Research Article: Premedication practices for delivery room intubations in premature infants in France: Results from the EPIPAGE 2 cohort study

Date Published: April 10, 2019

Publisher: Public Library of Science

Author(s): Elizabeth Walter-Nicolet, Emilie Courtois, Christophe Milesi, Pierre-Yves Ancel, Alain Beuchée, Pierre Tourneux, Valérie Benhammou, Ricardo Carbajal, Xavier Durrmeyer, Edgardo Szyld.


To assess premedication practices before tracheal intubation of premature newborns in the delivery room (DR).

From the national population-based prospective EPIPAGE 2 cohort in 2011, we extracted all live born preterms intubated in the DR in level-3 centers, without subsequent circulatory resuscitation. Studied outcomes included the rate and type of premedication, infants’ and maternities’ characteristics and survival and major neonatal morbidities at discharge from hospital. Univariate and multivariate analysis were performed and a generalized estimating equation was used to identify factors associated with premedication use.

Out of 1494 included neonates born in 65 maternities, 76 (5.1%) received a premedication. Midazolam was the most used drug accounting for 49% of the nine drugs regimens observed. Premedicated, as compared to non premedicated neonates, had a higher median [IQR] gestational age (30 [28–31] vs 28 [27–30] weeks, p<10−3), median birth weight (1391 [1037–1767] vs 1074 [840–1440] g, p<10−3) and median 1-minute Apgar score (8 [6–9] vs 6 [3–8], p<10−3). Using univariate analyses, premedication was significantly less frequent after maternal general anesthesia and during nighttime and survival without major morbidity was significantly higher among premedicated neonates (56/73 (81.4%) vs 870/1341 (69.3%), p = 0.028). Only 10 centers used premedication at least once and had characteristics comparable to the 55 other centers. In these 10 centers, premedication rates varied from 2% to 75%, and multivariate analysis identified gestational age and 1-minute Apgar score as independent factors associated with premedication use. Premedication rate before tracheal intubation was only 5.1% in the DR of level-3 maternities for premature neonates below 34 weeks of gestation in France in 2011 and seemed to be mainly associated with centers’ local policies.

Partial Text

Tracheal intubation is commonly performed in the delivery room (DR) for premature neonates. This procedure is associated with many adverse events such as bradycardia, hypoxia and increased intracranial pressure [1–4]. Awake intubation is especially associated with increased intracranial pressure, that can be partially prevented by premedication in neonates [1, 2]. In the Neonatal Intensive Care Unit (NICU), adverse tracheal intubation–associated events might be reduced by premedication use, especially paralysis [5]. In addition, an association was reported between the number of intubation attempts in the first 4 days of life and severe intra-ventricular hemorrhage (IVH) [6]. This study’s conclusion speculated that premedication might have a protective effect against IVH, but no evidence was provided. Finally tracheal intubation is painful [3, 7] but is paradoxically a procedure for which analgosedation is not systematically administered [7–9]. On the other hand, the transitional period at birth might expose neonates to a higher risk of adverse drug reactions in case of premedication. Altogether these observations establish a clinical equipoise concerning the use of premedication for non-emergent DR intubations. Currently, the American Academy of Pediatrics (AAP) recommends systematic premedication for neonatal intubation except for “resuscitation in the DR or for life-threatening situations”, based on available evidence and ethical considerations [3]. Those recommendations may theoretically be applied whatever the location of a patient, if all safety rules are gathered. Nevertheless, no clear guidance is provided for non-emergent intubations in the DR. This is probably due to the limited data available on the topic. Indeed, most observational studies on DR intubation did not mention premedication use [10] or reported a premedication rate ranging from 0% to 26%, varying with gestational age (GA) categories [5, 6, 11]. However, recent studies demonstrated the feasibility and suggested analgesic efficacy of premedication before DR intubation [12–14]. Considering that the DR setting was obviously different from the NICU setting, we decided to conduct a specific study on premedication practices in the DR. The aim of our study was to analyze the practices of premedication before tracheal intubation of premature infants’ in the DR of level-3 maternity-units, to describe outcomes before hospital discharge and to identify variables associated with premedication use at a national level using the French EPIPAGE 2 cohort [15].

To our knowledge, this is one of the first large descriptive studies to prospectively evaluate premedication before tracheal intubation in the DR for preterm neonates. A premedication was performed for about 5% of the selected population, in less than 15% of the level-3 maternity units and with a large variety of drugs regimens. Survival and severe neonatal morbidity at hospital discharge were not increased in premedicated infants. Only two patient’s independent factors, GA and 1 minute Apgar score, were associated with the use of premedication for intubation.