Intraperitoneal Ropivacaine Nebulization for Pain Control After Laparoscopic Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Peritoneal Nebulization of Ropivacaine for Postoperative Pain Control After Laparoscopic Cholecystectomy

Conditions
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Laparoscopic Cholecystectomy

Intervention / Treatment
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* Drug: Ropivacaine 50 mg
* Drug: Ropivacaine 100 mg
* Drug: Ropivacaine 150 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ropivacaine 50 mg<br>Preoperative nebulization of 50 mg of Ropivacaine in the peritoneal cavity | Drug: Ropivacaine 50 mg<br>* Preoperative nebulization of 50 mg of Ropivacaine in the peritoneal cavity<br>* Other names: Ropivacaine;|
| Experimental: Ropivacaine 100 mg<br>Preoperative nebulization of 100 mg of Ropivacaine in the peritoneal cavity | Drug: Ropivacaine 100 mg<br>* Preoperative nebulization of 100 mg of Ropivacaine in the peritoneal cavity<br>* Other names: Ropivacaine;|
| Experimental: Ropivacaine 150 mg<br>Preoperative nebulization of 150 mg of Ropivacaine in the peritoneal cavity | Drug: Ropivacaine 150 mg<br>* Preoperative nebulization of 150 mg of Ropivacaine in the peritoneal cavity<br>* Other names: Ropivacaine;|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Laparoscopic Cholecystectomy, Nebulization, Ropivacaine