Brown Pediatrics

Brown's Pediatric Residency Blog

Metabolism gone wild!

Case: Last week we talked about Jane, an otherwise healthy 2-week old girl. Let’s change the story a bit to hit on another consideration in infants. Instead of simply being febrile and fussy, let’s say that she comes back to the ED, this time afebrile, but lethargic with poor cap refill. How does our differential change now?



Image Credit: Pixabay

What are the important diagnostic considerations for neonates and infants who present very ill?

  1. Infection
  2. Metabolic/Endocrinologic
  3. Trauma
  4. Cardiac
  5. Surgical emergencies

For those of you who like acronyms, consider “THE MISFITS” in neonates and young children presenting with undifferentiated shock (adapted from post on PEM Playbook)

  • Trauma
  • Heart Disease/Hypovolemia
  • Endocrine Emergencies
  • Metabolic
  • Inborn errors of metabolism (to get this acronym to work, there may be some repetition)
  • Seizures
  • Formula problems (think too little or too much water)
  • Intestinal disasters
  • Toxins
  • Sepsis (while this is last, all very sick infants/children should be evaluated/treated for sepsis)


Today we will focus on the emergency management of inborn errors of metabolism (IEM), specifically at the immediate recognition and management.



Epidemiology and Etiology

IEMs are Individually rare, but more common in aggregate- 1/5000 live births for any IEM (Ewing, 2009)

Helpful to lump metabolic deficiencies into 3 broad categories (Saudabray, 2002)

  1. Disorders leading to intoxication (think urea cycle defects)
  2. Disorders involving energy metabolism (think hypoglycemia)
  3. Errors involving synthesis or catabolism of complex molecules (e.g. lysosomal storage disorders)
    • Note: Disorders in this category are rarely treatable in emergency

How do these children present?

  • Deterioration of consciousness is one of the more common presentations of IEMs (El-Hattab, 2015)
    • Other presenting features include vomiting, seizures, apnea, hepatic failure, and cardiac disease (heart failure, cardiomyopathy, arrhythmias)
  • Specific Presentation Patterns (Ewing, 2009)
    • Hypovolemia, hyponatremia, hyperkalemia: Consider adrenal insufficiency
    • Metabolic acidosis, hyperammonemia, ketotic hypoglycemia: Consider an organic acid defect
    • Encephalopathy, respiratory alkalosis, hyperammonemia: Consider a urea cycle disorder
  • Remember, “As the neonate has an apparently limited repertoire  of responses to severe overwhelming illness, the predominant clinical signs and symptoms can be nonspecific like poor feeding, lethargy, failure to thrive, etc.” (Saudabray, 2002)

What is the immediate workup? (El-Hattab, 2015)

Image Credit: Pixabay

  • Primary Workup

    • Glucose
    • Blood Gas with Lactate
    • Serum Chemistry (including BUN/SCr)
    • Urinalysis
    • Complete Blood Count (CBC) and Differential
  • Secondary Workup

    • Specific Findings from Initial Workup and/or Exam
      • Hypoglycemia: insulin, cortisol, growth hormone, β-hydroxybutryate, plasma acylcarnitine profile, plasma amino acids and urine organic acids
      • Encephalopathy: ammonia, Liver “Function” Test (sp. ALT, AST, bilirubin)
      • Suspected galactosemia: urine reducing substances

How do you stabilize? (Note: Do not wait for labs to return to begin stabilization!)

Image Credit: Pixabay

  • ABCs (patients can present altered, apneic and/or in shock)
  • Recall the 2 main categories leading to emergencies: IEMs leading to intoxication and those resulting in energy defects (Ewing, 2009)
    1. Give Energy
      • Dextrose
        • Bolus as needed to treat hypoglycemia
        • Maintenance with D10 solutions
    2. Remove Toxins
      • Make NPO
      • Intravenous Fluids
        • D10 Half-normal saline run at 1-1.5x maintenance rate
      • Hemodialysis if indicated
        • Severe Hyperammonemia (Urea Cycle defects)

Next Steps?

Consultation with a metabolic specialist is essential!

  • Will help direct further diagnostic workup
  • Will help determine if further medical interventions (medications, vitamins, cofactors, etc)



  1. Inborn errors of metabolism present non-specifically
  2. Always consider IEM when presented with unwell neonate or infant
  3. For critically ill presentations, IEMs can be broken down into 2 main categories: Toxin Accumulation and/or Deficient Energy
    • Emergent Treatment (following ABCs) are directed at these two issues

Faculty Reviewer: Chanika Phornphutkul, MD


  • El-Hattab AW. “Inborn Errors of Metabolism.” Clinc Perinatol. 2015;1-27
  • Ewing, PH et al. “Evidence-Based Management Of Metabolic Emergencies In The Pediatric Emergency Department.” Pediatric Emergency Medicine Practice. 2009;6(10)1-16
  • Horeczko, Tim. “The Undifferentiated Sick Infant.” PEM Playbook. Accessed: 5/3/2017
  • Saudabray JM et al. ” Clinical approach to inherited metabolic disorders in neonates: an overview.” Semin Neonatol. 2002;7(1)3-15


This is… Lumbar Puncture

Case: Jane is a 2 week-old, previously healthy, ex- full term girl who presents to the ED from her PCPs office after being found to have a temperature of 102.5 rectally. On exam, she is fussy but consolable and has an otherwise normal exam.  In addition to blood and urine studies, you plan to perform a lumbar puncture. What would be other indications and even contraindications for an LP? What are the various techniques? Should you use local anesthesia?  


Lumbar Puncture: The basics


  • The most common indication for lumbar puncture is to diagnose meningitis (Bonadio, 2014)
    • Other indications include diagnosing: demyelinating diseases, subarachnoid hemorrhage, or idiopathic intracranial hypertension (formerly pseudotumor cerebri)


  • Suspected intracranial pressure elevation
  • Clinical/Physiological Instability (hypotension, respiratory distress, status epilepticus)
  • Coagulopathy
  • Infection of overlying skin


Basics of setup

After discussing the case with the team, you decide that Jane has no contraindications and that it is important to rule out meningitis.  What do you need, and how do you set up?

1.  Equipment

  • Most (if not all) of your equipment will be included in a commercially available tray (Figure 1 as an example).
    • In general, you will need the following
      • Spinal needle (1.5″ or 3″ depending on the patient)
      • sterile gloves and drapes
      • Povidone-Iodine scrub
      • Monometer tune (to measure CSF pressure)
      • Sterile tubes for CSF collection


Figure 1: LP Tray (Picture from Bonadio, 2014)


2. Position 

  • In the younger child, and in those you need to measure CSF pressures, the child should be placed in the lateral decubitus position
  • In older children, the seated position can also be used (Figure 2)
  • Remember, the spinal cord ends around L2. Therefore, the needle should enter the L3/4 or L4/5 disc space
    • The L3/4 disc space will be transected by the line that connects the iliac crests (as seen in Figure 2).


Figure 2: LP Landmarks (Picture from Bonadio, 2014)


Maximizing Success

As you are gathering your materials, you begin wondering what can be done to maximize the success of your procedure.

1.)  Anesthesia

  • Topical (“EMLA”) vs local (1% lidocaine infiltration)
    • Use of local anesthetic associated with an increased odds ratio (OR = 2.2) for success (Baxter, 2006)
    • Other RCTs (Pinheiro et al, 1993; Nigrovic, 2007) found that local infiltration did not increase success, but statistically decreased the amount of struggling in infants.
      • Note: Despite not finding any differences in success rates between the two methods, it is important to note that local infiltration did not lead to decreased success (concern for a loss of landmarks, etc).

2.) Early stylet removal (“Cincinnati” Method)

  • In this method, the stylet is removed after puncturing the epidermis
    • Baxter et al found a trend towards increased success in residents employing this method, but this was not statistically significant (Baxter, 2006)
    • Nigrovic et al did find an association between leaving the stylet in and with the composite outcome of traumatic or unsuccessful lumbar puncture (Nigrovic, 2007)

Conclusion: Use an anesthetic (topical or local infiltrate) and consider removing the stylet early


Now that we know what we need, where we need to go, and what helps maximize success, how do we do the procedure?


NEJM Tutorial

Another Example from EM:RAP


Faculty Reviewer: Jeff Riese, MD


  • Baxter AL et al. “Local Anesthetic and Stylet Styles: Factors Associated with Resident Lumbar Puncture Success.” Pediatrics. 2006;117(3)876-881
  • Bonadio W. “Pediatric Lumbar Puncture and Cerebrospinal Fluid Analysis.” The Journal of Emergency Medicine. 2014;46(1)141-150.
  • Nigrovic et al. “Risk Factors for Traumatic or Unsuccessful Lumbar Punctures in Children.” Annals of Emergency Medicine. 2007;49(6)762-771
  • Pinheiro JM et al. “Role of Local Anesthesia During Lumbar Puncture in Neonates” Pediatrics. 1993;91(2)379-82


What’s that smell?

Post developed by Lynae Conyers, MD

Case: A 6yo previously healthy girl presents to clinic with her mother with the complaint of body odor and concerns that patient is “developing too early”. Mom reports onset of body odor a few months ago now requiring daily deodorant. Your exam reveals Tanner stage II to III pubic hair and a small amount of axillary hair. What might be going on in this patient? What other information should be obtained from history and physical exam and what are the next steps?


Image Credit: Pixabay

Precocious Puberty



  • Precocious puberty is the development of secondary sexual characteristics prior to age 8 in girls and prior to age 9 in boys



  • Peripheral (gonadotropin-independent) precocious puberty (PPP): adrenal or ovarian source of excess sex hormone production
  • Benign pubertal variants: non-progressive, isolated development (e.g. premature thelarche, premature adrenarche)
  • Central (gonadotropin-dependent) precocious puberty (CPP): early maturation of hypothalamic-pituitary-gonadal axis (Note: The discussion in this entry will focus on central precocious puberty.)


Before we discuss precocious puberty lets review normal puberty:



Figure 1: The hypothalamic-pituitary-gonadal axis

Image adapted from: Dixon JR et al, 2007


What physical exam findings herald the onset of puberty?

  • In girls puberty typically begins with thelarche (breast bud development).
  • In boys puberty typically begins with testicular enlargement.

When does puberty begin?

  • The onset of puberty is affected by many factors. Puberty typically occurs earlier in girls with early maternal menarche, obesity, and low birth weight. Racial and ethnic background also appears to play a role in the timing of puberty. Several cross-sectional studies in the US have noted earlier onset of puberty in African-American girls as compared to Caucasian girls. (Carel and Lager 2008)


Now that we’ve reviewed normal, let’s return to precocious puberty



How common is precocious puberty?

  • Precocious puberty is ten times more common in girls than boys.
  • In the US, the incidence is estimated at 1 in 5,000 to 10,000 girls. (Latronico et al. 2016)


What causes Central Precocious Puberty?

  • Early activation of pulsatile GnRH secretion. In other words, central precocious puberty is gonadotropin-dependent
    • Therefore, features include presence of breast buds, increased growth velocity, vaginal bleeding, pubic and axillary hair
    • Early GnRH secretion can be due to many causes (Figure 2):

Note: In girls, more than two-thirds of cases of central precocious puberty are idiopathic. An identifiable cause is much more common in boys. (Muir 2006)




  • Premature thelarche: presence of breast buds without any other signs of pubertal development; common in toddlers and often regresses
  • Premature adrenarche: presence of pubic hair, axillary hair, acne, and adult-type body odor without other features of puberty; may have some bone age advancement
  • Non-classical congenital adrenal hyperplasia: presence of pubic hair, axillary hair, acne and adult-type body odor, mild virilization
  • Peripheral causes: E.g. ovarian follicular cyst, McCune-Albright, hCG-secreting tumor, exogenous steroid exposure




  • Inquire about which features of puberty are present
  • Establish the timing of symptoms
  • Perform a neurologic ROS, including visual disturbances
  • Ask about family history of pubertal onset
  • Ask about exposure to estrogen or testosterone products and lavender or tea tree oil

Physical Exam

  • Assess linear growth
  • Evaluate for presence of breast buds (requires palpation in addition to inspection to help discern between adipose tissue and true breast buds)
  • Perform testicular exam in boys (enlargement greater than 3 ml is indicative of puberty)
  • Perform external vaginal exam to look for signs of estrogenization of the vaginal mucosa (bright pink/red is non-estrogenized while light, dull pink indicates estrogen exposure
  • Assign Tanner staging

Diagnostic Tests

Case courtesy of Dr Jeremy Jones, From the case rID: 23244

  • Hormone levels
    • If signs of central puberty (breast buds or testicular enlargement) then order LH, FSH and testosterone (boys)/ estradiol (girls)
    • If signs of adrenarche only (hair, body odor) then order DHEAS, testosterone, androstenedione and 17-OH progesterone
  • Bone age xrays
    • Typically advanced by at least two years in patients with precocious puberty
  • GnRH stimulation testing
    • Measurement of LH 15-60 minutes following GnRH stimulation
    • If the central pubertal axis is quiescent, one GnRH injection will not cause an increase in serum gonadotropin concentrations
  • Brain MRI
  • Pelvic ultrasound
  • Adrenal US (only if labs indicate concern for androgen secreting mass)



  • Treatment is dictated by the underlying cause if one is identified.
    • Treatment is particularly important for younger patients, male patients, and for patients whose skeletal age is advancing more than height age.
  • GnRH agonists (such as leuprolide) are the most effective medical therapy. Constant stimulation of the pituitary gland with GnRH agonists initially leads to short term pubertal stimulation followed by downregulation of GnRH receptors and decreased gonadotropin production.
  • Referral to a pediatric endocrinologist is essential. Even those with suspected benign pubertal variants need to be followed over to time to ensure no other evidence of true puberty develops.


Back to our case…

On further questioning, there have been no known exposures to estrogen products or tea tree oil. Review of systems is otherwise negative. Mom reports first menstruating at age 11. In addition the pubic and axillary hair, exam is notable for small breast buds. You review the patient’s growth chart and note she has grown 7cm in the past year. Based on these findings, you are concerned for central precocious puberty. You begin the evaluation with labs (FSH, LH and estradiol) and bone age xrays and arrange for short interval follow-up.


Faculty Reviewer: Bracha Goldsweig, MD



  • Carel JC, Leger J. Precocious puberty. NEJM 2008; 358:2366-77.
  • Dixon JR and Ahmed SF. Precocious puberty. Paediatr Child Health 2007; 17(9):343-48.
  • Latronico AC, Brito VN, Carel JC. Causes, diagnosis and treatment of central precocious puberty.  Lancet Diabetes Endocrinol 2016; 4:265-74.
  • Muir A. Precocious puberty. Pediatr Rev 2006; 27(10):373-81.
  • Neely EK and Crossen SS. Precocious puberty. Curr Opin Obstet Gynecol 2014; 26(5):332-38.


Too Much Pressure

Image Credit: Pixabay



Case: Andrew is a 16yo post-pubertal male without any past medical history who comes to clinic for his annual well-child check. His vitals at triage showed a blood pressure of 142/92. You note that he was seen in urgent care twice in the last 2 months with a similarly high blood pressures. His BMI is >95th percentile. How should you address his blood pressure today? Specifically, what further workup and/or treatment should be undertaken?



How is high blood pressure classified? (based on The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents)

  • Hypertension is defined as an average systolic blood pressure (SBP) and/or diastolic BP (DBP) that is ≥95th percentile for gender, age, and height on 3 occasions.
    • These 3 occasions needs to be separated by days-weeks
    • Note: Measures obtained by oscillometric devices (aka automatic BP machines) that exceed the 90th percentile should be repeated by auscultation.
  • Prehypertension in children is defined as average SBP or DBP levels that are ≥90th percentile but <95th percentile.
    • As with adults, adolescents with BP levels >120/80 mmHg should be considered prehypertensive.
  • A patient with BP levels ≥95th percentile in a physician’s office or clinic, who is normotensive outside a clinical setting, has “white-coat hypertension.”
    • Ambulatory BP monitoring (ABPM) is usually required to make this diagnosis.

Image Credit: Pixabay




  • The prevalence of primary and secondary hypertension is 4.5% and 13%, respectively (Gupta-Malhotra et al, 2015)
    • Given low screening rates, true prevalence may be higher
  • Children with essential (primary) hypertension tend to be older (>6), have a family history of hypertension (Gupta-Malhotra et al, 2015)
    • Conversely, infants and preschool-aged children with elevated blood pressure are more likely to have a secondary form of hypertension.


Etiology & Workup

  • While secondary causes of hypertension are more common in children than adults, children can also have primary hypertension (see Table below


<1yr old (%) 1-5 years (%) 6-12 years (%) 13-19years (%)
Respiratory (61) Respiratory (29) Essential (57) Essential (49)
Renal (13) Renal (27) Renal (27) Renal (20)
Medication Related (9) Essential (19) Neurological (7) Medication Related (11)

Table 1: Most common causes of hypertension by age (adapted from Gupta-Malhotra et al, 2015)

  • Workup for secondary causes should be individualized
    • Children with BPs ≥95th percentile (stage 1 hypertension) should have the following (NHBPEP, 2004; Ingelfinger JR, 2014):
      • Targeted History and Physical to elicit risk factors including: relevant past medical history, family history, medications and other exposures (e.g. stimulants, etc), and physical exam.
        • Retinal Exam also indicated for children with ≥Stage 1 HTN
      • Lab Studies: basic metabolic panel, complete blood count, urinalysis & culture
        • Other lab studies could include (if clinically indicated): fasting lipid panel and glucose, plasma renin, plasma and urine steroid levels, and/or plasma and urine catecholamines
      • Imaging: Renal ultrasound and echo



  • For children with pre-hypertension and Stage 1 hypertension, lifestyle changes are recommended first line (Ingelfinger JR, 2014).
    • Examples include: dynamic exercise, DASH diet (Couch SC et al, 2008)

Image Credit: Pixabay



  • For children who continue to be hypertensive despite lifestyle interventions, evidence of end organ damage, or evidence of secondary etiologies pharmacologic intervention may be required
    • No consensus exists for “optimal” first line agent
      • Acceptable regimens include: ACE inhibitors, calcium channel blockers, or diuretics (Dhull RS et al, 2016).


Back to the Case: Upon seeing Andrew, you repeat his blood pressure manually, which is also high. He has no other “red flags” on history or exam. Given his age and comorbidities (obesity), Andrew most likely has essential hypertension (3 readings >140/90). Initial workup should include: basic labs (BMP, CBC, and UA) and imaging (renal ultrasound and ECHO). Provided these are all reassuring, he should first undergo lifestyle interventions, with medical management initiated if his BPs do not normalize.



  1. “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Pediatrics Aug 2004, 114 (Supplement 2) 555-576
  2. Couch SC et al. “The Efficacy of a Clinic-based Behavioral Nutrition Intervention Emphasizing a DASH-type Diet for Adolescents with Elevated Blood Pressure.” J Pediatr. 2008;152(4)494-501
  3. Dhull RS et al. “Pharmacologic Treatment of Pediatric Hypertension.” Current Hypertension Reports. 2016;18:32
  4. Ingelfinger JR. “The Child or Adolescent with Elevated Blood Pressure.” NEJM. 2014;370:2316-2325
  5. Gupta-Malhotra M et al. “Essential Hypertension vs. Secondary Hypertension Among Children.” Am J Hypertens. 2015;28(1):73-80
  6. Sinaiko AR. “Hypertension in Children.” NEJM. 1996;335:1968-1973.
  7. Yang Q et al. “Trends in High Blood Pressure among United States Adolescents across Body Weight Category between 1988 and 2012.” JPeds. 2016;169:166-73.e3.

Pass the salt…

Post Created by: Dani Halpern, MD

Case: 5yo M comes into the ED with nausea, confusion, and headache. On exam, he is sleepy but noticeable uncomfortable. He has moist mucous membranes, pupils are reactive and he has no noticeable edema. Suddenly, he begins to have a generalized tonic-clonic seizures. Amid the chaos and his mother’s crying you check a BMP and lo and behold his Na comes back as 125!


Image credit:

What is the pathophysiology of hyponatremia?

When there is an acute drop in sodium in the blood, water is pulled into the intracellular fluid so cells, especially brain cells, begin to swell. This causes meningeal irritation and the manifested symptoms of nausea, confusion, headache, vomiting and eventually, seizures.

Effects of Hyponatremia on the Brain and Adaptive Responses

Image from: Adrogue HJ et al, 2000

What is the workup of hyponatremia?

Choice of diagnostic algorithms:

  • Classic algorithm begins with an evaluation of patient’s fluid status.
    • Hypovolemic hyponatremia: ↓↓Na/↓H20 Euvolemic hyponatremia: ↔Na/↑H20   Hypervolemic hyponatremia: ↑ Na/↑↑H20
    • This is notoriously difficult to do accurately and clinicians have been shown to be very inaccurate in their assessment with sensitivities ranging from 0.5-0.8 and specificities 0.3-0.5 (Chung HM et al, 1987)
  • Alternative algorithm: (Milionis HJ et al, 2002).

Application of Alternative Algorithm

(Adapted from Milionis HJ et al, 2002)

Step 1: Verify this is an accurate level and is not spuriously low

Step 2: Obtain serum osmolality: (normal 275-290)

  • Low serum osmolality: True hyponatremia
  • Normal serum osmolality: Results from either large volumes of isotonic fluid lacking sodium (most common = mannitol), or in cases of hyperparaproteinemia or hyperlipidemia/triglyceridemia, that latter cases being referred to as “pseudohyponatremia” (see below for illustration). This is only seen in labs that use flame photometry; newer methods using ion-specific electrode have nearly eliminated this entity (Androgue HJ et al, 2000).

  • Increased osmolality: Osmotically active substances (most commonly glucose), draw water out of cells, effectively diluting serum sodium
    • Correction is approximately 2 mEq Na for every 100 glucose is >100

Step 3: Obtain urine Osm and Urine Sodium

  • <100 mOsm/kg = Appropriate water Excretion
    • Primary polydipsia/ psychogenic water drinking
      • Adult needs to drink about 18L for noticeable decrease in Na
    • Low solute intake (e.g. malnutrition, “beer potomania”)
  • >100 mOsm/kg = impaired water excretion. Can be due to problems in 3 different locations in process of diluting urine (this is where urine sodium comes in):
    • <20 mEq/L: hypovolemia (most common cause) and other states of decreased effective arterial blood volume (e.g. cirrhosis, congestive heart failure, nephrotic syndrome (rare in the absence of concurrent renal failure or volume depletion))
    • >40 mEq/L: SIADH vs renal salt wasting (e.g. renal dysplasia, post-obstructive diuresis, post-ATN diuresis), diuretics [mostly thiazide diuretics, uncommon with loop diuretics], adrenal insufficiency, metabolic alkalosis) THIS IS WHERE CLINICAL ASSESSMENT OF VOLUME STATUS ACTUALLY MATTERS (SIADH: restrict water.  Salt wasting: give salt or stop drugs)

In summary, a diagnosis of SIADH requires SOsm < 275, Uosm >100, UNa >30 (Because the fact that urine sodium is not low suggests that the patient is not volume depleted)


Image Credit:

In general, treatment of hyponatremia must weigh the benefits of therapy against the risks of overcorrecting, namely, osmotic demyelination (Adrogue HJ et al, 2000).

General Principles

  1.  If the patient has severe symptoms (e.g. seizures, CNS depression), hypertonic saline (3-5cc/kg) should be administered (Brenkert TE et al, 2013)
  2. When correcting hyponatemia, the rate of correction should not exceed 8mmol/L on any day of treatment  (Adrogue HJ et al, 2000).
  3. Treat the underlying condition, as detailed above


And now a table for all the conditions that often get confused for one another: 

First test yourself:

SIADH Renal salt wasting Hypovolemia
Volume Status
Serum Na
Urine Na
Serum Osm
Urine Osm
Urine output




SIADH Renal salt wasting Hypovolemia
Volume Status Euvolemic Hypovolemic hypovolemic
Serum Na low low Low
Urine Na > 40 >>40 <20
Serum Osm low low low
Urine Osm > plasma Osm > plasma Osm >plasma Osm
Urine output Low high low
ADH high high high

Faculty Reviewer: R. Kremsdorf, MD


Adrogué HJ, Madias NE, and Madias NE. “Hyponatremia.” N Engl J Med. 2000;342:1581-1589

Brenkert TE et al. “Intravenous hypertonic saline use in the pediatric emergency department.” Pediatr Emerg Care. 2013 Jan;29(1):71-3.

Chung HM, Kluge R, Schrier RW, Anderson RJ. “Clinical assessment of extracellular fluid volume in hyponatremia.” Am J Med. 1987;83: 905-908

Milionis HJ, Liamis GL, Elisaf MS. “The hyponatremic patient: a systematic approach to laboratory diagnosis.” Canadian Medical Association Journal. 2002;166(8):1056-1062.

Fluid Therapy Part II: Resuscitation Fluids

Case Continued:  Clinically, you determine that Julius (2-year-old boy with an acute diarrheal illness) needs IV fluid resuscitation. Why give fluid?


Image courtesy of pixabay

When given for acute resuscitation (maintenance fluid will be addressed later), the goal of fluid administration is to reverse and correct circulatory insufficiency (Arikan et al, 2008).

  • In physiologic terms, fluid therapy rests aims to restore and/or increase oxygen delivery
    • Oxygen Delivery = CO x CaO2, where CO is the cardiac output (determined by heart rate and stroke volume) and CaO2 is the oxygen carrying capacity (determined by SaO2 and Hemoglobin).
    • The goal of administering fluids is to increase preload, which in turn increases stroke volume and ultimately oxygen delivery
      • THUS, each time fluid is administered, the goal is to increase stroke volume.
      • NOTE: the assessment of “fluid responsiveness” is a large topic, and will not be addressed later

Furthermore, many studies have illustrated an improvement in patient outcome with early administration of IVF (Mederios et al, 2015)- more on this later.

What to give: Theory  professor

Image courtesy of pixabay

  • Fluids are divided into 2 main categories: Crystalloids and Colloids
    • Colloids are defined as “fluids containing high molecular weight substances that remain in the intravascular compartment, thereby generating an oncotic pressure.” (Mitra et al, 2009)
      • Examples include: synthetic starches and albumin (natural)
    • Crystalloids are salt solutions of varying composition
      • In clinical practice, examples would include 0.9% saline solution, Ringer’s Lactate, and Hartmann’s solution (see Fluid Therapy: Part I for solution components)
        • Historical Note (Myburgh, 2014): “Normal Saline” was determined in the 1880s via experiments in lysing red blood cells, which indicated the amount of salt in human blood was 0.9%. Unfortunately, these studies were flawed and physiologically, human plasma is closer to 0.6% saline. Despite these findings, “normal” saline remains ubiquitous.
  • The choice of resuscitation fluid relies on Starling’s other formula, describing the determinants of fluid movement across semipermeable membranes (Myburgh, 2014)
    • The ideal solution would remain completely within the vascular space, with little extravasation into the interstitium
      • Based on this, colloids were initially thought to carry a theoretical benefit including: more rapid plasma expansion and correction of oncotic pressure (Medeiros et al, 2015)
  • Recent experiments into the glycocalyx layer of vascular endothelium have complicated this picture, indicating that in septic shock, damage to this layer contributes to vascular permeability, thereby limiting the benefits of colloids in actual practice

How does this theory play out in the real world?

In other words, in patients presenting with hypovolemia and/or shock, what fluid should be given to restore intravascular volume?

  • Colloids vs. Crystalloids
    • From our theoretical perspective, it would seem that colloids, though markedly more expensive, would be better
    • Pediatric-centered data is sparse, but studies comparing colloids and crystalloid in septic shock (usually dengue), fail to show convincing benefit of one solution over another (Mederios et al, 2015)
      • A recent meta-analysis of adult patients with sepsis indicates that synthetic colloids, specifically 6% HES, are associated with a higher rate of renal replacement therapy and mortality (Gattas et al, 2013)
      • Conversely, in adults, the use of albumin compared to crystalloid trends towards showing a 90 day mortality benefit  (Xu et al, 2014)
  • Chloride rich vs. balanced salt solutions
    • Recently, researchers have turned their attention to comparing chloride rich (e.g. normal saline) solutions with more physiologically balanced solutions (Ringer’s Lactate or Plasma-lyte)
      • These studies arose from observational studies showing (again, in adults) that hyperchloremia is associated with acute kidney injury (Suetrong et al, 2016)
        • In the recent SPLIT trial (randomized trial comparing NS and plasma-lyte), investigators failed to show any differences between the groups. In this study, the primary outcome was AKI, with secondary outcomes being use of RRT and in-hospital mortality (Young et al, 2015)
    • While such literature is sparse in the pediatric world, numerous case reports detail the association with normal saline and hyperchloremic metabolic acidosis (Skellett S et al, 2000).

Until further studies are performed, crystalloids should be used as first line therapy in fluid resuscitation in pediatrics, with attention paid to avoiding large volumes of chloride-rich fluids.


Now that we’ve chose a fluid, how to administer?

  • By convention, pediatric patients are given fluid boluses in 20 ml/kg aliquots. Unfortunately, the literature detailing how “20cc/kg” came to be is sparse.
  • The 2015 PALS (pediatric advanced life support) Guidelines indicate that in patients with signs of shock (diminished pulses, cool/pale/mottled skin, prolonged capillary refill, tachycardia, and altered mental status (particularly ominous), 20cc/kg should be administered over 5-10 minutes
  • In the United States, various studies have shown adherence to the PALS guidelines in children with shock is correlated with improved mortality (Carcillo et al, 2002; Han at al, 2003) and shorter length of stay (Paul et al, 2012)
  • However, the recent FEAST study (RCT Trial, population: children in sub-Saharan Africa), showed fluid bolus therapy was associated with increased mortality (Maitland et al, 2011).
    • Presently, Canadian investigators (SQUEEZE Investigators) are investigating this question (fluid sparing vs. usual care) with results of their pilot studying informing the feasibility of a multi-center trial (Parker et al, 2016).



  • Fluid, like any other intervention, has indications and contraindications
  • When deciding to give fluid boluses, determine the underlying pathophysiologic insult (sepsis vs. hypovolemia from ongoing losses) and intervene appropriately
  • Anticipate complications (fluid overload, metabolic derangements)
    • Case control studies from single institutions indicate that in the PICU setting, fluid overload is associated with higher morbidity (Sinitsky et al, 2015) and mortality (Sutawan et al, 2016).
    • Hyperchloremic metabolic acidosis with normal saline
  • Various retrospective studies show that adherence to PALS algorithm is associated with improved outcomes


Faculty Review: Lee Polikoff, MD



  • Arikan AA et al. “Pediatric Shock.” Signa Vitae. 2008;3(1)13-23
  • Carcillo JA et al. “Clinical practice parameters for hemodynamic support of pediatric and neonatal patients with septic shock.” Critical Care Med. 2002;30:1365-78
  • Gattas DJ. “Fluid resuscitation with 6% hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: Systematic review of effects on mortality and treatment with renal replacement therapy.” Intensive Care Medicine. 2013;39(4)558-568.
  • Han YY et al. “Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics. 2003;112: 793-99.
  • Maitland K et al. “Mortality after Fluid Bolus in African Children with Severe Infection.” NEJM. 2011;364:2483-2495.
  • Medeiros DN et al. “Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.” Pediatric Emergency Care. 2015;31(11)e11- e16.
  • Mitra S et al. “Are All Colloids Same (sic)? How to Select the Right Colloid?” Indian J Anaesth. 2009;53(5)592-607
  • Myburgh JA. “Fluid resuscitation in acute medicine: what is the current situation?” Journal of Internal Medicine. 2015;277; 58–68
  • Paul R et al. “Adherence to PALS Guidelines and Hospital Length of Stay.” Pediatrics. 2012;130(2):e273-280
  • Skellett S et al. “Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid administration.” Arch Dis Child. 2000; 83:514-516
  • Suetrong B et al. “Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients.” Critical Care. 2016; 20:315
  • Sutawan IB et al. “Association of fluid overload with mortality in pediatric intensive care unit.” Crit Care Shock. 2016;19:8-13
  • Young P et al. “Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit.” JAMA. 2015
  • Xu JY et al. “Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.” Critical Care. 2014;18:702



Image of the Week: 12/5

Case: A 20 month-old male presents to the ED with complaints of increasingly unsteady gait and vomiting, who on exam, is found to have bilateral papilledema. The following MRI is obtained. What do you see?


Sagittal T-1 Image


MRI Brain: T1- weighted Image


MRI Brain: Coronal FLAIR

Case courtesy of Dr Abdallah Khateeb , From the case rID: 45608

Diagnosis: Pilocytic Astrocytoma (formerly juvenile Pilocytic Astrocytoma)

Official Radiology Read (per Dr. Khateeb)

Impression: 1.) Large cystic mass at the right posterior fossa with peripheral thick nodular enhancement. 2.) Significant mass effect on the cerebellum and the fourth ventricle, crowded foramen magnum, signs of obstructive hydrocephalus and transependymal edema.


Pilocytic Astrocytoma is a WHO grade 1 tumor, and generally confers a favorable prognosis. In fact, these tumors are considered curable if the entire tumor is resected . As such, the primary goal of therapy is resection. Recurrence is rare, as is malignant spread. Tumors are most commonly found in the cerebellum, but are also found in the brainstem, supratentorial structures, and the hypothalamus (Burkhard  et al, 2003).  Prognosis is excellent, but relies on gross-total resection.

Imaging Findings (Lee et al, 1989)

  • A majority of tumors are oval or round  (as seen in our case)
  • A majority of tumors are cystic
  • On MRI, lesions are hypo- to isointense on T1 weight images and hyperintense on T2 series.

Faculty Reviewer: Brad DeNardo, MD


Burkhard C et al. “A population based study of the incidence and survival in patients with pilocytic astrocytoma.” J Neurosurg. 2003; 98: 1170-1174

Lee Y et al. “Juvenile Pilocytic Astrocytomas: CT and MR Characteristics.” AJNR. 1989; 10: 363-370


Fluid Therapy: Part 1


Image courtesy of Pixabay, Public Domain Pictures

Fluid therapy is likely one of the most common interventions performed in pediatrics. Until recently, fluid therapy wasn’t given much thought, “reflecting the long held notion that fluid therapy is straightforward and of little consequence to the patient” (Osteermann, 2012). This post will be the first in a likely 3-part series that looks at fluids and acid-base in the care of pediatric patients. 


Julius is a 2 year-old boy, who presents to the ED with an acute diarrheal illness, which started 3 days prior (his older brother had a similar illness 1 week prior, and is now well). Initially, Julius was drinking well, however mom notes that over the last day he has stopped drinking and doesn’t appear to be making wet diapers. On your exam, you note him to be fatigued, with dry mucus membranes and vitals are significant for mild tachypnea and moderate tachycardia.  You recognize that he is hypovolemic and want to start fluids. What should you use? (NOTE: in this context, many would make the argument for NG fluids, however in the context of the post we are going to assume that this is not possible).


Why do we use fluids?


Image courtesy of Pixabay, Public Domain Pictures

  • Fluids are used for 2 main reasons (Davidson et al, 2013):
    • Maintain intravascular volume (“Fill the Tank”)
    • Maintain water and electrolyte homeostasis (e.g. hypo- vs. hypernatremia)


Flashback to Med School: Fluid Compartments (Davidson et al, 2013):

  • Remember that “Total Body Water” (TBW) is about 60% of lean body weight
    • Note that neonates generally have much higher TBW (~75% of body weight) and TBW decreases with age


Adapted from Davidson et al, 2013

Tonicity vs Osmolality (Khurana, 2013)


Image courtesy of Pixabay, Public Domain Pictures

  • Osmolality (Osm) = moles of solute/kg of solvent
    • Depends on number of solute particles, not the specific type of particles
      • E.g. A 1 molar solution of NaCl has an osmotic concentration of 2 Osm, as NaCl will disociate into equal parts Na+ and Cl-
      • The osmolality of human intra- and extracellular fluid is 290 milliosmoles per kg (mOsm/kg)
        • This is largely determined by sodium, chloride, and bicarbonate (and to a lesser degree, glucose and urea).
  • Tonicity
    • Describes the movement of water between 2 compartments between a semi-permeable membrane (osmotic gradient)
      • In human physiology, everything is compared with that of human plasma
    • How does this apply to fluids we infuse?
      • Water will ALWAYS travel along its concentration gradient, from areas of low Osmolality to high Osmolality
        • Hypotonic fluids will result in the net influx of water into cells
        • Hypertonic fluids will draw fluids out of cells
    • As tonicity describes movement of water, it is only influenced by substances that cannot cross membrane
      • Substances that can freely cross membranes are called “ineffective osmoles” (e.g. dextrose, urea)

As such, osmolality does not equal tonicity

  • For example, the fluid D5 1/2NS is both hyperosmolar (owing to the dextrose) and hypotonic (again owing to the dextrose).

What is in the fluid we use?

 Common Fluid Choices and Their “Ingredients”

Human Body

Normal Saline (Isotonic)

Lactated Ringer’s (Isotonic)

D5 and 0.45% NaCl (Hypotonic)

Sodium 140 meq/L 154 130 77
Potassium 4 meq/L 0 4 0
Calcium 9 mg/dl 0 2.7 0
Chloride 102 meq/L 154 109 77
Lactate 0 0 28 0
Osmolality (mOsm) 298 308 273 406


How does one choose a fluid?

  • To choose a fluid, you must answer the question: What am I treating?
    • As mentioned earlier, this generally falls along the lines of: do I need to restore intravascular volume and/or do I need to provide daily requirements of water and electrolytes?
  • This question will be explored further on our next post, please stay tuned!


  • Fluid therapy is common in pediatrics, and should be approached like any other medication: Understand indications and any contraindications
  • Fluids can be classified by their osmolality (#moles solute/weight of solvent) and by tonicity (which describes the movement of water between a selectively permeable membrane)
    • Osmolality and Tonicity are related, but not equivalent. This is due to presence of “ineffective osmoles,” which are solutes than can freely cross membranes and therefore do not influence the movement of water
      • Hypotonic fluids will result in the net influx of water into cells
      • Hypertonic fluids will draw fluids out of cells
      • There will be no net movement of water with isotonic fluids

Faculty Reviewer: Lee Polikoff, MD

Sources (for table with various [ ]’s

Davidson D et al. “Fluid Management in Adults and Children: Core Curriculum 2014.” Am J Kidney Dis. 2013; 63(4)700-

Edelson JB et al. “Intravenous Fluid Management in the Pediatric Hospital Setting: Is Isotonic Fluid the Right Approach for all Patients.” Current Treatment Options in Pediatrics. 2015; 1:90-99.

Khurana, Indu. Textbook of Human Physiology for Dental Students, 2nd Ed. Elsevier. 2013. p18.

Ostermann M. “The importance of fluid therapy: No longer an innocent bystander.” Monitor. 2012;19(6).

Image of the Week: 10/28

Case: Tommy is a 6yo boy coming in for a sick appointment. His mother states that he has had a limp for “a while.” He is an active kid and she thought he had bruised himself and didn’t think too much of it. Now, 2 weeks later, he has not improved.  After a complete history and physical, an x-ray of the hips is obtained: 




AP Hip


Frog leg view

Diagnosis: Legg-Calve-Perthes Disease

Radiology Findings (courtesy of Radiopaedia):  The left superior femoral epiphysis is markedly flattened, sclerotic and appear to be undergoing fragmentation. Alignment is unremarkable and the pelvis and acetabulum appear normal. The Right hip appears normal.

Brief Summary:

  • Legg-Cavle-Perthes Disease is an idiopathic avascular necrosis of the femoral head
  • Generally affects children between 2-12 years of age and tends to be more common in boys as opposed to girls  (Hermann et al, 2015)
    • Bilateral in 10-20% of patients (Nigrovic, 2016)
  • Children tend to present with limp and limited range of motion of the hip.
    • Children may also initially present with knee pain or thigh pain
  • Plain films of the hips help make the diagnosis, though tend to normal early in the course [unlike case above, which likely details later stage findings] (Nigrovic, 2016)
    • MRI helpful in diagnosis early in disease process as well as detailing prognosis (Dillman et al, 2009)
      • findings include: proximal femoral necrosis, delayed contrast enhancement, abnormalities in the proximal femoral physis
  • Referral to orthopedic surgeon important for long term management
    • Once diagnosed, children should be made nonweight bearing until seen by orthopedist (Nigrovic, 2016)
  • Ongoing management is symptomatic (anti-inflammatory meds, physical therapy, limited activities), though there is a paucity of evidence to guide recommendations.

Faculty Reviewer: Alison Riese, MD


Case courtesy of Dr. Bruno Di Muzio, From the case rID: 12153

Dillman JR et al. “MRI of Legg-Calve-Perthes Disease.” American Journal of Radiology. 2009;193(5)1394- 1407.

Herman MJ et al. “The Limping Child.” Pediatrics in Review. 2015;36(5)184-197.

Nigrovic PA. “Overview of hip pain and childhood.” Accessed October, 2016.

Just another headache?


Case: John is a 6-year-old boy with a history of congenital hydrocephalus, status post ventriculo-peritoneal (VP) shunt, who presents with acute onset of headache, which is associated with nausea and vomiting. His mother is worried about a problem with the shunt. Should you be?



Answer: YES! The remainder of the post is dedicated to the ins and outs of shunts, but we cannot overstate the importance of parental insight. In one study, parental concern had a similar sensitivity and specificity as a CT scan (Kim et al, 2007)


A CT scan was completed on this patient (shown below), demonstrating a marked interval increase in ventricle  size, consistent with shunt failure. John was subsequently admitted to the neurosurgery service for operative revision of the shunt.



Non contrast Head CT: Axial Reformat

vp-shunt-fail-coronalNon-contrast Head CT: coronal imaging

What is a VP Shunt?

  • A VP shunts is a plastic catheter that diverts cerebrospinal fluid (CSF) from the lateral ventricles to the peritoneal cavity
    • While VP shunts are the most common, CSF can be diverted from the ventricles to the pleural cavity and the atria of the heart (VA shunt).

Why are they placed?

  • VP shunts are intended to palliate hydrocephalus, and are one of the most commonly performed neurosurgical procedures (Pietetti et al, 2007)
  • Epidemiological studies indicate the prevalence of VP shunts is 8.2/10,000 (Piatt et al, 2008). 
  • Unfortunately, VP shunts do not correct the underlying etiology of the hydrocephalus and are therefore not curative

What can go wrong with a shunt?

  • A variety of complications can occur with a VP shunt including: mechanical obstruction or over-drainage, infection, fracture, and/or migration (Piatt et al, 2008).
  • In the first year of placement, almost 40% of shunts fail (Kestle et al, 2000; Piatt et al, 2008)
    • The rates of infection (common cause of shunt failure) tend to be highest in the first 6 months of placement.

What symptoms should be concerning?

  • The most common symptoms include: nausea, vomiting, irritability, fever, or altered level of consciousness (Browd et al, 2006)
    • Specific findings and their Likelihood Ratio (Piatt et al, 2008)
      • Bulging Fontanel: 46.1
      • Decreased level of Consciousness: 26.2
      • Irritability: 13.7
  • Less common findings include: weakness, diplopia, cranial nerve palsies (CN VI especially), ataxia
  • Examination of the tract itself is very important (ventricular insertion site in skull generally traverses posterior to ear along neck). Some findings that could indicate problems:
    • Palpation of fracture
    • Erythema of tract may herald infection
    • Evidence of fluid collection over ventricular insertion site
  • Very Important to perform abdominal exam (Browd et al, 2006)
    • Abdominal Pain carries a likelihood ratio of 12.8 for failure
    • Other signs: ascites or intra-abdominal mass (pseuodocyst)

How can I evaluate a shunt?

  • Shunt Series:
    • What It Is: An anterior-posterior and lateral x-ray detailing the entire length of the catheter
    • Given poor sensitivity for shunt malfunction, authors do not recommend as first line (Boyle et al, 2015)
  • Head CT
    • Historically, the diagnostic standard for shunt malfunction
    • If enlarged ventricles are demonstrated on exam, this is consistent with shunt malfunction (Boyle et al, 2015)
    • Pros: Fast, sensitive; Con: large dose of radiation
  • FAST MRI (also known as: half-fournier acquisition single shit turbo-spin echo sequences)
    • Use single-section T2-weighted images, acquiring images in 1-4 minutes (Boyle et al, 2015)
    • Non-inferior to head CT* (Boyle et al, 2014)- Note: study not powered to compare sensitivities
    • Pro: No radiation; Con: variable access to MRI, cost (though notably less expensive than conventional MRI)

Diagnosing Shunt Malfunction

 Modality Reported Sensitivity Reported Specificity
Shunt Series 4- 26% 92-98%
Head CT 53-92% 76-93%
FAST MRI 51-59% 89- 93%
Experienced Parents 88.90% 62.20%

Adapted from Kim et al, 2007


  • VP shunts offer a mechanical “solution” (not cure), to patients who are otherwise unable to adequately drain CSF
  • Shunt malfunction and/or failure is common (40% fail in the first year of placement)
  • Failures can be mechanical (fracture, obstruction, dislodged) or related to infection
  • Symptoms of shunt failure are diverse and often non-specific
  • ALWAYS take parental concerns seriously!
Reviewer: Yunika Presson, CPNP (Department of Neurosurgery)


Blumstein H et al. “Utility of Radiography in Suspected Ventricular Shunt Malfunction.” The Journal of Emergency Medicine. 2009;36(1)50-54

Boyle TP et al. “Radiolgraphic Evaluation of Pediatric Cerebrospinal Fluid Shunt Malfunction in the Emergency Setting.” Pediatric Emergency Care. 2015;31(6)435-440

Boyle TPet al. Comparison of rapid cranial MRI to CT for ventricular shunt malfunction.”
Pediatrics. 2014;134(1)e47-e54

Browd SR et al. “Failure of Cerebrospinal Fluid Shunts: Part I: Obstruction and Mechanical Failure.” Pediatric Neurology. 2006;34(2)83-92

Kestle J et al. “Long-term Follow-up Data from the Shunt Design Trial.” Pediatric Neurosurgery. 2000;33(5)230-236

Kim TY et al. “Test Characteristics of Parent’s Visual Analog Scale Score in Predicting Ventriculoperitoneal Shunt Malfunction in the Pediatric Emergency Department.” Pediatric Emergency Care. 2007;23(8)549-552.

Piatt JH et al. “Clinical Diagnosis of Ventriculoperitoneal Shunt Failure Among Children with Hydrocephalus.” Pediatric Emergency Care. 2008;24(4)201- 210

Pitetti R. “Emergency Department Evaluation of Ventricular Shunt Malfunction: Is a shunt series really necessary?” Pediatric Emergency Care. 2007;23(3)137-141

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