cme hyponatraemia: an evidence-based approach hyponatremia · diagnostic pathway hyponatremia no...
TRANSCRIPT
4/19/2013
1
Newcastle Endocrinology
Hyponatremia a diagnostic approach
Dr Steve Ball The Medical School
CME Hyponatraemia: an evidence-based approach
Newcastle Endocrinology
The trouble with guidelines why we struggle
Too complex more information than need
Too simple
They don’t say anything useful
Contradictory
…..Evidence-based?
4/19/2013
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Newcastle Endocrinology
Diagnostic algorithms what’s new?
Design user-sensitive
Evidence-based approach weighting proportionate to
diagnostic utility urine osmolality
urine Na+
volume status
Newcastle Endocrinology
Traditional algorithms clinical assessment of volume status is not reliable
How good is assessment of volume status? hypovolemia, euvolemia, hypervolemia
sensitivity 0.49
specificity 0.47
independent of Na+ status
How useful is assessment of volume status? do algorithms based on volume status work?
frequent misdiagnosis
impact of removing ECF assessment substituting frurate excretion improves accuracy
Fenske W, Maier SKG, Blechschmidt A, Allolio B, Stork S. 2010 Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study The American Journal of Medicine 123: 652-657
Musch W, Thimpont J, Vandevelde D, Verhaeverbeke I, Berghmans T, Decaux G 1995. Combined fractional excretion of sodium and urea better predicts response to saline in hyponatremia than do usual clinical and biochemical parameters.The American Journal of Medicine 98: 348-355
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Newcastle Endocrinology
If ECF expanded consider Heart Failure Liver cirrhosis Nephrotic syndrome
≥30 mmol/L <30 mmol/L
Primary polydipsia Inappropriate iv. fluid Low solute intake Beer potomania
<100 mOsm/kg ≥100 mOsm/kg
No Urine osmolality
Low effective arterial volume
No If ECF contracted consider Vomiting Primary adrenal failure Renal salt wasting Cerebral salt wasting
Urine Na+
Yes Consider immediate treatment with 3% NaCl
Exclude non-hypotonic hyponatremia
Hyponatremia diagnostic pathway
Hyponatremia
No
< 100 mOsm/kg ≥ 100 mOsm/kg
< 30 mmol/l ≥ 30 mmol/l
Consider
-Primary polydipsia
-Low solute intake
-Beer potomania
Urine osmolality
Urine sodium
Exclude hyperglycemia and other
causes of non-hypotonic hyponatremia
Consider immediate treatment
with hypertonic saline
Hypotonic hyponatremia
Yes
If ECF contracted consider
-Vomiting
-1° adrenal insufficiency
-Renal salt wasting
-Cerebral salt wasting
If ECF normal consider
-SIADH
-2° adrenal insufficiency
-(Hypothyroidism)
Consider occult diuretics as
cause
If ECF expanded consider
-Heart failure
-Liver cirrhosis
-Nephrotic syndrome
If ECF contracted consider
-Diarrhea and vomiting
-Third spacing
-Remote diuretics
Consider diuretics as cause
Still consider all other causes
Patient on
diuretics?
Acute or severe
symptoms?
NoYes
Low effective arterial
blood volume
If ECF normal consider SIADH Secondary adrenal failure (Hypothyroidism)
If ECF contracted consider GI loss Third space loss Previous diuretic use
Consider occult diuretics
Patient on diuretics?
Acute or severe symptoms?
Yes Consider diuretics Consider all other processes
Newcastle Endocrinology
Diagnostic algorithm is it really hyponatremia?
Exclude non-hypotonic hyponatremia
e.g. hyperglycemia
4/19/2013
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Newcastle Endocrinology
Pseudohyponatremia causes
Context Serum osmolality Agent
Effective
osmolytes
Isotonic/hypertonic Glucose
Mannitol
Glycine
Sorbitol
HTK
Hyperosmolar contrast media
Ineffective
osmolytes
Isotonic /hypertonic Urea
Alcohols
Ethylene Glycol
Lactate
Artifact Isotonic Lipids
Immunoglobulin
Newcastle Endocrinology
Effect of solid-phase components low Na+ artifacts in dilution-based methods
Increased solid-phase fraction
Normal solid-phase fraction
Aqueous phase
Solid phase
Standard volume diluent added
Standard volume diluent added
4/19/2013
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Newcastle Endocrinology
Hyponatremia Na+ measurement by direct potentiometry
No dilution step independent of solid phase fraction
Aqueous phase
Solid phase
Newcastle Endocrinology
Diagnostic algorithm urine osmolality
Excess water intake uOsm <100 mOsm/kg
AVP action uOsm >pOsm
The ‘grey area’ SIAD & excess water intake?
Hsu Y-J, Chiu J-S, Lu K-C, Chau T, Lin S-H 2005. Biochemical and etiological characteristics of acute hyponatremia in the emergency department The Journal of Emergency Medicine 29: 369-374
Uri
ne o
sm
ola
lity
(m
Osm
ol/kg
)
-ve
Binary model
probability
of AVP action
No AVP action
Continuous model
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100
>pOsm
+ve Primary polydipsia Inappropriate iv. fluid Low solute intake Beer potomania
<100 mOsm/kg ≥100 mOsm/kg
No Urine osmolality
Urine Na+
4/19/2013
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Newcastle Endocrinology
Diagnostic algorithm why urine Na+ is central
≥30 mmol/L <30 mmol/L Low effective arterial
volume
Urine Na+
Newcastle Endocrinology
Diagnostic algorithm hypovolemia vs. euvolemia by uNa+
The effect of diuretics uNa+ <30 mmol/L (no diuretics)
sensitivity 1.0
specificity 0.69
uNa+ <30 mmol/L (diuretics) sensitivity 0.94
specificity 0.24
Fenske W, Maier SKG, Blechschmidt A, Allolio B, Stork S. 2010 Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study The American Journal of Medicine 123: 652-657
Thresholds & cut-offs uNa+ <30 mmol/L
sensitivity 0.87-1.0
specificity 0.52-0.83
uNa+ <20 or <50 mmol/L lower sensitivity
lower specificity
Hato T, Hellman R, Ng R 2010. Diagnostic value of urine sodium concentration in hyponatremia due to syndrome of inappropriate antidiuresis (SIAD) versus hypovolemia. American Journal of Kidney Diseases; 55: B63.
4/19/2013
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Newcastle Endocrinology
Additional diagnostic testing serum urate & fractional urate excretion
Diuretics uNa+ >30 mmol/L
not diagnostic
SIAD in patients on diuretics serum urate <4 mg/dl
fractional urate excretion >12%
Fenske W, Stork S, Koschker A-C, Blechschmidt K, Lorenz D, Wortmann S, Allolio B. 2008. Value of Fractional Uric Acid Excretion in Differential Diagnosis of Hyponatremic Patients on Diuretics. Journal of Clinical Endocrinology & Metabolism; 93: 2991-2997.
≥30 mmol/L
If ECF normal consider SIADH
Patient on diuretics?
Yes Consider diuretics Consider all other processes
Newcastle Endocrinology
Diagnosis of SIAD AVP fingerprint when there should be none
Essential features hyponatraemia
sOsm <275 mOsm/kg
uOsm >100 mOsm/kg sub-maximum dilution
urine Na+ >30 mmoles/L normal Na+ intake
absence of confounders hypovolaemia
non-osmotic AVP release
oedema
adrenal & thyroid function
Supporting features serum urate <0.24 mmol/L
fractional urate excretion >12%
fractional Na+ excretion >0.5-1%
fractional urea excretion >55%
serum urea <3.6 mmol/L
FIG. 7. Fluid intake, urine sodium, serum sodium
concentration, and body weight during a 7 day study of W.
F. Ainlmuni osmolality of urine (based on 2 X [Na] + [1K])
ranged from 280 to 440 on days 4 through 7.
Schwartz WB, Bennett W, Curelop S, Bartter FC. 1957 A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. The American Journal of Medicine 23: 529
4/19/2013
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Newcastle Endocrinology
Cerebral salt wasting natriuresis, hyponatremia & volume depletion
History
CSW vs. SIADH
Mechanisms sympathetic NS
pressure natriuresis
natriuretic peptides
Problems definition
diagnosis
mechanism
absence of understanding vs. evidence of absence
Characteristic SIAD CSW
Na+ balance - --
BP ↓
Circulating vol. ↑ ↓
Natruiretic peptides ↑ ↑
AVP ↑ ↑
PRA ↓ ↓
serum urate ↓ ↓
serum urea ↓ ↑
Newcastle Endocrinology
If ECF expanded consider Heart Failure Liver cirrhosis Nephrotic syndrome
≥30 mmol/L <30 mmol/L
Primary polydipsia Inappropriate iv. fluid Low solute intake Beer potomania
<100 mOsm/kg ≥100 mOsm/kg
No Urine osmolality
Low effective arterial volume
No If ECF contracted consider Vomiting Primary adrenal failure Renal salt wasting Cerebral salt wasting
Urine Na+
Yes Consider immediate treatment with 3% NaCl
Exclude non-hypotonic hyponatremia
Hyponatremia diagnostic pathway
Hyponatremia
No
< 100 mOsm/kg ≥ 100 mOsm/kg
< 30 mmol/l ≥ 30 mmol/l
Consider
-Primary polydipsia
-Low solute intake
-Beer potomania
Urine osmolality
Urine sodium
Exclude hyperglycemia and other
causes of non-hypotonic hyponatremia
Consider immediate treatment
with hypertonic saline
Hypotonic hyponatremia
Yes
If ECF contracted consider
-Vomiting
-1° adrenal insufficiency
-Renal salt wasting
-Cerebral salt wasting
If ECF normal consider
-SIADH
-2° adrenal insufficiency
-(Hypothyroidism)
Consider occult diuretics as
cause
If ECF expanded consider
-Heart failure
-Liver cirrhosis
-Nephrotic syndrome
If ECF contracted consider
-Diarrhea and vomiting
-Third spacing
-Remote diuretics
Consider diuretics as cause
Still consider all other causes
Patient on
diuretics?
Acute or severe
symptoms?
NoYes
Low effective arterial
blood volume
If ECF normal consider SIADH Secondary adrenal failure (Hypothyroidism)
If ECF contracted consider GI loss Third space loss Previous diuretic use
Consider occult diuretics
Patient on diuretics?
Acute or severe symptoms?
Yes Consider diuretics Consider all other processes
4/19/2013
9
Newcastle Endocrinology
Hyponatremia a diagnostic approach
Dr Steve Ball The Medical School
CME Hyponatraemia: an evidence-based approach