1. Cortisol, Insulin & Glucose and the Risk of Delirium in Older Adults with Hip Fracture Peter H. Bisschop, MD, PhD; Sophia E. de Rooij, MD, PhD; Aeilko H. Zwinderman, PhD; Hannah E. van Oosten, MD; and Barbara C. van Munster, MD, PhD The American Geriatrics Society 59:1692 - 1696 Lindsay Drevlow, PA-S2 November 28, 2011

2. Overview Delirium = severe neuropsychiatric syndrome Acute onset Fluctuating course of inattention Contributing factors: Preexisting functional/cognitive impairment, acute medical illness, trauma, surgery or medications 30 - 50% older adults with hip fx experience perioperative delirium

3. Overview Pathophysiology of Delirium Poorly understood Physiologic stress response metabolic changes Possible hypothalamic-pituitary-adrenal axis activation

4. H-P-A Axis

5. Overview Cortisol = major stress hormone Functions: Increase blood sugar via gluconeogenesis Suppress immune system Aid in fat, protein and carbohydrate metabolism Glucose and Insulin Counteracts insulin, causing hyperglycemia Inhibits peripheral utilization of glucose

6. Objective To determine the relationship b/t perioperative delirium and cortisol, glucose and insulin in older patients acutely admitted for hip fracture

7. Design and Setting Prospective cohort study Tertiary University Center

8. Participants Inclusion: Consecutive individuals aged 65+ acutely admitted for hip fx May 2005 - October 2008 143 patients Exclusion: Lack of surrogate or refusal to consent Inability to speak or understand Dutch/English 170 patients

9. Methods Confusion Assessment Scale Presence vs. Absence of delirium Delirium Observation Screening Scale Delirium Symptom Interview Subtyping Delirium Rating Scale-98 Severity Charleston Comorbidity Index Informant Questionnaire on Cognitive Decline-short form Katz ADL Index

10. Methods Blood Samples 1 pre-op, 1 - 3 post-op All collected around 11 am Kept on ice Centrifuged to separate plasma & serum Cortisol, Glucose and Insulin measured

11. Statistical Analyses T-tests and Mann-Whitney Tests Log transformation used to fulfill normality 4 separate analyses used to look at relationship b/t C, logG, logI and logI:G Random effect = participant # Fixed effects = day of sample, delirious state, age, sex, preexisting cognitive & functional impairment Logistic Regression Dependent variable = delirium Independent variables = C, G, I, I:G Samples of participants with preexisiting DM taken before/after delirium were excluded

12. Results 143 individuals 49% with delirium 51% without delirium 457 samples 196 with delirium 28 before 137 during 60 after 232 without delirium

13. Results Pre-admission cognitive/functional impairment more prevalent in pts WITH delirium Pre-operative cortisol related to cognitive impairment Delirium a/w higher cortisol and lower insulin in univariate analysis Not significant after correction for pre-existing cognitive/functional impairment in multivariate analysis No difference in insulin w/ or w/o delirium in either analysis

14. Results Odds Ratio (95% CI) p-value FactorUnivariate AnalysisMultivariate Analysis Cortisol, nmol/L1.003 (1.001 - 1.004) 0.004 Glucose, mmol/L0.98 (0.83 - 1.16) 0.81 Insulin, pmol/L1.00 (1.00 - 1.00) 0.61 Insulin:Glucose0.99 (0.96 - 1.02) 0.61 Sex (F:M)2.63 (1.03 - 6.75) 0.04 3.00 (1.01 - 8.93) 0.05 Age1.07 (1.01 - 1.14) 0.02 Preexisiting Cognitive Impairment 7.34 (2.88 - 18.7) <0.001 4.49 (1.46 - 13.8) 0.009 Preexisiting Functional Impairment 17.2 (6.2 - 47.8) <0.001 11.2 (3.76 - 33.2) < 0.001

15. Conclusion Negative study for cortisol, insulin and glucose & the risk of delirium in people with hip fracture

16. Limitations Results are not generalizable Abnormal glucose levels are only “defined” for diabetes Would suspect a correlation b/t cortisol and insulin

17. Level of Evidence: 2B

18. References Bisschop, P. H., de Rooij, S. E., Zwinderman, A. H., van Oosten, H. E. and van Munster, B. C. (2011), Cortisol, Insulin, and Glucose and the Risk of Delirium in Older Adults with Hip Fracture. Journal of the American Geriatrics Society, 59: 1692–1696. doi: 10.1111/j.1532-5415.2011.03575.x