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.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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Top 5 papers in neonatology: James Tooley at DFTB19

Cite this article as:
Team DFTB. Top 5 papers in neonatology: James Tooley at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22344

James Tooley is consultant neonatologist in Bristol. We gave him the task of bringing us a little more up-to-date with the neonatal literature.

 

 

Here are the papers he chose:-

Battaloglu E, Porter K. Management of pregnancy and obstetric complications in prehospital trauma care: prehospital resuscitative hysterotomy/perimortem caesarean section. Emerg Med J. 2017 May 1;34(5):318-25.

Foy KE, Mew E, Cook TM, Bower J, Knight P, Dean S, Herneman K, Marden B, Kelly FE. Paediatric intensive care and neonatal intensive care airway management in the United Kingdom: the PIC‐NIC survey. Anaesthesia. 2018 Nov;73(11):1337-44.

Qureshi MJ, Kumar M. Laryngeal mask airway versus bag‐mask ventilation or endotracheal intubation for neonatal resuscitation. Cochrane Database of Systematic Reviews. 2018(3).

Sproat T, Hearn R, Harigopal S. Outcome of babies with no detectable heart rate before 10 minutes of age, and the effect of gestation. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2017 May 1;102(3):F262-5.

Wilkinson, A.R., Ahluwalia, J., Cole, A., Crawford, D., Fyle, J., Gordon, A., Moorcraft, J., Pollard, T. and Roberts, T., 2009. Management of babies born extremely preterm at less than 26 weeks of gestation: a framework for clinical practice at the time of birth. Archives of Disease in Childhood-Fetal and Neonatal Edition94(1), pp.2-5.

 

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. 

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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An approach to the floppy infant

Cite this article as:
Taryn Miller. An approach to the floppy infant, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25882

You are a junior doctor doing a rotation in neonates. Your registrar asks you to assess a 2-day old baby who was found to be hypotonic on their baby check. They ask you your approach to assessing the “floppy infant”. Luckily, you have a stepwise approach to answer this question ready!

 

Step 1- Definition and terminology

What does the term floppy mean?

The word floppy can be used to mean:

  1. A decrease in muscle tone (hypotonia)
  2. A decrease in muscle power (weakness)
  3. Ligamentous laxity and an increased range of joint mobility

What does the term hypotonia mean?

It is defined as “resistance to passive movement around the joint

It’s assessed in two ways by clinicians 

  • Phasic tone: assessed by the response of the muscle to a rapid stretch (tendon reflexes)
  • Postural tone: measured by the response of the muscle to a sustained low-intensity stretch (maintaining posture against gravity = significant head lag on pull-to-sit, ragdoll posture on ventral suspension, slipping through the hands when the infant is held under their arms).

With that in mind, you go on to start your approach

 

Step 2 – A focused history

Discuss with mother and review the notes focusing in on specific risk factors that could give you a clue to the diagnosis

  • Antenatal history – Reduced fetal movements, polyhydramnios, breech presentation 
  • Family history – Muscle disease, stillbirth or consanguinity
  • Birth History – Labour, delivery, resuscitation, Apgar score and cord gases
  • History since delivery- Respiratory effort, feeding history, level of alertness, level of spontaneous activity and character of cry

 

Step 3 – Examination and clinical clues

As always, your examination should start with a top to toe assessment of the baby using an A-E approach. Specific to the floppy baby is your neurological examination.

Some clinical clues that may further help you:-

  • Poor swallowing ability as indicated by drooling and oropharyngeal pooling of secretions
  • The cry!!  Infants with consistent respiratory weakness have a weak cry
  • Paradoxical breathing pattern – intercostal muscles paralyzed with intact diaphragm

It is important to determine whether the hypotonia is central (upper motor neuron) or peripheral (lower motor neuron).

*open mouth with tented upper lip, poor seal when sucking, lack of facial expressions, ptosis

TIP- Examine the baby with mum in a familiar environment to increase the likelihood of the baby being alert but not unsettled or crying.

Remember that in the neonatal period, central causes account for two-thirds of all cases, with hypoxic ischaemic encephalopathy being the most common.

Now you have narrowed down the likely lesion type let’s think of some aetiologies. Time to think back to the corticospinal tract that you learned all those years ago in medical school to help you.

 

 

Step 4 – Investigations

So what next? Let us decide which investigations we think are appropriate according to our central or peripheral causes.

Central hypotonia

1st line to consider

  • Serum (Ca, Glucose, U&Es, Mg, PO4, LFTs, VBG, Lactate and ammonia)
  • Septic screen
  • Plasma AA
  • Urine organic acids
  • Cranial Ultrasound
  • Microarray CCG

2nd line to consider

  • MRI
  • EEG
  • Urine sample
  • Congenital viral infections

Peripheral hypotonia

1st line to consider

  • CK,
  • DNA for Muscular Dystrophy
  • Genetic testing for SMA
  • EDTA for Prader Willi
  • CXR
  • Echo
  • Microarray CCG

2nd line to consider

  • Neurology services for EMG/ NCS, muscle biopsy

 

Step 5 – Formulating a management plan

Management plans will differ from case to case but should include a multi-disciplinary team approach.

  • Hypotonia can cause a loss of airway control and diminished breathing effort therefore some babies will need:
    • Resuscitation at birth
    • Assistance in maintaining airway
    • Ongoing respiratory support
  • Regular physiotherapy: stretches aimed at the prevention of contractures, positioning.
  • Occupational therapy: important to facilitate activities of daily living
  • Vigorous treatment of respiratory infections, including annual influenza vaccination
  • Feeding strategies – Nasogastric tube or gastrotomy
  • Management of gastro-oesophageal reflux.
  • Evaluation and treatment of cardiac dysfunction
  • Parental counseling

Later:

  • Prevention and correction of scoliosis with orthopaedic input
  • Consideration to the ethical appropriateness of & considerations to the ethical appropriateness of CPR in the event of acute respiratory arrest
  • Follow up of general development and stimulation of learning.

Please note that with advances in treatment of SMA and potential gene therapy in DMD, early diagnosis is important. Initiation of early treatment is recommended for individuals with infantile-onset (Type 1) and pre-symptomatic SMA.

 

Selected references

Ahmed MI, Iqbal M, Hussain N. A structured approach to the assessment of a floppy neonate. J Pediatr Neurosci. 2016;11(1):2-6. doi:10.4103/1817-1745.181250

Leyenaar J, Camfield P, Camfield C. A schematic approach to hypotonia in infancy. Paediatr Child Health. 2005;10(7):397-400. doi:10.1093/pch/10.7.397

https://ggnc.azurewebsites.net/ggc-paediatric-guidelines/ggc-guidelines/neonatology/evaluation-of-the-floppy-infant/

Performing the newborn check

Cite this article as:
Taryn Miller. Performing the newborn check, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25986

There are two situations in which you would examine a newborn:

  • As part of the newborn screening examination as a “baby check”
  • In the emergency department

Both situations are slightly different, but the same structured approach can be applied

Before you begin…gather what you might need

  • Examine the baby in a warm, well-lit environment- get a blanket if needs be, or examine in the neonatal resuscitaire if available
  • Preferably with parent/ guardian present (if newborn screening exam, if not call parent)
  • Tongue depressor
  • Ophthalmoscope that works!
  • Stethoscope – In NICU/SCBU usually each baby will have their own special stethoscope. If you are using your own, make sure to give it a good wipe before and after use
  • Measuring tape for head circumference and a set of weighing scales to examine the baby without the nappy!
  • Keep the baby warm by wrapping them in a blanket or rocking the baby
  • Auscultate the lungs and heart in mum’s arms or when the baby is settled
  • If a newborn is unsettled or crying, consider whether the examination needs to be done at that exact moment. Perhaps suggest that the baby has a feed or a cuddle with mum or dad.

Before you begin

  1. Introduce yourself with “Hello, my name is…
  2. Check the name and DOB on the name band
  3. Explain to parent/guardian why it is important and what the examination will involve
  4. Gain consent
  5. Wash your hands and don gloves!

PS – don’t forget to congratulate mum, it is a really nice touch and makes the parent or guardian feel at ease.

Before the baby cries – Perform these things first!

Assessment of breathing (0:17) – Respiratory rate, look for respiratory distress – intercostal and subcostal recession, tracheal tugging, nasal flaring

Assessment of circulation (0:36) – Auscultate the heart rate (all four areas), auscultate the lungs, feel the femoral pulses on both sides

Abdomen (0:48)- Palpate the abdomen for organomegaly, specifically the liver and the spleen. And look for any hernias

Structured assessment – Top to toe (1:14)

Head (1:14)

General inspection – Look for facial asymmetry and dysmorphic features.
Fontanelle –Palpate the anterior and posterior fontanelles
Ears- Look for skin tags or pits
Mouth – Assess the hard and soft palate. Ideally, you should use a tongue depressor and look directly with a light. Use a gloved finger in the mouth to look at the sucking reflex

*Chest and abdomen as before*

Extremities (1:50)

Hands – count the fingers, and look at the creases, assess the grasp reflex
Feet – count the toes, and look at the grasp reflex
Genitalia – Check for hypospadias and feel both testes
Bottom – make sure the anus is patent

STOP – warn parents- what you are going to do and not “I’m going to drop your baby”!!

Reflexes (2:24)

Head lag (2:30)
Moro reflex (2:42)
Stepping reflex (2:45)
Tone and ventral suspension (2:49)

Spine (2:30) – Look at the sacrum for birthmarks, hairy patches, or for any sacral dimples 

Hips (3:04) – Perform Barlow’s and Ortolani’s test to assess for developmental dysplasia of the hip

And finally

Pre-and post-ductal saturations (3:12)  – right hand for pre-ductal saturations and post-ductal saturations can be either foot

Eyes – Check for the red reflex

TOP TIP! Wrap the baby in a blanket and sit them upwards, the baby should open their eyes and let you get a good look with the ophthalmoscope.

Look at the baby book and plot previous weight measurements and today’s weight on an age-specific growth chart along with the head circumference

This video was created by Bec Packton, Aarani Somaskanthan, Alice Munro, and Izolda Biro with special thanks to Lisa Crouch and baby James. Check out our YouTube channel for more great teaching.

Selected references

American Academy of Pediatrics. Ear Pits, Skin Tags, and Hearing Loss. AAP Grand Rounds. 2009 Jan 1;21(1):2-.DOI: 10.1542/gr.21-1-2

Assessing for a patent anus in a neonate – Turowski, C., Dingemann, J. & Gillick, J. Delayed diagnosis of imperforate anus: an unacceptable morbidity. Pediatr Surg Int 26, 1083–1086 (2010). https://doi.org/10.1007/s00383-010-2691-5

Pre and post ductal saturations – Rüegger, C., Bucher, H.U. & Mieth, R.A. Pulse oximetry in the newborn: Is the left hand pre- or post-ductal?. BMC Pediatr 10, 35 (2010). https://doi.org/10.1186/1471-2431-10-35

Plotting growth chart UK – https://www.rcpch.ac.uk/resources/uk-who-growth-charts-guidance-health-professionals & Plotting growth charts Australia https://www.rch.org.au/childgrowth/Growth_Charts/

Immunisations –  DFTB – Immunisation Quick reference

Bibliography and some other approaches

Queensland Maternity and Neonatal Clinical Guidelines Program – Neonatal Examination

Davies, Cartwright & Inglis, Pocket Notes on Neonatology, 2nd Ed. 2008. Elsevier: Australia

Examination Adapted from; Examination of the Newborn: A Practical Guide. Helen Baston, Heather Durward Pg 3

Neonatal ventilation basics

Cite this article as:
Jasmine Antoine. Neonatal ventilation basics, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.19875

A term infant is admitted to the intensive care nursery with severe respiratory distress. They are currently on CPAP 8cm H2O and FiO2 0.50  with no signs of improvement. You begin preparing for intubation. The nurse looking after the baby is setting up the ventilator. “What ventilator setting would you like, doctor”?

 

Before listing off some ventilator settings, there are several decisions that we need to make. What type of ventilation should we be using for this baby? What settings will we start them on? What do we need to do post ventilation? This post will begin to answer some of these questions, but as always, it is advisable to be guided by your unit policies and senior staff members.

 

Ventilation modes

This post will discuss the basics of conventional ventilation. High-frequency oscillatory ventilation (HFOV) is also commonly used in the nursery, particularly for extremely preterm infants or those with persistent pulmonary hypertension. Stay tuned for an upcoming post on HFOV.

Synchronized intermittent mandatory ventilation (SIMV)

This type of ventilation administers a set amount of mechanical breaths that are synchronized with the patient’s own inspiration. When the infant breaths above the set ventilator respiratory rate, these additional breaths do not receive a ventilator breath. This mode can be useful when weaning ventilation.

Synchronized intermittent positive pressure ventilation (SIPPV) or patient triggered ventilation (PTV) or Assist Control (AC)

This form of ventilation confusingly has many different names. It supports every breath the infant makes. The set ventilator respiratory rate is the backup number of breaths that will be mechanically administered if the infant makes no spontaneous breaths. Each mechanical breath is synchronized with the patient’s own inspiration.

Pressure support ventilation (PSV)

Similar to SIPPV in that every breath is supported with mechanical ventilation. However, the inspiratory time is limited depending on the infant’s own inflation. The infant sets their own mechanical breath rate and inspiratory time.

Volume controlled (VC) or volume guarantee

This mode of ventilation can be used with SIMV or SIPPV. The ventilator aims to deliver tidal volumes (VT) set by the clinician. A maximum peak inspiratory pressure (PIP) is set, the ventilator’s PIP will vary to reach the target volume.

 

So, which is better for our infant?

There have been no large prospective trials that have determined if SIMV or SIPPV is the superior format of ventilation. The choice of ventilation will largely depend on unit preference. Studies have illustrated that volume-controlled ventilation reduces the duration of ventilation, risk of pneumothorax, grade 3/4 intraventricular haemorrhage, and chronic neonatal lung disease.

 

So what’s on your ventilator screen?

Peak end expiratory pressure (PEEP):

The maximum pressure that provides continuous distension of the lungs. Usually between 6-8cmH20

Peak inspiratory pressure (PIP):

Maximum pressure used during inspiration. Consider the tidal volumes achieved to determine a suitable PIP. VT are usually around 4-5ml/kg.

Respiratory rate (RR):

Set number of mechanical breaths administered in a minute. Usually between 40-60. In SIMV the set RR is both the maximum and minimum rate while in SIPPV the RR is the minimum but not the maximum rate.

Inspiratory time (Ti):

Set time for inspiration during a breath. Usually between 0.3-0.5s

Patient Circuit Flow Rate or Rise Time or Rise Slope:

Depending on the manufacturer or the unit policy, one of these options will be available. If only the patient circuit flow rate is available then this is set 6 – 10 L/min. If rise time or slope is available then this is set to 30 – 50% of the Ti.

Pmax:

In the volume-controlled mode this is the maximum peak inspiratory pressure you wish the ventilator to administer to reach target tidal volumes. Usually set 5 cmH2O higher than the average PIP used to achieve the set tidal volume.

FiO2:

The amount of supplementary oxygen. Target saturations will depend on the gestational age and the underlying condition affecting the infant. Your unit’s policy on SpO2 targets should guide the FiO2 setting.

Many other ventilators exist

 

What are the ventilator measurements we should be aware of?

Minute volume (MV):

Amount of gaseous exchange in one minute. MV= VT x RR

Tidal volume (VT):

The amount of gas in an expiration. Usually around 4-5ml/kg.

Leak:

Traditionally in neonates, uncuffed tubes are used for intubation due to concerns regarding subglottic stenosis and pressure necrosis. As a result, most infants will have a percentage of leak. It will change during an infant’s respiratory cycle, it is usually greater in inspiration.

 

What do we need to do next?

After attaching our infant to the ventilator, clinical checks should once again be undertaken to ensure adequate ventilation. Review the infant, is there misting of ETT, equal air entry by auscultation, symmetrical chest rise, stable observations and adequate tidal volumes being achieved.

A post-intubation chest x-ray should be taken as early as possible to check the placement of the endotracheal tube. The ideal placement is between T1-3,  just above the carina.

An arterial gas should be undertaken post-intubation to check adequate ventilation, within an hour. The timing of the next gas will depend on the results, clinical condition and how old the patient is. Your boss will be able to give you some guidance.

 

Take-home messages

  • Avoiding mechanical ventilation using early continuous positive airway pressure (CPAP) with, or without, surfactant administration is the most effective way to reduce the risk of lung injury.
  • Using volume-controlled ventilation reduces the risk of chronic neonatal lung disease.
  • If you’re not sure where to start or how to alter ventilation, ask for your boss’ help.

 

Resources

Keszler M. State of the art in conventional mechanical ventilation. Journal of Perinatology. 2009 Apr;29(4):262.

Mechanical ventilation of the premature neonate. Respir Care. 2011 Sep;56(9):1298-311; discussion 1311-3. doi: 10.4187/respcare.01429