Clinical trial NCT02631304: Delirium in Elderly Undergoing Cardiac Surgery and the Significance of CholinEsterase Activity
Official title: Delirium in Elderly Undergoing Cardiac Surgery and the Significance of CholinEsterase Activity Measured by Point of Care Method - a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Complications
Keywords: Postoperative delirium
Cholinesterase activity
Buturylcholinesterase activity
Acetylcholinesterase activity
Elderly patients
Cardiac surgery
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2015-12-16
Enrollment: 100
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Tertiary care clinic

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Acetylcholinesterase (AChE) and buturylcholinesterase (BuChE) activity
timeFrame: 5 days
measure: Delirium
timeFrame: 5-45 days
Secondary outcomes:
measure: Pre-existing patient related risk factors
timeFrame: 1 day
measure: Identification of anticholinergic concomitant medication according to the PRISCUS list
timeFrame: 1 day
measure: Survey of treatment associated data
timeFrame: 45 days
measure: Cognitive function
timeFrame: 45 days
measure: Routine venous blood parameters
timeFrame: 5 days
measure: Inflammatory markers
timeFrame: 5 days
measure: Follow up measure of functional decline according to the IADL scale
timeFrame: 180 days
measure: Follow up measure of mortality
timeFrame: 180 days
measure: Follow up measure of the number of MACCE-events
timeFrame: 180 days
measure: Health related quality of life
timeFrame: 180 days
measure: Instrumental activities of daily living
timeFrame: 180 days
Other outcomes:
measure: Gender effect on delirium assessed by CAM-ICU/CAM
timeFrame: 5-45 days
measure: Gender effects on the peri-operative AChE and BuChE activity
timeFrame: 5-45 days
measure: Postoperative bleeding
timeFrame: 1 day
Locations:
city: Aachen
country: Germany
facility: Department of Anesthesiology, University Hospital Aachen
state: NRW
Study officials:
affiliation: Department of Anesthesiology, University Hospital Aachen, Germany
name: Ana Stevanovic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smulter N, Lingehall HC, Gustafson Y, Olofsson B, Engstrom 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.
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.
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.
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.
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.
citation: Distelmaier K, Winter MP, Rutzler 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.
citation: 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(1):38-45. doi: 10.2119/molmed.2013.00139.