Comparison of Lactated Ringer's Solution and PlasmaLyte-A as a Base Solution for Del Nido Cardioplegia

Study Overview
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Brief Summary
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Del Nido cardioplegia has been used exclusively for myocardial protection in pediatrics cardiac surgery for decades. Its unique properties including lidocaine which helps counteract potassium depolarization of the myocardial cell membrane, inhibition of intracellular calcium accumulation, preservation of intracellular high-energy phosphates, free-radical scavenging and acid-base buffering have been proven to be very effective for myocardial protection during cardiac surgery for congenital heart disease and acquired heart disease. Recent studies have proven its safety, efficacy, and cost-effectiveness for myocardial protection in adult cardiac surgery as a single dose cardioplegia which is typically administered in a single dose fashion or with extended dosing intervals. In contrast, Traditional blood cardioplegia is commonly administered approximately every 20 minutes. These characteristics of del Nido cardioplegia allow for fewer interruptions and improve surgical workflow. The base solution for del Nido cardioplegia is normally Plasma-Lyte A (Baxter Healthcare Corporation, Deerfield, IL, USA) which has an electrolyte composition similar to the extracellular fluid and is calcium-free. Unfortunately, an unavailability of PlasmaLyte-A in many countries precluding utilization of del Nido cardioplegia with its normal base solution in many cardiac centers. To access the benefits of del Nido cardioplegia, we utilize lactated Ringer's solution as the base solution. This prospective randomized study aimed to evaluate myocardial preservation and clinical outcomes when using lactated Ringer's solution compared with PlasmaLyte-A as a base solution for del Nido cardioplegia.

Detailed Description
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This clinical trial is performed at Ramathibodi hospital, Mahidol university inBangkok, Thailand. The protocol has been approved by institutional ethical committee (ref. ID 03-61-43) with informed consent required for all patients. The difference of 24 hour post-op troponin level between the del Nido cardioplegia and the blood cardioplegia group from previous randomized study were 2.3 (SD 2.1) and 7.0 (SD 14.7) ng/mL, respectively (p = 0.053). Our previous observational study also exhibited comparable results between modified del Nido cardioplegia and blood cardioplegia. The author estimated the sample size of 160 randomized patients to give 80% power at the 5% significant level (alpha 0.05, beta 0.2). Giving allowance for attrition, a sample size of 100 was chosen in each group. Patients aged 18 years or older undergoing elective cardiac surgery for acquired heart disease (including isolated coronary artery bypass grafting(CABG), isolated valve surgery, combined valve surgery, or concomitant CABG and valve surgery) are randomized 1:1 into lactated Ringer's solution (study group) and PlasmaLyte-A (control group). For patients randomized to lactated Ringer's solution (study group), lactated Ringer's solution is used as a base solution for del Nido cardioplegia. For patients randomized to PlasmaLyte-A (control group), PlasmaLyte-A (Baxter Healthcare Corporation, Deerfield, IL, USA) is used as a base solution for del Nido cardioplegia. Del Nido cardioplegia is delivered 1:4 with 1 part of oxygenated pump blood to 4 parts of cardioplegia solution. Del Nido cardioplegia can be delivered antegrade through aortic root catheter, directly through the coronary ostia or retrograde via the coronary sinus depending on the type of operation and degree of aortic valve insufficiency. Our protocol is to administer a single dose 20 mL/kg with maximum dose of 1000 mL for patients larger than 50 kg. After 90 minutes of aortic cross clamp time, the surgeon decides how much subsequent doses needs to be administered. If coronary bypass grafting is required, 5-10 mL of del Nido cardioplegia is administered via the saphenous vein graft or the radial artery graft to test the distal anastomosis. In our circuit, del Nido cardioplegia passes through a non-recirculating cardioplegia set with a coil heat exchanger and a delivery temperature of 4°C. It is generally administered over 1-2 minutes with system pressure 100-200 mmHg. Primary outcomes comprised assessments of myocardial injury, including troponin-T level at immediate post-op, 12 hour post-op, and 24 hour post-op. Secondary outcomes comprised assessments of additional measures of myocardial protection (including incidence of ventricular fibrillation after aortic cross-clamp removal; post-op left ventricular ejection fraction (LVEF) change; duration of inotrope/vasopressor requirement; and requirement for intra-aortic balloon pump (IABP) support), intraoperative outcomes (including total volume of cardioplegia; number of doses; total cardiopulmonary bypass (CPB) time; and aortic cross-clamp time), and clinical outcomes (including intensive care unit ICU) stay; hospital stay; incidence of postoperative atrial fibrillation or flutter; mortality; postoperative complications; and red cell transfusion). Patient characteristics and postoperative outcomes were as defined by the Society of Thoracic Surgeons (STS) Adult Cardiac Surgical Database. LVEF was assessed by transesophageal echocardiography before surgery and at the end of operation.

Official Title
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Comparison of Lactated Ringer's Solution and PlasmaLyte-A as a Base Solution for Del Nido Cardioplegia

Conditions
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Myocardial Injury

Intervention / Treatment
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* Drug: Lactated Ringer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age 18 years or older undergoing elective adult cardiac surgery Exclusion Criteria: Emergency surgery Patient who does not want to participate in the study Lidocaine allergy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactated Ringer's solution<br>For patients randomized to lactated Ringer's solution (study group), lactated Ringer's solution is used as a base solution for del Nido cardioplegia. | Drug: Lactated Ringer<br>* Comparison of Lactated Ringer's Solution and PlasmaLyte-A as a Base Solution for Del Nido Cardioplegia<br>* Other names: PlasmaLyte-A;|
| Active Comparator: PlasmaLyte-A<br>For patients randomized to PlasmaLyte-A (control group), PlasmaLyte-A (Baxter Healthcare Corporation, Deerfield, IL, USA) is used as a base solution for del Nido cardioplegia. | Drug: Lactated Ringer<br>* Comparison of Lactated Ringer's Solution and PlasmaLyte-A as a Base Solution for Del Nido Cardioplegia<br>* Other names: PlasmaLyte-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial injury | troponin-T level at 24 hour post-op | 24 hour post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of ventricular fibrillation after aortic cross-clamp removal | Ventricular fibrillation after aortic cross-clamp removal required defibrillation | Intra-operative period | 
| Post-op left ventricular ejection fraction (LVEF) change | Difference between pre-op and post-op LVEF. LVEF was assessed by transesophageal echocardiography before surgery and at the end of operation. | Intra-operative period | 
| Duration of inotrope/vasopressor requirement | Length of inotropic or vasopressor support in intensive care unit (hour) | up to 1 hour (During admission in intensive care unit) | 
| Incidence of intra-aortic balloon pump (IABP) insertion | Requirement for intra-aortic balloon pump (IABP) support | up to 1 hour (During admission in intensive care unit) | 
| Incidence of Operative mortality | Operative mortality includes both (1) all deaths occurring during the hospitalization in which the operation wasperformed, even if after 30 days; and (2) those deaths occurring after discharge from the hospital, but within 30 days ofthe procedure. | up to 1 month postoperatively | 
| Incidence of Permanent Stroke | Postoperative stroke (i.e., any confirmed neurological deficit of abrupt onset caused by a disturbance in blood supply tothe brain that did not resolve within 24 hours. | up to 1 month postoperatively | 
| Incidence of Renal Failure | Acute or worsening renal failure resulting in one or more of the following:1.Increase of serum creatinine to ≥ 4.0 with an increase of at least 0.5mg/dl or 3x most recent preoperativecreatinine level.2.A new requirement for dialysis postoperatively. | up to 1 month postoperatively | 
| Incidence of Prolonged Ventilation > 24 hours | Prolonged post-operative pulmonary ventilation > 24.0 hours. The hours of postoperative ventilation time include ORexit until extubation, plus any additional hours following reintubation. | up to 1 month postoperatively | 
| Incidence of Deep sternal wound infection | Deep sternal wound infection or mediastinitis (according to CDC definition) diagnosed within 30 days of the operationor any time during the hospitalization for the surgery | up to 1 month postoperatively | 
| Incidence of Reoperation for any reason | Reoperation for bleeding/tamponade, valvular dysfunction, graft occlusion, other cardiac reason, or non-cardiac reason | up to 1 month postoperatively | 
| Incidence of Major Morbidity or Operative Mortality | A composite endpoint defined as any of the outcomes listed above, including; Operative mortality, Permanent Stroke,Renal Failure, Prolonged Ventilation > 24 hours, Deep sternal wound infection, Reoperation for any reason. | up to 1 month postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myocardial protection, cardiac surgery, del Nido cardioplegia