Mother Ship by Francesca Segal

Cite this article as:
Mahima Chandrasekhar and Tara George. Mother Ship by Francesca Segal, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32838

A mother’s experience of the Neonatal Unit

Mother Ship by Francesca Segal chronicles the first 56 days, from birth to discharge, that the author’s twin, 30 week, premature babies spent in the NICU. She describes a journey that is far from smooth sailing; rocky and filled with turbulence from the start. At the same time, it is one filled with hope, longing and joy, which ultimately steers this ship to its destination: home. 

Book cover for Mother Ship

Segal describes how she expected her pregnancy to progress, and how divergent from reality it became. At times, her words are soaked in guilt and come through to the reader in waves: “we are encouraged to believe that a mother’s body is mad and clever… though mine was not quite mad and clever enough to sustain a pregnancy.” It is soothed, in part, by her well-timed jabs of humour, expressed through the rose-tinted glasses of nostalgia. She celebrates bonds forged through shared experiences between the mothers of the ‘milking shed’, makes us appreciate the enduring presence of her husband and prioritises hygiene in a way that would make every Infection Control team proud. 

Importantly, Segal highlights many areas for improvement in the way care is provided. Her observations of the NICU bring attention to the lightning-fast and disorientating ward rounds, the constant use of medical jargon, frighteningly alien words second only to the name of that town in Wales (you all know where I am speaking about), and reluctance in having to involve yet another ‘Mum’ in decision making. Despite this, she showers gratitude upon the healthcare professionals with whom she shares a complicated but respectful relationship.

The book evokes a cocktail of emotions, prompts you to give your mother a call, and makes you ever so fond of little ‘A-lette’ and ‘B-lette’. Mother or not, clinician or not, a treat for all who read.

Why I am recommending this book

Tara George (GP)

Mother Ship provides a window into a world that may be familiar to many of us in a work context but seen here through the eyes of a mother. Disorientating, frightening, a liminal place where babies born too small, too soon may live or may die. What really struck me was the camaraderie of “the milking shed”, the irreverent humour, the ability ultimately to be human when that was all she had left. It left me expanding the horizons of what the word “mother” really is.  There are important lessons for those of us who look after whole families as well as for paediatricians – leaving your newborn (safely?) in the hospital and being at home, a mother with no mothering to do. As a GP with some interest in perinatal mental health, it is clear how much mothers in the scenario need support but it is also made strikingly obvious how little time she has for anything other than sleep, travel, endless expressing of milk and being in the hospital.  The moment of absolute compassion and wisdom when the nurses send her and her husband out for dinner one night reaffirms for me how truly amazing NHS staff are at both the high tech bits of medicine and at the human side.  

Mahima Chandrasekhar (FY2)

Medical school has always highlighted the merits of clear communication, empathy and a multidisciplinary approach to decision making. We practiced a lot of these skills in simulated environments and attempted to apply our learning into the clinical environment, to varying degrees of success. Reading Mothership has provided me with the perspective of the mother. Apart from being an enjoyable and moving story, it has provided some constructive feedback on our communication as a health profession. This book has given me several points to reflect on:

‘Mum’ has a name!

It is often hard to remember all the names of all the children and parents. However, making that effort to ask for her name in the ward round will improve the quality of your rapport. It will also make the mother of your patient feel more like she is part of the team making decisions about the child: which she is.

The mother of your patient might be a patient too

Sometimes, the child is born via emergency C-Section, and the mother standing opposite you, less than a day after the operation, is on a cocktail of drugs to allow her to achieve basic functionality through the haze of pain. The information you are giving may not be absorbed in the way you intend, and something as small as offering her a chair to sit on, can make the world of a difference.

Avoid jargon

I often have to Google certain terms and abbreviations, especially when moving on to a new job. If it is confusing for a medical junior, I can imagine it being downright disorientating for a non-medical parent. Explaining the plan and developments in detail without jargon can help avoid unnecessary anxiety and misunderstandings.  

Involve parents in the decision making

Inevitably, parents will need to care for their children when discharged from hospital. Ensuring they are aware of the ongoing medical issues, red flags, NG tube training, basic life support, emergency numbers to call, is paramount for a safe discharge. Involve parents early, to avoid information dump at the end.

Being at the start of my medical career, everything is a learning point, and I could go on. You will make your own reflections, both personal and professional, when you pick up this book.

Mother Ship is an enjoyable learning experience on communication. A case-based discussion that is riveting and heart-warming, right in the comfort of your own home, with a warm cup of tea in hand and a rich environment for reflection. 

If you want to go deeper then please watch this heartfelt talk from neonatologist, Jasmine Antoine, about being the parent, not the practitioner in NICU.

Ultrasound Guided Peripheral Vascular Access

Cite this article as:
Trent Calcutt. Ultrasound Guided Peripheral Vascular Access, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.23253

One of my favourite things in paediatrics is the expanding role of ultrasound guided vascular access.

When I started as a paediatric registrar, I’d just finished an adult ICU term where I’d become spent a majority of time supporting provision of a vascular access service, and as part of this had become a PICC line insertion instructor. Eventually, I got to the point where I dreamt of abstract grey shapes. But then I started a paediatric job in a regional hospital where it seemed that ultrasound was used for vascular access rarely if at all. Initially, I thought there must have been something different about paediatric vascular access that I was unaware of. One day, when looking after a young lady with Rett’s who was known to be difficult to cannulate, I reached for the ultrasound. In the five years since, ultrasound has been a standard part of my practice in achieving vascular access in children, with technique adapted to fit the age of the patient.

Ultrasound-guided vascular access and paediatrics seem like such a natural partnership. The concept of a DIVA (“difficult IV access”) patient is receiving increasing interest and research. Criteria for a DIVA can include prematurity, inability to see or feel a vessel, or an episode of multiple prior attempts. These criteria would be met by a huge number of the kids we care for, in particular toddlers or the previously premature infant. 

Chonky baby arm
Spot the veins

Why is ultrasound not the first-line adjunct in these tricky kids? It’s probably multifactorial, but certainly, ultrasound is more difficult in children than adults. Its utility is varied in the NICU context and for infants under 2.5kg, although can still have a role with a modification to technique. It’s also harder to learn ultrasound in a population who are scared, angry, impatient and poorly tolerant of a prolonged period of needle-through-skin. For these reasons, I think that there is less appeal to replace the familiar (cannulating without an ultrasound), with the unfamiliar (cannulating with an ultrasound). As I’d experienced, this also leads to a culture where ultrasound is infrequently utilized, decreasing the likelihood of implementation by new or more junior staff.

Once the learning investment is made to reach a proficient level of ultrasound competency (about 20 cannulas in adults) the potential benefits are significant. Decreased time spent performing a procedure, decreased number of attempts and subsequent patient trauma, and increased cannula longevity are all achievable.

I’ve spent a lot of time thinking success optimisation in paediatric ultrasound guided cannulation, both during my own development of proficiency and then in an effort to verbalize this skill when educating others. Below are my 5 top tips to enhance your ultrasound-guided cannulation skills:

I’m hoping that some of these words may help avoid some bits of the inevitable trial and error process that comes with learning a new skill.

There is sometimes a general impression of both practical and personal inconvenience in using ultrasound for vascular access. An ultrasound may not be nearby. There is the fear of “looking silly” in front of other people, as turning on, adjusting, and then physically coordinating the use of the ultrasound may be unfamiliar. During the period of establishing proficiency, an approach to decreasing this sense of unfamiliarity is to get in the habit of bringing the ultrasound with you do a cannula. Turn on and optimize the ultrasound to view vessels, and spend a period mapping out candidates for cannulation using your non-cannulating hand. Draw on the patient with a skin pen if you want to keep track of the best sites. Then, discard the ultrasound and cannulate using whatever technique is most familiar to you, but with the added knowledge of vessel location, depth, size, and direction. If this becomes a routine and almost ritualistic process, the mental barrier created by a lack of familiarity with ultrasound settings and holding the transducer should decrease over time. It is a relatively small step from performing vascular mapping to placing a cannula under real-time ultrasound guidance.

The preparation otherwise is quite straightforward. In addition to the set up that you use for all other cannulas, you need the following four things:

  • An ultrasound with a linear array probe (the smaller the footprint and the higher the frequency, the better)
  • Sterile lubricating gel and some form of sterile barrier to cover your probe (this varies institutionally)
  • Cavilon wipe or skin prep (securement devices / dressings / tape doesn’t like to stick to ultrasound gel so will need some encouragement)
  • An extra person (one of your hands is out of action, so you need an additional person to perform the task that your non-dominant hand would normally do; this is typically stabilization of the distal limb)

The ultrasound sits on the opposite side of the bed to the operator, so as to minimize truncal movement in looking from the puncture site to screen. Aside from making sure the correct probe is selected, the only 3 settings you need to know how to adjust are depth (typically as shallow as possible), gain (similar to a ‘brightness’ setting to highlight blood-filled vessels), and a midline marker (for physical-digital landmark referencing).

As alluded to above, pre-scanning is a useful skill even in the absence of cannulating under real-time ultrasound guidance. It’s a good idea to scope out the most appropriate vessels and puncture sites prior to picking up your cannula. Essentially the objective is to place a cannula within a vessel with as few attempts as possible, as quickly as possible, with as little pain as possible, and in a site that will provide the greatest longevity. Characteristics of vessels that tend to correlate with these outcomes are:

  • long and straight stretches
  • vessel 6mm or less below the surface
  • vessels greater than 2mm in diameter
  • vessels that don’t cross a joint (provides freedom of movement and less extravasation)
  • vessels without upstream thrombosis or obstruction

Mid-forearm vessels often meet the above criteria.

The greater length of cannula able to be placed within the vessel can correlate with longevity, however larger cannula diameter may increase the phlebitis and decrease longevity. This requires consideration of the balance between length and diameter of device. Of the commonly available devices, a good balance is a blue cannula (22G). There are several specialised less widely available devices that are longer versions of small diameter cannulae (24G and 22G).

In practical terms, to find these vessels you can start in the antecubital fossa (more familiar area for most of us) and track them down, or plonk down on the forearm and pan circumferentially. Scanning in the short axis / transverse axis / cross-sectional view tends to work best in kids. To assess suitability, translate the probe up and down along a vessel to get an idea of the direction. If it’s running diagonally, rotate your probe until it’s running along the same plane as the vessel to act as a mental reminder of the angle/direction that you need to insert your cannula. Pick the specific spot on the vessel that you’d like to puncture, bearing in mind that you will be puncturing the skin millimetres back from that point. Pick the patch of the vein that is the longest, straightest, shallowest, and biggest. Have a second fallback site planned out elsewhere for if required. Lastly, make sure to track the vein proximally as far as you can to ensure that it doesn’t run into a large thrombosed/occluded/recannalizing patch of vessel.

Obscure angles make things more challenging, in my experience. Right angles and parallel lines are your friends because they assist in mental unburdening and allow you to devote energy to troubleshooting issues. As mentioned above, map the vessel prior to puncture. Part or all of a vein will often wander diagonally along its journey, so approaching from the wrong direction increases the likelihood of punching through the side of the vessel. The centre of the image corresponds to the arrow/marker along the long edge of the probe, so you have a reference point between digital (screen) and physical (skin). Use the ultrasound as a mental reminder of your plane of approach; rotate the probe until the vessel is consistently sitting in the very centre of your image as you plane up and down. In other words, the ultrasound image is perfectly perpendicular to the plane of the vessel.

Speaking of right angles, I prefer to keep the ultrasound at right angles to the surface that you’re scanning. Angling back and forth creates a loss of contact and a distorted image as the ultrasound bounces of structures and does not return to the transducer. This creates a less clear image where vessels artificially look larger. If you need to change your view, translate/glide the probe along the skin, rather than introducing angle. It can be useful to temporarily angle the transducer perpendicular to the shaft of the cannula if you lose sight of it as this will light it up more clearly.

This is a big one. Thinking of your cannulation as a two-phase puncture process is something that I find extremely helpful. Your objective is not to puncture the skin and end up inside the vessel in a single action, and in fact, attempting to do this seems decrease the likelihood of success. 

 

Puncture Phase 1

Puncture 1 is the process from skin puncture to positioning the tip of your cannula on the superficial wall of the vessel. To achieve this, align your probe to achieve a view with the vessel in the centre of the image. Puncture the skin with the cannula a few millimetres distal to the probe. This bit is painful, so do this with a decisive action so that 2-3 mm of the cannula is within the soft tissue. Increase your angle of insertion to 30-45°. Your next objective is to find the tip of the cannula. Moving your non-dominant (ultrasound) hand, translate/slide the probe towards the puncture site until a glimmering white dot becomes apparent in your image. Once you are convinced that you are viewing your cannula, you need to ensure that you are viewing the tip at all times.

The most important thing to remember is the only way to be certain that you are viewing the tip of your cannula is when the glimmering dot disappears when you move the probe 1mm proximally (away). It is frustratingly easy to think that you are viewing your cannula tip when instead you are halfway along the shaft, with the tip out the deep wall of the vessel. Maintain this view via a “walking” approach. For each 1-2mm advancement (step) of the cannula, make an equivalent proximal movement with your ultrasound probe (step). Move the ultrasound away so that you cannot see cannula tip anymore, and then advance the cannula into view. If needed, intermittently stop advancing your cannula and check your tip position as described above. I find advancing at 30-45° until you reach the vessel works well as minimal cannula is wasted on the journey there.

If you find yourself wandering off track, keep the ultrasound focused around the vessel as the centre of your image (as this is your target). Correcting if off centre is slightly counterintuitive. Move your cannulating hand away from the direction that you want to move your cannula tip (ie- moving right will move the tip left). Continue inserting until your cannula tip is sitting at 12 o’clock on top of your vessel. As you reach this point, the tip of the cannula may gently tent the roof of the vessel, turning an “O” shape into a “❤️” shape. This is a good test of correct positioning. Once you’ve reached this point, you’re ready for puncture phase 2!!

 Puncture Phase 2

Puncture 2 is the process of entering the vessel to feeding your cannula fully in. With the tip of your cannula in view and the roof of the vessel tented (❤️), continue incrementally advancing your cannula with tiny movement, walking the ultrasound forward to ensure the tip remains in view (as above). Gently decrease your angle of insertion so that the superficial wall is not tenting towards the deep wall but rather into the potential space of the proximal vessel. Eventually, your tented vessel (❤️) will suddenly encompass the cannula and return to a circular shape (O). This may be associated with a tactile pop. You can check for flashback for additional confirmation of vessel puncture, but I prefer to not take my eyes off the ultrasound screen at this point.

Continue decreasing your angle of insertion to maintain the tip of the cannula in the top 50% of the vessel (keep the sharp bevel away from the deep wall). This may eventually require you be pushing the cannula into the skin, which really requires your assistant to get out of the way. Don’t lose site of your tip! Continue to step forward; cannula then ultrasound. To check whether you are in the vessel and not in soft tissue or dragging on the vessel wall, waggle the tip of the cannula around gently (left, right, up, down). There should be absolutely no distortion of the soft tissue surrounding the vessel; completely free cannula tip movement. I tend to leave the metal stylet in until the plastic catheter is fully inserted to the hub because of greater visibility and added rigidity. This does, however, carry the risk of puncturing the back or sidewall of the vessel if you don’t keep a close eye on your cannula tip. At the very least, ensure 3-4mm of the cannula is inside the vessel lumen prior to gliding the plastic catheter off (to avoid tissuing / tearing the vessel roof). Once this is done, you’ve just successfully place a real-time ultrasound-guided cannula! Well done!

I think it’s reasonable with each healthcare interaction to measure success both in the resolution of issue (beneficence) and in minimization of harm / traumatic experience (non-maleficence). Vascular access is our commonest painful procedure, hence representing a significant potential burden of pain, anxiety, and trauma. Undertaking steps to minimize vascular access attempts, maximize speed/efficiency, and maximize cannula longevity are important considerations in the healthcare interaction. Even if we manage to achieve the elusive goal of a single puncture hospital admission, this still requires a single puncture. 

This discussion is not really directed towards addressing the specifics of analgesia and sedation but suffice to say that time permitting these should be used and optimized readily. A topical anaesthetic is valuable, although in the case of an ultrasound-guided cannula application by the operator is useful in ensuring good placement. Evidence is increasingly suggesting that topical anaesthetic is appropriate in all ages including neonates.

The power of social stories, rehearsal, music therapy, and just general distraction cannot be undervalued. There is a multitude of approaches to this. 

Unfortunately, it is not an uncommon experience to be in a situation where vascular access is required with a degree of clinical urgency. In this circumstance, oral/intranasal/topical medication may have not had time to work, and a specialist in distraction may not be readily available.

In this circumstance, I have found that playing calm and quiet music more useful than positioning a video in front of a child. Maintaining a minimum of people speaking, and using quiet calm voices is valuable. I have had some success using the ultrasound itself as a distraction modality while telling the child a story of the “doughnut that has lost its hole” (vein and cannula tip respectively) as the tip tracks toward the vessel. A variant is the “star that fell from the sky into the lake” (cannula tip and vein respectively). There are many approaches to pain reduction through distraction.

It is my sincere hope that these tips are of some practical and clinical value in your cannulating endeavours. If it makes a difference for a single child, then surely it’s worth it. Good luck!

Urine dipsticks

Cite this article as:
Laura Riddick. Urine dipsticks, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32596

This post will cover what’s what on a urine dipstick and clarify what it means when “it lights up like a Christmas tree

It’s 3 am and the 4-year-old with fever has finally produced a urine sample. You dip it and it lights up “positive for everything”. You’re sure it’s positive for infection, but what if the pH is 5.5? What does it mean that there is blood and protein in it?

Leukocytes

Surely white blood cells must mean an infection is present? If you have read the NICE UTI guidelines, so you know that is not necessarily the case.

The dipstick tests for leukocyte esterase. This is an enzyme produced by neutrophils and can be a sign of a urinary tract infection (white cells in urine = pyuria). These neutrophils, however, and the enzyme they produce can also be a sign of infection outside of the body such as vulvovaginitis. They may also be found in the presence of haematuria.

The overall sensitivity for leukocyte esterase is 49 – 79% with a specificity of 79 – 87%. As a result, it can be considered to be suggestive of “possible UTI”, and “probable UTI” if found with a positive nitrite sample (specificity increased to 99%).

What does this mean/bottom line: If positive and history suggestive (i.e. dysuria or fever) consider UTI and send for culture. If negative, then it is quite unlikely that there is an infection.

Nitrites

Nitrites are the breakdown product by gram-negative organisms such as E.coli. They are a more specific test (93-98%) than leukocytes but their sensitivity is lower (47-49%). The sensitivity is particularly poor as the urine needs to sit in the bladder for a while (at least 4 hours) for it to be positive.

What does this mean/bottom line: If it is positive, it is highly suggestive of infection. If it is negative, then does not necessarily rule out infection and needs correlation with leukocytes and presentation

Blood

Blood (haematuria) can be present for many reasons, so it is important to determine if there is microscopic (dipstick only) or macroscopic (visibly bloody). If blood is seen seen with leukocytes and/or nitrites then you should consider the child to have a UTI. If blood is seen with protein, then glomerulonephritis needs to be considered as a cause.

Causes of haematuria

  • Infection
  • Fever
  • Kidney stones
  • Glomerulonephritis
  • Renal tumour
  • Exercise
  • Trauma
  • Menstruation (doesn’t cause haematuria but will show up on dipstick so don’t forget to ask)

Isolated microscopic haematuria is common and only needs investigation if persistent, but make sure a blood pressure is checked as this is an often missed test. If haematuria is persistent it may need further investigation.

Reasons for further investigation

  • Macroscopic haematuria
  • Proteinuria
  • High blood pressure
  • Clinical oedema or features of fluid overload
  • Persisting microscopic haematuria (>2 occasions over 2-4 weeks apart)

Bottom line: If just microscopic haematuria on dipstick without explanation, then request a repeat sample with GP in 2-4 weeks. Don’t forget to check a blood pressure!

Protein

The body excretes a small amount which is usually not enough to pick up on dipstick.

If the body is “stressed” in illness or infection, it can cause proteinuria, however it is also a sign of inflammation or damage within the kidney and so further history and examination is required.

When there is proteinuria of 2+ or more occurs during illness or a UTI, it can be repeated in a couple of weeks to ensure that it does not persist when the patient is well.

If there is no illness or infection, you would need to consider other causes such as glomerulonephritis and nephrotic syndrome, examine for oedema, and send off a protein:creatinine ratio sample.

Bottom line: small amounts can be seen in illness, but large amounts needs review depending on how the patient is.

Glucose

This is not usually found in the urine, but small amounts can be detected if the patient is unwell, or is on steroids. If there is a large amount of glucose, consider checking a blood glucose to rule out diabetes, and see if there is any other evidence of kidney problems.

Ketones

A by-product from the breakdown of fat when sugar stores cannot be used. These can be seen in patients who have not been eating, vomiting and in DKA. It is always worth checking the blood glucose in these patients, as its absence in hypoglycaemic patients should alert you to a potential metabolic disorder.

Bottom line: Seen during periods of vomiting or not eating. Always check a blood glucose.

Bilirubin

Excessive bilirubin that is not dealt with in the liver is excreted in urine. Thus the presence of bilirubin in the urine can be seen in conjugated hyperbilirubinaemia, and therefore a feature of liver disease. If the urine dipstick measures urobilirubin then this can be seen normally on a dipstick (normal to 1+). A high urobilirubin could suggest haemolytic disease, as it reflects unconjugated bilirubin.

Bottom line: Bilirubin – not normal. Urobilinogen – normal (in small amounts)

Specific Gravity

This measures how dilute your urine is by comparing the solubility if the urine to water. If <1.005 then the urine is very dilute – do they drink a lot of water? If not the kidney may be unable to concentrate the urine, there it would be wise to consider checking a serum sodium and assess the patient for features of diabetes insipidus.

A high specific gravity means the urine is concentrated, and suggests that the patient may be dehydrated. If they do not appear hydrated, then does the patient appear oedematous? This could suggest systemic disease

A list of causes of high specific gravity

Bottom line: compare to the patient’s hydration status

pH

The urine pH varies and is usually slightly acidic. It can be influenced by diet and medication. Usually, alkaline urine is a product of vegetarian diets and medication. It can also be present in UTIs caused by urea splitting organisms, such as Proteus and Pseudomonas. It is seen in renal tubule anomalies or if the patient has metabolic alkalosis. Urinary acidosis is seen with high protein diets and can reflect systemic acidosis (for example, DKA, diarrhoea and vomiting)

Bottom line: Not very useful on its own.

Urine dipticks infographics

Selected references

https://litfl.com/dipstick-urinalysis/

https://patient.info/treatment-medication/urine-dipstick-test

Yates A. Urinalysis: how to interpret results. Nursing Times. 2016 Jun 8;112(2):1-3.

https://geekymedics.com/urinalysis-osce-guide/

https://www.mayoclinic.org/tests-procedures/urinalysis/about/pac-20384907

https://www.nice.org.uk/guidance/cg54/chapter/Recommendations#diagnosis

https://www.clinicalguidelines.scot.nhs.uk/nhsggc-paediatric-clinical-guidelines/nhsggc-guidelines/emergency-medicine/haematuria-management-and-investigation-in-paediatrics/

Fernandes DJ, Jaidev M, Castelino DN. Utility of dipstick test (nitrite and leukocyte esterase) and microscopic analysis of urine when compared to culture in the diagnosis of urinary tract infection in children. Int J Contemp Pediatr 2017;5:156-60

Jeng-Daw Tsai, Chun-Chen Lin, Stephan S. Yang, Diagnosis of pediatric urinary tract infections, Urological Science, Volume 27, Issue 3, 2016, Pages 131-134

Tsai JD, Lin CC, Yang SS. Diagnosis of pediatric urinary tract infections. Urological Science. 2016 Sep 1;27(3):131-4.

How to… set up the resuscitaire

Cite this article as:
Taryn Miller. How to… set up the resuscitaire, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.31358

Check that the resuscitaire is plugged in and connected to the oxygen and air 

  • On button 
  • Light button 

Top to bottom run through 

Top panel  

  • Clock or timer to time your resuscitation – (start, stop and reset) 
  • Temperature settings 
    • Pre-warm – The machine will automatically set to pre-warm
    • Manual – Use the up button to change to manual 
    • Up and down buttons – Dial up the temperature using these buttons in the manual setting  
    • Baby – If using a manual continuous saturation monitor plug into here and then set to baby 

Key locks the settings so it cannot be changed again unless you press it again

Blender 1:13

This blender corresponds to the Fio2 of the gas coming out of the auxiliary gas port
You can dial it up or down
Most people set the initial FIO2 to 0.21 so that you are resuscitating on air 

Suction 1:25

Turn on suction using the switch
Increase pressure by turning the suction dial 
When you occlude the suction device the needle on the dial will move up and down to show how much negative pressure is exerted 

Ventilation settings 1:40

Autobreath

T piece is attached to auxiliary gas port shown 

Working from left to right 

  • Rate – most people start with an initial rate of 40 breaths per minute 
  • PEEP – If you are not setting the peep with valve on top of the T piece device you can set it using the PEEP dial 
  • On and off switch for autobreath 
  • Airway pressure relief – also known as the peak inspiratory pressure – most people like to set this at a maximum of 30 to begin with 

Testing pressures: 2:13 

To test the pressures when the T-piece is connected to the gas outlet:  

  • PEEP = Occlude the valve inside the mask, the needle will move to the desired level of peep 
  • Peak inspiratory pressure – occlude the valve at the top of the T-piece

Flow rate 2:31

  • This dial controls the flow rate through the gas outlet 
  • Most people set it at 8 litres per minute 

Gas outlet 

  • Below this you have an alternative gas outlet that always runs on 100% oxygen 
  • You can attach a water or anaesthetic circuit here and adjust the flow rate in the same way as above using this dial 

Gas Supply 

  • These dials show much how air and oxygen are in the tanks behind the resuscitaire 
  • This switch should be used whenever the gases are in use

Resuscitaire run through 

There is a baby being born – get your resuscitaire ready and primed 

  1. Plug the resuscitaire in 
  2. Connect to the gases – black to air, white to oxygen 
  3. Turn the resuscitaire on and turn the light on 
  4. Select manual and turn the temperature all the way up 
  5. Set your blender to an fi02 of 21 
  6. Check your suction – one end connects underneath the resuscitaire, the other end connects to the yanker. Check it is working by occluding the end 
  7. Set your Autobreath settings – 
    • Rate of 40 breaths per minute 
    • Peep of 4 or 5 and turn the peep on  
    • Flow rate of 8 
    • Connect the tubing to the outlet
  8. Test the pressures  
    • Occlude the mask to check PEEP isn’t too high 
    • Occlude the valve at the top of the T-piece to check your peak inspiratory pressure 
  9. You should have a 250ml bag-valve-mask to attach in case you need to manually bag the baby 
  10. Have lots of towels 
  11. Oxygen saturation probe and stick it to the edge of the resuscitaire  
  12. Airway trolley near by 

How to… perform a lumbar puncture

Cite this article as:
Taryn Miller. How to… perform a lumbar puncture, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.31106

Performing a neonatal or paediatric lumbar puncture can be a daunting procedure but is an important part of the initial investigations of an unwell patient. However, it’s important to remember that a lumbar puncture should never delay administration of antibiotics that could be life-saving to a patient with suspected bacterial meningitis. 

Before the start of any procedure always ask, “Why are we doing this procedure? Are there any contraindications?”. 

The Royal Children’s hospital in Melbourne outline the indications and contraindications to performing a lumbar puncture as follows:

Indications

  • Suspected meningitis or encephalitis 
  • Suspected subarachnoid haemorrhage in the context of a normal CT scan 
  • To assist with the diagnosis of other CNS or neurometabolic conditions 

Contraindications

  • The febrile child with purpura where meningococcal infection is suspected 
  • Cardiovascular compromise/ shock 
  • Respiratory compromise 
  • Signs of raised intracranial pressure (diplopia, abnormal pupillary responses, abnormal motor posturing or papilledema) 
  • Coma: Absent or non-purposeful response to pain. 
  • Focal neurological signs or seizures 
  • Recent seizures 
  • Local infection around the area where the LP would be performed 
  • Coagulopathy/ thrombocytopenia 

The next important step is to gain verbal consent from the parents by explaining the procedure, risks and complications. 

Stop – As a parent, an initial septic workup of an unwell child can be an extremely stressful time. Try and explain the procedure with the risks and complications as concisely and clearly as you can without using medical jargon. It can be useful to think… if I were a parent what would I want to know?

It is useful to have your departments recommended lumbar puncture leaflet printed to give to the parents to read after the conversation. 

We would like to perform an investigation known as a lumbar puncture on your child. We do not perform this investigation unless it is absolutely necessary, and we think this is necessary to perform on your child today. 

This is a test that involves a small needle that is inserted into the back of your babies/ child’s spine to obtain a sample of the fluid that runs around the brain and the spinal cord. We usually do this test to identify whether your child has meningitis (infection of the lining of the brain). Sometimes we occasionally think your child is too ill to have a lumbar puncture and we will give antibiotics straight away to cover the most common types of bugs that cause meningitis. However, if possible, we like to perform a lumbar puncture that helps us identify: 1 ) if your child has meningitis by looking at the cells in the fluid, and 2) what type of bug is causing your child’s meningitis. This helps us choose the correct type of antibiotic and how long it is needed for. 

The procedure can be an uncomfortable procedure similar to performing a blood test. Most babies will be upset by being held in one position more than by the procedure itself. To minimise discomfort we will give pain relief such as sucrose or a pacifier to help. The procedure usually takes 30 minutes to perform. 

This can be a distressing procedure for parents to watch and we often offer parents not to be present while we perform the procedure. This can help increase the chance of success as it is a difficult procedure to perform. However, you are always more than welcome to be present. 

A lumbar puncture is a safe test and the risk of any serious complications such as bleeding, infection or damage to the nerves is extremely low. More common risks are that we are not able to get the sample we need or having to try more than once. Today we will only try twice and then stop if we are unsuccessful. 

Remember the parents may refuse a lumbar puncture and this should prompt us to think again and take some more time to re-discuss this with a senior and / or the parents. 

The procedure

Gather equipment and personnel 0:13  

Ensure that at least two people (the person performing the lumbar puncture and an assistant to hold) are present. It is often useful to have a third person to help as an assistant or with any other problems during the procedure. 

Equipment

  • Drapes or a sterile dressings pack 
  • Sterile gloves 
  • Sterile Gown 
  • Mask 
  • Spinal needle – 22G or 25G bevelled spinal needle with a stylet* 
  • Specimen pots x 2/3 
  • Chlorhexidine 0.5% in 70% alcohol solution with tint (chloraprep 3mls skin cleaning applicator) or your local alternative 
  • Local anaesthetic and/or sucrose 
  • Specimen pots x 2 
  • Labels 
  • Tegaderm for the site following removal of the needle 

For some more information on how to choose a correct spinal needle for the patient check this post from Henry.

Position 0:35

Position is everything for a paediatric lumbar puncture. A calm, cool and collected assistant who is confident in maintaining an adequate position is essential for improving the likelihood of success. 

You: Decide whether you are going to sit or stand for the procedure and set the bed height accordingly 

Patient: 

  • Position the patient in the left or right lateral position with their knees to their chest. Avoid over flexing the neck as this can cause respiratory compromise especially in younger neonatal patients. 
  • Position the patient so that the plane of their back is exactly perpendicular (90 degrees) to the bed. 
Lateral position for lumbar puncture

Landmarks: 

You are aiming for approximately the L3-L4 or L4-5 interspace. In neonates you can feel the ASIS and in older children you can feel the PSIS.  Invision a straight line between the top of the iliac crests intersecting your target area L3/4. 

Analgesia, anaesthesia, and sedation  1:15

  • All children should have a form of local anaesthetic used which can include: 
  • For the neonatal population oral sucrose can be used. 
Layers of the spine

The procedure 1:36

  • Prep the trolley by cleaning with a detergent wipe and allow it to dry before the procedure set up 
  • Open the dressings pack onto the clean trolley and using a non-touch technique drop the sterile gloves, cleaning solution and lumbar puncture needle into the sterile area. 
  • Wash hands and don sterile gloves 
  • Put a sterile drape under the patient’s buttocks, on the right and left side of the desired site and at the top leaving the spine exposed. It’s a good idea to keep the nappy on a neonate during the procedure and pull it slightly further down to prevent faeces accidentally sliding into the sterile field during the procedure. 
  • Clean the area using the chlorhexidine solution to disinfect the skin around the procedure site. Do not place the used swab on the sterile field but dispose of immediately in the bin. Wait for the skin to dry 
  • Take the tops off the specimen pots and keep them on your sterile field ready 
  • Identify the desired space as described above  
  • If using lignocaine infiltrate at this step 
  • Position the needle with the bevel facing up towards the ceiling
  • Direct the needle towards the umbilicus 
  • Resistance will be met often felt as the needle moves through the ligamentum flavum
  • Keep advancing slowly – a pop may be felt as the epidural space is now crossed and the subarachnoid space is entered a few millimetres more. 
  • Remove the stylet and check for CSF 
  • If CSF fluid Is present collect 6-10 drops of CSF in each container. Number the container depending on analyses required. 
  • Re-insert the stylet (to reduce the risk of head) and in one swift manoeuvre, remove the needle and stylet. 
  • Apply pressure to the site 
  • Use a tegaderm dressing so that the site is visible to staff to assess for infection 

Trouble-shooting

  • If, when you initially insert the needle the neonate or child moves, do not advance, keep the needle in place and wait. Allow the child to settle, and re-check the position, then continue to advance. 
  • If the CSF is blood stained this can still be collected for culture and if it runs clear can be collected for a cell count at this point.

For More useful tips for LP’s check out this post by dftb Ben Lawton. Pro tips for LPs in kids, Don’t Forget the Bubbles, 2015. Available at:
https://doi.org/10.31440/DFTB.7969

References 

Other references 

  1. https://www.rch.org.au/kidsinfo/fact_sheets/Lumbar_puncture/ 

Polycythaemia

Cite this article as:
Jilly Boden. Polycythaemia, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.30144

Its 3 am and you are called by a midwife on the postnatal ward to review a ‘jittery baby’ with a respiratory rate of 70. The midwife informs you that Alice is a term baby born via Cat 2 LSCS (failure to progress, Apgar 9,9) following an uncomplicated pregnancy (although she does note that mum has admitted to smoking cannabis occasionally during pregnancy). She is currently establishing breastfeeding.

On examination, Alice is settled but does have some mild tremors on handling. They settle on containment and don’t appear to be rhythmic or jerking in nature. She is centrally pink, with a red face and purple hands and feet. All observations, other than the respiratory rate are within normal limits.

You decide its likely Transient Tachypnoea of the Newborn but as part of your assessment, you obtain a capillary blood gas.

 The decision is made to give the baby a full top-up of formula feed (with mum’s consent) and to do formal, free-flowing venous bloods in an hour’s time to re-assess, but what is the next step?

Some definitions

The term polycythemia refers to a raised red cell concentration >2 standard deviations above the expected normal values. It can either be defined as a haematocrit from a peripheral venous sample being >65 percent or the haemoglobin is >22 g/dL however the former is more commonly used in clinical settings. 

Normal ranges: (neonatal capillary whole blood)

Haematocrit peaks maximally at the mean age of 2.8hrs. Although capillary blood gas samples are a helpful guide to the diagnosis, the sample on which treatment should be based must be from a peripheral venous sample. Studies have shown that the haematocrit from true venous samples (depending on capillary gas sample technique) can be up to 15% lower than the capillary sample.

Causes

Most cases of polycythaemia occur in normal healthy infants and may result from a variety of reasons, which can be broadly categorised into:

Increased red cell volume from increased transfusion, causes include:

  • Twin to twin transfusion
  • Delayed cord clamping*
  • Maternal hypertension

Placental insufficiency with increased foetal erythropoiesis secondary to intra-uterine hypoxia. This may occur in association with:

Other causes of polycythaemia include:

  • maternal substance use such as smoking
  • maternal diabetes
  • large for gestational age infant
  • chromosomal abnormality (such as Down syndrome).

* A note on delayed cord clamping:

Interestingly, although delayed cord clamping in IUGR babies has been shown to double the likelihood of polycythemia, a recent study found there was no increase in babies with symptomatic polycythemia and nor was there any increase in the need for partial exchange transfusion. Delayed cord clamping as also been found not to have an effect on hyperbilirubinemia.

Complications

An increased red cell mass results in an increased blood viscosity and reduced blood flow, impaired tissue oxygenation and a tendency to microthrombus formation. This is exacerbated by hypoxia, acidosis and/or poor perfusion.

Thrombosis may result in:

  • renal venous thrombosis
  • adrenal insufficiency
  • necrotising enterocolitis (NEC)
  • cerebral infarction that may affect long-term neurological outcome

Hyperviscosity of blood results in increased resistance to blood flow and decreased oxygen delivery. Viscosity exponentially increases when an infant has polycythemia. In the neonate, this can lead to abnormalities of central nervous system function, hypoglycemia, decreased renal function, cardiorespiratory distress, and coagulation disorders. Hyperviscosity has been reported to be associated with long-term motor and cognitive neurodevelopmental disorders.

Signs and symptoms 

The majority of newborns with polycythemia as asymptomatic (74-90%). In symptomatic infants, the hyperviscosity causes a decrease in tissue perfusion and metabolic complications such as hypoglycemia and hypocalcemia. They are responsible for clinical signs and symptoms including: 

  • apnoea
  • cyanosis
  • feeding problems
  • vomiting
  • irritability/lethargy
  • jitteriness/tremor
  • respiratory distress
  • seizures
  • hypoglycaemia 
  • jaundice 

The most commonly encountered problems in severely symptomatic newborns with polycythemia are central nervous system disorders.

Pathophysiology

In addition to cerebral blood flow, glucose carrying capacity also decreases in polycythemia. As a result, plasma glucose concentration, especially venous is lower than normal. Hypocalcemia and hyperbilirubinemia may also be seen in polycythemic newborns. The level of calcitonin gene-related peptide (CGRP) has been shown to be high in polycythemic newborns. This peptide regulates vascular tone, stimulates vasodilatation, and leads to hypocalcemia. High levels of CGRP suggest a role in response to polycythemia.

Management

A 2010 cochrane review found there to be: 

‘No proven clinically significant short or long‐term benefits of PET (Partial Exchange Transfusion) in polycythemic newborn infants who are clinically well or who have minor symptoms related to hyperviscosity. PET may lead to an increase in the risk of NEC. The data regarding developmental follow‐up are extremely imprecise due to the large number of surviving infants who were not assessed and, therefore, the true risks and benefits of PET are unclear.’

With this in mind, it is broadly accepted that PET should only be undertaken if it is thought to be the primary cause of the symptoms, rather than a byproduct of dehydration from other causes e.g. feeding difficulties or metabolic disorders.

 The formal bloods reported as Hb 215 g/L with a Hct of 69% and a repeat gas shows a glucose of 3.2 mmol/L. The midwifery staff report she seems less ‘jittery’ and a plan is made for full formula top-ups and daytime review to ensure resolution of symptoms. 

References

Garcia-Prats, J. A. (2019, September 1). Neonatal Polycythemia. Retrieved October 19, 2019, from https://www.uptodate.com/contents/neonatal-polycythemia.

Wu, A. H. B. (2006). Tietz clinical guide to laboratory tests (3rd ed.). St. Louis, MO: Saunders/Elsevier

Alsafadi, T. R., Hashmi, S., Youssef, H., Suliman, A., Abbas, H., & Albaloushi, M. (2014). Polycythemia in neonatal intensive care unit, risk factors, symptoms, pattern, and management controversy. Journal of Clinical Neonatology3(2), 93. doi: 10.4103/2249-4847.134683

Safer Care Victoria. (2018, October). Polycythaemia in neonates. Retrieved from https://www.bettersafercare.vic.gov.au/resources/clinical-guidance/maternity-and-newborn-clinical-network/polycythaemia-in-neonates.

Özek, E., Soll, R., & Schimmel, M. S. (2010). Partial exchange transfusion to prevent neurodevelopmental disability in infants with polycythemia. Cochrane Database of Systematic Reviews20(1). doi: 10.1002/14651858.cd005089.pub2

Sarici, S. U. (2016). Neonatal Polycythemia: A Review. Clinical Medical Reviews and Case Reports3(11). doi: 10.23937/2378-3656/1410142

Jeevasankar, M., Agarwal, R., Chawla, D., Paul, V. K., & Deorari, A. K. (2008). Polycythemia in the newborn. The Indian Journal of Pediatrics75(1), 68–72. doi: 10.1007/s12098-008-0010-0

A., D. A. P., Werner, E. J., & Christensen, R. D. (2013). Neonatal hematology pathogenesis, diagnosis, and management of hematologic problems. Cambridge: Cambridge Univ. Press. 171-186.

Saggese, G., Bertelloni, S., Baroncelli, G. I., & Cipolloni, C. (1992). Elevated calcitonin gene-related peptide in polycythemic newborn infants. Acta Paediatrica81(12), 966–968. doi: 10.1111/j.1651-2227.1992.tb12155.x

Hirschsprung Associated Enterocolitis

Cite this article as:
Peter Tormey. Hirschsprung Associated Enterocolitis, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28496

Michelle is a 5-year-old girl with a background of Hirschsprung’s Disease. She had a pull through procedure performed 6 months ago. She is on daily PR washouts.

She presents to ED acutely unwell with multiple episodes of brown vomiting. On examination she is lethargic, grey in colour and peripherally shut down. Her abdomen is distended.

What is Hirschprung’s Disease?

Hirschprung’s Disease (HD) is caused by the failure of neural crest cells to migrate completely during intestinal development.

The neural crest cells are progenitor cells for the enteric nervous system, which controls peristalsis, blood flow to the gut and secretions. The enteric ganglia are interconnected to form 2 plexi that extend along the length of the bowel: an out myenteric (Auerbach) plexus running the full length of the gut and an inner submucosal (Meissner) plexus, found in the small and large intestine. The absence of these plexi results in an aganglionic segment of colon, which fails to relax, causing a functional obstruction.

Interestingly, the timing of the arrest in migration of the neural crest cells influences the severity of disease. The cells migrate in a craniocaudal fashion, therefore, early arrest results in a longer segment of aganglionosis.

The incidence of HD is 1 in 5000 live births. The male-to-female ration is 4:1 in short segment disease but it is 1:1- 2:1 in long segment disease.

How do children with Hirschprung’s present?

How these children present depends on whether they have short or long-segment disease. Short-segment disease only involves the rectosigmoid colon and accounts for 80-85% of cases. In long-segment disease, the aganglionosis extends proximally to the sigmoid colon.

Those with long-segment disease are more severely affected and tend to present earlier, usually in the first few days after birth. They can present with any of the following features:

  • Abdominal distension
  • Bilious vomiting
  • Delayed passage of meconium
  • Enterocolitis

Those with short-segment disease may present later in childhood with constipation and failure to thrive.

What is “delayed” passage of meconium?

There is a big variation in the timing of first meconium passage in neonates, however, most healthy newborns will pass stool within the first 24 hours. All healthy newborns should pass their first stool within 48 hours.

Clark studied 395 term infants and found that 98.5% of them passed stool within the first 24 hours and 100% within 48 hours.

It is generally acknowledged that term infants who don’t pass stool within the first 48 hours should undergo careful evaluation and investigation. 60-90% of patients with HD will not pass meconium within 48 hours.

The differentials of delayed passage of meconium are listed below:

  • Meconium plug syndrome
  • Meconium ileus
  • Hirschsprung’s disease
  • Anorectal malformation
  • Intestinal atresia
  • Malrotation, volvulus
  • Hypoplastic left colon syndrome
  • Opioid use
  • Hypothyroidism
  • Sepsis
  • Prematurity, low birth weight

Hirschprung Associated Enterocolitis

Hirschsprung Associated Enterocolitis (HAEC) is a serious complication of HD. Patients can present critically unwell with haemodynamic instability, fever, vomiting, explosive diarrhoea and abdominal distension. An explosive release of gas or stool during rectal examination strongly supports a diagnosis of HD.

The incidence of HAEC ranges from 6-60% prior to pull-through surgery and 25-37% after surgery. HAEC can be potentially life-threatening. Swenson was one of the first to report on mortality in HAEC, reporting a mortality rate of 33% after HAEC, compared with 4% in HD patients without EC. The reported mortality in other studies varies greatly from 0 to 39%.

Mortality rates have improved in recent years, most likely due to improved supportive care in PICU and improved surgical expertise. The mortality rate in HAEC is now 1%.

Poor prognostic factors are: HAEC present at diagnosis of HD and postoperative HAEC.

While it can be seen in all children with HD, several features appear to be associated with an increased risk:

  • Trisomy 21
  • Long-segment disease
  • Previous HAEC
  • Post-op obstruction

The cause of HAEC is unknown. Several hypothesis have been proposed:

  • Dysbiosis of the intestinal microbiome
  • Impaired mucosal barrier function
  • Altered innate immune response
  • Bacterial translocation

Mild cases can present with symptoms of viral gastroenteritis, fever, mild abdominal distension and diarrhea. If it is not promptly recognized and treated it can progress to toxic megacolon, which can be fatal. 

It is important to remember that HAEC can also occur in children who have had surgical repair for HD. It is due to obstruction, which can be due to:

  • Retained aganglionosis
  • Transition zone pull-through
  • Dysmotility following pull-through
  • Anastamotic stricture

A high index of clinical suspicion is required to make the diagnosis. Abdominal x-ray is also helpful and usually shows significantly dilated bowel loops and air-fluid levels.

HAEC is an emergency. Prompt treatment is required with IV antibiotics, (e.g metronidazole, gentamicin, amoxicillin) fluid resuscitation and surgical evaluation, which may include rectal washouts or an emergency colostomy.

Which children with constipation do we need to worry about?

Constipation is a very common presentation to ED. When assessing these patients it is important to screen for any underlying abnormalities, including HD.

Constipation, with the following features should raise your suspicions for undiagnosed HD:

  • Neonates
  • History of delayed passage of meconium
  • Chronic, refractory constipation
  • Failure to thrive
  • Presence of other urogenital abnormalities
  • Family history of HD (the risk for a sibling is 200 times higher than the general population, (4% vs. 0.02%)
  • Associated syndromes:
    • Down Syndrome
    • Bardet-Biedl syndrome
    • Cartilage-hair hypoplasia
    • Congenital central hypoventilation syndrome
    • Multiple endocrine neoplasia type 2
    • Mowat Wilson syndrome
    • Smith-Lemli-Opitz syndrome
    • Waardenburg syndrome

How is Hirschprung’s diagnosed?

Abdominal x-ray may show dilated bowel loops, thickened bowel loops or air fluid levels. These findings, however, are non-specific.

Contrast enema is useful to demonstrate the functional obstruction seen with HD, as seen in the film below.

Contrast study demonstrating a stenotic segment in the sigmoid colon with dilation of the descending colon.
Case courtesy of Dr Mohammad Farghali Ali Tosson. From the case https://radiopaedia.org/cases/50255 rID: 50255

Definitive diagnosis is by rectal suction biopsy.

It is important to consider HD in children presenting to ED with constipation. You should have a low threshold for surgical referral, particularly if they have any risk factors listed above.

How is Hirschprung’s treated?

Treatment involves surgical resection of the aganglionic segment and anastomosis of the normal bowel to the anus, while preserving sphincter function.

Long term complications include:

  • Chronic constipation
  • Incontinence
  • Recurrent HAEC
  • Psychosocial issues

Did you know?

HD was first described by Harald Hirschsprung in 1886. He described 2 children with severe constipation, due to dilation and hypertrophy of the colon.

Lennander in 1900 was the first to suggest that the pathogenesis may be neurogenic in origin. Tittel then demonstrated in 1901 histiological findings indicating aganglionosis of the colon. In 1948 Swenson used motility studies to demonstrate absence of peristalsis in the aganglionic colon.  

The history of Hirschsprung’s Disease is an interesting and colourful one with many false starts and conflicting opinion. If you’re interested in reading more, look no further than this American Academy of Surgeons history of surgery article.

Michelle was fluid resuscitated and commenced on IV antibiotics. She was transferred to PICU due to haemodynamic instability. She was managed conservatively by the surgical team with regular rectal washouts.

Michelle has had several episodes of HAEC previously. This episode, in particular, was life-threatening. Her parents are finding it harder to perform the daily rectal washouts as she gets older. As a result, it was decided to perform an ileostomy to improve bowel management and to try and prevent HAEC.

References

1. Butler Tjaden NE, Trainor PA. The developmental etiology and pathogenesis of Hirschsprung disease. Vol. 162, Translational Research. Mosby Inc.; 2013. p. 1–15.

2. Congenital aganglionic megacolon (Hirschsprung disease) – UpToDate [Internet]. [cited 2020 Jul 7]. Available from: https://www-uptodate-com/contents/congenital-aganglionic-megacolon-hirschsprung-disease?search=hirschsprung disease children&source=search_result&selectedTitle=1~76&usage_type=default&display_rank=1

3. Haricharan RN, Georgeson KE. Hirschsprung disease. Semin Pediatr Surg [Internet]. 2008 Nov [cited 2020 Jul 20];17(4):266–75. Available from: https://pubmed.ncbi.nlm.nih.gov/19019295/

4. Ryan ET, Ecker JL, Christakis NA, Folkman J. Hirschsprung’s disease: Associated abnormalities and demography. J Pediatr Surg [Internet]. 1992 [cited 2020 Jul 20];27(1):76–81. Available from: https://pubmed.ncbi.nlm.nih.gov/1552451/

5. Clark DA. Times of First Void and First Stool in 500 Newborns [Internet]. Vol. 60, PEDIATRICS. 1977 [cited 2020 Jul 28]. Available from: www.aappublications.org/news

6.Loening-Baucke V, Kimura K. Failure to Pass Meconium: Diagnosing Neonatal Intestinal Obstruction. Am Fam Physician. 1999 Nov 1;60(7):2043.

7. Gosain A, Frykman PK, Cowles RA, Horton J, Levitt · Marc, David ·, et al. Guidelines for the diagnosis and management of Hirschsprung-associated enterocolitis. Pediatr Surg Int. 2017;33:517–21.

8. Swenson O, Davidson FZ. Similarities of Mechanical Intestinal Obstruction and Aganglionic Megacolon in the Newborn Infant. N Engl J Med [Internet]. 1960 Jan 14 [cited 2020 Jul 28];262(2):64–7.

9. Vieten D, Spicer R. Enterocolitis complicating Hirschsprung’s disease. Semin Pediatr Surg. 2004 Nov 1;13(4):263–72.

10. Murphy F, Puri P. New insights into the pathogenesis of Hirschsprung’s associated enterocolitis. Pediatr Surg Int [Internet]. 2005 Oct 30 [cited 2020 Jul 28];21(10):773–9. Available from: https://link-springer-com.proxy.library.rcsi.ie/article/10.1007/s00383-005-1551-1

11. Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet [Internet]. 1990 [cited 2020 Jul 20];46(3):568–80. Available from: /pmc/articles/PMC1683643/?report=abstract

12. Hirschsprung disease • LITFL • Medical Eponym Library [Internet]. [cited 2020 Jul 20]. Available from: https://litfl.com/hirschsprung-disease/

Metabolic presentations 3: Galactossaemia

Cite this article as:
Taciane Alegra. Metabolic presentations 3: Galactossaemia, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28602

It’s 11am on Easter Monday in Dublin. Emily is a 6 day old baby girl, born at 37 weeks via normal vaginal delivery across the Irish sea in Wales while her mother was visiting some friends. When Emily was 3 days old her mother returned to Ireland to stay with her own mother for some early baby support. Since day two of life Emily has been vomiting after feeding. She is bottle fed and since yesterday she has only been accepting half of each bottle. Her mother initially thought she was tired from the long trip but has brought her to the ED this morning because she has been quiet, hasn’t been crying as usual with nappy changes and seemed too sleepy to take this morning’s bottle. 

Emily was born in good condition by spontaneous vaginal delivery at 37/40. Her birth weight was 2.9kg. She was jaundiced on the second day of life, but below phototherapy levels. 

Social history: Emily’s parents are both healthy and from the Irish Traveller Community. 

Emily’s weight today is weight 2.45kg (a 16% drop below her birth weight). She’s jaundiced, lethargic, her anterior fontanelle is sunken, and Emily looks dehydrated. You can palpate the liver 2 cm below the right costal margin. No spleen palpable. Otherwise no positive findings. She’s afebrile with normal observations.

This baby has some red flags that will make anyone concerned. She is vomiting, lethargic, jaundiced, dehydrated, has hepatomegaly and has lost 16% of her birth weight. Emily is definitely sick. The list of potential diagnosis is extensive, but sepsis should always be the top of your list.

As you’re taking bloods for an FBC, U&E, LFT, ammonia and blood culture you’re told that Emily is hypoglycaemic so you collect additional bloods for a hypoglycaemia screen.

First, let’s correct the glucose!

Follow your local guideline regarding the initial investigation and management of hypoglycaemia and give 10% Dextrose 2mL/kg IV as soon as possible. 

Bloods should be be collected prior to treatment, but do not delay treatment due to problems collecting samples.

As this could be a metabolic presentation, instigate a generic management approach:

  • Clinical stabilisation
  • Antibiotics
  • Stop feeds
  • Give maintenance fluids with electrolytes to maintain hydration

The hypoglycaemia screen

The hypoglycemia workup should preferably be collected while the patient is hypoglycaemic, before giving glucose.

The basic screen aims to identify the most common endocrine or metabolic conditions responsible for hypoglycemia. Briefly, it involves: glucose, ketones (Beta-hydroxybutyrate), insulin, cortisol, Growth Hormone (GH), ammonia, lactate, free fat acids, serum amino acids, acylcarnitines profile (Guthrie card) and urine for organic acids and ketones. 

Discussing them in depth is beyond the scope of this post, but if you want to learn more, you can refer to this post by PaediatricFOAMed. 

Find out if your institution has a “hypoglycaemia kit” ready to go, as hypoglycaemia in a neonate can be a stressful situation that requires quick action. 

Emily’s blood sugar normalises. She has a full septic screen and is started on intravenous broad spectrum antibiotics. But, what’s her diagnosis?

Emily is hypoglycaemic with raised ketones, a normal response we would expect as she’s using fat as an alternative source of energy. However, in addition to this, Emily has hepatomegaly and raised liver enzymes, which together with hypoglycaemia, point towards a diagnosis of galactosaemia.

The worldwide incidence of classic galactosaemia is around  1:45,000 live births. Some countries screen for galactosaemia in their newborn screening programmes (Ireland, UK, New Zealand and some parts of Australia). Because of its autosomal recessive inheritance, galactosaemia is more common in some ethnic groups. 

In Ireland, around 1 in every 16,200 babies born each year may have galactosemia, however in the Irish Traveller community, this incidence is approximately 1 in 450 births, compared to only 1 in 36,000 in the non-traveller Irish population. Because of the high incidence in babies born to parents from the travelling community, these babies are specifically screened earlier, on day 1 of life, in Irish maternity hospitals.

High risk babies’ diets should exclude galactose, so newborn babies of Irish travelling families are given soy-based formula rather than breast feeds or standard formula until their screening test result is known.

A bit about galactosemia

As per definition, “galactosemia” refers to disorders of galactose metabolism that include classic galactosemia, clinical variant galactosemia, and biochemical variant galactosemia (Gene Reviews). The most common is classic galactosemia, an autosomal recessive disorder, that occurs due to a defect in the enzyme galactose-1-phosphate uridyl transferase (GALT), important in the transformation of galactose into energy.

Galactosemia presents after the affected patient receives the sugar galactose, present in milk. Accumulation of galactose-1-phosphate results in damage to the brain, liver, and kidney. The diagnosis is made by measuring the (GALT) enzyme activity (that will be low); by detecting elevated concentration of galactose-1-phosphate in erythrocytes (the substrate); or by testing if there are pathogenic mutations (two copies) in the GALT gene. The presence of a reducing substance in a routine urine specimen may be the first diagnostic clue.

Liver failure is a predominant finding in galactosemia and, besides that, the affected neonate presents with vomiting, hypoglycaemia due to an inability to metabolise glucose, feeding difficulty, seizures, irritability, jaundice, hepatomegaly, splenomegaly, cataracts and Escherichia coli sepsis

Treatment of the newborn requires the exclusion of all lactose sources from the diet, instead using lactose-free formulas. This must be started immediately after the disorder is suspected clinically, whilst awaiting screening results in high risk groups, or following a positive newborn screening results.

Interestingly, if the galactose-free diet is started early enough, the symptoms will disappear, jaundice will resolve within days, liver and kidney functions return to normal, liver cirrhosis may be prevented and cataracts may clear. 

Later in life…

Even patients treated from the very first few days of life can develop complications as they grow up. Galactosaemia represents a spectrum with symptoms varying from mild growth retardation, delayed speech development, verbal dyspraxia, difficulties in spatial orientation and visual perception, and mild intellectual deficit. Neuropsychological problems can appear during adolescence.  

Unfortunately, ovarian dysfunction is an almost inevitable consequence that can’t be prevented even by a strict diet. It is often seen early in infancy or childhood with hypergonadotropism. 

References

Berry JT. Classic Galactosemia and Clinical Variant Galactosemia In: Adam , HH. Ardinger, RA. Pagon, S. E. Wallis, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews® [online book].

 Berry, JT, Walter JH, Fridovich-Keil JL. Disorders of Galactose Metabolism. In: Saudubray J-M, Baumgartner MR, Walter JH. (editors) Inborn Metabolic Diseases. Diagnosis and treatment. 6th Edition. Springer 2016. 

HSE. A Practical Guide to Newborn Bloodspot Screening In Ireland. December 2018. https://www.hse.ie/eng/health/child/newbornscreening/newbornbloodspotscreening/information-for-professionals/a-practical-guide-to-newborn-bloodspot-screening-in-ireland.pdf 

Volcano

Managing Gastro-Oesophageal Reflux Disease

Cite this article as:
Sarah Davies. Managing Gastro-Oesophageal Reflux Disease, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29563

Isobel is a 10 week old, exclusively breast-fed, baby girl. She is brought into the Emergency Department with a history of frequent vomiting and poor weight gain. Her examination is normal, but when you ask Isobel’s exhausted-looking mother to put her to the breast, she becomes fractious and fussy, pulling away, arching her back, and taking very little feed at all.  

What are you going to do? 

At face value, this familiar presentation sounds like gastro-oesophageal reflux disease (GORD), although the differential for a ten-week old with vomiting and weight loss is wide.

Gastro-oesophageal reflux (GOR) is …the effortless retrograde passage of gastric contents into the oesophagus, with or without overt regurgitation. 

It is:

  • Physiological, due to low tone in the immature lower oesophageal sphincter
  • Common, occurring in up to 50% infants under 6m
  • Frequent – can happen up to x6/day

Gastro-oesophageal reflux disease (GORD) can be diagnosed clinically when GOR is accompanied by troublesome symptoms that affect everyday functioning (eg crying, back-arching, food refusal) and may lead to complications (eg failure to thrive).

Alternative diagnoses should be considered when there are additional red flag features (see below) indicative of a different pathology and under these circumstances, investigations should be tailored to rule these in or out.

*Some red flags overlap with symptoms directly related to GORD. The number, duration and severity of these should inform your decision to investigate on a case by case basis

As Isobel has symptoms of GORD with faltering growth you check her head circumference (which is appropriate), dip a urine (which is negative), and send some bloods for a faltering growth screen (although you strongly suspect they will come back as normal). You explain to Isobel’s mother that there is a stepwise approach to the management of GORD starting with non-pharmacological measures.

So, in the absence of red flag symptoms, do I need to prove its GORD?

In short, no. There is no single gold standard test for the diagnosis of GORD, hence the emphasis on clinical diagnosis. 

Invasive testing does have a place, though it is rarely the job of an ED clinician to be considering this. 

Endoscopy is used under the guidance of a Paediatric Gastroenterologist, for infants who fail to respond to optimal medical management. This will diagnose erosions and eosinophilic oesophagitis. 

pH MII (multi-channel intraluminal impedance) monitoring is used in children whose symptoms persist despite optimal medical therapy with normal endoscopy.   For a great explanation of this technique this previous DFTB post on reflux from 2016

Barium is out. Reliable biomarkers don’t yet exist. Scintigraphy, ultrasound and trial of a proton-pump inhibitor (PPI) are not useful in babies. 

OK, so I only need to investigate if I think there may be another cause for the symptom. But what should be my initial approach to treatment?

  • Positional management?
  • Avoiding overfeeding?
  • Thickening feeds?

Positional management – keeping the baby upright after feeds and elevating the head of the cot to sleep – is often advised for reflux. However, a study by Loots and colleagues in 2014 showed that regurgitation was only reduced through the use of side-lying positions which should NEVER be recommended due to the increased risk of SIDS. Head elevation made no difference at all despite some evidence that it can be beneficial in adults. 

And whilst a common-sense approach would support a move to smaller more frequent feedings and keeping a baby upright for 20-30 minutes after a feed, there isn’t any good quality evidence that confirms this. 

Feed thickeners have been shown repeatedly to reduce the frequency of visible regurgitation episodes in babies with reflux and in some studies to decrease cry/fuss behaviour too. They are safe and come highly recommended as a first-line intervention for babies with troublesome reflux. If you are going to advise a thickener for a breastfed infant, it’s important to suggest a carob bean-based product, such as Carobel, because the amylase in breast milk will digest the rice cereal-based thickeners such as Cerelac.  

Acupuncture, probiotics, massage, hypnotherapy have not yet been adequately studied for us to say one way or another if they are of any benefit. And alginates, probably the most familiar to us being Gaviscon? We’ll cover those shortly.

The key thing to remember for any intervention, is to reserve these for your patients with GORD. Happy, thriving, refluxy babies, typically outgrow their symptoms as they transition to solid food and should be left well alone

OK, but what if my patient has tried these already? What should I advise next? 

First, check how long they have persisted with the intervention. 

One of the biggest reasons for the simpler interventions not to help with GORD is that they are not given enough time to make a difference. Having said that, if a tired parent is repeatedly confronted with a grizzly, uncomfortable baby who is refusing to feed, asking them to persevere for two weeks with an intervention they don’t think is helping, may be practically difficult to achieve. 

In the UK, we have a choice of two key guidelines to help us with the next steps in reflux management.  

  1. NICE, last updated 2019

OR

  1. ESPGHAN/NASPGHAN 2018 joint consensus guidelines which are endorsed and recommended by our own BSPGHAN
  • European Society of Paediatric Gastroenterology, Hepatology and Nutrition
  • North American Society of Paediatric Gastroenterology, Hepatology and Nutrition
  • British Society of Paediatric Gastroenterology, Hepatology and Nutrition

Except that these guidelines differ a little on the advice they give for when simple measures don’t help…

NICE recommend a trial of Gaviscon first, and if that doesn’t work 4-8 weeks of a PPI such as omeprazole, and only then suggest a trial of cow’s milk protein exclusion (either through use of a hydrolysed formula or maternal dairy exclusion in breastfed infants) as a last resort, if reflux does not improve after ‘optimal medical management’. 

NASPGHAN/ESPGHAN on the other hand, suggest that ALL infants undergo an initial trial of cow’s milk protein exclusion, and only if this fails do they suggest the use of a PPI or hydrogen receptor antagonist (H2RA) such as Ranitidine. The bottom line is, that no-one has looked at the efficacy of a cow’s milk protein-free diet for symptom relief in babies presenting with reflux as the single symptom of cow’s milk protein intolerance (CMPI).  

The NASPGHAN team argues, that whilst there is no evidence on the topic, there are a number of babies with CMPI manifesting as reflux only who will benefit from this approach. They suggest eliminating cow’s milk protein from an infant’s diet for a minimum of 2 weeks, ideally four. If symptoms resolve and reappear on reintroduction then the diagnosis is clear. 

NASPGHAN then suggest babies who do not respond should be referred to secondary care services and started on a time-limited trial of PPI. 

This is largely so that infants are not left struggling on inadequate therapy for long periods of time, but also because their review found conflicting evidence around the benefit and side effect profile of these medications for young children. 

In six studies looking at PPI versus placebo, four studies showed no difference in regurgitation or other reflux associated symptoms between intervention and control groups. Three studies comparing H2RAs to placebo did show some benefit of the intervention, however, these studies were all in older children with biopsy-proven erosive oesophagitis up to 8 years of age.  Two studies showed endoscopic and histological and clinical features of GORD were reduced with H2RA over placebo, but these were in mixed-age groups including children up to 8 years old.

All studies showed a similar profile of side effects and between drug and placebo arms, however, one study demonstrated an increased rate of infection, in particular lower respiratory tract infection and diarrhoea in the PPI group. 

Given these findings, NASPGHAN cautiously recommends PPI or H2RA therapy in babies who have troublesome reflux despite trying a number of other non-pharmacological management options. 

Their key message is around early referral to secondary care, giving sufficient time for any one intervention to work, and making sure children are appropriately followed up.

So, what should I do? 

Given the somewhat conflicting advice outlined by these two well-respected groups, you could be left feeling unsure how to manage your next case. However, the genuine gap in the evidence market here does mean you are free to exercise your own clinical judgment and tailor your decision making to each individual refluxy baby, whilst empathetically taking on board the thoughts and preferences of the family.  This could, for some babies and parents, be medicine in itself. 

And what about alginates?

Two studies in the large literature review by the NASPGHAN/ESPAGHN group, compare Gavsicon to placebo. They show a reduction in visible regurgitation but no difference in reflux-associated symptoms. Furthermore, infants treated with alginate and then undergoing pH MII for 24 hours, showed no difference in the frequency of regurgitation events between groups. 

Chronic use of alginates causes constipation and poses a theoretical risk of milk-alkali syndrome, which is perhaps why the authors suggest use is limited to short term therapy. NICE do recommend a trial of Gaviscon therapy at an early stage in their pathway, as an alternative to feed thickener, but again on a time-limited basis with a planned review. 

Isobel’s mother had already tried two weeks of feed thickener on recommendation from the GP with no improvement. She was keen to avoid medication if possible so you agreed to a trial of dietary cow’s milk elimination for Mum who would continue to breastfeed and give top-ups with a hydrolysed formula if there was still no weight gain in a week. You gave her a sheet of dietary advice to ensure she maintained her own calcium intake and asked her to see the GP in 2 weeks for a review.  

Take home message

  • The vomiting infant has a wide differential – actively look for red flag features and investigate if you are concerned.
  • Infants with GORD need a management plan; infants with GOR, leave well alone
  • Start simply with an intervention that the family are happy to trial
  • Give time for it to work (up to two weeks)
  • Ensure follow-up for all and onward referral for infants who require acid-suppressive medication 

References

  1. Loots et al. Body positioning and medical therapy for infantile gastroesophageal reflux symptoms. Journal of Pediatric Gastroenterology and Nutrition 2014; 59 (2): 237-243. 
  2. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. JPGN 2018; 66(3): 516-554. 
  3. Winter et al. Efficacy and safety of pantoprazole delayed release granules for oral suspension in a placebo-controlled treatment withdrawal study in infants 1-11 months old with symptomatic GERD. JPGN 2010; 50: 609-618.  
  4. Orenstein et al. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. Journal of Pediatrics 2009; 154: 514-520e4. 
  5. Davidson et al. Efficacy and safety of once daily omeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. Journal of Pediatrics 2013; 163: 692-698.e1-2. 
  6. Winter et al. Esomeprazole for the treatment of GERD in infants ages 1-11 months. JPGN 2012; 55: 14-20. 
  7. Hussain et al. Safety and efficacy of delayed release rabeprazole in 1-11 month old infants with symptomatic GERD. JPGN 2014; 58: 226-236. 
  8. Moore et al. Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. Journal of Pediatrics 2003; 143: 219-223. 
  9. Cucchiara et al. Cimetidine treatment of reflux oesophagitis in children: an Italian multi-centric study. JPGN 1989; 8: 150-156. 
  10. Orenstein et al. Ranitidine, 75mg, over the counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux. Alimentary Pharmacology and Therapeutics 2002; 16: 899-907. 
  11. Simeone et al. Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of nizatidine. JPGN 1997; 25: 51-55. 
  12. Miller et al. Comparison of the efficacy and safety of a new aluminium free paediatric alginate preparation and placebo in infants with recurrent gastroesophageal reflux. Current Medicines and Research Opinion 1999; 15: 160-168. 
  13.  Ummarino et al. Effect of magnesium alginate plus simethicone on gastro-oesophageal reflux in infants. JPGN 2015; 60: 230-235.

The febrile infant conundrum

Cite this article as:
Dani Hall. The febrile infant conundrum, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28850

It’s fair to say that febrile infants can be challenging. Often presenting with insidious symptoms but looking reasonably okay, they may still have life-changing or life-limiting illnesses like sepsis or meningitis. You could argue that we should take the view of eliminating risk, performing septic screens on all febrile babies, and admitting for IV antibiotics until their cultures are returned. The vast majority will have a benign viral illness but at least you can rest assured you didn’t miss a seriously sick infant.

And that’s what we did when I started my paediatric training back when the dinosaurs roamed the earth – every baby under 6 months (yes, you heard it right, 6 months) with a fever got a full septic screen, including lumbar puncture, and was admitted to the ward for at least 48 hours pending cultures. But, from a health economics point of view, this is, let’s just say, perhaps not the best way to allocate healthcare resources.

Over the years, researchers have tried to rationalise our approach to febrile infants. 2013 saw the first NICE fever in under 5s guideline; a year later a group from Spain published the Step by Step approach to identifying young febrile infants at low risk for invasive bacterial infection; and last year, the PECARN group published a clinical prediction rule for febrile infants under 60 days, which had excellent sensitivity and negative predictive values to rule out serious bacterial infections.

Last month, the Spanish group published an article looking at the external validity of the PECARN rule in their dataset.

Velasco R, Gomez B, Benito J, et al. Accuracy of PECARN rule for predicting serious bacterial infection in infants with fever without a source. Archives of Disease in Childhood Published Online First: 19 August 2020

PICO image

Before we plunge into the paper, let’s stop and think about a couple of important definitions here:

Serious bacterial infection (SBI) is used to describe bacteraemia, meningitis and urinary tract infections, also including infections such as pneumonia, skin, bone and joint infections, bacterial gastroenteritis and sometimes ENT infections.

Invasive bacterial infection (IBI) are infections where bacteria are isolated from a normally sterile body fluid, such as blood, CSF, joint, bone etc. An IBI is a type of SBI in a sterile site.

Who did they study?

Velasco’s group looked back at their registry of infants with a fever without source from a busy paediatric ED (> 50,000 presentations a year) in a tertiary hospital. To match the cohort in the PECARN paper, they used the following inclusion and exclusion criteria:

Inclusion: infants younger than 60 days who presented with a recorded fever, or history of recorded fever, of >38 C over an 11 year period between 2007 (when they started measuring procalcitonin) and 2018.

Exclusion: any infants whose history and/or examination pointed towards a focus, whose results didn’t include those used in the PECARN rule (absolute neutrophil count, PCT, urine dip), who didn’t have culture results, who were critically ill on presentation or who had a past history of prematurity, unexplained jaundice, previous antibiotics or other significant past medical history.

What were they looking for?

The group were interested to see how the PECARN rule fared in their dataset by looking at how many infants were predicted to be low-risk and yet had an SBI or IBI to assess the external validity of the rule.

What did they find?

1247 infants were included in this study. Of these, 256 (20.5%) were diagnosed with an SBI, including 38 (3.1%) with an IBI.

Of the 256 infants with an SBI, 26 (10%) were considered low risk by the rule. Of the 38 with an IBI, 5 were considered low risk (13.2%) by the rule. The PECARN rule would have missed 10% of infants with an SBI.

The PECARN rule’s sensitivity dropped from 97.7% in the original study to 89.8% and specificity dropped to from 60% in the original study to 55.5%.

So, how did Velasco’s group calculate the sensitivities and specificities of the PECARN rule for different groups in their dataset? They’ve nicely shown their data in 2 x 2 contingency tables in their figures. This is the data for SBI.

Table of data from Velasco study

So, we can see that sensitivity (those patients testing positive for the SBI as a proportion of all patients who definitely have SBI) = 230 / 256 = 89.8%. This means that 10.2% are falsely negative.

Specificity (those patients who test negative for SBI as a proportion of all of those who don’t have SBI) = 550 / 991 = 55.5%. This means that 44.5% are falsely positive.

What about infants with a really short duration of fever?

When the group looked at infants with a history of less than 6 hours of fever (n=684, a little over half of the cohort), the sensitivity dropped further to 88.6%.

Why did the PECARN rule perform less well in this study?

The authors offer up a number of suggestions, some of which are outlined below.

The populations may be slightly different. Although the authors attempted to exclude ‘critically ill’ infants from this study (as the PECARN study excluded ‘critically ill infants’), a precise definition wasn’t coded in the original Spanish registry. Instead, they excluded infants from this study if they were ‘not well looking’ or admitted to ICU. Because of the way the data was coded, some critically ill infants may have been included in this study’s dataset, skewing the results.

The Spanish database was of febrile infants without a source, excluding babies with respiratory symptoms, which may explain why the rates of SBI and IBI were much higher in this study than the PECARN database of febrile infants. So, although the PECARN rule was highly sensitive in their group of febrile infants, as in this study it may not perform so well in febrile infants without a source.

This study showed that the PECARN rule performed less well in infants with a short duration of fever. Overall, infants in the PECARN study had a longer history of fever at presentation – over a third of the PECARN infants had fever >12 hours compared to 11% in this study. Over half of the infants in this study presented within the first 6 hours. Blood tests are less sensitive in the first few hours of a febrile illness and this may well partially explain why the rule performed less well outside the PECARN dataset.

It’s important not to ignore this study’s limitations. The PECARN dataset recruited infants from multiple centres, while the registry for this study came from only one ED. As this study was a secondary analysis of a dataset, a power calculation wasn’t performed. Generally, a minimum of 100 cases is recommended for validating a model, but only 38 infants in this study had an IBI.

Study bottom line

This study showed that in the Spanish dataset of infants under 60 days with a fever without source, the PECARN rule performed less well than in the original study. This was especially true for infants with a short history of less than 6 hours of fever.

Clinical bottom line by Damian Roland

In Kuppermann et al’s original 2019 study febrile infants 60 days and younger were demonstrated to be at low risk of SBIs using 3 laboratory test results: Urinalysis, Absolute Neutrophil Count (ANC), and serum procalcitonin (PCT) levels. The study was well designed and therefore compelling in providing a framework in which to manage these challenging presentations. However, with respect to knowledge translation, external validity is critical. The availability of PCT is a significant limiting factor to being able to show the PECARN approach could be reproduced internationally. While PCT is used in Europe and Australia, it’s certainly not widespread in the UK where I practice, and then it is only used routinely in a very small number of hospitals. This makes Velasco and colleagues’ work really important as they were able to replicate the requirements of the original study and helps answer an important question: should centres start introducing PCT into their diagnostic pathology panels? The results of this study will be interpreted differently by different observers as ultimately the question is of risk tolerance. Personally, a 10% false-negative rate (if this is indeed the case) for an outcome that could result in long term disability feels uncomfortable. Counselling a parent that they could return home without treatment knowing this would probably be quite challenging. I am not sure many departments would be rushing to buy point of care PCT.

However, there are two very important caveats.  Firstly, is the validation cohort different from my own local cohort? The prevalence of disease has a huge bearing on the accuracy of any test. Knowing the local incidence of SBI and IBI in your own institution is important (but actually getting the numbers is harder than you may think!). It is likely that the PECARN approach may perform more effectively in other centres. Importantly the original paper highlights that implementation may be more effective in the second month of life due to the impact of HSV and other peri-natal infections present at 0-30 days. Secondly, what is the threshold for undertaking the blood tests in the first place? Fever in an infant less than 3 months is an interesting area as it’s one of the very few presentations in which a solitary symptom or sign is independently predictive of risk. Regardless of how the child appears to a health care professional, there is a risk of SBI and IBI (of anywhere between 2-10%) just by having a fever. This does mean that sometimes there is variation in approaches when there is a history of fever rather than a documented fever (for fear of not wanting to do a battery on tests on a neonate who in front of you appears completely well and has normal observations). But more importantly, this has led to an approach where although blood tests are taken, the results are often disregarded as an LP will be done and antibiotics will be given regardless. There are many cultural practices that have evolved around the management of the febrile neonate both within individuals and institutions. While in a study situation these are controlled for, their influence in the real world can not be underestimated and this is why it’s so important we have some pragmatic studies in this area.

This study makes me more determined to define our incidence of SBI locally and work out what impact new approaches to management may have. I think all centres should probably be doing this. However knowing the potential uncertainty in the sensitivity of the PECARN approach means it’s unlikely to be adopted in the immediate future without further validation.  

**post blog addendum 1st September 2020**

While this blog was in post production phase Kuppermann and colleagues have released further data on implementing their original predictive rule. This work has been summarised by Dr. Kuppermann below (click on to go to the original thread) and provides useful context to the discussion about external validity and implementation – DR.

Metabolic presentations part 1: neonates

Cite this article as:
Taciane Alegra. Metabolic presentations part 1: neonates, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28423

You are working in the Paediatric Emergency Department and are called in to see a neonate with a history of irritability and seizures. You enter the room and are told the following: “Emma is a 3 day old, term baby who has been refusing feeds and crying excessively. Her mother says she has been irritable since birth. There has been no history of fever or cough. At home she had seizure-like activity with tonic posturing”. When you examine her, you find an awake, extremely irritable baby with flexed upper limbs flexed, extended lower limbs and global hyperreflexia. She is not dysmorphic and has no cardiac murmurs, respiratory distress or abdominal organomegaly.

Babies cry (a lot!) and we all know that, however Emma is presenting some red flags: she’s irritable and has an acute onset of seizures, without any obvious trigger.

The basics

In this post we will discuss some acute metabolic presentations in the neonatal period, how to identify potential problems and emergency treatment in the ED. You don’t need to make a diagnosis (bonus points if you do) but do need to remember that spotting the zebra will lead to more favourable outcomes. Metabolic diseases / disorders are also called inborn errors of metabolism (IEM).

How common are metabolic conditions?

Individually, metabolic conditions are rare, most having an incidence of less than 1 per 100,000 births. However, when considered collectively, the incidence may reach 1 in 800 to 1 in 2500 births (Applegarth et. al, 2000; Sanderson et.al, 2006). 

Remember: some symptoms can be unspecific and can mimic sepsis; or a child with an undiagnosed metabolic condition can decompensate with an intercurrent infection. 

An easy-to-understand classification by Saudubray divides the IEM in three groups of disorders, depending on how they present. 

Intoxication disorders

An acute or progressive intoxication from the accumulation of toxic compounds, usually small molecules. 

These usually present with a symptom-free interval and clinical signs of ‘intoxication’, which may be acute, although can be intermittent.

  • disorders of amino acid catabolism: e.g. phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia 
  • most organic acidurias: e.g. methylmalonic, propionic, isovaleric acidaemia
  • urea cycle defects: e.g. Ornithine transcarbamylase deficiency (OTC deficiency), Citrullinemia type I (ASS1 deficiency).
  • sugar intolerances: galactosemia
  • metals: Wilson’s, Menkes, hemochromatosis
  • porphyrias

Disorders involving energy metabolism

A deficiency in energy production or utilization, within the liver, myocardium, muscle, brain or other tissues. 

Common symptoms include hypoglycemia, hyperlactatemia, hepatomegaly, failure to thrive and cardiac failure. 

  • Mitochondrial defects: congenital lactic acidemias (defects of pyruvate transporter, pyruvate carboxylase, pyruvate dehydrogenase, and the Krebs cycle), mitochondrial respiratory chain disorders and the fatty acid oxidation defects (MCAD deficiency).
  • Cytoplasmic energy defects: disorders of glycogen metabolism (collectively known as glycogen storage diseases), hyperinsulinism.  

Complex molecules disorders

Problems in the synthesis or catabolism of complex molecules, leading to storage of big molecules. 

Symptoms are chronic, progressive and independent of intercurrent events or food intake. 

  • Mucopolysaccharidosis (I-IV, VI and VII). The eponymous names are used less frequently now, particularly in the literature, but you might come across them in clinical practice (MPS I, Hurler’s Syndrome; MPS II, Hunter’s Syndrome; MPS VI, Maroteaux- Lamy) 
  • Gaucher disease
  • Peroxisomal disorders: e.g. X-linked adrenoleukodystrophy (X-ALD) and Zellweger’s Syndrome.

Treatment strategies

Remember your biochemistry: a substrate is transformed by an enzyme into a product .

If there is a problem with the enzyme, the substrate will accumulate. If this substrate accumulation is a problem, we eliminate it, like avoiding protein in the diet or removing toxins with treatments such as ammonia scavengers.  If a lack of the product is the problem, we can supplement it (for example the administration of carbohydrate in glycogen storage disease). And for some diseases the  enzyme can be “corrected” with organ transplantation or enzyme replacement therapy.

A bonus on smells

Due to accumulation of “unusual” products in their body fluids, people with certain metabolic conditions have distinctive odours (better observed in urine, for practical reasons):

  • Maple syrup, burnt sugar, curry: Maple syrup urine disease
  • Sweaty feet: glutaric aciduria type II, isovaleric acidaemia
  • Cabbage: tyrosinemia
  • Mousy, musty: phenylketonuria
  • Rotting fish: trimethylaminuria
  • Swimming pool: Hawkinsinuria 

Back to Emma. You explain to Emma’s mother that there are lots of things that could be making her unwell so you’re going to send some tests to help work out what the problem is. You put in a cannula, take a gas, send some bloods to the lab and set her and her mother up to collect a urine.

Seeing that Emma has a metabolic acidosis on her gas you send a metabolic screen: plasma amino acids, urine organic acids, acylcarnitine profile. Her urine dip has some ketones but is otherwise unremarkable, except for a strange smell of sweaty feet…

Remembering a fabulous infographic about the importance of calculating the anion gap in children with a metabolic acidosis (and how to interpret them!), you get out your pen and paper and do the following calculations: 

Just as you’re pondering the causes of a raised anion gap, the lab phones with Emma’s blood results… Her ammonia is 184!

Emma has an acute neurological presentation, with metabolic acidosis, increased anion gap and mildly elevated ammonia, suggestive of an organic acidaemiaIn the context of a sick neonate with a raised anion gap, a normal lactate and normal ketones, think organic acids.

Are you familiar with ammonia?

A normal ammonia level is <50 mol/l but mildly raised values are common, up to 80 mol/l.

In neonates, any illness may be responsible for values up to 180 mol/l.

Artifactually high values can be caused by muscle activity, haemolysis or delay in separating the sample. Capillary samples are often haemolysed or contaminated and therefore should not be used.

There’s debate as to whether a level of >100 or 200 should be discussed with a metabolic specialist, but if in doubt, follow the RCPCH DeCon guideline and seek advice for any patient presenting with a level >100 mmol/l.

Urine organic acids and blood acylcarnitines will also be sent as part of this baby’s metabolic work-up. Although the results won’t be available in ED, the urine organic acid profile will confirm a diagnosis of an organic acidaemia, while the blood acylcarnitine profile will support the diagnosis as the organic acids conjugate with carnitines creating compounds such as isovalerylcarnitine.

The emergency treatment of suspected organic acidaemias

It’s important to think about your differentials. Sepsis is the most common – these conditions can mimic sepsis, or decompensation can be triggered by an infection, always cover with broad spectrum antibiotics. But don’t forget non-accidental injury and other differentials – the baby is likely to need a CT head if presenting encephalopathic or with seizures. If she continues to seize, load with an anticonvulsant.

 Specific emergency treatment of her metabolic presentation requires:

  • stopping sources of protein (milk)
  • avoiding catabolism (by giving glucose IV – 2mL/kg 10% glucose) 
  • rehydration (IV fluids resuscitation and maintenance)

What about that urine?

The “sweaty feet” smell of the urine points towards the diagnosis of Isovaleric Acidaemia. Remember that this condition can be part of the Newborn Screening in some countries (Ireland, UK, Australia, New Zealand).

Isovaleric acidaemia is a type of organic acidemia, inherited in an autosomal recessive way. It is caused by a problem with the enzyme that usually breaks down the amino acid leucine. This amino acid accumulates and is toxic at high levels, causing an ‘intoxication’ encephalopathy. The sweaty feet smell is stronger without treatment or  during acute exacerbations.

Maple Syrup Urine Disease (MSUD) is another organic acidaemia, associated with sweet smelling urine during decompensation. These children cannot break down leucine, valine and isoleucine. They may not have hypoglycaemia, hyperammonemia or acidosis and, if not picked up on newborn screening, can be diagnosed late, resulting in neurological sequelae.

Organic acidaemias: the take homes

  • Always measure the anion gap and send an ammonia sample in any sick neonate.
  • Sick neonates with metabolic acidosis, increased anion gap and mildly elevated ammonia may have an organic acidemia.
  • Treatment is to stop feeds, prevent catabolism with 10% dextrose (and standard electrolytes for IV maintenance) and cover for sepsis with IV antibiotics, whilst considering other differentials.

The next case feels like déjà vu…

The next baby you see is remarkably like Emma but with a subtle difference. Lucy is a 3 day old baby, presenting with poor feeding, irritability and seizures at home. There has been no fever, cough, coryza, or sick contacts. On examination she’s awake, extremely irritable, with upper limbs, extended lower limbs extended and global hyperreflexia. She has no dysmorphic features, cardiac murmur or abdominal organomegaly. You notice that she seems tachypnoeic at 70, although her lungs are clear. The rest of her observations are normal. 

The key differences between Emma and Lucy’s presentations is that Lucy is tachypnoeic and has a respiratory alkalosis; this should make you suspicious of hyperventilation. Always check an ammonia level in sick babies, but particularly in this case as hyperammonemia stimulates the brain stem respiratory centre, causing hyperventilation and, as consequence, respiratory alkalosis. 

The lab phones you with Lucy’s ammonia result…

Acute neurological presentations, with respiratory alkalosis and extremely elevated ammonia point towards a urea cycle disorder. Respiratory alkalosis is a common early finding caused by hyperventilation secondary to the effect of hyperammonemia on the brain stem, although later the respiratory rate slows as cerebral oedema develops and an acidosis is seen. Lucy also has a low urea and mildly deranged liver enzymes and INR, all of which support the diagnosis of a urea cycle disorder.

The emergency treatment of suspected urea cycle disorders

Overall the acute treatment is similar to the first case: cover for sepsis, manage seizures and consider differentials.

And as in the first suspected metabolic case:

  • stop sources of protein – stop feeds 
  • avoid catabolism – giving glucose IV – 2mL/kg 10% glucose 
  • rehydrate – IV fluids resuscitation and maintenance

In urea cycle disorders, the toxic metabolite is ammonia, so ammonia scavengers are used, all given intravenously:

  • sodium benzoate
  • phenylbutyrate 
  • arginine

A nice guideline on the management of hyperammonemia secondary to an undiagnosed cause can be found on the British Inherited and Metabolic Disease Group website.

Urea cycle disorders are autosomal recessive inborn errors of metabolism. A defect in one of the enzymes of the urea cycle, which is responsible for the metabolism of nitrogen waste from the breakdown of proteins, leads to an accumulation of ammonia as it cannot be metabolised to urea. The urea cycle is also the only endogenous source of the amino acids arginine, ornithine and citrulline.   The most common urea cycle disorder is Ornithine Transcarbamylase (OTC) deficiency. Unlike the other urea cycle disorders (which are autosomal recessive), OTC deficiency is x-linked recessive, meaning most cases occur in male infants. Female carriers tend to be asymptomatic.

CPSI: Carbomoyl Phosphate Synthetase; OTC: Ornithine Transcarbamylase; ASS: Arginosuccinate Acid Synthase; ASL: Arginosuccinate; ARG: Arginase

Classically, urea cycle disorders present in the neonatal period with vomiting, anorexia and lethargy that rapidly progresses to encephalopathy, coma and death if untreated. In these circumstances, ammonia accumulates leading to a very high plasma ammonia. 

Children presenting in infancy generally have less acute and more variable symptoms than in the neonatal period and include anorexia, lethargy, vomiting and failure to thrive, with poor developmental progress. Irritability and behavioural problems are also common. The liver is often enlarged but, as the symptoms are rarely specific, the illness is initially attributed to many different causes that include gastrointestinal disorders. The correct diagnosis is often only established when the patient develops a more obvious encephalopathy with changes in consciousness level and neurological signs. 

Adolescents and adults can present with encephalopathy and or chronic neurological signs. 

What are ammonia scavengers?

In urea cycle defects, ammonia cannot be converted to urea so instead is converted to glutamine and glycine. 

Ammonia scavengers phenylbutyrate and sodium benzoate offer alternative pathways for ammonia excretion through urinary pathways.

Phenylglutamine and hippurate are produced and are excreted in urine.

Urea cycle disorders: the take homes

  • Always measure the anion gap and send an ammonia sample in any sick neonate.
  • Sick neonates with respiratory alkalosis, normal anion gap and very elevated ammonia may have a urea cycle defect. 
  • Emergency treatment of urea cycle disorders is the same as for an organic acidaemia (stopping feeds, starting dextrose and rehydrating) PLUS intravenous ammonia scavengers.

Thank you to Dr Roshni Vara, Consultant in Paediatric Inherited Metabolic Disease at the Evelina London Children’s Hospital for her help with this post.

References

Adam , HH. Ardinger, RA. Pagon, S. E. Wallis, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews® [online book].

Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan;105(1):e10.

Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK.Arch Dis Child. 2006 Nov;91(11):896-9. 

Saudubray J-M, Baumgartner MR, Walter JH. (editors) Inborn Metabolic Diseases. Diagnosis and treatment. 6th Edition. Springer 2016. 

Going the extra millimetre in neonatal care: Hazel Talbot at DFTB19

Cite this article as:
Team DFTB. Going the extra millimetre in neonatal care: Hazel Talbot at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22282

Hazel Talbot graduated from one of the countries leading medical schools just one year after Andrew Tagg. Whilst he has fled the NHS for warmer climes she has remained in the UK and works as a neonatologist for Embrace, the Yorkshire and Humber Infant and Children’s Transport service, part of Sheffield Children’s Hospital. She is also an Honorary Consultant at Leeds Children’s Hospital where she is allowed to indulge her desire to look after kids in a slightly less restrictive space than in the back of an ambulance.

 

 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal. DFTB20 will be held in Brisbane, Australia.

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