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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
Results
Odds 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