Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room

• Newborns sedation quality [ Time Frame: during the 10 minutes of intubation ] [ Designated as safety issue: No ]
  The sedation quality of 2 newborns groups will be compared during the 10 minutes of intubation directly in delivery room and after on the film Pain evaluation done by a Specific clinical Score : the Faceless Acute Neonatal pain Scale (FANS) noted by two independent professional persons. And for Montpellier center, evaluation of pain by cutaneous conductance
  
  

• intubation quality [ Time Frame: during the 10 minutes of intubation ] [ Designated as safety issue: Yes ]
  Intubation quality will be evaluated and compared between the two groups by numbers of attempts, duration of glottis exposition (from introduction to withdrawal of laryngoscop)
  
  
• hemodynamic and respiratory tolerance [ Time Frame: during 24 hours after intubation ] [ Designated as safety issue: Yes ]

  Hemodynamic tolerance will be measured by Mean Arterial Pressure every 3 minutes before and after product instillation and during the intubation. After intubation, measure of Mean Arterial Pressure will be done every 10 minutes during 1 hour and after every hour until 24 hours. Cardiac frequency and cardiac fraquency variations will be measured and analyzed.

  Respiratory tolerance will be evaluated by continuing measure of SpO2, delay of instillation of surfactant dose and the need to administer un second dose of surfactant

  
  
• neurological outcome at 2 years within the 2 groups [ Time Frame: 2 years after the treatment ] [ Designated as safety issue: Yes ]
  Prevalence of neurological complications (intraventricular hemorragies, periventricular leucomalacies), development quotient at 2 years (Brunet Lezine scale)will be evaluated and compared between the two groups
  
  

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.