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

Description

Clinical Context Bilateral myringotomy with tympanostomy tube placement is performed in over 600,000 children annually in the United States for treatment of recurrent acute otitis media or chronic otitis media with effusion. Despite being a brief minimally invasive procedure, inadequate postoperative pain control is common and associated with emergence agitation, delayed discharge, increased rescue medication requirements, and parental anxiety.

Current Standard of Care Recent large retrospective cohort studies have established the efficacy of multimodal analgesia for pediatric myringotomy and tube placement. Combined intramuscular fentanyl and ketorolac resulted in approximately 23% of children experiencing moderate-to-severe pain in the Post-Anesthesia Care Unit, compared to over 50% with ketorolac alone. These findings support multimodal analgesia as the current standard but also highlight that nearly one in four children still experience inadequate pain control despite optimized systemic therapy.

Limitations of Current Approach The standard opioid-NSAID combination has several limitations: opioid-related side effects including respiratory depression, nausea, vomiting, and sedation; growing concerns about opioid exposure in children; NSAID contraindications in patients with renal impairment, bleeding disorders, or hypersensitivity; systemic distribution with potential for widespread effects; limited duration of action; and residual pain in high-risk subgroups such as younger children and those with normal middle ears.

Nerve of Arnold Block as Alternative The Nerve of Arnold, the auricular branch of the vagus nerve, provides sensory innervation to the posterior external auditory canal and tympanic membrane, which is the surgical site for myringotomy and tube placement. Blocking this nerve with local anesthetic offers theoretical advantages including opioid-sparing analgesia with elimination of opioid-related side effects, targeted analgesia directly at the surgical site, extended duration with long-acting local anesthetics, minimal systemic absorption and side effects, and applicability to patients with contraindications to systemic agents.

The technique involves subcutaneous injection of local anesthetic in the space between the mastoid process and the posterior wall of the external auditory canal. While anatomical studies support consistent nerve location and the block has been described in adult case reports, no randomized controlled trials have evaluated its efficacy and safety compared to standard care in pediatric patients.

Study Rationale There is a critical gap in high-quality evidence comparing regional anesthesia techniques to systemic analgesia for pediatric myringotomy and tube placement. This study addresses this gap and aligns with national priorities for opioid-sparing pain management strategies.

Study Design This is a prospective, randomized, double-blind, parallel-group, non-inferiority trial. Three hundred children aged 6 months to 6 years undergoing bilateral myringotomy with tympanostomy tube placement will be randomized in a 1:1 ratio to receive either standard care with intramuscular fentanyl and ketorolac or bilateral Nerve of Arnold block with bupivacaine. Randomization will use a computer-generated sequence with variable block sizes to prevent prediction of treatment assignment.

Blinding Strategy This is a double-blind study with patients, parents, anesthesiologists, surgeons, PACU nurses, and outcome assessors blinded to treatment assignment. Blinding is maintained through use of sham procedures. Patients in the standard care group receive sham Nerve of Arnold blocks with normal saline, while patients in the intervention group receive sham intramuscular injections with normal saline. Study medications are prepared and labeled by the investigational pharmacy with identical appearance.

Interventions Standard Care Group: Patients receive intramuscular fentanyl 2 micrograms per kilogram (maximum 100 micrograms) and intramuscular ketorolac 0.5 milligrams per kilogram (maximum 30 milligrams) administered after induction of anesthesia, plus sham bilateral Nerve of Arnold blocks with normal saline 0.2 milliliters per side.

Intervention Group: Patients receive bilateral Nerve of Arnold blocks with bupivacaine 0.25% solution with 1 in 200000 epinephrine ,0.2 milliliters per side with dexmedetomidine 5 mics per side as adjuvant, plus sham intramuscular injections with normal saline.

All patients receive standardized general anesthesia with sevoflurane and spontaneous ventilation via face mask or laryngeal mask airway. No additional intraoperative analgesics are administered beyond the study interventions.

Rescue Analgesia Protocol Rescue analgesia is available in the Post-Anesthesia Care Unit for patients with FLACC scale scores of 4 or greater, indicating moderate-to-severe pain. First-line rescue medication is oral acetaminophen 20 milligrams per kilogram. Second-line rescue is oral oxycodone 0.1 milligrams per kilogram or intravenous morphine 0.05 milligrams per kilogram for patients unable to take oral medications.

Non-Inferiority Margin The non-inferiority margin is set at 10 percentage points. This margin was selected based on clinical significance and risk-benefit considerations. An increase in the proportion with moderate-to-severe pain from approximately 23% to 33% would remain substantially better than historical controls with ketorolac alone and may be acceptable if offset by opioid-sparing benefits including reduced respiratory depression, nausea, vomiting, and sedation.

Sample Size A total of 300 patients will be enrolled, with 150 patients per group. This sample size provides 80% power to detect non-inferiority with a one-sided alpha of 0.025, assuming a baseline rate of 23.5% in the standard care group, an anticipated rate of 25-28% in the intervention group, and accounting for 10% dropout or protocol violations.

Statistical Analysis The primary analysis will use an intention-to-treat approach comparing the proportion of patients with FLACC scores of 4 or greater between groups. Non-inferiority will be declared if the upper bound of the one-sided 97.5% confidence interval for the difference in proportions (intervention minus standard care) is less than 10 percentage points. A per-protocol analysis will be conducted as a sensitivity analysis. Secondary outcomes will be analyzed using appropriate statistical tests including t-tests, chi-square tests, and multivariable regression models. Subgroup analyses will explore effect modification by age group and middle ear condition.

Safety Monitoring All patients will have continuous monitoring of heart rate, blood pressure, respiratory rate, and oxygen saturation during the Post-Anesthesia Care Unit stay. Adverse events will be recorded and graded according to Common Terminology Criteria for Adverse Events. A Data Safety Monitoring Committee will review safety data at regular intervals. Pre-specified stopping rules include rates of serious adverse events exceeding 5% in either group or significant imbalances in adverse events between groups.

Study Duration Patient enrollment is expected to occur over 18 to 24 months. Each patient will be followed for 24 hours after surgery. Total study duration is anticipated to be 30 months including enrollment, follow-up, data analysis, and manuscript preparation.