Local Anesthetic Nebulization and Instillation for Pain Control After Laparoscopic Surgery

Double Blind Randomized Phase III Controlled Trial Comparing the Effect of Intraperitoneal Nebulization of Ropivacaine With Intraperitoneal Instillation of Ropivacaine on Pain Control After Laparoscopic Cholecystectomy

Studies evaluating intraperitoneal local anesthetic instillation for pain relief after laparoscopic procedures have provided conflicting results. This randomized, double-blind study was designed to assess the effects of a novel intraperitoneal local anesthetic administration technique using nebulization on pain relief after laparoscopic cholecystectomy.

Study Overview

• Status: Completed
• Conditions: Laparoscopic Cholecystectomy
• Intervention / Treatment: Drug: Ropivacaine 100 mg; Drug: Ropivacaine 60 mg

Detailed Description

Studies evaluating intraperitoneal local anesthetic (LA) instillation for pain relief after laparoscopic cholecystectomy have provided conflicting results. One of the factors that might contribute to failure of the instillation technique may be related to inadequate distribution of local anesthetic throughout the peritoneal surface. In contrast, nebulization should provide a uniform spread of drugs throughout the peritoneal cavity and thus may be beneficial to improve pain relief after laparoscopic procedures. A recent study reported that bupivacaine nebulization significantly reduced pain after laparoscopic cholecystectomy compared with bupivacaine instillation in the gallbladder bed. However, these investigators used a custom-made nebulization system that needs a separate gas source and tubing that is cumbersome and may not be easily available.

Recently, the investigators reported that a microvibration-based nebulization device (Aeroneb Pro® system, Aerogen, Galway, Ireland) could be used for ropivacaine delivery into the insufflation gas required to create pneumorpeitoneum. The investigators hypothesized that intraperitoneal ropivacaine nebulization would provide superior pain relief after laparoscopic cholecystectomy than intraperitoneal ropivacaine instillation. This randomized, double blind, controlled clinical trial was designed to assess the analgesic efficacy of ropivacaine nebulization using the Aeroneb Pro® device laparoscopic cholecystectomy compared with intraperitoneal ropivacaine instillation.

• Study Type: Interventional
• Enrollment (Actual): 60
• 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 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Instillation; Instillation of Ropivacaine 100 mg in the abdominal cavity	Drug: Ropivacaine 100 mg; Instillation group received intraperitoneal instillation of ropivacaine 0.5%, 20 ml (100 mg) on the gall bladder after induction of pneumoperitoneum but before dissection of gall bladder plus and intraperitoneal nebulization of normal saline 3 ml before the start of gall bladder dissection and again at the end of surgery just before deflation of pneumoperitoneum. The first saline nebulization was performed over 5-6 minutes using the Aeroneb Pro® device through the umbilical port while the other ports were being inserted, while second nebulization was performed before the withdrawal of the ports
EXPERIMENTAL: Nebulization; Nebulization of Ropivacaine 60 mg in the abdominal cavity	Drug: Ropivacaine 60 mg; Nebulization grou received intraperitoneal instillation of saline 20 ml on the gall bladder after induction of pneumoperitoneum but before dissection of gall bladder plus intraperitoneal nebulization of ropivacaine 1% 3 ml (30 mg) the start of gall bladder dissection and again at the end of surgery just before deflation of pneumoperitoneum (total of 60 mg). The first ropivacaine nebulization was performed over 5-6 minutes using the Aeroneb Pro® device through the umbilical port while the other ports were being inserted, while second nebulization was performed before the withdrawal of the ports

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain	Postoperative pain was assessed by Visual analgue scale (VAS 0 to 100 points) at rest (static VAS) and after a deep inspiration or cough (dynamic VAS). The proportion of patients with adequate pain control after surgery (dynamic VAS < 3) will also be assessed.	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
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
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
Time to hospital discharge	We define hospital stay as the elapsed time between surgery and hospital discharge	48 hours

Collaborators and Investigators

• Sponsor: San Gerardo Hospital
• Collaborators: Hôpital de Hautepierre
• Investigators: Principal Investigator: Pablo M Ingelmo, MD, San Gerardo Hospital

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: April 1, 2008
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): May 1, 2009

Study Registration Dates

• First Submitted: November 24, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (ESTIMATE): November 25, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2010
• Last Update Submitted That Met QC Criteria: November 24, 2010
• Last Verified: March 1, 2008

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 04-2008