TACO Crossover TRIAL

A Cross-over Randomized Controlled Trial; Pulmonary Edema Detection After Fluid Loading With Blood Versus Saline in Patients After CABG

This is an open-label, prospective crossover randomized controlled trial to investigate wether TACO is solely hydrostatic pressure overload or arises from a combination of hydrostatic pressure overload and capillary leakage, by investigating the difference in change in static pressure parameters (PCWP), dynamic volume parameters (PICCO) as indirect measurements of volume status and capillary leakage after autologous transfusion or saline infusion. The investigators will estimate effective circulating volume following autologous transfusion or saline infusion. Furthermore, the investigators will investigate the effect of fluid loading on the microcirculation.

Study Overview

• Status: Completed
• Conditions: Transfusion-associated Circulatory Overload; Blood Transfusion Reaction
• Intervention / Treatment: Procedure: Autologous RBC transfusion; Procedure: Saline transfusion

Detailed Description

Coronary arterial bypass grafting surgery patients with reduced left ventricular function will be allocated to either infusion of 300mL saline with a subsequent autologous RBC (cell saver) transfusion of 300 mL at a rate of 10mL/min, or the same in the reversed order. Prior to start of the intervention, 15 minutes following start of infusion and a the end of infusion, the investigators will measure right-ventricular pressure and wedge pressure (PCWP), as well as extravascular lung water index (EVLWI) and CO estimation through PICCO® and Pulmonary Artery Catheter. The investigators will identify fluid responsiveness by performing a passive leg raise test (PLR). The investigators aim to measure total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI), and blood vessel diameters (Øbv) from the oral microcirculation by CytoCam microscope system. The investigators will estimate the effective circulating blood and plasma volume through dilutional infusion of indocyanine green prior to initial infusion, between and at the end of subsequent infusion.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum - Universiteit van Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age >18 years
2. Elective (non-redo) coronary arterial bypass grafting surgery
3. Reduced left ventricular ejection fraction (<55%)
4. Transfusion of autologous blood (cell saver blood, 300ml, HCT60%, 30min)
5. Informed consent

Exclusion Criteria:

1. Patients with no indication for autologous RBC transfusion
2. Patients with pulmonary hypertension, congenital heart disease, mitral or tricuspid valve disease.
3. Contraindications for PAC placement; coagulopathy, bundle branch block, defibrillator or pacemaker (risk of displacement). External pacemaker placed during surgery is no exclusion criterium.
4. Patients for acute, non-elective surgery
5. Chronic kidney disease stage 4 or higher (eGFR < 30)
6. Massive transfusion
7. Previous randomization in the current trial
8. Postoperative ongoing bleeding
9. Bypass duration > 2 hours
10. Infusion of high dose corticosteroids
11. Hemodynamic instability with a mean arterial pressure (MAP) < 60 mmHg, central venous pressure > 20 mmHg or dependence on high dosages of inotropic drugs after admittance to the ICU
12. Severe arrhythmias
13. Development of severe pulmonary edema during infusion of autologous blood or saline.
14. Elevated liver enzymes
15. Iodine allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Group A; Patients will receive infusion of 300mL saline with a subsequent autologous Red Blood Cells (RBC) transfusion of 300 mL at a rate of 10mL/min	Procedure: Autologous RBC transfusion; Autologous RBC transfusion 300ml 10 ml/min; Procedure: Saline transfusion; Saline transfusion 300ml 10ml/min
OTHER: Group B; Patients will receive infusion of 300mL autologous RBC with a subsequent saline transfusion of 300 mL at a rate of 10mL/min	Procedure: Autologous RBC transfusion; Autologous RBC transfusion 300ml 10 ml/min; Procedure: Saline transfusion; Saline transfusion 300ml 10ml/min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hydrostatic pressure overload	Hydrostatic pressure overload defined as delta pulmonary capillary wedge pressure	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Capillary leakage	Capillary leakage defined as delta extra vascular lung water index	1 hour
Cardiac output	Volume overload measured by cardiac output	1 hour
Mean arterial pressure	Volume overload measured by mean arterial pressure	1 hour
Pulse pressure variation	Volume overload measured by pulse pressure variation	1 hour
Stroke volume variation	Volume overload measured by stroke volume variation	1 hour
Extra vascular lung water index	Volume overload measured by extra vascular lung water index	1 hour
Systemic vascular resistance	Volume overload measured by systemic vascular resistance	1 hour
Colloid osmotic pressure	Colloid osmotic pressure measured by membrane colloid osmometer	1 hour
Estimated circulating volume	Estimated circulating blood volume measured by indocyanine green	1 hour
Estimated circulating volume	Estimated circulating plasma volume measured by indocyanine green	1 hour
Microcirculation	Total vessel density in the sublingual microcirculation measured by Cytocam	1 hour
Microcirculation	Perfused vessel density in the sublingual microcirculation measured by Cytocam	1 hour
Microcirculation	Proportion of perfused vessels in the sublingual microcirculation measured by Cytocam	1 hour
Microcirculation	Microvascular flow index in the sublingual microcirculation measured by Cytocam	1 hour
Microcirculation	Blood vessel diameters in the sublingual microcirculation measured by Cytocam	1 hour
Fluid responsiveness	Fluid responsiveness defined by Passive Leg Raise test (increase in cardiac output > 10%)	1 hour
TACO	Transfusion associated circulatory overload criteria 6 hours after infusion of autologous blood transfusion	6 hours

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Alexander Vlaar, MD PhD MBA, Academisch Medisch Centrum - Universiteit van Amsterdam

Publications and helpful links

General Publications

• Delaney M, Wendel S, Bercovitz RS, Cid J, Cohn C, Dunbar NM, Apelseth TO, Popovsky M, Stanworth SJ, Tinmouth A, Van De Watering L, Waters JH, Yazer M, Ziman A; Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Transfusion reactions: prevention, diagnosis, and treatment. Lancet. 2016 Dec 3;388(10061):2825-2836. doi: 10.1016/S0140-6736(15)01313-6. Epub 2016 Apr 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 16, 2017
• Primary Completion (ACTUAL): March 13, 2020
• Study Completion (ACTUAL): April 1, 2020

Study Registration Dates

• First Submitted: April 26, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (ACTUAL): May 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 4, 2020
• Last Update Submitted That Met QC Criteria: August 2, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hematologic Diseases; Transfusion Reaction
• Other Study ID Numbers: NL59191.018.16

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