Clinical trial NCT05049590: Acute Normovolemic Hemodilution in Complex Cardiac Surgery
Official title: Acute Normovolemic Hemodilution (ANH) in Complex Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Surgery
Acute Kidney Injury
Congenital Heart Disease
Aortic Surgery
Keywords: acute normovolemic hemodilution
complex cardiac surgery
transfusions
acute kidney injury
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2021-09-20
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Postoperative bleeding in cardiac surgery is a frequent complication, and cardiac surgery utilizes 15-20% of the national blood supply. Packed red blood cells (pRBCs) are associated with worse short and long term outcomes. For each unit transfused, there is an additive risk of mortality (death) and cardiac adverse events. Despite current guidelines and numerous approaches to bleeding reduction, \>50% of the patients undergoing cardiac surgery receive transfusions. Acute normovolemic hemodilution (ANH), a blood conservation technique that removes whole blood from a patient immediately prior to surgery, could be a valuable method to reduce transfusion in complex cardiac surgery. At the University of California, Los Angeles (UCLA), ANH is routinely utilized in patients who refuse allogenic blood transfusions such as Jehovah's Witnesses. ANH has been shown to be safe with minimal risk to patients. ANH has been studied in simple cardiac surgery, such as coronary artery bypass grafting, however it has not been studied in complex cardiac surgery, such as aortic surgery and adult congenital heart disease. ANH has been demonstrated to reduce pRBC transfusion in lower risk cardiac surgery without any significant complications. Complex heart surgery utilizes more blood products. This study could identify the benefits of ANH in a higher risk surgical group.

Detailed description: Adult patients undergoing complex heart surgery will be randomized to 1 of 2 groups using block randomization: the intervention arm receiving acute normovolemic hemodilution (ANH) or the control arm receiving standard of care.

As day of surgery hemoglobin (Hgb)/hematocrit (Hct) is critical to the final determination for study participation, patients will be randomized to control or intervention arms after the first intraoperative arterial blood gas (ABG) is obtained. The Hb/Hct obtained from this ABG is used to determine the postdilutional hematocrit using specific pre-ANH and post-ANH equations. Patients with pre-ANH or post-ANH postdilutional Hct lower than 22-24 will not be eligible for inclusion in the ANH arm of the study.

For the Study Group: Using sterile techniques, ANH is performed by removing 8-10cc/kg of whole blood with a maximum of 700cc, from the patient in the OR prior to incision. Whole blood will be collected and stored at room temperature. Hemodynamics are assessed during whole blood removal to ensure adequate stability. ANH will be discontinued if the patient becomes hemodynamically unstable (i.e. significant hypotension greater than 20% reduction from pre-ANH, unstable arrhythmia, evidence of myocardial ischemia or evidence of worsening myocardial function). After whole blood removal, the patient is hydrated to maintain isovolemia with an equivalent volume of crystalloid and/or colloid given, and the blood is stored in the OR at room temperature. After cardiopulmonary bypass (CPB) is complete, the whole blood is returned to the patient. Whole blood stored at room temperature will be transfused within 8 hours of initial collection. After 8 hours, ANH whole blood will be considered expired and will be transfused back to the patient prior to expiration and not discarded. Laboratory coagulation and ROTEM studies (assess blood clotting) will be resent after the ANH blood is returned to the patient. Transfusion requirement will be continuously reassessed based upon laboratory values and surgical assessment of clinical bleeding.

For the Control Group: Blood conservation will not be performed in the OR. Coagulation labs (i.e. platelet count, fibrinogen level and ROTEM studies) are sent while the patient in on bypass. After separation from bypass, coagulation laboratory studies and clinical bleeding are assessed in collaboration with the surgeon. Based on laboratory values and surgical assessment, allogenic transfusions (donor/recipient not the same person) occur in a targeted fashion (i.e. clinical bleeding with platelet count less than 150 x10E3/uL and a ROTEM results indicative of inadequate clot strength will result in platelet transfusion). Transfusion requirements are continuously reassessed based upon updated laboratory values and surgical assessment of clinical bleeding.

Data will also be collected and recorded from the medical record for both groups.

Eligibility criteria: Inclusion Criteria:

* Adult patients presenting for elective cardiac surgery
* Surgical procedures to include:

  * Redo surgery
  * Adult congenital heart disease surgery (ACHD)
  * Aortic surgery including aortic surgery requiring deep hypothermic circulatory arrest

Exclusion Criteria:

* low risk cardiac surgery
* cardiac surgery not requiring cardiopulmonary bypass
* baseline anemia (Hgb \< 13 for men and 12 for women)
* post-dilution Hct \< 21-24 (basis for this is increased risk of AKI on CPB with Hct 21-22)
* preop treatment for anemia
* high-risk ischemia lesions (critical left main, multi-vessel disease, active/recent chest pain, unstable angina, presence of a balloon pump, recent history of myocardial infarction (MI) either non-ST elevation MI (NSTEMI) / ST-elevation MI (STEMI), regional wall motion abnormalities on echo)
* low left ventricular systolic function (LVEF \< 35-40%) - decompensated heart failure
* Hypertrophic obstructive cardiomyopathy (HOCM) patients with significant left ventricular outflow tract (LVOT) gradients
* history of recent blood transfusion
* history of recent gastrointestinal (GI) bleed
* patient refusal to participate in the study
* severe aortic stenosis (AS) with reduced LVEF
* pulmonary hypertension
* underlying significant liver disease impairing synthetic function (elevated PT/INR or PTT) at baseline
* clotting disorders, inherited or acquired or iatrogenic coagulopathy (i.e. thrombocytopenia, pancytopenia)
* baseline chronic kidney disease (CKD) stage 3/above or End-stage renal disease (ESRD) +/- hemodialysis
* hemodynamically unstable patients including sepsis/recently treated sepsis
* preoperative extracorporeal membrane oxygenation (ECMO) or high suspicion for postoperative ECMO
* emergent cases

Primary outcomes:
measure: Packed red blood cells (pRBC)
timeFrame: 24 hours
measure: Packed red blood cells (pRBC)
timeFrame: 48 hours
measure: Packed red blood cells (pRBC)
timeFrame: 72 hours
Secondary outcomes:
measure: Maximum Intraoperative Vasoactive-Inotropic Score
timeFrame: Conclusion of intraoperative procedure
measure: Maximum 24 Hour Vasoactive-Inotropic Score
timeFrame: 24 hours
measure: Maximum 48 Hour Vasoactive-Inotropic Score
timeFrame: 48 hours
measure: Maximum 72 Hour Vasoactive-Inotropic Score
timeFrame: 72 hours
measure: Acute Kidney Injury (AKI)
timeFrame: 72 hours
measure: 24 Hour Chest Tube Output
timeFrame: 24 Hours
measure: 48 Hour Chest Tube Output
timeFrame: 48 Hours
measure: 72 Hour Chest Tube Output
timeFrame: 72 Hours
measure: 24 Hour Prothrombin time (PT)
timeFrame: 24 hours
measure: 48 Hour Prothrombin time (PT)
timeFrame: 48 hours
measure: 72 Hour Prothrombin time (PT)
timeFrame: 72 hours
measure: 24 Hour International Normalized Ratio (INR)
timeFrame: 24 hours
measure: 48 Hour International Normalized Ratio (INR)
timeFrame: 48 hours
measure: 72 Hour International Normalized Ratio (INR)
timeFrame: 72 hours
measure: 24 Hour Activated Partial Thromboplastin time (aPTT)
timeFrame: 24 hours
measure: 48 Hour Activated Partial Thromboplastin time (aPTT)
timeFrame: 48 hours
measure: 72 Hour Activated Partial Thromboplastin time (aPTT)
timeFrame: 72 hours
measure: 24 Hour Fibrinogen
timeFrame: 24 hours
measure: 48 Hour Fibrinogen
timeFrame: 48 hours
measure: 72 Hour Fibrinogen
timeFrame: 72 hours
measure: 24 Hour Platelet Count
timeFrame: 24 hours
measure: 48 Hour Platelet Count
timeFrame: 48 hours
measure: 72 Hour Platelet Count
timeFrame: 72 hours
measure: 24 Hour Hemoglobin (Hgb)
timeFrame: 24 hours
measure: 48 Hour Hemoglobin (Hgb)
timeFrame: 48 hours
measure: 72 Hour Hemoglobin (Hgb)
timeFrame: 72 hours
measure: 24 Hour Hematocrit (Hct)
timeFrame: 24 hours
measure: 48 Hour Hematocrit (Hct)
timeFrame: 48 hours
measure: 72 Hour Hematocrit (Hct)
timeFrame: 72 hours
measure: Rotational Thromboelastometry FIBTEM Maximum Clot Firmness (FIBTEM MCF)
timeFrame: During intraoperative period
measure: Rotational Thromboelastometry HEPTEM/EXTEM Maximum Clot Firmness (HEPTEM/EXTEM MCF)
timeFrame: During intraoperative period
measure: Rotational Thromboelastometry EXTEM Clotting Time (EXTEM CT)
timeFrame: During intraoperative period
measure: Rotational Thromboelastometry EXTEM Clotting Time (EXTEM A20)
timeFrame: During intraoperative period
measure: Rotational Thromboelastometry HEPTEM Clotting Time (HEPTEM CT)
timeFrame: During intraoperative period
measure: Post-cardiopulmonary bypass HEPTEM/EXTEM MCF
timeFrame: In the operating room (OR) during surgery.
measure: Cerebral oximetry using near infrared spectroscopy derived tissue oxygenation as a marker of perfusion
timeFrame: In the OR during surgery.
measure: Change in mixed venous oxygen saturation as a marker of perfusion
timeFrame: 72 hours
measure: Perfusion markers (lactate)
timeFrame: 72 hours
measure: Delirium
timeFrame: Two times per day for up 72 hours post-op or until discharge from the ICU, whichever came first
measure: Number of patients with infection/sepsis
timeFrame: 72 hours post-op or until discharge from the ICU, whichever came first
measure: Mortality
timeFrame: An average of 5-10 days until discharge from the hospital, whichever came first
measure: Platelets (PLT)
timeFrame: 24 hours
measure: Platelets (PLT)
timeFrame: 48 hours
measure: Platelets (PLT)
timeFrame: 72 hours
measure: Fresh frozen plasma (FFP)
timeFrame: 24 hours
measure: Fresh frozen plasma (FFP)
timeFrame: 48 hours
measure: Fresh frozen plasma (FFP)
timeFrame: 72 hours
measure: Cryoprecipitate (cryo)
timeFrame: 24 hours
measure: Cryoprecipitate (cryo)
timeFrame: 48 hours
measure: Cryoprecipitate (cryo)
timeFrame: 72 hours
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Lorraine Lubin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barile L, Fominskiy E, Di Tomasso N, Alpizar Castro LE, Landoni G, De Luca M, Bignami E, Sala A, Zangrillo A, Monaco F. Acute Normovolemic Hemodilution Reduces Allogeneic Red Blood Cell Transfusion in Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Trials. Anesth Analg. 2017 Mar;124(3):743-752. doi: 10.1213/ANE.0000000000001609.
citation: Zhou ZF, Jia XP, Sun K, Zhang FJ, Yu LN, Xing T, Yan M. Mild volume acute normovolemic hemodilution is associated with lower intraoperative transfusion and postoperative pulmonary infection in patients undergoing cardiac surgery -- a retrospective, propensity matching study. BMC Anesthesiol. 2017 Jan 26;17(1):13. doi: 10.1186/s12871-017-0305-7.