Jump to content

JOIN THE DISCUSSION!

Want to join the discussions?

Sign up for a free membership! 

If you are a member already, log in!

(lost your password? reset it here)

99nicu.org 99nicu.org
  • Blog Entries

    • By AllThingsNeonatal in All Things Neonatal
         0
      If you work in Neonatology you no doubt have listened to people talk in rounds or at other educational sessions about the importance of opening the lung. Many units in the past were what you might call “peepaphobic” but over time and with improvements in technology many centers are adopting an attitude that you use enough PEEP to open the lung. There are some caveats to this of course such as there being upper limits to what units are comfortable and not just relying on PEEP but adding in surfactant when necessary to improve pulmonary compliance.
      When we think about giving nitric oxide the importance of opening the lung can’t be stressed enough. I have heard it said many times when a baby has been found to be a “non responder” to inhaled nitric oxide that they may have been so because the lung wasn’t open. What we mean by this is that the distal alveoli are open. One can administer all the iNO in the world but if the majority of alveoli are collapsed the drug can’t get to the pulmonary vasculature and cause the pulmonary vasodilation that is so sorely needed in the presence of hypoxemic respiratory failure. Surfactant and inhaled nitric oxide in the presence of hypoxemic respiratory failure could be a great combo as one would help open the alveoli and then the iNO could address any pulmonary vasoconstriction which might be exacerbating the hypoxemic state.
      Study Tests This Theory
      Researchers in Chile led by Gonzalez A published Early use of combined exogenous surfactant and inhaled nitric oxide reduces treatment failure in persistent pulmonary hypertension of the newborn: a randomized controlled trial in the Journal of Perinatology. The concept of this study was to compare in a double blind RCT for 100 patients (based on a power calculation looking for a 25% reduction in treatment failure) whether provision of surfactant as up to 2 doses and iNO would be better than just iNO alone. Included infants needed an oxygenation index (OI = MAPXFiO2/pO2) of 20 or more to qualify and treatment failure was an OI of 40 or more. The patients recruited were similar in common characteristics including types of conditions that would benefit from iNO. RDS, meconium aspiration syndrome and pneumonia certainly have been shown to benefit from surfactant before while in the PPHN category that is questionable. In order to ensure that it was not just the primary disease but pulmonary hypertension that was present as well, all patients required confirmation of pulmonary hypertension prior to enrollment via ECHO with either a TR jet indicating a pulmonary pressure at least 2/3 of systemic or right to left shunting at the ductal or atrial level.
      The results of the study demonstrated a clear difference in the primary outcome.
      Patients receiving the combination of surfactant prior to starting iNO showed a faster reduction in OI than those receiving iNO alone. In fact the reduction in primary outcome of treatment failure was over 50% different while the power calculation had been based on only a 25% difference. That’s ok as this means there were more than enough patients to demonstrate a difference. As a secondary outcome the rate of ECMO or death was also different between the groups favouring use of surfactant.
      It works so now what?
      Who doesn’t like seeing a study that confirms what you have long believed. I feel that this study validates the teaching I received throughout the years about ensuring the lung is open before giving iNO. There are some caveats to this however. About 90% of the patients studied had conditions present (RDS, MAS, pneumonia) for which surfactant would have been indicated anyway. If this study had been done let’s say in patients with asphyxia induced pulmonary hypertension and clear lungs the surfactant may have made no difference as the lungs were already open. I mention this as I don’t think readers of this analysis need to jump to the conclusion that every time there is a patient with PPHN that you MUST give surfactant. What I think this illustrates though is the importance of first asking the question if iNO is being considered “Have I opened the lungs?”. The next time you encounter such a patient consider whether you are using enough PEEP and whether surfactant is indicated. The bottom line is if the lung isn’t open then all the iNO in the world isn’t going to make much difference!
    • By AllThingsNeonatal in All Things Neonatal
         0
      It seems so simple doesn’t it. Shouldn’t we just be able to feed milk whether it be from humans or cows and our preemies will just adapt? I have often written about human milk diets vs those with bovine but this week an intriguing article came my way that really gave me some pause to say hmmm. Human milk diets have been shown to reduce the risk of necrotizing enterocolitis (NEC) compared to use of formula. The use of bovine human milk fortifiers falls somewhere in the middle I suppose as the diet in that case is mostly human milk with some bovine sprinkled in so to speak. If NEC is something that these infants are at increased risk of then what might be going at a tissue level when infants are exposed to human milk alone vs other bovine ingestions?
      Near Infrared Spectroscopy May Tell Us the Answer
      Dani C et from Italy just published an elegant study entitled EFFECT ON SPLANCHNIC OXYGENATION OF BREAST MILK, FORTIFIED BREASTMILK, AND FORMULA MILK IN PRETERM INFANTS. The study looked at the use of two particular measurements from regional splanchnic NIRS application. One is called splanchnic regional oxygenation (rSO2S) and the other splanchnic fractional oxygen extraction ratio (FOES). The rSO2S tells you how much oxygen is in the gut at a tissue level and FOES which is calculated by using systemic oxygenation (SpO2) using the formula (SpO2-rSO2S)/SpO2). So FOES will be high when rSO2S is low meaning the gut relative to the rest of the body is consuming more oxygen. For this study, increments in feedings were standardized for all infants. The study was done once patients were on full bolus feedings for one week.
      The authors designed a study that needed 15 infants in three different groups with the first being human milk, then human milk + bovine fortifier and then the last formula fed infants. NIRS data was recorded 30 minutes before a feed (T0), 30 minutes after a bolus feed (T1) and then 2 hours after a bolus feed (T2). In the end the authors recruited 18 per arm. What the authors found is what I am having trouble not running with in terms of its meaning.
      Looking at the data, babies who were fed exclusively mothers own milk experienced no change at all in rSO2S at any time points. Interestingly the value even trended higher after a feed. Infants who received fortified human milk experienced a decrease in this value from before the feed to 30 minutes afterwards but then recovered by 2 hours. Formula fed infants though simply dropped from exposure to formula after 30 minutes through 2 hours and the FOES rose over that time demonstrating a greater amount of oxygen extraction by the gut.
      What is the meaning of all this?
      Bovine sources of nutrition in the form of fortifier seem to cause the gut to become more metabolically active and consume more oxygen at least for the first 30 minutes after a feeding. Formula tends to have a progressive increase in oxygen extraction over the first two hours post feed. This may be reflective of stress in the gut as it works harder to absorb and process nutrients from a bovine source and perhaps in a dose response fashion, a little bovine content as in fortifier causes some short term increase in oxygen demand vs pure bovine formula causing a sustained increase in oxygen need.
      This situation sets up an interesting concept. The NIRS results if you recall are from babies who have reached full feeds for one week. What if these same studies had been done in babies who were just in the process of increasing feeds? If infants consuming bovine sources of nutrition need more oxygen in the gut, might this explain why in the presence of acidosis, congenital heart defects or even with a PDA causing changes in end diastolic flow that they don’t tolerate in many cases anything other than human milk?
      I am not aware of any such studies looking at feeding advancement but it does really make me wonder what we would see as we advance feedings using our protocols? It is tempting to place abdominal NIRS sensors on the bellies of preterm infants who are just starting out on HMF and see what happens? If the rSO2S was going down and/or the FOES was rising, would you stop the bovine fortification if it reached a certain point? What would happen if a human milk fortifier was used instead of a bovine source? Any difference?
      So many questions and in my mind a great area for research. I can’t wait to see where this all goes.
       
    • By Jelli KA in Bubbly Girl in NICU
         0
      Today I sharing ‘tis post from HUGES a great. Organization dedicated to humanizing care in intensive care settings and emergency services. I particularly by this webinar on humanize. Management starting with leading with empathy, simply things that can be hard to achieve, but make us think Speakers suggests a few things to start with :   J. Carlos March - Profesor  EASP {Escuela Salud Publica- Public Health Institute of Andalucia}  Director of School of patient. @joancmarch Focus aligning Humility, vision and Values. Suggests   Emphasizing clear communication so that it flows with the team. Those we should aim to think in we . Leading can choose the words we say to br Proactive with self care and link up with stake holder in the community. Be awareness t ok to question , as when we question we can find ways to things better and learn.   Chelo Nurse , Nursing Director ( Poniente Region) gives a glimpse Difference humanizing project going on. @cheloArtero   Support each other and encourage the team to mindfully disconnect. For example Dosify info in this time of corovirus,so it not in a constant loop Have a dynamic & shared metrology to features to perinatal programs Cuidado co mimo in NICU : NICU care beyond family centered. Siempre en mi Mi. Supporting mums in perinatal death.  
    • By AllThingsNeonatal in All Things Neonatal
         3
      Intubate-Surfactant- Extubate or INSURE has been around for awhile. The concept is to place an ETT while an infant is first on CPAP and then after pushing surfactant in quickly remove the ETT and put back on CPAP. This does not always go as planned though. If after surfactant the FiO2 remains above 30% many people would keep the ETT in place as they would surmise that the infant would fail if the tube was removed. They would probably be right.
      Sustained inflations have fallen out of favour ever since the SAIL trial results were published and written about here . Having said that, the concept of using sustained inflation is to open the lung and expand closed alveoli to improve both oxygenation and gas exchange. Much like giving inhale nitric oxide to a collapsed lung is unlikely to make much difference, the question could be asked whether giving surfactant to a lung that is most collapsed will fail to deliver this compliance improving medication to the areas of the lung that most sorely need it. Our Italian colleagues therefore decided to undertake a study to look at providing surfactant to lungs after a recruitment manouver and see if this made a difference to the meaningful outcome of extubation failure after surfactant provision. The results are intriguing and as such here we go in looking at the study.
      Optimizing Lung Expansion
      The trial is the Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial and involved 35 NICUs in Italy. All infants enrolled were born from 24 + 0 weeks to 27 6/7 weeks gestational age at birth and all < 24 hours of age at enrollment. Each baby had to be on CPAP at the time of randomization and meet prespecified failure criteria of FiO2 of 0·30 or greater for target SpO2 of 87% to 94% for at least 30 min or in 10 Infants for rapid deterioration of clinical status or if pCO2 was > 65 mm Hg with a pH less than 7·20. Regardless of which arm they were randomized to all infants received 1-2 sustained inflation breaths using 25 cm H2O for 10-15 secs using a t-piece resuscitator after being started on CPAP as was the practice at the time. After randomization which could not be blinded, patients were then either given surfactant via INSURE without any further strategy for opening the lung or received the IN-REC-SUR-E approach. The latter involved putting the infant on high frequency oscillation starting with settings of mean airway pressure 8 cm H2O; frequency 15 Hz; ΔP15 cm H2O; and inspiration to expiration ratio of 1:2. Using this modality infants underwent stepwise recruitment methods prior to administering surfactant (poractant). The primary outome was the need for mechanical ventilation within the first 72 h of life. Infants met the primary outcome if they were not extubated within
      30 min after surfactant administration or required reintubation before 72 h of life.
      The Results
      Based on a power calculation the authors needed 103 infants in each arm and they recruited 107 in the treatment and 111 in the control arm. In the per-protcol allocation 101 received the treatment and 111 the contol. While the strategies for extubation were not set out to be equal (units were allowed to extubate to anywhere from +6 to +8 for pressure levels), the groups were not different 7·0 cm H2O, SD 0·4 for the experimental group and control arms. Given the steps taken to open the lung in the lung recruitment arm, the FiO2 was lower at 28% prior to surfactant provision in the treatment group than in the usual INSURE approach at 42% prior to surfactant provision. All infants were extubated within 30 minutes of receiving surfactant. As the results demonstrate, whether there was an intention to treat analysis or per-protocol analysis the babies who received the intervention were more likely to remain extubated. The number needed to treat was 7 which is a pretty powerful measure. Interestingly, looking at secondary outcomes there are some interesting trends as well including less mortality which on a per-protocol analysis was significant but also a trend towards more PVL at 9% in the treatment arm and 4% in the control. The mean times to surfactant administration were 4 hours in the treatment group and 3 hours in the control but the high frequency manoeuvre had a mean duration of only 30 minutes. It is possible that the use of high frequency could have blown off CO2 to very low levels but I am uncertain if the short reduction in pCO2 could have contributed significantly to reduced cerebral perfusion if that trend is representative of something. Interestingly, pneumothroaces were not different between groups as no doubt as a reader you might wonder if use of high pressures to recruit the lungs when they are non compliant might have led to air leaks.
      So it worked, now what?

      First of all, the results to me make a lot of sense. Opening the lung before delivering surfactant and then seeing better chances of staying extubated doesn’t really surprise me. Some questions that come up now for me would be how this strategy would fare in those who are older at birth. I suspect given the greater chest wall support and lower likelihood of severe RDS this strategy might be even more effective at reducing FiO2 or perhaps CPAP need in terms of duration after extubation. I would think it unlikely to make a difference in reintubation though as most would remain extubated regardless. That is for another study though with a different outcome.
      There will be centres that don’t like the use of HFOV for recruitment so what other strategies could be used in lieu of this? I hate to say it but there will also be calls to have a much larger study specifically designed to look at the secondary outcomes. Would a larger study find a significant increase in PVL or demonstrate that it was just a random finding? Might mortality be proven to be lower and even more so?
      Regardless of the above what I think this paper does is give us reason to pause before giving INSURE and ask ourselves if we have done what we can to open the lung after intubating before rushing to squirt the surfactant in. Maybe increasing the provided PEEP and lowering the FiO2 somewhat before giving surfactant will help with distribution and increase your chances of first being able to extubate and secondly when you do keeping the tube out!
×
×
  • Create New...