If you work in Neonatology or in Pediatrics for that matter there is no doubt that at some point you took the neonatal resuscitation program (NRP). Ideally you should be recertified every year or two years depending on your profession. In the course you are taught that the depth of chest compressions required to achieve the best chances of ROSC is 1/3 the diameter of the chest. The evidence to support this comes from a CT evaluation of neonatal thoraces in the paper Evaluation of the neonatal resuscitation program’s recommended chest compression depth using computerized tomography imaging. In this study the authors found that using a mathematic model the 1/3 chest compression recommendation should in theory yield the best hemodynamic outcome.
What about ROSC?
Hemodynamics is one thing in a model but what about real life? I don’t think you could reasonably do an RCT these days with the outcome of interest being ROSC in humans. What research ethics board would allow you to randomize to the outcome of death in babies and deviate from an international organizations recommendations for best practice? My former colleagues in Edmonton had an answer to this issue though by using a piglet model to test the hypothesis that 33% is indeed better than either 12.5%, 24% or 40% chest compression depth. Their paper Assessment of optimal chest compression depth during neonatal cardiopulmonary resuscitation: a randomised controlled animal trial tackles just that question.
How did they do it? In an animal lab that is equipped with a mechanical device to simulate chest compressions they were able to instrument piglets and after asphyxiating them with an occluded ETT they began the process of trying to revive them. After being asphyxiated they initiated a combination of PPV with a neopuff and gave epinephrine (0.02 mg/kg/dose) intravenously2 min after the start of positive pressure ventilation and every 3 min until ROSC with a maximum of three doses, with a maximum resuscitation time of 10 min. The groups were divided in the following manner.
What did they find?
Two very interesting things came out of the study. The first was that they abandoned the 12.5% group early in the study when it became apparent that no piglet would survive using this depth. The other thing they found in support of greater depths of 33 and 40% compression depth is shown in the following graph.
The authors found that in terms of systolic and diastolic blood pressure the best chances in particular for systolic blood pressure were the 33 and 40% compression depths. Looking at the bottom right figure it is also evident that cerebral blood flow increases with increasing depth of compression.
With respect to the primary outcome they found this:
“The median (IQR) time to ROSC was 600 (600–600) s, 135 (90–589) s, 85 (71–158)* s and 116 (63–173)* s for the 12.5%, 25%, 33% and 40% AP depth groups, respectively (p<0.001 vs 12.5% AP depth group). The number of piglets that achieved ROSC was 0 (0%), 6 (75%), 7 (88%)** and 7 (88%)** in the 12.5%, 25%, 33% and 40% AP depth groups, respectively (*p<0.05 and **p<0.005 vs 12.5% AP depth group).
Of note, one of the piglets randomized to 40% depth of compression had pulmonary contusions at autopsy.
Putting it all together
The article supports the use of 33-40% chest compression but it raises an important point in my mind. The study used a mechanical device to ensure the percentage compression and it is clear that if you fall below these numbers the ROSC and hemodynamics is impaired while if you go to high you run the risk of damaging the lungs (I know it was just one but a previous study demonstrated harm at 50% compression depth as well).
This raises the question about failed resuscitations. Do we know how deep we are actually compressing during these situations? Sure, everyone can recite that we should be compressing to 1/3 of the chest diameter but what are we actually doing? In some cases are we not doing enough and in other cases doing way to much? I would imagine the answer to this question is yes. I do wonder as we continue to automate so much in our world through advances in technology if doing the same in neonatal resuscitation is not that far off. When our hands are sweaty and tremulous with adrenaline coursing through our veins how good are we really at controlling the precise depth of compression. Time will tell what happens but what is clear to me is that precision matters and really how precise can we be?
If you are reading this and have a baby in the NICU with respiratory distress syndrome (RDS) otherwise known as hyaline membrane disease you might be surprised to know that it is because of the same condition that modern NICUs exist. The newspaper clipping from above sparked a multibillion dollar expansion of research to find a cure for the condition that took the life of President Kennedy’s preterm infant Patrick Bouvier Kennedy. He died of complications of RDS as there was nothing other than oxygen to treat him with. After his death the President committeed dollars to research to find a treatment and from that came surfactant and modern ventilators to support these little ones.
What is surfactant and what is it’s relationship to RDS?
When you take a breath (all of us including you reading this) oxygen travels down your windpipe (trachea) down into your lung and goes left and right down what are called your mainstem bronchi and then travels to the deep parts of the lung eventually finding its way to your tiny air sacs called alveoli (there are millions of them). Each alveolus has a substance in it called surfactant which helps to reduce the surface tension in the sac allowing it to open to receive oxygen and then shrink to get rid of carbon dioxide that the blood stream brings to these sacs to eliminate. Preterm infants don’t have enough surfactant and therefore the tension is high and the sacs are hard to open and easily collapse. Think of surface tension like blowing up those latex balloons as a child. Very hard to get them started but once those little balloons open a little it is much easier! The x-ray above shows you what the lungs of a newborn with RDS look like. They are described as having a “ground glass” appearance which if you recall is the white glass that you write on using a grease pencil when you are using a microscope slide. Remember that?
Before your infant was born you may have received two needles in your buttocks. These needles contain steroid that helps your unborn baby make surfactant so that when they are born they have a better chance of breathing on their own.
Things we can do after birth
Even with steroids the lungs may be “sticky” after birth and difficult to open. The way this will look to you is that when your baby takes a breath since it is so difficult the skin in between the ribs may seem to suck in. That is because the lungs are working so hard to take breath in that the negative pressure is seen on the chest. If your baby is doing that we can start them on something called CPAP which is a machine that uses a mask covering the nose and blows air into the chest. This air is under pressure and helps get oxygen into the lungs and gives them the assist they need to overcome the resistance to opening.
Some babies need more than this though and will need surfactant put into the lungs. The way this is done is typically by one of two ways. One option is to put a plastic tube in between the vocal cords and then squirt in surfactant (we get it from cow’s or pigs) and then typically the tube is withdrawn (you may hear people call it the INSURE technique – INtubate, SURfactant, Extubate). For some babies who still need oxygen after the tube is put in they may need to remain on the ventilator to help them breathe for awhile. The other technique is the LISA (Less Invasive Surfactant Administration). This is a newer way of giving surfactant and typically involves putting a baby on CPAP and then looking at the vocal cords and putting a thin catheter in between them. Surfactant is then squirted into the trachea and the catheter taken out. The difference between the two methods is that in the LISA method your baby is breathing on their own throughout the procedure while receiving CPAP.
Even if no surfactant is given the good news is that while RDS typically worsens over the first 2-3 days, by day 3-4 your baby will start to make their own surfactant. When that happens they will start to feel better and breathe easier. Come to think of it you will too.
Much has been written on the topic of cord clamping. There is delayed cord clamping of course but institutions differ on the recommended duration. Thirty seconds, one minute or two or even sometimes three have been advocated for but in the end do we really know what is right? Then there is also the possibility of cord milking which has gained variable traction over the years. A recent review was published here.
Take the Guessing Out of the Picture?
Up until the time of birth there is very little pulmonary blood flow. Typically, about 10% of the cardiac output passes through the lungs and the remained either moves up the ascending aorta or bypasses the lungs via the ductus arteriosus. After birth as the lung expands, pulmonary vascular resistance rapidly decreases allowing cardiac output to take on the familiar pattern which we all live with. Blood returning from the systemic venous circulation no longer bypasses the lung but instead flows through pulmonary capillaries picking up oxygen along the way. One can imagine then that if a baby is born and the cord is clamped right away, blood returning from the systemic circulation continues to bypass the lung which could lead to hypoxemia and reflexive bradycardia. This has been described previously by Blank et al in their paper Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition.
The cord was clamped after each of the following was achieved for an infant indicating successful transition with opening of the lung and establishment of an FRC.
1. Establishment of adequate breathing (average tidal volume ≥4 mL/kg) on CPAP. They used a mask capable of measuring expired tidal volumes.
2. HR above 100 bpm
3. SpO2 above 25th percentile using FiO2 <0.4
In this way, the cord was only clamped once the baby appeared to have physiologically made the transition from dependence on umbilical cord blood flow to ventilation perfusion matching in the lung. Although 82 mothers consented only 37 preterm infants were included in the end. Exclusion criteria were signs of placental abruption or placenta praevia, signs of severe fetal distress determined by the clinician and the necessity for an emergency caesarean section ordered to be executed within 15 min. This really was a proof of concept study but the results are definitely worth looking at.
How Did These Babies Do?
There are many interesting findings from this study. The mean time of cord clamping was 4 minutes and 23 seconds (IQR 3:00 – 5:11). Heart rate was 113 (81–143) and 144 (129–155) bpm at 1 min and 5 min
after birth. Only one patient developed bradycardia to <60 BPM but this was during a mask readjustement. The main issue noted as far as adverse events was hypothermia with a mean temperature of 36.0 degrees at NICU admission. Almost 50% of infants had a temperature below 36 degrees. Although the authors clearly indicate that they took measures to prevent heat loss it would appear that this could be improved upon!
What stands out most to me is the lengthy duration of cord clamping. This study which used a physiologic basis to determine when to clamp a cord has demonstrated that even at 1 minute of waiting that is likely only 1/4 of the time needed to wait for lung expansion to occur to any significant degree. I can’t help but wonder how many of the patients we see between 26-35 weeks who have a low heart rate after delivery might have a higher heart rate if they were given far more time than we currently provide for cord clamping.
I can also see why cord milking may be less effective. Yes, you will increase circulating blood volume which may help with hemodynamic stability but perhaps the key here is lung expansion. You can transfuse all the blood you want but if it has nowhere to go just how effective is it?
As we do more work in this area I have to believe that as a Neonatal community we need to prepare ourselves for the coming of the longer delay for cord clamping. Do we need to really have the “Concord” in every delivery or perhaps it is time to truly look at durations of 3-4 minutes before the team clamps the cord.
A Mother’s arms are full of tenderness and children sleep soundly in them – Victor Hugo
The NICU is a loud and chaotic place, that can be painful to be in at times. Its hard to get a good nights sleep (especially for the nurses!). When you think about how much our infants are handled and disturbed, poked and prodded, all in almost continual daylight, it’s a wonder they get any sleep.
For normal neurodevelopment the infant needs both active and quiet sleep. Sleep in an infant is divided into REM (active sleep) and NON-REM (quiet sleep). During quiet sleep you see very little movement and a regular breathing pattern, whereas active sleep involves movement with an irregular breathing pattern.
The importance of Quiet Sleep:
• Without it, the infant doesn’t get enough active sleep.
• Provides the infant with a break from the busy NICU environment.
• Lessons the release of glucocorticoids (Increased cortisol can cause neuronal cell death).
• Necessary for brain development.
• Increased quiet sleep = decreased risk of SIDS.
The importance of Active Sleep:
• Active sleep promotes brain maturation (US DHHS, 2003; Mirmiran, 1995).
• Most memory consolidation and learning occurs in this state (Smith, 2003).
• Nerve cell connections are restructured (synaptic plasticity) (Marks et al., 1995).
Due to the NICU environment, the infant ends up having slower sleep organization maturation and with increased cortisol they are more apt to have a disturbed and less restful sleep.
A complete cycle of sleep includes moving from active sleep to quiet sleep and back to active sleep. Full term and preterms >32 weeks postconceptional age will need about 60-70 minutes for a cycle. Infants <32 weeks postconceptional age will need about 90 minutes. So when infants come out for KC, we try to plan for at least that amount of time.
You will see when infants are placed in KC, the infant settles and goes into a deep sleep. To accommodate this, you will need comfortable chairs for the parent and good support for their arms. You also want to make sure they have had something to eat or drink, pumped breast milk, used the washroom and had something for pain if needed. Don’t be surprised if your parent falls asleep as well; oxytocin will end up kicking in (the cuddle hormone) and they often find it hard to stay awake. We also provide warmed blankets for our parents to encourage everyone to get comfortable and rest. Snoring is a common side effect of KC in our unit…
While in KC, the infants have a deep sleep with less arousal and better sleep organization than when not in KC (Ludington-Hoe et al., 2006)
In Scher et al.’s study (2009) they found that infants’ brain maturation was accelerated and brain complexity increased with 1.5 hours of KC/day for 4 days/wk from 32-40wks pma. Enhanced development in five sensory areas of the brain was shown with KC that was not seen in infants who did not get KC (both preterm and full term).
With all the evidence pointing to KC being beneficial for a good night’s sleep, I find it difficult to understand why so many are skeptical of it!
Sleep is that golden chain that ties health and our bodies together – Thomas Dekker
One of the first things a student of any discipline caring for newborns is how to calculate the apgar score at birth. Over 60 years ago Virginia Apgar created this score as a means of giving care providers a consistent snapshot of what an infant was like in the first minute then fifth and if needed 10, 15 and so on if resuscitation was ongoing. For sure it has served a useful purpose as an apgar score of 0 and 0 gives one cause for real worry. What about a baby with an apgar of 3 and 7 or 4 and 8? There are certainly infants who have done very well who initially had low apgar scores and conversely those who had higher apgar scores who have had very significant deleterious outcomes including death. I don’t mean to suggest that the apgar scores don’t provide any useful predictive value as they are used as part of the criteria to determine if a baby merits whole body cooling or not. The question is though after 60+ years, has another score been created to provide similar information but enhance the predictive value derived from a score?
The Neonatal Resuscitation and Adaptation Score (NRAS)
Back in 2015 Jurdi et al published Evaluation of a Comprehensive Delivery Room Neonatal Resuscitation and Adaptation Score (NRAS) Compared to the Apgar Score. This new score added into a ten point score resuscitative actions taken at the 1 and 5 minute time points to create a more functional score that included interventions. The other thing this new score addressed was more recent data that indicated a blue baby at birth is normal (which is why we have eliminated asking the question “is the baby pink?” in NRP. Knowing that, the colour of the baby in the apgar score may not really be that relevant. Take for example a baby with an apgar score of 3 at one minute who could have a HR over 100 and be limp, blue and with shallow breathing. Such a baby might get a few positive pressure breaths and then within 10 seconds be breathing quite well and crying. Conversely, they might be getting ongoing PPV for several minutes and need oxygen. Were they also getting chest compressions? If I only told you the apgar score you wouldn’t have much to go on. Now look at the NRAS and compare the information gathered using two cardiovascular (C1&2), one neurological test (N1) and two respiratory assessments (R1&2).
The authors in this study performed a pilot study on only on 17 patients really as a proof of concept that the score could be taught and implemented. Providers reported both scores and found “superior interrater reliability (P < .001) and respiratory component reliability (P < .001) for all gestational ages compared to the Apgar score.”
A Bigger Study Was Needed
The same group in 2018 this time led by Witcher published Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability. The primary outcome was the ability of a low score to predict mortality with a study design that was a non-inferiority trial. All attended deliveries were meant to have both scores done but due to limited numbers of trained personnel who could appropriately administer both scores just under 90% of the total deliveries were assigned scores for comparison. The authors sought to recruit 450 infants to show that a low NRAS score (0–3) would not be inferior to a similar Apgar at predicting death. Interestingly an interim analysis found the NRAS to be superior to Apgar when 75.5% of the 450 were enrolled, so the study was stopped. What led the apgar score to perform poorly in predicting mortality (there were only 12 deaths though in the cohort) was the fact that 49 patients with a 1 minute apgar score of 0-3 survived compared to only 7 infants with a low NRAS score.
The other interesting finding was the ability of the NRAS to predict the need for respiratory support at 48 hours with a one minute apgar score of 0-3 being found in 39% of those on support compared to 100% of those with a low NRAS. Also at 5 minutes a score of 4-6 for the apgar was found in 48% of those with respiratory support at 48 hours vs 87% of those with a similar range NRAS. These findings were statistically significant while a host of other conditions such as sepsis, hypoglycemia, hypothermia and others were no different in terms of predictive ability of the scores.
An Even Bigger Study is Needed
To be sure, this study is still small and missed just over 90% of all deliveries so it is possible there is some bias that is not being detected here. I do think there is something here though which a bigger study that has an army of people equipped to provide the scoring will add to this ongoing story. Every practitioner who resuscitates an infant is asked at some point in those first minutes to hour “will my baby be ok?”. The truth is that the apgar score has never lived up to the hope that it would help us provide an accurate clairvoyant picture of what lies ahead for an infant. Where this score gives me hope is that a score which would at the very least help me predict whether an infant would likely still be needing respiratory support in 48 hours provides the basic answer to the most common question we get in the unit once admitted; “when can I take my baby home”. Using this score I could respond with some greater confidence in saying “I think your infant will be on support for at least 48 hours”. The bigger question though which thankfully we don’t have to address too often for the sickest babies at birth is “will my baby survive?”. If a larger study demonstrates this score to provide a greater degree of accuracy then the “Tipping Point” might just be that to switching over to the NRAS and leaving the apgar score behind. That will never happen overnight but medicine is always evolving and with time you the reader may find yourself becoming very familiar with this score!