Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06378827
Status:
RECRUITING
Last Update Posted:
2024-04-23
First Post:
2024-04-13
Brief Title:
Intraoperative Dexmedetomidine and Coronary Artery Bypass Graft Surgery
Sponsor:
University of Novi Sad
Organization:
University of Novi Sad
Study Overview
Official Title:
The Effect of Intraoperative Dexmedetomidine on Renal Function After Coronary Artery Bypass Graft Surgery
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a prospective randomized clinical trial designed to determine the effect of intraoperative dexmedetomidine administration on renal function after coronary artery bypass graft surgery
Detailed Description:
This study will include patients admitted to the Clinic for Cardiovascular Surgery of the Institute of Cardiovascular Diseases of Vojvodina planned for elective coronary artery bypass graft surgery CABG Basic demographic and anthropometric data gender age height weight and body mass index and data on comorbidities therapy and allergies will be recorded The day before surgery all patients will undergo transthoracic echocardiography on the basis of which the ejection fraction of the left ventricle will be determined and recorded After the entire examination the New York Heart Association NYHA class American Society of Anaesthesiologists physical status ASA score and Estimate risk of in-hospital death after cardiac surgery score EuroSCORE II will be determined The method and purpose of the research will be explained to all patients after which informed consent for participation in the research will be obtained
The patients will be divided into two groups experimental and control using the randomization method All patients will have blood drawn for laboratory and biochemical analyses the morning before surgery urea creatinine cystatin C IL-6 hemoglobin leukocytes platelets glycemia aspartate aminotransferase AST alanine transaminase ALT lactate dehydrogenase LDH direct and total bilirubin fibrinogen CRP CK-MB hS troponin I electrolytes Na and K and lactates With the help of the Cockcroft-Gault formula the estimated glomerular filtration rate eGFR and creatinine clearance CCr will be determined The values of all these analyses will be defined as basal values
The anesthetic and surgical protocol as well as the postoperative treatment will be standardized Half an hour before arriving in the operating room patients will receive about 005 mgkg of midazolam per os as premedication Upon arrival in the operating room electrodes for continuous monitoring of the electrocardiogram ECG electrodes for assessing the depth of anesthesia and pulse oximetry for monitoring pulse saturation SpO2 will be attached to all patients Anesthetist nurses will place a peripheral venous cannula usually in one of the veins of the right arm through which infusion solutions will be applied in the perioperative period and if necessary transfusions of autologous blood resuspended erythrocytes platelets and fresh frozen plasma The anesthesiologist will place the arterial cannula mostly in the left radial artery for continuous monitoring of arterial blood pressure values After adequate preoxygenation 8 lmin 3 min via a ventilation mask the intravenous anesthesia will be administered with a combination of the benzodiazepine midazolam about 005 mgkg the opioid analgesic sufentanil about 015 µgkg intravenous anesthetic propofol about 1 mgkg and the neuromuscular relaxant rocuronium bromide about 08 mgkg After endotracheal intubation patients will be on mechanical lung ventilation MLV - volume-controlled ventilation mode with a tidal volume of 6-8 mlkg of ideal body weight a respiratory rate of 12min FiO2 of 05 a positive end-expiratory pressure PEEP of 5 cmH2O and an inspiratory ratio to expirium - IE 12 The flow of fresh gases at the MLV in all patients will be 3 lmin Correction of MLV parameters will be done based on partial pressures of oxygen PaO2 and carbon dioxide PaCO2 in arterial blood with the aim of maintaining PaO2 100 mmHg and PaCO2 35-45 mmHg A three-lumen central venous catheter CVC will be placed mainly in the right interior jugular vein All patients will be placed with a urinary catheter to monitor hourly diuresis as well as a nasopharyngeal probe to monitor nasopharyngeal temperature
Dexmedetomidine solution will be prepared by diluting one ampoule of dexmedetomidine 200µg2ml with 48 ml of saline solution to obtain a dexmedetomidine solution of 4µgml Patients from the experimental group will receive a continuous infusion of dexmedetomidine at a dose of 05 µgkgh until the end of the operation Patients in the control group will receive the same volume of saline solution
Anesthesia will be maintained with the inhaled anesthetic sevoflurane with target depth of anesthesia values between 40 and 60 as measured by entropy A continuous intravenous infusion of sufentanil 05-1 µgkgh will be used for intraoperative analgesia Neuromuscular relaxation will be maintained by intermittent bolus doses of rocuronium bromide on average about 04 mgkgh All patients will receive an intravenous antibiotic Ceftriaxone 1g half an hour before the surgical incision and in cases of allergy to cephalosporins Vancomycin 500 mg All patients are prescribed tranexamic acid according to the protocol
All operations will be performed through a medial sternotomy approach To achieve total heparinization heparin will be prescribed at a dose of 300-400 IUkg After 5 minutes from the administration of heparin arterial blood will be drawn to determine the activated coagulation time ie ACT After reaching the value of ACT 480 s cardiopulmonary bypass CPB will be started During that period the inhalation anesthetic will be turned off and anesthesia will be maintained with a continuous infusion of propofol During the application of the CBP pump MLV will be performed with a tidal volume of 2-3 mlkg of ideal body weight a respiratory rate of 10min an FiO2 of 05 and a PEEP of 5 cmH2O Membrane oxygenators will be used for CPB which will be primed with 1500 ml of Hartmanns solution and 2500 IU of heparin The flow rate of the CPB non-pulsating pump will be 2-24 lminm2 The value of mean arterial pressure during CPB will be maintained between 50 and 80 mmHg Hemoglobin values will be maintained above 8 gdl and hematocrit values will be above 022 In cases of lower values resuspended erythrocytes will be prescribed Crystalloid cardioplegic solution or blood cardioplegia will be used to stop and protect the myocardium All operations will be performed under conditions of mild hypothermia 33-34C It will be recorded whether the heart after removing the aortic clamp worked spontaneously whether it was defibrillated with an internal defibrillator or whether a temporary pacemaker was applied To reverse the effect of heparin after the completion of CPB and removal of the cannula for CPB protamine sulfate will be prescribed at a dose of 1 mg per 100 IU of heparin
During the operation the anesthesiologist will record the values of systolic and diastolic arterial blood pressure and heart rate every 5 minutes the values of central venous pressure SpO2 and depth of anesthesia every 15 minutes as well as hourly diuresis in the anesthesia chart The presence of significant arterial hypotension mean arterial pressure 65 mmHg or 50 mmHg during CPB lasting at least 5 min will be recorded and whether it lasted 5-15 15-30 or longer than 30 min will be recorded The length of application of the aortic clamp the length of application of the CPB pump and the length of the operation will be recorded The total doses of propofol mg sufentanil µg and the volume of sevoflurane ml administered during the operation will be recorded as well as the total volume of Hartmanns solution cardioplegia solution and eventual transfusion of autologous blood resuspended erythrocytes platelets and fresh frozen plasma It will be recorded whether the patient was prescribed antihypertensives sympathomimetics parasympatholytics inotropics and vasopressor support in what doses and for what period of time if a continuous infusion was used
After surgery the patients will be sedated with a continuous infusion of propofol about 2 mgkgh and on MLV and will be transferred to the ICU where after meeting the criteria necessary for separation from MLV they will be extubated Continuous monitoring ECG invasive arterial pressure central venous pressure SpO2 hourly diuresis body temperature arterial blood gas analysis continues during the stay of patients in the intensive care unit ICU and in the semi-intensive care unit On the first three days the day of surgery and the first two postoperative days the presence of mean arterial pressure 65 mmHg will be recorded and it will be noted whether it lasted less than 1 hour 1-3 hours 3-6 hours or more than 6 hours The intake of crystalloid solutions resuspended erythrocytes fresh frozen plasma and platelets will be monitored and recorded Daily diuresis daily blood loss the amount of prescribed diuretics during 24 hours as well as the use of inotropes will be recorded During the first three days the presence of oliguria 05 mlkg will be recorded and noted whether it lasted 6-12 hours or longer than 12 hours the presence of severe oliguria 03 mlkg lasting longer than 24 hours or the presence of anuria lasting longer than 12 hours
On the first postoperative day all laboratory and biochemical analyses that were performed preoperatively will be repeated urea creatinine cystatin C IL-6 hemoglobin leukocytes platelets glycemia AST ALT LDH direct to total bilirubin fibrinogen CRP CK-MB hS troponin I Na K and lactates On the second postoperative day serum cystatin C creatinine Na K and lactate analyses will be repeated Creatinine values will be determined on the third and fifth postoperative day Based on each new creatinine value eGFR and CCr will be determined
For all patients the length of postoperative MLV in hours the length of stay in the ICU in days the length of hospitalization after surgery in days and possibly death will be recorded
The primary objective of the study will be to monitor and compare between groups indicators of renal function serum creatinine cystatin C diuresis eGFR and CCr The changes of all these values in relation to the basal values will be monitored in order to determine when the greatest changes in the values of the indicators of renal function occur Of particular importance will be the correlation between serum cystatin C and creatinine values During the first three days daily diuresis the volume of prescribed liquids the administration and doses of diuretics and the values of Na K and lactate will be monitored and compared The frequency of the occurrence of acute kidney injury AKI will be monitored The diagnosis of AKI will be based on the criteria of the KDIGO guide
The change of inflammatory markers IL-6 CRP leukocytes fibrinogen in relation to basal values is also one of the primary goals of the research Inflammatory markers will be checked on the first postoperative day when the inflammatory response is most pronounced A correlation will be made between IL-6 and other inflammatory markers that are in routine clinical use CRP leukocytes and fibrinogen in order to determine which inflammatory marker correlates best with IL-6 A correlation between IL-6 values and serum creatinine and cystatin C values will also be performed in order to determine whether impairment of renal function is related to the intensity of the inflammatory response
The patients will be divided into two groups experimental and control using the randomization method All patients will have blood drawn for laboratory and biochemical analyses the morning before surgery urea creatinine cystatin C IL-6 hemoglobin leukocytes platelets glycemia aspartate aminotransferase AST alanine transaminase ALT lactate dehydrogenase LDH direct and total bilirubin fibrinogen CRP CK-MB hS troponin I electrolytes Na and K and lactates With the help of the Cockcroft-Gault formula the estimated glomerular filtration rate eGFR and creatinine clearance CCr will be determined The values of all these analyses will be defined as basal values
The anesthetic and surgical protocol as well as the postoperative treatment will be standardized Half an hour before arriving in the operating room patients will receive about 005 mgkg of midazolam per os as premedication Upon arrival in the operating room electrodes for continuous monitoring of the electrocardiogram ECG electrodes for assessing the depth of anesthesia and pulse oximetry for monitoring pulse saturation SpO2 will be attached to all patients Anesthetist nurses will place a peripheral venous cannula usually in one of the veins of the right arm through which infusion solutions will be applied in the perioperative period and if necessary transfusions of autologous blood resuspended erythrocytes platelets and fresh frozen plasma The anesthesiologist will place the arterial cannula mostly in the left radial artery for continuous monitoring of arterial blood pressure values After adequate preoxygenation 8 lmin 3 min via a ventilation mask the intravenous anesthesia will be administered with a combination of the benzodiazepine midazolam about 005 mgkg the opioid analgesic sufentanil about 015 µgkg intravenous anesthetic propofol about 1 mgkg and the neuromuscular relaxant rocuronium bromide about 08 mgkg After endotracheal intubation patients will be on mechanical lung ventilation MLV - volume-controlled ventilation mode with a tidal volume of 6-8 mlkg of ideal body weight a respiratory rate of 12min FiO2 of 05 a positive end-expiratory pressure PEEP of 5 cmH2O and an inspiratory ratio to expirium - IE 12 The flow of fresh gases at the MLV in all patients will be 3 lmin Correction of MLV parameters will be done based on partial pressures of oxygen PaO2 and carbon dioxide PaCO2 in arterial blood with the aim of maintaining PaO2 100 mmHg and PaCO2 35-45 mmHg A three-lumen central venous catheter CVC will be placed mainly in the right interior jugular vein All patients will be placed with a urinary catheter to monitor hourly diuresis as well as a nasopharyngeal probe to monitor nasopharyngeal temperature
Dexmedetomidine solution will be prepared by diluting one ampoule of dexmedetomidine 200µg2ml with 48 ml of saline solution to obtain a dexmedetomidine solution of 4µgml Patients from the experimental group will receive a continuous infusion of dexmedetomidine at a dose of 05 µgkgh until the end of the operation Patients in the control group will receive the same volume of saline solution
Anesthesia will be maintained with the inhaled anesthetic sevoflurane with target depth of anesthesia values between 40 and 60 as measured by entropy A continuous intravenous infusion of sufentanil 05-1 µgkgh will be used for intraoperative analgesia Neuromuscular relaxation will be maintained by intermittent bolus doses of rocuronium bromide on average about 04 mgkgh All patients will receive an intravenous antibiotic Ceftriaxone 1g half an hour before the surgical incision and in cases of allergy to cephalosporins Vancomycin 500 mg All patients are prescribed tranexamic acid according to the protocol
All operations will be performed through a medial sternotomy approach To achieve total heparinization heparin will be prescribed at a dose of 300-400 IUkg After 5 minutes from the administration of heparin arterial blood will be drawn to determine the activated coagulation time ie ACT After reaching the value of ACT 480 s cardiopulmonary bypass CPB will be started During that period the inhalation anesthetic will be turned off and anesthesia will be maintained with a continuous infusion of propofol During the application of the CBP pump MLV will be performed with a tidal volume of 2-3 mlkg of ideal body weight a respiratory rate of 10min an FiO2 of 05 and a PEEP of 5 cmH2O Membrane oxygenators will be used for CPB which will be primed with 1500 ml of Hartmanns solution and 2500 IU of heparin The flow rate of the CPB non-pulsating pump will be 2-24 lminm2 The value of mean arterial pressure during CPB will be maintained between 50 and 80 mmHg Hemoglobin values will be maintained above 8 gdl and hematocrit values will be above 022 In cases of lower values resuspended erythrocytes will be prescribed Crystalloid cardioplegic solution or blood cardioplegia will be used to stop and protect the myocardium All operations will be performed under conditions of mild hypothermia 33-34C It will be recorded whether the heart after removing the aortic clamp worked spontaneously whether it was defibrillated with an internal defibrillator or whether a temporary pacemaker was applied To reverse the effect of heparin after the completion of CPB and removal of the cannula for CPB protamine sulfate will be prescribed at a dose of 1 mg per 100 IU of heparin
During the operation the anesthesiologist will record the values of systolic and diastolic arterial blood pressure and heart rate every 5 minutes the values of central venous pressure SpO2 and depth of anesthesia every 15 minutes as well as hourly diuresis in the anesthesia chart The presence of significant arterial hypotension mean arterial pressure 65 mmHg or 50 mmHg during CPB lasting at least 5 min will be recorded and whether it lasted 5-15 15-30 or longer than 30 min will be recorded The length of application of the aortic clamp the length of application of the CPB pump and the length of the operation will be recorded The total doses of propofol mg sufentanil µg and the volume of sevoflurane ml administered during the operation will be recorded as well as the total volume of Hartmanns solution cardioplegia solution and eventual transfusion of autologous blood resuspended erythrocytes platelets and fresh frozen plasma It will be recorded whether the patient was prescribed antihypertensives sympathomimetics parasympatholytics inotropics and vasopressor support in what doses and for what period of time if a continuous infusion was used
After surgery the patients will be sedated with a continuous infusion of propofol about 2 mgkgh and on MLV and will be transferred to the ICU where after meeting the criteria necessary for separation from MLV they will be extubated Continuous monitoring ECG invasive arterial pressure central venous pressure SpO2 hourly diuresis body temperature arterial blood gas analysis continues during the stay of patients in the intensive care unit ICU and in the semi-intensive care unit On the first three days the day of surgery and the first two postoperative days the presence of mean arterial pressure 65 mmHg will be recorded and it will be noted whether it lasted less than 1 hour 1-3 hours 3-6 hours or more than 6 hours The intake of crystalloid solutions resuspended erythrocytes fresh frozen plasma and platelets will be monitored and recorded Daily diuresis daily blood loss the amount of prescribed diuretics during 24 hours as well as the use of inotropes will be recorded During the first three days the presence of oliguria 05 mlkg will be recorded and noted whether it lasted 6-12 hours or longer than 12 hours the presence of severe oliguria 03 mlkg lasting longer than 24 hours or the presence of anuria lasting longer than 12 hours
On the first postoperative day all laboratory and biochemical analyses that were performed preoperatively will be repeated urea creatinine cystatin C IL-6 hemoglobin leukocytes platelets glycemia AST ALT LDH direct to total bilirubin fibrinogen CRP CK-MB hS troponin I Na K and lactates On the second postoperative day serum cystatin C creatinine Na K and lactate analyses will be repeated Creatinine values will be determined on the third and fifth postoperative day Based on each new creatinine value eGFR and CCr will be determined
For all patients the length of postoperative MLV in hours the length of stay in the ICU in days the length of hospitalization after surgery in days and possibly death will be recorded
The primary objective of the study will be to monitor and compare between groups indicators of renal function serum creatinine cystatin C diuresis eGFR and CCr The changes of all these values in relation to the basal values will be monitored in order to determine when the greatest changes in the values of the indicators of renal function occur Of particular importance will be the correlation between serum cystatin C and creatinine values During the first three days daily diuresis the volume of prescribed liquids the administration and doses of diuretics and the values of Na K and lactate will be monitored and compared The frequency of the occurrence of acute kidney injury AKI will be monitored The diagnosis of AKI will be based on the criteria of the KDIGO guide
The change of inflammatory markers IL-6 CRP leukocytes fibrinogen in relation to basal values is also one of the primary goals of the research Inflammatory markers will be checked on the first postoperative day when the inflammatory response is most pronounced A correlation will be made between IL-6 and other inflammatory markers that are in routine clinical use CRP leukocytes and fibrinogen in order to determine which inflammatory marker correlates best with IL-6 A correlation between IL-6 values and serum creatinine and cystatin C values will also be performed in order to determine whether impairment of renal function is related to the intensity of the inflammatory response
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None