Tranexamic Acid Dose and Confusion After Cardiac Surgery

Are Higher Doses of Tranexamic Acid Associated With a Lower Incidence of Post-operative Delirium After Cardiac Surgery? A Retrospective Cohort Study

Delirium is one of the most common complications after cardiac surgery and occurs with an incidence of 3 - 70%.

Both predisposing factors (age, diabetes, severity of cardiac disease, atrial fibrillation) and precipitating factors (type of surgery, duration of cardiopulmonary bypass (CPB) and surgery, ventilator time in ICU, highest temperature in intensive care (ICU)) are difficult to influence. Post-operative delirium is a devastating complication, leading to longer ICU and hospital stay, increased incidence of discharge to nursing facility and poorer long-term cognitive outcome.

Despite the impact this complication has on individuals, their families and healthcare resources, little is known about the causes and potential preventative measures.

It is thought that systemic inflammation compromising the integrity of the blood brain barrier is an important contributing factor. Recent data suggests that antifibrinolytics like tranexamic acid (TXA) might be able to lessen the inflammation of the nervous system caused by surgery and CPB through the inhibition of plasmin production, thereby stabilising the blood brain barrier. Worldwide, the use of TXA has become standard of care in cardiac surgery and other types of surgery with a high risk of bleeding. It has been shown to reduce bleeding by 25% and significantly reduce the rate of transfusion in cardiac and noncardiac surgery.

At Royal Papworth hospital it is routine practice to administer 2g of TXA before commencing CPB irrespective of patients' body weight. We are hypothesising that there is a weight-based effect of TXA on neurological outcomes after cardiac surgery, showing a signal that a higher dose per kg bodyweight will lead to less delirium measured with the Richmond Agitation-Sedation Score (RASS). We intend to analyse 4 years' worth of patient data (05/2018 - 08/2022); the necessary information is routinely collected on using the hospital anaesthetic and ICU record.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Surgery
• Intervention / Treatment: Drug: Tranexamic acid

Detailed Description

There will be no patient contact at any point of this retrospective analysis. The data collected will have been routinely collected on the hospital's electronic systems as part of routine clinical care and data collection.

This is a very new field of interest in cardiac anaesthesia / surgery. No clinical data is currently available apart from recent preliminary data suggesting that Tranexamic Acid (TXA) improves the inflammatory reaction the nervous system has to surgery and cardiopulmonary bypass. The first trial in this area, a RCT (TXA vs no TXA) in abdominal surgery, has only just started recruiting (Tranexamic Acid to Reduce Delirium After Gastrointestinal Surgery: the TRIGS-D Trial; clinicaltrials.gov).

The statistical methods will be determined once data distribution is known; the interdependence of primary and secondary outcome measures will be determined by multivariate regression analysis.

At this stage it is not possible to devise a prospective randomised controlled trial similar the TRIGS-D study in cardiac surgery as giving TXA is considered standard of care. It might be possible, however, to design a RCT comparing different TXA dosing regimens once the the results of this retrospective analysis are available.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Royal Papworth Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All patients undergoing elective or in-house urgent cardiac surgery at RPH between 05/2018 and 08/2022

Description

Inclusion Criteria:

All patients undergoing elective or in-house urgent cardiac surgery at RPH between 05/2018 and 08/2022

Exclusion Criteria:

Patients undergoing

• operations involving deep hypothermic circulatory arrest,
• operations involving thoracic vessels other than the ascending aorta,
• solid organ transplantation or mechanical assist device implantation,
• emergency operations

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Richmond Agitation Sedation Score	Up to 48hours after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
30 day mortality	Up to 30 days after surgery

Collaborators and Investigators

• Sponsor: Papworth Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: IRAS 323740

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No