Pediatric emergency medicine trisk 610

TABLE 95.6
POSTMORTEM SPECIMENS COLLECTED AT AUTOPSY a


Postmortem specimens Analyses
Blood a
10-mL EDTA tube

Chromosome analysis

4–6 filter paper spots

DNA analysis (requires PCR
amplification)

5-mL heparinized tube

Tandem mass spectrometry for
organic acidemias, urea cycle
defects, fatty acid oxidation
defects
Acylcarnitines
Amino acids
Bile acids

Urine a
Urine 10 mL in 1–2-mL Amino acids
aliquots
Organic acids
Acylcarnitines
Bile acids

Cerebrospinal fluid (CSF)
CSF 3–5 mL in 1-mL
Glucose
aliquots
Lactate, pyruvate
Glycine, serine
Neurotransmitters
Organic acids
Aqueous humor
Aqueous humor
Organic acids

Skin biopsy a
Skin—2 samples, 3-mm Chromosome analysis
diameter each
DNA analysis
Enzyme activity

Comments on collection, storage
Obtain blood by vascular access or
intracardiac puncture
For filter paper spots, apply free-flow
blood to filter paper, saturate through
to back, do not layer drops
Air-dry 3–4 hrs, do not heat. Place in
envelope, refrigerate

Freeze plasma at −20°C or −70°C, store
erythrocytes at 4°C

Collect by bladder catheterization,
suprapubic aspiration
If unsuccessful, irrigate bladder with 20mL normal saline and collect or
perform intrabladder swabs at autopsy
Freeze at −20°C or −70°C
If not collected for clinical care, may be
appropriate to collect postmortem
Freeze at −20°C or −70°C

May be appropriate if blood not
available
Collect by intraocular puncture at
autopsy
Freeze at −20°C or −70°C
Best collected premortem or
immediately postmortem, usually
viable 2–3 days, 1 wk may be helpful
to discuss with specialist
Skin, punch, or incisional biopsy, sterile
technique, 2 sites—flexor surface
forearm, anterior thigh, transport in
sterile tube completely filled with
tissue culture media, viral culture


media (do not use culture media if
planning for microscopic studies),
normal saline without preservative, or
normal saline–soaked sterile gauze in
sterile tube, freeze at –70°C

Fibroblast culture provides unlimited
specimen
Organ biopsy
Brain b
Heart muscle b
Liver a 1 cm3 , 10–20
mg, ≤0.5 cm thick
Kidney b

Histochemical light and/or electron Biopsy potentially affected organs,
microscopy
collect within 1–2 hrs after death
Enzyme activity
Biochemical metabolites
Mitochondrial studies

Spleen b
Skeletal muscle 20–50
mg, ≤0.5-cm thick
Bile
Bile 2 mL

Needle or open incisional biopsy, sterile
technique, wrap in aluminum foil, dry
ice, freeze at −70°C, screw-top
airtight vial
Some assays may need to be performed
on fresh specimens

Bile acids

Acylcarnitines

a If

family declines autopsy but gives permission for specimen collection, or if unable to obtain autopsy within hours of death, collect blood,
urine, and CSF; perform punch or open incisional biopsy of skin and needle biopsy of liver and skeletal muscle; take photographs of
dysmorphic features; and obtain radiologic studies to evaluate for neurologic, cardiac, or skeletal abnormalities. Obtain parental permission.
Tests that are not accurate using postmortem specimens are those for serum amino acids, lactate, pyruvate, and total and free carnitine
assessment. Consider developing postmortem specimen collection kit for ED that contains necessary equipment, specimen containers, and
institution-specific instructions.
b Obtain an autopsy if autopsy permission granted.
EDTA, ethylenediaminetetraacetic acid; PCR, polymerase chain reaction; ED, emergency department.

Hyperammonemia is the hallmark of urea cycle defects but also occurs in organic acidemias and fatty
acid oxidation defects as a consequence of secondary inhibition of the urea cycle. Ammonia levels are
typically highest in urea cycle defects and may exceed 1,000 μg/dL. Ammonia levels in organic
acidemias are usually less than 500 μg/dL during decompensation but may exceed 1,000 μg/dL.
Hyperammonemia in fatty acid oxidation defects, if present, is usually less than 250 μg/dL. Transient
hyperammonemia of the newborn should be considered in the differential diagnosis, particularly if
hyperammonemia is present on the first day of life. Hyperammonemia directly stimulates the respiratory
center, resulting in tachypnea. Ammonia level higher than 250 μg/dL with respiratory alkalosis in the
absence of metabolic acidosis is highly suggestive of a urea cycle defect. Proper collection and handling
of blood for ammonia determination is critical to prevent falsely elevated values. Abnormal levels should
be confirmed immediately using proper technique for drawing and handling.
Patients with urea cycle defects may have compensatory metabolic acidosis. Patients with organic
acidemias and fatty acid oxidation defects and hyperammonemia have primary metabolic acidosis usually
without respiratory alkalosis. Patients with hyperammonemia due to organic acidemias usually have
marked ketosis and normal glucose level, whereas those with fatty acid oxidation defects usually have
hypoketotic hypoglycemia. Even during minor illnesses, protein catabolism may result in
hyperammonemia. In patients with hyperammonemia, liver function should be evaluated. Mild elevation

of transaminases may be seen in metabolic disorders in each category. Plasma should be sent for amino


acids and acylcarnitines evaluation, and urine for organic acids, acylglycines, and orotic acid evaluation.
Liver dysfunction due to causes other than IEM, including primary liver disease, hepatic infection, toxic
insult, sepsis, and asphyxia, may also cause hyperammonemia.
Imaging studies. In the ED, imaging studies may be useful to guide management of potential acutely
life-threatening organ system failure, particularly cerebral edema, hemorrhagic or thrombotic stroke, or
cardiac failure. Imaging studies to aid in diagnosis and long-term management are rarely appropriate in
the ED setting.
Management
Initial treatment of IEMs is aimed at correcting acute metabolic abnormalities with an empiric focus on
preventing further catabolism. Even the apparently stable patient may deteriorate rapidly. For patients
with IEMs of amino acid or carbohydrate metabolism, treatment is aimed at elimination of toxic
metabolites. For disorders of fatty acid oxidation or gluconeogenesis and glycogenolysis, therapy is
aimed at correcting the energy deficiency. In patients with lysosomal, mitochondrial, and peroxisomal
disorders, emergent treatment is aimed at ameliorating the effects of organ dysfunction and usually
involves temporizing measures that do not have long-term impact on the inevitable progressive,
degenerative course of these disorders. As always, airway, breathing, and circulation must be addressed
first. Treatment for a potential IEM should be started empirically as soon as the diagnosis is considered (
Table 95.7 ).
All oral intake should be stopped to prevent the introduction of potentially harmful protein or sugars.
Fluid bolus(es), as clinically indicated, should be normal saline, 10 mL/kg for neonates or patients with
concern of heart failure and 20 mL/kg for infants and children. Ringer lactate should be avoided because
it can worsen acidosis. The initial fluid bolus should be followed by dextrose-containing (typically at a
dextrose concentration of at least 10%) IV fluids typically administered at 1.5 times maintenance rate to
prevent catabolism.
Hypoglycemia. Hypoglycemia, if present, should be corrected by dextrose bolus instead of adding D10
to bolus fluid; 0.25 to 1 g/kg as 10% dextrose for neonates, and 10% or 25% dextrose for those beyond
the neonatal period. Hydration after fluid/dextrose bolus should be with D10 to D15 in ½ normal saline at

1 to 1.5 times maintenance to maintain serum glucose level at 120 to 170 mg/dL, with the goal of
preventing catabolism. Large, rapid fluctuations in glucose level should be avoided. Correction of
hypoglycemia with glucose will improve most conditions with the exception of primary lactic acidosis
due to disorders of gluconeogenesis involving pyruvate metabolism.
Acidosis. Sodium bicarbonate may be used in some limited circumstances for the immediate treatment
of metabolic acidosis, however, is likely to have minimal impact if the underlying metabolic cause is not
treated. Rapid and/or overcorrection of acidosis may have adverse CNS effects. In the patient with
hyperammonemia, alkalization of the blood favors the conversion of NH4 + to NH3 , which crosses the
blood–brain barrier more readily and may cause cerebral edema and/or hemorrhage. Furthermore,
alkalization of the urine decreases excretion of ammonia. Ultimately, definitive treatment of acidosis
requires removal of the abnormal metabolites either by restricting dietary intake, or in severe cases, by
dialysis, preferably hemodialysis.
Hyperammonemia. Significant hyperammonemia is life threatening and must be treated immediately.
Treatment protocols for hyperammonemia in neonates and infants and children are detailed on the New
England Consortium website and as per their site are meant to be used in consultation with an IEM
specialist:
. The goals of emergent treatment of
hyperammonemia are to eliminate protein intake, prevent catabolism, and enhance the elimination of
ammonia. Central venous access is required for treatment. Fluid containing 10% to 20% dextrose at a rate
of 1 to 1.5 times maintenance to maintain serum glucose level at 120 to 170 mg/dL should be
administered to prevent catabolism and enhance elimination of ammonia. If hyperglycemia occurs,