Delirium in Elderly Undergoing Cardiac Surgery and the Significance of CholinEsterase Activity

Postoperative Complications Clinical Trial

— DECCEP  

Official title:

Delirium in Elderly Undergoing Cardiac Surgery and the Significance of CholinEsterase Activity Measured by Point of Care Method - a Prospective Observational Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02631304
• Other study ID #: 15-162
• Status: Completed
• First received: December 9, 2015
• Last updated: April 10, 2018
• Start date: July 2015
• Est. completion date: November 2016

Study information

• Verified date: April 2018
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to assess the association between the "point-of-care" (POC) measured ChE activity (Acetylcholinesterase (ChE) + Buturylcholinesterase (ChE)) and postoperative delirium in elderly patients undergoing cardiac surgery.

Furthermore the investigators aim to identify factors, which influence the baseline levels and the time course of ChE activity.

Description:

Cardiac surgery in elderly patients is associated with serious complications, like increased morbidity, mortality and postoperative delirium with further hazardous consequences. The incidence of postoperative delirium in elderly is reported with a range from 36.6% - 54.9%. The pathophysiology of delirium is complex and the interaction of the cholinergic system and inflammation reaction is a relevant precipitant factor. It was suggested that there is a strong association between the perioperative plasma ChE activity and the inflammatory response in patients developing delirium. Patients showed a significant reduction of the total ChE activity after orthopaedic surgery, with significant lower pre- and postoperative values of AChE and BuChE and increased inflammatory response in patients developing postoperative delirium. It remains unclear if these results are applicable to other patient populations and which factors have influenced the low preoperative ChE levels. In patients suffering from a cardiac disease, a reduced total ChE respectively BuChE activity was significantly associated with mortality and long-term major adverse cardiovascular events. The investigators hypothesize that the ChE activity in peripheral blood can be used as a potential biomarker, to early detect patients at high risk for postoperative delirium.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent

• = 65 years of age

• Scheduled to undergo elective cardiac surgery (coronary artery bypass graft (CABG), valve surgery, combined CABG-valve surgery) with the use of CPB

• Both genders

Exclusion Criteria:

• Planned deep hypothermic arrest

• Acute / emergency procedures

• Surgery without extracorporeal circulation (ECC)

• Patients with a history of pseudocholinesterase deficiency

• Employees of the respective study centres

• Illiteracy

• Severe communication difficulties and severe vision or hearing problems

• Patients legally unable to give written informed consent

• non-fluency in German language

• Severe psychiatric or neuropsychiatric disorders

• MMSE < 24 points, short geriatric depression scale (GDS) = 10 points

• Recent (<6 months) history of alcohol or drug abuse

• The participation in a drug or device trial within the previous 30 days

Related Conditions & MeSH terms

• Delirium
• Postoperative Complications

Intervention

Procedure:
• Elective cardiac surgery
Coronary artery bypass graft (CABG), valve surgery, combined CABG-valve surgery

Locations

Country	Name	City	State
Germany	Department of Anesthesiology, University Hospital Aachen	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Arbel Y, Shenhar-Tsarfaty S, Waiskopf N, Finkelstein A, Halkin A, Revivo M, Berliner S, Herz I, Shapira I, Keren G, Soreq H, Banai S. Decline in serum cholinesterase activities predicts 2-year major adverse cardiac events. Mol Med. 2014 Feb 12;20:38-45. doi: 10.2119/molmed.2013.00139. — View Citation

Cerejeira J, Batista P, Nogueira V, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. Low preoperative plasma cholinesterase activity as a risk marker of postoperative delirium in elderly patients. Age Ageing. 2011 Sep;40(5):621-6. doi: 10.1093/ageing/afr053. Epub 2011 May 15. — View Citation

Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. The immunology of delirium. Neuroimmunomodulation. 2014;21(2-3):72-8. doi: 10.1159/000356526. Epub 2014 Feb 14. Review. — View Citation

Distelmaier K, Winter MP, Rützler K, Heinz G, Lang IM, Maurer G, Koinig H, Steinlechner B, Niessner A, Goliasch G. Serum butyrylcholinesterase predicts survival after extracorporeal membrane oxygenation after cardiovascular surgery. Crit Care. 2014 Jan 30;18(1):R24. doi: 10.1186/cc13711. — View Citation

Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. doi: 10.1016/S0140-6736(13)60688-1. Epub 2013 Aug 28. Review. — View Citation

Rudolph JL, Inouye SK, Jones RN, Yang FM, Fong TG, Levkoff SE, Marcantonio ER. Delirium: an independent predictor of functional decline after cardiac surgery. J Am Geriatr Soc. 2010 Apr;58(4):643-9. doi: 10.1111/j.1532-5415.2010.02762.x. Epub 2010 Mar 22. — View Citation

Smulter N, Lingehall HC, Gustafson Y, Olofsson B, Engström KG. Delirium after cardiac surgery: incidence and risk factors. Interact Cardiovasc Thorac Surg. 2013 Nov;17(5):790-6. doi: 10.1093/icvts/ivt323. Epub 2013 Jul 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gender effect on delirium assessed by CAM-ICU/CAM	Analysis of the association of postoperative delirium until 5.POD respective discharge day and the gender of the patient	5-45 days
Other	Gender effects on the peri-operative AChE and BuChE activity	Measurement of the AChE and BuChE activity until 3.-5.POD. Analysis of the association of the gender of the patient and the peri-operative time-course of the AChE and BuChE activity until the 3. respective 5.POD.	5-45 days
Other	Postoperative bleeding	Measured 12 hours after surgery	1 day
Primary	Acetylcholinesterase (AChE) and buturylcholinesterase (BuChE) activity	The perioperative AChE and BuChE activity will be assessed in the whole blood by a "point-of-care" measuring instrument (ChE check mobile ®) and the association to the incidence and duration of postoperative delirium will be determined. It will be assessed preoperative and maximum until the 5th postoperative day (POD), minimum until the 3.POD.	5 days
Primary	Delirium	Postoperative delirium will be assessed preoperative and daily with the CAM / CAM-ICU test until the 5.POD and on the discharge day from hospital. The incidence of postoperative delirium will be associated with the perioperative AChE and BuChE time course.	5-45 days
Secondary	Pre-existing patient related risk factors	Influence of pre-existing patient related risk factors ( demographic data, medical and surgical history assessed preoperative) on postoperative delirium and the AChE and BuChE activity.	1 day
Secondary	Identification of anticholinergic concomitant medication according to the PRISCUS list	Number of participants with preoperative anticholinergic medication	1 day
Secondary	Survey of treatment associated data	Survey of treatment associated data until discharge (organ dysfunctions, postoperative pain, ICU length of stay, hospital length of stay, duration of mechanical ventilation, readmission rate to ICU, operation time, surgery, anaesthesia, intraoperative and postoperative volume load, postoperative mortality, comorbidities)	45 days
Secondary	Cognitive function	Assessment of the cognitive function preoperative and on 3.POD and at discharge,by mini mental state examination (MMSE)	45 days
Secondary	Routine venous blood parameters	Correlation of AChE and BuChE activity and routine venous blood parameters (Hb, Platelets, Leucocytes, INR, PTT, liver-enzymes (AST, ALT, y-GT, total Bilirubin), Creatinine, BUN, Albumin, sodium and potassium) and the influence on postoperative delirium	5 days
Secondary	Inflammatory markers	Correlation of AChE and BuChE activity to inflammatory markers in serum and the influence on postoperative delirium	5 days
Secondary	Follow up measure of functional decline according to the IADL scale	Patients will be followed up by phone on the 30. and 180.POD. Association of AChE and BuChE activity and the functional decline on the 30. and 180.POD. The preoperative IADL scale will be compared to the data on the 30. and 180.POD to assess the functional decline	180 days
Secondary	Follow up measure of mortality	Patients will be followed up by phone on the 30. and 180.POD. Determination of the association between the peri-operative AChE and BuChE activity and the mortality on the 30. and 180.POD	180 days
Secondary	Follow up measure of the number of MACCE-events	Patients will be followed up by phone on the 30. and 180.POD. Association of AChE and BuChE activity and the postoperative major adverse cardiovascular and cerebral events (MACCE) on the 30. and 180.POD. The number of events will be assessed.	180 days
Secondary	Health related quality of life	Health related quality of life measured by EuroQuol EQ-5D-5L test preoperative, on 30.POD and 180. POD	180 days
Secondary	Instrumental activities of daily living	The Lawton Instrumental Activities of Daily Living (IADL) Scale measured preoperative, on 30.POD and 180. POD	180 days