Efficacy of Intravenous Acetaminophen as Analgesic Adjuvant Therapy in Children Undergoing Posterior Fossa Surgery
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Locations
- 1
- Primary Endpoint
- Daily opioid consumption (mg/kg/24 hours using morphine equivalent)
Study Overview
Brief Summary
Uncontrolled pain after posterior fossa surgery and associated negative side effects of conventional opioid therapy causes significant morbidity and mortality in infants and children. Intravenous (IV) acetaminophen has been shown to be effective in treating mild to moderate pain, and moderate to severe pain in conjunction with adjuvant opioids in children. However, it is unknown if IV acetaminophen is effective as analgesic adjuvant therapy in children undergoing posterior fossa surgery. In this prospective, randomized controlled trial, the investigators aim to determine whether the addition of IV acetaminophen for 24 hours can lead to reduction in postoperative pain and opioid requirement after neurosurgical procedures of the posterior fossa compared with conventional therapy.
Detailed Description
The primary goal of this study is to compare the efficacy of IV acetaminophen to placebo in pediatric patients undergoing posterior fossa surgery, with the primary outcome measure being postoperative opioid requirements (morphine equivalent mg/kg). This will be a prospective, randomized, double blind control trial. The patient, research team, surgeon, and anesthesiologist will all be blinded to the patient's treatment group. Patients will receive either IV acetaminophen or equal volume normal saline (placebo) in the perioperative period.
The interventional component of this study involves the intraoperative and postoperative administration of IV acetaminophen. Intraoperative and postoperative data pertaining to adverse events would be collected for safety monitoring purposes.
Enrolled subjects will be randomized to receive either IV acetaminophen or equal volume saline placebo during surgery and for 24 hours postoperatively. According to a computer-generated table of random number assignments, each patient will be randomly assigned to receive one of the following two treatment groups:
Treatment group 1:
IV acetaminophen 15 mg/kg (1.5 mL/kg) IV loading dose prior to incision, followed by a 15 mg/kg (1.5 mL/kg) dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively). This dosing regimen was chosen based on pharmacokinetic data and recommended dosing guidelines for IV acetaminophen in children 2 to 12 years of age.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 2 Years to 12 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Any child undergoing posterior fossa surgery, including surgery for Chiari Malformation
- •The subject's American Society of Anesthesiologists physical status is 1, 2 or 3
- •Males and females 2 to 12 years old (minorities will be included) - recommended dosing of IV acetaminophen in children is approved for children 2 to 12 years of age
- •Written informed consent from parent/guardian
Exclusion Criteria
- •Subjects with known or suspected hypersensitivity reaction to acetaminophen
- •Presence or prior history of a known liver disease or coagulation disorder:
- •History of abnormal liver function
- •History of prior liver transplantation
- •Subjects who are on anticoagulant therapy (Coumadin, heparin, aspirin, etc.)
- •History of prior acetaminophen overdose
- •Subjects with the need for mechanical ventilation prior to surgery or postoperatively - unable to assess accurate pain scores in this context
- •The subject has a history or a family (parent or sibling) history of malignant hyperthermia
- •The subject had a recent opioid exposure (within 1 month of surgery)
- •The subject is obese (body mass index >30 kg/m2)
- •The subject is an American Society of Anesthesiologist physical status classification of 4 or greater
- •The subject is scheduled for a surgical sub-procedure
- •Subjects who have been previously enrolled in this protocol may not be enrolled again
Arms & Interventions
IV acetaminophen
IV acetaminophen 15 mg/kg (1.5 mL/kg) IV loading dose prior to incision, followed by a 15 mg/kg (1.5 mL/kg) dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively)
Intervention: IV acetaminophen (Drug)
normal saline
normal saline (placebo control) 1.5 mL/kg IV loading dose prior to incision, followed by a 1.5 mL/kg dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively)
Intervention: normal saline (Drug)
Outcomes
Primary Outcomes
Daily opioid consumption (mg/kg/24 hours using morphine equivalent)
Time Frame: 72 hours postoperatively
Equianalgesic conversion of opioid consumption to morphine equivalent will be used
Secondary Outcomes
- Average daily sedation scores using University of Michigan Sedation Scale(72 hours postoperatively)
- Incidence of opioid-induced side effects(72 hours postoperatively)
- Average daily pain scores using Wong-Baker Faces or Numeric Pain Scale(72 hours postoperatively)
Investigators
Srijaya K. Reddy, MD, MBA
MD
Children's National Research Institute