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CompletedNCT02349152Updated Apr 21, 2020Results posted

Remifentanil and Glycemic Response in Cardiac Surgery

A Phase 4 interventional study of Remifentanil and Fentanyl in Heart Diseases and Hyperglycemia, sponsored by Kathirvel Subramaniam. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-04-21.

Sponsored by Kathirvel Subramaniam · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
116
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Heart Diseases
  • Hyperglycemia

Keywords

  • Cardiopulmonary bypass
  • Heart surgery
03

In context

Heart Diseases

2,135 studies on the registry are indexed under Heart Diseases; 252 are open to participants now.

This study's enrollment of 116 is below the median of 129 across 931 interventional studies indexed under Heart Diseases.

Browse Heart Diseases studies →

Lead sponsor

Kathirvel Subramaniam is the lead sponsor of 5 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
116 participants (actual)

Study arms

  • Experimental
    Remifentanil group

    Half of subjects enrolled will be randomized to the remifentanil group

    Drug: Remifentanil

  • Active comparator
    Fentanyl group

    Half of subjects enrolled will be randomized to the fentanyl group

    Drug: Fentanyl

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.

    Also known as: Ultiva

  • 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.

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl)

    Blood glucose measured every hour

    Time frame: Intraoperative period; Induction to end of surgery

  4. Postoperative Blood Glucose

    Mean and peak blood glucose levels postoperatively

    Time frame: From ICU Admission (After Surgery) Until 24 hours postoperatively

  5. Total Postoperative Regular Insulin

    Total units of regular insulin required post-operatively

    Time frame: From ICU Admission (After Surgery) Until 24 hours postoperatively

  6. 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

  7. 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)

  8. 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)

  9. 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)

  10. 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

  11. Postoperative Pain

    Pain scores; Every day 6 hour for 48 hours postoperative period

    Time frame: Every day 6 hour for 48 hours postoperative period

  12. 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

  13. Wound Hyperalgesia

    Von frey hair objective testing

    Time frame: 96 hours postoperatively

  14. 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

  15. 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

07

Results

Posted May 14, 2018

Participant flow

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.

Participant flow — Overall Study
MilestoneRemifentanil GroupFentanyl Group
Started6056
Completed5452
Not completed64

Outcome measures

PrimaryBlood 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
Reported as:
Count of participants · Participants
Blood Glucose Values (More Than One ) > 180 mg%
ParticipantsRemifentanil GroupFentanyl Group
Blood Glucose Values (More Than One ) > 180 mg%1733
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 0.001 · Risk ratio (rr): 1.9 · 95% CI 1.3 to 3.0
SecondaryInsulin Requirement

Average dose of insulin (Units/ml) calculated for each group in the intraoperative period

Time frame:
Intraoperative period; Induction to end of surgery
Reported as:
Median · Units/ml
Insulin Requirement
Units/mlRemifentanil GroupFentanyl Group
Insulin Requirement2.9 (0.0 to 35.1)8.1 (0.0 to 46.7)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.004
SecondaryNumber 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
Reported as:
Median · number of glucose values >180mg%
Number of Blood Glucose Values > 180 mg%
number of glucose values >180mg%Remifentanil GroupFentanyl Group
Number of Blood Glucose Values > 180 mg%1.2 (0 to 7)2 (0 to 6)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · Fisher Exact · p = 0.01
SecondaryMean, Peak and Trough Intraoperative Blood Glucose (mg/dl)

Blood glucose measured every hour

Time frame:
Intraoperative period; Induction to end of surgery
Reported as:
Median · Mg/dL
Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl)
Mg/dLRemifentanil GroupFentanyl Group
Mean Introperative Blood Glucose141 (84 to 292)156 (68 to 348)
Peak Intraoperative Blood Glucose178 (110 to 292)205 (133 to 348)
Lowest Intraoperative Blood Glucose117 (84 to 195)120 (68 to 178)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.0003
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.98
SecondaryPostoperative Blood Glucose

Mean and peak blood glucose levels postoperatively

Time frame:
From ICU Admission (After Surgery) Until 24 hours postoperatively
Reported as:
Median · mg/dl
Postoperative Blood Glucose
mg/dlRemifentanil GroupFentanyl Group
Mean Postoperative Blood Glucose139 (62 to 309)139 (70 to 270)
Peak Postoperative Blood Glucose185 (136 to 309)175 (127 to 270)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.14
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.25
SecondaryTotal Postoperative Regular Insulin

Total units of regular insulin required post-operatively

Time frame:
From ICU Admission (After Surgery) Until 24 hours postoperatively
Reported as:
Median · International Units
Total Postoperative Regular Insulin
International UnitsRemifentanil GroupFentanyl Group
Total Postoperative Regular Insulin28.1 (0 to 196)23.5 (0 to 158)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.49
SecondaryIntraoperative 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

No measurements were reported for this outcome.

SecondaryStress 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)
Reported as:
Median · µg/dl
Stress Hormone Levels-Cortisol (µg/dl)
µg/dlRemifentanil GroupFentanyl Group
Serum Cortisol Prebypass12 (2.0 to 21.0)12 (3.0 to 26.0)
Serum Cortisol 30 Minute After Start of CPB6.0 (1.0 to 19.0)24.5 (7.0 to 43.0)
Serum Cortisol End of CPB5.0 (1.0 to 15.0)29.0 (6.0 to 52.0)
Serum Cortisol End of Surgery8.5 (2.0 to 27.0)28.0 (7.0 to 56.0)
Serum Cortisol Postoperative (8 Hours)36.0 (14.0 to 81.0)45.0 (8.0 to 80.0)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.401
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.021
SecondaryInflammatory 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)
Reported as:
Median · pg/ml
Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml)
pg/mlRemifentanil GroupFentanyl Group
IL-1b Pre-bypass1.2 (0.9 to 9.1)1.2 (1.0 to 3.1)
IL-1b CPB-301.1 (1.0 to 6.3)1.1 (0.9 to 3.0)
IL-1b CPB-END1.2 (0.9 to 5.7)1.2 (0.9 to 2.8)
IL-1b post-bypass1.1 (0.9 to 7.5)1.3 (0.9 to 3.4)
IL-1b 8-HR1.2 (0.9 to 6.1)1.2 (0.7 to 3.8)
IL-6 Pre-bypass2.8 (1.0 to 329)2.6 (0.8 to 38.5)
IL-6 CPB-307.4 (1.3 to 58.7)10.3 (1.8 to 148)
IL-6 CPB-END77.2 (5.3 to 1499)78.3 (6.6 to 3478)
IL-6 post-bypass136 (17.2 to 2504)90.9 (13.2 to 8564)
IL-6 8HR93.6 (5.1 to 2473)92.3 (16.7 to 12128)
TNFa-Pre-bypass11.7 (2.1 to 29.7)10.4 (3.1 to 24.6)
TNFa CPB-3014.4 (5.5 to 49.7)12.6 (4.1 to 26.6)
TNFa CPB-END18.2 (6.0 to 51.9)14.8 (3.6 to 56.5)
TNFa post-bypass24.0 (5.3 to 136)17.2 (4.5 to 52.2)
TNFa 8HR15.4 (1.1 to 41.8)11.2 (4.5 to 44.7)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.580
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.815
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.715
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.330
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.651
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.439
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.284
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.779
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.274
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.601
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.315
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.062
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.090
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.004
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.074
SecondaryStress 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)
Reported as:
Median · pg/ml
Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml)
pg/mlRemifentanil GroupFentanyl Group
ACTH pre-bypass7.4 (1.6 to 52.1)7.4 (2.1 to 36.6)
ACTH CPB-304.4 (1.8 to 27.4)57.8 (2.2 to 691)
ACTH CPB-END4.4 (1.8 to 382)30.7 (2.9 to 1167)
ACTH post-bypass8.0 (1.6 to 179)49.1 (2.7 to 6719)
ACTH 8-hr77.0 (3.0 to 1022)41.3 (1.8 to 3351)
GH-Pre-bypass495 (3.2 to 74329)872 (20.0 to 14106)
GH-CPB-30826 (26.0 to 88613)3202 (355 to 192177)
GH-CPB-END947 (16.7 to 252584)2545 (117 to 169125)
GH-post-bypass37364 (138 to 257569)4461 (180 to 185442)
GH-8HR3658 (217 to 213721)2696 (145 to 208259)
Glucagon pre-bypass229 (4.6 to 2715)192 (5.1 to 2242)
Glucagon CPB-30259 (4.8 to 1366)338 (6.2 to 2635)
Glucagon CPB-End401 (5.7 to 3226)481 (8.2 to 3979)
Glucagon post-bypass315 (5.0 to 2557)408 (6.8 to 2691)
Glucagon 8-HR570 (7.5 to 2019)459 (5.0 to 4002)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.740
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.014
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.100
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = <0.0001
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.009
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.046
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.695
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.455
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.059
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.175
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.062
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.261
SecondarySociety 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
Reported as:
Number · participants
Society of Thoracic Surgery Patient Outcomes
participantsRemifentanil GroupFentanyl Group
30 day Mortality16
30 day Readmission310
Cerebral Vascular Accident02
Prolonged mechanical ventilation88
renal failure33
atrial fibrillation2418
cardiac arrest33
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 0.06
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 0.03
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 0.24
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 0.93
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 1
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 0.10
  • Remifentanil Group vs Fentanyl Group · Chi-squared · p = 1
SecondaryPostoperative Pain

Pain scores; Every day 6 hour for 48 hours postoperative period

Time frame:
Every day 6 hour for 48 hours postoperative period
Reported as:
Mean · score on a scale
Postoperative Pain
score on a scaleRemifentanil GroupFentanyl Group
Hours 0-66.63 ± 1.667.18 ± 2.37
Hrs 7-126.53 ± 2.236.09 ± 2.19
Hrs 13-186.59 ± 2.075.18 ± 2.76
Hrs 19-245.88 ± 2.285.73 ± 2.38
Hrs 25-305.94 ± 5.945.65 ± 2.25
Hrs 31-365.89 ± 2.315.94 ± 2.44
Hrs 37-425.57 ± 2.355.18 ± 2.70
Hrs 43-485.08 ± 2.745.10 ± 3.11
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.205
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.339
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.006
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.747
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.568
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.924
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.501
  • Remifentanil Group vs Fentanyl Group · t-test, 2 sided · p = 0.977
SecondaryEmergence 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
Reported as:
Median · Hours
Emergence From Anesthesia
HoursRemifentanil GroupFentanyl Group
Emergence From Anesthesia3 (0 to 141)2.5 (0 to 258)
SecondaryWound Hyperalgesia

Von frey hair objective testing

Time frame:
96 hours postoperatively
Reported as:
Mean · g/mm^2
Wound Hyperalgesia
g/mm^2Remifentanil GroupFentanyl Group
Preop pain threshold3.24 ± 0.943.30 ± 1.08
48 Hr pain threshold3.71 ± 1.003.83 ± 1.28
96 hr pain threshold3.60 ± 1.083.72 ± 1.30
SecondaryDevelopment 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
Reported as:
Median · score on a scale
Development of Chronic Pain
score on a scaleRemifentanil GroupFentanyl Group
S-LANSS 1 mo1 (0 to 8)3 (0 to 8)
S-LANSS 3 mo0 (0 to 8)0 (0 to 6)
S-LANSS 6 mo0 (0 to 3)0 (0 to 3)
S-LANSS 12 mo0 (0 to 3)0 (0 to 3)
SecondaryGlycemic 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
Reported as:
Mean · Percent of Mean Glucose Level
Glycemic Variability
Percent of Mean Glucose LevelRemifentanil GroupFentanyl Group
Glycemic Variability0.2 (0.1 to 0.3)0.2 (0.1 to 0.4)
Statistical analysis
  • Remifentanil Group vs Fentanyl Group · Wilcoxon (Mann-Whitney) · p = 0.350

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Remifentanil Group3/54 (5.6%)1/54 (1.9%)28/54 (51.9%)
Fentanyl Group6/52 (11.5%)5/52 (9.6%)27/52 (51.9%)
Most frequent serious events
Most frequent serious events
EventRemifentanil GroupFentanyl Group
Pleural effusionRespiratory, thoracic and mediastinal disorders0/543/52
PneumoniaRespiratory, thoracic and mediastinal disorders0/541/52
Pericardial effusion/tamponadeCardiac disorders0/541/52
StrokeNervous system disorders1/540/52
Most frequent other events
Showing 10 of 16
Most frequent other events
EventRemifentanil GroupFentanyl Group
Any postoperative complicationSurgical and medical procedures28/5427/52
Prolonged Mechanical Ventilation (>72 hours)Respiratory, thoracic and mediastinal disorders8/548/52
ReintubationRespiratory, thoracic and mediastinal disorders5/547/52
Readmission within 30 daysGeneral disorders2/545/52
SepsisSurgical and medical procedures4/544/52
PneumoniaRespiratory, thoracic and mediastinal disorders4/543/52
Renal FailureRenal and urinary disorders3/543/52
DialysisRenal and urinary disorders3/543/52
Cardiac ArrestCardiac disorders3/543/52
Multisystem Organ FailureGeneral disorders3/542/52

Baseline characteristics

Age, Continuous
Age, Continuous(years)Remifentanil GroupFentanyl GroupTotal
Mean70.0 (32.0 to 84.0)71.0 (46.0 to 86.0)70.5 (32.0 to 86.0)
Sex: Female, Male
Sex: Female, Male(Participants)Remifentanil GroupFentanyl GroupTotal
Female191433
Male353873
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Remifentanil GroupFentanyl GroupTotal
Count of participants——0
Region of Enrollment
Region of Enrollment(participants)Remifentanil GroupFentanyl GroupTotal
United States5452106
08

Study locations

1 site
  • UPMC Presbyterian Hospital
    Pittsburgh, Pennsylvania 15213, United States
09

References and documents

Publications

  • Doenst T, Wijeysundera D, Karkouti K, Zechner C, Maganti M, Rao V, Borger MA. Hyperglycemia during cardiopulmonary bypass is an independent risk factor for mortality in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2005 Oct;130(4):1144. doi: 10.1016/j.jtcvs.2005.05.049. PubMed 16214532 ↗
  • Ihn CH, Joo JD, Choi JW, Kim DW, Jeon YS, Kim YS, Jung HS, Kwon SY. Comparison of stress hormone response, interleukin-6 and anaesthetic characteristics of two anaesthetic techniques: volatile induction and maintenance of anaesthesia using sevoflurane versus total intravenous anaesthesia using propofol and remifentanil. J Int Med Res. 2009 Nov-Dec;37(6):1760-71. doi: 10.1177/147323000903700612. PubMed 20146874 ↗
  • Subramaniam B, Lerner A, Novack V, Khabbaz K, Paryente-Wiesmann M, Hess P, Talmor D. Increased glycemic variability in patients with elevated preoperative HbA1C predicts adverse outcomes following coronary artery bypass grafting surgery. Anesth Analg. 2014 Feb;118(2):277-287. doi: 10.1213/ANE.0000000000000100. PubMed 24445629 ↗
  • Shinoda T, Murakami W, Takamichi Y, Iizuka H, Tanaka M, Kuwasako Y. Effect of remifentanil infusion rate on stress response in orthopedic surgery using a tourniquet application. BMC Anesthesiol. 2013 Jul 10;13:14. doi: 10.1186/1471-2253-13-14. eCollection 2013. PubMed 23837943 ↗
  • Cok OY, Ozkose Z, Pasaoglu H, Yardim S. Glucose response during craniotomy: propofol-remifentanil versus isoflurane-remifentanil. Minerva Anestesiol. 2011 Dec;77(12):1141-8. Epub 2011 May 20. PubMed 21602751 ↗
  • Lazar HL, McDonnell M, Chipkin SR, Furnary AP, Engelman RM, Sadhu AR, Bridges CR, Haan CK, Svedjeholm R, Taegtmeyer H, Shemin RJ; Society of Thoracic Surgeons Blood Glucose Guideline Task Force. The Society of Thoracic Surgeons practice guideline series: Blood glucose management during adult cardiac surgery. Ann Thorac Surg. 2009 Feb;87(2):663-9. doi: 10.1016/j.athoracsur.2008.11.011. No abstract available. PubMed 19161815 ↗
  • Subramaniam K, Sciortino C, Ruppert K, Monroe A, Esper S, Boisen M, Marquez J, Hayanga H, Badhwar V. Remifentanil and perioperative glycaemic response in cardiac surgery: an open-label randomised trial. Br J Anaesth. 2020 Jun;124(6):684-692. doi: 10.1016/j.bja.2020.01.028. Epub 2020 Apr 2. PubMed 32247539 ↗

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jan 2016 to primary completion in Dec 2016, 11 months.

Results were first posted in May 2018, 1 year 5 months after primary completion.

Of 24 phase 4 interventional studies under Heart Diseases, half reached primary completion within 51 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 75. This study's 11 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 13, 2015
First posted
Jan 28, 2015
StartActual
Jan 2016
Primary completionActual
Dec 2016
CompletionActual
Dec 2017
Results first posted
May 14, 2018
Last update
Apr 21, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 21, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02349152
Lead sponsor
Kathirvel Subramaniam
Collaborators
Mylan Inc.
Responsible party
Kathirvel Subramaniam (Visiting Associate Professor in Anesthesiology, University of Pittsburgh) — Sponsor-investigator
First posted
Jan 28, 2015
Start date
Jan 2016
Primary completion
Dec 2016
Completion
Dec 2017
Results posted
May 14, 2018
Last update
Apr 21, 2020

Study contacts

Kathrivel Subramaniam, MD
principal investigator · University of Pittsburgh Medical Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2020. You cannot join it, but the record below documents what was studied.

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Discussion

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Remifentanil

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Heart Diseases →

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Kathirvel Subramaniam

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