Comparing Intramuscular Fentanyl and Ketorolac With Nerve of Arnold (NOA) Block for Bilateral Myringotomy

NCT07276906 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 2387143-1
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Bilateral myringotomy with tympanostomy tube (BMT) placement is one of the most common pediatric surgical procedures. Despite its brief duration, many children experience significant postoperative pain. Current standard care typically involves intramuscular (IM) administration of an opioid (fentanyl) combined with a non-steroidal anti-inflammatory drug (ketorolac). While this multimodal approach provides adequate pain control for approximately 75% of children, it is associated with opioid-related side effects including respiratory depression, nausea, vomiting, and sedation. Additionally, nearly one-quarter of children still experience moderate-to-severe pain despite this regimen. The Nerve of Arnold block is a regional anesthesia technique that involves injection of local anesthetic near the auricular branch of the vagus nerve, which provides sensory innervation to the external auditory canal and tympanic membrane. This technique offers the potential for targeted, opioid-sparing analgesia with extended duration and minimal systemic side effects. However, high-quality evidence comparing this regional technique to standard systemic analgesia in pediatric patients is lacking. Study Objective: This study aims to determine whether the Nerve of Arnold block is non-inferior to the standard combination of IM fentanyl and IM ketorolac in controlling postoperative pain in children undergoing BMT placement. Study Design: This is a prospective, randomized, double-blind, non-inferiority trial. Three hundred children aged 6 months to 6 years scheduled for bilateral myringotomy with tympanostomy tube placement will be randomized 1:1 to receive either: (1) Standard care: IM fentanyl (1-2 mcg/kg) plus IM ketorolac (0.5 mg/kg) with sham Nerve of Arnold block, or (2) Intervention: Bilateral Nerve of Arnold block with bupivacaine 0.25% plus sham IM injections. Both patients and outcome assessors will be blinded to treatment assignments. Primary Outcome: The proportion of patients experiencing moderate-to-severe pain (Face, Legs, Activity, Cry, Consolability \[FLACC\] scale score ≥4) in the Post-Anesthesia Care Unit (PACU). Non-inferiority will be declared if the upper bound of the 95% confidence interval for the difference in proportions is less than 10 percentage points. Secondary Outcomes: Secondary outcomes include mean and maximum FLACC scores, rescue analgesic requirements, respiratory depression, postoperative nausea and vomiting, PACU length of stay, parent satisfaction, and pain at 24 hours postoperatively. Clinical Significance: If the Nerve of Arnold block is shown to be non-inferior to standard care, it could provide a valuable opioid-sparing alternative for postoperative pain management in pediatric ear surgery, potentially reducing opioid-related adverse events while maintaining effective analgesia. This would be particularly beneficial for patients with contraindications to opioids or NSAIDs and aligns with national efforts to reduce opioid exposure in pediatric populations.

Conditions

Postoperative Pain

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Moderate-to-Severe Pain (FLACC Score ≥4) During PACU Stay

  Number of participants experiencing at least one FLACC (Face, Legs, Activity, Cry, Consolability) scale score of 4 or greater during Post-Anesthesia Care Unit stay. FLACC is a validated behavioral pain assessment tool scored 0-10, with scores ≥4 indicating moderate-to-severe pain. FLACC scores assessed every 15 minutes during PACU stay.

  From PACU admission to PACU discharge, up to 1 hour

Secondary Outcomes (8)

• Highest FLACC Pain Score During PACU Stay

  From PACU admission to meeting PACU discharge criteria

• Number of Participants Requiring Rescue Analgesia

  From PACU admission to meeting PACU discharge criteria

• Number of Participants with Respiratory Depression

  From PACU admission to meeting PACU discharge criteria

• Number of Participants with Postoperative Nausea and Vomiting

  From PACU admission to meeting PACU discharge criteria

• Number of Participants with Emergence Agitation

  From PACU admission to meeting PACU discharge criteria

Study Arms (2)

IM Arm standard Care

ACTIVE COMPARATOR

Patients receive intramuscular fentanyl 2 mcg/kg (maximum 100 mcg) plus intramuscular ketorolac 0.5 mg/kg (maximum 30 mg) after induction of anesthesia. Sham bilateral Nerve of Arnold block with normal saline 0.2 mL per side is performed to maintain blinding.

Drug: Fentanyl; Drug: Ketorolac; Procedure: Sham Nerve of Arnold Block

Nerve block arm

EXPERIMENTAL

Patients receive bilateral Nerve of Arnold block with bupivacaine 0.25% with epinephrine 1:200,000 (0.2 mL per side) plus dexmedetomidine 5 mcg per side (maximum total bupivacaine dose 2.5 mg/kg) after induction of anesthesia. sham intramuscular injection with normal saline is performed to maintain blinding.

Procedure: Nerve of Arnold Block; Procedure: Sham Intramuscular Injection; Drug: Dexmedetomidine; Drug: Bupivacaine

Interventions

Ketorolac DRUG

Intramuscular ketorolac 0.5 mg/kg (maximum 30 mg) administered after induction of anesthesia

Also known as: Toradol

IM Arm standard Care

Nerve of Arnold Block PROCEDURE

Bilateral Nerve of Arnold block with bupivacaine 0.25%, 0.2 mL per side (total 0.4 mL), administered after induction of anesthesia

Nerve block arm

Sham Nerve of Arnold Block PROCEDURE

Bilateral sham Nerve of Arnold block with normal saline 0.2 mL per side to maintain blinding

IM Arm standard Care

Dexmedetomidine DRUG

Dexmedetomidine 5 mcg per side (10 mcg total) added to bupivacaine solution for Nerve of Arnold block as adjuvant to prolong block duration

Also known as: Precedex

Nerve block arm

Bupivacaine DRUG

Bupivacaine 0.25% with epinephrine 1:200,000, 0.2 mL per side (total 0.4 mL, maximum 2.5 mg/kg) for bilateral Nerve of Arnold block

Also known as: Marcaine, Sensorcaine

Nerve block arm

Fentanyl DRUG

Intramuscular fentanyl 2 mcg/kg (maximum 100 mcg) administered after induction of anesthesia

IM Arm standard Care

Sham Intramuscular Injection PROCEDURE

sham intramuscular injections with normal saline to maintain blinding

Nerve block arm

Eligibility Criteria

• Age: 6 Months - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 months to 6 years
• Scheduled bilateral myringotomy with tube placement
• ASA physical status I-II
• Parent/guardian consent

You may not qualify if:

• Allergy to study medications (fentanyl, ketorolac, bupivacaine)
• Renal impairment or contraindication to ketorolac
• Bleeding disorder or anticoagulation
• Significant obstructive sleep apnea (AHI \>10)
• Concurrent surgical procedures beyond BMT
• Unilateral procedure only
• Recent analgesic use (\<24 hours)

Sponsors & Collaborators

• University of South Alabama: lead

Study Sites (1)

Children and Woman's Hospital

Mobile, Alabama, 36604, United States

Location

Related Publications (3)

• Cook-Sather SD, Castella G, Zhang B, Mensinger JL, Galvez J, Wetmore RF. Principal Factors Associated With Ketorolac-Refractory Pain Behavior After Pediatric Myringotomy and Pressure Equalization Tube Placement: A Retrospective Cohort Study. Anesth Analg. 2020 Mar;130(3):730-739. doi: 10.1213/ANE.0000000000004226.

  PMID: 31082971 BACKGROUND

• Voronov P, Tobin MJ, Billings K, Cote CJ, Iyer A, Suresh S. Postoperative pain relief in infants undergoing myringotomy and tube placement: comparison of a novel regional anesthetic block to intranasal fentanyl--a pilot analysis. Paediatr Anaesth. 2008 Dec;18(12):1196-201. doi: 10.1111/j.1460-9592.2008.02789.x.

  PMID: 19076574 BACKGROUND

• Cohen WG, Zhang B, Lee DR, Ampah SB, Sobol SE, Cook-Sather SD. Middle Ear Condition at the Time of Pediatric Myringotomy Tube Placement: Pain Associations Following Intraoperative Fentanyl/Ketorolac and Seasonal Variation. Anesth Analg. 2023 May 1;136(5):975-985. doi: 10.1213/ANE.0000000000006230. Epub 2022 Nov 2.

  PMID: 36525380 RESULT

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Fentanyl; Ketorolac; Ketorolac Tromethamine; Dexmedetomidine; Bupivacaine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Imidazoles; Azoles; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Central Study Contacts

Karthik Swamy, MD

CONTACT

251-471-7045; kswamy@health.southalabama.edu

Karthik Swamy

CONTACT

251-471-7045; kswamy@health.southalabama.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pediatric Anesthesiology, Principal Investigator, Assistant Professor

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 11, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)