Cognitive Dysfunction Following Cardiac Surgery

NCT02767713 | Unknown Phase 4 DMC

• 1 other identifier: SPLIT1984
• Study Type: interventional
• Target: 171
• Locations: 0 countries
• Sites: N/A

Brief Summary

Postoperative cognitive dysfunction (POCD) is the most common complication after cardiac surgery. This prospective study was conducted to investigate the mechanisms of development of POCD following cardiac surgery taking into account surgical technique (with use or no use of extracorporeal circulation). The investigators focused on the role of inflammatory and stress response to surgical procedure as potential factors involved in the pathogenesis of cognitive dysfunction. Systematic inflammatory response in patients undergoing on-pump or off-pump surgery was analyzed by measuring serum levels of C reactive protein (CRP) and occurrence of systemic inflammatory response syndrome (SIRS). Stress response to surgery was evaluated following cortisol levels and its daily variations. The degree of cognitive dysfunction was assessed based on serum levels of S100β. The effect of dexamethasone on the levels of stress and inflammatory response biomarkers, serum levels of S100β, as well as on the development of POCD was compared with control group that received normal saline.

Conditions

Postoperative Cognitive Dysfunction

Keywords

Cognition Disorders; Cardiac Surgical Procedures; dexamethasone

Outcome Measures

Primary Outcomes (1)

• Difference in occurrence of postoperative cognitive dysfunction between control and intervention group at six days after surgery as determined by using a validated battery of cognitive tests

  Difference in occurrence of postoperative cognitive dysfunction between control and intervention group at sixth postoperative day as determined by using a validated battery of cognitive tests that assess global cognitive function, psychomotor speed, visual-motor coordination, concentration, attention, short-term memory, learning curve and aspects of executive functioning. Time points of assessment are two days before surgery and six days after surgery in both study arms.

  9 days

Secondary Outcomes (8)

• Change in serum levels of S100β protein from baseline to first postoperative day

  3 days

• Difference in S100β serum protein levels between control and intervention group on the day of surgery and first postoperative day

  7 days

• Change in serum cortisol levels from baseline to fifth postoperative day

  7 days

• Difference in serum cortisol levels between control and intervention group on the first, third and fifth postoperative days

  7 days

• Change in serum C reactive protein levels from baseline to fifth postoperative day

  7 days

Study Arms (2)

Dexamethasone

EXPERIMENTAL

Dexamethasone dose of 0.1 mg/kg was administered intravenously 10h before surgery

Drug: Dexamethasone

Control

PLACEBO COMPARATOR

Equal volume of normal saline (placebo) was administered intravenously 10h before surgery

Other: Placebo

Interventions

Dexamethasone DRUG

Intravenous dexamethasone (0.1 mg/kg) was administered 10 hours before surgery.

Also known as: Dexasone

Dexamethasone

Placebo OTHER

Normal saline (placebo) in the equal volume as active treatment was administered 10 hours before surgery.

Also known as: Inactive substance

Control

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants undergoing cardiac surgery: coronary artery bypass grafting, heart valve surgery or a combined procedure,
• Procedure must be elective

You may not qualify if:

• Symptomatic cerebrovascular disease,
• Cerebrovascular incident in last 3 years,
• Neurodegenerative disease,
• Psychiatric disease,
• Visual, hearing or motor impairment interfering with cognitive testing,
• Carotid artery stenosis ( ≥50%),
• Myocardial infarction within last 3 months,
• Left ventricular ejection fraction of ≤35%,
• Previous cardiac or carotid surgery,
• Uncontrolled systemic hypertension (blood pressure≥180/110 mmHg),
• Corticosteroid-dependent asthma,
• Chronic obstructive pulmonary disease (COPD),
• Malignancy, liver disease (aspartate transaminase (AST), alanine transaminase (ALT) or bilirubin ˃1.5x above reference range),
• Kidney disease (serum creatinine ˃1.7 mg/dl or blood urea nitrogen ˃50 mg/dL),
• Uncontrolled diabetes mellitus (postprandial glucose ˃200 mg/dL or hemoglobin A1c ˃9%),

Sponsors & Collaborators

• Clinical Hospital Center, Split: lead

Related Publications (13)

• Ottens TH, Dieleman JM, Sauer AM, Peelen LM, Nierich AP, de Groot WJ, Nathoe HM, Buijsrogge MP, Kalkman CJ, van Dijk D; DExamethasone for Cardiac Surgery (DECS) Study Group. Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial. Anesthesiology. 2014 Sep;121(3):492-500. doi: 10.1097/ALN.0000000000000336.

  PMID: 25225745 BACKGROUND

• Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001 Feb 8;344(6):395-402. doi: 10.1056/NEJM200102083440601.

  PMID: 11172175 BACKGROUND

• Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, Aggarwal A, Marschall K, Graham SH, Ley C. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med. 1996 Dec 19;335(25):1857-63. doi: 10.1056/NEJM199612193352501.

  PMID: 8948560 BACKGROUND

• Hudetz JA, Gandhi SD, Iqbal Z, Patterson KM, Pagel PS. Elevated postoperative inflammatory biomarkers are associated with short- and medium-term cognitive dysfunction after coronary artery surgery. J Anesth. 2011 Feb;25(1):1-9. doi: 10.1007/s00540-010-1042-y.

  PMID: 21061037 BACKGROUND

• Rasmussen LS, O'Brien JT, Silverstein JH, Johnson TW, Siersma VD, Canet J, Jolles J, Hanning CD, Kuipers HM, Abildstrom H, Papaioannou A, Raeder J, Yli-Hankala A, Sneyd JR, Munoz L, Moller JT; ISPOCD2 Investigators. Is peri-operative cortisol secretion related to post-operative cognitive dysfunction? Acta Anaesthesiol Scand. 2005 Oct;49(9):1225-31. doi: 10.1111/j.1399-6576.2005.00791.x.

  PMID: 16146456 BACKGROUND

• Mu DL, Li LH, Wang DX, Li N, Shan GJ, Li J, Yu QJ, Shi CX. High postoperative serum cortisol level is associated with increased risk of cognitive dysfunction early after coronary artery bypass graft surgery: a prospective cohort study. PLoS One. 2013 Oct 15;8(10):e77637. doi: 10.1371/journal.pone.0077637. eCollection 2013.

  PMID: 24143249 BACKGROUND

• Phillips-Bute B, Mathew JP, Blumenthal JA, Grocott HP, Laskowitz DT, Jones RH, Mark DB, Newman MF. Association of neurocognitive function and quality of life 1 year after coronary artery bypass graft (CABG) surgery. Psychosom Med. 2006 May-Jun;68(3):369-75. doi: 10.1097/01.psy.0000221272.77984.e2.

  PMID: 16738066 BACKGROUND

• Jensen BO, Hughes P, Rasmussen LS, Pedersen PU, Steinbruchel DA. Cognitive outcomes in elderly high-risk patients after off-pump versus conventional coronary artery bypass grafting: a randomized trial. Circulation. 2006 Jun 20;113(24):2790-5. doi: 10.1161/CIRCULATIONAHA.105.587931. Epub 2006 Jun 12.

  PMID: 16769915 BACKGROUND

• Parolari A, Camera M, Alamanni F, Naliato M, Polvani GL, Agrifoglio M, Brambilla M, Biancardi C, Mussoni L, Biglioli P, Tremoli E. Systemic inflammation after on-pump and off-pump coronary bypass surgery: a one-month follow-up. Ann Thorac Surg. 2007 Sep;84(3):823-8. doi: 10.1016/j.athoracsur.2007.04.048.

  PMID: 17720383 BACKGROUND

• Canet J, Raeder J, Rasmussen LS, Enlund M, Kuipers HM, Hanning CD, Jolles J, Korttila K, Siersma VD, Dodds C, Abildstrom H, Sneyd JR, Vila P, Johnson T, Munoz Corsini L, Silverstein JH, Nielsen IK, Moller JT; ISPOCD2 investigators. Cognitive dysfunction after minor surgery in the elderly. Acta Anaesthesiol Scand. 2003 Nov;47(10):1204-10. doi: 10.1046/j.1399-6576.2003.00238.x.

  PMID: 14616316 BACKGROUND

• Ernest CS, Worcester MU, Tatoulis J, Elliott PC, Murphy BM, Higgins RO, Le Grande MR, Goble AJ. Neurocognitive outcomes in off-pump versus on-pump bypass surgery: a randomized controlled trial. Ann Thorac Surg. 2006 Jun;81(6):2105-14. doi: 10.1016/j.athoracsur.2006.01.008.

  PMID: 16731138 BACKGROUND

• Glumac S, Kardum G, Sodic L, Bulat C, Covic I, Carev M, Karanovic N. Longitudinal assessment of preoperative dexamethasone administration on cognitive function after cardiac surgery: a 4-year follow-up of a randomized controlled trial. BMC Anesthesiol. 2021 Apr 23;21(1):129. doi: 10.1186/s12871-021-01348-z.

  PMID: 33892653 DERIVED

• Glumac S, Kardum G, Sodic L, Supe-Domic D, Karanovic N. Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial. Eur J Anaesthesiol. 2017 Nov;34(11):776-784. doi: 10.1097/EJA.0000000000000647.

  PMID: 28985195 DERIVED

MeSH Terms

Conditions

Postoperative Cognitive Complications; Cognition Disorders

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Nenad Karanovic, MD, PhD

  Clinical Hospital Center, Split

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 10, 2016
• Study Start: March 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 10, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share