We can always learn and we can always do better. At least that is something that I believe in. In our approach to resuscitating newborns one simple rule is clear. Fluid must be replaced by air after birth and the way to oxygenate and remove CO2 is to establish a functional residual capacity. The functional residual capacity is the volume of air left in the lung after a tidal volume of air is expelled in a spontaneously breathing infant and is shown in the figure. Traditionally, to establish this volume in a newborn who is apneic, you begin PPV or in the spontaneously breathing baby with respiratory distress provide CPAP to help inflate the lungs and establish FRC.
Is there another way?
Something that has been discussed now for some time and was commented on in the most recent version of NRP was the concept of using sustained inflation (SI) to achieve FRC. I have written about this topic previously and came to a conclusion that it wasn’t quite ready for prime time yet in the piece Is It Time To Use Sustained Lung Inflation In NRP?
The conclusion as well in the NRP textbook was the following:
“There are insufficient data regarding short and long-term safety and the most appropriate duration and pressure of inflation to support routine application of sustained inflation of greater than 5 seconds’ duration to the transitioning newborn (Class IIb, LOE B-R). Further studies using carefully designed protocols are needed”
So what now could be causing me to revisit this concept? I will be frank and admit that whenever I see research out of my old unit in Edmonton I feel compelled to read it and this time was no different. The Edmonton group continues to do wonderful work in the area of resuscitation and expand the body of literature in such areas as sustained inflation.
Can you predict how much of a sustained inflation is needed?
This is the crux of a recent study using end tidal CO2 measurement to determine whether the lung has indeed established an FRC or not. Dr. Schmolzer’s group in their paper (Using exhaled CO2 to guide initial respiratory support at birth: a randomised controlled trial) used end tidal CO2 levels above 20 mmHg to indicate that FRC had been established. If you have less CO2 being released the concept would be that the lung is actually not open. There are some important numbers in this study that need to be acknowledged. The first is the population that they looked at which were infants under 32 6/7 weeks and the second is the incidence of BPD (need for O2 or respiratory support at 36 weeks) which in their unit was 49%. This is a BIG number as in comparison for infants under 1500g our own local incidence is about 11%. If you were to add larger infants closer to 33 weeks our number would be lower due to dilution. With such a large number though in Edmonton it allowed them to shoot for a 40% reduction in BPD (50% down to 30%). To accomplish this they needed 93 infants in each group to show a difference this big.
So what did they do?
For this study they divided the groups in two when the infant wouldn’t breathe in the delivery room. The SI group received a PIP of 24 using a T-piece resuscitator for an initial 20 seconds. If the pCO2 as measured by the ETCO2 remained less than 20 they received an additional 10 seconds of SI. In the PPV group after 30 seconds of PPV the infants received an increase of PIP if pCO2 remained below 20 or a decrease in PIP if above 20. In both arms after this phase of the study NRP was then followed as per usual guidelines.
The results though just didn’t come through for the primary outcome although ventilation did show a difference.
|Duration of mechanical ventilation (hrs)
The reduction in hours of ventilation was impressive although no difference in BPD was seen. The problem though with all of this is what happened after recruitment into the study. Although they started with many more patients than they needed, by the end they had only 76 in the SI group and 86 in the PPV group. Why is this a problem? If you have less patients than you needed based on the power calculation then you actually didn’t have enough patients enrolled to show a difference. The additional compounding fact here is that of the Hawthorne Effect. Simply put, patients who are in a study tend to do better by being in a study. The observed rate of BPD was 33% during the study. If the observed rate is lower than expected when the power calculation was done it means that the number needed to show a difference was even larger than the amount they originally thought was needed. In the end they just didn’t have the numbers to show a difference so there isn’t much to conclude.
What I do like though
I have a feeling or a hunch that with a larger sample size there could be something here. Using end tidal pCO2 to determine if the lung is open is in and of itself I believe a strategy to consider whether giving PPV or one day SI. We already use colorimetric devices to determine ETT placement but using a quantitative measure to ascertain the extent of open lung seems promising to me. I for one look forward to the continued work of the Neonatal Resuscitation–Stabilization–Triage team (RST team) and congratulate them on the great work that they continue doing.
I would consider myself fairly open minded when it comes to care in the NICU. I wouldn’t call myself a maverick or careless but I certainly am open to new techniques or technologies that may offer a better level of care for the babies in our unit. When it comes to “non-Western” concepts though such as therapeutic touch, chiropractic manipulations of infants and acupuncture (needle or otherwise) I have generally been a skeptic. I have written about such topics before with the most popular post being Laser acupuncture for neonatal abstinence syndrome. My conclusion there was that I was not a fan of the strategy but perhaps I could be more open to non traditional therapies.
This would appear to be the newest and perhaps strangest (to me at least) approach to pain relief that I have seen. I do love name of this study; the MAGNIFIC trial consisted of a pilot study on the use of auricular magnetic acupuncture to alleviate pain in the NICU from heel lances. The study was published in Acta Paediatrica this month; Magnetic Non-Invasive Acupuncture for Infant Comfort (MAGNIFIC) – A single-blinded randomized controlled pilot trial. The goal here was to measure pain scores using the PIPP scoring system for pain in the neonate before during and after a painful experience (heel lance) in the NICU. Being a pilot study it was small with only 20 needed per arm based on the power calculation to detect a 20% difference in scores. The intervention used small magnets placed at specific locations on the ear of the infant at least two hours before the heel lance was to occur. Before I get into the results, the authors of the study provide references to explain how the therapy works. Looking at the references I have to admit I was not able to obtain complete papers but the evidence is generally it would appear from adult patients. The explanation has to do with the magnetic field increasing blood flow to the area the magnet is applied to and in addition another reference suggests that there are affects the orbitofrontal and limbic regions which then impacts neurohormonal responses as seen in functional MRI. The evidence to support this is I would have thought would be pretty sparse but I was surprised to find a literature review on the subject that looked at 42 studies on the topic. The finding was that 88% of the studies reported a therapeutic effect. The conclusion though of the review was that the quality of the included studies was a bit sketchy for the most part so was not able to find that this should be a recommended therapy.
So what were the results?
Despite my clear skepticism what this study did well was that aside from the magnets, the intervention was the same. Twenty one babies received the magnetic treatments vs 19 placebo. There was a difference in the gestational ages of the babies with the magnet treated infants being about two weeks older (35 vs 33 weeks). What difference that might in and of itself have on the PIPPs scoring I am not sure. The stickers were applied to the ears with and without magnets in a randomized fashion and the nurses instructed to score them using the PIPP scoring system. Interestingly, as per their unit policy all babies received sucrose as well before the intervention of a heel lance so I suppose the information gleaned here would be the use of magnets as an adjunctive treatment. No difference was noted in the two groups before and after the heel lance but during the procedure the magnet treated infants had a difference in means (SD): 5.9 (3.7) v 8.3 (4.7), p=0.04). No differences were found in secondary measures such as HR or saturation and no adverse effects were noted. The authors conclusions were that it was feasible and appears safe and as with most pilot studies warrants further larger studies to verify the results.
Should we run out and buy it?
One of the issues I have with the study is that in the introduction they mention that this treatment might be useful where kangaroo care (KC) is not such as a critically ill infant. Having placed infants who are quite sick in KC and watched wonderful stability arise I am not sure if the unit in question under utilizes this important modality for comfort.
The second and perhaps biggest issue I have here is that although the primary outcome was reached it does seem that there was some fishing going on here. By that I mean there were three PIPP scores examined (before, during and after) and one barely reached statistical significance. My hunch is that indeed this was reached by chance rather than it being a real difference.
The last concern is that while the intervention was done in a blinded and randomized fashion, the evidence supporting the use of this in the first place is not strong. Taking this into account and adding the previous concern in as well and I have strong doubts that this is indeed “for real”. I doubt this will be the last we will hear about it and while my skepticism continues I have to admit if a larger study is produced I will be willing and interested to read it.
I had the pleasure of meeting the author of a paper I am about to comment on this week while at the 99 NICU conference in Stockholm. Dr. Ohlin from Orebro University in Sweden presented very interesting work on their unit’s “scrub the hub” campaign. As he pointed out, many places attempt to reduce coagulase negative staphylococcal infections by introducing central line bundles but seldom is there one thing that is changed in a bundle that allows for a before and after comparison like his team was able to do. I was so impressed by this work and at the same time concerned about another strategy to reduce infection that I felt compelled to make a comment here.
Scrub the hub!
Dr. Ohlin and the first author Dr. Bjorkman published Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec reduced neonatal sepsis back in 2015. They compared a 16.5 month period in their unit when they rolled out a CLABI reduction bundle to a period of 8.5 months afterwards when they made one change. Nurses as is done in the units I work in were commonly scrubbing the hub before they injected the line with a medication but in the second epoch the standard changed to be a specified 15 second scrub instead of being left up to the individual nurse. With permission from Dr. Ohlin here is a picture of the hubs highlighting bacterial growth without scrubbing, then for a duration less than 15 seconds and then with 15 seconds.
In the first epoch they had 9 confirmed CLABSIs and 0 confirmed in the second after their intervention. The rate of CLABSI then in the first epoch was 1.5% vs 0% in the second group. As with any study looking at sepsis, definitions are important and while they didn’t do paired cultures to rule out contamination (one positive and one negative as is the definition in our hospitals) they did refer each patient to a senior Neonatologist to help determine whether each case should be considered a true positive or not. Given that they made no changes to practice or other definitions in diagnosing infections during that time perhaps the results were indeed real. Presumably if they had missed an infection and not treated it in the second epoch the patient would have declared themselves so I think it is reasonable to say that 8.5 months without a CLABSI after their intervention is a success. As Dr. Ohlin points out the scrub duration may also help due to the abrasion of the hub surface removing a bacterial film. Regardless of the reason, perhaps a 15 second scrub is a good idea for all?
The lazy person’s solution – the SwabCap
One way to get around human nature or people being distracted might be to cover each luer lock with a cap containing 70% isopropyl alcohol. In this way when you go to access the line there should be no bacteria or labour required to scrub anything since the entry of the line is bathed in alcohol already. This was the subject of a systematic review from the Netherlands entitled Antiseptic barrier cap effective in reducing central line-associated bloodstream infections: A systematic review and meta-analysis. The reviews ultimately examined 9 articles that met their inclusion criteria and found the following; use of the antiseptic barrier cap was effective in reducing CLABSIs (IRR = 0.59, 95% CI = 0.45–0.77, P < 0.001). Moreover, they concluded that this was an intervention worth adding to central-line maintenance bundles. Having said that, the studies were mostly adult and therefore the question of whether minute quantities of isopropyl alcohol might be injected with medications was not a concern when they made their conclusion.
What about using such caps in ELBW infants
Sauron et al in St. Justine Hospital in Montreal chose to look at these caps more carefully after they were implemented in their NICU. The reason for taking a look at them was due to several luer valves malfunctioning. The authors created an in-vitro model to answer this question by creating a closed system in which they could put a cap on the end of a line with a luer lock and then inject a flush, followed by a simulated medication (saline) and then a flush and collect the injected materials in a glass vial that was sealed to prevent evaporative loss of any isopropyl alcohol. They further estimated the safe amount of isopropyl alcohol from Pediatric studies would be 1% of the critical threshold of this alcohol and using a 500g infant’s volume of distribution came up with a threshold of 14 mmol/L. The study then compared using the SwabCap over two different valve leur lock systems they had in their units (SmartSite and CARESITE valves) vs. using the strategy of “scrub the hub”.
The results were quite concerning and are shown below.
|SwabCap on Smart Site Valve
||Incubator 35 degrees
|SwabCap on CARESITE valve
||Incubator 35 degrees
|Isopropyl alcohol pad on CARESITE Valve
Certainly, the Smart Site valve allowed considerable amounts of isopropyl alcohol to enter the line but the CARESITE while better still allowed entry compared to the control arm which allowed none. Beyond the introduction of the alcohol into the system in all cases considerable clouding of the valves occurred with repeated capping of the system with new caps as was done with each med injection since each was single use. In lines that were not accessed contact with the cap was left for 96 hours as per recommendations from the manufacturer and these changes occurred as well.
While a reduction in CLABSI is something we all need to strive to obtain, it is better to take the more difficult path and “scrub the hub” and by that for 15 seconds which incidentally is the same recommended duration for hand hygiene in both of our units. Perhaps in larger term infant’s seepage of isopropyl alcohol into the lines would not be as concerning as their larger volume of distribution would lead to lower levels but I would ask the question “should any isopropyl alcohol be injected into any baby?”. I think not and perhaps by reading this post you will ask the same thing if your unit is using these caps.
- Thank you to Örebro University Hospital for their permission in using the photo for the post
Look around you. Technology is increasingly becoming pervasive in our everyday lives both at home and at work. The promise of technology in the home is to make our lives easier. Automating tasks such as when the lights turn on or what music plays while you eat dinner (all scripted) are offered by several competitors. In the workplace, technology offers hopes of reducing medical error and thereby enhancing safety and accuracy of patient care. The electronic health record while being a nuisance to some does offer protection against incorrect order writing since the algorithms embedded in the software warn you any time you stray. What follows is a bit of a story if you will of an emerging technology that has caught my eye and starts like many tales as a creative idea for one purpose that may actually have benefits in other situations.
In 2012 students in Australia rose to the challenge and designed a digital stethoscope that could be paired with a smartphone. The stethoscope was able to send the audio it was receiving to the smartphone for analysis and provide an interpretation. The goal here was to help diagnose childhood pneumonia with a stethoscope that would be affordable to the masses, even “Dr. Mom” as the following video documents. Imagine before calling your health line in your city having this $20 tool in your hands that had already told you your child had breath sounds compatible with pneumonia. Might help with moving you up the triage queue in your local emergency department.
Shifting the goal to helping with newborns
Of course breath sounds are not the only audio captured in a stethoscope. Heart sounds are captured as well and the speed of the beats could offer another method of confirming the heart is actually beating. Now we have ECG, pulse oximetry, auscultation and palpation of the umbilical stump to utilize as well so why do you need another tool? It comes down to accuracy. When our own heart rates are running high, how confident are we in what we feel at the stump (is that our own pulse we are feeling?). In a review on measurement of HR by Phillipos E et al from Edmonton, Alberta, auscultation was found to take an average of 17 seconds to produce a number and in 1/3 of situations was incorrect. The error in many cases would have led to changes in management during resuscitation. Palpation of the umbilical cord is far worse. In one study “cord pulsations were impalpable at the time of assessment in 5 (19%) infants, and clinical assessment underestimated the ECG HR with a mean (SD) difference between auscultation and palpation and ECG HR of − 14 (21) and − 21 (21) beats min –1″. In another study, 55% of the time providers were incorrect when they thought the HR was under 100 BPM. This leaves the door open for something else. Might that something be the digital stethoscope?
How does the digital stethoscope fare?
Kevac AC et al decided to look at the use of the Stethocloud to measure HR after birth in infants >26 weeks gestational age at birth. The opted to use the ECG leads as the gold standard which arguably is the most accurate method we have for detecting HR. The good news was that the time to signal acquisition was pretty impressive. The median time to first heart rate with the stethoscope was 2 secs (IQR 1-7 seconds). In comparison the time for a pulse oximeter to pick up HR is variable but may be as long as one minute. In low perfusion states it may be even longer or unable to pick up a good signal. The bad news was the accuracy as shown in the Bland Altman plot. The tendency of the stethoscope was to underestimate the EKG HR by about 7 BPM. Two standard deviations though had it underestimate by almost 60 BPM or overestimate by about 50 BPM. For the purposes of resuscitation, this range is far to great. The mean is acceptable but the precision around that mean is to wide. The other issue noted was the frequent missing data from loss of contact with the patient. Could you imagine for example having a baby who has a heart rate of 50 by the stethoscope but by EKG 100? Big difference in approach, especially if you didn’t have EKG leads on to confirm. The authors note that the accuracy is not sufficient and felt that an improvement in the software algorithms might help.
Another go at it
So as suggested, the same group after having a new version with improved software decided to go at it again. This time Gaertner VD et al restricted the study to term infants. Forty four infants went through the same process again with the stethoscope output being compared to EKG lead results. This time around the results are far more impressive. There was virtually no difference between the ECG and the stethoscope with a 95% confidence interval as shown in the graphs with A being for all recordings and B being those without crying (which would interfere with the acquiring of HR). A maximal difference of +/- 18 BPM for all infants is better than what one gets with auscultation or palpation in terms of accuracy and let’s not forget the 2 second acquisition time!
Should you buy one?
I think this story is evolving and it wouldn’t surprise me if we do see something like this in our future. It certainly removes the element of human error from measuring. It is faster to get a signal than even the time it takes to get your leads on. Where I think it may have a role though is for the patient who has truly no pulse. In such a case you can have an EKG HR but the patient could be in pulseless electrical activity. Typically in this case people struggle to feel a pulse with the accuracy being poor in such situations. Using a device that relies on an actual heart contraction to make a sound provides the team with real information. Concurrent with this technology is also the rise of point of care ultrasound which could look at actual cardiac contractions but this requires training that makes it less generalizable. Putting a stethoscope on a chest is something we all learn to do regardless of our training background.
I think they could be on to something here but perhaps a little more evidence and in particular a study in the preterm infant would be helpful to demonstrate similar accuracy.
I don’t envy our nurses who care for babies withdrawing from various opiates and other substances. These assignments are definitely a challenge and require a great deal of patience and depending on the shrillness of an infant’s cry a good set of earplugs. Nonetheless we do our best with these infants to keep them calm and avoid as much stimulation as we can as we attempt to minimize the excitability of their nervous system.
Over 40 years ago the Finnegan Neonatal Abstinence scoring system was developed to assist medical teams by providing as objective a system as possible to compare one infant to another and determine when and if a patient should be treated pharmacologically. Unfortunately there is a problem inherent with this scoring system. It is the same problem that exists when you don’t have a blinded research trial. Imagine you are caring for an infant and you were given no history about drug exposure. How might you score a patient like that compared to one in which you are told has been exposed to illicit substances? Your senses are heightened and moreover if you were told this baby is “withdrawing terribly” or “is awful at night” you are biased. How are you likely to score such a patient when they are “on the edge” of being counted as a 1 or a 0 in a category? I bet in many cases, especially if you haven’t taken care of many such patients you err on the side of caution and score them on the high side. It is human nature. When the possible outcome of failing to recognize a withdrawing patient is a seizure, no one wants to be on when it happens having their scoring questioned. Have a look at the scoring tool though.
There is a lot of stuff in there to check off! What if it could be simpler?
The ESC Tool
In early May, news began to break of an abstract being presented at the Pediatric Academic Society meeting. The news story from the AAP can be found here. The ESC tool is a three question tool used to assess whether an infant requires treatment for withdrawal.
E – Eat (is an infant is able to eat 1 or more ounce per feeding)
S – Sleeping (sleep for an hour or longer undisturbed)
C – Console (Be consoled in 10 minutes or less.)
If all three criteria are met, the patient does not need treatment. If one or more criteria are not met the housestaff are notified and first non-pharmacologic and then pharmacologic means are employed if necessary to control symptoms.
The authors did something quite interesting. They looked at 50 patients with 201 hospital days with prenatal exposures to opiates and applied the ESC criteria to guide treatment. Concurrently they captured the Finnegan scores but did not use them to guide treatment.
The findings I hope you will agree are quite interesting!
“FNASS scores indicated starting morphine in 30 infants (60%). Morphine was actually started on only 6 patients (12%) (p< 0.0001) based on the ESC approach. The FNASS led protocol directed initiating or increasing meds on 24.6% of days compared to 2.7% of days using the ESC approach (p< 0.0001). The FNASS approach directed that morphine was either not started or decreased on 65.8% of days compared with 94.4% of days using the ESC approach (p< 0.0001). There were no readmissions or reported adverse events.
Pretty amazing but…
The ESC approach greatly reduced the need for treatment and as the authors state there were no readmissions or reported adverse events. What we don’t know and will be needed I suspect before anyone will adopt this strategy (which I have to say again is so much simpler that current approaches) is how these children do in the long run. If the system is undertreating withdrawal, could we see downstream impacts of a “kinder and gentler” approach? One outcome that will be reported soon in the next month is length of stay. I am eagerly awaiting further results as I for one think that a simpler approach to these patients may be just what the doctor ordered. I think the nurses might thank us as well but we will see just how appropriate it is!
The Abstract reporting these findings can be found below
Novel Approach to Evaluating and Treating Infants with Neonatal Abstinence Syndrome
I have often said that if this came to pass as a mandatory requirement that I would make an announcement shortly thereafter that I was moving on to another career. I think people thought I was kidding but I can put in writing for all to see that I am serious! The subject has been discussed for some time as I can recall such talks with colleagues both in my current position and in other centres. The gist of the argument for staying in-house is that continuity is improved over that period and efficiency gained by avoiding handovers twice a day . How many times have you heard at signover that extubation will be considered for the following morning or to keep the status quo for another issue such as feeding until the next day. No doubt this is influenced by a new set of eyes being in the unit and a change in approach to being one of “putting out fires” overnight. The question then is whether having one Neonatologist there for 24 hours leads to better consistency and with it better outcomes. With respect to PICUs the AAP has previously recommended that 24 hour in-house coverage by an intensivist be the standard so should Neonatology follow suit?
A Tale of Two Periods
My friends in Calgary, Alberta underwent a change in practice in 2001 in which they transitioned from having an in-house model of Neonatologist coverage for 24 hours a day to one similar to our own centres where the Neonatologist after handover late afternoon could take call from home. An article hot off the presses entitled Twenty-Four hour in-house neonatologist coverage and long-term neurodevelopmental outcomes of preterm infants seeks to help answer this question. The team undertook a retrospective analysis of 387 infants born at < 28 weeks gestational age during the periods of 1998-2000 (24 hour period, N=179 infants) vs 2002 – 2004 (day coverage, N= 208 infants) with the goal of looking at the big picture being follow-up for developmental outcome at 3 years. This is an important outcome as one can look at lots of short term outcomes (which they also did) but in the end what matters most is whether the infants survive and if they do are they any different in the long term.
As with any such study it is important to look at whether the infants in the two periods are comparable in terms of risk factors for adverse outcome. Some differences do exist that are worth noting.
Increased risk factors in the 24 hour group
- Maternal smoking
- Smaller birthweight (875 vs 922 g)
- Confirmed sepsis (23% vs 14%)
- Postnatal steroids (45% vs 8%) – but duration of ventilation longer in the day coverage group likely due to less postnatal steroids ( 31 vs 21 days)
All of these factors would predict a worse outcome for these infants but in the end for the primary outcome of neurodevelopmental impairment there was no difference. Even after controlling for postnatal steroids, birth weight, sex and 5 minute apgar score there was still no difference.
What might this mean?
Looking at this with a glass is half full view one might say that with all of the factors above predicting worse outcome for infants, the fact that the groups are not different in outcome may mean that the 24 hour model does indeed confer a benefit. Maybe having a Neonatologist around the clock means that care is made that much better to offset the effect of these other risk factors? On the other hand another explanation could also be that the reason there is no difference is that the sample just isn’t big enough to show a difference. In other words the size of the study might be underpowered to find a difference in developmental outcome.
One of the conclusions in this study is that the presence of a Neonatologist around the clock may have led to earlier extubation and account for the nearly 10 day difference in duration of ventilation. While I would love to believe that for personal reasons I don’t think we can ignore the fact that in the earlier epoch almost 50% of the babies received postnatal steroids compared to 8% in the later period. Postnatal steroids work and they do so by helping us get babies off ventilators. It is hard to ignore that point although I woudl like to take credit for such an achievement.
For now it would appear that I don’t feel compelled to stay overnight in the hospital unless it is necessary due to patient condition necessitating me having my eye on the patient. I am not sure where our field will go in the future but for now I don’t see the evidence being there for a change in practice. With that I will retire to my bedroom while I am on call and get some rest (I hope).