Propofol Versus Sevoflurane Recovery After Gynecological Surgery

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01755234
• Collaborator: (none)
• Enrollment: 90
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

80% of 25 million American who undergo surgery describe moderate to severe pain. The use of multimodal analgesic techniques can attenuate patient's postoperative pain and several different medication have been found to be effective. Pain can significantly affect patient's quality of recovery after surgery. Volatile anesthetics can increase sensitivity to pain at the low concentrations present on emergence from anesthesia. Propofol may have analgesic effect at sedative doses. The effects of propofol,when used for anesthesia maintenance, on postoperative pain have demonstrated controversial results with some investigators showing a potential benefit whereas others have not shown any benefit. Propofol for maintenance of anesthesia has been advocated as an strategy for high risk patients even though it has shown controversial results on reduction of Post operative nausea and vomiting. A comparison of propofol vs.volatile anesthetic in regards to the time required by patients to meet discharge criteria has also shown conflicting results.The QOR 40 is a validated instrument that has been specifically developed to evaluate patients recovery after anesthesia and surgery.

The purpose of this study is to compare the effects of maintenance of anesthesia with two agents (Propofol and Sevoflurane) on quality of recovery after ambulatory surgery

Significance: the results of this study can lead to the discovery of an anesthesia technique that is associated with a better recovery for patients after ambulatory surgery.

Research question is: do patients anesthetized with propofol have a better quality of recovery after ambulatory anesthesia than patients anesthetized with Sevoflurane? The hypothesis: patients anesthetized with propofol will have better quality of recovery than patients anesthetized with Sevoflurane after ambulatory surgery.

Condition or Disease	Intervention/Treatment	Phase
Surgery; Anesthesia	Drug: Sevoflurane; Drug: Propofol	Phase 4

Detailed Description

Subjects will be recruited up to the day of surgery. 90 subjects will be randomly allocated into 2 groups, using a computer generated table of random numbers: anesthetic maintenance with Sevoflurane or anesthetic maintenance with Propofol . Subjects will be premedicated with intravenous (IV) midazolam 0.04 mg/kg. Routine ASA monitors will be applied. Anesthesia will be induced with remifentanil infusion started at 0.1 mcg/kg/minute titrated to keep blood pressure within 20% of the baseline and propofol 1.0 -2.0 mg/kg or sevoflurane induction. Tracheal intubation will be facilitated with rocuronium (0.6 mg/kg) or succinylcholine (1-2mg /kg). Anesthesia will be maintained with Sevoflurane or a Propofol infusion titrated to keep a bispectral index between 40-60, remifentanil infusion started at 0.1mcg/kg/min titrated to keep blood pressure within 20 % of baseline values, and rocuronium that will be administered at the discretion of the anesthesiologist. Upon termination of the surgery, neuromuscular blockade will be antagonized with a combination of neostigmine 0.05mg/kg and glycopyrrolate 0.01 mg/kg. Subjects will also receive Ketorolac 30 mg IV after discontinuation of remifentanil for postoperative pain control. Ondansetron 4 mg IV will be administered to decrease postoperative nausea and vomiting. Subjects will receive IV hydromorphone 0.4 mg q 5 minutes as needed to achieve a verbal rating score for pain <4 out of 10.They will also receive reglan 10 mg IV as a rescue antiemetic, if not effective, a second dose of Zofran 4 mg IV will be given in PACU. 24 hours after surgery a QOR 40 will be administered to the patient by one of the investigators. The primary and secondary outcomes will be assessed by an independent observer who will be blinded to group allocation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of Propofol vs. Sevoflurane Administered During Anesthesia Maintenance on Early and Late Recovery After Gynecological Surgery
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sevoflurane Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube)	Drug: Sevoflurane; Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube; Other Names: Sevoflurane,Ultane
Active Comparator: Propofol Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60	Drug: Propofol; Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60; Other Names: Propofol,Diprivan

Outcome Measures

Primary Outcome Measures

1. Quality of Recovery Score 24 Hours Post Operative [24 hours after the surgical procedure]

   Quality of recovery score 24 hours after the surgical procedure.Score of 40 is poor recovery and a score of 200 is good recovery.

Secondary Outcome Measures

1. Mg of Morphine Equivalents (IV) [PACU admission to discharge]

   Total opioid use in the post operative care unit (Mg of morphine equivalents)

2. Pain in Post Anesthesia Care Unit [Time in the post anesthesia care unit]

   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). 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.

3. Opioid Use Discharge From Post Anesthesia Care Unit to 24 Hours After PACU Discharge. [Discharge from PACU to 24 hours post operative after PACU discharge.]

   Opioid use in mg of morphine equivalents from discharge from the post anesthesia care unit to 24 hours after PACU discharge.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women

• Age 18-64

• Patients undergoing ambulatory surgery

• ASA PS I, II

Exclusion Criteria:

• Chronic opioid use

• Pregnant patient

Drop Out : patient or surgeon request

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Prentice Women's Hospital	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

• Boccara G, Mann C, Pouzeratte Y, Bellavoir A, Rouvier A, Colson P. Improved postoperative analgesia with isoflurane than with propofol anaesthesia. Can J Anaesth. 1998 Sep;45(9):839-42.
• Cheng SS, Yeh J, Flood P. Anesthesia matters: patients anesthetized with propofol have less postoperative pain than those anesthetized with isoflurane. Anesth Analg. 2008 Jan;106(1):264-9, table of contents. doi: 10.1213/01.ane.0000287653.77372.d9.
• Hand R Jr, Riley GP, Nick ML, Shott S, Faut-Callahan M. The analgesic effects of subhypnotic doses of propofol in human volunteers with experimentally induced tourniquet pain. AANA J. 2001 Dec;69(6):466-70.
• Montes FR, Trillos JE, Rincón IE, Giraldo JC, Rincón JD, Vanegas MV, Charris H. Comparison of total intravenous anesthesia and sevoflurane-fentanyl anesthesia for outpatient otorhinolaryngeal surgery. J Clin Anesth. 2002 Aug;14(5):324-8.
• Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5.
• Röhm KD, Piper SN, Suttner S, Schuler S, Boldt J. Early recovery, cognitive function and costs of a desflurane inhalational vs. a total intravenous anaesthesia regimen in long-term surgery. Acta Anaesthesiol Scand. 2006 Jan;50(1):14-8. Retraction in: Acta Anaesthesiol Scand. 2011 Aug;55(7):903.
• Visser K, Hassink EA, Bonsel GJ, Moen J, Kalkman CJ. Randomized controlled trial of total intravenous anesthesia with propofol versus inhalation anesthesia with isoflurane-nitrous oxide: postoperative nausea with vomiting and economic analysis. Anesthesiology. 2001 Sep;95(3):616-26.
• Watson KR, Shah MV. Clinical comparison of 'single agent' anaesthesia with sevoflurane versus target controlled infusion of propofol. Br J Anaesth. 2000 Oct;85(4):541-6.
• White PF, Kehlet H. Improving postoperative pain management: what are the unresolved issues? Anesthesiology. 2010 Jan;112(1):220-5. doi: 10.1097/ALN.0b013e3181c6316e. Review.
• White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg. 2005 Nov;101(5 Suppl):S5-S22. doi: 10.1213/01.ANE.0000177099.28914.A7. Review.
• Zhang Y, Eger EI 2nd, Dutton RC, Sonner JM. Inhaled anesthetics have hyperalgesic effects at 0.1 minimum alveolar anesthetic concentration. Anesth Analg. 2000 Aug;91(2):462-6.

• Responsible Party: Gildasio De Oliveira, Prinipal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT01755234
• Other Study ID Numbers: STU00070833
• First Posted: Dec 24, 2012
• 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, Prinipal Investigator, Northwestern University: Outpatient; Surgery; Anesthesia
• Additional relevant MeSH terms: Propofol; Sevoflurane

Study Results

Participant Flow

Recruitment Details	Subjects were recruited 12/2012-04/2014. 101 subjects were assessed for eligibility, 4 did not meet inclusion criteria and 7 declined to participate. 90 subjects were randomized.

Arm/Group Title	Sevoflurane	Propofol
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube	Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60
Period Title: Overall Study
STARTED	45	45
COMPLETED	30	37
NOT COMPLETED	15	8

Baseline Characteristics

Arm/Group Title	Sevoflurane	Propofol	Total
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube	Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60	Total of all reporting groups
Overall Participants	45	45	90
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	45 100%	45 100%	90 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	45 100%	45 100%	90 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%	45 100%	90 100%

Outcome Measures

1. Primary Outcome

Title	Quality of Recovery Score 24 Hours Post Operative
Description	Quality of recovery score 24 hours after the surgical procedure.Score of 40 is poor recovery and a score of 200 is good recovery.
Time Frame	24 hours after the surgical procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sevoflurane	Propofol
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube	Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60
Measure Participants	30	37
Median (Inter-Quartile Range) [units on a scale]	175	176

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sevoflurane, Propofol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Mg of Morphine Equivalents (IV)
Description	Total opioid use in the post operative care unit (Mg of morphine equivalents)
Time Frame	PACU admission to discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sevoflurane	Propofol
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube	Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60
Measure Participants	30	37
Median (Inter-Quartile Range) [miligrams of morphine equivalents]	9	9.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sevoflurane, Propofol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Pain in Post Anesthesia Care Unit
Description	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). 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sevoflurane	Propofol
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube	Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60
Measure Participants	30	37
Median (Inter-Quartile Range) [Pain Score * minutes in PACU]	270	240

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sevoflurane, Propofol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.96
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Opioid Use Discharge From Post Anesthesia Care Unit to 24 Hours After PACU Discharge.
Description	Opioid use in mg of morphine equivalents from discharge from the post anesthesia care unit to 24 hours after PACU discharge.
Time Frame	Discharge from PACU to 24 hours post operative after PACU discharge.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sevoflurane	Propofol
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube	Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60
Measure Participants	30	37
Median (Inter-Quartile Range) [mg morphine equivalents]	30	25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sevoflurane, Propofol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.84
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Time in the post anesthesia care unit.
Adverse Event Reporting Description	Nausea experienced in the post anesthesia care unit
Arm/Group Title	Sevoflurane		Propofol
Arm/Group Description	Sevoflurane administered by inhalation (laryngeal mask airway or endotracheal tube) Sevoflurane: Sevfoflurane inhaled administered by laryngeal mask airway or endotracheal tube		Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60 Propofol: Propofol administered via intravenous catheter at an initial rate of 1.0 -2.0 mg/kg then the Propofol infusion rate will be titrated to keep a bispectral index between 40-60
All Cause Mortality
	Sevoflurane		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sevoflurane		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Sevoflurane		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/30 (43.3%)		11/37 (29.7%)
Gastrointestinal disorders
Nausea	13/30 (43.3%)	13	11/37 (29.7%)	11
Vomiting	3/30 (10%)	3	1/37 (2.7%)	1

Limitations/Caveats

We only studied patients undergoing outpatient laparoscopic gynecological surgery, therefore, our results cannot be generalizable to other surgical procedures. We also administered remifentanil which is has been linked to hyperalgesia.

More Information

Certain Agreements

All Principal Investigators ARE 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.