So how do we improve resuscitation of newborn babies, and specifically of the preterm? Although I am a “true believer (TM)” in evidence based practice it is obvious that every individual change in neonatal practice will not (and cannot) be preceded by large RCTs showing improvement in life-long quality-of-life measures. We have to make some changes based on evidence of acute and/or physiologic effects and on likelihoods, that is, how likely is it that this improved short term finding, or improvement in physiology, will be harmful in the long term, and how much does it seem that the babies might benefit from changing practice. If we couple such considerations with on-going surveillance of outcomes to assure that we are not causing unexpected harm, then we can progress.
In a sense this is how neonatology has progressed since the beginning; many of the things that we do now have not been based on RCTs, but rather on the observation that our outcomes are improving, so the last group of changes we made are probably OK. A publication (Battin MR, Knight DB, Kuschel CA, Howie RN. Improvement in mortality of very low birthweight infants and the changing pattern of neonatal mortality: The 50-year experience of one perinatal centre. Journal of Paediatrics and Child Health. 2012;48(7):596-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1754.2012.02425.x/abstract) recently documented and quantified the enormous advances in neonatal care that have occurred during the lifetime of many of the senior neonatologists who are still working (like me). I still remember my first 26 week survivor. We now expect over 90% survival at 26 weeks. Just think about that a minute. From 100% mortality to 90% survival in one professional career.
This has occurred in the context of very few individual trials that have documented improved mortality, and despite numerous well-documented disasters. When we have carefully and thoughtfully introduced modest changes in practice and evaluated them as we go along, we have been able to improve survival and improve outcomes.
A case in point is controlling and limiting tidal volumes during resuscitation. Animal models show that a few over-large breaths during resuscitation can initiate lung injury. We will never be able to prove this in actual clinical practice, and in fact the animal models are of questionable relevance. Some being mature, some with normal lungs etc. Nevertheless it seems that over-distending lungs is bad for them, especially fragile premature lungs. On the other hand if you give very large pressures, but don’t cause overdistension that is probably of not much concern. Unfortunately a manometer is an easy thing to make and use. A tidal volume monitor less so. We already know that just looking at the chest movement is an almost useless practice, we really can’t tell if a baby is getting adequate or inadequate tidal volumes. We can sometimes get an idea that a baby is getting much too large tidal volumes so we still need to keep our eyes open during resuscitation. But is it worth the cost, the training and the organisation required to have a working tidal volume monitor for every preterm resuscitation?
A group from England confirmed recently the enormous variability in achieved tidal volumes from 0 to 19 mL/kg. This group was using tidal volume monitors for the study, but they appear to have been resuscitating the babies in a conventional fashion, watching chest rise rather than trying to achieve a specific tidal volume. (Murthy V, Dattani N, Peacock JL, Fox GF, Campbell ME, Milner AD, Greenough A: The first five inflations during resuscitation of prematurely born infants. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012, 97(4):F249-F253.http://fn.bmj.com/content/97/4/F249.full) The publication was specifically looking at whether applied breaths that occurred when the baby was also trying to breathe were different to those where the baby was apneic. As you might expect, if the baby helped then the tidal volumes were larger, and there was less leak around the mask. When the baby didn’t breathe, the breaths were enormously variable and there was often a large leak between the face mask and the baby’s face.
In a study from the amazing group in Melbourne, Georg Schmolzer and colleagues showed that if you actually take note of what the volume monitor shows you, then you adjust the mask position more frequently, leading to less leakage, and you have fewer over-large breaths. They did this study using a tidal volume monitor for every baby, but hiding the display for a randomized half of the babies. (Schmölzer GM, Morley CJ, Wong C, Dawson JA, Kamlin COF, Donath SM, Hooper SB, Davis PG: Respiratory function monitor guidance of mask ventilation in the delivery room: A feasibility study. The Journal of Pediatrics 2012, 160(3):377-381.e372. http://www.sciencedirect.com/science/article/pii/S0022347611009310)
Another study, with a design that was not as strong, without randomization for example, also suggests that using a tidal volume monitor can help to reduce the over-large breaths that can otherwise occur. (Kelm M, Dold SK, Hartung J, Breckwoldt J, Schmalisch G, Roehr CC: Manual neonatal ventilation training: A respiratory function monitor helps to reduce peak inspiratory pressures and tidal volumes during resuscitation. J Perinat Med 2012, 0(0):1-4. http://www.degruyter.com/view/j/jpme.ahead-of-print/jpm-2012-0023/jpm-2012-0023.xml) After training with the tidal volume monitor the operators were less likely to give high pressure and high volume breaths.
Another study using a lung model has also shown that just displaying the tidal volume dramatically improves the number of appropriate breaths that providers give. (Bowman TA, Paget-Brown A, Carroll J, Gurka MJ, Kattwinkel J: Sensing and responding to compliance changes during manual ventilation using a lung model: Can we teach healthcare providers to improve? The Journal of Pediatrics 2012, 160(3):372-376.e371. http://www.sciencedirect.com/science/article/pii/S0022347611009425)
Now in the past I have been told by certain providers (doctors, RTs and others) that it is important to use a flow-inflating bag, because they can feel how stiff the lungs are when they ventilate with one. I myself was taught this way, but over the years have become very sceptical that this is true, if the bag is a bit more distended, or the resistance of the airway is changed, or there is more or less leak, we can easily be misled. I recently found this older study (Spears RS, Yeh A, Fisher DM, Zwass MS: The “educated hand”. Can anesthesiologists assess changes in neonatal pulmonary compliance manually? Anesthesiology 1991, 75(4):693-696) which clearly showed that even when the change in compliance is not at all subtle (i.e. complete tube occlusion) operators are not capable of detecting the change in compliance during manual ventilation. In this study with a lung model the investigators at some point clamped the tube. The subjects knew this was going to happen, they didn’t know when. Even though they were expecting the tube to occlude at some point, they still were not able to tell when it occurred!
We cannot tell during manual ventilation when compliance changes or how much tidal volume we are giving without a monitor. Does this matter? I think it might, compliance and tidal volumes change rapidly during resuscitation, leaks are common and airway obstruction is also very common. Sometimes we cause airway obstruction, not by our technique, but by giving surfactant. Georg Schmolzer and that amazing Melbourne group showed that when we give surfactant in the delivery room, 25% of the babies have episodes of complete airway obstruction, and have dramatic and rapid changes in tidal volume. (Schmölzer G, Kamlin C, Dawson J, Morley C, Davis P: Tidal volume delivery during surfactant administration in the delivery room. Intensive Care Medicine 2011, 37(11):1833-1839. http://www.springerlink.com/content/m774p2642706275p/fulltext.html). Without the tidal volume monitor detection of such episodes is delayed and inadequate, and responses are likely to be partial.
Tidal volume monitoring during neonatal resuscitation is clearly an improvement in short term goals and in achieving more normal respiratory physiology. The equipment to be used, training and quality control will have to be studied so that we can institute this change most effectively.
I doubt that we will ever have large RCTs with long term clinical outcomes to support this change, but using the principle of likelihoods, it is time we figured out how to institute this change, made the change, and then evaluated if there really is an improvement in outcomes.