treatment of hypotonic hyponatremia - bsim...treatment of hypotonic hyponatremia ... - hypertonic...
Post on 12-Feb-2020
17 Views
Preview:
TRANSCRIPT
TREATMENT OF TREATMENT OF HYPOTONIC HYPOTONIC
HYPONATREMIAHYPONATREMIA
BSIM 2010 BSIM 2010 -- LeuvenLeuven
G. Decaux, MD, PhD (Erasme, Brussels, ULB)G. Decaux, MD, PhD (Erasme, Brussels, ULB)General Internal MedicineGeneral Internal Medicine
Na+e + K+
e
[ Na ] =
TBW
♂ 60 y BW 66 kg, TBW ± 33 L, SNa 140 mEq/L
TBW 1 L → SNa: 3% (or 4.2 mEq/L)
Retention or los of 33 mEq of Na+ or K+
→ SNa: 1 mEq/L
♀ 80 y BW 60 kg, TBW ± 25 L, SNa 140 mEq/L
TBW 1 L → SNa: 4% (or 5.6 mEq/L)
Retention or los of 25 mEq of Na+ or K+
→ SNa: 1 mEq/L
Data obtained from a rat model of SIADH
SNa (mEq/l)
90% survival
10% mortality
NaCl
24hr
24hr 72hr
NaCl
140
105
140
105
140
105
80-90% mortality (by ODS)
100% survival
100% survival
In rats increase of SNa by 15 mEq/l/d
is well tolerated (even acutely)
Re-induction of hyponatremia after overcorrection
reduces mortality particularly if rats are still
asymptomatic
NaCl
DDAVP
water
12580% survival
80-90% mortality
24hr 72hr
12-24hr
Soupart et al. Kidney Intern 1994; 45: 193-200
SNa 140 mEq/L
Na
x K+x
x
x
x
x
x
xx
xx
OO (organic osmolytes: Myo-
inositol, taurine,…)
Acute 20% dilution
x
x
x
x
x
x
x
xx
x
Brain volume expansion (skull tolerate 8-10%)
Nausea, emesis, headaches, coma, seizure
Risk of brain herniation, respiratory arrest and non
cardiogenic pulmonary oedema (hypoxemia)
H2O
H2O
x K+
(OO)
I
II
SNa 118 mEq/L Ventricular collapse
SNa 118 mEq/L
Na
x K+
x
x
xx
x
OO (Myo-inositol, taurine,…)
Rapid correction of SNa
SNa 140 mEq/LIntracellular hyperionisation and OO
depletion (5-7 days to reaccumulate)
Apoptose of the astrocytes
→ ODS (or CPM)
(Urea protect the cell from apoptosis)
48hr
H2O
Brain adaptation (24-48hr) by intracellular
solute depletion
Paucisymptomatic
xx
x
x
x
x
x x
x x
H2O
x
Na
I
ACUTE (< 48 hr) (usually < 125 mEq/l)
Generally hospital acquired
- Post operative
- Excessive IV hypotonic fluids with inappropriate antidiuresis
- Post-TURP syndrome (Uterine surgery with glycine irrigant, …)
- Oxytocine
- Recent thiazides prescription
- Polydypsia (acquired generally outside the hospital) (beer potomania)
- Exercise induced (acquired outside the hospital)
- Ecstasy
- Colonoscopy preparation (PEG plus excessive water intake)
- Desmopressin therapy for nocturnal enuresis
GENERALLY SYMPTOMATIC
Severe symptoms sometimes explosive in nature (coma, seizure)
- Hypertonic saline (NaCl 3%) furosemide (20-40 mg)
Rate of IV infusion: 1-2 ml/kg b.w./hr (increases the SNa by 1-2 mEq/l/hr and 2-4 mEq/l/hr if combined with
furosemide)
OR
- Bolus infusion of 150 ml of 3% NaCl repeat 10 min later if no improvement
- TARGET: interrupt correction when symptoms disappear
(rapid normalisation of the serum sodium usually safe but rarely necessary). Check SNa after 30 min, to be sure that
SNa is increasing (then each 2-4hr)
PROMPT CORRECTION MANDATORY
CHRONIC (> 48hr), subacute or unknown duration
Acquired outside the hospital
- Edema states
- SIADH
- Diuretics
- Digestive losses, excessive sweating, third space
- Salt losing nephropathy
- Cerebral salt wasting syndrome
- Polydypsia (often acute surimposed upon chronic hyponatremia)
- Endocrine (hypocorticism and hypoaldosteronism, hypothyroidism)
SYMPTOMATIC ASYMPTOMATIC
SYMPTOMATIC
- Obviously, electrolyte-free water intake must be
withheld
- NaCl 3% by controlled IV infusion
Rate of infusion 1-2 ml/kg b.w./hr during
4-5hr
OR
- 1 L NaCl 0.9%/12hr with urea (IV or by gastric
tube) 0.5 to 1 g/kg b.w. in one or two doses during
the first 24hr (except if volume depletion)
- TARGET: interrupt correction
if symptoms improvement and/or
- SNa > 10 mEq/l/24hr
INITIAL RAPID BUT LIMITEDCORRECTION
ASYMPTOMATIC
- Conservative measures:
. Withdrawal of causative factors(drugs, ...)
. Water restriction (SIADH, Edema states)
. Oral urea 0.5 gr/kg/24hr in one or two
doses (SIADH)
. Furosemide with salt supplements
(SIADH)
. Isotonic saline if salt depletion
. Captopril + Furosemide (heart failure)
. Dialysis (renal failure, cirrhosis)
. Hormonal substitution
. Fluorohydrocortisone (cerebral salt
wasting syndrome)
. V2 antagonist (Conivaptan; Tolvaptan)
NO NEED FOR RAPID CORRECTION
TABLE 2: RISK FACTORS FOR MYELINOLYSIS
• Major risk factors: daily magnitude of the SNa increase (SNa/24hr < 10-15 mEq/l)
• Hypokaliemia (SNa/24hr < 10 mEq/l/24hr)
• Alcoholism, malnutrition, cirrhosis… (SNa< 10 mEq/l)
• (most cases of myelinolysis: initial SNa < 115 mEq/l and SNa > 12 mEq/l/24hr)
• Isolated cases occurred after SNa of only 9 to10 mEq/l
General recommendations
- Salt depletion is treated by isotonic saline
- Initial rapid correction if severe symptoms
- Maximum SNa correction: 10-12 mEq/l/24hr and less than
8 mEq/l/24hr if associated risk factors for myelinolysis
(hypokalemia, malnutrition, alcoholism, liver disease, burns,
hypocorticism)
- Normalize kalemia before or during SNa correction
- Serum sodium must be initially monitored at least every 4 hours
- Administration of DDAVP if correction is too rapid
- Decrease SNa by DDAVP and “water” if necessary
Decaux G, Soupart A. Am J Med Sci 2003; 326(1): 25-30
Oya et al. Neurology 2001
Urea: intravenous* or by gastric tube 0.5 g/kg
b.w. (to max 1 g/kg b.w.) will increase osmolality
by 15 (to 30) mosm/kg H2O in 30 min
May be repeated if needed each 8-12hr
Urea protects against ODS
*Ureaphil (Abbott): bottle with 40 gm powder of sterile
urea to dilute with 105 ml of 5% glucose to obtain a final
volume of 135 ml of a 30% urea solution
ALTERNATIVE TREATMENTALTERNATIVE TREATMENTTO HYPERTONIC SALINETO HYPERTONIC SALINE
Javid M. Lancet 1961
Javid M. Surg. Clin. North Am. 1958, Aug, 38 (4): 907-928
Javid, Settlage. JAMA 1956, March 17; 160 (11): 943-949
Decreases rapidly brain edema
Increases SNa by osmotic diuresis and salt retention
No risk of inducing or increasing potassium deficit
(as with furosemide)
Easy to apply (electrolytes monitoring each 4hrs)
Decreases the risk of myelinolysis
USE OF UREA FOR TREATMENT OF USE OF UREA FOR TREATMENT OF SYMPTOMATIC HYPONATREMIASYMPTOMATIC HYPONATREMIA
Decaux G. et al. JAMA 1982; 247: 471-474
100
105
110
115
120
125
130
135
0 1 2
Days
SN
A (
mE
q/L
)
Isotonic saline
(1 or 2 L/day)
Urea
(0.5-1 g/kg/day)
-1 0 1 2
Days
0 4 hr 8 hr
Days
90
60
30
Urea (mg/dl)
1 L/12 hr
isotonic saline
urea(0.5 g/kg)
Figure 2
(
)A
(n = 35)
C(n = 10)
B(n = 12)
*
*
*
*
**
*
*
*
Decaux et al. Critical Care 2010; 14: R184
Easy formula: 1 ml/kg/hr of 3% NaCl will increase
SNa by 1 mmol/l/hr (assuming no renal
excretion !)
Example: - 60 kg woman with SIADH and a SNa of
110 mEq/l and and intended increase of 8 mEq/l
We will need to infuse 480 ml NaCl 3%
- or TBW (30 L) x 8 mEq/l = 240 mEq Na
or 240/513 = 0.468 l Na Cl 3%
CAUTION WITH HYPERTONICCAUTION WITH HYPERTONICSALINE (NACL 3%) INFUSIONSALINE (NACL 3%) INFUSION
Effect of diuresis and urine composition on SNa during
hypertonic saline infusion in the same patient
UNa + K Uosm Water excreted (WE) NTBW SNa
for 468 ml NaCl 3% (TBW + 0.46 - WE)
75 220 240/75 = 3.2 l 27.26 11
170 510 240/170 = 1.41 l 29.05 3.6
300 900 240/300 = 0.8 l 29.6 1
Decaux G., Soupart A. Am J Med Sci 2003; 326 (1): 25-30
Frequently spontaneous correction secondary to high
dilute urine output combined with water restriction
Often mixed disorder (solute depletion component)
1 or 2 of isotonic saline + KCl 30 mmol/l over 24hr
If SNa very low (< 110 mEq/l) likely SNa increase of no
more than 10-15 mEq/l/24hr
HYPONATREMIA RELATED TO HYPONATREMIA RELATED TO POLYDYPSIA OR BEER DRINKERSPOLYDYPSIA OR BEER DRINKERS
Most frequently elderly women
High risk of myelinolysis
Slow correction: 1 or 2 L isotonic saline with 40 mmol KCl/l
DIURETIC RELATED HYPONATREMIADIURETIC RELATED HYPONATREMIA
Excess NaCl administration
Potassium supplementation (SNa = Nae + Ke / H2O)
Unexpected increase in electrolyte free water
excretion (due to spontaneous hypoosmotic
polyuria, ADH inhibition by volume expansion, or
high solute output)
OVERCORRECTION OF OVERCORRECTION OF HYPONATREMIAHYPONATREMIA
Asymptomatic or early symptomatic
Decrease rapidly SNa (DDAVP + electrolyte
free water) so that SNa/24hr stay under 10 mEq/l
Other therapeutic options in myelinolysis:
- Thyreotropin releasing hormone (?)
- Immunoglobulins (?)
- Plasmapheresis (?)
- Corticosteroids (?)
- Minocycline (data obtained in rats)
OVERCORRECTION OF SNAOVERCORRECTION OF SNA
Is asymptomatic hyponatremia really
asymptomatic?
x
y
Posture and Gait Evaluation
• RSScan International® Platform
• Thousands of Pressure Sensors
• Measure displacement of the Pressure Center of the patient in different conditions
Renneboog B., Musch W. et al. Am J Med 2006
Response Time (RT)
Median RT in Hyponatremia: 673±182 msec.
Median RT in Normonatremia: 615±184 msec.
Difference = 58 msec (p<0.001)
ATTENTION TESTS
MEDIAN RESPONSE LATENCIES
0
100
200
300
400
500
600
700
800
900
1000
128 138
MEAN NATREMIA (mEq/L)
LA
TE
NC
Y (
ms
ec
)
Visual Vigilance
Digit Span
GO/NOGO
Intermodal Comparison
Divided Attention (sounds)
Divided Attention
(sounds+squares)
Phasic Alert 1-4
Phasic Alert 2-3
Renneboog B., Musch W. et al. Am J Med 2006
Renneboog B., Musch W. et al. Am J Med 2006
Table 1 : Baseline characteristics of patients and controls and site of bone fracture in patients.
Cases
Controls
SNa < 135
n = 76
SNa > 135
n = 446
Overall
n = 522
SNa < 135
n = 21
SNa> 135
n = 501
Overall
n = 522
Mean age (yrs) 81 ± 9 81± 8 80 ± 8 85 ± 6 81± 7 81 ± 7
Male/ Female 18/58 117/329 135 / 387 9 / 12 126/375 135 / 387
Mean SNa (mEq/L) 131. 3 ± 2.9 140.1 ± 3.2 138.8 ± 4.4 131. 4 ± 3.2 140.8 ± 7.7 140.43± 3.4
Hip and femoral fractures 44 242 286 NA*
Upper Limb Fractures 20 139 159
Fracture of other sites 12 65 77
* NA: Non applicable
Table 3: Prevalence of hyponatremia in patients and controls and Odds ratios
for bone fracture associated with hyponatremia
Patients (%)
n = 522
Controls (%)
n = 522
Unadjusted OR (CI) Adjusted OR (CI)
Hyponatremia 76 (14.55) 21 (4.23) 3.89 (2.35 - 6.45)* 4.12 (2.34 -7.59)*
OR: Odds ratio. CI: 95% confidence interval; * P< 0.001
Gankam Kengne F. et al. QJM 2008; 101: 583-588
Decaux G., Soupart A., Vassart G.Lancet 2008
Decaux G., Soupart A., Vassart G.Lancet 2008
Decaux G., Soupart A., Vassart G.Lancet 2008
W. Schrier, et al. N. Engl. J. Med. 2006; 355: 2099-2112
Table: Effect of urea in hypothetical case of inappropriate secretion of antidiuretic hormone compared with normal person receiving same intake of food and fluid
(Food intake shown as amount of solute of excretion in urine)
Daily intake Urinary composition
Urine volume (L/day)
Water balance (L/day)
Normal 500 mmol solute; 2 L Water*
250 mmol/L 2 0
Inappropriate secretion of hormone
500 mmol solute; 2 L Water*
500 mmol/L 1 + 1
Inappropriate secretion of hormone treated with 30 g urea daily
500 mmol solute; 500 mmol urea;2 L Water
500 mmol/L 2 0
*Intake minus insensible loss. Conversion: SI to traditional units – Intake and urinary composition:1 mmol = 1 mOsmol
Decaux G. et al. Br Med J 1981; 283: 1081-1083
Decaux G.Am J Med 2001; 110 (7): 582-584
CONSEQUENCES OF CHRONIC (>48hr) CONSEQUENCES OF CHRONIC (>48hr) HYPONATREMIAHYPONATREMIA
Mild to moderate chronic hyponatremia (HN) generally
considered « asymptomatic »: symptoms subtle and
difficult to detect
HN associated with
– Attention and posture deficit, gait instability
– Increased falls (> elderly)
– Bone fracture (non-vertebral > vertebral) (e.g. odds ratio BF/HN
4.1, mean SNa 131 mEq/l)
– Role of chronic HN in induction of osteoporosis (?)
THERAPEUTIC OPTIONS IN SIADHTHERAPEUTIC OPTIONS IN SIADH
Fluid restriction (< 1-1.5 l/day)
Furosemide + oral NaCl supplement (+ K sparing
diuretics)
Urea oral (15-30 g/day)
Demeclocycline
Vaptans (AVP-V2 receptor antagonists)
– Conivaptan* (IV, V1a/V2) (Vaprisol®)
– Tolvaptan* (oral, V2) (Samsca®)
– Satavaptan (oral, V2)
– Lexivaptan (oral, V2) (in development)
*FDA approved
Decaux G., Musch W., Soupart A. Acta Clin Belgica 2010
40mg Furosemide
NaCl 3g P.O.
115
120
125
130
135
140
-2 -1 0 1 2
Days
SN
A (
mE
q/L
)
Urea (mg/dl) 100
90
80
70
60
50
40
30
20
(
) *
* *
Isotonic saline or halfIsotonic saline
Urea(15-120 g/d)
Decaux et al. Critical Care 2010; 14: R184
Evolution of SNa and blood urea in 50 patients before and after urea therapy in ICU
Months0 2 4 6 8 10 12 0 2 4 6 8 10 12
140
135
130
125
SNa
(mEq/l) VAPTANS UREADRUG
HOLIDAY
8 DAYS
Figure 1
N = 12
Soupart A., Decaux G. Submitted
TOLERANCE TO VAPTANS AND UREA (1)TOLERANCE TO VAPTANS AND UREA (1)
Vaptans (about 10-20% failure)
– Thirst
– Orthostatic hypotension
– Nausea
– Polyuria
– Hypernatremia (≈ 5%) or overcorrection
(> 8 mEq/l/24hr) (≈ 10%)
Urea
– Poor palatal taste (decreases with time), gastric intolerance:
withdrawal (≈ 15%)
Take after meal + orange juice
– Contraindications
• Gastric ulcer, hemorrhage
• Renal failure
• Liver failure, hepatic encephalopathy
TOLERANCE TO VAPTANS AND UREA (2)TOLERANCE TO VAPTANS AND UREA (2)
Both treatments well tolerated, no major side effects
Vaptans
– One patient stopped Tolvaptan for excessive thirst
Urea
– One episode of hypernatremia (155 mEq/l) at admission for
pneumonia
Complete recovery
Drug holiday
– One patient falled during dry holiday period (Satavaptan) with wrist
fracture (SNa 123 mEq/l)
Second fall after urea withdrawal with a hip fracture (SNa 126 mEq/l)
CONCLUSIONSCONCLUSIONS
Urea shows similar efficacy than vaptans for
treatment of chronic hyponatremia due to
SIADH
Tolerance is good in both groups
Vaptan will likely be particularly useful for
hyponatremia associated with cirrhosis and
cardiac failure
top related