Early respiratory management of preterm infants immediately after birth should be as gentle as possible. With this so-called developmental approach, unnecessary invasive methods can be avoided or at least postponed. This kind of "soft landing" allows cardiorespiratory transition with fewer adverse outcomes. Less invasive surfactant administration (LISA) is a technique that involves delivery of surfactant to a spontaneously breathing infant through a thin catheter. This technique minimizes the risk for neonatal lung injury caused by positive pressure ventilation. LISA is nowadays widely used in neonatal intensive care units (NICU). Although less invasive, newborns exposed to this procedure need premedication prior the procedure. There is no consensus, which drug would be the optimal premedication for LISA and the research on this topic is lacking. An ideal premedication would treat the procedural pain without suppressing the infant's own breathing. The sedation and analgesia should start fast but the effect should be short-acting with as few adverse effects as possible. The aim of this randomized, controlled trial (RCT) is to evaluate the feasibility, efficacy and safety of LISA protocol with the premedication of either ketamine or fentanyl by investigating whether one or the other is associated with lower rate of adverse events, hence would be preferred choice for premedication protocol.

All infants fulfilling the inclusion criteria during the study period are asked to participate in this randomized controlled trial of LISA premedication. Written informed parental consent is acquired from all of the participants. After the consent, individuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. The investigators and medical staff are blinded to the fact which study medication is given. This study is a pilot study and 20 patients are recruited for both groups. Randomization is done in the blocks of four.

S-ketamine (Ketanest-S 5 mg/ml) or fentanyl (Fentanyl-Hamel diluted to 5 μg/ml) is used as a masked study drug. Both study drug solutions appear equally transparent. Drug administration is started with glucopyrrolate (Robinul 0.2 mg/ml), which is given intravenously at a dose of 5 µg/kg. Thereafter, the masked study drug is administered intravenously slowly in one to two minute injection of 0.2 ml/kg. In this way, doses of S-ketamine 1 mg/kg or alternatively fentanyl 1 μg/kg is received. After five minutes (from the beginning of administration of the study drug), videolaryngoscopy is started. If the study drug does not have sufficient effect, the study drug may be repeated with the same dose. If study drug fails to give appropriate conditions to LISA procedure, midazolam 0,1 mg/kg can be used as an additional drug.

Inclusion Criteria:

• Gestational age at birth ≥26 weeks
• Respiratory insufficiency managed with non-invasive respiratory support (nasal continuous positive airway pressure or high-flow)
• Requirement for oxygen to maintain oxygen saturation in the target range and need for surfactant treatment (according to clinician's assessment)
• If further doses of surfactant are needed, patient can be re-randomized

Exclusion Criteria:

• Severe RDS with high oxygen requirements, severe respiratory acidosis and/or widespread atelectasis radiologically, such that ongoing ventilator support will be necessary after surfactant therapy (intubation in preferable to LISA if FiO2 >40% at GA <28 weeks and >60% at GA ≥28 weeks)
• Maxillo-facial, tracheal or known pulmonary malformations
• Any known chromosomal abnormality or severe malformation
• An alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia)

The investigators and medical staff are blinded to the fact which study medication is given. A pharmacist or a nurse not participating in treatment of the child in question prepares the drug. Preparation of the study drug is done in a different location than where the treatment takes place.