Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery

Vanderbilt University Medical Center653 enrolled

Overview

Aim1a: Statin naive patient's scheduled for cardiac surgery will be randomized to 80mg atorvastatin or placebo on the day prior to surgery and then 40mg daily thereafter until hospital discharge to test the hypothesis that short-term atorvastatin use decreases: 1. acute kidney injury following cardiac surgery. 2. postoperative delirium following cardiac surgery. Aim1b: Patients using statins preoperatively will be randomized to atorvastatin 80mg or placebo on day of surgery and 40mg or placebo on postop day 1 with resumption of preoperative statin therapy on postop day 2 to test the hypothesis that short-term atorvastatin use decreases: 1. acute kidney injury following cardiac surgery. 2. postoperative delirium following cardiac surgery. Endpoints include glomerular filtration, urine and plasma markers of renal dysfunction, markers of oxidative stress, mitochondrial function, systemic inflammatory markers, delirium, dialysis, stroke, myocardial infarction, time to extubation, ICU length of stay, and death.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

653

Conditions

Acute Kidney Injury Post-Operative Delirium Icu Delirium

Interventions

atorvastatinDRUG

Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.

placeboDRUG

Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * open heart surgery Exclusion Criteria: * acute coronary syndrome with troponin leak or unrelenting angina * liver dysfunction (transaminases 2x normal) * history of myopathy or liver dysfunction on prior statin therapy * use of potent CYP3A4 inhibitors such as antifungal azoles, macrolide antibiotics, HIV protease inhibitors, and nefazodone. * pregnancy or breast feeding * cyclosporine use * dialysis * history of kidney transplant * fibrate users who cannot stop fibrate use.

Outcomes

Primary Outcomes

Number of Participants With Acute Kidney Injury

Time frame: postoperative day 2

Number of Participants With Delirium

Time frame: while in ICU (about 2 days)

Secondary Outcomes

Number of Participants Requiring Dialysis

Time frame: while in ICU (about 2 days)

Liver Enzyme: Aspartate Aminotransferase Level

Time frame: postoperative day 1

Number of Participants With Stroke

Time frame: while in ICU (about 2 days)

Number of Participants That Died

Time frame: until postoperative hospital discharge (about 7 days)

Mitochondrial Function--mtDNA Copy Number

mtDNA copy number

Time frame: anesthesia induction and POD 1

Mitochondrial Function--lactate / Pyruvate Ratio

lactate / pyruvate ratio

Time frame: anesthesia induction, after CPB, and POD 1

Mitochondrial Function--PGC-1alpha RNA Expression

PGC-1alpha RNA expression

Time frame: anesthesia induction and POD 1

Urine Markers of Renal Injury

tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7

Time frame: anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and Post op Day (POD) 1, 2, 3

Plasma Markers of Oxidative Stress: f2-Isoprostanes

Time frame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Plasma Markers of Oxidative Stress: Isofurans

Time frame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Urine Markers of Oxidative Stress: f2-Isoprostanes

Time frame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Urine Markers of Oxidative Stress: Isofurans

Time frame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)

measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)

Time frame: anesthesia induction, ICU admission, and POD 1

Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)

measurements of blood brain barrier disruption (S100 calcium-binding protein B)

Time frame: anesthesia induction, ICU admission, and POD 1

Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes