Heart Diseases, Hyperglycemia
Conditions
Keywords
Cardiopulmonary bypass, Heart surgery
Brief summary
This study evaluates the effect of using remifentanil during cardiopulmonary bypass surgery to supress the hyperglycemic response in perioperative period. Half of the participants will receive continuous intravenous remifentanil during surgery, while the other half will receive intermittent intravenous fentanyl during surgery. Intermittent intravenous fentanyl administration is this institution's standard of care.
Detailed description
Stress-induced hyperglycemia is a well-known phenomena that occurs during cardiopulmonary bypass surgery. Hyperglycemia increases the incidence of major adverse events and mortality in patients undergoing cardiac surgery. Remifentanil, an ultra-short acting opioid analgesic, has been shown to reduce the stress response to cardiopulmonary bypass when compared to intermittent fentanyl and inhalation anesthesia. This in turn, will reduce the occurence of perioperative hyperglycemia, glycemic variability and insulin requirements in patients undergoing cardiac surgery. NOTE; Primary Outcome changed on 06/15/2015-Change Approved by University of Pittsburgh IRB on 06/22/2015- First patient enrolled January 2016. Primary outcome measure; Percentage of patients with two or more than two intraoperative blood glucose levels more than 180 mg% in both groups will be estimated and the difference in this parameter between the two groups will form the primary outcome measure of this study.
Interventions
DRUGRemifentanil
Subjects in the experimental group will receive remifentanil infusion 0.1-0.4ug/kg/minute before induction of anesthesia and continued until skin closure. During cardiopulmonary bypass, remifentanil infusion will be increased to 0.5-1 ug/kg/min as hemodynamically tolerated.
DRUGFentanyl
Subjects in the control group will initially receive intermittent boluses of Fentanyl in the range of 50-250 ug. Additional fentanyl can be given titrated to hemodynamic parameters throughout surgery.
Sponsors
Mylan Inc.
Kathirvel Subramaniam
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Open cardiac surgery through sternotomy approach (coronary artery bypass, valve surgery, and any other open heart surgeries) * Surgery with use of cardiopulmonary bypass * Patients over 18 years of age * Both female and male genders * All races
Exclusion criteria
* Minimally invasive heart surgery through thoracotomy approach * Patients receiving regional analgesia such as intrathecal morphine * Patients undergoing procedures under deep hypothermic circulatory arrest * Patients with active infections such as acute infective endocarditis * Emergency surgery * Patients undergoing transplantations and ventricular assist device insertion * Patients on any mechanical circulatory support preoperatively * Patient's refusal * Allergy to remifentanil * Positive pregnancy test * Morbid obesity * End stage liver and kidney disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Glucose Values (More Than One ) > 180 mg% | Intraoperative period | Percentage of patients with two or more intraoperative blood glucose levels greater than 180 mg/dl. Percentage in both groups will be estimated, then the difference in this statistic will form the primary outcome measure of this study. (Primary Outcome changed on 06/15/2015-Change Approved by University of Pittsburgh IRB on 06/22/2015- First patient enrolled January 2016) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Blood Glucose | From ICU Admission (After Surgery) Until 24 hours postoperatively | Mean and peak blood glucose levels postoperatively |
| Insulin Requirement | Intraoperative period; Induction to end of surgery | Average dose of insulin (Units/ml) calculated for each group in the intraoperative period |
| Number of Blood Glucose Values > 180 mg% | Intraoperative period, Induction to end of surgery | Blood glucose values that exceed 180 mg% will be counted |
| Total Postoperative Regular Insulin | From ICU Admission (After Surgery) Until 24 hours postoperatively | Total units of regular insulin required post-operatively |
| Intraoperative Pre-cardiopulmonary Bypass Hemodynamic Stability | induction of anesthesia till systemic heparinization before cardiopulmonary bypass | Blood pressure (systolic, diastolic and mean), Heart rate every 5 minutes from induction of anesthesia till systemic heparinization before cardiopulmonary bypass |
| Stress Hormone Levels-Cortisol (µg/dl) | Perioperative period (Intraoperatively and 8 hours postoperatively) | Serum cortisol levels (measured as µg/dl) taken at: Prebypass, cardiopulmonary bypass (2 samples: at start of bypass and end of bypass), postbypass, ICU 8 hours postoperative period |
| Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | Perioperative period (Intraoperatively and 8 hours postoperatively) | Inflammatory mediator levels, Interleukin-1b (IL-1b), Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFa) (all measured in pg/ml) taken at: Prebypass, cardiopulmonary bypass (2 samples:30 min start of bypass (CPB-30) and end of bypass (CPB-END), postbypass, ICU 8 hours postoperative period |
| Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Intraoperative period; Induction to end of surgery | Blood glucose measured every hour |
| Society of Thoracic Surgery Patient Outcomes | 30 day outcomes | Postoperative outcomes collected from the Society of Thoracic Surgery (STS) database. 30 day Mortality (outcome 1) and 30 day Readmission (outcome 2) cerebral vascular accident(outcome 3), prolonged mechanical ventilation (outcome 4), renal failure (outcome 5), atrial fibrillation (outcome 6), cardiac arrest (outcome 7) |
| Postoperative Pain | Every day 6 hour for 48 hours postoperative period | Pain scores; Every day 6 hour for 48 hours postoperative period |
| Emergence From Anesthesia | Immediate postoperative period until 30 days post-operatively | Time to extubation after completion of surgery in the operating room and intensive care unit |
| Wound Hyperalgesia | 96 hours postoperatively | Von frey hair objective testing |
| Development of Chronic Pain | 1, 3, 6 and 12 months after discharge from the hospital | Telephonic call Numeric pain scale; Scale is 0-10, with 10 being the highest pain. |
| Glycemic Variability | From the start of induction till 24 hours postoperatively | Coefficient of variation in blood glucose levels. Denotes how large the fluctuations in blood glucose are. Higher numbers indicate increased variation. |
| Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Perioperative period (Intraoperatively and 8 hours postoperatively) | Adreno-corticotrophic hormone (ACTH), Growth Hormone (GH) and Glucagon (measured as pg/ml) taken at: Prebypass, cardiopulmonary bypass (2 samples: 30 mins after start of bypass (CPB 30) and end of bypass (CPB END), post-bypass and ICU 8 hours postoperative period |
Countries
United States
Participant flow
Recruitment details
The first subject was recruited 01-06-2016. The final subject was recruited 12-28-2016. All enrolled subjects were recruited at Presbyterian Hospital in Pittsburgh, Pennsylvania.
Pre-assignment details
No pre-assignment necessary for enrollment
Participants by arm
| Arm | Count |
|---|---|
| Remifentanil Group Half of subjects enrolled will be randomized to the remifentanil group
Remifentanil: Subjects in the experimental group will receive remifentanil infusion 0.1-0.4ug/kg/minute before induction of anesthesia and continued until skin closure. During cardiopulmonary bypass, remifentanil infusion will be increased to 0.5-1 ug/kg/min as hemodynamically tolerated. | 54 |
| Fentanyl Group Half of subjects enrolled will be randomized to the fentanyl group
Fentanyl: Subjects in the control group will initially receive intermittent boluses of Fentanyl in the range of 50-250 ug. Additional fentanyl can be given titrated to hemodynamic parameters throughout surgery. | 52 |
| Total | 106 |
Baseline characteristics
| Characteristic | Fentanyl Group | Total | Remifentanil Group |
|---|---|---|---|
| Age, Continuous | 71.0 years | 70.5 years | 70.0 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 52 participants | 106 participants | 54 participants |
| Sex: Female, Male Female | 14 Participants | 33 Participants | 19 Participants |
| Sex: Female, Male Male | 38 Participants | 73 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 54 | 6 / 52 |
| other Total, other adverse events | 28 / 54 | 27 / 52 |
| serious Total, serious adverse events | 1 / 54 | 5 / 52 |
Outcome results
Primary
Blood Glucose Values (More Than One ) > 180 mg%
Percentage of patients with two or more intraoperative blood glucose levels greater than 180 mg/dl. Percentage in both groups will be estimated, then the difference in this statistic will form the primary outcome measure of this study. (Primary Outcome changed on 06/15/2015-Change Approved by University of Pittsburgh IRB on 06/22/2015- First patient enrolled January 2016)
Time frame: Intraoperative period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remifentanil Group | Blood Glucose Values (More Than One ) > 180 mg% | 17 Participants |
| Fentanyl Group | Blood Glucose Values (More Than One ) > 180 mg% | 33 Participants |
Comparison: The null hypothesis that there was no difference in the percentage of patients with two or more blood glucose values greater than 180mg/dl between the two groups. Power calculation was performed based on the assumption that continuous remifentanil infusion would reduce the percentage of patients with unacceptable blood glucose values (more than one BG\>180 mg/dl) to an absolute value of 20%.p-value: 0.00195% CI: [1.3, 3]Chi-squared
Secondary
Development of Chronic Pain
Telephonic call Numeric pain scale; Scale is 0-10, with 10 being the highest pain.
Time frame: 1, 3, 6 and 12 months after discharge from the hospital
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil Group | Development of Chronic Pain | S-LANSS 1 mo | 1 score on a scale |
| Remifentanil Group | Development of Chronic Pain | S-LANSS 3 mo | 0 score on a scale |
| Remifentanil Group | Development of Chronic Pain | S-LANSS 6 mo | 0 score on a scale |
| Remifentanil Group | Development of Chronic Pain | S-LANSS 12 mo | 0 score on a scale |
| Fentanyl Group | Development of Chronic Pain | S-LANSS 12 mo | 0 score on a scale |
| Fentanyl Group | Development of Chronic Pain | S-LANSS 1 mo | 3 score on a scale |
| Fentanyl Group | Development of Chronic Pain | S-LANSS 6 mo | 0 score on a scale |
| Fentanyl Group | Development of Chronic Pain | S-LANSS 3 mo | 0 score on a scale |
Secondary
Emergence From Anesthesia
Time to extubation after completion of surgery in the operating room and intensive care unit
Time frame: Immediate postoperative period until 30 days post-operatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil Group | Emergence From Anesthesia | 3 Hours |
| Fentanyl Group | Emergence From Anesthesia | 2.5 Hours |
Secondary
Glycemic Variability
Coefficient of variation in blood glucose levels. Denotes how large the fluctuations in blood glucose are. Higher numbers indicate increased variation.
Time frame: From the start of induction till 24 hours postoperatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Remifentanil Group | Glycemic Variability | 0.2 Percent of Mean Glucose Level |
| Fentanyl Group | Glycemic Variability | 0.2 Percent of Mean Glucose Level |
p-value: 0.35Wilcoxon (Mann-Whitney)
Secondary
Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml)
Inflammatory mediator levels, Interleukin-1b (IL-1b), Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFa) (all measured in pg/ml) taken at: Prebypass, cardiopulmonary bypass (2 samples:30 min start of bypass (CPB-30) and end of bypass (CPB-END), postbypass, ICU 8 hours postoperative period
Time frame: Perioperative period (Intraoperatively and 8 hours postoperatively)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b 8-HR | 1.2 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 post-bypass | 136 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b CPB-30 | 1.1 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 8HR | 93.6 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 Pre-bypass | 2.8 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa-Pre-bypass | 11.7 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b post-bypass | 1.1 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa CPB-30 | 14.4 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 CPB-30 | 7.4 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa CPB-END | 18.2 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b CPB-END | 1.2 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa post-bypass | 24.0 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 CPB-END | 77.2 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa 8HR | 15.4 pg/ml |
| Remifentanil Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b Pre-bypass | 1.2 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa 8HR | 11.2 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b Pre-bypass | 1.2 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b CPB-30 | 1.1 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b CPB-END | 1.2 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b post-bypass | 1.3 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-1b 8-HR | 1.2 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 Pre-bypass | 2.6 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 CPB-30 | 10.3 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 CPB-END | 78.3 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 post-bypass | 90.9 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | IL-6 8HR | 92.3 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa-Pre-bypass | 10.4 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa CPB-30 | 12.6 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa CPB-END | 14.8 pg/ml |
| Fentanyl Group | Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml) | TNFa post-bypass | 17.2 pg/ml |
Comparison: Analyzing the IL-1b Pre bypassp-value: 0.58t-test, 2 sided
Comparison: Analyzing the IL-1b CPB-30p-value: 0.815t-test, 2 sided
Comparison: Analyzing the CPB-ENDp-value: 0.715t-test, 2 sided
Comparison: Analyzing the IL-1b post-bypassp-value: 0.33t-test, 2 sided
Comparison: Analyzing the IL-1b 8 HRp-value: 0.651t-test, 2 sided
Comparison: Analyzing the IL-6 Pre bypassp-value: 0.439t-test, 2 sided
Comparison: Analyzing the IL-6 CPB-30p-value: 0.284t-test, 2 sided
Comparison: Analyzing the CPB-ENDp-value: 0.779t-test, 2 sided
Comparison: Analyzing the IL-6 post-bypassp-value: 0.274t-test, 2 sided
Comparison: Analyzing the IL-6 8HRp-value: 0.601t-test, 2 sided
Comparison: Analyzing the TNFa Pre-bypassp-value: 0.315t-test, 2 sided
Comparison: Analyzing the TNFa CPB-30p-value: 0.062t-test, 2 sided
Comparison: Analyzing the TNFa CPB-ENDp-value: 0.09t-test, 2 sided
Comparison: Analyzing the TNFa- post-bypassp-value: 0.004t-test, 2 sided
Comparison: Analyzing the TNFa-8HRp-value: 0.074t-test, 2 sided
Secondary
Insulin Requirement
Average dose of insulin (Units/ml) calculated for each group in the intraoperative period
Time frame: Intraoperative period; Induction to end of surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil Group | Insulin Requirement | 2.9 Units/ml |
| Fentanyl Group | Insulin Requirement | 8.1 Units/ml |
p-value: 0.004t-test, 2 sided
Secondary
Intraoperative Pre-cardiopulmonary Bypass Hemodynamic Stability
Blood pressure (systolic, diastolic and mean), Heart rate every 5 minutes from induction of anesthesia till systemic heparinization before cardiopulmonary bypass
Time frame: induction of anesthesia till systemic heparinization before cardiopulmonary bypass
Population: Resources not available to analyze
Secondary
Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl)
Blood glucose measured every hour
Time frame: Intraoperative period; Induction to end of surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil Group | Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Mean Introperative Blood Glucose | 141 Mg/dL |
| Remifentanil Group | Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Peak Intraoperative Blood Glucose | 178 Mg/dL |
| Remifentanil Group | Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Lowest Intraoperative Blood Glucose | 117 Mg/dL |
| Fentanyl Group | Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Mean Introperative Blood Glucose | 156 Mg/dL |
| Fentanyl Group | Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Peak Intraoperative Blood Glucose | 205 Mg/dL |
| Fentanyl Group | Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl) | Lowest Intraoperative Blood Glucose | 120 Mg/dL |
Comparison: Mean Intraoperative Blood Glucosep-value: 0.0001t-test, 2 sided
Comparison: Peak Intraoperative Blood Glucosep-value: 0.0003t-test, 2 sided
Comparison: Lowest Intraoperative Blood Glucosep-value: 0.98t-test, 2 sided
Secondary
Number of Blood Glucose Values > 180 mg%
Blood glucose values that exceed 180 mg% will be counted
Time frame: Intraoperative period, Induction to end of surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil Group | Number of Blood Glucose Values > 180 mg% | 1.2 number of glucose values >180mg% |
| Fentanyl Group | Number of Blood Glucose Values > 180 mg% | 2 number of glucose values >180mg% |
p-value: 0.01Fisher Exact
Secondary
Postoperative Blood Glucose
Mean and peak blood glucose levels postoperatively
Time frame: From ICU Admission (After Surgery) Until 24 hours postoperatively
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil Group | Postoperative Blood Glucose | Mean Postoperative Blood Glucose | 139 mg/dl |
| Remifentanil Group | Postoperative Blood Glucose | Peak Postoperative Blood Glucose | 185 mg/dl |
| Fentanyl Group | Postoperative Blood Glucose | Peak Postoperative Blood Glucose | 175 mg/dl |
| Fentanyl Group | Postoperative Blood Glucose | Mean Postoperative Blood Glucose | 139 mg/dl |
Comparison: Mean post-operative glucosep-value: 0.14t-test, 2 sided
Comparison: Peak Postoperative Blood Glucosep-value: 0.25t-test, 2 sided
Secondary
Postoperative Pain
Pain scores; Every day 6 hour for 48 hours postoperative period
Time frame: Every day 6 hour for 48 hours postoperative period
Population: This is a mixed model analysis to account for missing VAS values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil Group | Postoperative Pain | Hours 0-6 | 6.63 score on a scale | Standard Deviation 1.66 |
| Remifentanil Group | Postoperative Pain | Hrs 7-12 | 6.53 score on a scale | Standard Deviation 2.23 |
| Remifentanil Group | Postoperative Pain | Hrs 13-18 | 6.59 score on a scale | Standard Deviation 2.07 |
| Remifentanil Group | Postoperative Pain | Hrs 19-24 | 5.88 score on a scale | Standard Deviation 2.28 |
| Remifentanil Group | Postoperative Pain | Hrs 25-30 | 5.94 score on a scale | Standard Deviation 5.94 |
| Remifentanil Group | Postoperative Pain | Hrs 31-36 | 5.89 score on a scale | Standard Deviation 2.31 |
| Remifentanil Group | Postoperative Pain | Hrs 37-42 | 5.57 score on a scale | Standard Deviation 2.35 |
| Remifentanil Group | Postoperative Pain | Hrs 43-48 | 5.08 score on a scale | Standard Deviation 2.74 |
| Fentanyl Group | Postoperative Pain | Hrs 43-48 | 5.10 score on a scale | Standard Deviation 3.11 |
| Fentanyl Group | Postoperative Pain | Hours 0-6 | 7.18 score on a scale | Standard Deviation 2.37 |
| Fentanyl Group | Postoperative Pain | Hrs 25-30 | 5.65 score on a scale | Standard Deviation 2.25 |
| Fentanyl Group | Postoperative Pain | Hrs 7-12 | 6.09 score on a scale | Standard Deviation 2.19 |
| Fentanyl Group | Postoperative Pain | Hrs 37-42 | 5.18 score on a scale | Standard Deviation 2.7 |
| Fentanyl Group | Postoperative Pain | Hrs 13-18 | 5.18 score on a scale | Standard Deviation 2.76 |
| Fentanyl Group | Postoperative Pain | Hrs 31-36 | 5.94 score on a scale | Standard Deviation 2.44 |
| Fentanyl Group | Postoperative Pain | Hrs 19-24 | 5.73 score on a scale | Standard Deviation 2.38 |
Comparison: Hrs 7-12p-value: 0.339t-test, 2 sided
Comparison: Hrs 13-18p-value: 0.006t-test, 2 sided
Comparison: Hrs 0-6p-value: 0.205t-test, 2 sided
Comparison: Hrs 19-24p-value: 0.747t-test, 2 sided
Comparison: Hrs 25-30p-value: 0.568t-test, 2 sided
Comparison: Hrs 31-36p-value: 0.924t-test, 2 sided
Comparison: Hrs 37-42p-value: 0.501t-test, 2 sided
Comparison: Hrs 43-48p-value: 0.977t-test, 2 sided
Secondary
Society of Thoracic Surgery Patient Outcomes
Postoperative outcomes collected from the Society of Thoracic Surgery (STS) database. 30 day Mortality (outcome 1) and 30 day Readmission (outcome 2) cerebral vascular accident(outcome 3), prolonged mechanical ventilation (outcome 4), renal failure (outcome 5), atrial fibrillation (outcome 6), cardiac arrest (outcome 7)
Time frame: 30 day outcomes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | Cerebral Vascular Accident | 0 participants |
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | renal failure | 3 participants |
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | 30 day Readmission | 3 participants |
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | atrial fibrillation | 24 participants |
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | Prolonged mechanical ventilation | 8 participants |
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | cardiac arrest | 3 participants |
| Remifentanil Group | Society of Thoracic Surgery Patient Outcomes | 30 day Mortality | 1 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | cardiac arrest | 3 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | 30 day Mortality | 6 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | 30 day Readmission | 10 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | Cerebral Vascular Accident | 2 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | Prolonged mechanical ventilation | 8 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | renal failure | 3 participants |
| Fentanyl Group | Society of Thoracic Surgery Patient Outcomes | atrial fibrillation | 18 participants |
Comparison: 30-day mortalityp-value: 0.06Chi-squared
Comparison: 30-day readmissionp-value: 0.03Chi-squared
Comparison: Cerebral Vascular Accidentp-value: 0.24Chi-squared
Comparison: Prolonged Mechanical Ventilationp-value: 0.93Chi-squared
Comparison: Renal Failurep-value: 1Chi-squared
Comparison: Atrial Fibrillationp-value: 0.1Chi-squared
Comparison: cardiac arrestp-value: 1Chi-squared
Secondary
Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml)
Adreno-corticotrophic hormone (ACTH), Growth Hormone (GH) and Glucagon (measured as pg/ml) taken at: Prebypass, cardiopulmonary bypass (2 samples: 30 mins after start of bypass (CPB 30) and end of bypass (CPB END), post-bypass and ICU 8 hours postoperative period
Time frame: Perioperative period (Intraoperatively and 8 hours postoperatively)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon CPB-30 | 259 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon CPB-End | 401 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH pre-bypass | 7.4 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH CPB-30 | 4.4 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH CPB-END | 4.4 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH post-bypass | 8.0 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH 8-hr | 77.0 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-Pre-bypass | 495 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-CPB-30 | 826 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-CPB-END | 947 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-post-bypass | 37364 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-8HR | 3658 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon pre-bypass | 229 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon post-bypass | 315 pg/ml |
| Remifentanil Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon 8-HR | 570 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon post-bypass | 408 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon CPB-30 | 338 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-CPB-30 | 3202 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon pre-bypass | 192 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH pre-bypass | 7.4 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-CPB-END | 2545 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH CPB-30 | 57.8 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon CPB-End | 481 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH CPB-END | 30.7 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-post-bypass | 4461 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH post-bypass | 49.1 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | Glucagon 8-HR | 459 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | ACTH 8-hr | 41.3 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-8HR | 2696 pg/ml |
| Fentanyl Group | Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml) | GH-Pre-bypass | 872 pg/ml |
Comparison: Analyzing the ACTH Pre-bypass groupp-value: 0.74t-test, 2 sided
Comparison: Analyzing the ACTH CPB-30 group.p-value: <0.0001t-test, 2 sided
Comparison: Analyzing the ACTH CPB-ENDp-value: <0.0001t-test, 2 sided
Comparison: Analyzing the ACTH post-bypassp-value: <0.0001t-test, 2 sided
Comparison: Analyzing the ACTH 8-hrp-value: 0.014t-test, 2 sided
Comparison: Analyzing the GH- Pre-bypassp-value: 0.1t-test, 2 sided
Comparison: GH-CPB-30p-value: <0.0001t-test, 2 sided
Comparison: Analyzing the GH-CPB-ENDp-value: 0.009t-test, 2 sided
Comparison: GH-Post-bypassp-value: 0.046t-test, 2 sided
Comparison: Analyzing the GH-8-hrp-value: 0.695t-test, 2 sided
Comparison: Analyzing the Glucagon Pre Bypassp-value: 0.455t-test, 2 sided
Comparison: Analyzing the Glucagon CPB-30p-value: 0.059t-test, 2 sided
Comparison: Analyzing the Glucagon CPB-ENDp-value: 0.175t-test, 2 sided
Comparison: Analyzing the Glucagon Post-bypassp-value: 0.062t-test, 2 sided
Comparison: Analyzing the Glucagon 8-hrp-value: 0.261t-test, 2 sided
Secondary
Stress Hormone Levels-Cortisol (µg/dl)
Serum cortisol levels (measured as µg/dl) taken at: Prebypass, cardiopulmonary bypass (2 samples: at start of bypass and end of bypass), postbypass, ICU 8 hours postoperative period
Time frame: Perioperative period (Intraoperatively and 8 hours postoperatively)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol 30 Minute After Start of CPB | 6.0 µg/dl |
| Remifentanil Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol End of Surgery | 8.5 µg/dl |
| Remifentanil Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol End of CPB | 5.0 µg/dl |
| Remifentanil Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol Postoperative (8 Hours) | 36.0 µg/dl |
| Remifentanil Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol Prebypass | 12 µg/dl |
| Fentanyl Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol Postoperative (8 Hours) | 45.0 µg/dl |
| Fentanyl Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol Prebypass | 12 µg/dl |
| Fentanyl Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol 30 Minute After Start of CPB | 24.5 µg/dl |
| Fentanyl Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol End of CPB | 29.0 µg/dl |
| Fentanyl Group | Stress Hormone Levels-Cortisol (µg/dl) | Serum Cortisol End of Surgery | 28.0 µg/dl |
Comparison: Prebypassp-value: 0.401t-test, 2 sided
Comparison: 30 minutes after the start of CPBp-value: <0.0001t-test, 2 sided
Comparison: End of CPBp-value: <0.0001t-test, 2 sided
Comparison: End of Surgeryp-value: <0.0001t-test, 2 sided
Comparison: Postoperative (8 hours)p-value: 0.021t-test, 2 sided
Secondary
Total Postoperative Regular Insulin
Total units of regular insulin required post-operatively
Time frame: From ICU Admission (After Surgery) Until 24 hours postoperatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil Group | Total Postoperative Regular Insulin | 28.1 International Units |
| Fentanyl Group | Total Postoperative Regular Insulin | 23.5 International Units |
p-value: 0.49t-test, 2 sided
Secondary
Wound Hyperalgesia
Von frey hair objective testing
Time frame: 96 hours postoperatively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil Group | Wound Hyperalgesia | Preop pain threshold | 3.24 g/mm^2 | Standard Deviation 0.94 |
| Remifentanil Group | Wound Hyperalgesia | 48 Hr pain threshold | 3.71 g/mm^2 | Standard Deviation 1 |
| Remifentanil Group | Wound Hyperalgesia | 96 hr pain threshold | 3.60 g/mm^2 | Standard Deviation 1.08 |
| Fentanyl Group | Wound Hyperalgesia | Preop pain threshold | 3.30 g/mm^2 | Standard Deviation 1.08 |
| Fentanyl Group | Wound Hyperalgesia | 48 Hr pain threshold | 3.83 g/mm^2 | Standard Deviation 1.28 |
| Fentanyl Group | Wound Hyperalgesia | 96 hr pain threshold | 3.72 g/mm^2 | Standard Deviation 1.3 |