To Evaluate if Dexmedetomidine Infusion Provides Renal Protection in Patients Undergoing Coronary Artery Bypass Graft
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      OBJECTIVE: Aim of this study is to follow and compare the changes in serum creatinine and
      urine output up to 48 hours of surgery in patients receiving dexmedetomidine infusion in
      addition to standard protocol (Experimental Group) as compared to the patients receiving
      standard protocol alone. (Control Group) in patients undergoing isolated coronary artery
      bypass grafting surgery (CABG) at a tertiary care cardiac center of Karachi, Pakistan.

      STUDY DESIGN: Randomized control trial

      PLACE & DURATION OF STUDY: The research will be conducted in the Department of Anesthesia &
      Intensive Care, National Institute of Cardiovascular Diseases (NICVD), Karachi. 6 months
      (01/08/2021 to 31/1/2022).

      DATA COLLECTION PROCEDURE: This study was conducted among 60 patients allocated randomly into
      two groups. In the study group (group D), dexmedetomidine was given as an infusion of 0.4
      μg/kg/h from induction of anesthesia for 24 hours. In the control group (group C), the
      patients were receiving an equal volume of normal saline.

      PRIMARY OUTCOME: The primary outcome of the study was Serum Creatinine (mg/dl) which was
      measured before the surgery at baseline and then 48 hours after surgery.

      SECONDARY OUTCOMES: The secondary outcomes were incidence of urine output per hour for up to
      48 hours after surgery, operative time from induction of anesthesia till skin closure, aortic
      cross-clamp time from application of aortic cross-clamping till aortic declamping, CPB time
      from connecting the patient to extracorporeal circulation till termination of CPB, duration
      of ICU stay from transferring the patient from the operating room to the ICU till patient
      discharge to the ward, episodes of bradycardia and hypotension, dosage of inotropics and
      hemoglobin levels at baseline and up to 48 hours.

      KEYWORDS: cardiac surgery-associated acute kidney injury, dexmedetomidine, serum creatinine.
    

Detailed description: 
      INTRODUCTION:

      The incidence of cardiac surgery-associated acute kidney injury (CSA-AKI) varies from 5 to
      42%.1 This percentage was found to be 7.86% according to study conducted in Pakistan. 2
      Severe CSA-AKI is independently associated with three to eight-fold higher perioperative
      mortality, prolonged ICU and hospital length of stay, and increased cost of care.3 The
      etiology of renal injury is mainly due to elevation of renin levels as a result of
      sympathetic overactivity in addition to nephrotoxic inflammatory and hemodynamic components.4
      The risk risk factors, even for those patients with complete renal recovery.3 As yet, there
      is no definite strategy for preventing AKI after cardiac surgery.5

      Dexmedetomidine is a selective and potent α2-adrenoceptor agonist that is used for its
      anxiolytic, sedative, and analgesic properties.6 It decreases central nervous system
      sympathetic outflow in a dose-dependent manner and has opioid-sparing analgesic effects.
      There is increasing evidence of its organ-protective properties against ischemic and hypoxic
      injury, including cardioprotection, neuroprotection, and renoprotection.7,8 Peng et al. in
      his meta-analysis has highlighted the significant role of dexmedetomidine in reducing AKI
      after bypass surgeries.8 Then, R.Shi and H-T. Toe have also pointed out the promising
      renoprotective role of Dexmedetomidine in CABG surgeries. 10 Kidney Disease Improving Global
      Outcomes (KDIGO) is one of the latest classifications of identifying AKI and is commonly used
      in various studies. 11 In 2016, Ammar AS et al. in their study documented the reno-protective
      role of peri-operative dexmedetomidine infusion in cardiac surgery.4 The aim of this study is
      to use infusion of dexmedetomidine for renal protection in cardiac surgeries.

      PATIENTS AND METHODS:

      The aim of this study was to compare the changes in serum creatinine and urine output up to
      48 hours of surgery in patients receiving dexmedetomidine infusion in addition to standard
      protocol as compared to the patients receiving standard protocol alone, and see if
      dexmedetomidine infusion reduced the incidence of Acute Kidney Injury (AKI) in patients
      undergoing coronary artery bypass graft surgery (CABG) in a tertiary cardiac center of
      Karachi, Pakistan. This study, a randomized control trial, was conducted in the Department of
      Anesthesia & Intensive Care, National Institute of Cardiovascular Diseases (NICVD), Karachi,
      for a period of 6 months (01/08/2021 to 31/1/2022), after approval from the ethical review
      committee of NICVD, Karachi.

      Sample size for the study was calculated using G*Power version 3.1.9.2 using method of sample
      size calculation for two-sided hypothesis testing of two independent mean. Taking mean and
      standard deviation of serum creatinine after 48 hours of CABG in Dexmedetomidine and control
      group reported by Ammar AS et al. [3], at 5% level of significance and 90% power of test, the
      minimum required sample size of n=6 patients in each group was calculated. Considering the
      design effect, a sample size of 30 patients in each group was decided. N = 60 = 30 (control)
      + 30 (treatment).

      Patients aged between 18 and 65 years, undergoing isolated coronary artery bypass grafting,
      and having ASA physical status class IV were included in the study. All patients with
      preoperative renal impairment (elevated creatinine and blood urea nitrogen levels), on
      diuretic use, preexisting hepatic or pulmonary disease, peripheral vascular disease, previous
      cardiac surgery, emergency surgery, reopening surgeries, surgeries requiring a deep
      hypothermic circulatory arrest, preoperative use of inotropes or vasopressors, perioperative
      use of diuretics, perioperative episode of CPR, preoperative hemoglobin level less than 12
      mg/dl, hematological disorders and with morbid obesity were excluded.

      Preoperatively, careful assessment of the cardiovascular system and investigations for the
      exclusion criteria and routine investigations which included complete blood count,
      coagulation profile, liver, and renal function tests, blood grouping, chest radiography, ECG,
      and echocardiography was done. On the day of surgery in the Operation Theatre (OT), wide bore
      intravenous cannula(16G) was inserted. Midazolam (0.01-0.02 mg/kg) was given as
      premedication. Arterial cannulation was applied under local anesthesia in the radial artery.
      In the operative room, pulse oximeter (SpO2), a five-lead ECG, and invasive arterial blood
      pressure monitoring was applied. Doses of induction was adjusted according to the
      hemodynamics and myocardial function of the patient. Anesthesia was induced by propofol (1-5
      mg/kg) in addition to nalbuphine (0.1-0.2 mg/kg) and atracurium (0.6 mg/kg). After
      preoxygenation for 3 min and finally, a suitable-sized endotracheal tube was inserted, and
      the patient was connected to IPPV. Anesthesia was maintained with an inhalational agent
      (isoflurane) (1-2%) in 100% oxygen with the intent to maintain the mean arterial blood
      pressure and heart rate within 20% of the baseline. Atracurium will be administered, at a
      dose of 0.1-0.2 mg/kg to maintain muscle relaxation throughout the procedure. We divided a
      total of 60 patients after informed and written consent, in to two groups using computer
      generated random allocation based on Bernoulli distribution with probability of success
      (allocation of treatment group) as 0.50. In Dexmedetomidine Group (Group D), patients
      received Dexmedetomidine infusion in addition to standard management protocol (0.4 μg/kg/h
      from induction of anesthesia till the end of surgery). Whereas, in Control Group (Group C)
      patients allocated to this group will receive standard management protocol alone. We have
      used Kidney Disease Improving Global Outcomes (KDIGO) protocol in order to evaluate incidence
      of acute kidney injury. This protocol defines acute kidney injury as increase in serum
      creatinine more than 0.3mg/dl within 48 hours OR urine volume of less than 0.5ml/kg/hr for 6
      hours. 12 After induction of anesthesia, central venous line, urinary catheter, and
      temperature probe was inserted. Before skin incision additional nalbuphine was injected.
      Arterial blood gases, serum Na and K, hematocrit, and blood glucose was measured after
      induction of anesthesia, during CPB, after weaning from CPB and according to needs. Activated
      clotting time was measured at baseline, 3 min after heparin administration, during CPB, and
      finally after reversal of heparin with protamine sulfate. The primary outcome of the study
      was Serum Creatinine (mg/dl) which was measured before the surgery at baseline and then 48
      hours after surgery. The secondary outcomes were incidence of urine output per hour for up to
      48 hours after surgery, operative time from induction of anesthesia till skin closure, aortic
      cross-clamp time from application of aortic cross-clamping till aortic declamping, CPB time
      from connecting the patient to extracorporeal circulation till termination of CPB, duration
      of ICU stay from transferring the patient from the operating room to the ICU till patient
      discharge to the ward, episodes of bradycardia and hypotension, dosage of inotropics and
      hemoglobin levels at baseline and then up to 48 hours. . Hypotension was defined as decrease
      in systolic blood pressure < 90mmHg.12 Bradycardia was defined as heart rate less than 60
      beats/min. 12 The staff involved in the clinical care and members of the study group
      obtaining the data were blinded to randomization for the period of data achievement and
      analysis. Group allocation was revealed after the final statistical analysis.

      Data was analyzed using IBM SPSS version 21, data was summarized by computing descriptive
      statistics such as mean ± SD for continuous response variables (including serum creatinine
      (ng/dL), urine output, and creatinine clearance) and frequency (%) for categorical response
      variables. Treatment and control group was compared for baseline characteristics and outcomes
      by conducting Chi-square test (for categorical variables) and independent sample t-test (for
      continuous response variables). Relative risk (95% CI) of AKI and other adverse outcomes were
      computed for treatment groups. Two-sided p-value of ≤ 0.05 was taken as criteria for
      statistical significance.
    

Intervention name(s): Dexmedetomidine; Normal Saline
Intervention type(s): Drug; Drug
Intervention description(s): DOSAGE FORM: IV Infusion DOSAGE: 0.4 mcg/kg/hr; DOSAGE FORM: IV Infusion DOSAGE: Equal Volume
Other intervention name(s): sedatives (Precedex); crystalloid fluid
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study was conducted among 60 patients allocated randomly into two groups. In the study group (group D), dexmedetomidine was given as an infusion of 0.4 μg/kg/h from induction of anesthesia for 24 hours. In the control group (group C), the patients were receiving an equal volume of normal saline. The primary outcome of the study was Serum Creatinine (mg/dl) which was measured before the surgery as baseline and then at 48 hours after surgery.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention