Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00454428 |
| Other study ID # |
27579 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
March 29, 2007 |
| Last updated |
March 29, 2007 |
Study information
| Verified date |
March 2006 |
| Source |
University of Cantanzaro |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Italy: Ethics Committee |
| Study type |
Interventional
|
Clinical Trial Summary
Linear flow during cardiopulmonary bypass (CPB) frequently induces renal damage.
We will evaluate whether automatic intra-aortic balloon pump (IABP) induce pulsatile
perfusion preserves renal function in patients undergoing myocardial revascularization at
different risk for renal damage.
100 patients undergoing preoperative IABP will be stratified for renal function.
Intervention. The patients will be randomized to non-pulsatile CPB during cardioplegic
arrest or automatic IABP induced pulsatile CPB.
Renal function, daily diuretics, complication rate, lactatemia and other biochemical indices
will be compared in patients.
We will prospectively enrolle 100 patients undergoing isolated primary high-risk coronary
artery bypass grafting for severe left main stem disease (70% narrowing) or left-main
equivalent three-vessels coronary disease. On admission to our institution, the patients
will be stratified for renal function according to KDOQI and randomly assigned to Group A or
Group B. We will exclude from the study patients older than 75 years, and/or with kidney
disease ≥ Stage 4 (GFR 15 – 29 ml/min/1.73 m2), and/or with other splanchnic organ
comorbidities (liver or mesenteric impairment, abdominal aortic aneurysm, abdominal arteries
vasculopathy), and/or severe autoimmune disease.
The patients randomized to Group A (n=50) will receive a preoperative IABP treatment before
induction of anesthesia, with IABP turned off during cardioplegic arrest, and restarted with
a 1:1 IABP mode immediately after cross-clamp removal (as is the traditionally adopted
perioperative IABP support); the other 50 (Group B) will receive standard preoperative
treatment with IABP, which will switche into an automatic 80 bpm mode during cross-clamp
time, and switche again into a 1:1 IABP after cross-clamp removal, in order to achieve a
pulsatile perfusion during the entire intra-operative time-course.
The patients will be stratified in 2 subgroups according to the preoperative renal function:
a subgroup will include 64 patients (32 allocated in Group A and 32 in Group B) with stage 1
or 2 [Stage 1: GFR ≥90 ml/min/1.73 m2 – Stage 2: GFR 60 - 89 ml/min/1.73 m2] and therefore
considered at lower-risk for post-CPB renal damage; the remaining 36 (18 for each group)
with KDOQI Stage 3 of kidney disease (GFR 30 – 59 ml/min/1.73 m2) will be considered at
higher-risk for perioperative renal complications [19].
Description:
Linear flow during cardiopulmonary bypass (CPB) frequently induces renal damage.
We will evaluate whether automatic intra-aortic balloon pump (IABP) induced pulsatile
perfusion preserves renal function in patients undergoing myocardial revascularization at
different risk for renal damage.
100 patients undergoing preoperative IABP will be stratified for renal function.
Intervention. The patients will be randomized to non-pulsatile CPB during cardioplegic
arrest or automatic IABP induced pulsatile CPB.
Renal function, daily diuretics, complication rate, lactatemia and other biochemical indices
will be compared in patients.
We will prospectively enrolle 100 patients undergoing isolated primary high-risk coronary
artery bypass grafting for severe left main stem disease (70% narrowing) or left-main
equivalent three-vessels coronary disease. On admission to our institution, the patients
will be stratified for renal function according to KDOQI and randomly assigned to Group A or
Group B. We will exclude from the study patients older than 75 years, and/or with kidney
disease ≥ Stage 4 (GFR 15 – 29 ml/min/1.73 m2), and/or with other splanchnic organ
comorbidities (liver or mesenteric impairment, abdominal aortic aneurysm, abdominal arteries
vasculopathy), and/or severe autoimmune disease.
The patients randomized to Group A (n=50) will receive a preoperative IABP treatment before
induction of anesthesia, with IABP turned off during cardioplegic arrest, and restarted with
a 1:1 IABP mode immediately after cross-clamp removal (as is the traditionally adopted
perioperative IABP support); the other 50 (Group B) will receive standard preoperative
treatment with IABP, which will switche into an automatic 80 bpm mode during cross-clamp
time, and switche again into a 1:1 IABP after cross-clamp removal, in order to achieve a
pulsatile perfusion during the entire intra-operative time-course.
The patients will be stratified in 2 subgroups according to the preoperative renal function:
a subgroup will include 64 patients (32 allocated in Group A and 32 in Group B) with stage 1
or 2 [Stage 1: GFR ≥90 ml/min/1.73 m2 – Stage 2: GFR 60 - 89 ml/min/1.73 m2] and therefore
considere at lower-risk for post-CPB renal damage; the remaining 36 (18 for each group) with
KDOQI Stage 3 of kidney disease (GFR 30 – 59 ml/min/1.73 m2) will be considered at
higher-risk for perioperative renal complications [19].
The study protocol has been approved by the institution’s Ethical Committee/Institutional
Review Board, and informed consent will be obtained from each patient.
Anesthesia Anesthetic technique will be standardized: induction will consiste of i.v.
propofol infusion (3 mg/kg) combined with fentanyl (0.10 mg/Kg). Neuromuscular blockade will
be achieved by 4 mg/h pancuronium bromide, and lungs will be ventilated to normocapnia with
air and oxygen (45-50%). Propofol infusion (150-200 μg/Kg per min) and isoflurane (0.5%
inspired concentration) will maintaine anesthesia. Inotropes will be started immediately
after aortic cross-clamp removal to maintain adequate mean systemic pressure, always
starting with enoximone at a dosage of 5 μg/Kg/min. The need for further increase in
inotropes will be record: inotropes will be defined as “low-dose” when enoximone will be
administered at a dosage 5 μg/Kg/min, “medium-dose” when enoximone will be between 6 and 10
μg/Kg/min, or dobutamine will add at a dosage between 5 and 10 μg/Kg/min, and “high-dose”
when enoximone or dobutamine will be >10 μg/Kg/min or epinephrine add at any dose.
Surgical technique and cardiopulmonary bypass According to our Institutional policy we will
insert IABP (7.5 or 8 Fr, 34 or 40 ml according to the body surface area; balloon Datascope
Corp., Fairfield, NJ, connected to a Datascope pump [Datascope Corp, Fairfield, NJ])
percutaneously with the “sheetless” technique, through the best femoral artery, before
induction of anesthesia, in order to better support the perioperative hemodynamic of
patients undergoing surgery for severe left main stem or 3-vessels left-main equivalent
disease. The correct placement of IABP will be always assessed by postoperative chest X-ray
or transesophageal echocardiography. Patients will receive anticoagulation with enoxaparin,
with a target activated partial thromboplastin time >40 seconds, starting when the
postoperative bleeding was controlled (usually within 6 hours). IABP will be withdrawn when
hemodynamic stability will restore (i.e., a cardiac index 2.0 L/m2 per minute with only
minimal pharmacologic inotropic support, dobutamine or enoximone at 5 µg/kg per minute). CPB
and surgical techniques will be standardized and not changed during the study period.
Heparin will be given at a dose of 300 IU/kg to achieve a target activated clotting time of
480 seconds or above. Blood recovery with an autotransfusion device (Autotrans Dideco,
Mirandola, Modena, Italy) will be performed intraoperatively in all cases. A level of
hemoglobin lower than 8 g/dl will be used as an indication for blood transfusion. Standard
CPB circuit will be used. The extracorporeal circuit will be primed with 1000 ml of Ringer’s
Lactate solution and 40 mg of heparin. Systemic temperature will be kept between 32 and 34°
C. Myocardial protection will be achieved with intermittent antegrade and retrograde
hyperkalemic blood cardioplegia. Total CPB flow will be maintained at 2.6 L/min-1/m-2. In
Group A patients, IABP will be turned off during cardioplegic arrest, maintaining a standard
non-pulsatile CPB; Group B patients will undergo IABP-induced pulsatile CPB during
cardioplegic arrest, with pulsatile flow maintained by an automatic 80 bpm mode until aortic
declamping.
Endpoints The primary endpoint of this study is the evaluation of the renal function as
assessed by measuring GFR in the perioperative period. In all patients will be evaluated
perioperative renal function, in-hospital mortality and morbidity, and complications,
in-hospital and intensive therapy unit (ITU) stay, IABP-related complications. Renal
function is primarily evaluated by GFR calculated using the abbreviated Modification of Diet
in Renal Disease (MDRD) study equation, recommended by KDOQI as the preferred equation for
the calculation of GFR in adults (taking into account serum creatinine, age, race, gender)
[22] and, secondarily, by other indices, such as urine output, need for diuretics, blood
urea nitrogen (BUN). Plasma lactate concentrations will be measured to indirectly assess the
adequacy of tissue perfusion [20] Acute renal insufficiency (ARI) is defined as a decrease
greater than 50% over preoperative value of calculated GFR. Acute renal failure (ARF) is
defined as any postoperative renal insufficiency requiring first-time hemofiltration,
dialysis or any other renal replacement therapy (RRT). In-hospital mortality is defined as
any death occurring during hospital stay or in the first 30 postoperative days. Hospital
morbidity is defined as any complication requiring specific therapy or causing a delay in
hospital or ITU discharge. IABP-related complications is defined as any aortic dissection or
perforation, limb or mesenteric ischemia, or infection or hemorrhage at the balloon entry
point.
Biochemical analysis All patients will undergo pre- and perioperatively routine laboratory
investigations, including standard hemogram, serum levels of creatinine, urea nitrogen,
calcium, phosphate, glucose, albumin, electrolytes, albumin, transaminases,
-glutamyl-transpeptidase, lactic acid dehydrogenase, bilirubin, acid-base parameters,
troponin I and lactic acid. The determinations of the majority of these parameters will be
conducted preoperatively before anesthetic induction, and at 12, 24, 48, and 72 hours
postoperatively. In order to evaluate the adequacy of myocardial protection techniques,
Troponin I will be measured on coronary sinus blood samples, obtained from the retrograde
cardioplegic cannula, 10 minutes following completion of proximal anastomoses. The Troponin
I assays will be carried out using diagnostic kits provided by Beckman Coulter (Fullerton,
California; AccuTnITM Access Immunoassay System).
Statistical analysis Statistical analysis will be performed by the SPSS program for Windows,
version 10.1 (SPSS Inc, Chicago, IL). Continuous variables will be presented as mean ±
standard deviation, and categorical variables as absolute numbers and/or percentages. Data
will be checked for normality before statistical analysis. Normally-distributed continuous
variables will be compared using the unpaired t test, whereas the Mann-Whitney U test will
be used for those variables that are not normally distributed. Categorical variables will be
analyzed using either the chi-square test or Fischer's exact test. Comparison between and
within groups will be made using two-way analysis of variance for repeated measures.
Comparisons will be considered significant if p<0.05.
