Excessive Amount of Blood / Fluid TransfusionNCT02953951
Blood Transfusions in Coronary Artery Bypass Surgery
An observational study of Excessive Amount of Blood / Fluid Transfusion, run by Universita di Verona at 1 site in Italy.
Trial summary
The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether transfusions of stored allogenic blood or intraoperative autologous salvaged blood result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Excessive Amount of Blood / Fluid Transfusion
- What is being tested?
- blood transfusion
- How many people
- 95 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2014to Dec 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: consecutive patients undergoing elective isolated CABG with cardiopulmonary bypass (CPB) at our institution between January 2014 and May 2014.
Who may be able to join
- elective CABG surgery
Who cannot join
- vasopressors/inotropes during surgery
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Blood Transfusions May Impair Endothelium-dependent Vasodilatation in Isolated Left Mammary Arterial Artery Rings and Peripheral Artery Tonometry During Coronary Artery Bypass Surgery
The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether transfusions of stored allogenic blood or intraoperative autologous salvaged blood result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood flow measured in isolated left mammary artery rings and by peripheral artery tonometry in patients undergoing CABG surgery.
Read the detailed description
Introduction
Several studies have implicated red blood cell (RBC) transfusion as a risk factor for increased morbidity as well as short- and long-term mortality after coronary artery bypass graft surgery (CABG). Interestingly, this effect is most pronounced among patients undergoing isolated CABG, suggesting that a harmful mechanism of RBC transfusion is not generalizable to all types of surgical procedures but instead may be specific to those patients.
The mechanisms by which blood transfusion may contribute to organ injury, dysfunction and death remain uncertain. Besides the quantity of RBC transfusions, the quality of the product has also been associated with differences in mortality and morbidity.
The use of intraoperative cell salvage and autologous blood transfusion has become an important method of blood conservation. The main aim of autologous transfusion is to reduce the need for allogeneic blood transfusion and its associated complications. However hemolysis and high cell-free hemoglobin (fHb) contents are associated with cell washing devices that collect anticoagulated shed or recovered blood, wash and separate the RBC by centrifugation, and re-infuse the RBC.
fHb is a potent scavenger of nitric oxide (NO), which mediates endothelium-dependent vasodilation, and may therefore be responsible for microvascular perfusion disturbances (arterial spasm). Indeed endothelial dysfunction and persistent microvascular alterations are associated with organ failure and death.
Increasing hemolysis and release of fHb were also documented as a function of time during prolonged RBC storage. Transfusion of RBC stored for less than 14 days has been associated with favourable outcomes when compared with transfusion of RBC stored for a prolonged time. Changes in red cell structure and function during blood banking and storage have been referred to as the red cell storage lesion.
The present study aimed to assess whether transfusion of stored allogeneic blood or intraoperative autologous salvaged blood results in differently increased circulating fHb levels and plasma NO consumption with effects on arterial NO-dependent blood flow in patients undergoing CABG surgery.
Methods
Study design This single-centre, prospective observational cohort study was based on consecutive patients undergoing elective isolated CABG with cardiopulmonary bypass (CPB) at our institution between January 2014 and May 2014. Perioperative and postoperative data were collected prospectively. The study protocol was approved by the Institution's Ethical Committee/Institutional Review Board.
Surgery Anaesthesia was standardized and maintained with propofol, sufentanil and vecuronium. Surgery was always performed through median sternotomy. LIMA was harvested as a pedicle, anastomosed to the left anterior descending artery in all cases, and never used as a free graft. CPB circuit included a Sorin phosphorylcholine-coated tubing set (Sorin Group SpA, Milano, Italy), a Jostra roller pump (Jostra, Maquet Cardiopulmonary, Hirrlingen, Germany), and a hollow fiber membrane coated oxygenator, which incorporated also a 40 μm filter (Sorin Synthesis™, Sorin Group Spa, Milano, Italy). Heparin was given at a dose of 300 IU/kg to achieve a target activated clotting time of 480 s or above. The extracorporeal circuit was primed with 1400 mL of Ringer's lactate solution and 5000 IU of heparin. A non-pulsatile CPB flow was established at 2.4 L/min. Buckberg crystalloid cardioplegic solution was used to maintain cardioplegia during aortic cross-clamping. Infusion of 4 mg/kg of protamine was used to neutralize heparin after finishing the CPB. Residual blood was sucked from the venous reservoir into the cell saver collection reservoir using a dual lumen tube connected to a vacuum pump and subsequently transferred to the 125-ml centrifuge bowl of the cell saver (Cell Saver 5; Haemonetics, Braintree, MA, USA). Cells were washed using 2000 ml bags NaCl 0.9% with 30.000 IU of heparin (Athena Pharma, Rome, Italy). The following cell saver program was used for the cell saver: 5600 r.p.m., filling and washing rate of 250 ml/min, emptying rate 250 ml/min, wash volume 1000 ml. Concentrated blood cells were drained into a patient labelled soft collection bag.
Transfusion protocol Transfusion of packed RBC was indicated at Hb levels < 7 g/l during CPB. After the end of CPB an Hb level < 9 g/l indicated requirement of autologous salvaged concentrated blood cells and/or packed RBC.
- Being tested
- blood transfusion
- Keywords
- blood transfusion, free hemoglobin, nitric oxide, endothelium-dependent vasodilatation, peripheral artery tonometry, cardiac surgery.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood transfusionOther
blood transfusion different sources
| Study group | Role | What they receive |
|---|---|---|
| Stored Blood Cells | Blood transfusion:
Stored blood cells transfused patients Receives: Other: blood transfusion | |
| Autologous Salvaged Blood | Blood transfusion:
Autologous salvaged blood transfused patients Receives: Other: blood transfusion | |
| Control | Blood transfusion: No transfusion patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in free hemoglobin plasma level (mg/dl)
analyzed by derivative spectrometry
Measured: 1) beginning of surgery, 2) after 12 hours
Secondary outcomes (3)
Endothelium-dependent arterial relaxation (in vitro)
arterial rings assay
Measured: after 12 hours
Endothelium-dependent arterial relaxation (in vivo)
Peripheral artery tonometry
Measured: after 12 hours
Change in Nitric oxyde consumption (umol/l)
Nitric Oxide Analyzer (Sievers)
Measured: 1) beginning of surgery, 2) after 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2016 (estimated)
- Study startJan 2014
- Primary completionMay 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Excessive Amount of Blood / Fluid TransfusionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universita di Verona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessio Rungatscher, Universita di Verona
- Investigators
- Alessio Rungatscher, MD, PhD, Principal investigator, Universita di Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02953951
- Sponsor's protocol ID
- CIRSAL-1231
- Status last verified
- Oct 2016
- First submitted
- 16 Oct 2016
- Last updated
- 3 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Transfusions May Impair Endothelium-dependent Vasodilatation in Isolated Left Mammary Arterial Artery Rings and Peripheral Artery Tonometry During Coronary Artery Bypass Surgery
- ClinicalTrials.gov ID
- NCT02953951
- Acronym / sponsor ID
- CIRSAL-1231
- Keywords
- blood transfusion, free hemoglobin, nitric oxide, endothelium-dependent vasodilatation, peripheral artery tonometry, cardiac surgery.
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Universita di VeronaUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- May 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 3 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether transfusions of stored allogenic blood or intraoperative autologous salvaged blood result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood flow measured in isolated left mammary artery rings and by peripheral artery tonometry in patients undergoing CABG surgery.
Detailed description
Introduction
Several studies have implicated red blood cell (RBC) transfusion as a risk factor for increased morbidity as well as short- and long-term mortality after coronary artery bypass graft surgery (CABG). Interestingly, this effect is most pronounced among patients undergoing isolated CABG, suggesting that a harmful mechanism of RBC transfusion is not generalizable to all types of surgical procedures but instead may be specific to those patients.
The mechanisms by which blood transfusion may contribute to organ injury, dysfunction and death remain uncertain. Besides the quantity of RBC transfusions, the quality of the product has also been associated with differences in mortality and morbidity.
The use of intraoperative cell salvage and autologous blood transfusion has become an important method of blood conservation. The main aim of autologous transfusion is to reduce the need for allogeneic blood transfusion and its associated complications. However hemolysis and high cell-free hemoglobin (fHb) contents are associated with cell washing devices that collect anticoagulated shed or recovered blood, wash and separate the RBC by centrifugation, and re-infuse the RBC.
fHb is a potent scavenger of nitric oxide (NO), which mediates endothelium-dependent vasodilation, and may therefore be responsible for microvascular perfusion disturbances (arterial spasm). Indeed endothelial dysfunction and persistent microvascular alterations are associated with organ failure and death.
Increasing hemolysis and release of fHb were also documented as a function of time during prolonged RBC storage. Transfusion of RBC stored for less than 14 days has been associated with favourable outcomes when compared with transfusion of RBC stored for a prolonged time. Changes in red cell structure and function during blood banking and storage have been referred to as the red cell storage lesion.
The present study aimed to assess whether transfusion of stored allogeneic blood or intraoperative autologous salvaged blood results in differently increased circulating fHb levels and plasma NO consumption with effects on arterial NO-dependent blood flow in patients undergoing CABG surgery.
Methods
Study design This single-centre, prospective observational cohort study was based on consecutive patients undergoing elective isolated CABG with cardiopulmonary bypass (CPB) at our institution between January 2014 and May 2014. Perioperative and postoperative data were collected prospectively. The study protocol was approved by the Institution's Ethical Committee/Institutional Review Board.
Surgery Anaesthesia was standardized and maintained with propofol, sufentanil and vecuronium. Surgery was always performed through median sternotomy. LIMA was harvested as a pedicle, anastomosed to the left anterior descending artery in all cases, and never used as a free graft. CPB circuit included a Sorin phosphorylcholine-coated tubing set (Sorin Group SpA, Milano, Italy), a Jostra roller pump (Jostra, Maquet Cardiopulmonary, Hirrlingen, Germany), and a hollow fiber membrane coated oxygenator, which incorporated also a 40 μm filter (Sorin Synthesis™, Sorin Group Spa, Milano, Italy). Heparin was given at a dose of 300 IU/kg to achieve a target activated clotting time of 480 s or above. The extracorporeal circuit was primed with 1400 mL of Ringer's lactate solution and 5000 IU of heparin. A non-pulsatile CPB flow was established at 2.4 L/min. Buckberg crystalloid cardioplegic solution was used to maintain cardioplegia during aortic cross-clamping. Infusion of 4 mg/kg of protamine was used to neutralize heparin after finishing the CPB. Residual blood was sucked from the venous reservoir into the cell saver collection reservoir using a dual lumen tube connected to a vacuum pump and subsequently transferred to the 125-ml centrifuge bowl of the cell saver (Cell Saver 5; Haemonetics, Braintree, MA, USA). Cells were washed using 2000 ml bags NaCl 0.9% with 30.000 IU of heparin (Athena Pharma, Rome, Italy). The following cell saver program was used for the cell saver: 5600 r.p.m., filling and washing rate of 250 ml/min, emptying rate 250 ml/min, wash volume 1000 ml. Concentrated blood cells were drained into a patient labelled soft collection bag.
Transfusion protocol Transfusion of packed RBC was indicated at Hb levels < 7 g/l during CPB. After the end of CPB an Hb level < 9 g/l indicated requirement of autologous salvaged concentrated blood cells and/or packed RBC.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Stored Blood Cells | – | Other: blood transfusionBlood transfusion: Stored blood cells transfused patients |
| Autologous Salvaged Blood | – | Other: blood transfusionBlood transfusion: Autologous salvaged blood transfused patients |
| Control | – | –Blood transfusion: No transfusion patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- consecutive patients undergoing elective isolated CABG with cardiopulmonary bypass (CPB) at our institution between January 2014 and May 2014.
Key inclusion criteria (1 listed)
- elective CABG surgery
Key exclusion criteria (1 listed)
- vasopressors/inotropes during surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood transfusionblood transfusion different sources | Other | Autologous Salvaged Blood, Stored Blood Cells |
Primary outcome
Change in free hemoglobin plasma level (mg/dl)
Time frame: 1) beginning of surgery, 2) after 12 hours
analyzed by derivative spectrometry
3 secondary outcomes
Endothelium-dependent arterial relaxation (in vitro)
Time frame: after 12 hours
Endothelium-dependent arterial relaxation (in vivo)
Time frame: after 12 hours
Change in Nitric oxyde consumption (umol/l)
Time frame: 1) beginning of surgery, 2) after 12 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessio Rungatscher, MD, PhD principal investigator
Universita di Verona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Excessive Amount of Blood / Fluid Transfusion, run by Universita di Verona at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in free hemoglobin plasma level (mg/dl) (time frame: 1) beginning of surgery, 2) after 12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2016; AzTrials last refreshed its copy on 6 Nov 2026.