Clinical trial NCT03135457: TACO Crossover TRIAL
Official title: A Cross-over Randomized Controlled Trial; Pulmonary Edema Detection After Fluid Loading With Blood Versus Saline in Patients After CABG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Transfusion-associated Circulatory Overload
Blood Transfusion Reaction
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2017-05-01
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Open-label, prospective cross-over randomized controlled trial.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hydrostatic pressure overload
timeFrame: 1 hour
Secondary outcomes:
measure: Capillary leakage
timeFrame: 1 hour
measure: Cardiac output
timeFrame: 1 hour
measure: Mean arterial pressure
timeFrame: 1 hour
measure: Pulse pressure variation
timeFrame: 1 hour
measure: Stroke volume variation
timeFrame: 1 hour
measure: Extra vascular lung water index
timeFrame: 1 hour
measure: Systemic vascular resistance
timeFrame: 1 hour
measure: Colloid osmotic pressure
timeFrame: 1 hour
measure: Estimated circulating volume
timeFrame: 1 hour
measure: Estimated circulating volume
timeFrame: 1 hour
measure: Microcirculation
timeFrame: 1 hour
measure: Microcirculation
timeFrame: 1 hour
measure: Microcirculation
timeFrame: 1 hour
measure: Microcirculation
timeFrame: 1 hour
measure: Microcirculation
timeFrame: 1 hour
measure: Fluid responsiveness
timeFrame: 1 hour
measure: TACO
timeFrame: 6 hours
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum - Universiteit van Amsterdam
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam
name: Alexander Vlaar, MD PhD MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.