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

NCT ID: NCT01517828

Last Updated: 2014-12-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2016-05-31

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.

Conditions

Respiratory Distress Syndrome; Prematurity of Fetus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ketamine Arm

Phial of Ketamine (50mg/5ml) will be used and the dose administered will be 2 mg/kg.

Group Type: EXPERIMENTAL

Sedation by ketamine

Intervention Type: DRUG

Kétamine (50mg/5ml, Panpharma): for a posology of 2 mg/kg: dose of 0.2 ml/kg Intranasal administration with a 1 ml syringe. Kétamine is a derivated of phencyclidine with a sedative, anesthesic, analgesic and amnesiant activity. Ketamine keeps also a protective reflex of upper respiratory tracts.

One injection will be done and if after 7 minutes, newborn is not correctly sedated another dose of same product will be done.

Midazolam Arm

Phials of midazolam (5mg/5ml)will be used and the dose administered will be 0.2 ml/kg.

Group Type: ACTIVE_COMPARATOR

Sedation with Midazolam

Intervention Type: DRUG

Midazolam (phyal of 5mg/5ml, Mylan S.A.S.) for a posology of 0.2 mg/kg: dose of 0.2 ml/kg Instillation in intranasal with a syringe of 1 ml. Midazolam is an imidazobenzodiazépine, witj a sedative and hypnotic activity,anxiolytic, anti convulsive and muscle relaxant proprieties.

One injection will be done and if after 7 minutes, newborn is not correctly sedated another dose of same product will be done.

Interventions

Sedation by ketamine

Kétamine (50mg/5ml, Panpharma): for a posology of 2 mg/kg: dose of 0.2 ml/kg Intranasal administration with a 1 ml syringe. Kétamine is a derivated of phencyclidine with a sedative, anesthesic, analgesic and amnesiant activity. Ketamine keeps also a protective reflex of upper respiratory tracts.

One injection will be done and if after 7 minutes, newborn is not correctly sedated another dose of same product will be done.

Intervention Type: DRUG

Sedation with Midazolam

Midazolam (phyal of 5mg/5ml, Mylan S.A.S.) for a posology of 0.2 mg/kg: dose of 0.2 ml/kg Instillation in intranasal with a syringe of 1 ml. Midazolam is an imidazobenzodiazépine, witj a sedative and hypnotic activity,anxiolytic, anti convulsive and muscle relaxant proprieties.

One injection will be done and if after 7 minutes, newborn is not correctly sedated another dose of same product will be done.

Intervention Type: DRUG

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

• Maximum Eligible Age: 2 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe CM MILESI, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Locations

Centre Hospitalier Universitaire

Montpellier, , France

Centre Hospitalier Universitaire

Nîmes, , France

Centre Hospitalier Général

Perpignan, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 28818854 (View on PubMed)

Other Identifiers

2011-003216-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UF8736

Identifier Type: -

Identifier Source: org_study_id