Effect of Ketorolac on Post Adenotonsillectomy Pain

Ketorolac as a Strategy for Reducing Post-operative Opioid Requirements in Children With Obstructive Sleep Apnea Undergoing Adenotonsillectomy: a Randomized Controlled Trial

This randomized prospective study aims to determine the effect of ketorolac on the total dose of morphine required to achieve postoperative analgesia in children with obstructive sleep apnea (OSA) undergoing adenotonsillectomy. Participants will be randomly assigned to a study group where they will receive ketorolac in addition to the standard of care treatment or will receive only the standard of care pain management. The researchers hypothesize that by administering ketorolac at the end of the procedure once hemostasis has been achieved, it will be possible to decrease the amount of morphine administered in the post-anesthesia care unit (PACU). This study aims to provide a more comprehensive understanding of the efficacy and safety of the current standard post-operative analgesic regimen employed at the study institution, in which opioid analgesia currently plays a prominent role.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Ketorolac; Drug: Standard of Care

Detailed Description

Obstructive sleep apnea (OSA) as an indication for adenotonsillectomy has increased significantly over the past ten years, and now has surpassed recurrent tonsillitis as the most common indication for this procedure. Opioids continue to be the most commonly administered pain medication for these procedures. Studies have shown that patients with OSA have significantly increased sensitivity to opioids that results in post-operative respiratory depression and apnea when administered via standard opioid dosing protocols. Children with OSA were shown to have a nearly fivefold increase in the odds of developing respiratory complications when compared to their counterparts with tonsillitis. Ketorolac possesses similar efficacy to morphine without the problematic complications of respiratory depression, nausea and vomiting, which are commonly seen post-adenotonsillectomy. Importantly, when combined with opioids, ketorolac is opioid-sparing. This synergistic effect means that a similar level of analgesia is achieved using a lower dose of opioid. However, there continues to be concern about using ketorolac due to the potential risk of post-operative bleeding from anti-platelet activity.

This randomized, prospective study aims to determine the effect of ketorolac on the total dose of morphine required to achieve postoperative analgesia in children with OSA undergoing adenotonsillectomy. Participants will be randomly assigned to receive ketorolac or to not receive ketorolac. The post-anesthesia care unit (PACU) nurses, who will be blinded to ketorolac administration, will evaluate the patients using the Face, Legs, Activity, Cry, Consolability (FLACC) scale scores at 10 minutes post-op, 20 minutes post-op and at time of PACU discharge. For patients with a FLACC score of 6-10, morphine (0.05mg/kg) will be administered. For patients with FLACC scores of 3-5, morphine (0.025mg/kg) will be administered. The total amount of opioid required to obtain a FLACC score of less than 3 will be evaluated as the primary outcome. The secondary outcomes to be evaluated will be PACU FLACC scores, time required in PACU, incidence of post-tonsillectomy bleeding and total pain medications administered during hospital admission.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Laura Gilbertson, MD; Phone Number: 404-785-6670; Email: laura.gilbertson@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Childrens Healthcare of Atlanta, Egleston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of sleep disordered breathing or obstructive sleep apnea
• Children undergoing elective tonsillectomy or adenotonsillectomy at Children's Healthcare of Atlanta Egleston location
• Parent or legal guardian willing to participate, and able to understand and sign the provided informed consent

Exclusion Criteria:

• Known coagulation defect
• Patients on longstanding NSAID therapy
• Known renal impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketorolac; Participants randomized to the ketorolac group will receive 0.5mg/kg IV at the end of the adenotonsillectomy procedure, once hemostasis has been achieved	Drug: Ketorolac; Patients in this group will receive 0.5mg/kg of ketorolac, administered intravenously.; Other Names: Toradol; Drug: Standard of Care; All patients will undergo inhalational induction with nitrous oxide and sevoflurane. After intravenous (IV) placement, 1-3mg/kg of propofol and 1mcg/kg of fentanyl will be administered. After induction, 0.5mg/kg of dexamethasone and an IV infusion of 15mg/kg of acetaminophen will be administered. During surgery, 0.5mcg/kg of dexmedetomidine and 0.1mg/kg ondansetron will be given. A rescue dose of 0.5-1mcg/kg of IV Fentanyl will be available for use at the end of the procedure. The decision to administer will be left to the discretion of the attending anesthesiologist. The choice to give this will be made based on variables including patient's condition and a 20% increase in the heart rate and blood pressure. The PACU nurses, who will be blinded to ketorolac administration, will evaluate the patients using FLACC scores. For patients with a FLACC score of 6-10, morphine 0.05mg/kg will be administered. For patients with FLACC scores of 3-5, morphine 0.025mg/kg will be administered.; Other Names: Decadron; Precedex; Diprivan; Zofran; Morphine; Ultane; Sojourn
Active Comparator: Standard of Care; Participants randomized to this group will receive the pain management standard of care for the adenotonsillectomy procedure.	Drug: Standard of Care; All patients will undergo inhalational induction with nitrous oxide and sevoflurane. After intravenous (IV) placement, 1-3mg/kg of propofol and 1mcg/kg of fentanyl will be administered. After induction, 0.5mg/kg of dexamethasone and an IV infusion of 15mg/kg of acetaminophen will be administered. During surgery, 0.5mcg/kg of dexmedetomidine and 0.1mg/kg ondansetron will be given. A rescue dose of 0.5-1mcg/kg of IV Fentanyl will be available for use at the end of the procedure. The decision to administer will be left to the discretion of the attending anesthesiologist. The choice to give this will be made based on variables including patient's condition and a 20% increase in the heart rate and blood pressure. The PACU nurses, who will be blinded to ketorolac administration, will evaluate the patients using FLACC scores. For patients with a FLACC score of 6-10, morphine 0.05mg/kg will be administered. For patients with FLACC scores of 3-5, morphine 0.025mg/kg will be administered.; Other Names: Decadron; Precedex; Diprivan; Zofran; Morphine; Ultane; Sojourn

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Anesthesia Care Unit (PACU) Morphine Requirements	The total postoperative morphine dosage required to achieve analgesia (defined as a Face, Legs, Activity, Cry, Consolability (FLACC) Scale score of less than 3) in children with obstructive sleep apnea undergoing adenotonsillectomy will be compared between study arms to examine the effect of ketorolac administration.	Until PACU discharge (typically within 3 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Face, Legs, Activity, Cry, Consolability (FLACC) Scale Score	Post-Anesthesia Care Unit (PACU) nurses will evaluate the patients using Face, Legs, Activity, Cry, Consolability (FLACC) Scale scores at 10 minutes post-op, 20 minutes post-op and at time of PACU discharge. Each category is scored as 0 (no indication of pain), 1 (indication of moderate pain), or 2 (visibly experiencing severe pain). Total scores range from 0 to 10, with higher scores indicating more pain.	10 minutes post-op, 20 minutes post-op, PACU discharge (typically within 3 hours)
Post-Anesthesia Care Unit (PACU) Recovery Time	The duration of time that a participant is in the Post-Anesthesia Care Unit (PACU), following surgery, measured in minutes.	Until PACU discharge (typically within 3 hours)
Incidence of Post-Tonsillectomy Bleeding	Participants will be monitored for post-tonsillectomy bleeding. Post-surgical bleeding typically occurs within 7 days.	Until complete recovery (typically within 7 days after surgery)
Pain Medication Administration	The total amount of pain medications administered during hospitalization will be examined.	Surgery through hospital discharge (typically within 2 days)

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Laura Gilbertson, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2018
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): August 22, 2023

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 12, 2018
• First Posted (Actual): March 16, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pediatrics; Adenotonsillectomy; Opioids; Anesthesiology; Post-surgical pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Analgesics, Opioid; Narcotics; Ketorolac; Morphine
• Other Study ID Numbers: IRB00097738

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No