Sugammadex vs Neostigmine Reversal in Pediatric Appendectomy

Study Overview
=================
Brief Summary
-----------------
This study is designed as a randomized controlled trial with patients assigned to neuromuscular reversal with either sugammadex or neostigmine/glycopyrrolate reversal. The study will not be blinded to the anesthesiologist to allow for appropriate decision-making on timing and dosage of reversal. This is a single-center study.

Detailed Description
-----------------
Patients presenting to the operating room for laparoscopic appendectomy with a diagnosis of acute appendicitis require rapid sequence induction (RSI) due to significant vomiting and concern for increased gastric content. For this reason, succinylcholine-accompanied by neostigmine-is predominately used in adults for RSI to prevent potential aspiration. Unfortunately, in pediatric patients, there are many concerns about the use of succinylcholine, including complications such as bradycardia, hyperkalemia, dysrhythmias, and cardiac arrest from undiagnosed skeletal muscle myopathy. For many anesthesiologists, these concerns prompted the decision to use a non-depolarizing muscle relaxant such as rocuronium for induction. However, if the standard RSI dose is used, it often results in residual paralysis at the end of short procedures such as laparoscopic appendectomies. It has recently been demonstrated that prolonged paralysis is prevalent even at low doses of rocuronium in pediatric patients. For these reasons, it is imperative to find a way to provide adequate and safe RSI conditions for intubation, appropriate muscle relaxation for laparoscopic procedures, and the ability to quickly reverse neuromuscular blockade in this pediatric population. Sugammadex has the potential to allow for the utilization of an appropriate RSI dose of rocuronium for intubation, as it provides the ability to reverse neuromuscular blockade earlier than the neostigmine reversal, which is currently the standard of care. Retrospective reviews have shown the use of Sugammadex in pediatric patients to be safe and effective. However, there has not been prospective data about the effect on operating room efficiency on brief pediatric procedures such as laparoscopic appendectomies-one of the most common urgent pediatric surgeries performed. There are numerous other potential benefits of using sugammadex over typical reversal including the quicker return of bowel function, faster time to tolerance of an oral diet, and decreased exposure to volatile anesthesia. The return of bowel function is particularly important in pediatric patients undergoing laparoscopic procedures. The research team hypothesis is that the utilization of sugammadex in pediatrics results in a quicker return to bowel function. This has previously been demonstrated in adults, but data is lacking in the pediatric population. Researchers also hypothesize that patients receiving sugammadex versus neostigmine reversal will have an improved time to tolerance of an oral diet, which may impact wound healing and nutrition. As anesthesiologists often under-dose rocuronium in these short procedures, due to a lack of quick reversal options, high levels of volatile anesthesia are utilized to compensate for inadequate muscle relaxation. With the use of sugammadex allowing for proper muscle relaxation throughout the entire case, researchers hypothesize that patients will have a lower total volatile anesthetic exposure during the procedure. This is exceedingly important in pediatric anesthesia, where the detrimental effects of volatile anesthetics on the developing brain have been demonstrated in numerous animal studies.

Official Title
-----------------
Effectiveness of Sugammadex Versus Neostigmine on Neuromuscular Reversal in Pediatric Patients Undergoing Laparoscopic Appendectomy for Acute Appendicitis: A Randomized Controlled Trial

Conditions
-----------------
Surgery, Appendicitis

Intervention / Treatment
-----------------
* Drug: Sugammadex
* Drug: Neostigmine/Glycopyrrolate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients 2-17 years of age Diagnosis of acute appendicitis Patient undergoing laparoscopic appendectomy at Children's Healthcare of Atlanta- Egleston. Parent or Legal Authorized Representative willing to participate, able to understand and sign an informed consent Exclusion Criteria: Patient with an allergy to Sugammadex or Neostigmine History of renal dysfunction Parent or legal guardian unwilling or unable or unable to understand the informed consent

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex<br>The reversal agent, Sugammadex, will be administered at the start of closure. | Drug: Sugammadex<br>* Participants will receive 4mg/kg for a TOF 0-1 and 2mg/kg for a train of four (TOF) 2 or greater.<br>* Other names: Intervention Group;|
| Active Comparator: Neostigmine/Glycopyrrolate<br>The reversal agent, Neostigmine, will be administered at the start of closure. | Drug: Neostigmine/Glycopyrrolate<br>* Participants will receive 0.07mg/kg of Neostigmine and 0.01mg/kg of Glycopyrrolate, administered by anesthesia once at least two twitches are present.<br>* Other names: Regular Care;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total hours from surgery end to out of the operating room (OR) | Hours from surgery end to out of the OR will be evaluated via the Epic computer chart after discharge from the hospital. | Up to 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total hours to first bowel movement | Hours to first bowel movement will be evaluated via the Epic computer record after discharge from the hospital | Up to 72 hours | 
| Total hours to tolerance of an oral diet | The research team will evaluate via the Epic computer record after discharge from the hospital | Up to 72 hours | 
| Total hours of inhalational anesthesia exposure | will be evaluated via the Epic computer record after discharge from the hospital | Up to 5 hours (depending on length of surgical procedure) | 
| Length of stay (hours) in the Post-anesthesia care unit (PACU) | PACU length of stay will be evaluated via the Epic computer record after discharge from the hospital | Up to 5 hours (depending on post anesthesia recovery) | 
| Hospital length of stay (LoS) | Hospital LoS will be evaluated via the Epic computer record after discharge from the hospital | Up to 14 days (depending on length of hospitalization) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
laparoscopic