SPRAY: Surgical Pain Control With Ropivacaine by Atomized Delivery

• Sponsor: Loyola University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01480089
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

The purpose of this trial is to determine the effect of spraying a local anesthetic called Ropivacaine (numbing medicine) into the abdominal cavity prior to surgery. Ropivacaine is a local anesthetic used to block pain in the body. There are studies showing that Ropivacaine decreases the pain of surgery with minimally invasive (laparoscopic) appendix and gallbladder removal but has not been tried in robotic pelvic surgery.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Intraperitoneal Ropivacaine (AIR); Drug: Atomized Intraperitoneal Saline (AIS)	Phase 4

Detailed Description

Practice guidelines from the American Society of Anesthesiologists peri-operative techniques for pain management have remained essentially unchanged over the last 10 years (3). Current acute pain-management strategies include 1.) Epidural or intrathecal opioids 2.) Patient-controlled devices delivering systemic opioids and 3.) Regional techniques such as peripheral nerve blocks and post-incisional infiltration with local anesthetics.

The use of epidural and systemic opioids results in significant side-effects such as post-operative nausea and ileus which often lead to increased hospital stay. The literature supporting the benefit of preincisional infiltration with anesthetics remains equivocal.

A recently published study describes the use of intraperitoneal Ropivacaine (2mh/kg) during laparoscopic appendectomy(4). The study was a randomized, double-blinded, placebo-controlled study using Ropivacaine (vs placebo) injected through the laparoscopic ports prior to the start of the appendectomy in 63 patients(4).

Patients treated with Ropivacaine had a significant decrease in visual analog pain scores post-operatively and had decreased narcotic use during their hospital stay compared to placebo. There were no side-effects found with the one-time use of the Ropivacaine.

The results of the above study and review of an additional 24 randomized controlled trials conducted from 1993-2003 are not felt to be generalizable to pelvic surgery where port placement and the operative procedures vary significantly. Hence this study was undertaken to investigate the role of intraperitoneal Ropivacaine as an adjuvant to muscle relaxants and narcotics at the time of pelvic surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Surgical Pain Control With Ropivacaine by Atomized Delivery
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Atomized Intraperitoneal Saline (AIS) Participants randomized to this arm will be given atomized intraperitoneal saline(AIS).	Drug: Atomized Intraperitoneal Saline (AIS); Atomized saline will be administered to the peritoneal cavity at the completion of surgery.; Other Names: Placebo
Active Comparator: Intraperitoneal Ropivacaine(AIR) Participants randomized to this arm will receive atomized intraperitoneal ropivacaine (AIR).	Drug: Intraperitoneal Ropivacaine (AIR); Ropivacaine 2 mg/kg per lean body mass up to no more than 200mg total dose will be atomized and delivered into the peritoneal cavity at the completion of surgery.; Other Names: Ropivacaine

Outcome Measures

Primary Outcome Measures

1. Post-op Pain With Atomized Intraperitoneal Ropivacaine (AIR) [2 hours after surgery]

   Participants are asked to rate their pain level using the visual analog scale (VAS). The VAS is a measurement of pain where respondents specify their level of pain by indicating a position along a continuous line between two end-points. The VAS used in this study was a horizontal line of 100 mm length anchored by two word descriptors - one word at each end: No pain (left end) and Very Severe Pain (right end). The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks. The VAS range is 0 to 100.

Secondary Outcome Measures

1. Post-op Pain With Atomized Intraperitoneal Ropivacaine (AIR) [12 hours after surgery]

   Participants are asked to rate their pain level using the visual analog scale (VAS). The VAS is a measurement of pain where respondents specify their level of pain by indicating a position along a continuous line between two end-points. The VAS used in this study was a horizontal line of 100 mm length anchored by two word descriptors - one word at each end: No pain (left end) and Very Severe Pain (right end). The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks. The VAS range is 0 to 100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Consent to undergo robotic assisted gynecologic or urologic surgery

• Between the ages of 18 and 75

• Able to consent, fill out study documents, and complete all study procedures and follow-up visits

Exclusion Criteria:

• Patients with an allergy to local anesthetics

• Patients with severe underlying cardiovascular, renal or hepatic disease

• Pregnant patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola University Medical Center	Maywood	Illinois	United States	60153

Sponsors and Collaborators

• Loyola University

Investigators

• Principal Investigator: Elizabeth Mueller, MD, Loyola 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.
• Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540. doi: 10.1213/01.ANE.0000068822.10113.9E.
• Bleckner LL, Bina S, Kwon KH, McKnight G, Dragovich A, Buckenmaier CC 3rd. Serum ropivacaine concentrations and systemic local anesthetic toxicity in trauma patients receiving long-term continuous peripheral nerve block catheters. Anesth Analg. 2010 Feb 1;110(2):630-4. doi: 10.1213/ANE.0b013e3181c76a33. Epub 2009 Dec 2.
• Boddy AP, Mehta S, Rhodes M. The effect of intraperitoneal local anesthesia in laparoscopic cholecystectomy: a systematic review and meta-analysis. Anesth Analg. 2006 Sep;103(3):682-8. Review.
• Hartog CS, Rothaug J, Goettermann A, Zimmer A, Meissner W. Room for improvement: nurses' and physicians' views of a post-operative pain management program. Acta Anaesthesiol Scand. 2010 Mar;54(3):277-83. doi: 10.1111/j.1399-6576.2009.02161.x. Epub 2009 Nov 12.
• Kang H, Kim BG. Intraperitoneal ropivacaine for effective pain relief after laparoscopic appendectomy: a prospective, randomized, double-blind, placebo-controlled study. J Int Med Res. 2010 May-Jun;38(3):821-32.
• Labaille T, Mazoit JX, Paqueron X, Franco D, Benhamou D. The clinical efficacy and pharmacokinetics of intraperitoneal ropivacaine for laparoscopic cholecystectomy. Anesth Analg. 2002 Jan;94(1):100-5, table of contents.
• McClure JH. Ropivacaine. Br J Anaesth. 1996 Feb;76(2):300-7. Review.
• Mueller ER, Kenton K, Anger JT, Bresee C, Tarnay C. Cosmetic Appearance of Port-site Scars 1 Year After Laparoscopic Versus Robotic Sacrocolpopexy: A Supplementary Study of the ACCESS Clinical Trial. J Minim Invasive Gynecol. 2016 Sep-Oct;23(6):917-21. doi: 10.1016/j.jmig.2016.05.001. Epub 2016 May 12.

• Responsible Party: Elizabeth Mueller, Associate Professor, Loyola University
• ClinicalTrials.gov Identifier: NCT01480089
• Other Study ID Numbers: 203353
• First Posted: Nov 28, 2011
• Last Update Posted: Jul 27, 2016
• Last Verified: Jun 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Elizabeth Mueller, Associate Professor, Loyola University: Surgical Pain Management; Robotic surgery; Ropivacaine
• Additional relevant MeSH terms: Ropivacaine

Study Results

Participant Flow

Recruitment Details	Women undergoing minimally invasive laparoscopic surgery in urogynecology, benign gynecology, and gynecologic-oncology clinics were recruited. All women who were scheduled to undergo a minimally invasive hysterectomy for benign and cancerous conditions between February 2012 and March 2013 were invited to participate.
Pre-assignment Detail	One enrolled participant was excluded from the trial before assignment to groups because her physician prescribed Ropivacaine and, consequently, the participant was converted to open label before study drug was assigned or administered.

Arm/Group Title	Atomized Intraperitoneal Saline (AIS)	Intraperitoneal Ropivacaine(AIR)
Arm/Group Description	Participants randomized to this arm are given atomized intraperitoneal saline(AIS) to the peritoneal cavity at the completion of surgery.	Participants randomized to this arm receive atomized intraperitoneal ropivacaine (AIR). That is, 2 mg/kg of lean body mass up to no more than 200mg total dose is atomized and delivered into the peritoneal cavity at the completion of surgery.
Period Title: Overall Study
STARTED	25	30
COMPLETED	25	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intraperitoneal Ropivacaine(AIR)	Atomized Intraperitoneal Saline (AIS)	Total
Arm/Group Description	Participants randomized to this arm receive atomized intraperitoneal ropivacaine (AIR). That is, 2 mg/kg of lean body mass up to no more than 200mg total dose is atomized and delivered into the peritoneal cavity at the completion of surgery.	Participants randomized to this arm are given atomized intraperitoneal saline(AIS) to the peritoneal cavity at the completion of surgery.	Total of all reporting groups
Overall Participants	25	30	55
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54.6	58.8	56.9
Sex: Female, Male (Count of Participants)
Female	25 100%	30 100%	55 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	21 84%	22 73.3%	43 78.2%
Black	2 8%	5 16.7%	7 12.7%
Hispanic	1 4%	2 6.7%	3 5.5%
Asian	1 4%	1 3.3%	2 3.6%
Surgical Approach (participants) [Number]
Laparoscopic	11 44%	11 36.7%	22 40%
Robotic	14 56%	19 63.3%	33 60%
Attending Specialty (participants) [Number]
Benign Gynecology	2 8%	4 13.3%	6 10.9%
Urogynecology	12 48%	14 46.7%	26 47.3%
Gynecologic Oncology	11 44%	12 40%	23 41.8%
Length of Hospital Stay (participants) [Number]
Less than 24 hours	0 0%	0 0%	0 0%
24 to 48 hours	19 76%	23 76.7%	42 76.4%
Greater than 48 hours	6 24%	7 23.3%	13 23.6%

Outcome Measures

1. Primary Outcome

Title	Post-op Pain With Atomized Intraperitoneal Ropivacaine (AIR)
Description	Participants are asked to rate their pain level using the visual analog scale (VAS). The VAS is a measurement of pain where respondents specify their level of pain by indicating a position along a continuous line between two end-points. The VAS used in this study was a horizontal line of 100 mm length anchored by two word descriptors - one word at each end: No pain (left end) and Very Severe Pain (right end). The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks. The VAS range is 0 to 100.
Time Frame	2 hours after surgery

Outcome Measure Data

Analysis Population Description

All individuals randomized are included in this analysis.

Arm/Group Title	Intraperitoneal Ropivacaine(AIR)	Atomized Intraperitoneal Saline (AIS)
Arm/Group Description	Participants randomized to this arm receive atomized intraperitoneal ropivacaine (AIR). That is, 2 mg/kg of lean body mass up to no more than 200mg total dose is atomized and delivered into the peritoneal cavity at the completion of surgery.	Participants randomized to this arm are given atomized intraperitoneal saline(AIS) to the peritoneal cavity at the completion of surgery.
Measure Participants	25	30
Mean (Standard Deviation) [millimeters]	2.536 (2.7)	3.844 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intraperitoneal Ropivacaine(AIR), Atomized Intraperitoneal Saline (AIS)
	Comments	The null hypothesis is that the mean VAS score 2 hours post surgery is equivalent for individuals randomized to Intraperitoneal Ropivacaine(AIR) and those randomized to Atomized Intraperitoneal Saline (AIS).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.098
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.308
	Confidence Interval	(2-Sided) 95%; -2.830 to 0.214
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.777
	Estimation Comments

2. Secondary Outcome

Title	Post-op Pain With Atomized Intraperitoneal Ropivacaine (AIR)
Description	Participants are asked to rate their pain level using the visual analog scale (VAS). The VAS is a measurement of pain where respondents specify their level of pain by indicating a position along a continuous line between two end-points. The VAS used in this study was a horizontal line of 100 mm length anchored by two word descriptors - one word at each end: No pain (left end) and Very Severe Pain (right end). The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks. The VAS range is 0 to 100.
Time Frame	12 hours after surgery

Outcome Measure Data

Analysis Population Description

All individuals randomized are included in this analysis.

Arm/Group Title	Intraperitoneal Ropivacaine(AIR)	Atomized Intraperitoneal Saline (AIS)
Arm/Group Description	Participants randomized to this arm receive atomized intraperitoneal ropivacaine (AIR). That is, 2 mg/kg of lean body mass up to no more than 200mg total dose is atomized and delivered into the peritoneal cavity at the completion of surgery.	Participants randomized to this arm are given atomized intraperitoneal saline(AIS) to the peritoneal cavity at the completion of surgery.
Measure Participants	25	30
Mean (Standard Deviation) [millimeters]	2.154 (1.9)	2.219 (2.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intraperitoneal Ropivacaine(AIR), Atomized Intraperitoneal Saline (AIS)
	Comments	The null hypothesis is that the mean VAS score 12 hours post surgery is equivalent for individuals randomized to Intraperitoneal Ropivacaine(AIR) and those randomized to Atomized Intraperitoneal Saline (AIS).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.90
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.065
	Confidence Interval	(2-Sided) 95%; -1.103 to 0.973
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.530
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected between August 19, 2011 and February 20, 2013 (1 year, 6.1 months)
Arm/Group Title	Intraperitoneal Ropivacaine(AIR)		Atomized Intraperitoneal Saline (AIS)
Arm/Group Description	Participants randomized to this arm receive atomized intraperitoneal ropivacaine (AIR). That is, 2 mg/kg of lean body mass up to no more than 200mg total dose is atomized and delivered into the peritoneal cavity at the completion of surgery.		Participants randomized to this arm are given atomized intraperitoneal saline(AIS) to the peritoneal cavity at the completion of surgery.
All Cause Mortality
	Intraperitoneal Ropivacaine(AIR)		Atomized Intraperitoneal Saline (AIS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intraperitoneal Ropivacaine(AIR)		Atomized Intraperitoneal Saline (AIS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Intraperitoneal Ropivacaine(AIR)		Atomized Intraperitoneal Saline (AIS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/30 (0%)

Limitations/Caveats

There are no caveats to report.

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.