Low Dose Continuous Furosemide Effect on Cardiac Surgery Patients With Kidney Dysfunction

Chronic kidney disease is an independent risk factor for cardiovascular disease associated with increased mortality rate during cardiac surgery in proportion to the kidney function. Chronic kidney disease is defined by decreased glomerular filtration rate (GFR) as classified by Kidney Disease: Improving Global Outcome (KDIGO). Deterioration of kidney function has a complex and multifactorial pathophysiologic derangement. In order to counter kidney injury associated with cardiac surgery, several pharmacologic and non-pharmacologic interventions have been studied to prevent perioperative deterioration of kidney function. Diuretics as pharmacologic measure are often used post-cardiac surgery to treat fluid overload and managing patient with acute kidney injury by preventing anuria. Loop diuretics (furosemide) may improve renal blood flow, decrease reabsorption in renal tubules, decrease oxygen demand and energy consumption (blocking potassium/sodium/2cloride co-transport in loop of Henle), and prevent hypoxic injury of renal medulla. Low dose continuous furosemide hypothetically has a protective effect on cardiac surgery patients with kidney dysfunction, measured improved glomerular filtration rate, decreased indication for therapeutic furosemide infusion, and decreased need of renal replacement therapy. On the other hand, administration of furosemide is rather harmful in severe kidney dysfunction. Therefore, the objective of this study is to determine the protective effect of low-dose continuous furosemide perioperative in cardiac surgery patients with mild to moderate kidney dysfunction.

The study was a double-blind randomized controlled trial to determine the protective effect of low-dose continuous furosemide perioperative in cardiac surgery patients with mild to moderate kidney dysfunction. Ethical clearance for the study was approved by Institutional Review Board of National Cardiovascular Center Harapan Kita. Patients eligible for the study was recruited and written informed consent was obtained after clear explanation of the study. Allocation of furosemide and control group was done using simple computer randomization by staff who was not involved in the study. Furosemide infusion and normal saline was prepared by independent pharmacist blinded to the study. Furosemide solution was prepared to contain 40 mg of furosemide diluted with normal saline to a total volume of 40 cc (1 mg / 1 cc) and control solution was prepared to contain only 40 cc of normal saline. Both solution was packaged in 50-cc syringe and prepared in similar fashion. The solution was administered after induction of anesthesia with rate of 2 cc per hour for 12 hours.

Baseline participant were collected before surgery. All cardiac surgery procedure was done in concordance to hospital standard operating procedure. The primary outcomes of the study were glomerular filtration rate, need of diuretic infusion dose after intervention, need of renal replacement therapy and the secondary outcomes were ICU length of stay and in hospital mortality. The calculated sample size estimated was 41 participants per group, accounting for drop-out rate, expected sample size was 45 participants per group (90 participants in total).

Eligibility Criteria:
Inclusion Criteria:

* Age 18 to 65 years old.
* Patient planned with elective cardiac surgery such as CABG, one cardiac valve replacement, one cardiac valve repair or two valves, CABG and replacement/repair one cardiac valve.
* Cardiac surgery performed using cardiopulmonary bypass machine.
* Patient with mild to moderate kidney dysfunction (GFR 30-89 mL/min/1.73m2) and never got renal replacement therapy before.

Exclusion Criteria:

* Cardiac ejection fraction \<40%.
* Patient with new preoperative acute renal failure by any cause.
* Sudden shift in cardiac surgery timing (emergency cardiac surgery or repeated procedure).
* Complex cardiac disease associated with intra aortic balloon pump use, replacement of more than two cardiac valves, coronary artery disease with severe valve disease, and patient with pulmonary hypertension, and cardiac surgery procedures for congenital heart disease.
* Patient with aortic abnormality, and/or has direct effect on renal artery.
* Patients concurrently enrolled in other study with other drugs being studied.
* Patient with hemodynamic disturbance caused by hemorrhage, sepsis, anaphylactic, or cardiogenic shock.
* Patient refuses to participate in the study.