Pain
Conditions
Keywords
Males or females, 18 years of age or older., Non-emergency, cardiac surgery, midline sternotomy.
Brief summary
Evaluate the efficacy of IV acetaminophen; compared to a placebo, in reducing opioid consumption and/or pain intensity scores after cardiac surgery.
Interventions
DRUGPlacebo
Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
DRUGIV Acetaminophen
Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* \- Males or females 18 years of age or older. * Non-emergency cardiac surgery via a midline sternotomy at Cleveland Clinic Main Campus.
Exclusion criteria
1. Redo cardiac surgery. 2. Combined CABG (Coronary Artery Bypass Graft)& valve replacement, multiple valve replacements, Ascending aortic or aortic arch surgery. 3. Weight \< 50 Kg or Body mass index \> 38 kg/m2. 4. Left ventricle EF ¡Ü 35% ,Right ventricular moderate or severe dysfunction. 5. Severe (3-4 +) Tricuspid Regurgitation. 6. Recent stroke (within 6 months). 7. Severe lung disease requiring home O2 therapy. 8. Preoperative renal insufficiency (Creatinine \> 2.0) or on dialysis. 9. History of liver cirrhosis or active liver disease. 10. Chronic pain conditions controlled by preoperative opioid administration. 11. Known allergy to acetaminophen or fentanyl.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Opioid Consumption | End of surgery through 24 hours after surgery | Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing opioid consumption a after cardiac surgery. Total opioid consumption is defined as the total amount amount of opioids administered to patients converted to mg morphine equivalents. |
| Pain Intensity | End of surgery through 24 hours after surgery | Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing pain intensity scores after cardiac surgery. Pain scores were measured on the Numeric Rating scale, ranging from 0 to 10 (where 0 indicates no pain and 10 indicates the worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Mechanical Ventilation (Minutes) | End of surgery until the initial end of ventilation or date of death from any cause, whichever came first, assessed up to 1 week. | Evaluate whether IV acetaminophen reduced duration of Mechanical Ventilation. |
| Intensive Care Unit (ICU) Length of Stay | End of surgery through discharge from ICU | Evaluate whether IV acetaminophen reduced intensive care unit (ICU) Length of Stay. |
| Hospital Length of Stay | end of surgery through hospital discharge | Evaluate whether IV acetaminophen hospital length of stay |
| Postoperative Nausea and Vomiting | End of surgery through 24 hours after surgery | Incidence of any postoperative nausea and vomiting within 24 hours after surgery was collected. |
| Aspartate Aminotransferase (AST); U/L | Two days after surgery or date of death from any cause, whichever came first | — |
| Total Bilirubin (mg/dL) | Measured at 1 day and 2 days after surgery | — |
| Alanine Aminotransferase (ALT); U/L | Two days after surgery or date of death from any cause, whichever came first | — |
| Postoperative Sedation | Measured at 8, 16, and 24 hours after surgery | Postoperative sedation was assessed using the Richmond Agitation Sedation Scale (RASS). It ranges from -5 to +4, where -5 indicates no response to voice or physical stimulation and +4 indicates overtly combative or violent and immediate danger to staff. Lower the value, better the sedation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV Acetaminophen Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.
IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. | 73 |
| Placebo Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids. | 74 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Eligible surgery cancelled | 1 | 1 |
| Overall Study | Other reasons | 1 | 0 |
Baseline characteristics
| Characteristic | IV Acetaminophen | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 14 | 59 years STANDARD_DEVIATION 14 | 60.5 years STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Male | 49 Participants | 50 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 73 | 0 / 74 |
| serious Total, serious adverse events | 0 / 73 | 0 / 74 |
Outcome results
Primary
Cumulative Opioid Consumption
Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing opioid consumption a after cardiac surgery. Total opioid consumption is defined as the total amount amount of opioids administered to patients converted to mg morphine equivalents.
Time frame: End of surgery through 24 hours after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Acetaminophen | Cumulative Opioid Consumption | 97 mg morphine equivalents |
| Placebo | Cumulative Opioid Consumption | 117 mg morphine equivalents |
p-value: 0.08Regression, Linear
p-value: 0.28Regression, Linear
Primary
Pain Intensity
Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing pain intensity scores after cardiac surgery. Pain scores were measured on the Numeric Rating scale, ranging from 0 to 10 (where 0 indicates no pain and 10 indicates the worst pain imaginable).
Time frame: End of surgery through 24 hours after surgery
Population: All patients had at least one postoperative pain scores. Some patients did not have a pain score at particular time points if they were unavailable (e.g., at a test), unable to speak (e.g., intubated), asleep, or similar reasons. We report any available pain scores at each time they were collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Acetaminophen | Pain Intensity | overall pain scores | 3.1 units on a scale | Standard Deviation 1.6 |
| IV Acetaminophen | Pain Intensity | 4 hours after surgery | 4.6 units on a scale | Standard Deviation 2.9 |
| IV Acetaminophen | Pain Intensity | 6 hours after surgery | 3.5 units on a scale | Standard Deviation 2.4 |
| IV Acetaminophen | Pain Intensity | 8 hours after surgery | 3.2 units on a scale | Standard Deviation 2.6 |
| IV Acetaminophen | Pain Intensity | 12 hours after surgery | 2.4 units on a scale | Standard Deviation 2.5 |
| IV Acetaminophen | Pain Intensity | 16 hours after surgery | 3.0 units on a scale | Standard Deviation 2.4 |
| IV Acetaminophen | Pain Intensity | 20 hours after surgery | 2.9 units on a scale | Standard Deviation 2.1 |
| IV Acetaminophen | Pain Intensity | 24 hours after surgery | 2.5 units on a scale | Standard Deviation 2.1 |
| Placebo | Pain Intensity | 24 hours after surgery | 3.5 units on a scale | Standard Deviation 2 |
| Placebo | Pain Intensity | overall pain scores | 4.0 units on a scale | Standard Deviation 1.4 |
| Placebo | Pain Intensity | 12 hours after surgery | 3.5 units on a scale | Standard Deviation 2.6 |
| Placebo | Pain Intensity | 4 hours after surgery | 5.0 units on a scale | Standard Deviation 3.1 |
| Placebo | Pain Intensity | 20 hours after surgery | 4.2 units on a scale | Standard Deviation 2 |
| Placebo | Pain Intensity | 6 hours after surgery | 4.4 units on a scale | Standard Deviation 2.4 |
| Placebo | Pain Intensity | 16 hours after surgery | 3.6 units on a scale | Standard Deviation 2.4 |
| Placebo | Pain Intensity | 8 hours after surgery | 4.4 units on a scale | Standard Deviation 2.3 |
p-value: <0.001Regression, Linear
p-value: <0.001Regression, Linear
Secondary
Alanine Aminotransferase (ALT); U/L
Time frame: Two days after surgery or date of death from any cause, whichever came first
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Acetaminophen | Alanine Aminotransferase (ALT); U/L | Overall ALT | 18 U/L |
| IV Acetaminophen | Alanine Aminotransferase (ALT); U/L | postoperative day 1 ALT | 18 U/L |
| IV Acetaminophen | Alanine Aminotransferase (ALT); U/L | postoperative day 2 ALT | 17 U/L |
| Placebo | Alanine Aminotransferase (ALT); U/L | Overall ALT | 19 U/L |
| Placebo | Alanine Aminotransferase (ALT); U/L | postoperative day 1 ALT | 19 U/L |
| Placebo | Alanine Aminotransferase (ALT); U/L | postoperative day 2 ALT | 18 U/L |
p-value: 0.3199.4% CI: [0.9, 1.2]Regression, Linear
Secondary
Aspartate Aminotransferase (AST); U/L
Time frame: Two days after surgery or date of death from any cause, whichever came first
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Acetaminophen | Aspartate Aminotransferase (AST); U/L | Overall AST | 35 U/L |
| IV Acetaminophen | Aspartate Aminotransferase (AST); U/L | postoperative day 1 AST | 40 U/L |
| IV Acetaminophen | Aspartate Aminotransferase (AST); U/L | postoperative day 2 AST | 31 U/L |
| Placebo | Aspartate Aminotransferase (AST); U/L | Overall AST | 33 U/L |
| Placebo | Aspartate Aminotransferase (AST); U/L | postoperative day 1 AST | 40 U/L |
| Placebo | Aspartate Aminotransferase (AST); U/L | postoperative day 2 AST | 31 U/L |
p-value: 0.9899.4% CI: [0.8, 1.2]Regression, Linear
Secondary
Duration of Mechanical Ventilation (Minutes)
Evaluate whether IV acetaminophen reduced duration of Mechanical Ventilation.
Time frame: End of surgery until the initial end of ventilation or date of death from any cause, whichever came first, assessed up to 1 week.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Acetaminophen | Duration of Mechanical Ventilation (Minutes) | 214 minutes |
| Placebo | Duration of Mechanical Ventilation (Minutes) | 190 minutes |
p-value: 0.4699.4% CI: [0.52, 3.2]Regression, Linear
Secondary
Hospital Length of Stay
Evaluate whether IV acetaminophen hospital length of stay
Time frame: end of surgery through hospital discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Acetaminophen | Hospital Length of Stay | 6.2 days |
| Placebo | Hospital Length of Stay | 6.1 days |
p-value: 0.1299.4% CI: [0.94, 1.2]Regression, Linear
Secondary
Intensive Care Unit (ICU) Length of Stay
Evaluate whether IV acetaminophen reduced intensive care unit (ICU) Length of Stay.
Time frame: End of surgery through discharge from ICU
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Acetaminophen | Intensive Care Unit (ICU) Length of Stay | 214 hours |
| Placebo | Intensive Care Unit (ICU) Length of Stay | 190 hours |
p-value: 0.3899.4% CI: [0.74, 1.2]Regression, Linear
Secondary
Postoperative Nausea and Vomiting
Incidence of any postoperative nausea and vomiting within 24 hours after surgery was collected.
Time frame: End of surgery through 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Acetaminophen | Postoperative Nausea and Vomiting | 16 Participants |
| Placebo | Postoperative Nausea and Vomiting | 21 Participants |
p-value: 0.3599.4% CI: [0.34, 1.7]Regression, Logistic
Secondary
Postoperative Sedation
Postoperative sedation was assessed using the Richmond Agitation Sedation Scale (RASS). It ranges from -5 to +4, where -5 indicates no response to voice or physical stimulation and +4 indicates overtly combative or violent and immediate danger to staff. Lower the value, better the sedation.
Time frame: Measured at 8, 16, and 24 hours after surgery
Population: RASS scores were not collected at certain time points if patients were not available (e.g., patient was away at a test) or if staff were not available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Acetaminophen | Postoperative Sedation | 8 hours after surgery | 0 units on a scale |
| IV Acetaminophen | Postoperative Sedation | 16 hours after surgery | 0 units on a scale |
| IV Acetaminophen | Postoperative Sedation | 24 hours after surgery | 0 units on a scale |
| Placebo | Postoperative Sedation | 8 hours after surgery | 0 units on a scale |
| Placebo | Postoperative Sedation | 16 hours after surgery | 0 units on a scale |
| Placebo | Postoperative Sedation | 24 hours after surgery | 0 units on a scale |
Comparison: Analysis at 8 hours after surgery.p-value: 0.1399.8% CI: [0, 0]Wilcoxon (Mann-Whitney)
Comparison: Analysis at 16 hours after surgery.p-value: 0.4499.8% CI: [0, 0]Wilcoxon (Mann-Whitney)
Comparison: Analysis at 24 hours after surgeryp-value: 0.3899.8% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Total Bilirubin (mg/dL)
Time frame: Measured at 1 day and 2 days after surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Acetaminophen | Total Bilirubin (mg/dL) | postoperative day 2 bilirubin | 0.6 mg/dL |
| IV Acetaminophen | Total Bilirubin (mg/dL) | overall bilirubin | 0.7 mg/dL |
| IV Acetaminophen | Total Bilirubin (mg/dL) | postoperative day 1 bilirubin | 0.7 mg/dL |
| Placebo | Total Bilirubin (mg/dL) | postoperative day 2 bilirubin | 0.6 mg/dL |
| Placebo | Total Bilirubin (mg/dL) | overall bilirubin | 0.7 mg/dL |
| Placebo | Total Bilirubin (mg/dL) | postoperative day 1 bilirubin | 0.7 mg/dL |
p-value: 0.499.4% CI: [0.87, 1.3]Regression, Linear