Acute Pain, Hyperalgesia
Conditions
Keywords
Cardiac surgery, Acute Pain, Wound Hyperalgesia, Intravenous Acetaminophen, Patient Satisfaction
Brief summary
Patients undergoing cardiac surgery experience significant postoperative pain, which may impact postoperative outcomes. The aim of this single center, double-blind, randomized, placebo controlled trial is to determine if intravenous (IV) acetaminophen will significantly decrease 24 hour postoperative opioid consumption.
Detailed description
Subjects will be randomized to a placebo or treatment group in a 1:1 ratio in blocks of 10 using an online randomization tool. The randomization table numbers for the subjects who are randomized, but subsequently withdrew consent after enrollment or had their case cancelled will be also included. Only the research pharmacists will have access to the securely-stored randomized group allocation list, which will remain blinded until statistical analysis is completed. A research pharmacist will prepare 100 mL normal saline infusion bags, which contain either 1,000 mg IV acetaminophen or placebo. Identical in appearance, the bags will be then delivered to either the operating room satellite pharmacy or ICU. The subjects will receive a total of 6 doses of 1,000 mg IV acetaminophen or placebo at the following time points: (1) immediately after anesthesia induction, but prior to the incision, (2) at the end of surgery with (3) four additional doses administered postoperatively in the ICU every 6 hours for the first 24 hours. The first ICU dose will be administered 6 hours after the arrival in the ICU. The intraoperative study drug doses will be administered by one of the investigators (SJ or PR) and postoperative ICU study drug doses will be administered by nursing staff. Anesthesia and Pain Management All of the study subjects will undergo cardiac surgery under general anesthesia. The cardiac surgery procedures will include standard midline sternotomy and in cases involving coronary artery bypass grafting, harvesting of saphenous vein and internal mammary artery grafts. Cardiopulmonary bypass will be conducted using membrane oxygenation. All subjects will undergo standardized induction per current practice at our institution with lidocaine (1-1.5 mg/kg), fentanyl (5-10 μg/kg), etomidate (0.2 mg/kg) and either rocuronium (1 mg/kg) or vecuronium (0.1 mg/kg). Succinylcholine (1-1.5 mg/kg) will be used when rapid sequence induction is appropriate. The anesthesia will be maintained with isoflurane. The intraoperative analgesia will consist of fentanyl or hydromorphone boluses, which will be administered at the discretion of the anesthesia provider. Postoperative pain management will consist of nursing fentanyl boluses while patients were sedated and mechanically ventilated. Following extubation, patients will receive oral oxycodone (5 to 10 mg orally every 3 hours as needed) with intravenous hydromorphone or morphine boluses for breakthrough pain. Opioid Consumption At the end of the surgery, subjects will be transferred to the ICU while intubated and sedated on a propofol infusion. The time of arrival to the ICU will be considered time 0 for the purpose of postoperative study drug dosing and further evaluations. The 24 hour opioid consumption will be obtained from the electronic medication administration record and will be expressed in morphine equivalents per standard opioid conversions. Secondary Outcomes The secondary outcomes will include 48 hour postoperative opioid consumption. The ICU nursing staff will be trained to use pain diaries containing an eleven point (0 to 10) Numeric Rating Scale (NRS). Pain assessments at rest and with movement will be recorded by the nursing staff at 6, 12, 18 and 24 hours postoperatively while one of the investigators will record pain assessments at 48 hours postoperatively. At the same times postoperatively, patients will be also assessed for opioid related adverse effects including nausea and vomiting, pruritus, respiratory depression, dizziness and sedation using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). In addition, the ICU nursing staff will be instructed to complete the Extubation Criteria checklist for each 2-hour time period until extubation and the ICU Discharge Criteria checklist for each 4-hour time period until discharge from the ICU. A short Patient Satisfaction Survey will be also completed during the 24 and 48 hour follow up visits. The extent to which subjects overall pain experience met their expectations will be converted to the Likert scale with the following values: not at all (1), a little (2), a fair amount (3), very much (4) and extremely well (5). Wound hyperalgesia at 24 and 48 hours postoperatively will be measured using a method previously described by Stubhaug et al. In brief, the lateral right chest area will be first stimulated where no pain sensation is experienced using a 180 gram von Frey filament (# 6.45). The filament will be then moved toward the incision in 1 cm steps until a distinct change in perception (painful, sore, or sharp feeling) is reported and the remaining distance to the incision will be noted. If no change in sensation appears, stimulation will be stopped at 4 cm from the incision. Wound hyperalgesia will be determined by testing the right side of the chest along five horizontal lines vertically separated by 2 cm at right angles to the incision. Only the right side of the chest will be chosen to avoid confounding skin sensation changes from the left internal mammary artery harvesting. The distance (in cm) from the incision to the point where sensations changed will be measured 5 times and the average distance will be used as wound hyperalgesia. Data and Statistical Analysis A power analysis determined that 35 patients in each group will be needed to have an 80% chance to detect a 30% difference in mean 24 hour cumulative opioid consumption for the first 24 hour period after surgery using 2-sided t-tests with a set α level of 0.05, and an anticipated dropout rate of less than 15%. Fisher's exact or Chi-squared and t-tests will be used to compare patient characteristics and intraoperative variables between the placebo and treatment group. Outcome variables will be compared between groups using t-tests and analysis of covariance controlling for age, sex, body mass index (BMI) and intraoperative hydromorphone. Scatter plots will be used to display the data to look for interactions, outliers and skewed distributions. The best fit line will be assessed by the F-test on the interaction between age and treatment group in an analysis of covariance. The analyses will be performed using SPSS software, version 15 (SPSS Inc., Chicago, IL). All reported P values will be 2-sided, and a significance level of P \< 0.05 will be used.
Interventions
DRUGIV acetaminophen
Total of 6 doses of 1,000 mg IV acetaminophen at the following time points: (1) immediately after anesthesia induction, but prior to the incision, (2) at the end of surgery with (3) four additional doses administered postoperatively in the ICU every 6 hours for the first 24 hours.
DRUGPlacebo
Total of 6 doses of 100 mL of normal saline at the following time points: (1) immediately after anesthesia induction, but prior to the incision, (2) at the end of surgery with (3) four additional doses administered postoperatively in the ICU every 6 hours for the first 24 hours.
Sponsors
Mallinckrodt
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* (1) subjects who clinically consented to elective sternotomy for coronary artery bypass grafting (CABG), heart valve repair or replacement under general anesthesia, and (2) ages between 18 and 75 years
Exclusion criteria
* (1) subject refusal, (2) non-English speaking, (3) previous chronic or neuropathic pain, (4) previous chronic use of opioids, (5) history of psychiatric disorder, (6) allergy to acetaminophen, (7) severely impaired liver and kidney function and (8) previous sternotomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24 Hour Postoperative Opioid Consumption | 24 hours after arriving in ICU | The 24 hour postoperative opioid consumption will be obtained from the electronic medication administration record and expressed in morphine equivalents. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24 Hour Postoperative Pain Scores at Rest | 24 hours after arriving in ICU | Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable). |
| 48 Hour Postoperative Pain Scores at Rest | 48 hours after arriving in ICU | Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable). |
| 24 Hour Postoperative Pain Scores With Movement | 24 hours after arriving in ICU | Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable). |
| 48 Hour Postoperative Pain Scores With Movement | 48 hours after arriving in ICU | Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable). |
| 24 Hour Wound Hyperalgesia | 24 hours after arriving in ICU | Wound hyperalgesia will be determined by testing the right side of the chest along five horizontal lines vertically separated by 2 cm at right angles to the incision using 180 gram von Frey filament (# 6.45). |
| 48 Hour Wound Hyperalgesia | 48 hours after arriving in ICU | Wound hyperalgesia will be determined by testing the right side of the chest along five horizontal lines vertically separated by 2 cm at right angles to the incision using 180 gram von Frey filament (# 6.45). |
| Length of Mechanical Ventilation | From the time of arrival in ICU until extubation | The length of mechanical ventilation will be determined based on the Extubation Criteria checklist that will be completed by nursing staff every 2 hours until extubation. |
| Length of ICU Stay | From the time of arrival in ICU until ICU discharge | The length of ICU stay will be determined based on the ICU Discharge Criteria checklist that will be completed by nursing staff every 4 hours until ICU discharge. |
| 48 Hour Patient Satisfaction | 48 hours after arriving in ICU | The extent to which subjects overall pain experience met their expectations question responses were converted to the Likert scale with the following values: not at all (1), a little (2), a fair amount (3), very much (4) and extremely well (5). |
| 48 Hour Postoperative Opioid Consumption | 48 hours after arriving in ICU | 48 hour postoperative opioid consumption will be obtained from the electronic medication administration record and expressed in morphine equivalents. |
| 48 Hour Nausea | 48 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of nausea was defined as numeric scale response 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 24 Hour Pruritus | 24 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of pruritus was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 48 Hour Pruritus | 48 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of pruritus was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 24 Hour Sedation | 24 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of sedation was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 48 Hour Sedation | 48 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of sedation was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 24 Hour Respiratory Depression | 24 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of respiratory depression was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 48 Hour Respiratory Depression | 48 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of respiratory depression was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 24 Hour Dizziness | 24 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of dizziness was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 48 Hour Dizziness | 48 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of dizziness was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
| 24 Hour Nausea | 24 hours after arriving in ICU | Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of nausea was defined as numeric scale response 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV Acetaminophen Study subjects receiving IV acetaminophen
IV acetaminophen: Total of 6 doses of 1,000 mg IV acetaminophen at the following time points: (1) immediately after anesthesia induction, but prior to the incision, (2) at the end of surgery with (3) four additional doses administered postoperatively in the ICU every 6 hours for the first 24 hours. | 33 |
| Normal Saline Study subjects receiving placebo | 35 |
| Total | 68 |
Baseline characteristics
| Characteristic | IV Acetaminophen | Normal Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 13 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 22 Participants | 47 Participants |
| Region of Enrollment United States | 33 participants | 35 participants | 68 participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 16 Participants |
| Sex: Female, Male Male | 29 Participants | 23 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 33 |
| serious Total, serious adverse events | 0 / 35 | 0 / 33 |
Outcome results
Primary
24 Hour Postoperative Opioid Consumption
The 24 hour postoperative opioid consumption will be obtained from the electronic medication administration record and expressed in morphine equivalents.
Time frame: 24 hours after arriving in ICU
Population: Missing data for 1 study subject in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 24 Hour Postoperative Opioid Consumption | 62.3 mg | Standard Deviation 29.5 |
| IV Acetaminophen | 24 Hour Postoperative Opioid Consumption | 45.6 mg | Standard Deviation 29.5 |
p-value: 0.02495% CI: [2.3, 31.1]t-test, 2 sided
p-value: 0.013ANCOVA
Secondary
24 Hour Dizziness
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of dizziness was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 24 hours after arriving in ICU
Population: Missing data on 3 study subjects in normal saline group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 24 Hour Dizziness | 20 participants |
| IV Acetaminophen | 24 Hour Dizziness | 17 participants |
p-value: 0.455Fisher Exact
Secondary
24 Hour Nausea
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of nausea was defined as numeric scale response 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 24 hours after arriving in ICU
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 24 Hour Nausea | 25 participants |
| IV Acetaminophen | 24 Hour Nausea | 26 participants |
p-value: 0.58Fisher Exact
Secondary
24 Hour Postoperative Pain Scores at Rest
Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable).
Time frame: 24 hours after arriving in ICU
Population: Missing data for 3 study subjects in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 24 Hour Postoperative Pain Scores at Rest | 3.9 units on a scale | Standard Deviation 2.3 |
| IV Acetaminophen | 24 Hour Postoperative Pain Scores at Rest | 3.7 units on a scale | Standard Deviation 2.3 |
p-value: 0.724t-test, 2 sided
p-value: 0.51ANCOVA
Secondary
24 Hour Postoperative Pain Scores With Movement
Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable).
Time frame: 24 hours after arriving in ICU
Population: Missing data on 3 study subjects in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 24 Hour Postoperative Pain Scores With Movement | 6.3 units on a scale | Standard Deviation 2.5 |
| IV Acetaminophen | 24 Hour Postoperative Pain Scores With Movement | 6.0 units on a scale | Standard Deviation 2.5 |
p-value: 0.6t-test, 2 sided
p-value: 0.509ANCOVA
Secondary
24 Hour Pruritus
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of pruritus was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 24 hours after arriving in ICU
Population: Missing data on 3 study subjects in normal saline group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 24 Hour Pruritus | 4 participants |
| IV Acetaminophen | 24 Hour Pruritus | 7 participants |
p-value: 0.511Fisher Exact
Secondary
24 Hour Respiratory Depression
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of respiratory depression was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 24 hours after arriving in ICU
Population: Missing data on 3 study subjects in normal saline group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 24 Hour Respiratory Depression | 2 participants |
| IV Acetaminophen | 24 Hour Respiratory Depression | 2 participants |
p-value: 1Fisher Exact
Secondary
24 Hour Sedation
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of sedation was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 24 hours after arriving in ICU
Population: Missing data on 3 study subjects in normal saline group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 24 Hour Sedation | 8 participants |
| IV Acetaminophen | 24 Hour Sedation | 8 participants |
p-value: 1Fisher Exact
Secondary
24 Hour Wound Hyperalgesia
Wound hyperalgesia will be determined by testing the right side of the chest along five horizontal lines vertically separated by 2 cm at right angles to the incision using 180 gram von Frey filament (# 6.45).
Time frame: 24 hours after arriving in ICU
Population: Missing data on 3 study subjects in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 24 Hour Wound Hyperalgesia | 4.8 cm | Standard Deviation 4.3 |
| IV Acetaminophen | 24 Hour Wound Hyperalgesia | 4.5 cm | Standard Deviation 3.8 |
p-value: 0.771t-test, 2 sided
p-value: 0.927ANCOVA
Secondary
48 Hour Dizziness
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of dizziness was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 7 study subjects in normal saline group and 4 study subjects in IV acetaminophen group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 48 Hour Dizziness | 9 participants |
| IV Acetaminophen | 48 Hour Dizziness | 10 participants |
p-value: 1Fisher Exact
Secondary
48 Hour Nausea
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of nausea was defined as numeric scale response 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 48 hours after arriving in ICU
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 48 Hour Nausea | 12 participants |
| IV Acetaminophen | 48 Hour Nausea | 14 participants |
p-value: 0.619Fisher Exact
Secondary
48 Hour Patient Satisfaction
The extent to which subjects overall pain experience met their expectations question responses were converted to the Likert scale with the following values: not at all (1), a little (2), a fair amount (3), very much (4) and extremely well (5).
Time frame: 48 hours after arriving in ICU
Population: Questionnaire not completed by 12 study subjects in normal saline group and 10 study subjects in IV acetaminophen group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 48 Hour Patient Satisfaction | 2.3 units on a scale | Standard Deviation 1.2 |
| IV Acetaminophen | 48 Hour Patient Satisfaction | 2.8 units on a scale | Standard Deviation 0.9 |
p-value: 0.104t-test, 2 sided
Secondary
48 Hour Postoperative Opioid Consumption
48 hour postoperative opioid consumption will be obtained from the electronic medication administration record and expressed in morphine equivalents.
Time frame: 48 hours after arriving in ICU
Population: Missing data for 1 study subject in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 48 Hour Postoperative Opioid Consumption | 105.1 mg | Standard Deviation 42.1 |
| IV Acetaminophen | 48 Hour Postoperative Opioid Consumption | 85.1 mg | Standard Deviation 42.3 |
p-value: 0.059t-test, 2 sided
p-value: 0.02ANCOVA
Secondary
48 Hour Postoperative Pain Scores at Rest
Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 2 study subjects in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 48 Hour Postoperative Pain Scores at Rest | 2.4 units on a scale | Standard Deviation 2.2 |
| IV Acetaminophen | 48 Hour Postoperative Pain Scores at Rest | 2.0 units on a scale | Standard Deviation 1.8 |
p-value: 0.397t-test, 2 sided
p-value: 0.458ANCOVA
Secondary
48 Hour Postoperative Pain Scores With Movement
Pain scores at rest will be recorded on Numeric Rating Scale by nursing staff. The Numeric Rating Scale ranges from 0 to 10 (0 - no pain, 1-2-3 - mild pain, 4-5-6 - moderate pain, 7-8-9 - severe pain, 10 - worst pain imaginable).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 2 study subjects in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 48 Hour Postoperative Pain Scores With Movement | 5.1 units on a scale | Standard Deviation 2.9 |
| IV Acetaminophen | 48 Hour Postoperative Pain Scores With Movement | 4.6 units on a scale | Standard Deviation 2 |
p-value: 0.399t-test, 2 sided
p-value: 0.395ANCOVA
Secondary
48 Hour Pruritus
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of pruritus was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 8 study subjects in normal saline group and 6 study subjects in IV acetaminophen group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 48 Hour Pruritus | 4 participants |
| IV Acetaminophen | 48 Hour Pruritus | 7 participants |
p-value: 0.501Fisher Exact
Secondary
48 Hour Respiratory Depression
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of respiratory depression was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 6 study subjects in normal saline group and 3 study subjects in IV acetaminophen group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 48 Hour Respiratory Depression | 1 participants |
| IV Acetaminophen | 48 Hour Respiratory Depression | 0 participants |
p-value: 0.492Fisher Exact
Secondary
48 Hour Sedation
Opioid related adverse effects were recorded using a numeric scale (0 = no adverse effects, 1 = mild adverse effects not requiring treatment, 2 = moderate adverse effects requiring treatment and 3 = severe adverse effects refractory to treatment). Presence of sedation was defined as numeric scale response 1 (mild adverse effects not requiring treatment), 2 (moderate adverse effects requiring treatment) or 3 (severe adverse effects refractory to treatment).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 6 study subjects in normal saline group and 3 study subjects in IV acetaminophen group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Saline | 48 Hour Sedation | 6 participants |
| IV Acetaminophen | 48 Hour Sedation | 3 participants |
p-value: 0.299Fisher Exact
Secondary
48 Hour Wound Hyperalgesia
Wound hyperalgesia will be determined by testing the right side of the chest along five horizontal lines vertically separated by 2 cm at right angles to the incision using 180 gram von Frey filament (# 6.45).
Time frame: 48 hours after arriving in ICU
Population: Missing data on 2 study subjects in normal saline group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | 48 Hour Wound Hyperalgesia | 4.6 cm | Standard Deviation 3.9 |
| IV Acetaminophen | 48 Hour Wound Hyperalgesia | 5.0 cm | Standard Deviation 3.5 |
p-value: 0.644t-test, 2 sided
p-value: 0.16ANCOVA
Secondary
Length of ICU Stay
The length of ICU stay will be determined based on the ICU Discharge Criteria checklist that will be completed by nursing staff every 4 hours until ICU discharge.
Time frame: From the time of arrival in ICU until ICU discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | Length of ICU Stay | 67 hours | Standard Deviation 35 |
| IV Acetaminophen | Length of ICU Stay | 61 hours | Standard Deviation 27 |
p-value: 0.508t-test, 2 sided
p-value: 0.905ANCOVA
Secondary
Length of Mechanical Ventilation
The length of mechanical ventilation will be determined based on the Extubation Criteria checklist that will be completed by nursing staff every 2 hours until extubation.
Time frame: From the time of arrival in ICU until extubation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Saline | Length of Mechanical Ventilation | 407 minutes | Standard Deviation 683 |
| IV Acetaminophen | Length of Mechanical Ventilation | 360 minutes | Standard Deviation 276 |
p-value: 0.71t-test, 2 sided
p-value: 0.475ANCOVA