Analgesia in Laparoscopic Cholecystectomy

• Sponsor: University of Athens (Other)
• Overall Status: Completed
• CT.gov ID: NCT01388946
• Collaborator: (none)
• Enrollment: 110
• Locations: 2
• Arms: 2
• Duration (Months): 44.1
• Patients Per Site: 55
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The investigators hypothesis is that perioperative infusion of 0.75 ropivacaine in patients undergoing laparoscopic cholecystectomy may modify the intensity of postoperative pain or the analgesic consumption during the first 24 hours.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative; Chronic Postoperative Pain	Drug: Ropivacaine 0.75; Drug: Normal saline	N/A

Detailed Description

Patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive via a subcutaneous catheter 2 ml per hour of 0.75 ropivacaine or same volume of normal saline. The catheter was inserted after induction of general anesthesia and before beginning of surgery and continued for the first 24 postoperative hours. The solutions were administered by means of an elastomeric pump. Before induction of anesthesia metoclopramide 10 mg, ranitidine 50 mg and droperidol 0.75 mg were given intravenously. In the operating room the routine monitoring was applied. Anesthesia was induced with thiopental 5-6 mg/kg, fentanyl 2 μg/kg, and rocuronium 0.6 mg/kg, and maintained with sevoflurane 1-1.5 Minimum Alveolar Concentration (MAC) in a nitrous oxide/oxygen mixture. After induction of anesthesia diclofenac 75 mg I.V was given within 30 min. Before wound closure each hole was infiltrated with 2 ml of ropivacaine 0.75 or normal saline. At the end of surgery neuromuscular block was reversed with sugammadex 2 mg/kg., the patient was extubated and transferred to the Post-anesthesia Care Unit (PACU).

Intra-operatively, the intra-abdominal pressure, the rate of carbon dioxide insufflation and the total amount of carbon dioxide insufflated are recorded every 5 minutes.

Besides the ropivacaine infusion in the operative site, postoperative analgesia is assured in the PACU with paracetamol 1 gr and tramadol 100 mg if Visual Analogue Scale (VAS) score is above 40 mm.In the ward Lonarid tablets are given instead.

VAS values and analgesic consumption are recorded in the PACU, and 2, 4, 8, 24 and 48 hours after surgery.

The catheter is removed 24 hours after surgery. One and three months after surgery patients are interviewed by phone for the presence of pain due to surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Perioperative Ropivacaine Wound Infusion in Laparoscopic Cholecystectomy. A Randomized Controlled Double-blind Trial
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ropivacaine 0.75 Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours	Drug: Ropivacaine 0.75; Other Names: Naropeine
Placebo Comparator: Normal saline Continuous infusion of normal saline 2 ml/h for 24 hours	Drug: Normal saline; Other Names: 0.9% saline

Outcome Measures

Primary Outcome Measures

1. VAS Score Changes ( Cough) During 24 h Postoperatively [24 h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

Secondary Outcome Measures

1. Pain Scores in the Postoperative Care Unit (PACU) at Rest [in PACU]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

2. Pain Scores at Rest 2 h Postoperatively [2 h postoperatively]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

3. Pain Scores at Rest 4 h Postoperatively [4 h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

4. Pain Scores at Rest 8 h Postoperatively [8 h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

5. Pain Scores at Rest 24 h Postoperatively [24h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

6. Pain Scores at Rest 48 h Postoperatively [48 h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

7. Pain Scores During Cough in the PACU [PACU]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

8. Pain Scores During Cough 2 h Postoperatively [2 h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

9. Pain Scores During Cough 4 h Postoperatively [4 h]

   Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

10. Pain Scores During Cough 8 h Postoperatively [8 h]

    Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

11. Pain Scores During Cough 48 h Postoperatively [48 h]

    Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.

12. Chronic Pain [one month postoperatively]

    Number and incidence of patients with persisting pain (burning pain, loss of sensation) one month postoperatively

13. Chronic Pain [three months]

    Number and incidence of patients with persisting pain (burning pain, loss of sensation) three month postoperatively

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients aged 30-70 years American Society of Anesthesiology (ASA) physical status I-III

• Scheduled for laparoscopic cholecystectomy

Exclusion Criteria:

• Patients with chronic pain and/or on analgesics for the last month,

• Patients with central nervous, kidney and liver disease, or allergy to local anesthetics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Anesthesia, St Savas Hospital	Athens		Greece	11522
2	Aretaieio Hospital	Athens		Greece	11528

Sponsors and Collaborators

• University of Athens

Investigators

• Principal Investigator: Emilia Vassi, St Savvas Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Argyro Fassoulaki, MD, PhD, DEAA, University of Athens
• ClinicalTrials.gov Identifier: NCT01388946
• Other Study ID Numbers: 149/27.5.10 & Σ-147/03-08-10
• First Posted: Jul 7, 2011
• Last Update Posted: Jul 6, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Argyro Fassoulaki, MD, PhD, DEAA, University of Athens: acute postoperative pain; late pain; chronic pain; wound irrigation with local anesthetic
• Additional relevant MeSH terms: Pain, Postoperative; Ropivacaine

Study Results

Participant Flow

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Period Title: Overall Study
STARTED	55	55
COMPLETED	49	52
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Ropivacaine 0.75	Normal Saline	Total
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline	Total of all reporting groups
Overall Participants	55	55	110
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	49 89.1%	48 87.3%	97 88.2%
>=65 years	6 10.9%	7 12.7%	13 11.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (11.2)	48 (12.5)	50 (11.9)
Sex: Female, Male (Count of Participants)
Female	38 69.1%	41 74.5%	79 71.8%
Male	17 30.9%	14 25.5%	31 28.2%
Region of Enrollment (participants) [Number]
Greece	55 100%	55 100%	110 100%

Outcome Measures

1. Primary Outcome

Title	VAS Score Changes ( Cough) During 24 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	24 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary (VAS score at cough) and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	32 (26)	31 (25)

2. Secondary Outcome

Title	Pain Scores in the Postoperative Care Unit (PACU) at Rest
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	in PACU

Outcome Measure Data

Analysis Population Description

Below is the mean and standard deviation of the VAS scores in PACU at rest Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	36 (25)	46 (21)

3. Secondary Outcome

Title	Pain Scores at Rest 2 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	2 h postoperatively

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery. Below are the VAS values (mean and standard deviation) 2 h postoperatively at rest

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	26 (21)	30 (23)

4. Secondary Outcome

Title	Pain Scores at Rest 4 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	4 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) at rest 4 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	16 (18)	22 (20)

5. Secondary Outcome

Title	Pain Scores at Rest 8 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	8 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) at rest 8 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	17 (22)	20 (21)

6. Secondary Outcome

Title	Pain Scores at Rest 24 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	24h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) at rest 24 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	14 (16)	15 (21)

7. Secondary Outcome

Title	Pain Scores at Rest 48 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	48 h

Outcome Measure Data

Analysis Population Description

50 patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. 1 patient in this group presented ileus after the first 24 h assessment, remaining 49 patients for assessment at 48 hours postoperatively Below are the VAS values (mean and standard deviation) at rest 48 hours postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	49	52
Mean (Standard Deviation) [mm]	8 (11)	12 (15)

8. Secondary Outcome

Title	Pain Scores During Cough in the PACU
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	PACU

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) during cough in PACU

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	42 (27)	55 (24)

9. Secondary Outcome

Title	Pain Scores During Cough 2 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	2 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) during cough 2 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	36 (27)	55 (24)

10. Secondary Outcome

Title	Pain Scores During Cough 4 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	4 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) during cough 4 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	25 (19)	34 (23)

11. Secondary Outcome

Title	Pain Scores During Cough 8 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	8 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) 8 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	50	52
Mean (Standard Deviation) [mm]	29 (25)	34 (24)

12. Secondary Outcome

Title	Pain Scores During Cough 48 h Postoperatively
Description	Visual Analogue Scale (VAS) measuring pain intensity (mm) with total range 0-100 and with 0 representing no pain and 100 representing possible worst pain.
Time Frame	48 h

Outcome Measure Data

Analysis Population Description

Fifty patients in the Ropivacaine group were analyzed for the primary and secondary outcomes 24 hours postoperatively. One patient in this group presented ileus after the first 24 h and was not assessed for pain 48 h after surgery Below are the VAS values (mean and standard deviation) during cough 48 h postoperatively

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	49	52
Mean (Standard Deviation) [mm]	18 (17)	26 (21)

13. Secondary Outcome

Title	Chronic Pain
Description	Number and incidence of patients with persisting pain (burning pain, loss of sensation) one month postoperatively
Time Frame	one month postoperatively

Outcome Measure Data

Analysis Population Description

Below the number of patients with pain one month postoperatively For the chronic pain assessment in the control group we had two dropouts as contact for two patients was not feasible.

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	49	50
Number [number of participants]	5 9.1%	7 12.7%

14. Secondary Outcome

Title	Chronic Pain
Description	Number and incidence of patients with persisting pain (burning pain, loss of sensation) three month postoperatively
Time Frame	three months

Outcome Measure Data

Analysis Population Description

Below the number of patients with pain three months postoperatively. For the chronic pain assessment in the control group we had two dropouts as contact for two patients was not feasible.

Arm/Group Title	Ropivacaine 0.75	Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75	Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
Measure Participants	49	50
Number [Number of participants]	2 3.6%	4 7.3%

Adverse Events

Time Frame	According to study design no adverse events were planned to be collected but in case of adverse events these are routinely included in patient's records for 24 hours postoperatively
Arm/Group Title	Ropivacaine 0.75		Normal Saline
Arm/Group Description	Continuous infusion of ropivacaine 7.5 mg/ml, 2 ml/h for 24 hours Ropivacaine 0.75		Continuous infusion of normal saline 2 ml/h for 24 hours Normal saline
All Cause Mortality
	Ropivacaine 0.75		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ropivacaine 0.75		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Ropivacaine 0.75		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/55 (0%)

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.