Effects of Microplegia on Transfusion Rates After Cardiac Surgery

NCT ID: NCT05076604

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-25
• Study Completion Date: 2023-08-01

Brief Summary

This is a prospective, randomized study that is studying the rate of red blood cell (RBC) transfusion rates after planned heart (cardiac) surgery. The study will be conducted at Barnes-Jewish Hospital.

Cardioplegia refers to the method of stopping (arresting) the heart in order to perform heart surgery. However, cardioplegia has also come to refer to the solution to achieve cardiac arrest as well as the machinery in which to deliver the solution. This study will investigate our current Standard Cardioplegia (diluted 4:1 blood cardioplegia) versus Microplegia (undiluted blood cardioplegia) to determine if Microplegia reduces peri-operative blood transfusion rates as compared to Standard Cardioplegia. All forms of cardioplegia will be delivered using the MPS2 Microplegia delivery machine by Quest Medical, Inc.

Patients will be randomized to receive undiluted microplegia or standard 4:1 cardioplegia. The patient and the surgeon will be blinded to the randomization.

Patients will be followed for 30 days post-operatively (or until their initial standard of care post-operative follow up visit with cardiac surgery if that appointment falls outside of the 30 day post-operative window) for the development of any adverse events as well as documentation of blood products given.

We will draw one tube of blood for troponin levels at four time points; 1 draw before surgery (this may be done during the intraoperative period), and 3 draws post-operatively: ICU arrival, 12 hours post-ICU arrival and 24 hours post-ICU arrival. This is to closely monitor the patient for any heart tissue injury.

Detailed Description

Cardioplegia was first introduced as a method to protect the heart during cardiac surgery in the 1950s (1). Initially, it consisted of a crystalloid solution and in the 1970s Follette and colleagues proposed that blood was the best mode of delivery of cardioplegia as it is rich in nutrients and oxygen (2). Blood has better osmotic, buffering, and antioxidant qualities that are needed by ischemic myocardium. More recent studies comparing blood and crystalloid cardioplegias showed that there was less cardiac edema, and recovery of ventricular function was more rapid with blood based cardioplegia (3). A meta-analysis of over 5000 patients corroborated these findings and showed that blood based cardioplegia reduced the incidence of postoperative low cardiac output syndrome and was associated with less myocardial damage (4).

Standard diluted blood cardioplegia can also be modified to undiluted blood cardioplegia also known as microplegia. To compare the cardioprotection of 4:1 blood:crystalloid cardioplegia to microplegia, McCann et al randomized 20 pigs to either group. Cardiac edema was measured using histologic morphometrics and echocardiogram. It was noted that both edema percentage and left ventricular mass were significantly more decreased in the microplegia group. Furthermore, all animals receiving microplegia were successfully weaned off cardiopulmonary bypass, whereas only 40% of those receiving standard cardioplegia were successfully weaned (5).

More recently, Algarni et al. showed decreased prevalence of low cardiac output syndrome in patients who received microplegia (n=2,630) (6). Another study compared microplegia and standard cardioplegia in patients undergoing coronary artery bypass grafting and found that the microplegia group had lower troponin levels during the post-operative course. Moreover, microplegia resulted in lower transfusion rates and decreased length of hospital stay (7).

A high rate of patients undergoing cardiac surgery require red blood cell transfusions (RBC). Red blood cell transfusions are strongly associated with both infection and ischemic postoperative morbidity, length of stay, increased early and late mortality, and overall hospital costs (8). Given that previous studies have shown that microplegia is associated with less transfusions, it would be reasonable to incorporate this into practice at Washington University.

Conditions

Aortic Valve Disease; Mitral Valve Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Cardioplegia

4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood.

Group Type: ACTIVE_COMPARATOR

Cardioplegia Solution

Intervention Type: DRUG

The microplegia solution that is standard of care for all cardiac surgery patients, and which all study subjects will receive is:

Induction 240 mL Baxter Cardioplegia Solution 10. 5 mL Potassium Chloride 2 meq/ml (21 meq) 250.5 mL total volume

Maintenance 747 mL Baxter Cardioplegia Solution 3.4 mL Potassium Chloride 2 meq/ml (6.75 meq) 750.4 mL total volume

Subjects will be randomly assigned to 4:1 cardioplegia or nondiluted microplegia.

4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood.

Nondiluted microplegia consists of all parts human blood.

Microplegia

Nondiluted microplegia consists of all parts human blood.

Group Type: ACTIVE_COMPARATOR

Microplegic Solution No. 1

Intervention Type: DRUG

The microplegia solution that is standard of care for all cardiac surgery patients, and which all study subjects will receive is:

Induction 240 mL Baxter Cardioplegia Solution 10. 5 mL Potassium Chloride 2 meq/ml (21 meq) 250.5 mL total volume

Maintenance 747 mL Baxter Cardioplegia Solution 3.4 mL Potassium Chloride 2 meq/ml (6.75 meq) 750.4 mL total volume

Subjects will be randomly assigned to 4:1 cardioplegia or nondiluted microplegia.

4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood.

Nondiluted microplegia consists of all parts human blood.

Interventions

Cardioplegia Solution

The microplegia solution that is standard of care for all cardiac surgery patients, and which all study subjects will receive is:

Induction 240 mL Baxter Cardioplegia Solution 10. 5 mL Potassium Chloride 2 meq/ml (21 meq) 250.5 mL total volume

Maintenance 747 mL Baxter Cardioplegia Solution 3.4 mL Potassium Chloride 2 meq/ml (6.75 meq) 750.4 mL total volume

Subjects will be randomly assigned to 4:1 cardioplegia or nondiluted microplegia.

4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood.

Nondiluted microplegia consists of all parts human blood.

Intervention Type: DRUG

Microplegic Solution No. 1

The microplegia solution that is standard of care for all cardiac surgery patients, and which all study subjects will receive is:

Induction 240 mL Baxter Cardioplegia Solution 10. 5 mL Potassium Chloride 2 meq/ml (21 meq) 250.5 mL total volume

Maintenance 747 mL Baxter Cardioplegia Solution 3.4 mL Potassium Chloride 2 meq/ml (6.75 meq) 750.4 mL total volume

Subjects will be randomly assigned to 4:1 cardioplegia or nondiluted microplegia.

4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood.

Nondiluted microplegia consists of all parts human blood.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Are to undergo non-emergent cardiac surgery
• >18 years of age
• Willing and able to provide informed consent

Exclusion Criteria

• History of endocarditis
• Dialysis-dependent renal failure
• Currently on pre-operative mechanical circulatory support (i.e. ECMO, LVAD or intra-aortic balloon pump [IABP])
• Contraindication to receiving a blood transfusion (i.e. Jehovah's Witness)
• Emergency procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quest Medical, Inc

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Spencer J Melby, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

Follette DM, Fey K, Buckberg GD, Helly JJ Jr, Steed DL, Foglia RP, Maloney JV Jr. Reducing postischemic damage by temporary modification of reperfusate calcium, potassium, pH, and osmolarity. J Thorac Cardiovasc Surg. 1981 Aug;82(2):221-38.

Reference Type: BACKGROUND

PMID: 7253686 (View on PubMed)

Fremes SE, Christakis GT, Weisel RD, Mickle DA, Madonik MM, Ivanov J, Harding R, Seawright SJ, Houle S, McLaughlin PR, et al. A clinical trial of blood and crystalloid cardioplegia. J Thorac Cardiovasc Surg. 1984 Nov;88(5 Pt 1):726-41.

Reference Type: BACKGROUND

PMID: 6387286 (View on PubMed)

Guru V, Omura J, Alghamdi AA, Weisel R, Fremes SE. Is blood superior to crystalloid cardioplegia? A meta-analysis of randomized clinical trials. Circulation. 2006 Jul 4;114(1 Suppl):I331-8. doi: 10.1161/CIRCULATIONAHA.105.001644.

Reference Type: BACKGROUND

PMID: 16820596 (View on PubMed)

McCann UG 2nd, Lutz CJ, Picone AL, Searles B, Gatto LA, Dilip KA, Nieman GF. Whole blood cardioplegia (minicardioplegia) reduces myocardial edema after ischemic injury and cardiopulmonary bypass. J Extra Corpor Technol. 2006 Mar;38(1):14-21.

Reference Type: BACKGROUND

PMID: 16637518 (View on PubMed)

Algarni KD, Weisel RD, Caldarone CA, Maganti M, Tsang K, Yau TM. Microplegia during coronary artery bypass grafting was associated with less low cardiac output syndrome: a propensity-matched comparison. Ann Thorac Surg. 2013 May;95(5):1532-8. doi: 10.1016/j.athoracsur.2012.09.056.

Reference Type: BACKGROUND

PMID: 23608252 (View on PubMed)

Onorati F, Santini F, Dandale R, Ucci G, Pechlivanidis K, Menon T, Chiominto B, Mazzucco A, Faggian G. "Polarizing" microplegia improves cardiac cycle efficiency after CABG for unstable angina. Int J Cardiol. 2013 Sep 10;167(6):2739-46. doi: 10.1016/j.ijcard.2012.06.099. Epub 2012 Jul 12.

Reference Type: BACKGROUND

PMID: 22795715 (View on PubMed)

Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007 Nov 27;116(22):2544-52. doi: 10.1161/CIRCULATIONAHA.107.698977. Epub 2007 Nov 12.

Reference Type: BACKGROUND

PMID: 17998460 (View on PubMed)

BIGELOW WG, LINDSAY WK, GREENWOOD WF. Hypothermia; its possible role in cardiac surgery: an investigation of factors governing survival in dogs at low body temperatures. Ann Surg. 1950 Nov;132(5):849-66. doi: 10.1097/00000658-195011000-00001. No abstract available.

Reference Type: RESULT

PMID: 14771796 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

201801103

Identifier Type: -

Identifier Source: org_study_id