Nebulized Analgesia for Laparoscopic Appendectomy Trial — NALA  

Appendicitis Clinical Trial

Official title: Evaluation of the Effect of Intraperitoneal Nebulized Ropivacaine on Morphine Consumption After Laparoscopic Appendectomy in Children. A Prospective, Randomized Double Blind Clinical Trial

Status Recruiting

Clinical Trial Summary

The objective of this study is to assess whether the administration of nebulized intra-peritoneal ropivacaine at the onset of surgery, compared with nebulized saline, reduces morphine consumption after laparoscopic appendectomy surgery in children and adolescents.

Clinical Trial Description

The laparoscopic approach to pediatric appendectomy is gaining in popularity and has been demonstrated to reduce complications and improve resource utilization. The procedure has a documented association with high postoperative pain intensity, and is associated with substantial pain (pain scores >4 for >60% of the time) in 33% of patients. This is due to surgical manipulation, but also to the intraperitoneal insufflation of carbon dioxide required during laparoscopy which results in in peritoneal stretching, diaphragmatic irritation, changes in intra-abdominal pH as well as retention of insufflation gas in the abdominal cavity after surgery.

Opioid analgesics, especially morphine, are the most common pharmacological option for treating postoperative pain in pediatric patients. Although morphine is generally considered safe to use in pediatric patients, physicians and caregivers often hesitate to prescribe or administer opioids because of the perceived risk of addiction or undesirable side effects. Efforts to mitigate the use of opioids as systemic analgesia after surgery appears warranted. The topical administration of analgesics/anesthetics via the peritoneum is biologically advantageous as intra-abdominal gas insufflation and the resultant increased intra-abdominal pressure generates peritoneal inflammation and neuronal rupture with a linear relationship between abdominal compliance during the procedure and the severity of postoperative pain.

Intraperitoneal nebulization of local a anesthetic agent is a relatively novel approach to pain management after laparoscopy. Intraperitoneal nebulization of local anesthetic allows a uniform dispersion of the agent throughout the peritoneum and combines the analgesic benefits of gas conditioning and local anesthetic instillation. Microvibration-based aerosol humidification devices (i.e. cold nebulization) deliver significant amounts of local anesthetics in the abdominal cavity. Animal studies have confirmed the safety and bioavailability of nebulized ropivicaine in the abdominal cavity. The pharmacokinetics of nebulized ropivacaine 3 mg/kg is similar to that of instilled ropivacaine and maximal ropivacaine concentrations have been found to lie well within safe ranges. Human studies have confirmed favorable pharmacokinetics and pharmacodynamics of nebulized ropivacaine. Peak concentration is attained between 10 and 30 minutes following the end of aerosolized ropivacaine delivery. Aerosolized intraperitoneal local anesthetic is feasible, with ropivacaine concentrations remaining within safe levels.

In previous randomized controlled trials in adults, nebulization of ropivacaine 30 mg with the Aeroneb Pro system either before or after laparoscopic cholecystectomy reduces postoperative pain (effect size - 33% to - 50%) as well as completely prevents shoulder pain compared with nebulization of saline. Patients receiving ropivacaine nebulization consumed significantly less morphine than those in the control group (effects size 40% to -56%). Patients receiving ropivacaine nebulization mobilized quicker than those receiving placebo with a 33% reduction on unassisted walking time after surgery. The duration of analgesia after both pre- and postoperative nebulization (up to 48 hours) was significantly longer than the expected duration of ropivacaine, based on its mechanism of action. No adverse events were reported during the conduct of these trials. Ropivicaine nebulization has also been evaluated in the context of gynecological surgery; patients receiving Ropivacaine 30 mg before or after surgical stimulation reported significantly less postoperative pain (-50%) and consumed significant less morphine (-40%) and walked without assistance than those receiving ropivacaine instillation during the first 24 hours after surgery. Furthermore, the administration of intraperitoneal aerosolized bupivacaine just prior to incising the peri-renal fascia appears to be a simple, effective and low-cost method to reduce postoperative pain in children undergoing laparoscopic pyeloplasty in children.

Given the consistently safe and favorable results documented with adult patients, the working study hypothesis is that the intra-abdominal administration of nebulized ropivacaine immediately before the onset of surgery will reduce post-operative pain and morphine consumption after laparoscopic appendectomy in children and adolescents. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Appendicitis

• NCT number: NCT02624089
• Study type: Interventional
• Source: McGill University Health Center
• Contact: Robert Baird, MDCM MSc
• Phone: 514 412 4400
• Email: robert.baird@mcgill.ca
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2016
• Completion date: July 2017