decrease in the inci-

dence of delirium after cardiac operations. Ann Thorac Surg2012;93:1439–48.