Delirium, Intraoperative Cerebral Perfusion and EEG Abnormalities After Total Hip Arthroplasty

Pathophysiology of Delirium in Patients Undergoing Total Hip Arthroplasty: Role of Intraoperative Cerebral Perfusion and EEG Abnormalities

The overall objective of this study is to test for perturbations in intraoperative electroencephalogram (EEG) , cerebral blood flow (CBF), cerebral metabolic rate of oxygen consumption (CMRO2), oxygen extraction fraction (OEF), and serum and cerebral spinal fluid biomarkers associated with delirium in high risk population having elective hip arthroplasty at Penn Presbyterian Medical Center (PPMC).

Study Overview

• Status: Terminated
• Conditions: Delirium; Elderly; Hip Arthroplasty
• Intervention / Treatment: Procedure: Blood Draw; Procedure: Cerebral Spinal Fluid collection; Device: Electroencephalogram; Device: Cerebral blood flow and oxygen extraction fraction

Detailed Description

All prospective patients will be given a copy of the informed consent which explains the details and responsibilities of the study.

Each patient will have a preoperative baseline 3D-CAM and MOCA to document preoperative cognitive function and possible criteria for exclusion.

1. The 3D -Confusion Assessment Method (CAM) test is a clinician evaluation and algorithm for the binary determination of presence or absence of delirium.
2. Montreal Confusion Assessment (MOCA) - to be given preoperatively to determine if element of pre-existing cognitive impairment

Intraoperatively each patient will have a NIR Optode patch placed to measure intraoperative cerebral blood flow and oxygen extraction fraction and cerebral metabolic rate of oxygen consumption.

A non-invasive frontal EEG patch will be placed prior to or at the start of anesthesia. Anesthetic depth will be measured using the SEDline® by Masimo. Continuous raw EEG, spectral edge, compressed spectral analysis and percentage suppressed will be recorded from the SEDline® monitor.

The investigators will be drawing blood from patients who agree to participate in the study. Preoperative blood sampling will be done while the investigators place the intravenous line, or if present, from an arterial line.

If a spinal anesthetic is being used, 5 mL of cerebral spinal fluid (CSF) will be collected at the time of dural puncture prior to the administration of the neuraxial blockade.

Members of the research team will administer 3D-CAM testing on post-operative days 1 and 2.

• Study Type: Observational
• Enrollment (Actual): 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients undergoing total joint arthroplasty who are 65 years of age and older.

Description

Inclusion Criteria:

1. Patients 65 years of age and over scheduled for elective total joint arthroplasty
2. Mentally competent and able to give consent for enrollment in the study
3. Patients at any age with a pre-existing diagnosis of dementia or acquired cognitive deficit. Consented by legally authorized representative (LAR).

Exclusion Criteria:

1. Patients currently delirious
2. Acute neurological disease like stroke or brain tumor
3. Current alcohol or substance abuse at risk of postoperative withdrawal

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Delirium; Subjects undergoing elective total joint arthroplasty determined to have delirium by post operative 3D-CAM. Data collected on intraoperative cerebral blood flow and oxygen extraction fraction. CSF collected for biomarkers. Blood colelcted for biomarkers.	Procedure: Blood Draw; 5 mL of blood from the patients preoperative, postoperative, 1 day and 2 days after surgery for a total of 20 mL.; Procedure: Cerebral Spinal Fluid collection; Fluid collected at the time of dural puncture if patients will undergo spinal anesthesia; Other Names: CSF; Device: Electroencephalogram; Test used to detect abnormalities related to electrical activity of the brain will be done during surgery.; Other Names: EEG; Device: Cerebral blood flow and oxygen extraction fraction; NIRS measurement of Cerebral blood flow and cerebral tissue oxygen concentration.
Non-delirium; Subjects undergoing elective total joint arthroplasty determined not to have delirium by post oeprative 3D-CAM. Data collected on intraoperative cerebral blood flow and oxygen extraction fraction. CSF collected for biomarkers. Blood colelcted for biomarkers.	Procedure: Blood Draw; 5 mL of blood from the patients preoperative, postoperative, 1 day and 2 days after surgery for a total of 20 mL.; Procedure: Cerebral Spinal Fluid collection; Fluid collected at the time of dural puncture if patients will undergo spinal anesthesia; Other Names: CSF; Device: Electroencephalogram; Test used to detect abnormalities related to electrical activity of the brain will be done during surgery.; Other Names: EEG; Device: Cerebral blood flow and oxygen extraction fraction; NIRS measurement of Cerebral blood flow and cerebral tissue oxygen concentration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium Rating Scale	The severity of delirium in this patient population as quantified by the DRS	change from Baseline through day 2 post op
Serum biomarkers	The change in serum biomarkers S100β in patients who are diagnosed with delirium by DRS.	change from Baseline through day 2 post op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cerebral blood flow	Changes in CBF from the norm in the patients who develop delirium	change from Baseline through 3 hours
Confusion Assessment Method	Changes in patient performance to determine the presence or absence of delirium as measured by the CAM test	change from Baseline through day 2 post op

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Andrew W Kofke, MD MBA FCCM, University of Pennsylvania

Publications and helpful links

General Publications

• Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8. doi: 10.7326/0003-4819-113-12-941.
• Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):229-42. doi: 10.1176/jnp.13.2.229. Erratum In: J Neuropsychiatry Clin Neurosci 2001 Summer;13(3):433.
• Fong TG, Bogardus ST Jr, Daftary A, Auerbach E, Blumenfeld H, Modur S, Leo-Summers L, Seibyl J, Inouye SK. Cerebral perfusion changes in older delirious patients using 99mTc HMPAO SPECT. J Gerontol A Biol Sci Med Sci. 2006 Dec;61(12):1294-9. doi: 10.1093/gerona/61.12.1294.
• Gokgoz L, Gunaydin S, Sinci V, Unlu M, Boratav C, Babacan A, Soncul H, Halit V, Inanir S, Ersoz A. Psychiatric complications of cardiac surgery postoperative delirium syndrome. Scand Cardiovasc J. 1997;31(4):217-22. doi: 10.3109/14017439709041749.
• Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968 Jul;114(512):797-811. doi: 10.1192/bjp.114.512.797. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimate): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: cerebral blood flow; Confusion Assessment Method; serum biomarkers; modified Blessed Dementia Rating scale; Delirium Rating Scale-98
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium
• Other Study ID Numbers: 822008