Intraperitoneal Ropivacaine Nebulization for Pain Control After Laparoscopic Surgery

Peritoneal Nebulization of Ropivacaine for Postoperative Pain Control After Laparoscopic Cholecystectomy

The purpose of this study is to assess if intraperitoneal nebulization of Ropivacaine 50 mg, 100 mg or 150 mg may prevent the use of morphine during the first day after laparoscopic cholecystectomy.

Study Overview

• Status: Completed
• Conditions: Laparoscopic Cholecystectomy
• Intervention / Treatment: Drug: Ropivacaine 50 mg; Drug: Ropivacaine 100 mg; Drug: Ropivacaine 150 mg

Detailed Description

Intraperitoneal aerosolization of Bupivacaine 50 mg after laparoscopic cholecystectomy has been proved to significantly reduce postoperative pain, morphine consumption and incidence of postoperative nausea and vomiting in comparison with patients receiving direct instillation of Bupivacaine 50 mg or placebo.

Ropivacaine can be effectively administrated with non-heating nebulizers (AeronebPro®). In a recent study our group found that nebulization of Ropivacaine 30 mg with the AeronebPro® before or after laparoscopic cholecystectomy significantly reduced postoperative pain and morphine consumption. Nonetheless, most patients still need strong opioid based analgesia after surgery.

We hypothesize that intraperitoneal nebulization of Ropivacaine 100 mg and 150 mg (maximum recommended dose in adults 300 mg or up to 3 mg/kg) may prevent the use of morphine during the first day after surgery maintaining ropivacaine plasma levels below toxic concentration.

• Study Type: Interventional
• Enrollment (Anticipated): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • MB
    • Monza, MB, Italy, 20052
      • San Gerardo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Females and Males 18-75 years old
• ASA Score I-III
• Scheduled for laparoscopic cholecystectomy
• Free from pain in preoperative period
• Not using analgesic drugs before surgery
• Without cognitive impairment or mental retardation
• Written informed consent

Exclusion Criteria:

• Emergency/urgency surgery
• Postoperative admission in an intensive care unit
• Cognitive impairment or mental retardation
• Progressive degenerative diseases of the CNS
• Seizures or chronic therapy with antiepileptic drugs
• Severe hepatic or renal impairment
• Pregnancy or lactation
• Allergy to one of the specific drugs under study
• Acute infection or inflammatory chronic disease
• Alcohol or drug addiction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ropivacaine 50 mg; Preoperative nebulization of 50 mg of Ropivacaine in the peritoneal cavity	Drug: Ropivacaine 50 mg; Preoperative nebulization of 50 mg of Ropivacaine in the peritoneal cavity; Other Names: Ropivacaine; Nebulization
EXPERIMENTAL: Ropivacaine 100 mg; Preoperative nebulization of 100 mg of Ropivacaine in the peritoneal cavity	Drug: Ropivacaine 100 mg; Preoperative nebulization of 100 mg of Ropivacaine in the peritoneal cavity; Other Names: Ropivacaine; Nebulization
EXPERIMENTAL: Ropivacaine 150 mg; Preoperative nebulization of 150 mg of Ropivacaine in the peritoneal cavity	Drug: Ropivacaine 150 mg; Preoperative nebulization of 150 mg of Ropivacaine in the peritoneal cavity; Other Names: Ropivacaine; Nebulization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine consumption (mg)	The total dose of morphine at every evaluation after awakening will be quantified using the PACU clinical chart and/or PCA infusers memory display	Up to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of unassisted walking	Unassisted walking time is defined as the time in hours between PACU discharge and when the patient is able to walk out of his room and back to bed without any assistance.	Up to 48 hours
Hospital morbidity	All complications or adverse effects associated or possibly associated with the interventions under study, surgery or anesthesia will be quantified using the anesthesia charts, surgical charts, surgical database.	Up to 48 hours
Ropivacaine pharmacokinetics profile: Plasma Concentration of Ropivacaine	We will perform a pharmacokinetic analysis through venous samples collected at 20, 40, 60, 90, 240, and 360 minutes after the end of nebulization.	Up to 360 minutes
Ropivacaine pharmacokinetics profile: Tissue drug analysis	Tissue samples (at least 2 g of tissue) from parietal peritoneum will be taken at the end of surgery . The supernatant will be analised with mass-spectrometry	Up to 2 hours
Postoperative Pain	Postoperative pain will be assessed by numeric ranking scale (NRS 0 to 10 points) at rest (static NRS) and after a deep inspiration or cough (dynamic NRS). Pain after surgery will be differentiated as abdominal, wall pain, port wound pain and/or shoulder pain. The proportion of patients with adequate pain control after surgery (dynamic NRS < 3) will also be assessed.	Up to 48 hours
Time and condition for hospital discharge	We define hospital stay as the elapsed time between surgery and hospital discharge, in days. We also evaluate the hospital stay with the post-anesthetic discharge scoring system (Modified-PADSS).	Up to 48 hours
Quality of life after surgery	Quality of life will be assessed using the SF-36 questionnaire	Four weeks after surgery

Collaborators and Investigators

• Sponsor: San Gerardo Hospital
• Collaborators: IRCCS Policlinico S. Matteo; University of Milano Bicocca; Azienda L'ULSS 15 Alta Padovana; Gruppo Ospedaliero San Donato, Policlinico San Pietro, Ponte San Pietro, Bergamo; Azienda U.S.L. della Valle d'Aosta, Ospedale Regionale Umberto Parini
• Investigators: Study Chair: Massimo Allegri, MD, Servizio Anestesia e Rianimazione I e Terapia del Dolore, Fondazione IRCCS Policlinico San Matteo, Pavia; Study Chair: Mario Regazzi, MD, Head of Clinical PK and TDM Laboratory, Foundation IRCCS Policlinico San Matteo, Pavia; Study Chair: Ernesto Pizzirani, MD, U.O.C. Anestesia e Rianimazione. A.O. U.L.S.S.15 "Alta Padovana", Presidio Camposampiero. Camposampiero - Padova; Study Chair: Fiorenza Franceschi, MD, U.O.C. Anestesia e Rianimazione. A.O. U.L.S.S.15 "Alta Padovana", Presidio Camposampiero. Camposampiero - Padova; Study Chair: Armando Alborghetti, MD, U.O.C. Anestesia e Rianimazione. Ospedale di Ponte San Pietro. Bergamo; Study Chair: Alessandro Albani, MD, U.O. Anestesia e Rianimazione. Ospedale Regionale "U. Parini", Aosta; Study Chair: Pierre Diemusch, MD, Servizio di Anestesia e rianimazione chirurgica. Hospital de Hautepierre. Università di Strasburgo.

Publications and helpful links

General Publications

• Alkhamesi NA, Peck DH, Lomax D, Darzi AW. Intraperitoneal aerosolization of bupivacaine reduces postoperative pain in laparoscopic surgery: a randomized prospective controlled double-blinded clinical trial. Surg Endosc. 2007 Apr;21(4):602-6. doi: 10.1007/s00464-006-9087-6. Epub 2006 Dec 16.
• Greib N, Schlotterbeck H, Dow WA, Joshi GP, Geny B, Diemunsch PA. An evaluation of gas humidifying devices as a means of intraperitoneal local anesthetic administration for laparoscopic surgery. Anesth Analg. 2008 Aug;107(2):549-51. doi: 10.1213/ane.0b013e318176fa1c.
• Schlotterbeck H, Schaeffer R, Dow WA, Diemunsch P. Cold nebulization used to prevent heat loss during laparoscopic surgery: an experimental study in pigs. Surg Endosc. 2008 Dec;22(12):2616-20. doi: 10.1007/s00464-008-9841-z. Epub 2008 Mar 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 11, 2010
• First Posted (ESTIMATE): June 14, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 19, 2011
• Last Update Submitted That Met QC Criteria: May 18, 2011
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Nebulization; Ropivacaine; Laparoscopic Cholecystectomy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Ropivacaine
• Other Study ID Numbers: AR HSG 01 2010