Can’t intubate to give surfactant? Maybe try this!

Can’t intubate to give surfactant? Maybe try this!

Intubation is not an easy skill to maintain with the declining opportunities that exist as we move more and more to supporting neonates with CPAP.  In the tertiary centres this is true and even more so in rural centres or non academic sites where the number of deliveries are lower and the number of infants born before 37 weeks gestational age even smaller.  If you are a practitioner working in such a centre you may relate to the following scenario.  A woman comes in unexpectedly at 33 weeks gestational age and is in active labour.  She is assessed and found to be 8 cm and is too far along to transport.  The provider calls for support but there will be an estimated two hours for a team to arrive to retrieve the infant who is about to be born.  The baby is born 30 minutes later and develops significant respiratory distress.  There is a t-piece resuscitator available but despite application the baby needs 40% oxygen and continues to work hard to breathe.  A call is made to the transport team who asks if you can intubate and give surfactant.  Your reply is that you haven’t intubated in quite some time and aren’t sure if you can do it.  It is in this scenario that the following strategy might be helpful.

Surfactant Administration Through and Laryngeal Mask Airway (LMA)

Use of an LMA has been taught for years in NRP now as a good choice to support ventilation when one can’t intubate.  The device is easy enough to insert and given that it has a central lumen through which gases are exchanged it provides a means by which surfactant could be instilled through a catheter placed down the lumen of the device.  Roberts KD et al published an interesting unmasked but randomized study on this topic Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial. Due to size limitations (ELBWs are too small to use this in using LMA devices) the eligible infants included those from 28 0/7 to 35 6/7 weeks and ≥1250 g.  The infants needed to all be on CPAP +6 first and then fell into one of two treatment groups based on the following inclusion criteria: age ≤36 hours,
(FiO2) 0.30-0.40 for ≥30 minutes (target SpO2 88% and 92%), and chest radiograph and clinical presentation consistent with RDS.
Exclusion criteria included prior mechanical ventilation or surfactant administration, major congenital anomalies, abnormality of the airway, respiratory distress because of an etiology other than RDS, or an Apgar score <5 at 5 minutes of age.

Procedure & Primary Outcome

After the LMA was placed a y-connector was attached to the proximal end.  On one side a CO2 detector was placed and then a bag valve mask in order to provide manual breaths and confirm placement over the airway.  The other port was used to advance a catheter and administer curosurf in 2 mL aliquots.  Prior to and then at the conclusion of the procedure the stomach contents were aspirated and the amount of surfactant determined to provide an estimate of how much surfactant was delivered to the lungs.  The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life.  Treatment failure was defined upfront and required 2 of the following: (1) FiO2 >0.40 for >30
minutes (to maintain SpO2 between 88% and 92%), (2) PCO2 >65 mmHg on arterial or capillary blood gas or >70 on venous blood gas, or (3) pH <7.22 or 1 of the following: (1)  recurrent or severe apnea, (2) hemodynamic instability requiring pressors, (3) repeat surfactant dose, or (4) deemed necessary by medical provider.

Did it work?

It actually did. Of the 103 patients enrolled (50 LMA and 53 control) 38% required intubation in the LMA group vs 64% in the control arm.  The authors did not reach their desired enrollment based on their power calculation but that is ok given that they found a difference.  What is really interesting is that they found a difference in the clinical end point despite many infants clearly not receiving a full dose of surfactant as measured by gastric aspirate. Roughly 25% of the infants were found to have not received any surfactant, 20% had >50% of the dose in the stomach and the other 50+% had < 10% of the dose in the stomach meaning that the majority was in fact deposited in the lungs.  I suppose it shouldn’t come as a surprise that among the secondary outcomes the duration length of mechanical ventilation did not differ between two groups which I presume occurred due to the babies needing intubation being similar.  If you needed it you needed it so to speak. Further evidence though of the effectiveness of the therapy was that the average FiO2 30 minutes after being treated was significantly lower in the group with the LMA treatment 27 vs 35%.  What would have been interesting to see is if you excluded the patients who received little or no surfactant, how did the ones treated with intratracheal deposition of the dose fare?  One nice thing to see though was the lack of harm as evidenced by no increased rate of pneumothorax, prolonged ventilation or higher oxygen.

Should we do this routinely?

There was a 26% reduction in intubations in te LMA group which if we take this as the absolute risk reduction means that for every 4 patients treated with an LMA surfactant approach, one patient will avoid intubation.  That is pretty darn good!  If we also take into account that in the real world, if we thought that little of the surfactant entered the lung we would reapply the mask and try the treatment again.  Even if we didn’t do it right away we might do it hours later.

In a tertiary care centre, this approach may not be needed as a primary method.  If you fail to intubate though for surfactant this might well be a safe approach to try while waiting for a more definitive airway.  Importantly this won’t help you below 28 weeks or 1250g as the LMA is too small but with smaller LMAs might this be possible.  Stay tuned as I suspect this is not the last we will hear of this strategy!

Giving surfactant through an LMA. Time to ditch the endotracheal tube?

Giving surfactant through an LMA. Time to ditch the endotracheal tube?

 

In the spirit of full disclosure I have to admit I have never placed a laryngeal mask airway (LMA) in a newborn of any gestational age.  I have played with them in simulated environments and on many occasion mentioned that they are a great alternative to an ETT especially in those situations where intubation may not be possible due to the skill of the provider or the difficulty of the airway in the setting of micrognathia for example.

In recent years though we have heard of examples of surfactant delivery via these same devices although typically these were only case reports. More recently a small randomized study of 26 infants by Attridge et al demonstrated in the group randomized to surfactant administration through an LMA that oxygen requirements were reduced after dosing.  This small pilot provides sufficient evidence to show that it is possible to provide surfactant and that at least some gets into the airway of the newborn.  This proof of concept though while interesting, did not answer the question of whether such delivery of surfactant would be the same or better than through an ETT.  As readers of my blog posts know, my usual stance on things is that the less invasive the better and as I look through the literature, I am drawn to concepts such as this to see if they can be added to our toolbox of non or less invasive strategies in the newborn.

A Minimally Invasive Technique For The Masses?

This past month, a small study by Pinheiro et al sought to answer this question by using 61 newborns between 29 0/7 – 36 6/7 weeks and greater than 1000g and randomizing them to either surfactant via the INSURE technique or LMA.  I cannot stress enough so will get it out of the way at the start that this strategy is not for those <1000g as the LMA is not designed to fit them properly and the results (to be shown) should not be generalized to this population. Furthermore then study included only those infants who needed surfactant between 4 – 48 hours of age, were on CPAP of at least 5 cm H2O and were receiving FiO2 between 30 – 60%.  All infants given surfactant via the insure technique were premedicated with atropine and morphine while those having an LMA received atropine only.  The primary outcome of the study was need for subsequent intubation or naloxone within 1 hour of surfactant administration.  The study was stopped early after an interim analysis (done as the fellow involved was finishing their fellowship – on a side note I find this an odd reason to stop) demonstrated better outcomes in the group randomized to the LMA.

Before we get into the results let’s address the possible shortcomings of the study as they might already be bouncing around your heads.  This study could not be blinded and therefore there could be a significant bias to the results.  The authors did have predetermined criteria for reintubation and although not presented, indicate that those participating stuck to these criteria so we may have to acknowledge they did the best they could here.  Secondly the study did not reach their numbers for enrolment based on their power calculation.  This may be ok though as they found a difference which is significant.  If they had found no difference I don’t think I would be even writing this entry!  Lastly this study used a dose of surfactant at 3 mL/kg.  How well would this work with the formulation that we use BLES that requires 5 mL/kg?

What were the results?

Intervention Failure LMA Group ETT group p
Any failure 9 (30%) 23(77%) <0.001
Early failure 1 (3%) 20 (67%) <0.001
Late failure 8 (27%) 3 (10%) 0.181

What do these results tell us?  The majority of failures occurred within an hour of delivery of surfactant in the ETT group?  How does this make any sense?  Gastric aspirates for those in the LMA group but not the INSURE group suggest some surfactant missed the lung in the former so one would think the intubation group should have received more surfactant overall however it would appear to be the premedication.  The rate of needing surfactant afterwards is no different and in fact there is a trend to needing reintubation more often in the LMA group but the study was likely underpowered to detect this difference.  Only two patients were given naloxone to reverse the respiratory depressive effects of morphine in those given the INSURE technique so I can’t help but speculate that if this practice was more frequent many of the reintubations might have been avoided.  This group was quite aggressive in sticking to the concept of INSURE as they aimed to extubate following surfactant after 5 – 15 minutes.  I am a strong advocate of providing RSI to those being electively intubated but if the goal is to extubate quickly then I believe one must be ready to administer naloxone soon after extubation if signs of respiratory depression are present and this did not happen effectively in this study.  Some may argue those getting the INSURE technique should not be given any premedication at all but that is a debate that will go on for years I am sure but they may have a valid point given this data.

Importantly complications following either procedure were minimal and no different in either group.

Where do we go from here?

Despite some of the points above I think this study could prove to be important for several reasons.  I think it demonstrates that in larger preterm infants it is possible to avoid any mechanical ventilation and still administer surfactant.  Many studies using the minimally invasive surfactant treatment (MIST) approach have been done but these still require the skill of laryngoscopy which takes a fair bit of skill to master.  The LMA on the other hand is quite easy to place and is a skill that can be taught widely.  Secondly, we know that even a brief period of over distension from PPV can be harmful to the lung therefore a strategy which avoids intubation and direct pressure to the lung may offer some longer term benefit although again this was not the study to demonstrate that.

Lastly, I see this as a strategy to look at in more rural locations where access to highly skilled level III care may not be readily available.  We routinely field calls from rural sites with preterm infants born with RDS and the health care provider either is unable to intubate or is reluctant to try in favour of using high flow oxygen via mask.  Many do not have CPAP either to support such infants so by the time our Neonatal Transport team arrives the RDS is quite significant.  Why not try surfactant through the LMA?  If it is poorly seated over the airway and the dose goes into the stomach I don’t see them being in any worse shape than if they waited for the team to arrive.  If some or all of the dose gets in though there could be real benefit.

Might this be right for your centre?  As we think about outreach education and NRP I think this may well become a strong reason to spend a little more time on LMA training.  We may be on to something!