Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency Intubation: A Randomized Clinical Trial

Abstract

Importance: Propofol or a combination of a synthetic opioid and muscle relaxant are both recommended for premedication before neonatal intubation but have yet to be compared.

Objective: To compare prolonged desaturation during neonatal nasotracheal intubation after premedication with atropine-propofol vs atropine-atracurium-sufentanil treatment.

Design, setting, and participants: Multicenter, double-blind, randomized clinical trial (2012-2016) in 6 NICUs in France that included 173 neonates requiring nonemergency intubation. The study was interrupted due to expired study kits and lack of funding.

Interventions: Eighty-nine participants were randomly assigned to the atropine-propofol group and 82 to the atropine-atracurium-sufentanil group before nasotracheal intubation.

Main outcomes and measures: The primary outcome was prolonged desaturation (Spo2 <80% lasting > 60 seconds), using intention-to-treat analysis using mixed models. Secondary outcomes assessed the characteristics of the procedure and its tolerance.

Results: Of 173 neonates randomized (mean gestational age, 30.6 weeks; mean birth weight, 1502 g; 71 girls), 171 (99%) completed the trial. Of 89 infants, 53 (59.6%) in the atropine-propofol group vs 54 of 82 (65.9%) in the atropine-atracurium-sufentanil group achieved the primary outcome (adjusted RD, -6.4; 95% CI, -21.0 to 8.1; P = .38). The atropine-propofol group had a longer mean procedure duration than did the atropine-atracurium-sufentanil group (adjusted RD, 1.7 minutes; 95% CI, 0.1-3.3 minutes; P = .04); a less frequent excellent quality of sedation rate, 51.7% (45 of 87) vs 92.6% (75 of 81; P < .001); a shorter median time to respiratory recovery, 14 minutes (IQR, 8-34 minutes) vs 33 minutes (IQR, 15-56 minutes; P = .002), and shorter median time to limb movement recovery, 18 minutes (IQR, 10-43 minutes) vs 36 minutes (IQR, 19-65 minutes; P = .003). In the 60 minutes after inclusion, Spo2 was preserved significantly better in the atropine-propofol group (time × treatment interaction P = .02). Of the atropine-propofol group 20.6% had head ultrasound scans that showed worsening intracranial hemorrhaging (any or increased intraventricular hemorrhage) in the 7 days after randomization vs 17.6% in the atropine-atracurium-sufentanil group (adjusted RD, 1.2; 95% CI, -13.1 to 15.5, P = .87). Severe adverse events occurred in 11% of the atropine-propofol group and in 20% of the atropine-atracurium-sufentanil group.

Conclusions and relevance: Among neonates undergoing nonemergency nasotracheal intubation, the frequency of prolonged desaturation did not differ significantly between atropine used with propofol or atropine used with atracurium and sufentanil. However, the study may have been underpowered to detect a clinically important difference, and further research may be warranted.

Trial registration: ClinicalTrials.gov Identifier: NCT01490580, EudraCT number: 2009-014885-25.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Durrmeyer reports receiving grants from the French Health Ministry, nonfinancial support from Masimo Inc; personal fees and nonfinancial support from Chiesi Pharmaceuticals. Dr Tourneux reports receiving personal fees from Chiesi SAS for consulting and serving as a speaker for a meeting, and nonfinancial support from Abbvie for attending a conference; Dr Levy reports receiving grant support from French Health Ministry, Pfizer, Merck Sharp & Dohme, Sanofi, and GlaxoSmithKline and personal fees and nonfinancial support from Pfizer, all to her institution. Dr Jung reports grants from the French Health Ministry. No other disclosures are reported.

Figures

Figure 1.. Population Flowchart of Premedication Prior to Neonatal Intubation

Figure 2.. Changes From Baseline Over Time

The x-axis includes the time before and after first drug injection (denoted as “0”) in minutes. The y-axis shows difference from the baseline value. Each point represents the mean value and the error bars, 2 standard deviations.