Cardiac Disease, Chronic Kidney Disease
Conditions
Keywords
Furosemide, Kidney Dysfunction, Glomerular Filtration Rate
Brief summary
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.
Detailed description
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).
Interventions
DRUGFurosemide in 0.9 % NaCl 100 Mg/100 mL (1 mg/mL)
Furosemide 2 mg/hour infusion for 12 hours since induction
DRUGNaCl 0.9%
NaCl 0.9% 2 cc/hour for a period of 12 hours since anesthetic induction
Sponsors
National Cardiovascular Center Harapan Kita Hospital Indonesia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Allocation group was blinded for participants, care provider, and investigators
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Replacement Therapy | 28 days (or until hospital discharge) | number of participant with Renal Replacement Therapy |
| Glomerular Filtration Rate at 120 Hours From Drug Infusion | 120 hours from drug infusion | Glomerular Filtration Rate measured at 120 hours from the initiation of drug infusion |
| Therapeutic Dose of Continuous Diuretic Infusion | 28 days (or until hospital discharge) | number of participants with Therapeutic Dose of Continuous Diuretic Infusion |
| Glomerular Filtration Rate at Baseline | baseline / before induction to anesthesia | Glomerular Filtration Rate measured at baseline |
| Glomerular Filtration Rate at 12 Hours From Drug Infusion | 12 hours from drug infusion | Glomerular Filtration Rate measured at 12 hours from the initiation of drug infusion |
| Glomerular Filtration Rate at 24 Hours From Drug Infusion | 24 hours after from infusion | Glomerular Filtration Rate measured at 24 hours from the initiation of drug infusion |
| Glomerular Filtration Rate at 48 Hours From Drug Infusion | 48 hours from drug infusion | Glomerular Filtration Rate measured at 48 hours from the initiation of drug infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In Hospital Mortality | 28 days (or until hospital discharge) | number of In Hospital mortality |
| ICU Length of Stay | 28 days (or until hospital discharge) | The length of stay in ICU |
Countries
Indonesia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Furosemide Low dose continuous furosemide 2 mg/hour for a period of 12 hours since anesthetic induction
Furosemide: Furosemide 2 mg/hour for 12 hours since induction | 45 |
| Control NaCl 0.9% 2 cc/hour for a period of 12 hours since anesthetic induction
Control: NaCl 0.9% 2 cc/hour for a period of 12 hours since anesthetic induction | 45 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Furosemide | Total | Control |
|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 7 | 58 years STANDARD_DEVIATION 8 | 57 years STANDARD_DEVIATION 8 |
| Height | 161.6 centimeter STANDARD_DEVIATION 7.93 | 161.2 centimeter STANDARD_DEVIATION 7.64 | 160.6 centimeter STANDARD_DEVIATION 7.4 |
| patient with history of daily use of ACEI/ARB history of ACE-i/ARB | 30 Participants | 62 Participants | 32 Participants |
| patient with history of daily use of ACEI/ARB no history of ACE-i/ARB | 15 Participants | 28 Participants | 13 Participants |
| patient with history of daily use of Diuretic History of Diuretics | 19 Participants | 44 Participants | 25 Participants |
| patient with history of daily use of Diuretic no History of Diuretics | 26 Participants | 46 Participants | 20 Participants |
| percentage of Left Ventricular ejection fraction | 56.91 % STANDARD_DEVIATION 9.48 | 55.92 % STANDARD_DEVIATION 9.58 | 54.93 % STANDARD_DEVIATION 9.68 |
| percentage of patient with pre-operation Comorbid score 1-2 (mild condition) | 41 Participants | 82 Participants | 41 Participants |
| percentage of patient with pre-operation Comorbid score 3-4 (moderate condition) | 3 Participants | 7 Participants | 4 Participants |
| percentage of patient with pre-operation Comorbid score >5 (severe condition) | 1 Participants | 1 Participants | 0 Participants |
| percentage of patient with pre operation renal Dysfunction mildly impaired | 22 Participants | 44 Participants | 22 Participants |
| percentage of patient with pre operation renal Dysfunction moderately impaired | 23 Participants | 46 Participants | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 45 Participants | 90 Participants | 45 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 19 Participants | 12 Participants |
| Sex: Female, Male Male | 38 Participants | 71 Participants | 33 Participants |
| Type of operation CABG | 36 Participants | 65 Participants | 29 Participants |
| Type of operation CABG + Valve Surgery | 1 Participants | 1 Participants | 0 Participants |
| Type of operation Valve surgery | 8 Participants | 24 Participants | 16 Participants |
| Weight | 68.7 kilogram STANDARD_DEVIATION 10.7 | 67.7 kilogram STANDARD_DEVIATION 13.5 | 66.7 kilogram STANDARD_DEVIATION 16 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 43 | 1 / 44 |
| other Total, other adverse events | 0 / 43 | 0 / 44 |
| serious Total, serious adverse events | 0 / 43 | 0 / 44 |
Outcome results
Primary
Glomerular Filtration Rate at 120 Hours From Drug Infusion
Glomerular Filtration Rate measured at 120 hours from the initiation of drug infusion
Time frame: 120 hours from drug infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Glomerular Filtration Rate at 120 Hours From Drug Infusion | 49 mL/mnt/1.73 m^2 |
| Control | Glomerular Filtration Rate at 120 Hours From Drug Infusion | 50 mL/mnt/1.73 m^2 |
Primary
Glomerular Filtration Rate at 12 Hours From Drug Infusion
Glomerular Filtration Rate measured at 12 hours from the initiation of drug infusion
Time frame: 12 hours from drug infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Glomerular Filtration Rate at 12 Hours From Drug Infusion | 45 mL/mnt/1.73 m^2 |
| Control | Glomerular Filtration Rate at 12 Hours From Drug Infusion | 46 mL/mnt/1.73 m^2 |
Primary
Glomerular Filtration Rate at 24 Hours From Drug Infusion
Glomerular Filtration Rate measured at 24 hours from the initiation of drug infusion
Time frame: 24 hours after from infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Glomerular Filtration Rate at 24 Hours From Drug Infusion | 39.5 mL/mnt/1.73 m^2 |
| Control | Glomerular Filtration Rate at 24 Hours From Drug Infusion | 38 mL/mnt/1.73 m^2 |
Primary
Glomerular Filtration Rate at 48 Hours From Drug Infusion
Glomerular Filtration Rate measured at 48 hours from the initiation of drug infusion
Time frame: 48 hours from drug infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Glomerular Filtration Rate at 48 Hours From Drug Infusion | 41 mL/mnt/1.73 m^2 |
| Control | Glomerular Filtration Rate at 48 Hours From Drug Infusion | 41.5 mL/mnt/1.73 m^2 |
Primary
Glomerular Filtration Rate at Baseline
Glomerular Filtration Rate measured at baseline
Time frame: baseline / before induction to anesthesia
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Glomerular Filtration Rate at Baseline | 56 mL/mnt/1.73 m^2 |
| Control | Glomerular Filtration Rate at Baseline | 67 mL/mnt/1.73 m^2 |
Primary
Renal Replacement Therapy
number of participant with Renal Replacement Therapy
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Furosemide | Renal Replacement Therapy | 4 Participants |
| Control | Renal Replacement Therapy | 1 Participants |
Primary
Therapeutic Dose of Continuous Diuretic Infusion
number of participants with Therapeutic Dose of Continuous Diuretic Infusion
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Furosemide | Therapeutic Dose of Continuous Diuretic Infusion | 10 Participants |
| Control | Therapeutic Dose of Continuous Diuretic Infusion | 23 Participants |
Secondary
ICU Length of Stay
The length of stay in ICU
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | ICU Length of Stay | 27 hours |
| Control | ICU Length of Stay | 24 hours |
Secondary
In Hospital Mortality
number of In Hospital mortality
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Furosemide | In Hospital Mortality | 1 Participants |
| Control | In Hospital Mortality | 1 Participants |