Clinical trial NCT01517828: Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room
Official title: Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Respiratory Distress Syndrome
Prematurity of Fetus
Keywords: Intubation
Delivery room
Sedation
Analgesia
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2012-01-25
Enrollment: 62
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anesthesia is rarely used to intubate newborns in delivery room because of the very difficulty of accessing veins. The investigators hypothesized that intranasal administration of sedative would be an effective alternative. -Midazolam and Ketamine are two drugs used during neonates' intubation. They are also used intranasally in the absence of venous access-In a pilot study the investigators have demonstrated that sedation with Midazolam was effective in 67% of the patients. Efficiency was defined by a specific pain score: FANS \< 4 (Faceless Acute Neonatal Pain Scale) and by an impedancemetric Pain monitor \< 0.2 spike/s.

The investigators hypothesized that intranasal ketamine would increase procedure effectiveness from 67 to 90%.

* Main objective: To compare newborns sedation quality as they are sedated either by intranasal Midazolam or by intranasal Ketamine during intubation in delivery room.
* Secondary Objectives: To compare intubation quality, hemodynamic and respiratory tolerance, and neurological outcomeat 2 years within the two groups.

Detailed description: Randomized, double blind prospective multicenter study. Patients:-Inclusion criteria: (1) neonates in delivery room (2) Presence of repiratory distress syndrom requiring intubation (Silverman score\> 3 and / or FiO2 greater than 30 % in premature infants under 30 weeks and over 40% after 30 weeks (3) hemodynamic stability (mean arterial pressure\> 3° percentile)

* Exclusion criteria: (1) Need for intubation in extreme emergency (pneumothorax, meconium aspiration, congenital diaphragmatic hernia, perinatal asphyxia) (2) Birth in the absence of an independent appraiser (3) mother under general anesthesia.
* Number of subjects required: 120 patients (60 per group) over a period of two years. This number was calculated to show a difference in sedation effectiveness from 67 to 90% with an alpha risk of 5% and a beta risk of 20%.
* Study design:

After obtaining parental consent, patients will be randomized in "Midazolam" arm or in "Ketamine" arm . Midazolam (0.2mg/kg = 0.2ml/kg) or Ketamine (2mg/kg = 0.2 ml/kg) are instilled in the nose, using a 1 ml syringe. The gesture will be directed by a physician having yet successfully completed a minimum of 50 intubations. After sedation completion, intubation decision will be taken at the onset of muscle relaxation or on the occurrence of apnea.

* The clinical pain score will be evaluated on film a posteriori by two independent observers using a scale of hetero pain assessment.-Pain will be evaluated through the study of skin conductance.
* The quality of intubation will be judged by the number of attempts required and by the duration of glottis exposure.
* Hemodynamic and respiratory tolerances will be judged by measuring respectively variations in blood pressure, heart rate, FiO2 and the oxygen saturation.

The neurological follow-up will be carried out according to Brunet-Lezine developmental scale at the age of 2 years.

Eligibility criteria: Inclusion Criteria:

* Neonates in delivery room
* Presence of respiratory distress syndrom requiring intubation (Silverman score\> 3 and / or FiO2 greater than 30 % in premature infants under 30 weeks and over 40% after 30 weeks
* Hemodynamic stability (mean arterial pressure\> 3° percentile)

Exclusion Criteria:

* Need for intubation in extreme emergency (pneumothorax, meconium aspiration, congenital diaphragmatic hernia, perinatal asphyxia)
* Birth in the absence of an independent appraiser
* Mother under general anesthesia

Primary outcomes:
measure: Newborns sedation quality
timeFrame: during the 10 minutes of intubation
Secondary outcomes:
measure: intubation quality
timeFrame: during the 10 minutes of intubation
measure: hemodynamic and respiratory tolerance
timeFrame: during 24 hours after intubation
measure: neurological outcome at 2 years within the 2 groups
timeFrame: 2 years after the treatment
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire
city: Nimes
country: France
facility: Centre Hospitalier Universitaire
city: Perpignan
country: France
facility: Centre Hospitalier Général
Study officials:
affiliation: University Hospital, Montpellier
name: Christophe CM MILESI, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Milesi C, Baleine J, Mura T, Benito-Castro F, Ferragu F, Thiriez G, Thevenot P, Combes C, Carbajal R, Cambonie G. Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F221-F226. doi: 10.1136/archdischild-2017-312808. Epub 2017 Aug 17.