Anemia, Bleeding, Coronary Artery Disease, Coronary Disease, Coronary Occlusion, Coronary Stenosis, Epigenetic Disorder, Systemic Inflammatory Response
Conditions
Brief summary
Anemia poses risks during coronary artery bypass grafting (CABG), increasing complications and mortality rates. Blood transfusions in cardiac surgery have negative outcomes, prompting the use of erythropoietin in Patient Blood Management (PBM) to limit transfusion needs and enhance postoperative recovery. EPO can reduce blood component requirements, adverse events, and inflammation in anemic CABG patients. A study aims to minimize transfusions through a PBM anemia treatment protocol for CABG patients, comparing outcomes in three groups: a Control Group (CG), a Non-PBM Group (NPBMG) treated with blood components, and a PBM Group (GPBM) treated with EPO. Parameters include post-op stay, mortality, cardiovascular events, non-cardiovascular events, ICU time, mechanical ventilation duration, vasoactive drug use, inflammatory responses, and cardiac cell death. Analysis will consider demographic and clinical factors, with expectations that GPBM will yield superior results compared to NPBMG and similar or better outcomes than CG.
Detailed description
Anemia increases the risk of postoperative complications and mortality in patients undergoing coronary artery bypass grafting (CABG). In addition, the use of blood transfusions during cardiac surgery is associated with adverse effects and unfavorable outcomes. To reduce the need for transfusions and improve post-operative results, erythropoietin is used as part of Patient Blood Management (PBM). In anemic patients undergoing CABG, the use of Erythropoietin (EPO) can eliminate the need for blood components during and after surgery, as well as reduce adverse events and inflammation. The objectives of the proposed study are to reduce or eliminate the number of transfusions in the intraoperative and postoperative context by means of a Patient Blood Management (PBM) anemia treatment protocol for anemic patients who will undergo Coronary Artery Bypass Graft Surgery (CABG). The proposed study is a prospective, non-controlled interventional study to be carried out with anemic patients awaiting CABG surgery at Hospital São Paulo. There will be three groups of 40 participants each: Control Group (CG) of non-anemic individuals preoperatively; Non- PBM Group (NPBMG) of anemic individuals preoperatively and treated with blood components according to need; PBM Group (GPBM) of anemic individuals preoperatively and treated with EPO. The following parameters will be compared: length of postoperative hospital stay; mortality; postoperative cardiovascular events: clinical stroke, perioperative infarction, surgical reoperation due to bleeding; non- cardiovascular events: surgical site-associated infection and acute renal dysfunction; time in postoperative intensive care; time on mechanical ventilation; need for vasoactive drug use; inflammatory process and intra- and postoperative cardiac cell death. Confounding factors such as demographic and clinical parameters will be included in the analysis. It is expected that the GPBM will obtain the best results in relation to the GNPBM, similar to or better than the CG.
Interventions
DRUGErythropoietin
* Treatment regimen for hospitalized patients awaiting non-urgent surgeries: Administer EPO 600 IU/kg/week via subcutaneous (SC) or intravenous (IV) route, followed by 300 IU/kg/day via SC or IV 10 days before surgery. If ferritin \< 100 ng/dL, supplement with IV iron (Iron hydroxide up to 600 mg/week or Ferric carboxymaltose up to 1000 mg/week). * Treatment regimen for hospitalized patients awaiting non-urgent surgeries with less than 5 days until surgery: Administer 40000 UI of EPO intravenous (IV) attack and supplement with IV iron (Iron hydroxide up to 600 mg/week or Ferric carboxymaltose up to 2000 mg/week), then 300UI/Kg/day IV or SC of EPO until day of surgery.
PROCEDUREblood transfusion
After surgery, this group will receive one unit of RBC at the moment of ICU admission. Hb \> 8 g/dl: 1 unit of RBC. HB \< 8 g/dl: 2 units of RBC.
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
Randomized (intervention group) for anemic patients Non-randomized (control group) for non-anemic patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Eletive surgery; * Only CABG as procedure; * Off pump CABG candidate.
Exclusion criteria
* Age \> 80 years; * Chronic dialytic kidney disease; * Chronic rheumatologic disease; * Men with Hb levels \> 13 g/dl and \< 8g/dl; * Women with Hb levels \> 12 g/dl and \< 8g/dl; * Presence of another heart disease requiring surgical intervention; * Presence of hepatic insufficiency; * Presence of any implantable electronic cardiac device in any cardiac chambers; * Pregnancy; * Diagnosis of malignant neoplasia; * Thrombophilias; * Need for Erythropoietin treatment due to any other disease. * Recent ischemic event (\< 3 months). * Ejection fraction \<30%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean number of units of Red Blood Cells (RBC) | Until perioperative day 3 | Compare the need of blood transfusion in the perioperative period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | From time of ICU medical discharge until time of Hospital discharge (Up to 14 days). | Days |
| Length of mechanical ventilation | From time of intubation by anesthesia team until time of extubation by ICU team (Up to 240 hours). | Hours |
| Need of Dyalisis (Acute Kidney Disease) | Based on KDIGO classification of Acute Kdney Injury, level III of the classification. (Up to 120 hours from ICU admission, accountable from the time Dyalisis is indicated). | Needing of dyalisis in peoperative period |
| Perioperative infection | Until perioperative day 3 | Anytype |
| Bleeding | From time of admission on ICU until hour 24th after admission (accountable amount from how many chest tubes the patient was admitted). | Thorax drain tubes bleeding (ml) |
| Epigenetics alterations | Until perioperative day 3 | . Differentially methylated regions (DMRs) and differentially methylated loci (DMLs) will be considered to determine if these regions are hypermethylated or hypomethylated in the comparison between groups. |
| Length of ICU stay | From time of admission after surgery to time of clinical conditions of discharge (time of ICU medical discharge, not time of ICU room exit). Up to 240 hours. | Hours |
| Perioperative myocardial infarction | Until perioperative day 3 | According to type 5 Myocardial ischemia |
| Stroke | Until perioperative day 3 | Any level of neurological deficit |
| Hemoglobin levels | Until perioperative day 3 and at discharge | Accountable in g/dl |
| All-cause mortality | From day of the intervention (if intervention group) or from the moment of surgery (if control group) until day of hospital discharge (death from any cause accountable as in-hospital mortality). | Death from any cause accountable as in-hospital mortality |
| Cardiovascular mortality | From day of the intervention (if intervention group) or from the moment of surgery (if control group) until day of hospital discharge (any cardiovascular reason as main cause of death accountable as in-hospital mortality).) | any cardiovascular reason as main cause of death accountable as in-hospital mortality |
| Inflammatory response | Until perioperative day 3 | A total of 25 μl of serum per patient will be used for the detection of the following analytes: IL-1β, IL-6, IL-10, TNF-α, CRP, and NT-ProBNP. |
Countries
Brazil
Outcome results
None listed