Nebulized Analgesia for Laparoscopic Appendectomy Trial

Appendicitis Clinical Trial

— NALA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02624089
• Other study ID #: 14-120-PED
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: December 3, 2015
• Last updated: March 21, 2016
• Start date: January 2016
• Est. completion date: July 2017

Study information

• Verified date: March 2016
• Source: McGill University Health Center
• Contact: Robert Baird, MDCM MSc
• Phone: 514 412 4400
• Email: robert.baird[@]mcgill.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 18 Years

Eligibility

Inclusion Criteria:

• Children and adolescents aged 7-18 years old

• ASA Score I (American Society of Anesthesiologists classification) [Appendix 1]: a normal healthy patient.

• ASA Score II (American Society of Anesthesiologists classification): A patient with mild systemic disease

• Patients scheduled for laparoscopic appendectomy surgery

• Uncomplicated appendicitis

• Hemodynamically stable patient

• No evidence of appendiceal perforation based on preoperative clinical and imaging assessment

• Diagnosed to have simple acute appendicitis by intraoperative laparoscopy

• Patients who have provided a written informed assent

• Caregivers who have provided a written informed consent

Exclusion Criteria:

• ASA Score III (American Society of Anesthesiologists classification): A patient with severe systemic disease

• ASA Score IV (American Society of Anesthesiologists classification): A patient with severe systemic disease that is a constant threat to life

• ASA Score V (American Society of Anesthesiologists classification): A moribund patient who is not expected to survive without the operation

• Hemodynamically unstable patient

• Evidence of appendiceal perforation on based on preoperative clinical and imaging assessment

• Perforated or gangrenous appendicitis diagnosed during laparoscopic surgery

• Postoperative admission in an intensive care unit with sedation or ventilatory assistance

• Cognitive impairment or mental retardation

• Progressive degenerative diseases of the CNS

• Seizures or chronic therapy with antiepileptic drugs

• Severe hepatic or renal impairment

• Allergy to one of the specific drugs under study

• Alcohol or drug addiction

• Failure to successfully undergo a laparoscopic appendectomy

• A significant communication problem including language barrier, precluding phone follow up

• Participation in a concomitant research study

• Inability to assure complete follow up

• Failure to acquire informed consent and assent

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

Intervention

Drug:
• Ropivacaine
Ropivicaine will be administered via in-line nebulization using the Aeroneb Pro™ system
• Normal saline
Normal saline will be administered via in-line nebulization using the Aeroneb Pro™ system

Locations

Country	Name	City	State
Canada	Montreal Children's Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University Health Center	Montreal Children's Hospital of the MUHC

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-operative morphine consumption	The total dose of Morphine (in mg/kg) and the route of administration received after surgery will be recorded. The oral morphine dose will be converted as 1mg IV= 2mg PO.	During hospital admission (24-48 hours)	No
Secondary	Post-operative Pain	This will be serially evaluated using a Visual Analog Score	During hospital admission (24-48 hours)	No
Secondary	Time to unassisted walking		During hospital admission (24-48 hours)	No
Secondary	In-hospital length of stay		During hospital admission (24-48 hours)	No
Secondary	Postoperative recovery quality	This will be evaluated via a standardized telephone questionnaire	Two weeks after hospital discharge	No
Secondary	Surgeon satisfaction	this will be evaluated via a questionnaire	Immediately after surgery	No