5th Pediatric Endocrine Update

Indonesian Pediatric Society

Malang 19-20 May 2017
 Disclosures
Nothing to Disclose
 Introduction
Hiponatremia:
Insidens 25% anak rawat inap
Variasi gejala klinis dari tidak khas sampai berat
Kedaruratan, kegawatan
mortalitas, morbiditas & LOS
Etiologi / patofisiologi berbeda tatalaksana
berbeda ketepatan diagnosis penting

Reid. Pediatrics in Review. 2013;34:417-9.

 Definition
Hyponatremia: plasma sodium < 135 mEq/L
Natrium : H2O Natrium dalam ECF
Gejala klinis bila Na <125 mEq/L atau pe kadar
natrium terlalu cepat
Risiko tinggi
Anak
Pasien post-op
Trauma/infeksi SSP
Penyakit paru
Hipoksia
Definition of hyponatraemia based on
biochemical severity
MILD hyponatraemia : serum sodium
concentration 130 - 135 mmol/L
MODERATE hyponatraemia: serum sodium
concentration 125 - 129 mmol/L
PROFOUND hyponatraemia: < 125 mmol/L
Definition of hyponatraemia based on
time of development
ACUTE hyponatraemia as hyponatraemia
that is documented to exist < 48 h.
CHRONIC hyponatraemia as hyponatraemia
that is documented to exist 48 h.
If the hyponatraemia cannot be classified,
considered as chronic, unless there is clinical
or anamnestic evidence of the contrary
Definition of hyponatraemia based on
symptoms
MODERATELY SYMPTOMATIC hyponatraemia
as any biochemical degree of hyponatraemia
in the presence of moderately severe
symptoms of hyponatraemia
SEVERELY SYMPTOMATIC hyponatraemia as
any biochemical degree of hyponatraemia in
the presence of severe symptoms of
hyponatraemia
 Hyponatraemia based on symptoms
Severity Symptom
Moderately severe Nausea without vomiting
Confusion
Headache
Severe Vomiting
Cardio-respiratory distress
Abnormal and deep
somnolence
Seizures
Coma
Arginine Vasopressin
 Homeostasis
Homeostatic mechanisms
protecting against
changes in volume and
sodium concentration
sympathetic activity,
reninangiotensin
aldosterone system Na
resorption by kidneys,
hypothalamic arginine
vasopressin (ADH)
prompts resorption of H2O

(Espay, 2014)
 Arginine Vasopressin
Principle sites of action: the kidney and blood
vessels.
AVP acts on renal collecting ducts via
V2 receptors to increase water permeability
decreased urine output increases blood
volume, cardiac output and arterial pressure.
AVP binds to V1 receptors on vascular smooth
muscle to cause vasoconstriction
http://www.cvphysiology.com/Blood%20Pressure/BP016
 280 mosm 280 mosm

NORMAL Sel H2O

ICF ECF

ISOTONIC FLUID DEFICIT

280 mosm 280

280mosm
mosm

Sel H2O

280 mosm 260 mosm

Sel H2O
HYPONATREMIA

Natrium: main osmotic ECF

 Etiology
Common
Administration of hypotonic fluids, intravenous or
enteral (e.g. excessively dilute formula or 0.18% NaCl)
Conditions with impaired free water excretion and high
anti-diuretic hormone levels
Meningitis, encephalitis, pneumonia, bronchiolitis, sepsis
Surgery, pain, nausea and vomiting
Relative excess fluid intake in a child receiving
exogenous anti-diuretic agents (eg Desmopressin for
nocturnal enuresis)
Gastrointestinal fluid losses

(RCH Melbourne Clinical Guideline, 2016)

 Etiology
Less common
Adrenal insufficiency (Congenital Adrenal
Hyperplasia, Addison's Disease )
Defect in renal tubular absorption, including
obstructive uropathy
Psychogenic polydipsia

(RCH Melbourne Clinical Guideline, 2016)

 Hyponatremia
True hyponatremia
Pseudohyponatremia:
plasma osmolality is normal (isotonic) but sodium
values low: hyperlipidemia or hyperproteinemia
plasma osmolality is high (hypertonic) but sodium
values low: hyperglycemia or mannitol intake
[Na]corrected=
[Na]measured+1.6([glucose]100mg/dL)
100

(Espay, 2014)
seizures in patients with hyponatremia medical emergency that should
be managed with rapid but partial correction of the serum sodium.

DIAGNOSTIC
 HYPONATREMIA
ALGORITM DIAGNOSIS OF
EXCLUDE HYERGLYCEMIA AND OTHER CAUSES
OF NON-HYPOTONIC HYPONATREMIA
HYPONATRAEMIA
HYPOTONIC HYPONATREMIA

ACUTE OR
SEVERE YES
SYMPTOMS?
Consider immediate
treatment with hypertonic
saline

NO

URINE OSMOLALITY
 URINE OSMOLALITY
ALGORITM DIAGNOSIS OF
HYPONATRAEMIA 100 mOsm/kg > 100 mOsm/kg
Consider
Primary polydipsia URINE SODIUM
Low solute intake
Beer potamania

30 mmol/L > 30 mmol/L

LOW EFFECTIVE
DIURETICS
ARTERIAL VOLUME
OR
KIDNEY
HYPERVOLEMIA DISEASE NO
Heart failure
YES
Liver failure
Nephrotic syndrome
HYPOVOLEMIA NORMOVOLEMIA
HYPOVOLEMIA Vomiting SIADH
Diarrhea,vomiting Addison y ACTH deficiency
Third spacing Renal salt wasting Hypothyroidism
Remote diuretics Cerebral salt wasting Occult diuretics
Occult diuretics
 HYPOVOLEMIC HYPONATREMIA
EXTRARENAL LOSSES
Gastrointestinal (emesis, diarrhea)
Skin (sweating or burns)
Third space losses (bowel obstruction, peritonitis, sepsis)
RENAL LOSSES
Thiazide or loop diuretics
Osmotic diuresis
Postobstructive diuresis
Polyuric phase of acute tubular necrosis
Juvenile nephronophthisis (OMIM 256100/606966/602088/604387/611498)
Autosomal recessive polycystic kidney disease (OMIM 263200)
Tubulointerstitial nephritis
Obstructive uropathy
Cerebral salt wasting
Proximal (type II) renal tubular acidosis (OMIM 604278) *
Lack of aldosterone effect (high serum potassium):
Absence of aldosterone (e.g., 21-hydroxylase deficiency [OMIM 201910])
Pseudohypoaldosteronism type I (OMIM 264350/177735)
Urinary tract obstruction and/or infection
 EUVOLEMIC HYPONATREMIA
Syndrome of inappropriate antidiuretic hormone secretion
Nephrogenic syndrome of inappropriate antidiuresis (OMIM 304800)
Desmopressin acetate
Glucocorticoid deficiency
Hypothyroidism
Water intoxication:
Iatrogenic (excess hypotonic intravenous fluids)
Feeding infants excessive water products
Swimming lessons
Tap water enema
Child abuse
Psychogenic polydipsia
Diluted formula
Beer potomania
Exercise-induced hyponatremia
 HYPERVOLEMIC HYPONATREMIA
Heart failure
Cirrhosis
Nephrotic syndrome
Acute, chronic kidney injury
Capillary leak caused by sepsis
Hypoalbuminemia caused by gastrointestinal disease (protein-losing
enteropathy)
 Differentiating CSW & SIADH
CSW SIADH Diabetes Insipidus
Plasma Volume
Salt Balance Negative Variable
Dehydration Present Absent Present
Weight / no change
Pulmonary Capillary Wedge / no change
Pressure
Central Venous Pressure / no change
Hematocrit / Normal
Serum Osmolality / Normal
BUN/Creatinine Ratio Normal
Urine Sodium Concentration Significantly Normal
Serum Uric Acid Concentration / Normal
Urine Output
Serum Albumin Concentration Normal
 Urin
Pemeriksaan UNa : berguna untuk evaluasi
hiponatremia dan GGA
Hypovolemic hyponatremia: tubulus renalis
reabsorpsi natrium sebanyak mungkin
UNa < 20 mEq/L.
SIADH: euvolemic hyponatremia ekskresi
natrium urin normal UNa > 40 mEq/L
Bartter and Schwartz criteria for SIADH
Decreased plasma osmolality (<275 mosm/kg)
Inappropriately concentrated urine (>100
mosm/kg) for hyponatremia
Euvolemic
Elevated urine Na (>20 mEq/L)
Exclude hipothyroidism, hypocortisolism and
diuretic use.
Drugs commonly associated with development
of SIADH
MANAGEMENT
 Principles of treatment in
hyponatremia
The most common and devastating effects of
hyponatremia are of CNS origin. Therefore, identifying
the risk factors that lead to hyponatremia and
instituting prompt treatment while avoiding
complications is crucial.
Although cerebral adaptation to low serum Na occurs
slowly, it protects the brain from deleterious effects of
hypo-osmolality. However, this protective mechanism
leaves the brain susceptible to osmotic demyelination
syndrome (ODS) during treatment, especially in
persons with chronic hyponatremia, if the correction is
rapid.

http://emedicine.medscape.com/article/907841-treatment
Effects of hyponatremia on the brain
and adaptive mechanism
 Management of hypovolemic
hyponatremia
Immediate goal : correct volume depletion with
normal saline.
Hemodynamically stable: correct hyponatremia
No consensus of optimal treatment of symptomatic
hyponatremia.
Relatively small increase in the serum Na
concentration (5%) substantially reduce cerebral
edema.
Recommended rate of correction 8-12 mEq/L/day.
In patients with seizure, 3% NaCl should be given
while volume depletion is being corrected.

http://emedicine.medscape.com/article/907841-treatment
 Management of normovolemic
hyponatremia
Syndrome of inappropriate antidiuretic hormone
secretion (SIADH)
fluid restriction (administration of normal saline)
Neurological emergency
3% NaCl + furosemide IV: raise serum Na until
symptoms resolve symptoms typically resolve with
rise in sodium of 3-7 mEq/L.
Dose of 3% NaCl : 1-2 mL/Kg
correction does not exceed 8 mEq/L/d
Furosemide: balance volume expansion by 3% Na
infusion
Dose 1-2 mg/kg

http://emedicine.medscape.com/article/907841-treatment
 Equations used in managing
hyponatremia
To estimate the effect of 1 L of any
infusate on serum Na concentration:
Change in Na concentration
= (infusate Na level - serum
Na level)/(total body water
+ 1)
Change in serum Na level =
[(infusate Na level +
infusate K level) - serum Na
level]/(total body water + 1)
Na concentrations of various fluids
used in pediatric practice
3% NaCl in water - 513 mEq/L
0.9% NaCl in water - 154
mEq/L
Ringer lactate solution - 130
mEq/L
0.45% NaCl in water - 77
mEq/L
0.2% NaCl in water - 34 mEq/L
5% dextrose in water - 0
mEq/L
http://emedicine.medscape.com/article/907841-treatment
 Medicolegal Pitfalls
Failure to consider the possibility of sampling error,
pseudohyponatremia (hyperglycemia,
hyperproteinemia, or hyperlipidemia)
Failure to recognize high-risk groups: patients on
diuretics, infants, postoperative patients, and patients
with malignancy.
Failure to recognize
severe acute hyponatremia ongoing risk of brainstem
herniation must correct it promptly
chronic hyponatremia rapid correction (>0.5 mEq/L/h or
12 mEq/L/d) risk of osmotic demyelination syndrome.