Fentanyl and Rocuronium for Tracheal Intubation in Newborns

Official title

Effect of the Association of Fentanyl and Rocuronium on First-Attempt Success Rate of Tracheal Intubation in Newborns: A Randomized Clinical Trial

Overview

Tracheal intubation is a common and critical procedure in neonatal intensive care units (NICU). Despite its clinical importance, first-attempt success rates remain low (approximately 50%), and adverse events - including oxygen desaturation, bradycardia, and airway trauma - are frequent. Premedication with neuromuscular blocking agents has been associated with improved intubation conditions and fewer adverse events in neonates. This randomized, double-blind, parallel-group clinical trial (NEORIN) aims to evaluate whether the addition of rocuronium (0,6 mg/kg IV) to standard fentanyl premedication (1 mcg/kg IV) improves first-attempt success rates of tracheal intubation in newborns admitted to the NICU of Maternidade Ana Braga, Manaus, Brazil. The control group will receive fentanyl plus saline placebo. Sugammadex (16 mg/kg IV) is available as a reversal agent in case of prolonged neuromuscular blockade. A secondary aim is to assess neonatologists' and residents' knowledge of and barriers to the use of neuromuscular blocking agents in neonatal intubation.

Detailed description

Neonatal tracheal intubation is performed in approximately 15-20% of NICU admissions. First-attempt success rates are approximately 49%, and adverse tracheal intubation-associated events (TIAEs) occur in up to 18% of procedures, with severe oxygen desaturation in up to 48% (NEAR4NEOS registry, Foglia et al., 2019). Premedication with neuromuscular blocking agents has been independently associated with a 62% reduction in adverse events (aOR 0.38; 95% CI 0.25-0.57).

Rocuronium is a non-depolarizing neuromuscular blocking agent with rapid onset, stable hemodynamic profile, and full reversibility with sugammadex, making it a safe choice for neonatal premedication.

The NEORIN trial will enroll 102 newborns (51 per group) with postnatal age ≤28 days or corrected gestational age \<44 weeks, requiring non-emergent tracheal intubation. Randomization will be performed in variable-sized permuted blocks (4 and 6), with allocation concealment through sequential opaque sealed envelopes.

Intervention group: fentanyl 1 mcg/kg IV + rocuronium 0.6 mg/kg IV. Control group: fentanyl 1 mcg/kg IV + saline placebo (equivalent volume). Sugammadex is available at the bedside throughout the study as a mandatory safety requirement.

The primary composite outcome is first-attempt intubation success without physiological instability, defined as correct tube placement on the first laryngoscopy attempt confirmed by colorimetric CO2 detection, with no SpO2 drop \>20% from baseline and no bradycardia (HR \<100 bpm). All procedures will be video-recorded for blinded outcome assessment.

A secondary descriptive study will assess neonatologists' and residents' knowledge of and barriers to neuromuscular blocking agent use in neonatal intubation, using a structured questionnaire applied before the start of the clinical trial.

Interventions

• Drug Rocuronium Bromide 10 MG/ML
  Rocuronium 0.6 mg/kg IV, single dose, administered as a bolus after fentanyl 1 mcg/kg IV, approximately 60 seconds before laryngoscopy
• Drug Fentanyl 1 mcg/kg IV, single dose, administered before non-emergent tracheal intubation.
  Fentanyl 1 mcg/kg IV, single dose, administered before non-emergent tracheal intubation in both groups.

Primary outcome measures

• First-attempt intubation success without physiological instability [Time frame: During the intubation procedure, from first laryngoscopy attempt to confirmation of tube position (up to 5 minutes)]

Secondary outcome measures (7)

• Total number of intubation attempts [Time frame: During the intubation procedure, from first laryngoscopy attempt to successful intubation (up to 5 minutes)]
• Procedure duration [Time frame: From first laryngoscopy attempt to confirmation of endotracheal tube position, assessed during the intubation procedure (up to 5 minutes)]
• Severe oxygen desaturation [Time frame: During the intubation procedure, from first laryngoscopy attempt to successful intubation (up to 5 minutes)]
• Bradycardia during intubation [Time frame: During the intubation procedure, from first laryngoscopy attempt to confirmation of tube position (up to 5 minutes)]
• Need for additional maneuvers [Time frame: During the intubation procedure, from first laryngoscopy attempt to confirmation of tube position (up to 5 minutes)]
• Medication-related adverse events [Time frame: During the intubation procedure, from first laryngoscopy attempt to confirmation of tube position (up to 5 minutes)]
• Knowledge and barriers to neuromuscular blocking agent use [Time frame: At the time of enrollment, before the intubation procedure, assessed once per participant]

Eligibility criteria

Inclusion criteria

• Newborns admitted to the NICU, ≤28 postnatal days OR corrected gestational age <44 weeks
• Indication for non-emergent orotracheal intubation (≥5 minutes between decision to intubate and start of laryngoscopy)
• Informed consent signed by legal guardians

Exclusion criteria

• Upper airway malformations
• Use of neuromuscular blocking agent in the 24 hours prior to enrollment
• Known hypersensitivity to fentanyl or rocuronium
• Severe hemodynamic instability (ongoing shock)
• Anticipated difficult airway (micrognathia, cleft palate, or similar)
• Cyanotic congenital heart disease with critical instability
• Neonatal abstinence syndrome
• Concurrent enrollment in another interventional clinical trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Maternidade Ana Braga - UTI Neonatal — Manaus

Publications

• Lin JD, Fang WF, Tang KT, Cheng CW. Effects of exogenous melatonin on clinical and pathological features of a human thyroglobulin-induced experimental autoimmune thyroiditis mouse model. Sci Rep. 2019 Apr 10;9(1):5886. doi: 10.1038/s41598-019-42442-0. PMID 30971749
• Smith FJ, Holman CD, Moorin RE, Tsokos N. Lifetime risk of undergoing surgery for pelvic organ prolapse. Obstet Gynecol. 2010 Nov;116(5):1096-100. doi: 10.1097/AOG.0b013e3181f73729. PMID 20966694
• Krick J, Gray M, Umoren R, Lee G, Sawyer T. Premedication with paralysis improves intubation success and decreases adverse events in very low birth weight infants: a prospective cohort study. J Perinatol. 2018 Jun;38(6):681-686. doi: 10.1038/s41372-018-0082-2. Epub 2018 Feb 21. PMID 29467520
• Herrick HM, Glass KM, Johnston LC, Singh N, Shults J, Ades A, Nadkarni V, Nishisaki A, Foglia EE; for the NEAR4NEOS Investigators. Comparison of Neonatal Intubation Practice and Outcomes between the Neonatal Intensive Care Unit and Delivery Room. Neonatology. 2020;117(1):65-72. doi: 10.1159/000502611. Epub 2019 Sep 27. PMID 31563910
• Foglia EE, Ades A, Sawyer T, Glass KM, Singh N, Jung P, Quek BH, Johnston LC, Barry J, Zenge J, Moussa A, Kim JH, DeMeo SD, Napolitano N, Nadkarni V, Nishisaki A; NEAR4NEOS Investigators. Neonatal Intubation Practice and Outcomes: An International Registry Study. Pediatrics. 2019 Jan;143(1):e20180902. doi: 10.1542/peds.2018-0902. Epub 2018 Dec 11. PMID 30538147

Identifiers

NCT: NCT07650552 · NEORIN-2026-MAB/UEA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗