Mitral Valve Stenosis With Incompetence or Regurgitation Clinical Trial
Official title:
The Effects of Levosimendan on Renal Function in Patients With Low Ejection Fraction Undergoing Mitral Valve Surgery.
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery will be investigated in a prospective, double-blinded, randomized clinical trial using serum creatinine (sCr)milligram in deciliter (mg/dL) values, calculated estimated glomerular filtration(eGFR)(ml/min/1.73 m2) rates and perioperative clinical follow-up parameters.
Introduction:
The coronary and peripheral vasodilatory properties of levosimendan has recently been
investigated in patients with heart failure. It is considered as a promising alternative to
conventional inotropic agents for patients with low LVEF. However, the effects of
levosimendan on renal functions in patients undergoing open heart surgeries with CPB are not
well studied in randomized clinical trials.
The primary goal of our study was to investigate the effects of levosimendan on 1- renal
function by evaluation of serum creatinine (mg/dL) values and calculated estimated
glomerular filtration(eGFR)(ml/min/1.73 m2) rates.
Our secondary goal was to determine clinical outcomes including;
1-need for renal replacement therapy (RRT) in patients with low ejection fraction undergoing
mitral valve repair or replacement surgery with cardiopulmonary bypass (CPB).
Inclusion and exclusion criterions include as listed below. Patients included into the study
had a diagnosis of mitral valve insufficiency with or without coronary artery disease and a
left ventricular ejection fraction (LVEF) of ≤ 45 %.
Exclusion criteria were unstable angina, diabetes mellitus treated with insulin, clinical
findings of acute or chronic renal failure (serum creatinine (sCr)> 1.5 mg/dL), severe
hepatic disease (alanine aminotransferase or aspartate aminotransferase > 100 U litre/L),
severe chronic obstructive pulmonary disease (forced expired volume in 1 s < 50 % of
predicted or < 2.0 litre), a history of prior coronary artery bypass graft (CABG) surgery or
myocardial infarction (MI) within the previous month, emergent operations, patients on
inotropic support before operation, aortic valvular disease, and infective endocarditis.
The study protocol:
The patients will be randomized into two groups. Randomization into two groups was performed
using sealed envelopes and the sequentially numbered assignments of the participant which
will be concealed in an envelope and will be opened after anesthesia induction by a health
care personnel. The observers will be blinded to the inotropic protocol. Caregivers will not
be blinded, but they will not participate in data collection or data interpretation.
In the levosimendan group, a loading it of levosimendan (6 μg/kg) will be administered after
removal of the aortic cross-clamp, followed by an infusion of levosimendan at a dose of 0.1
μg/kg/min in addition to standard inotropic therapy (one or more agent including;
dobutamine, epinephrine or norepinephrine)for 24 hours. In the control group, only standard
inotropic therapy will be administered.
The need for renal replacement therapy (RRT)will be provided to all patients under the
following criterions: 1- when urine output was less than 100 mL within the last 8 hours, 2-
with no response to 50 mg intravenous dose of furosemide, 3- urine sodium concentration
should be > 40 milliequivalent/liter (mEq/L) before administration of furosemide, 4- blood
urea nitrogen (BUN) level > 50 mg/dl 5-additional presence of one or more of the following
factors such as; a- increase in serum creatinine level > 50% from preoperative value, b-
presence of metabolic acidosis, c- presence of hypervolemia, d- presence of hyperkalemia
(potassium ion level > 5 Meq/L).
The study parameters:
The demographic data includes; age, weight, height, body mass index and gender. The
cardiovascular risk factors including; diabetes mellitus, hypertension,
hypercholesterolemia, obesity, history of smoking as well as history of chronic obstructive
pulmonary disease and peripheral vascular disease were sought.
Echocardiographic data were performed to evaluate the ejection fraction and valvular
functions by the same cardiologist using a Vivid 3 echocardiography device (Healthcare
General Electronics,Hamburg,Germany) before operation and on first hour, 12 and 24 hour
after operation.
Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure (MPAP) >25 mmHg
at rest. The diagnosis of PH depends on direct measurement of the mean PAP by right heart
catheterization. However, we used Doppler echocardiographic study to provide an estimate of
the pulmonary artery systolic pressure (PASP)and mean PAP is calculated with the formula:
mean PAP = 0.65 PASP + 0.55 mmHg.
The risk of operation will be evaluated using the European System for the Cardiac Operation
Risk Evaluation scale (EuroSCORE).
Acute kidney injury (AKI) is defined as increase in serum creatinine from baseline by > 50 %
within 48 hours postoperatively.
SCr levels will be collected on preoperative and postoperative days 1, 3 and 10 and and eGFR
will be calculated according to the abbreviated Modification of Diet in Renal Disease (MDRD)
equation.
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Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention