Addition of Vitamin B Complex to Prime Solution in Cobalamin-Deficient Patients to Prevent Postoperative Delirium

  • Ertan Demirdas Cardiovascular Surgery Department, Medicine Faculty, Bozok University, Yozgat, Turkey
  • Kivanc Atilgan Cardiovascular Surgery Department, Medicine Faculty, Bozok University, Yozgat, Turkey


Objective: In this study, we investigated whether the addition of vitamin B complex to prime solution for cardiopulmonary bypass (CPB) in cobalamin-deficient patients undergoing on-pump coronary artery bypass grafting (CABG) helps prevent the development of postoperative delirium (POD).

Materials and Methods: In the present study, 69 of 138 patients with serum vitamin B12 levels <200 pg/mL based on the blood sample taken within 1 week prior to on-pump CABG between January 2013 and December 2017 were enrolled. The control group included 69 patients. Vitamin B complex (25 mg vitamin B1, thiamine hydrochloride; 2.734 mg vitamin B2, riboflavin phosphate ester monosodium; 5 mg vitamin B6, pyridoxine hydrochloride; 15 mcg vitamin B12; 50 mg niacinamide; and 17.2 mg D-panthenol) was added to the prime solution for CPB in the study group. The Intensive Care Delirium Screening Checklist (ICDSC) was used for the diagnosis of POD, and the severity of delirium was assessed by using the Delirium Rating Scale-Revised-98 (DRS-R-98).

Results: Twenty-nine patients in the control group (42%) and 18 patients (26%) in the study group developed POD
(P = .017); delirium severity scores were higher in the control group (16.5 ± 2.9 versus 15.03 ± 2.48; P = .034). Logistic regression analyses showed vitamin B complex was an independent protective factor for preventing the development of POD in patients undergoing on-pump CABG (odds ratio [OR]: 0.23; 95% confidence interval [95% CI]: 0.06-0.83; P = .025).

Conclusion: On the basis of the results of our study, the addition of vitamin B complex to the prime solution for CPB decreases the incidence of POD in cobalamin-deficient patients undergoing on-pump CABG.


Adamis D, van Munster BC, Macdonald AJ. 2009. The genetics of deliria. Int Rev Psychiatry 21(1):20-9.

Allen LH. 2009. How common is vitamin B-12 deficiency? Am J Clin Nutr 89(2):693S-696S.

Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. 2001. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 27:859-64.

Birch CS, Brasch NE, McCaddon A, Williams JH. 2009. A novel role for vitamin B(12): cobalamins are intracellular antioxidants in vitro. Free Radic Biol Med 47(2):184-8.

Boldyrev AA, Johnson P. 2007. Homocysteine and its derivatives as possible modulators of neuronal and non-neuronal cell glutamate receptors in Alzheimer’s disease. J Alzheimers Dis 11(2):219-228.

Bor MV, Lydeking-Olsen E, Møller J, Nexø E. 2006. A daily intake of approximately 6 microg vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women. Am J Clin Nutr 83:52-8.

Cerejeira J, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. 2010. The neuroinflammatory hypothesis of delirium. Acta Neuropathol 119(6):737-54.

Clarke R, Grimley Evans J, Schneede J, et al. 2004. Vitamin B12 and folate deficiency in later life. Age Ageing 33(1):34-41.

Cunningham CC, Maclullich A. 2013. At the extreme end of the psychoneuroimmunological spectrum: delirium as a maladaptive sickness behaviour response. Brain Behav Immun 28:1-13.

Dasgupta M, Dumbrell AC. 2006. Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J Am Geriatr Soc 54(10):1578-89.

Field RR, Wall MH. 2013. Delirium: past, present, and future. Semin Cardiothorac Vasc Anesth 17:170-9.

Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. 2008. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci 63(7):764-72.

Inouye SK, Bogardus ST Jr, Charpentier PA, et al. 1999. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 340(9):669-76.

Jayaram N, Rao MG, Narasimha A, et al. 2013. Vitamin B12 levels and psychiatric symptomatology: a case series. J Neuropsychiatry Clin Neurosci 25(2):150-2.

Kazmierski J, Banys A, Latek J, et al. 2014. Mild cognitive impairment with associated inflammatory and cortisol alterations as independent risk factor for postoperative delirium. Dement Geriatr Cogn Disord 38(1-2):65-78.

Kazmierski J, Banys A, Latek J, Bourke J, Jaszewski R. 2013. Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium: a prospective cohort study. Crit Care 17(2):R38.

Koster S, Hensens AG, van der Palen J. 2009. The long-term cognitive and functional outcomes of postoperative delirium after cardiac surgery. Ann Thorac Surg 87(5):1469-74.

Kruman II, Culmsee C, Chan SL, et al. 2000. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 20(18):6920-6.

Lachner C, Steinle NI, Regenold WT. 2012. The neuropsychiatry of vitamin B12 deficiency in elderly patients. J Neuropsychiatry Clin Neurosci 24(1):5-15.

Mangnall LT, Gallagher R, Stein-Parbury J. 2011. Postoperative delirium after colorectal surgery in older patients. Am J Crit Care 20(1):45-55.

Matté C, Mackedanz V, Stefanello FM, et al. 2009. Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int 54(1):7-13.

McDonagh DL, Berger M, Mathew JP, Graffagnino C, Milano CA, Newman MF. 2014 Neurological complications of cardiac surgery. Lancet Neurol 13(5):490-502.

McLean ED, Allen LH, Neumann CG, et al. 2007. Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods. J Nutr 137(3):676-82.

Moore E, Mander A, Ames D, Carne R, Sanders K, Watters D. 2012. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr 24(4):541-56.

Mu DL, Wang DX, Li LH, et al. 2010. High serum cortisol level is associated with increased risk for delirium after coronary artery bypass graft surgery: a prospective cohort study. Crit Care 14(6):R238.

Refsum H, Yajnik CS, Gadkari M, et al. 2001. Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J Clin Nutr 74(2):233-41.

Ritter C, Tomasi CD, Dal-Pizzol F, et al. 2014. Inflammation biomarkers and delirium in critically ill patients. Crit Care 18(3):R106.

Robinson TN, Eiseman B. 2008. Postoperative delirium in the elderly: diagnosis and management. Clin Interv Aging 3(2):351-5.

Rush EC, Katre P, Yajnik CS. 2014. Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease. Eur J Clin Nutr 68(1):2-7.

Sanford AM, Flaherty JH. 2014. Do nutrients play a role in delirium? Curr Opin Clin Nutr Metab Care 17(1):45-50.

Scalabrino G, Veber D, Mutti E. 2008. Experimental and clinical evidence of the role of cytokines and growth factors in the pathogenesis of acquired cobalamin-deficient leukoneuropathy. Brain Res Rev 59(1):42-54.

Schreier AM. 2010. Nursing care, delirium, and pain management for the hospitalized older adult. Pain Manag Nurs 11(3):177-85.

Siekmann JH, Allen LH, Bwibo NO, Demment MW, Murphy SP, Neumann CG. 2003. Kenyan school children have multiple micronutrient deficiencies, but increased plasma vitamin B-12 is the only detectable micronutrient response to meat or milk supplementation. J Nutr 133(11 suppl 2):3972S-3980S.

Silverstein JH, Timberger M, Reich DL, Uysal S. 2007. Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesthesiology 106(3):622-8.

Sockalingam S, Parekh N, Bogoch II, et al. 2005. Delirium in the postoperative cardiac patient: a review. J Card Surg 20(6):560-7.