Evaluation of the Neonatal Autonomic Stress During Intubations Under Propofol in a Population of Premature Infants Under 33 w'GA (PROPOSURF)

Hyaline membrane disease is one of the leading causes of morbidity and mortality in premature newborns in industrialized countries. For 30 years, the management of the hyaline membranes disease has been transformed by intratracheal administration of exogenous surfactant (Curosurf®) at birth or in the following hours. In order to limit the harmful effects in terms of barotrauma of mechanical ventilation, several methods have been developed over the last decades, aiming at limiting the mechanical ventilation to the profile of non-invasive ventilation: Thus the administration of surfactant has become faster (although invasive) and if possible followed by immediate extubation following the INSURE (INtubation / SURfactant / Extubation) or LISA (Less-Invasive Surfactant Administration) procedure.

Given the fragility of the children concerned and their low weight, this invasive gesture has long been carried out without premedication. However, taking into account the pain induced and potential hemodynamic consequences of the gesture, neonatal societies now recommend the use of anesthetic before intubation, with a short duration sedative.

Propofol is a general anesthetic that combines these conditions and is widely used in pediatric anesthesia.

In that way, since 2016, the invetigators have modified the sedation protocol for intubation in our department and have recommended Propofol as first-line treatment for term and preterm newborn. A lot of study showed its hemodynamic safety in preterms. However, the investigators lack data on the autonomic stress really observed during intubation in this population. The investigators therefore propose to evaluate these physiological data in a non-randomized prospective observational study in premature infants under 33 weeks of gestational amenorrhea (GA), during a sedation protocol for intubation and surfactant administration according the INSURE or LISA technique, with standardized doses of propofol : 1mg/kg for preterm infants with a birthweight less than 1.5kg and 1.5mg/kg for higher birthweight.

Study Overview

• Status: Completed
• Conditions: Preterm Infant; Hyaline Membrane Disease
• Intervention / Treatment: Other: electrocardiogram

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• France
  • Saint-Étienne, France, 42055
    • Chu de Saint Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Preterm neonates (< 33 weeks GA) admitted to the tertiary Neonatal Intensive Care Unit of Saint-Etienne hospital requiring in the first week of life, an elective tracheal intubation for surfactant administration by INSURE or LISA methods

Description

Inclusion Criteria:

• breathing rate > 60 cycles/min
• Silverman scale > 3 and < 6
• FiO2 > 30% and < 60%
• collected consent from parents

Exclusion Criteria:

• Preterm neonates with Intraventricular hemorrhage grade III & IV
• Preterm neonates with hemodynamic instability
• Preterm neonates with congenital heart disease
• Preterm neonates with severe congenital malformation
• Preterm neonates already sedated and/or under invasive mechanical ventilation
• FiO2 > 60%
• Silverman scale > 6
• Use of amines for maintaining blood pressure
• Use of sedatives or analgesics during the last 24 hours (except paracetamol and ibuprofen)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Preterm neonates (< 33 weeks GA); Preterm neonates requiring in the first week of life, an elective tracheal intubation for surfactant administration by INSURE or LISA methods.	Other: electrocardiogram; Autonomic and hemodynamic evaluation with different indices (LF, heart rate, Systolic, diastolic and mean arterial blood pressure, SaO2) during a sedation protocol for intubation and surfactant administration according the INSURE or LISA technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-time LF values (low frequency)	represent the well-being sympathetic activity of the autonomic nervous system; measured with electrocardiogram	during surfactant administration procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rate	- measured with electrocardiogram	during surfactant administration procedure
systolic arterial blood pressure	- measured with a blood pressure cuff	during surfactant administration procedure
diastolic arterial blood pressure	- measured with a blood pressure cuff	during surfactant administration procedure
Oxygen saturation	- measured by pulse oximetry	during surfactant administration procedure

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Hugues PATURAL, Chu de Saint Etienne

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): August 23, 2022

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: propofol; surfactant; INSURE (Intubation / surfactant / extubation); LISA (Less-invasive surfactant administration)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome; Hyaline Membrane Disease
• Other Study ID Numbers: 18CH129; 2018-003233-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No