I knew it was a matter of time before a study looking at this strategy came out. Whether you intubate using INSURE or a LISA/MIST technique (passing a semi-rigid catheter through the vocal cords to give surfactant while a baby is on CPAP) there would have to be those that argue the placement of the laryngoscope blade in the mouth and passage of the catheter through the trachea must be uncomfortable. Given such concerns, why wouldn’t you want to provide some sedation to the patient? The main concern would be suppression of respiratory drive and need for intubation or PPV. LISA/MIST usage has been found in systematic reviews to lead to less risk of BPD but what if sedation leads to more PPV especially with uncontrolled tidal volumes on these fragile lungs? Will the benefits remain?

Propofol Before MIST

Dekker et al published Sedation during minimal invasive surfactant therapy: a randomised controlled trial in which they looked at infants receiving surfactant administration by MIST in infants born at 26 – 36 weeks with stratification of results into two groups (26–31+6 and 32–36+6 weeks). The intervention was to give a relatively small dose of propofol 1 mg/kg compared to the typical dose of 2.5 mg/kg prior to using MIST. Physicians were unblinded to the intervention but nurses were asked (they were blinded) to determine the COMFORTneo score as a measure of discomfort or pain. The primary outcome was the percentage of infants with a score <14 during the procedure. A power calculation to determine numbers needed for the study indicated 39 per arm and was based on a previous study (not using propofol though). While it does not appear that a sham was used for a placebo arm, sucrose was utilized for additional comfort in both arms.

The Results Please

Sedation seemed to work even at this lower dose of propofol as the group who received it had a higher percentage with a score <14 (32/42 (76%) vs 8/36 (22%), p<0.001). Moreover, the overall mean scores were also lower (12±3 vs 17±4; p<0.001). When looking at rates of complications though some interesting but perhaps not surprising findings emerge.

A greater risk of desaturation events existed in the group receiving even a low dose of propofol.  Not surprisingly with a greater risk of oxygen desaturation there was a need for more nasal intermittent mechanical ventilation (93% vs 47%).  Finally, while the numbers are small the incidence of grade 3 or 4 IVH was 0 in the group that received no sedation and 5% in the group that did.  While non significant it is worth pointing out that as with all of the listed complications, this study was underpowered for any meaningful secondary outcome conclusions.  Given what we know about the interaction of positive pressure ventilation and risks of IVH it is just something to raise an eyebrow at for now.

What is the biggest problem with the study?

As I see it the absence of the placebo group such that the Neonatologists knew who received propofol and who did not makes it difficult to know if there really was a true need for PPV.  In the sedation group the percentage of babies that received nasal IMV almost matches perfectly those that experienced desaturation events (93 and 91%) but in the non-sedated group it was 47% and 69%.  Were Neonatologists more apt to let the desaturations sit without PPV if they knew the infant did not get propofol and conversely assume they needed PPV if they received a sedative?  It seems to me that the study would have been improved with the use of the sham procedure.  The scoring by the nurses who were blinded shows that even with a lower dose of propofol than normal though it still provides some sedation.

I would stay tuned in this area as I am sure this will not be the last we hear of this but for now I would suggest that sedation for MIST/LISA should not be routinely done, at least based on this study.