Given that many preterm infants as they near term equivalent age are ready to go home it is common practice to discontinue caffeine sometime between 33-34 weeks PMA. We do this as we try to time the readiness for discharge in terms of feeding, to the desire to see how infants fare off caffeine. In general, most units I believe try to send babies home without caffeine so we do our best to judge the right timing in stopping this medication. After a period of 5-7 days we generally declare the infant safe to be off caffeine and then move on to other issues preventing them from going home to their families. This strategy generally works well for those infants who are born at later gestations but as Rhein LM et al demonstrated in their paper Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial., after caffeine is stopped, the number of intermittent hypoxic (IH) events are not trivial between 35-39 weeks. Caffeine it would seem may still offer some benefit to those infants who seem otherwise ready to discontinue the medication. What the authors noted in this randomized controlled trial was that the difference caffeine made when continued past 34 weeks was limited to reducing these IH events only from 35-36 weeks but the effect didn’t last past that. Why might that have been? Well it could be that the babies after 36 weeks don’t have enough events to really show a difference or it could be that the dose of caffeine isn’t enough by that point. The latter may well be the case as the metabolism of caffeine ramps up during later gestations and changes from a half life greater than a day in the smallest infants to many hours closer to term. Maybe the caffeine just clears faster?
Follow-up Study attempts to answer that very question.
Recognizing the possibility that levels of caffeine were falling too low after 36 weeks the authors of the previous study begun anew to ask the same question but this time looking at caffeine levels in saliva to ensure that sufficient levels were obtained to demonstrate a difference in the outcome of frequency of IH. In this study, they compared the original cohort of patients who did not receive caffeine after planned discontinuation (N=53) to 27 infants who were randomized to one of two caffeine treatments once the decision to stop caffeine was made. Until 36 weeks PMA each patient was given a standard 10 mg/kg of caffeine case and then randomized to two different strategies. The two dosing strategies were 14 mg/kg of caffeine citrate (equals 7 mg/kg of caffeine base) vs 20 mg/kg (10 mg/kg caffeine base) which both started once the patient reached 36 weeks in anticipation of increased clearance. Salivary caffeine levels were measured just prior to stopping the usual dose of caffeine and then one week after starting 10 mg/kg dosing and then at 37 and 38 weeks respectively on the higher dosing. Adequate serum levels are understood to be > 20 mcg/ml and salivary and plasma concentrations have been shown to have a high level of agreement previously so salivary measurement seems like a good approach. Given that it was a small study it is work noting that the average age of the group that did not receive caffeine was 29.1 weeks compared to the caffeine groups at 27.9 weeks. This becomes important in the context of the results in that earlier gestational age patients would be expected to have more apnea which is not what was observed suggesting a beneficial effect of caffeine even at this later gestational age. Each patient was to be monitored with an oximeter until 40 weeks as per unit guidelines.
So does caffeine make a difference once term gestation is reached?
A total of 32 infants were enrolled with 12 infants receiving the 14 mg/kg and 14 the 20 mg/kg dosing. All infants irrespective of assigned group had caffeine concentrations above 20 mcg/mL ensuring that a therapeutic dose had been received. The intent had been to look at babies out to 40 weeks with pulse oximetry even when discharged but owing to drop off in compliance with monitoring for a minimum of 10 hours per PMA week the analysis was restricted to infants at 37 and 38 weeks which still meant extension past 36 weeks as had been looked at already in the previous study. The design of this study then compared infants receiving known therapeutic dosing at this GA range with a previous cohort from the last study that did not receive caffeine after clinicians had determined it was no longer needed.
The outcomes here were measured in seconds per 24 hours of intermittent hypoxia (An IH event was defined as a decrease in SaO2 by ⩾ 10% from baseline and lasting for ⩾5 s). For graphical purposes the authors chose to display the number of seconds oxygen saturation fell below 90% per day and grouped the two caffeine patients together given that the salivary levels in both were therapeutic. As shown a significant difference in events was seen at all gestational ages.
Putting it into context
The scale used I find interesting and I can’t help but wonder if it was done intentionally to provide impact. The outcome here is measured in seconds and when you are speaking about a mean of 1200 vs 600 seconds it sounds very dramatic but changing that into minutes you are talking about 20 vs 10 minutes a day. Even allowing for the interquartile ranges it really is not more than 50 minutes of saturation less than 90% at 36 weeks. The difference of course as you increase in gestation becomes less as well. When looking at the amount of time spent under 80% for the groups at the three different gestational ages there is still a difference but the amount of time at 36, 27 and 38 weeks was 229, 118 and 84 seconds respectively without caffeine (about 4, 2 and 1 minute per day respectively) vs 83, 41, and 22 seconds in the caffeine groups. I can’t help but think this is a case of statistical significance with questionable clinical significance. The authors don’t indicate that any patients were readmitted with “blue spells” who were being monitored at home which then leaves the sole question in my mind being “Do these brief periods of hypoxemia matter?” In the absence of a long-term follow-up study I would have to say I don’t know but while I have always been a fan of caffeine I am just not sure.
Should we be in a rush to stop caffeine? Well, given that the long term results of the CAP study suggest the drug is safe in the preterm population I would suggest there is no reason to be concerned about continuing caffeine a little longer. If the goal is getting patients home and discharging on caffeine is something you are comfortable with then continuing past 35 weeks is something that may have clinical impact. At the very least I remain comfortable in my own practice of not being in a rush to stop this medication and on occasion sending a patient home with it as well.
It is hard to believe that I gave birth as it were to All Things Neonatal in February of 2015. After 170 published posts and so many wonderful experiences it was time for a change. I have moved the entire blog over to this new location which allows me a great deal more control over the look and feel of the site. It has been a great journey and I have gained many friends along the way. These experiences and interactions with parents, nurses, doctors, respiratory therapists, dieticians and many others have let to a tremendous amount of shared knowledge and I hope that you the reader are better for it. I am also pleased to say that the blogging and other social media venues have taken me far beyond the borders of Manitoba and allowed me to learn from others as well. As you take a look around the site you will notice there are some changes to the layout and the overall look that I hope you like. I also hope that the next 170 blog posts are as interesting to you as the first batch.
If you want to change your bookmark for the site it is now at www.allthingsneonatal.com
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When I think back to my early days as a medical student, one of the first lessons on the physical exam involves checking central and peripheral perfusion as part of the cardiac exam. In the newborn to assess the hemodynamic status I have often taught that while the blood pressure is a nice number to have it is important to remember that it is a number that is the product of two important factors; resistance and flow. It is possible then that a newborn with a low blood pressure could have good flow but poor vascular tone (warm shock) or poor flow and increased vascular tone (cardiogenic shock or hypovolemia). Similarly, the baby with good perfusion could be in septic shock and be vasodilated with good flow. In other words the use of capillary and blood pressure may not tell you what you really want to know.
Is there a better way?
As I have written about previously, point of care ultrasound is on the rise in Neonatology. As more trainees are being taught the skill and equipment more readily available opportunities abound for testing various hypotheses about the benefit of such technology. In addition to my role as a clinical Neonatologist I am also the Medical Director of the Child Health Transport Team and have pondered about a future where ultrasound is taken on retrievals to enhance patient assessment. I was delighted therefore to see a small but interesting study published on this very topic this past month. Browning Carmo KB and colleagues shared their experience in retrieving 44 infants in their paper Feasibility and utility of portable ultrasound during retrieval of sick preterm infants. The study amounted to a proof of concept and took 7 years to complete in large part due to the rare availability of staff who were trained in ultrasound to retrieve patients. These were mostly small higher risk patients (median birthweight, 1130 g (680–1960 g) and median gestation, 27 weeks (23–30)). Availability of a laptop based ultrasound device made this study possible now that there are nearly palm sized and tablet based ultrasound units this study would be even more feasible now (sometimes they were unable to send a three person team due to weight reasons when factoring in the ultrasound equipment). Without going into great detail the measurements included cardiac (structural and hemodynamic) & head ultrasounds. Bringing things full circle it is the hemodynamic assessment that I found the most interesting.
Can we rely on capillary refill?
From previous work normal values for SVC flow are >50 ml/kg/min and for Right ventricular output > 150 ml/kg/min. These thresholds if not met have been correlated with adverse long term outcomes and in the short term need for inotropic support. In the absence of these ultrasound measurements one would use capillary refill and blood pressure to determine the clinical status but how accurate is it?
First of all out of the 44 patients retrieved, assessment in the field demonstrated 27 (61%) had evidence using these parameters of low systemic blood flow. After admission to the NICU 8 had persistent low systemic blood flow with the patients shown below in the table. The striking finding (at least to me) is that 6 out of 8 had capillary refill times < 2 seconds. With respect to blood pressure 5/8 had mean blood pressures that would be considered normal or even elevated despite clearly compromised systemic blood flow. To answer the question I have posed in this section I think the answer is that capillary refill and I would also add blood pressure are not telling you the whole story. I suspect in these patients the numbers were masking the true status of the patient.
How safe is transport?
One other aspect of the study which I hope would provide some relief to those of us who transport patients long distance is that the head ultrasound findings before and after transport were unchanged. Transport with all of it’s movement to and fro and vibrations would not seem to put babies at risk of intracranial bleeding.
Where do we go from here?
Before we all jump on the bandwagon and spend a great deal of money buying such equipment it needs to be said “larger studies are needed” looking at such things as IVH. Although it is reassuring that patients with IVH did not have extension of such bleeding after transport, it needs to be recognized that with such a small study I am not comfortable saying that the case is closed. What I am concerned about though is the lack of correlation between SVC and RVO measurements and the findings we have used for ages to estimate hemodynamic status in patients.
There will be those who resist such change as it does require effort to acquire a new set of skills. I do see this happening though as we move forward if we want to have the most accurate assessment of clinical status in our patients. As equipment with high resolution becomes increasingly available at lower price points, how long can we afford not to adapt?
It is hard to be a Neonatologist who took the path through Pediatrics first and not use a Dr. Seuss quote from time to time. If your unit is anything like ours where you work I imagine you feel as if you are bursting at the seams. As the population grows so do our patient volumes. I often quote the number 10% as being the number of patients we see out of all deliveries each year in our units. When I am asked why our numbers are so high I counter that the answer is simple. For every extra 100 births we get 10 admissions. It is easy though to get lost in the chaos of managing a unit in such busy times and not take a moment to look back and see how far we have come. What did life look like 30 years ago or 25 years ago? In Winnipeg, we are preparing to make a big move into a beautiful new facility in 2018. This will see us unify three units into one which is no easy task but will mean a capacity of 60 beds compared to the 55 operational beds we have at the moment.
In 2017 we are routinely resuscitating infants as young as 23 weeks and now with weights under 500g at times. Whereas in the past anyone under 1000g was considered quite high risk, now the anticipated survival for a 28 week infant at 1000g is at or above 95%. Even in my short career which began in 1998 in terms of Pediatrics and then 2001 in Neonatology our approach in terms of comfort with the smallest infants has eased greatly. What inspired this post though was a series of newspaper clippings from 1986 and 1991 that made me take a moment to look up at the sky and mutter “huh”. When you take a trip down memory lane and read these posts I think you will agree we have come a LONG way and (in truth) in a very short time.
1986 – Opening of the New NICU at Children’s Hospital
This unit was built with 3.5 million dollars. Imagine how far that would go now…
The unit had a capacity of 18 beds but opened with only 12 and a nursing staff of 60 (compare that to 150 now!). They couldn’t open more beds due to the lack of available nurses with sufficient skills.
My favourite comment to provide some perspective was that 5 to 10 years before this time the estimated survival for infants under 1000g was 15%!
Have we ever come a long way in family centred care. Can you imagine having a baby born now at 695g whose family wouldn’t get to hold them till almost 3.5 months of age?! That is what happened in the case described in this article.
1991 – Opening of the new Intermediate Care Nursery
Did you know the old unit had 19 beds (was originally 9 babies) and expanded to 27 at this time?
It cost 3.1 million to build this unit.
The long and the short of it is that yes things are busy and in fact busier than they have ever been. Do not lose sight however wherever your practice is that you are part of a story for the ages. Things that were once thought impossible or miracles are now everyday events and you have been part of it. For those of you who read this post this will likely bring about a lot of nostalgia for you. Thirty years in medicine is not a long time and we have accomplished so much along the way. For those of you who are just starting out, imagine where we will be in 30 years from now. I for one can’t wait to read about it and wonder where we will have gone by then.
If there is one thing that keeps coming back as a lesson again and again in life it is the importance of communication. Whether it be in the home or at work, too many of our “problems” in the workplace come down to whether or not our teams talk to one another effectively.
A tremendous source of stress of course is the unknown. When a baby is born in the field we can only rely on the information being presented to us via telephone contact. In the melee that occurs on arrival of a potentially sick patient, details can be missed.
The following video illustrates such a situation and I believe aptly provides a good example of how to communicate in such a way that the stress of the situation is relieved. If we can all strive to slow things down just a little we may find that communication eliminates much of the tension in such a situation.
If you are looking to “slow” down your life and improve things such as communication style you may want to have a look at the book “In Praise of Slow” as we head into the weekend. It’s all about slowing things down to actually improve efficiency. The world is moving pretty quickly these days and couldn’t we all do with a little more efficiency and less wasted time? In Neonatology we are confronted with surprises every day, often with little notice. If we can slow things down and pass on the needed information to the right people at the right time we will help to reduce errors if we can just get it right the first time!
As you can tell I am a big fan of simulation in helping to create high functioning teams! More of these videos can be accessed on my Youtube channel at
All Things Neonatal YouTube
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Lastly a big thank you to NS, RH and GS without whom none of this would have been possible!
Aside from me donning the costume in the above picture for the Kangaroo Challenge 2017 I learned something new today. Before I get into what I learned, let me say that I had the opportunity to put so many smiles on parents faces by walking around in this full body costume that I am grateful to Diane for finding this costume and Sue (you both know who you are) for purchasing it. Handing out cookies to the parents and children at the bedside and seeing them smile while knowing that they were under significant stress gave me the opportunity to interact with parents in a very different way than I am accustomed to as a Neonatologist so I am so thankful to have had that experience and yes if called upon I will do it again!
We even made the local news! CTV newscast
I posted the above picture on my Facebook page and to my surprise many of the comments led me to believe that Kangaroo Care is still something that needs a little nudging to get the word out about. I found this actually quite surprising given how immersed we are in Winnipeg with this strategy. When I think about new interventions in Neonatology it is synonymous in virtually all cases with an influx of dollars to achieve usher in the new program. Here is a program that is virtually free but only requires a commitment from families to spend the time at the bedside with their baby in the NICU.
I have been asked by many of my nursing colleagues to write something about Kangaroo care on this site and so here it is…
What is it?
You have likely heard of Kangaroo Care and you may have even seen some children receiving it in your hospital. Why is this so important?
Kangaroo Care (KC) or Skin to Skin Care (STS) is an ideal method of involving parents in the care of their premature infant. It fosters bonding between parents and their hospitalized infant, encourages the family to be with their child and thereby exposes them to other elements of neonatal care that they can take part in. While we know that many units are practising Kangaroo Care there is a big difference between having KC in your unit and doing everything you can to maximize the opportunity that your families have to participate.
There is much more to KC than simply holding a baby against your chest. For a demonstration of KC please watch the accompanying video and show it to any one in your units that may need a visual demonstration. This excellent video is from Nationwide Children’s Hospital and walks you through all of the important steps to get it right and maximize benefit.
Kangaroo Care Video
Before you reach the conclusion that KC only serves to enhance the parental experience it does so much more than that. The practice began in Bogota Columbia in 1979 in order to deal with a shortage of incubators and associated rampant hospital infections. The results of their intervention were dramatic and lead to the spread of this strategy worldwide. The person credited with helping to spread the word and establish KC as a standard of care in many NICUs is Nils Bergman and his story and commentary can be found here http://bit.ly/1cqIXlm
The effects of KC are dramatic and effective to reduce many important morbidities and conclusively has led to a reduction in death arguably the most important outcome. An analysis of effect has been the subject of several Cochrane Collaboration reviews with the most recent one being found here.
To summarize though, the use of KC or STS care has resulted in the following overall benefits to premature infants at discharge or 40 – 41 weeks’ postmenstrual age:
mortality (typical RR 0.68, 95% CI 0.48 to 0.96)
nosocomial infection/sepsis (typical RR 0.57, 95% CI 0.40 to 0.80)
hypothermia (typical RR 0.23, 95% CI 0.10 to 0.55)
KMC was found to increase some measures of infant growth, breastfeeding, and mother-infant attachment
To put this in perspective, medicine is littered with great medications that never achieved such impact as simply putting your child against your chest. This is another shining example of doing more with less. This is not to say that modern medicine and technology does not have its place in the NICU but KC is simply too powerful a strategy not to use and promote routinely in the NICU.
Please join me in championing this wonderful technique and make a difference to all of our babies!
A sample of our parent letter to promote KC is found in the link below.
Parent letter II