Dexmedetomidine, Postoperative Acute Kidney Injury, Cardiopulmonary Bypass Graft, Postoperative Complications
Conditions
Keywords
Cardiac surgery-associated acute kidney injury, Dexmedetomidine, Coronary artery bypass grafting, Cardiopulmonary bypass, Renal protection, Vasoactive-inotropic score
Brief summary
Acute kidney injury (AKI) is one of the most frequent complications of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB). Even small postoperative rises in serum creatinine are associated with longer intensive care stay and higher mortality. Ischemia-reperfusion injury, the systemic inflammatory response elicited by contact of blood with the bypass circuit, and heightened perioperative sympathetic activity are believed to contribute to its development. Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist used as a sedative and anesthetic adjunct. It attenuates sympathetic outflow and has shown anti-inflammatory and organ-protective properties in experimental models and in some cardiac surgical populations, but whether it reduces AKI after on-pump CABG surgery has not been established. This is a prospective, randomized, double-blind, placebo-controlled, single-center trial in adults undergoing elective CABG surgery with CPB. One hundred patients aged 18-80 years, ASA physical status II or III, with a preoperative serum creatinine below 1.5 mg/dL are allocated 1:1 to a dexmedetomidine group (n=50) or a control group (n=50). Patients in the dexmedetomidine group receive a loading dose of 1 microgram/kg over 15 minutes after central venous catheterization, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of CPB. Patients in the control group receive an equal volume of 0.9% sodium chloride over the same period and with the same infusion scheme. In both groups the infusion is stopped when CPB begins; no study drug is given during bypass or postoperatively. Anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow a standardized protocol with identical numerical thresholds in both groups, applied by clinicians unaware of group allocation. The primary outcome is the incidence of postoperative AKI within the first 72 hours, staged according to the serum creatinine criteria of the KDIGO 2012 classification. Secondary outcomes are systemic inflammatory markers (white blood cell count, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin), vasoactive drug requirement quantified by the vasoactive-inotropic score, need for renal replacement therapy, time to extubation, intensive care unit and hospital length of stay, and 30-day and 90-day mortality. All patients are followed until postoperative day 90. All variables assessed in the study are parameters obtained as part of routine clinical care in this patient population; no additional intervention or additional laboratory test is performed for study purposes.
Detailed description
Acute kidney injury (AKI) is one of the most frequent complications of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB). Even small postoperative rises in serum creatinine are associated with longer intensive care stay and higher mortality. Ischemia-reperfusion injury, the systemic inflammatory response elicited by contact of blood with the bypass circuit, and heightened perioperative sympathetic activity are believed to contribute to its development. Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist used as a sedative and anesthetic adjunct. It attenuates sympathetic outflow and has shown anti-inflammatory and organ-protective properties in experimental models and in some cardiac surgical populations, but whether it reduces AKI after on-pump CABG surgery has not been established. This is a prospective, randomized, double-blind, placebo-controlled, single-center trial in adults undergoing elective CABG surgery with CPB. One hundred patients aged 18-80 years, ASA physical status II or III, with a preoperative serum creatinine below 1.5 mg/dL are allocated 1:1 to a dexmedetomidine group (n=50) or a control group (n=50). Patients in the dexmedetomidine group receive a loading dose of 1 microgram/kg over 15 minutes after central venous catheterization, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of CPB. Patients in the control group receive an equal volume of 0.9% sodium chloride over the same period and with the same infusion scheme. In both groups the infusion is stopped when CPB begins; no study drug is given during bypass or postoperatively. Anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow a standardized protocol with identical numerical thresholds in both groups, applied by clinicians unaware of group allocation. The primary outcome is the incidence of postoperative AKI within the first 72 hours, staged according to the serum creatinine criteria of the KDIGO 2012 classification. Secondary outcomes are systemic inflammatory markers (white blood cell count, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin), vasoactive drug requirement quantified by the vasoactive-inotropic score, need for renal replacement therapy, time to extubation, intensive care unit and hospital length of stay, and 30-day and 90-day mortality. All patients are followed until postoperative day 90. All variables assessed in the study are parameters obtained as part of routine clinical care in this patient population; no additional intervention or additional laboratory test is performed for study purposes.
Interventions
DRUGDexmedetomidine
Intravenous dexmedetomidine, started after central venous catheterization and a 5-minute period of hemodynamic stabilization: loading dose 1 microgram/kg over 15 minutes, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of cardiopulmonary bypass. The infusion is prepared by a physician who is not involved in intraoperative or postoperative care, in a syringe indistinguishable from the placebo syringe.
Intravenous 0.9% sodium chloride in a volume equal to that of the study drug, administered over the same time intervals and with the same infusion scheme as dexmedetomidine (15-minute loading infusion followed by a maintenance infusion until the start of cardiopulmonary bypass).
Sponsors
Bursa City Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years * Scheduled for elective coronary artery bypass graft surgery with cardiopulmonary bypass at the study center * American Society of Anesthesiologists (ASA) physical status class II or III * Preoperative serum creatinine below 1.5 mg/dL * Written informed consent obtained at the preoperative visit
Exclusion criteria
* Left main coronary artery stenosis greater than 50% * Severe valvular dysfunction * Severe left ventricular hypertrophy or cardiomyopathy * Arrhythmia causing significant hemodynamic compromise * Left ventricular ejection fraction below 35% * Acute coronary syndrome or cardiovascular surgery within the preceding month * Estimated glomerular filtration rate below 15 mL/min/1.73 m2 * Nephropathy due to uncontrolled hypertension and/or diabetes mellitus * Treatment of hypertension with a combination of an angiotensin-converting enzyme inhibitor, a diuretic and an alpha-2 adrenergic agonist * Morbid obesity * Hepatic dysfunction attributable to substance abuse or alcoholism * Previous severe drug allergy during administration of dexmedetomidine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative acute kidney injury (KDIGO serum creatinine criterion) | From the preoperative baseline measurement to postoperative hour 72 | Number and percentage of participants developing acute kidney injury (AKI) of any stage (stage 1 or higher) according to the serum creatinine criterion of the KDIGO 2012 classification. The preoperative serum creatinine value is taken as the baseline; serum creatinine is measured at postoperative hours 0, 24, 48 and 72. AKI is defined as an increase in serum creatinine of 0.3 mg/dL or more from baseline within 48 hours, or a rise to 1.5 times baseline or higher, or the need for renal replacement therapy. The urine output criterion of the KDIGO classification is not applied. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vasoactive-inotropic score | After separation from cardiopulmonary bypass, at intensive care unit admission (postoperative hour 0) and at postoperative hour 24 | Intensity of vasoactive and inotropic support, calculated from the infusion rates being administered at each time point as: dopamine (mcg/kg/min) + dobutamine (mcg/kg/min) + 100 x epinephrine (mcg/kg/min) + 100 x norepinephrine(mcg/kg/min). Doses are converted to mcg/kg/min by dividing the infusion rate by the patient's body weight; the score is taken as zero in participants receiving no vasoactive drug, and higher scores indicate greater vasoactive support. The score is reported separately for each time point and, in addition, as two derived variables: maximum score (the highest of the T2, T3 and T4 values) and postoperative maximum score (the highest of the T3 and T4 values only, which excludes the transient support required during separation from cardiopulmonary bypass). |
| Systemic immune-inflammatory response | Preoperative baseline, at intensive care unit admission (postoperative hour 0) and at postoperative hour 24 | Systemic immune-inflammatory response assessed from the following laboratory parameters: total white blood cell count (10\^3/microliter), absolute neutrophil count (10\^3/microliter), absolute lymphocyte count (10\^3/microliter), neutrophil-to-lymphocyte ratio (unitless, calculated as absolute neutrophil count divided by absolute lymphocyte count), C-reactive protein concentration (mg/L) and procalcitonin concentration (ng/mL). Each parameter is measured from venous blood samples obtained as part of routine clinical care and is reported separately; the preoperative value serves as the within-patient reference. |
| Time to extubation | From ICU admission to extubation, assessed up to postoperative day 7 | Duration of postoperative mechanical ventilation in hours, calculated from the ICU admission and extubation timestamps recorded in the hospital information management system. |
| Length of intensive care unit stay | From ICU admission to ICU discharge, assessed up to postoperative day 30 | Duration of ICU stay in hours, calculated from the admission and discharge timestamps recorded in the hospital information management system. |
| Length of hospital stay | From surgery to hospital discharge, assessed up to postoperative day 30 | Duration of postoperative hospital stay in days, from the day of surgery to the day of hospital discharge. |
Countries
Turkey (Türkiye)
Outcome results
None listed