Other Intraoperative Cardiac Functional Disturbances During Cardiac Surgery
Conditions
Keywords
cardiopulmonary bypass, reperfusion ventricular fibrillation, ventricular fibrillation, amiodarone, lidocaine, cardiac surgery
Brief summary
This was a prospective, randomized, double blinded study in which patients undergoing a cardiopulmonary bypass (CPB) with aortic cross clamping were randomly assigned to receive amiodarone, lidocaine, or saline placebo prior to removal of the aortic cross clamp. (CPB is a technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the body.) Specifically, we will test the hypothesis that amiodarone is superior to both lidocaine and placebo in the prevention of a severely abnormal heart rhythm when the blood flow is restored to the heart after the aortic cross clamp is removed.
Detailed description
This was a prospective, randomized, double blinded study in which patients undergoing cardiopulmonary bypass with aortic cross clamping were randomly assigned to receive amiodarone, lidocaine, or saline placebo prior to removal of the aortic cross clamp. Specifically, we will test the hypothesis that amiodarone administration decreases the incidence of ventricular fibrillation, the number of defibrillation attempts and the total energy and current required for defibrillation should ventricular fibrillation occur.
Interventions
DRUGLidocaine
Lidocaine is a class I (sodium channel block) antiarrhythmic drug
DRUGAmiodarone
300 mg
DRUGPlacebo
Saline
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing cardiac surgery that was expected to include cross-clamping of the aorta
Exclusion criteria
* Women wishing to become pregnant within 6 months of surgery * Allergy to amiodarone * History of organ dysfunction due to previous amiodarone use * Patients who require more than mild systemic hypothermia (\<32 degrees C) during cardiopulmonary bypass * Patients who require more than one bypass run or more than one period of aortic cross-clamping
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Participants Experiencing Ventricular Fibrillation Requiring Defibrillation During the 60 Minute Period Following Myocardial Reperfusion | Participants were followed from randomization through the 60 minute period following myocardial reperfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Arrhythmias Other Than Ventricular Fibrillation | Participants were followed from randomization through the 60 minute period following myocardial reperfusion. | Number of participants per arm who experienced arrhythmias other than ventricular fibrillation while in the ICU. |
| Incidence of Arrhythmias in the Post-Operative Period | Participants were followed from dismissal from the ICU until dismissal from the hospital. | Number of participants per arm who experienced arrhythmias while on floor care following dismissal from the ICU. |
| Number of Defibrillation Attempts | Participants were followed from randomization through the 60 minute period following myocardial reperfusion. | — |
| Time to Discharge From the Intensive Care Unit | Participants were followed from the date of randomization until the date of discharge from the Intensive Care Unit, assessed up to 40 days. | — |
| Time to Discharge From the Hospital | Participants were followed from the date of randomization until the date of discharge from the hospital, assessed up to 60 days. | — |
| Use of Vasopressors | Participants were followed from randomization until time to discharge from the hospital. | Number of participants per arm who required the use of vasopressors in the post-operative period. |
Countries
United States
Participant flow
Recruitment details
Adult patients presenting for cardiac surgery in which aortic cross clamping was anticipated were recruited between 11/2007 and 6/2010
Participants by arm
| Arm | Count |
|---|---|
| Lidocaine 1.5 mg /kg Subjects randomized to receive Lidocaine 1.5 mg/kg via the cardiopulmonary reservoir prior to the removal of the aortic cross clamp. | 115 |
| Amiodarone 300 mg Subjects randomized to receive Amiodarone 300 mg IV(followed by 150 mg IV if needed) via the cardiopulmonary reservoir prior to the removal of the aortic cross clamp. | 115 |
| Placebo (Saline) Subjects randomized to receive placebo (saline) via the cardiopulmonary reservoir prior to the removal of the aortic cross clamp. | 112 |
| Total | 342 |
Baseline characteristics
| Characteristic | Lidocaine 1.5 mg /kg | Total | Placebo (Saline) | Amiodarone 300 mg |
|---|---|---|---|---|
| Age Continuous | 62.7 years STANDARD_DEVIATION 13.9 | 63.2 years STANDARD_DEVIATION 13 | 63.6 years STANDARD_DEVIATION 13 | 63.3 years STANDARD_DEVIATION 13.6 |
| History of Dysrhythmias Atrial Fibrillation | 22 Participants | 62 Participants | 17 Participants | 23 Participants |
| History of Dysrhythmias Atrial Flutter | 2 Participants | 7 Participants | 1 Participants | 4 Participants |
| History of Dysrhythmias Unknown or Not Reported | 88 Participants | 267 Participants | 91 Participants | 88 Participants |
| History of Dysrhythmias Ventricular | 3 Participants | 6 Participants | 3 Participants | 0 Participants |
| Left Ventricular Ejection Fraction (%) | 62.7 Percentage STANDARD_DEVIATION 11.5 | 62.75 Percentage STANDARD_DEVIATION 11 | 62.8 Percentage STANDARD_DEVIATION 11.7 | 62.7 Percentage STANDARD_DEVIATION 10.8 |
| Medical History/Comorbidities Chronic Obstructive Pulmonary Disease (COPD) | 7 Participants | 15 Participants | 5 Participants | 3 Participants |
| Medical History/Comorbidities Diabetes Mellitus | 14 Participants | 44 Participants | 14 Participants | 16 Participants |
| Medical History/Comorbidities Hypertension | 37 Participants | 140 Participants | 48 Participants | 55 Participants |
| Medical History/Comorbidities Unknown or Not Reported | 57 Participants | 143 Participants | 45 Participants | 41 Participants |
| Preoperative Medications ACE Inhibitor/Angiotensin Receptor Blocker (ARB) | 31 Participants | 103 Participants | 29 Participants | 43 Participants |
| Preoperative Medications Amiodarone | 7 Participants | 14 Participants | 2 Participants | 5 Participants |
| Preoperative Medications Beta blocker | 73 Participants | 213 Participants | 73 Participants | 67 Participants |
| Preoperative Medications Digoxin | 4 Participants | 18 Participants | 7 Participants | 7 Participants |
| Preoperative Medications Statin | 42 Participants | 148 Participants | 60 Participants | 46 Participants |
| Sex: Female, Male Female | 34 Participants | 105 Participants | 30 Participants | 41 Participants |
| Sex: Female, Male Male | 81 Participants | 237 Participants | 82 Participants | 74 Participants |
| Type of Operation Coronary Artery Bypass Grafting only | 15 Participants | 53 Participants | 20 Participants | 18 Participants |
| Type of Operation Multiple Procedures | 33 Participants | 85 Participants | 27 Participants | 25 Participants |
| Type of Operation Septal Myectomy | 30 Participants | 98 Participants | 34 Participants | 34 Participants |
| Type of Operation Valve only | 37 Participants | 106 Participants | 31 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 115 | 0 / 115 | 0 / 112 |
| serious Total, serious adverse events | 0 / 115 | 0 / 115 | 0 / 112 |
Outcome results
Primary
Participants Experiencing Ventricular Fibrillation Requiring Defibrillation During the 60 Minute Period Following Myocardial Reperfusion
Time frame: Participants were followed from randomization through the 60 minute period following myocardial reperfusion.
Population: Intention to Treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lidocaine 1.5 mg /kg | Participants Experiencing Ventricular Fibrillation Requiring Defibrillation During the 60 Minute Period Following Myocardial Reperfusion | 66 Participants |
| Amiodarone 300 mg | Participants Experiencing Ventricular Fibrillation Requiring Defibrillation During the 60 Minute Period Following Myocardial Reperfusion | 60 Participants |
| Placebo (Saline) | Participants Experiencing Ventricular Fibrillation Requiring Defibrillation During the 60 Minute Period Following Myocardial Reperfusion | 70 Participants |
Comparison: The expected overall incidence of ventricular fibrillation after removal of the aortic clamp is at least 70%. Using a chi square analysis with 80% power and an alpha of 0.0167, we estimate that we will need 113 patients in each group to show a 30% reduction in the incidence of ventricular fibrillation with amiodarone.p-value: 0.42795% CI: [0.48, 1.37]Regression, Logistic
p-value: 0.11795% CI: [0.39, 1.11]Regression, Logistic
p-value: 0.43395% CI: [0.47, 1.37]Regression, Logistic
Secondary
Incidence of Arrhythmias in the Post-Operative Period
Number of participants per arm who experienced arrhythmias while on floor care following dismissal from the ICU.
Time frame: Participants were followed from dismissal from the ICU until dismissal from the hospital.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lidocaine 1.5 mg /kg | Incidence of Arrhythmias in the Post-Operative Period | Atrial fibrillation | 56 Participants |
| Lidocaine 1.5 mg /kg | Incidence of Arrhythmias in the Post-Operative Period | Ventricular tachycardia | 2 Participants |
| Lidocaine 1.5 mg /kg | Incidence of Arrhythmias in the Post-Operative Period | Other arrhythmias | 36 Participants |
| Amiodarone 300 mg | Incidence of Arrhythmias in the Post-Operative Period | Atrial fibrillation | 49 Participants |
| Amiodarone 300 mg | Incidence of Arrhythmias in the Post-Operative Period | Ventricular tachycardia | 2 Participants |
| Amiodarone 300 mg | Incidence of Arrhythmias in the Post-Operative Period | Other arrhythmias | 42 Participants |
| Placebo (Saline) | Incidence of Arrhythmias in the Post-Operative Period | Ventricular tachycardia | 3 Participants |
| Placebo (Saline) | Incidence of Arrhythmias in the Post-Operative Period | Other arrhythmias | 24 Participants |
| Placebo (Saline) | Incidence of Arrhythmias in the Post-Operative Period | Atrial fibrillation | 38 Participants |
Secondary
Incidence of Arrhythmias Other Than Ventricular Fibrillation
Number of participants per arm who experienced arrhythmias other than ventricular fibrillation while in the ICU.
Time frame: Participants were followed from randomization through the 60 minute period following myocardial reperfusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lidocaine 1.5 mg /kg | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Atrial fibrillation | 21 Participants |
| Lidocaine 1.5 mg /kg | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Ventricular tachycardia | 3 Participants |
| Lidocaine 1.5 mg /kg | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Other arrhythmias | 27 Participants |
| Amiodarone 300 mg | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Atrial fibrillation | 23 Participants |
| Amiodarone 300 mg | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Ventricular tachycardia | 2 Participants |
| Amiodarone 300 mg | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Other arrhythmias | 35 Participants |
| Placebo (Saline) | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Ventricular tachycardia | 0 Participants |
| Placebo (Saline) | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Other arrhythmias | 27 Participants |
| Placebo (Saline) | Incidence of Arrhythmias Other Than Ventricular Fibrillation | Atrial fibrillation | 18 Participants |
Secondary
Number of Defibrillation Attempts
Time frame: Participants were followed from randomization through the 60 minute period following myocardial reperfusion.
Population: Intention to Treat (IIT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lidocaine 1.5 mg /kg | Number of Defibrillation Attempts | 1 - 3 Attempts | 53 Participants |
| Lidocaine 1.5 mg /kg | Number of Defibrillation Attempts | 0 Attempts | 46 Participants |
| Lidocaine 1.5 mg /kg | Number of Defibrillation Attempts | > 3 Attempts | 16 Participants |
| Amiodarone 300 mg | Number of Defibrillation Attempts | 1 - 3 Attempts | 43 Participants |
| Amiodarone 300 mg | Number of Defibrillation Attempts | 0 Attempts | 57 Participants |
| Amiodarone 300 mg | Number of Defibrillation Attempts | > 3 Attempts | 15 Participants |
| Placebo (Saline) | Number of Defibrillation Attempts | 0 Attempts | 40 Participants |
| Placebo (Saline) | Number of Defibrillation Attempts | > 3 Attempts | 14 Participants |
| Placebo (Saline) | Number of Defibrillation Attempts | 1 - 3 Attempts | 46 Participants |
p-value: 0.21595% CI: [0.45, 1.19]Regression, Logistic
p-value: 0.00895% CI: [0.32, 0.84]Regression, Logistic
p-value: 0.42495% CI: [0.52, 1.33]Regression, Logistic
Secondary
Time to Discharge From the Hospital
Time frame: Participants were followed from the date of randomization until the date of discharge from the hospital, assessed up to 60 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine 1.5 mg /kg | Time to Discharge From the Hospital | 6.183 Days | Standard Deviation 2.833 |
| Amiodarone 300 mg | Time to Discharge From the Hospital | 7.5 Days | Standard Deviation 8.545 |
| Placebo (Saline) | Time to Discharge From the Hospital | 9.423 Days | Standard Deviation 34.572 |
Secondary
Time to Discharge From the Intensive Care Unit
Time frame: Participants were followed from the date of randomization until the date of discharge from the Intensive Care Unit, assessed up to 40 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine 1.5 mg /kg | Time to Discharge From the Intensive Care Unit | 1.357 Days | Standard Deviation 0.948 |
| Amiodarone 300 mg | Time to Discharge From the Intensive Care Unit | 5.329 Days | Standard Deviation 34.515 |
| Placebo (Saline) | Time to Discharge From the Intensive Care Unit | 4.847 Days | Standard Deviation 34.622 |
Secondary
Use of Vasopressors
Number of participants per arm who required the use of vasopressors in the post-operative period.
Time frame: Participants were followed from randomization until time to discharge from the hospital.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lidocaine 1.5 mg /kg | Use of Vasopressors | Norepinephrine | 0 Participants |
| Lidocaine 1.5 mg /kg | Use of Vasopressors | Epinephrine | 1 Participants |
| Lidocaine 1.5 mg /kg | Use of Vasopressors | Vasopressin | 0 Participants |
| Amiodarone 300 mg | Use of Vasopressors | Norepinephrine | 0 Participants |
| Amiodarone 300 mg | Use of Vasopressors | Epinephrine | 1 Participants |
| Amiodarone 300 mg | Use of Vasopressors | Vasopressin | 2 Participants |
| Placebo (Saline) | Use of Vasopressors | Epinephrine | 0 Participants |
| Placebo (Saline) | Use of Vasopressors | Vasopressin | 0 Participants |
| Placebo (Saline) | Use of Vasopressors | Norepinephrine | 0 Participants |