CarDolMev: IV Acetaminophen as an Adjunct Analgesic in Cardiac Surgery

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01544062
• Collaborator: Mallinckrodt (Industry)
• Enrollment: 68
• Location: 1
• Arms: 2
• Duration (Months): 25
• Patients Per Site Per Month: 2.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Pain; Hyperalgesia	Drug: IV acetaminophen; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Perioperative Intravenous Acetaminophen as an Adjunct Analgesic in Cardiac Surgery Patients
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV acetaminophen Study subjects receiving IV acetaminophen	Drug: 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.; Other Names: Ofirmev
Placebo Comparator: Normal saline Study subjects receiving placebo	Drug: Placebo; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

3. 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).

4. 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).

5. 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).

6. 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).

7. 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).

8. 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.

9. 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.

10. 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).

11. 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).

12. 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).

13. 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).

14. 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).

15. 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).

16. 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).

17. 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).

18. 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).

19. 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).

20. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Washington Medical Center, Department of ANesthesiology and Pain Medicine	Seattle	Washington	United States	98195

Sponsors and Collaborators

• University of Washington
• Mallinckrodt

Investigators

• Study Director: Lisa Flint, BS, University of Washington
• Principal Investigator: Srdjan Jelacic, MD, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Srdjan Jelacic, Assistant Professor, University of Washington
• ClinicalTrials.gov Identifier: NCT01544062
• Other Study ID Numbers: 42204-D
• First Posted: Mar 5, 2012
• Last Update Posted: Jun 21, 2016
• Last Verified: May 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Srdjan Jelacic, Assistant Professor, University of Washington: Cardiac surgery; Acute Pain; Wound Hyperalgesia; Intravenous Acetaminophen; Patient Satisfaction
• Additional relevant MeSH terms: Hyperalgesia; Acute Pain; Acetaminophen

Study Results

Participant Flow

Arm/Group Title	IV Acetaminophen	Normal Saline
Arm/Group Description	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.	Study subjects receiving placebo
Period Title: Overall Study
STARTED	33	35
COMPLETED	33	35
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	IV Acetaminophen	Normal Saline	Total
Arm/Group Description	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.	Study subjects receiving placebo	Total of all reporting groups
Overall Participants	33	35	68
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	25 75.8%	22 62.9%	47 69.1%
>=65 years	8 24.2%	13 37.1%	21 30.9%
Sex: Female, Male (Count of Participants)
Female	4 12.1%	12 34.3%	16 23.5%
Male	29 87.9%	23 65.7%	52 76.5%
Region of Enrollment (participants) [Number]
United States	33 100%	35 100%	68 100%

Outcome Measures

1. Primary Outcome

Title	24 Hour Postoperative Opioid Consumption
Description	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

Outcome Measure Data

Analysis Population Description

Missing data for 1 study subject in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	34	33
Mean (Standard Deviation) [mg]	62.3 (29.5)	45.6 (29.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 95%; 2.3 to 31.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	48 Hour Postoperative Opioid Consumption
Description	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

Outcome Measure Data

Analysis Population Description

Missing data for 1 study subject in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo	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.
Measure Participants	34	33
Mean (Standard Deviation) [mg]	105.1 (42.1)	85.1 (42.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	24 Hour Postoperative Pain Scores at Rest
Description	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

Outcome Measure Data

Analysis Population Description

Missing data for 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo	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.
Measure Participants	32	33
Mean (Standard Deviation) [units on a scale]	3.9 (2.3)	3.7 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.724
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.510
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	48 Hour Postoperative Pain Scores at Rest
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 2 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo	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.
Measure Participants	33	33
Mean (Standard Deviation) [units on a scale]	2.4 (2.2)	2.0 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.397
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.458
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	24 Hour Postoperative Pain Scores With Movement
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo	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.
Measure Participants	32	33
Mean (Standard Deviation) [units on a scale]	6.3 (2.5)	6.0 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.600
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.509
	Comments
	Method	ANCOVA
	Comments	controlling for age, sex and body mass index

6. Secondary Outcome

Title	48 Hour Postoperative Pain Scores With Movement
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 2 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo	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.
Measure Participants	33	33
Mean (Standard Deviation) [units on a scale]	5.1 (2.9)	4.6 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.399
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.395
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	24 Hour Wound Hyperalgesia
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	32	33
Mean (Standard Deviation) [cm]	4.8 (4.3)	4.5 (3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.771
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.927
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	48 Hour Wound Hyperalgesia
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 2 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	33	33
Mean (Standard Deviation) [cm]	4.6 (3.9)	5.0 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.644
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Length of Mechanical Ventilation
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	35	33
Mean (Standard Deviation) [minutes]	407 (683)	360 (276)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.710
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Length of ICU Stay
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	35	33
Mean (Standard Deviation) [hours]	67 (35)	61 (27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.508
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.905
	Comments	controlling for age, sex and body mass index
	Method	ANCOVA
	Comments

11. Secondary Outcome

Title	48 Hour Patient Satisfaction
Description	"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

Outcome Measure Data

Analysis Population Description

Questionnaire not completed by 12 study subjects in normal saline group and 10 study subjects in IV acetaminophen group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	23	23
Mean (Standard Deviation) [units on a scale]	2.3 (1.2)	2.8 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.104
	Comments
	Method	t-test, 2 sided
	Comments

12. Secondary Outcome

Title	24 Hour Nausea
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	35	33
Number [participants]	25 75.8%	26 74.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.580
	Comments
	Method	Fisher Exact
	Comments

13. Secondary Outcome

Title	48 Hour Nausea
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	35	33
Number [participants]	12 36.4%	14 40%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.619
	Comments
	Method	Fisher Exact
	Comments

14. Secondary Outcome

Title	24 Hour Pruritus
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	32	33
Number [participants]	4 12.1%	7 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.511
	Comments
	Method	Fisher Exact
	Comments

15. Secondary Outcome

Title	48 Hour Pruritus
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 8 study subjects in normal saline group and 6 study subjects in IV acetaminophen group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	27	27
Number [participants]	4 12.1%	7 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.501
	Comments
	Method	Fisher Exact
	Comments

16. Secondary Outcome

Title	24 Hour Sedation
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	32	33
Number [participants]	8 24.2%	8 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

17. Secondary Outcome

Title	48 Hour Sedation
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 6 study subjects in normal saline group and 3 study subjects in IV acetaminophen group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	29	30
Number [participants]	6 18.2%	3 8.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.299
	Comments
	Method	Fisher Exact
	Comments

18. Secondary Outcome

Title	24 Hour Respiratory Depression
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	32	33
Number [participants]	2 6.1%	2 5.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

19. Secondary Outcome

Title	48 Hour Respiratory Depression
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 6 study subjects in normal saline group and 3 study subjects in IV acetaminophen group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	29	30
Number [participants]	1 3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.492
	Comments
	Method	Fisher Exact
	Comments

20. Secondary Outcome

Title	24 Hour Dizziness
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 3 study subjects in normal saline group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	32	33
Number [participants]	20 60.6%	17 48.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.455
	Comments
	Method	Fisher Exact
	Comments

21. Secondary Outcome

Title	48 Hour Dizziness
Description	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

Outcome Measure Data

Analysis Population Description

Missing data on 7 study subjects in normal saline group and 4 study subjects in IV acetaminophen group.

Arm/Group Title	Normal Saline	IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.	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.
Measure Participants	28	29
Number [participants]	9 27.3%	10 28.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Saline, IV Acetaminophen
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	18 month period between July 2012 and December 2013
Arm/Group Title	Normal Saline		IV Acetaminophen
Arm/Group Description	Study subjects receiving placebo Placebo: 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.		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.
All Cause Mortality
	Normal Saline		IV Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Normal Saline		IV Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Normal Saline		IV Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/33 (0%)

Limitations/Caveats

several subjects received intraoperative hydromorphone while others only received intraoperative fentanyl significantly greater proportion of females in the placebo group

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.