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, PhDThe American Geriatrics Society 59:1692 - 1696

Lindsay Drevlow, PA-S2

November 28, 2011

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

Overview Pathophysiology of Delirium

Poorly understood Physiologic stress response metabolic

changes Possible hypothalamic-pituitary-adrenal axis

activation

H-P-A Axis

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

Objective To determine the relationship b/t

perioperative delirium and cortisol, glucose and insulin in older patients acutely admitted for hip fracture

Design and Setting Prospective cohort study

Tertiary University Center

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

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

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

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

Results 143 individuals

49% with delirium 51% without delirium

457 samples 196 with delirium

28 before 137 during 60 after

232 without delirium

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

ResultsOdds Ratio (95% CI) p-value

Factor Univariate Analysis Multivariate Analysis

Cortisol, nmol/L 1.003 (1.001 - 1.004) 0.004

Glucose, mmol/L 0.98 (0.83 - 1.16) 0.81

Insulin, pmol/L 1.00 (1.00 - 1.00) 0.61

Insulin:Glucose 0.99 (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

Age 1.07 (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

Conclusion Negative study for cortisol, insulin and

glucose & the risk of delirium in people with hip fracture

Limitations Results are not generalizable Abnormal glucose levels are only “defined”

for diabetes Would suspect a correlation b/t cortisol and

insulin

Level of Evidence: 2B

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