Perioperative Systemic Acetaminophen to Improve Postoperative Quality of Recovery After Ambulatory Breast Surgery

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01852955
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Duration (Months): 13
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

Recent evidence demonstrates that perioperative pain continues to be poorly managed among ambulatory surgical patients. More importantly, few interventions that minimize postoperative pain have also shown to improve patient overall quality of post-surgical recovery. Ketorolac has been used to minimize perioperative pain despite the lack of evidence for its use when administered as a single dose preventive strategy.Ketorolac has also been associated with a higher incidence of perioperative hematomas and the need for surgical re-exploration after breast surgery.

Systemic acetaminophen has become recently available in The United States. In contrast to ketorolac, systemic acetaminophen has not been reported to have adverse side effects on patients undergoing breast surgery. Although evidence suggests that a single dose perioperative acetaminophen reduces postoperative pain, it remains unknown if a single dose intravenous acetaminophen improves postoperative quality of recovery after ambulatory surgery.

The main objective of the current investigation is to evaluate the effect of a single dose systemic acetaminophen on postoperative quality of recovery after ambulatory breast surgery. We also seek to determine if systemic acetaminophen would decrease postoperative pain and the time to hospital discharge in the same population.

Significance: The current project evaluates a potential intervention to improve perioperative pain and recovery after ambulatory breast surgery. Postoperative pain in the ambulatory surgical patients has been shown consistently to be poorly managed.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: IV acetaminophen; Drug: Placebo	N/A

Detailed Description

Patients will be recruited up to the day of surgery. They will be then randomized using a computer generated table of random numbers to two groups: Group A (IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure) and Group B (placebo group-same volume of saline solution administered in the same fashion).This dose has been commonly used in other studies involving IV acetaminophen.6 Both drugs will be identical and will be prepared by hospital pharmacy. After placement of standard ASA monitors, induction will be performed with 0.1mcg/kg/min of remifentanil IV, propofol 1.5-2.5 mg/kg IV and succinylcholine 1-2 mg/kg IV. Tracheal intubation will be performed using a MAC 3 blade and a size 7 endotracheal tube. Maintenance will be achieved with remifentanil infusion titrated to keep the blood pressure within 20% of baseline values and sevoflurane titrated to keep a bispectral index monitor between 40 and 60. Patients will receive ondansetron 4mg IV and dexamethasone 4 mg IV for postoperative nausea and vomiting prophylaxis. In the recovery room patients will receive hydromorphone IV in divided doses to keep pain <4/10(scale where 0 means no pain and 10 is the worst pain) and metoclopramide 10 mg IV as rescue antiemetic. Data will be collected by a research assistant blinded to the group allocation. Data collected will involve pain at PACU arrival (NRS-0-10), presence of nausea and vomiting, severity of nausea and vomiting, total opioid consumption in PACU, time to discharge using a Modified Postanaesthetic Discharge Scoring System (MPADSS) 9, total opioid consumption 24 hours, QoR40 24hours after surgery.8

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Perioperative Systemic Acetaminophen to Improve Postoperative Quality of Recovery After Ambulatory Breast Surgery
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IV acetaminophen Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure.	Drug: IV acetaminophen; Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure
Placebo Comparator: Placebo Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen	Drug: Placebo; Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen

Outcome Measures

Primary Outcome Measures

1. Quality of Recovery at 24 Hours(QoR-40 Instrument) [24 hours after the surgical procedure]

   Quality of recovery score 24 hours after the surgical procedure. Total score range of 40 (poor recovery) and a score of 200 (good recovery).

Secondary Outcome Measures

1. Postoperative Opioid Consumption [24 hour]

   Postoperative opioid consumption over 24 hours. Converted into oral mg of morpine equivalents.

2. Postoperative Pain in the Post Anesthesia Care Unit [Time in the post anesthesia care unit after surgery (average of 5 hours)]

   Postoperative pain within the post anesthesia care unit after surgery. Area under the numeric rating scale for pain versus time curve in the post anesthesia care unit (score * min).Numeric rating scale for pain on a scale of 0-10 (0 is no pain and 10 is high pain) versus time curve in the post anesthesia care unit ( score * min). Area under a curve units of the horizontal axis multiplied by the units of the vertical axis. A higher value indicates more pain and time in the Post Anesthesia Care Unit.The range is 0 pain to x time in minutes x 1 hour to 5 hour ( 60-300 minutes) . The pain scores were collected at 15 minute intervals from the time of admission to the PACU. The area under the NRS pain scale versus time curve was calculated using the trapezoidal method as an indicator of pain burden during early recovery (Graph Pad Prism ver 5.03, Graph Pad Software INC.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatient lumpectomy

• ASA I and II

• Age between 18-70

Exclusion:

• Pregnancy

• History of liver disease

• Unable to understand the informed consent

• Chronic pain with use of opioid in the last week

• Allergy to acetaminophen

Drop-out: surgeon or patient request

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Gildasio De Oliveira, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

• American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012 Feb;116(2):248-73. doi: 10.1097/ALN.0b013e31823c1030.
• Cawthorn TR, Phelan R, Davidson JS, Turner KE. Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty. Can J Anaesth. 2012 May;59(5):466-72. doi: 10.1007/s12630-012-9682-z. Epub 2012 Mar 21.
• De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. Anesth Analg. 2012 Feb;114(2):424-33. doi: 10.1213/ANE.0b013e3182334d68. Epub 2011 Sep 29. Review.
• De Oliveira GS Jr, Ahmad S, Fitzgerald PC, Marcus RJ, Altman CS, Panjwani AS, McCarthy RJ. Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery. Br J Anaesth. 2011 Sep;107(3):362-71. doi: 10.1093/bja/aer156. Epub 2011 Jun 13.
• De Oliveira GS Jr, Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg. 2012 Aug;115(2):262-7. doi: 10.1213/ANE.0b013e318257a380. Epub 2012 May 14.
• McNicol ED, Tzortzopoulou A, Cepeda MS, Francia MB, Farhat T, Schumann R. Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: a systematic review and meta-analysis. Br J Anaesth. 2011 Jun;106(6):764-75. doi: 10.1093/bja/aer107. Epub 2011 May 9. Review.

• Responsible Party: Gildasio De Oliveira, Principal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT01852955
• Other Study ID Numbers: STU00078104
• First Posted: May 14, 2013
• Last Update Posted: Mar 14, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Gildasio De Oliveira, Principal Investigator, Northwestern University: Outpatient; Surgery; Breast; Pain
• Additional relevant MeSH terms: Acetaminophen

Study Results

Participant Flow

Arm/Group Title	IV Acetaminophen	Placebo
Arm/Group Description	Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure. IV acetaminophen: Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure	Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen Placebo: Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen
Period Title: Overall Study
STARTED	35	35
COMPLETED	33	32
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	IV Acetaminophen	Placebo	Total
Arm/Group Description	Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure. IV acetaminophen: Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure	Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen Placebo: Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen	Total of all reporting groups
Overall Participants	33	32	65
Age, Customized (years) [Mean (Full Range) ]
Age	60	52	55
Sex: Female, Male (Count of Participants)
Female	33 100%	32 100%	65 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	33 100%	32 100%	65 100%

Outcome Measures

1. Primary Outcome

Title	Quality of Recovery at 24 Hours(QoR-40 Instrument)
Description	Quality of recovery score 24 hours after the surgical procedure. Total score range of 40 (poor recovery) and a score of 200 (good recovery).
Time Frame	24 hours after the surgical procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Acetaminophen	Placebo
Arm/Group Description	Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure. IV acetaminophen: Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure	Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen Placebo: Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen
Measure Participants	33	32
Median (Inter-Quartile Range) [units on a scale]	189	183

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Acetaminophen, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.01
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Postoperative Opioid Consumption
Description	Postoperative opioid consumption over 24 hours. Converted into oral mg of morpine equivalents.
Time Frame	24 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Acetaminophen	Placebo
Arm/Group Description	Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure. IV acetaminophen: Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure	Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen Placebo: Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen
Measure Participants	33	32
Median (Inter-Quartile Range) [oral mg of morpine equivalents]	20	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Acetaminophen, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Postoperative Pain in the Post Anesthesia Care Unit
Description	Postoperative pain within the post anesthesia care unit after surgery. Area under the numeric rating scale for pain versus time curve in the post anesthesia care unit (score * min).Numeric rating scale for pain on a scale of 0-10 (0 is no pain and 10 is high pain) versus time curve in the post anesthesia care unit ( score * min). Area under a curve units of the horizontal axis multiplied by the units of the vertical axis. A higher value indicates more pain and time in the Post Anesthesia Care Unit.The range is 0 pain to x time in minutes x 1 hour to 5 hour ( 60-300 minutes) . The pain scores were collected at 15 minute intervals from the time of admission to the PACU. The area under the NRS pain scale versus time curve was calculated using the trapezoidal method as an indicator of pain burden during early recovery (Graph Pad Prism ver 5.03, Graph Pad Software INC.
Time Frame	Time in the post anesthesia care unit after surgery (average of 5 hours)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Acetaminophen	Placebo
Arm/Group Description	Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure. IV acetaminophen: Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure	Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen Placebo: Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen
Measure Participants	33	32
Median (Inter-Quartile Range) [(units on a scale * minutes]	255	240

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.36
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Development of nausea 24 hours after surgery.
Arm/Group Title	IV Acetaminophen		Placebo
Arm/Group Description	Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure. IV acetaminophen: Administration of IV acetaminophen 1000 mg over 15 minutes at the start of surgical closure		Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen Placebo: Administration of placebo (sterile normal saline)group-same volume of saline solution administered in the same fashion as the acetaminophen
All Cause Mortality
	IV Acetaminophen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IV Acetaminophen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	IV Acetaminophen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/33 (48.5%)		12/32 (37.5%)
Gastrointestinal disorders
Vomiting	3/33 (9.1%)	3	1/32 (3.1%)	1
Nausea	13/33 (39.4%)	13	11/32 (34.4%)	11

Limitations/Caveats

[Not Specified]

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.