régulation de la natrémie : des concepts physiopathologiques à la pratique clinique bertrand...

Régulation de la natrémie :

des concepts physiopathologiques à

la pratique clinique

Bertrand Souweine, Clermont-Ferrand

Concepts physiopathologiques

NATREMIE

Taux de sodium dans le sang (Larousse, 1997)

Natrémie est mesurée habituellement dans le sérum

Natrémie exprimée en millimol/L

Raisonnement :

/ Kg H2O plasmatique

en milliosmol

Rappels physiopathologiques

Osmolarité : nb osmol / kg de plasma

Osmolalité : nb osmol / kg d’eau

Aquaporines Prix Nobel de chimie 2003

Edelman I, JCI 1958Edelman I, JCI 1958

H2O

Na

Rappels physiopathologiques

L’eau diffuse librement entre les compartiments

L’eau diffuse librement à travers la plupart des membranes

Certaines molécules (urée éthanol) diffusent également librement

Tonomoles : molécules non librement diffusibles

Les tonomoles induisent un gradient osmotique transfert d’eau

Eau diffuse pour égaliser [molécules] pression osmotiqueA l’équilibre, la pression osmotique est partout identique

H2O

TonomolesA, B, AB, CN=12

A

B

B

BA

AB

A

BC

AA

A

4 tonomoles dans compartiment 2

(C2)

8 tonomoles dans compartiment 1

(C1)

Nb Tonomole C1 /Vol C1 = Nb Tonomole C2 / Vol C2 8 / Vol C1 = 4 / Vol C2 Vol C1 / Vol C2 = 2

H2O

Transfert d’eau entre C1 et C2 [tonomole] C1 = [tonomole] C2

Eau diffuse pour égaliser [molécules] A l’équilibre, la pression osmotique est partout

identique

A

B

B

BA

AB

A

BC

AA

A

H2O

4 tonomoles / unité de volume

UréeN=12

UréeUréeUrée

Urée

Urée

Urée

Urée

Urée

Urée

UréeUrée

Urée

Osmolalité = 8 / unité de volume

60% Poids

Extracellulaire

1/3

Intracellulaire

2/3

Secteur interstitiel 3/4

Secteur vasculaire 1/4

Secteur

Cellulaire

Compartiments hydriques

Eau : 2/3 du poids de l’organisme

Verbalis 2003

Schematic representation of body fluid compartments in man

a 70-kg adult

Osmolalité Nae + Ke

=

H2O totale

Osmolalité Solutés EC + Soluté IC

=

H2O totale

= 285 mosmol/kgH2O

Na+> 90% Solutés EC K+ > 90% Solutés IC

Osmolalité 2 x (Nae + Ke)

=

H2O totale

A l’équilibre, l’osmolalité est partout identique

POsmol = Interstitielosmol = Cellosmol

PNa reflète l’osmolalité

K+

Na+

K+

Na+

Na+

Intracellulaire

ExtracellulaireInterstitiel

Vasculaire

Na+ = 15 mmol/L

K+

Na+

Na+

K +

Na+

K +K+

Na+

K+

Na+

K+

Na+

Na+

Intracellulaire


Vasculaire

Na+ = 15 mmol/L

K+

Na+

K+

Na+

Na+

K +

Na+

K +

Na+

K +

Na+

K +K+

Na+

K+

Na+

K+

Na+

Na+

Intracellulaire


Vasculaire

Na+ = 15 mmol/L

K+

Na+

K+

Na+

Na+

K +

Na+

K +

Na+

K +

Na+

K +K+

Na+

K+

Na+

K+

Na+

Na+

Intracellulaire


Vasculaire

Na+ = 15 mmol/L

K+

Na+

K+

Na+

Na+

K +

Na+

K +

Na+

K +

Na+

K +


Osmolalité2 x (Nae + Ke)

=

H2O totale

Si numérateur constant [2x(Nae+Ke)]

osmolalité inverse du dénominateur H2O totale

Osmolalité reflète l’hydratation cellulaire

PNa reflète l’hydratation cellulaire

Si POsmol (PNA) ; et 2x(Nae+Ke)= constant ; H2O totale

Hypernatrémie reflète une deshydratation cellulaire

Osmolalité reflète H2O totale


=

H2O totale


=

H2O totale

Si POsmol (PNA) ; et 2x(Nae+Ke)= constant ; H2O totale

Hyponatrémie reflète une hyperhydratation cellulaire

Si Osmolalité constante

toute osmEC // de VEC

Osmolalité reflète H2O totale Capital Na reflète VEC


=

H2O totale


=

H2O totale

OsmolalitéEC

osmEC

VEC

== OsmolalitéEC

osmEC

VEC

==

osmEC 2 x Na ;

capital Na reflète VEC

Si osmEC [capital Na] et Posmol = Constant VEC

Si osmEC [capital Na] et Posmol= Constant VEC

Typically daily water balance in a normal human

Source Water intake Source Water outputmL/day mL/day

Ingested water 1400 Urine 1500Water content of food 850 Skin 500Water of oxidation 350 Respiratory tract 400

Stool 200Total 2600 2660

Shiau YF, Ann Intern Med 1985

Les sorties de Na de K et d’eau sont réglées au niveau du rein

Adaptation du capital Na pour maintenir la volémie

Adaptation de la tonicité pour maintenir le volume cellulaire

Proximal convoluted tubule

Short loop nephron: absence of thin ascending limb70-80% of human nephrons

Long loop nephron

Distal convoluted tubule

Connecting tubule

Collecting duct

Thin descending limb

Thick ascending limb

Thin ascending limb

apical apicalbasal basal

Réabsorption tubulaire NaCl

Proximal tubuleIsoosmotic to plasma:water is isoosmotically reabsorbedNa+is the major driving force

Fluid volume entering the bend: upper limit of the urine flow if no further water reabsorpsion occurs

Thick ascending limb:diluting segment:separation of solutes from waterNa+/K+/2Cl-

Impermeable for water:osmolality decreases along the lenght

Ascending limbs: impermeable for water

Thin decending limbpermeable for water (AQP1)solute impermeable

From fish to philosopher: the story of our environmentSmith H 1953

The early provertebrates resided in a salt water environementwhose composition was similar to that of their own extracellular fluid. Therefore these animals could ingest salt water freely without altering the composition of their miluieu interieur

As early vertebrates migrated into freshwater streams the development of a more water impermeable tegument was necessary to avoid fluid dilution by the hypoosmotic fresh water environement

the concentrating capacity of the mammalian kidney contributed to the evolution of various

biologic species including man.

the glomerulus developed enabling the fish to filtrate excess fluid from the blood

the subsequent development of the tubule in vertebrates was seminal for preservation of sodium and excretion af excess solute-free water

Mécanisme de concentration à contre courant

d‘après Rose BD

The water permeability of the collecting tubules is extremely low but increases in the presence of AVP

d‘après Rose BD

Basolateral membrane

Urine

Apical membrane

Sang

Distal tube of the nephron

V2

Gs

cAMPATP

PKA

Adenylate cyclate

C-terminus phosphorylation

of AQP-2

AQP-2 insertion

Cytosolic storage vesicles

AVP

H2O

AQP-3

H2O

AQP-3

H2O

D’après Burton Rose

% du volume filtré encore présent dans le tube

d‘après Rose BD







d‘après Rose BD

Thick ascending limbReabsorption of Na+/K+/Cl-

Increase in interstitium tonicityDelivery of hypotonic fluid to distal tubeUrea poorly reabsorbed and retained in the tubule

Under vasopressin, tubular fluid equlibrates with the hypertonic interstitiumlow urea permeability allow its concentration to increase

Urea is reabsorbed and constitutes a significant component of the medullar interstitial tonicity

The increase in interstitial tonicity creates the obsmotic gradientthat abstracts water from the descending limb

[Na] in the tubular > interstitium passive reabsorption of NaCl in the water impermeable thin ascending limb

Model of urinary concentration

Cl-/Na+ Generation of medullary hypertonicity by• normal functioning of thick ascending limb• urea delivery• normal medullar blood flow

Mechanisms of urine concentration

⇘ Cl-/Na+ reabsorption Loop diuretics, osmotic diuretics, interstitial disease

H2ONa+/Cl-

Glomerular filtration

⇘ by age, renal disease

delivery of water determinedby glomerular filtration rate,proximal tubule H2O and solute reabsorption

H2O

Na+/Cl-

Thiazide: no impact on concentrating capacity

ureamembranes permeable to urea

⇘ [urea] medullary urea movement into the medulla

⇘ dietary intake of protein

⇗ AVP release/action: nephrogenic or central diabetes insipidus

vasopressin H2O

Mechanisms of urine dilution

Cl-/Na+ ⇘ Cl-/Na+ reabsorption loop diuretics, osmotic diuretics, interstitial disease

Collecting duct impermeable to water in absence of vasopressin or other antidiuretic substances⇗ water permeability by AVP, drugs

⇘ age, volume depletion, CHF, cirrhosis, nephrotic syndrome

Glomerular filtration

H2ONa+/Cl- delivery of water determined

by glomerular filtration rate,proximal tubule H2O reabsorptionand Na+/Cl- reabsorption

Thiazide diuretics

⇘ Na+/Cl- reabsorptionalter diluting capacity not concentrating capacity

Na+/Cl-

Adaptation de la tonicité

1% de osmolalité mécanisme d’adaptation

Contrôle des entrées : soif

Contrôle des sorties : excrétion rénale H2O régie par l’ADH

Sécrétion d’ADH : 2 stimuliHypovolémie et Hypotension indépendamment de la tonicitéHypertonie plasmatique

Rein : réabsorption/sécrétion H2O et Na indépendamment 50 mosmol/L <Uosmol < 1200 mosmol/L

d’après Robertson GL

AVP secretion in response to increases in plasma osmolality versus decreases in blood volume or blood pressure in human

subjects

d’après Robertson GL

Relationship between plasma AVP concentrations and plasma osmolality under conditions of varying blood volume and

pressure


1.11

Plasma water sodium : [Na+]pw

[Na+]pw = 1.11(Nae + Ke)/TBW - 25.6

- 25.6

Total body water osmolality = plasma water osmolality

[Na+]pw = 1.11(Nae + Ke)/TBW - 25.6

G/ Ø = slope

[Na+]pw = G/ Ø(Nae + Ke)/TBW -

y-intercept =

Nguyen, AmJ Physiol Ren Physiol 2004

[Na+]pw = 1.11(Nae + Ke)/TBW - 25.6

[Na+]pw = G/ Ø.(Nae + Ke)/TBW -

Ø: effectiveness of ions as independent osmotically active particles Osmotic coefficient for NaCl = 0.93 and for NaHCO3 = 0.96 [104/128 x 0.93] + [24/128 x 0.96]

Ø = 0.94


Both Ke and [K+]pw must independently affect [Na+]pw

ECF ICF

Ke in a 70-kg man, TBW = 42 liters,

KICF = 3,750 mmol (150 mmol/l x 25 liters)

KISF = 62 mmol (4.4 mmol/l x 14 liters)

KPl = 14 mmol (4.6 mmol/l x 3 liters)

Quantitatively, Ke will have a net incremental effect on the [Na+]pw

Ke and [K+]PW


y-intercept =


Titze J, AJKD 2002

do not contribute to the distribution of water between the EC and IC spaces

failure to consider osmotically inactive Nae and Ke will result in an overestimation of [Na+]pw


OsmolECF = osmotically active, extracellular non-Na+ and non-K+ osmoles OsmolICF = osmotically active, intracellular non-Na+ and non-K+ osmoles

osmolICF will tend to increase [Na+]pwosmolPl tend to lower [Na+]pw

osmolECF + osmolICF will tend to increase [Na+]pw

VPl = 1/5 de VEC

osmolECF will tend to increase [Na+]pw


Plasma water non-Na+ and non-K+ osmoles: glucose, Ca2+, Mg2+, Cl-…

Plasma water non-Na+ and non-K+ osmoles: glucose, Ca2+, Mg2+, Cl-… will have a dilutional effect by obligating the retention of water in the plasma space

↓[Na+]pw

H2O

Plasma I SF I CF

osmolpw

↓[Na+]pw

H2OH2O

Plasma I SF I CFPlasma I SF I CF

osmolpw


Physiological parameters that determine [Na+]PW

Parameter

G/Ø ⇗

(Nae + Ke)/TBW ⇗

(Naosm inactive + Kosm inactive)/TBW ⇘

(osmolECF + osmolICF)/TBW ⇗

[K+]PW ⇘

osmolPW/VPW ⇘

Effect of increase in the parameter

on [Na+]PW

Kurt I, Kidney int 2005

Quantification of renal water excretionCosmol = osmolar clairancevolume needed to excrete solutes at the the concentration of solutes in the plasma

Cwater = volume of free-solute water that had been added or subtracted from the isotonic portion of the urine (Cosmol) to create either hypotonic or hypertonic urine

V = urine volumeUosmol osmolurine = Uosmol x V

Posmol

Cosmol = Volume of urine Isotonic to plasma

Cwater = free solute water

Quantification of renal water excretionCwater = V x (1-Uosmol/Posmol)

V = Cosmol + Cwater Cwater = V - Cosmol

Cosmol = (Uosmol x V)/Posmol

Cwater = V - (Uosmol x V)/Posmol = V x (1-Uosmol/Posmol)

Hypotonic urine = Uosmol < Posmol and Cwater > 0

Isotonic urine = Uosmol = Posmol and Cwater = 0

Hypertonic urine = Uosmol > Posmol and Cwater < 0Excretion of free water in a polyuric patient without water intake:

the patient become hypernatremic

Failure to ecrete free water in settings of increase water intake: the patient become hyponatremic

Quantification of renal water excretion

Uurea is a major component of Uosmol

urea crosses cell membrane readily

urea do not influence PNa and vasopressin release

Posmol = 310 mosmolKg, PNa = 144 mmol/L

Uosmol = 620 mosmol, UNa = 5 mmol/L, UK = 43 mmol/L

Diurèse = 1 L

OsmolU

V

Cwater = V x (1-Uosm/Posm) = 1 x (1-620/310) = 1 x (1-2) = -1 litre

Réponse rénale est-elle vraiment adéquate ?

Cwater(e)= V x (1-[UNa+UK/PNa])

Cwater(e)= 1 x (1-[5+43/144]) = 1x (1-0.33) = +0.67 litre

La réponse rénale est inadéquate

=

Posmol

Cosmol

=

+ Cwater

+

Quantification of renal water excretion

Cwater(e)= V x (1-[UNa+UK] / PNa)

Plasmaosmol 280-290 mOsmol/KgH2O

Decrease

Suppression of thirst

Suppression of

vasopressin

Increase

Stimulation of thirst

Stimulation of vasopressin

Dilute

urine

Disorder involving urine dilution with

water intake

Hyponatremia

Disorder involving urine

concentration with water intake

Hypernatremia

Concentrated urine

Parikh C

Dysnatrémieen pratique clinique

Palewsky PM Ann Intern Med 1996

PNa >150 mmol/L in 0.2% of the 7836 patients admitted to a general hospital during a 3-month study period

Hypernatremia

PNa > 144 (?)

Primary Diagnoses for Patients with Hypernatremia PNa >150 mmol/L


Outcome Data


In 14 patients (14%), hypernatremia was judged to have contributed to associated morbidity and decreased functional

status at hospital discharge

Polderman KH CCM 1999

PNa > 149 mmol/L

8.7% 5.7%

Dans cette étude, pas d’impact pronostique de l’hypernatrémie présente à l’admission

SAPS II PNa >144 1 point !

Hypernatremia

Assess volume status

Euvolemia(no edema)

⇘ total body waterno change in total body Na

Hypovolemia⇘ total body water ++

⇘ total body Na

Hypervolemia⇗ total body water⇗ total body Na ++

UNa analysis

< 20 mmol/L variable> 20 mmol/L > 20 mmol/L

Extra renal losses

VomitingDiarrheaExcess sweatingFistulae

< 20 mmol/L

Hypernatremia

Renal losses

Osmotic or loop diureticsPostobstructionIntrinsic renal disease


Hypovolemia⇘ total body water ++

⇘ total body Na

UNa analysis

> 20 mmol/L

Parikh C

Hypervolemia⇗ total body water⇗ total body Na ++

> 20 mmol/L

Sodium gains

Primary hyper- aldosteronismCushingHypertonic dialysis fluid infusion

Euvolemia(no edema)

⇘ total body waterno change in total body Na

Renal losses

Diabetes insipidusHypodypsia

variable

Extra renal losses

Respiratorydermal

Hyponatrémie PNa <136 mmol/L, Adrogué HJ, NEJM 2000 PNa <134 mmol/L, Yeates KE, CMAJ 2004

Relationship between PNa and [Na+]PW

Y intercept

Naosm active

volemia (hypovolemia, euvolemia, hypervolemia)

Cwater(e)

measure UNa

Na = 138 mmol

Protides 70 g

PNa = 138 mmol/L

Osmolarité plasmatique

1 litre de plasma

Na = 138 mmol

Protides 70 g

PNa = 138 mmol/L


1 litre de plasma 930 mL d ’eau plasmatique

Protides précipités

Na = 138 mmol

Osmolalité liée au Na138 / 0.93 = 148 mmol/L

Osmolalité plasmatique

930 mL d ’eau plasmatique


Na = 138 mmol



930

mL

d’e

au p

lasm

atiq

ue



Na = 138 mmol





Na = 138 mmol



930

mL

d’e

au p

lasm

atiq

ue



Protides - glucides



Protides - glucides



810

mL

d’e

au p

lasm

atiq

ue

Protides - glucides



Protides - glucides



810

mL

d’e

au p

lasm

atiq

ue

Idem avec triglycérides, mannitol, éthanol, méthanol, éthylène glycol…

Isotonic hyponatremia

Na = 120 mmol

Glucose = 50 mmol/L

Protides : 70 g/L

PNa = 120 mmol/L

PNa c = 138 mmol


1 litre de plasma

Na = 120 mmol

Glucose = 50 mmol/L

Protides : 70 g/L

PNa = 120 mmol/L

PNa c = 138 mmol


1 litre de plasma

Isotonic hyponatremia

Isotonic fluid

isotonic mannitol…

Retention of large amounts of isotonic fluid

Occurrence without any transmembrane shift in water

Hypertonic hyponatremia

H2O

Solutes confined to the extracellular compartment: hyperglycemia, hypertonic mannitol…

Shift of water from inside cells to the extracellular space

Sick cell syndromeFlear and Singh 1973

Solutés

Hyponatrémie avec TO élargi

Guglielminotti, CCM 2002Guglielminotti CCM 2003Gill, Clin Biochem 2005

55 patients consécutifs avec PNa <130 mmol/L ; 22/55 TO élargi

23 opérations du genou consécutives, G1 (N=19) Na > -2 mmol/L et Posmol + G2 (N=14) Na < -2 mmol/L EFW non différents entre G1 et G2

19 patients consécutifs PNa <130 mmol/L ; 4 ont osmol >7 mosmol/kgAnomalies mb lymphocytaire sans // avec osmol

Hoorn NDT 2006

Aux urgences (St Antoine) sur 47018 passages en 2001, (Offenstadt 2003)

PNa <130 mmol/L, 1.5%PNa <120 mmol/L, 0.2%

Aux urgences (Lee 2000) sur 3784PNa < 130 mmol/L, 0.4%

En réanimation (St Antoine) sur 865 admissions en 2001, (Offenstadt 2003)

PNa <130 mmol/L, 14.8%PNa <120 mmol/L, 2.1%

Cub-Réa 1997-2001 ; 96193 patients, 1332 (1.4%) PNa <121 mmol/L

Hyponatrémie, incidence

4123 patients de gériatrie (Terzian 1994)

Hyponatrémie : 16% de décès hospitalier vs 8% (RR=1.95)

184 patients avec (Ellis SJ, 1995) PNa < 120 mmol/L

Coma : 11% ; DC attribuable : 4.3%

435 insuffisants cardiaques (Chin 1996) PNa < 135 mmol/L,

OR décès hospitalier : 2.2 [1.3-4.0] ; DDS allongée

171 insuffisants cardiaques (Krumholz 1999)

DDS allongée

168 patients (Nzerue 2003)

PNa < 115 mmol/L52.9% symptomatiques

4031 patients avec insuf card (Lee Jama 2003)

PNA < 136 mmol/L décès à J30 OR=1.53[1.14-2.05] ; à 1 an OR=1.46[1.19-

1.80]

Hyponatrémie : Pronostic ?

Scores génériques

SAPS II, PNa <125 mmol/L 5 points cf GCS 11-13 ou PAS entre 70-99

MPM : non

APACHE III, PNa <119 mmol/L 3 points (Hte >55%)

Scores de défaillances viscérales PNa généralement absente

Hyponatrémie : Pronostic ?

Caractéristiques des patients ayant une hyponatrémie en réanimation(source Cub-Réa 1997-2001, d'après Offenstadt 2003)

PNa <121 mmol/L Pas d'hyponatrémie pNo patients 1332 94861 <0,01Age (ans) 59,1+/-16,8 55,5+/-19 <0,01Femme (%) 50,4 41,8 <0,05Charlson = 2* 11+/-32 9+/-29 <0,01IGS2 42,3+/-19,6 36,9+/-22,1 <0,01IGS2, corrigé 37,3Oméga total 107,7+/-209,4 99,5+/-211,8 nsmortalité en réanimation (%) 17+/-37 17+/-37 nsmortalité hospitalière (%) 24+/-43 21+/-41 <0,05

*, >1 comorbidité ou 1 si comorbidité sévère

Incidence = 1.4%

Verbalis 2004

Hyponatremia


Hypovolemia⇘ total body water

⇘ total body Na

Hypervolemia⇗ total body water ++

⇗ total body Na

Euvolemia*(no edema)

⇗ total body waterno change in total body Na

> 20 mmol/L < 20 mmol/L > 20 mmol/L > 20 mmol/L< 20 mmol/L

UNa analysis

Parikh C

*The presence of normal or low BUN or serum uric acid levels are helpful laboratory correlates of normal ECF volume

Extra renal losses

VomitingDiarrheaThird spacing of fluids pancreatitis burns

< 20 mmol/L

Euvolemia(no edema)


Glucocorticoid deficiencyHypothyroidismStressDrugsSIADH

> 20 mmol/L

Hyponatremia

Renal losses

Diuretic excessMineralocorticoid deficiencySalt loss nephropathyRenal tubular acidosisKetonuriaOsmotic diuresisCerebral salt wasting



⇘ total body Na

UNa analysis

> 20 mmol/L


⇗ total body Na

> 20 mmol/L

Acute orChronique

Renal failure

< 20 mmol/L

Nephrotic syndromeCirrhosis

Cardiac Failure

Parikh C

Extra renal losses


< 20 mmol/L

Euvolemia(no edema)



> 20 mmol/L

Hyponatremia

Renal losses




⇘ total body Na

UNa analysis

> 20 mmol/L


⇗ total body Na

> 20 mmol/L

Acute orChronique

Renal failure

< 20 mmol/L


Cardiac Failure

< 20 mmol/L

Primary polydipsiaPoor dietary intake

Hyponatremia


UNa analysis

Extra renal losses


< 20 mmol/L

Renal losses



⇘ total body Na

> 20 mmol/L


⇗ total body Na

< 20 mmol/L


Cardiac Failure

Sécrétion d’ADH « volodépendante »

Absence d’ADH

< 20 mmol/L

Primary polydipsiaPoor dietary intake

Euvolemia(no edema)



> 20 mmol/L

Sécrétion d’ADH non « volodépendante »

> 20 mmol/L

Acute orChronique

Renal failure

Réduction néphronique

Principes thérapeutiques

Traitement symptomatique des conséquences de l’hyponatrémie

Traitement étiologique / éviction du facteur déclenchant

Traitement de l’hyponatrémie proprement dite

Principes thérapeutiques1) Ce qui est simple

Traitement symptomatique des conséquences de l’hyponatrémie

Coma : protection des voies aériennes / ventilation mécanique Convulsions : traitement anti-comitial

Traitement étiologique / éviction du facteur déclenchant

Hypovolémie absolue : apports de cristalloïdesrelative : diurétiques +/- albumine (Ascite / S Néphrotique)

Déficit hormonal : substitution

Éviction du médicament / toxique

Traitement de l’hyponatrémie proprement dite

Domaine de la médecine non factuelle…

« eminence based medicine or common sense medicine »

Hyponatrémie symptomatique ou non symptomatique (?)

Hyponatrémie aiguë ou chronique (?)

Sterns 1990

Treatement of hyponatremia

Prompt correction of serum Na may significantly improve survival

N=168

PNa < 115 mmol/L

à H48 : Survivants : PNA=127 mmol/L vs DC : PNa=119 mmol/L (P=0.0016)

FDR indépendant du caractère symptomatique ou non de l’hyponatrémie

Nzerue 2003


Licata 2003

HSS : 150 mL (1.4-4.6%) twice a day

NYHA Stage IV, EF <35%Furosemide in both groups 500mg-1000mg twice a dayDeath rate : 24/53 vs 47/54 ; p <0.001


The outcome in both group 1 and 2 patients, who were treated with intravenous sodium chloride therapy, was significantly better (P<.01) than that in group 3 patients, who were treated with fluid restriction.

Arieff 1999

G1, IV sodium chloride before the onset of repisatory insuficiency, G2, IV sodium chloride after respiratory insuficiency

N=17 N=22

N=14

0.7 mmol/L 0.8 mmol/L 0.1 mmol/L

mmol/L per hour

At present there is no consensus regarding the optimal treatment of

symptomatic hyponatremia

Horacio Adrogué

Current recommendations suggest the pace of correction be sufficient to reverse the manifestations of hypotonicity but not so rapid as to create significant risk for osmotic demyelination.

The rate of correction should be 8 mEq/l/day; for patients with severe symptoms, the initial rate should be 1–2 mEq/l/h. These limits may be exceeded with caution when the risks associated with continued hypotonicity are greater than those of osmotic demyelination.

Thus, although the benefits of prompt and aggressive treatment of hyponatremia have been demonstrated, it is important to remember that overly rapid correction of symptomatic hyponatremia can lead to osmotic demyelination and significant permanent neurologic deficits Adrogué 2005

Enfant 15 ans, Poids 40 kg / 1m70

PNa = 105 mmol/L, Uurée= 15 mmol/L, UNa = 10 mmol/L, UK = 10 mmol/L

Posmol = 220 milliosmol/KgH2O

Diurèse 1200 mL/hUosmol = [15 + 2x(10+10)] = 55 mmol/L,,

H2O = 0,6 x P x [(140/PNa) – 1] = 11 L, Cwater = 1 - 55/220 = +740 mL/L

Traitement : 9% NaCL : 2 L en 12 heures (600 mmol NaCl )

Elimination de la charge hydrique en 9 h

Furosémide 20 mg Uosmol = Posmol inhibition de Cwater positive

Si la dilution urinaire est adéquate le furosémide inhibe le pouvoir de dilution des urines et s’oppose à l’excrétion d’eau

libre

Hoorn Nephrol Dial Transplant 2006

T0, H2O = 0,6 x P 42L et PNa = 110 mmol/L Natot = H2O x PNa = 4400 mmol

H12, [H20 = 42L + H2O (1L)] = 43L Natot = 4400 (euvolémie)

PNa= 4400/43 = 102 mmol/L

En cas d’hyponatrémie avec dilution urinaire inadéquate, si l’hyperADH n’est pas volodépendant,

des apports isotoniques au plasma mais hypotoniques aux urines aggravent l’hyponatrémie

Homme 70 kg, SIADH, (euvolémique)PNa = 110 mmol/L, Uurée= 440 mmol/L, UNa = 60 mmol/L, UK = 20 mmol/LUosmol [440 + 2x(60+20)] = 600 mmol/LTraitement : 2 L de NaCl 9% en 12 heures soit 600 mmol NaCl SIADH en euvolémie élimination des 600 mmol

[Uosmol = 600 mmol/L] élimination des 600 mmol dans 1 litre de diurèseApports = 2 L gain net H2O = (2L - 1L) = 1L

régulation de la natrémie : des concepts physiopathologiques à la pratique clinique bertrand...

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