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

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

Tonomoles A, B, AB, C A N=12 A H2O H2O AB B C B Eau diffuse pour égaliser [molécules]  pression osmotique A l’équilibre, la pression osmotique est partout identique 8 tonomoles dans compartiment 1 (C1) 4 tonomoles dans compartiment 2 (C2) Tonomoles A, B, AB, C N=12 A B A AB B C H2O Transfert d’eau entre C1 et C2  [tonomole] C1 = [tonomole] C2 H2O Osmolalité mesure la concentration de l’ensemble des molécule par kg d’eau La tonicité somme des concentrations de l’ensemble des substances diffusibles et non diffusibles dissoute dans 1 kg d’eau Nb Tonomole C1 /Vol C1 = Nb Tonomole C2 / Vol C2 8 / Vol C1 = 4 / Vol C2  Vol C1 / Vol C2 = 2

Eau diffuse pour égaliser [molécules] A l’équilibre, la pression osmotique est partout identique Urée A B A AB B C Urée N=12 H2O Osmolalité mesure la concentration de l’ensemble des molécule par kg d’eau La tonicité somme des concentrations de l’ensemble des substances diffusibles et non diffusibles dissoute dans 1 kg d’eau 4 tonomoles / unité de volume Osmolalité = 8 / unité de volume

Secteur interstitiel 3/4 Compartiments hydriques Eau : 2/3 du poids de l’organisme 60% Poids Extra cellulaire 1/3 Intra cellulaire 2/3 Secteur interstitiel 3/4 Secteur vasculaire 1/4 Secteur Cellulaire

Schematic representation of body fluid compartments in man a 70-kg adult Verbalis 2003

Osmolalité Solutés EC + Soluté IC = H2O totale = 285 mosmol/kgH2O Na+> 90% Solutés EC K+ > 90% Solutés IC Osmolalité Nae + Ke = H2O totale Osmolalité 2 x (Nae + Ke) = H2O totale A l’équilibre, l’osmolalité est partout identique POsmol = Interstitielosmol = Cellosmol PNa reflète l’osmolalité

Osmolalité reflète 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 Si POsmol (PNA)  ; et 2x(Nae+Ke)= constant ;  H2O totale Hyponatrémie reflète une hyperhydratation cellulaire

Osmolalité reflète H2O totale Capital Na reflète VEC Si Osmolalité constante toute   osmEC   // de 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 

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 Shiau YF, Ann Intern Med 1985

Connecting tubule Collecting duct Proximal convoluted tubule Distal convoluted tubule Short loop nephron: absence of thin ascending limb 70-80% of human nephrons Long loop nephron Thick ascending limb Thin descending limb Thin ascending limb

Réabsorption tubulaire NaCl basal apical Le mécanisme général de la réabsorption de Na dans le néphron s’appuie sur la création d’un gradient électrochimique liée à la pompe Na-K ATPase basolatérale. Ce gradient autorise le transport de Na de la lumière vers l’espace interstitiel. Au pole apical (urinaire de la cellule) existe des transporteurs de Na couplés à un co-transport (molécules : glu, aa ;..) ou ions (K,Cl,NH4,H). Seul le collecteur exprime des transporteurs apicaux de Na non couplés. Au niveau de la BLA Le transporteur NaKCL2 permet le transport de ces ions. Le Na/K est extrusé au pole basal par Na-K-ATPase. Le Cl est extrusé par 2 transporteurs ClC-Ka et ClC-Kb qui se couplent à une protéine Barterine pour constituer le canal. L’extrusion du K au pole luminale au travers de ROMK permet de créer un gradient électrochimique entre la lumière et l’interstitium pour faciliter la diffusion intercellulaire des cations (Ca2+, Mg, K).

Proximal tubule Isoosmotic to plasma: water is isoosmotically reabsorbed Na+is the major driving force Ascending limbs: impermeable for water Thick ascending limb: diluting segment: separation of solutes from water Na+/K+/2Cl- Impermeable for water: osmolality decreases along the lenght Thin decending limb permeable for water (AQP1) solute impermeable Fluid volume entering the bend: upper limit of the urine flow if no further water reabsorpsion occurs

From fish to philosopher: the story of our environment Smith 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

Cytosolic storage vesicles Distal tube of the nephron Basolateral membrane Apical membrane H2O Cytosolic storage vesicles C-terminus phosphorylation of AQP-2 Gs cAMP ATP PKA Adenylate cyclate AQP-2 insertion AVP V2 Sang Urine

Model of urinary concentration Thick ascending limb Reabsorption of Na+/K+/Cl- Increase in interstitium tonicity Delivery of hypotonic fluid to distal tube Urea poorly reabsorbed and retained in the tubule Under vasopressin, tubular fluid equlibrates with the hypertonic interstitium low 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 gradient that abstracts water from the descending limb [Na] in the tubular > interstitium passive reabsorption of NaCl in the water impermeable thin ascending limb

Mechanisms of urine concentration Na+/Cl- Thiazide: no impact on concentrating capacity H2O Na+/Cl- Glomerular filtration ⇘ by age, renal disease delivery of water determined by glomerular filtration rate, proximal tubule H2O and solute reabsorption H2O Cl-/Na+ Generation of medullary hypertonicity by normal functioning of thick ascending limb urea delivery normal medullar blood flow ⇘ Cl-/Na+ reabsorption Loop diuretics, osmotic diuretics, interstitial disease urea membranes 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 Thiazide diuretics ⇘ Na+/Cl- reabsorption alter diluting capacity not concentrating capacity Na+/Cl- ⇘ age, volume depletion, CHF, cirrhosis, nephrotic syndrome Glomerular filtration H2O Na+/Cl- delivery of water determined by glomerular filtration rate, proximal tubule H2O reabsorption and Na+/Cl- reabsorption 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

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 stimuli Hypovolémie et Hypotension indépendamment de la tonicité Hypertonie plasmatique Rein : réabsorption/sécrétion H2O et Na indépendamment 50 mosmol/L <Uosmol < 1200 mosmol/L

AVP secretion in response to increases in plasma osmolality versus decreases in blood volume or blood pressure in human subjects Comparative sensitivity of 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 d’après Robertson GL

Plasma water sodium : [Na+]pw [Na+]pw = 1.11(Nae + Ke)/TBW - 25.6

[Na+]pw = 1.11(Nae + Ke)/TBW - 25.6 Total body water osmolality = plasma water osmolality [Na+]pw = G/ Ø(Nae + Ke)/TBW - G/ Ø = slope y-intercept = Nguyen, AmJ Physiol Ren Physiol 2004

Ø: effectiveness of ions as independent osmotically active particles [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 Nguyen, AmJ Physiol Ren Physiol 2004

Ke and [K+]PW 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 Nguyen, AmJ Physiol Ren Physiol 2004

y-intercept = Nguyen, AmJ Physiol Ren Physiol 2004

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 exchangeable Na+ in bone and a major portion of intracellular K+ are bound and are, therefore, osmotically inactive Titze et al. (21) reported Na+ accumulation in an osmotically inactive form in human subjects in a terrestrial space station simulation study and suggested the existence of an osmotically inactive Na+ reservoir that exchanges Na+ with the extracellular space. these findings provide convincing evidence for the existence of an osmotically inactive Na+ and K+ reservoir. These osmotically inactive Nae and Ke are "ineffective osmoles," and they do not contribute to the distribution of water between the extracellular and intracellular spaces. Because Nae and Ke in the Edelman equation include osmotically active as well as osmotically inactive components, failure to consider osmotically inactive Nae and Ke will result in an overestimation of [Na+]pw. (OsmolECF + osmolICF)/TBW Nguyen, AmJ Physiol Ren Physiol 2004

osmolPl tend to lower [Na+]pw osmolICF will tend to increase [Na+]pw OsmolECF = osmotically active, extracellular non-Na+ and non-K+ osmoles OsmolICF = osmotically active, intracellular non-Na+ and non-K+ osmoles osmolPl tend to lower [Na+]pw osmolICF will tend to increase [Na+]pw VPl = 1/5 de VEC osmolECF will tend to increase [Na+]pw the presence of osmotically active, non-Na+ and non-K+ osmoles in the intracellular compartment (osmolICF) will tend to increase [Na+]pw by promoting the osmotic shift of water from the plasma space into the intracellular compartment non-Na+ and non-K+ osmoles in the extracellular compartment (osmolECF) include osmoles in both the plasma space and the ISF the presence of osmotically active, non-Na+ and non-K+ osmoles in the plasma space will promote water shift from the ISF and intracellular compartment to the plasma space, thereby lowering the [Na+]pw. Because only one-fifth of the extracellular fluid (ECF) is confined to the plasma space (18), it is not surprising that quantitatively the presence of osmotically active, non-Na+ and non-K+ osmoles in the extracellular compartment (osmolECF) will have a net effect of increasing [Na+]pw osmolECF + osmolICF will tend to increase [Na+]pw Nguyen, AmJ Physiol Ren Physiol 2004

Plasma water non-Na+ and non-K+ osmoles: glucose, Ca2+, Mg2+, Cl-… the presence of osmotically active, plasma water non-Na+ and non-K+ osmoles (for example, glucose, Ca2+, Mg2+, Cl-, ) will have a dilutional effect on [Na+]pw by obligating the retention of water in the plasma space 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 Nguyen, AmJ Physiol Ren Physiol 2004

Physiological parameters that determine [Na+]PW (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 excretion Cosmol = osmolar clairance volume 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 Cosmol = Volume of urine Isotonic to plasma V = urine volume Uosmol osmolurine = Uosmol x V Posmol Cwater = free solute water

Quantification of renal water excretion Cwater = 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 < 0 Excretion 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 = Posmol Cosmol + Cwater 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

Quantification of renal water excretion Cwater(e)= V x (1-[UNa+UK] / PNa)

Suppression of vasopressin Increase Plasmaosmol 280-290 mOsmol/KgH2O Decrease Suppression of thirst Suppression of vasopressin Increase Stimulation of thirst Stimulation of vasopressin Dilute urine Concentrated urine Disorder involving urine dilution with water intake Hyponatremia Disorder involving urine concentration with water intake Hypernatremia Parikh C

Dysnatrémie en pratique clinique

Hypernatremia PNa > 144 (?) PNa >150 mmol/L in 0.2% of the 7836 patients admitted to a general hospital during a 3-month study period Palewsky PM Ann Intern Med 1996

Primary Diagnoses for Patients with Hypernatremia PNa >150 mmol/L Palewsky PM Ann Intern Med 1996

Palewsky PM Ann Intern Med 1996

Outcome Data In 14 patients (14%), hypernatremia was judged to have contributed to associated morbidity and decreased functional status at hospital discharge Palewsky PM Ann Intern Med 1996

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 ! Polderman KH CCM 1999

no change in total body Na Hypernatremia Assess volume status Euvolemia (no edema) ⇘ total body water no 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

no change in total body Na Hypernatremia Renal losses Osmotic or loop diuretics Postobstruction Intrinsic renal disease Assess volume status Hypovolemia ⇘ total body water ++ ⇘ total body Na UNa analysis > 20 mmol/L Hypervolemia ⇗ total body water ⇗ total body Na ++ > 20 mmol/L Sodium gains Primary hyper- aldosteronism Cushing Hypertonic dialysis fluid infusion Euvolemia (no edema) ⇘ total body water no change in total body Na Renal losses Diabetes insipidus Hypodypsia variable Extra renal losses Respiratory dermal Extra renal losses Vomiting Diarrhea Excess sweating Fistulae < 20 mmol/L Parikh C

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

Relationship between PNa and [Na+]PW

Isotonic hyponatremia Relationship between PNa and [Na+]PW Isotonic hyponatremia Idem avec triglycérides, mannitol, éthanol, méthanol, éthylène glycol…

Isotonic hyponatremia Retention of large amounts of isotonic fluid Isotonic fluid Occurrence without any transmembrane shift in water isotonic mannitol…

Hypertonic hyponatremia Shift of water from inside cells to the extracellular space H2O Solutes confined to the extracellular compartment: hyperglycemia, hypertonic mannitol…

Sick cell syndrome Solutés Hyponatrémie avec TO élargi Flear and Singh 1973 Solutés Hyponatrémie avec TO élargi 55 patients consécutifs avec PNa <130 mmol/L ; 22/55 TO élargi 23 opérations du genou consécutives, G1 (N=19) DNa > -2 mmol/L et DPosmol +  G2 (N=14) DNa < -2 mmol/L EFW non différents entre G1 et G2 19 patients consécutifs PNa <130 mmol/L ; 4 ont Dosmol >7 mosmol/kg Anomalies mb lymphocytaire sans // avec Dosmol Guglielminotti, CCM 2002 Guglielminotti CCM 2003 Gill, Clin Biochem 2005

Hoorn NDT 2006

Hyponatrémie, incidence 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 3784 PNa < 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 : Pronostic ? 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/L 52.9% 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

Incidence = 1.4%

Verbalis 2004

no change in total body Na Hyponatremia Assess volume status Hypovolemia ⇘ total body water ⇘ total body Na Hypervolemia ⇗ total body water ++ ⇗ total body Na Euvolemia* (no edema) ⇗ total body water no change in total body Na UNa analysis > 20 mmol/L < 20 mmol/L *The presence of normal or low BUN or serum uric acid levels are helpful laboratory correlates of normal ECF volume Parikh C

no change in total body Na Hyponatremia Renal losses Diuretic excess Mineralocorticoid deficiency Salt loss nephropathy Renal tubular acidosis Ketonuria Osmotic diuresis Cerebral salt wasting Assess volume status Hypovolemia ⇘ total body water ⇘ total body Na UNa analysis > 20 mmol/L Hypervolemia ⇗ total body water ++ ⇗ total body Na > 20 mmol/L Acute or Chronique Renal failure Euvolemia (no edema) ⇗ total body water no change in total body Na Glucocorticoid deficiency Hypothyroidism Stress Drugs SIADH > 20 mmol/L < 20 mmol/L Nephrotic syndrome Cirrhosis Cardiac Failure Extra renal losses Vomiting Diarrhea Third spacing of fluids pancreatitis burns < 20 mmol/L Parikh C

no change in total body Na Hyponatremia Assess volume status Hypovolemia ⇘ total body water ⇘ total body Na Euvolemia (no edema) ⇗ total body water no change in total body Na Hypervolemia ⇗ total body water ++ ⇗ total body Na UNa analysis > 20 mmol/L < 20 mmol/L > 20 mmol/L > 20 mmol/L < 20 mmol/L Renal losses Diuretic excess Mineralocorticoid deficiency Salt loss nephropathy Renal tubular acidosis Ketonuria Osmotic diuresis Cerebral salt wasting Extra renal losses Vomiting Diarrhea Third spacing of fluids pancreatitis burns Glucocorticoid deficiency Hypothyroidism Stress Drugs SIADH Acute or Chronique Renal failure Nephrotic syndrome Cirrhosis Cardiac Failure < 20 mmol/L Primary polydipsia Poor dietary intake

no change in total body Na UNa analysis Extra renal losses Vomiting Diarrhea Third spacing of fluids pancreatitis burns < 20 mmol/L Renal losses Diuretic excess Mineralocorticoid deficiency Salt loss nephropathy Renal tubular acidosis Ketonuria Osmotic diuresis Cerebral salt wasting Hypovolemia ⇘ total body water ⇘ total body Na > 20 mmol/L Hypervolemia ⇗ total body water ++ ⇗ total body Na Nephrotic syndrome Cirrhosis Cardiac Failure Sécrétion d’ADH « volodépendante » Hyponatremia Glucocorticoid deficiency Hypothyroidism Stress Drugs SIADH > 20 mmol/L Sécrétion d’ADH non « volodépendante » Assess volume status Absence d’ADH < 20 mmol/L Primary polydipsia Poor dietary intake Euvolemia (no edema) ⇗ total body water no change in total body Na > 20 mmol/L Acute or Chronique 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 thérapeutiques 1) 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 cristalloïdes relative : 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 (?)

Treatement of hyponatremia 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

Treatement of hyponatremia 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 day Death 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

Si la dilution urinaire est adéquate le furosémide inhibe le pouvoir de dilution des urines et s’oppose à l’excrétion d’eau libre 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/h Uosmol = [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

Hoorn Nephrol Dial Transplant 2006

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/L Uosmol  [440 + 2x(60+20)] = 600 mmol/L Traitement : 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 diurèse Apports = 2 L  gain net H2O = (2L - 1L) = 1L T0, H2O = 0,6 x P  42L et PNa = 110 mmol/L Natot = H2O x PNa = 4400 mmol H12, [H20 = 42L + DH2O (1L)] = 43L Natot = 4400 (euvolémie) PNa= 4400/43 = 102 mmol/L