Cleveland Clinic Journal of Medicine 2010 VAIDYA 715 26

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EDUCATIONAL OBJECTIVE: Readers will treat hyponatremia appropriately, taking care to avoid overcorrection

Management of hyponatremia:Providing treatment and avoiding harm ■ ABSTRACT

Hyponatremia, in its most severe orm, requires urgent

inusion o hypertonic saline to correct cerebral edema.However, overly rapid correction o chronic hyponatremiacan cause osmotic demyelination syndrome. The authorsreview the treatment o hyponatremia in order to provideclinicians with a sound approach in a variety o settingsin which severity, symptoms, and underlying diseasestates inuence therapy. Also discussed is the currentrole o vasopressin antagonists in treatment.

■ KEY POINTS

Some hyponatremic patients present with acute, lie-threatening cerebral edema due to severe hyponatremia.In others, the hyponatremia may be chronic and lesssevere, causing relatively ew symptoms, but represent-ing an important, independent marker o poor prognosisdue to an underlying disease (eg, heart ailure).

Even patients with chronic, less severe hyponatremiamay have subtle symptoms o neurocognitive dysunc-tion and a higher risk o bone ractures.

Overly rapid correction o chronic hyponatremia orundercorrection o acute symptomatic hyponatremia canlead to serious neurologic injury.

Treatment strategies vary depending on the extracellularuid volume status and the cause o hyponatremia.

Vasopressin antagonists (“vaptans”), a new class o aquaretic agents, specifcally target the mechanism driv-ing hyponatremia in some patients.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 • NUMBER 10 OCTOBER 2010 715

Hyponatremia, dd s su sducc blw 135 l/L, s

h s qul cud lc-

l dsds. I 1981, Fl l1

dh 15% h hslzd s hdls sdu ccs lw h 134l/L, h cu h w usg h.

H s ss l lb- c sul bldcllc. I l, c b du xcssvw k , s , h bl h kd xc w culd whcud w k. Ps wh sg-c udlg cdc, hc, l

dsuc gs sk dvlgh, scd h scls duc h (ADH).Ohs sk clud sv s(scll sug w), ld -s hzd ducs, s wh -lg schc llss, d duchls.

I hs cl, w vw h cu d chc h, hszgh c bsg h h hsv ss d kg c

s h su sdu lvl dl, whchc cus ulgc dsuc.

Gudls gg h2 bsd sl scv suds dx , sc w scv sud-s hv b d. Ds h uc vdc-bsd cds, w wll c dgs - hu d l suds d cssusgudls x ls. W wll cusll h ccl dgsc csd-s css .

REVIEW

doi:10.3949/ccjm.77a.08051

CREDITCME

CHIRAG VAIDYA, MDTuts University School o Medicine;Renal Division, Baystate MedicalCenter, Springfeld, MA

WARREN HO, MDNephrologist/Hospitalist, FranklinSquare Hospital, Baltimore, MD

BENJAMIN J. FREDA, DOAssistant Proessor o Medicine, Tuts Uni-versity School o Medicine, Renal Division,Baystate Medical Center, Springfeld, MA



716 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 • NUMBER 10 OCTOBER 2010

■ SYMPTOMATIC VS ASYMPTOMATIC

Subsqu scs wll ddss hucchs w clcl sgs:

Symptomatic hyponatremia, , wh s-v sgs ss cbl d—dcl gc; d

Asymptomatic hyponatremia, , whusus sgs ss cbl d.

■ KEY DIAGNOSTIC STEPSWHEN STARTING TREATMENT

Th h bgs bcg ul h-sl s, ssss-g s clcl sgcc, d dgs cus (TABLE 1).

Th clcl d lb vlus h ud ch wh h. Th lbhd kg svl dgscdscs wll b dscussd h bf dh xdd h g x. Thd s d h vw h d-

gsc vlu h.3

Conrm that the patient truly hashypo-osmolar hyponatremiaTh su sll shuld b sud c h s lw (, < 275 Os/kg).

I dd, h l su sdu c-c c b sud usg bld gsdvc sudh (s blw) ssuscd. Ths hd uss dc - d bsss h dlul s hcssg vus sls.4

Rationale. Th clcl csqucs h du w vg h-sl xcllul fud h l-vl hsl h cll. Thsw v c cus gssv c-bl d, sulg scu sgs

d ss hdch d x szus d c. Bu sgc fud shsd cbl d ccu l h xcl-lul fud s h-sl lv h -cllul fud.

I c, h c ccu svlsus whch h xcllul fud s h-sl. A cs cv lssls (subscs h xcllul fudh d dl v css h lsb) c cus w v u clls, sulg slcl h-. Ths b s hglc wh l cs d hs b gv.I hs sus, h ls s h sc v hc h cllul fud, -sulg v w h cllsd h clcl csqucs lg h h. Il, hs qud h h.

Oh sus whch h ss bu sscd wh u h-c clud ss xcss ld h bld (sudh). Als, us hc fud s ug, cl-cs us b su h bld sls dw xll h s v.

Are there signicant signs or symptomso cerebral edema?H c cus b swllg whh cd sc h skull s w shs h xcllul fud h clls. D-dg udlg sk cs (TABLE 2)5 d h sv d du h-

(s blw), hs sul sgs

TABLE 1

Clinical approach to the patientwith hyponatremia

1 Confrm the patient truly has a hypo-osmolar state by checkingserum osmolality

2 Assess or serious signs or symptoms suggesting cerebral edema

3 Determine the duration o development o hyponatremia(less or more than 48 hours)

4 Assess the patient’s extracellular uid volume status using clinicalexamination and laboratory testing (spot urine sodium, serum uric acid)

5 Check the urine osmolality to see i the urine is appropriately dilute(< 100 mOsm/kg) or inappropriately concentrated (≥ 100 mOsm/kg)

6 Assess or underlying causes o hyponatremia that may correctrapidly with treatment (eg, hyponatremia induced by thiazide diuretics)

7 Assess the patient’s medications (intravenous antibiotics, inusions)and nutritional intake (total parenteral nutrition, tube-eeding)or sources o water

8 Look or drugs the patient is taking that potentiate antidiuretichormone action (ie, selective serotonin uptake inhibitors)

See text or details

HYPONATREMIA




VAIDYA AND COLLEAGUES

ss cbl d, cludg vsulchgs, cl ulgc chgs, ch-lh, s dss, d szus.Ull, b h c ccu.

Ps d b ssssd quckl bcushs wh sus ulgc sgs s-s hugh b ld h -qu ug wh hc sl cs h su sdu cc,gdlss h udlg vlu sus, hcus h, h s.

Determine the duration o hyponatremiaO shuld sc wh h h- sd, s s du s dg h c cc.

Th b bgs d hwh us, d h cbl d sxl wh 2 3 ds (FIGURE 1).6

A h s h, w vs h xcllul fud clls, ulld b sss. Th b c dcs h u w g h us(d hus gul s vlu) b csgh fw w h su h cbsl fud v csd s-l hdulc ssu.7

Ov h x svl ds, gcslus (g, ssu d sdu sls) dvus gc slus sd u h clls. I s wh hs css hshd ccu, h-

wh hc fuds ss h ls

sll s h h clls c cuh vusl sd sls. I hssu, vl d cc c cusxcssv lss cllul w, sulg cll shkg d sc dlsd. Osc dl usullss dug h l v l sus,wh wsg ulgc uc d v-us ulgc sgs, cludg ss d ul-l v dh.6

I s wh cu-s h(, wh s wh h s 48 hus), wh h bv cbl ds hv hd ccu cll, d ccs ulkl sul sc dl.

I vw h sus sk sc d-l, h g dvl h- c b dd, shuldssu s chc (> 48 hus) d vdd vcc (s dscuss blw h cc).

O h h hd, s wh hv s-v ulgc sgs ss lld h su sdu csd ugl s lvls, gdlss h g s(s blw suggsd ch). Subsqu h— h susdu lvl hs b sd ugh vsulgc ss—wll b fucd bh du h h, wh culvdc vl d cc, scll

s wh chc h.

Signicant

fuid shits and

cerebral edema

occur only i the

extracellular

fuid is

hypo-osmolar

relative to the

intracellular

fuid

TABLE 2

Risk factors for cerebral edema

RISK FACTORS PATHOPHYSIOLOGIC MECHANISM

Children (under age 16) Higher brain-to-intracranial volume ratio

Women (especiallypremenopausal)

Sex steroids (estrogens) inhibit brain adaptation

Increased vasopressin levels

Cerebral vasoconstriction and hypoperusion o brain tissue

Hypoxemia Impaired brain adaptation

Ecstasy use Inappropriate antidiuretic hormone secretion

ADApTED FROM MORITz ML, AyUs JC. ThE pAThOphysIOLOgy AND TREATMENT OF hypONATRAEMIC ENCEphALOpAThy: AN UpDATE. NEphROL DIALTRANspLANT 2003; 18:2486–2491, By pERMIssION OF ThE EUROpEAN RENAL AssOCIATION AND EUROpEAN DIALysIs AND TRANspLANT AssOCIATION.




M The danger o overly aggressivecorrection o hyponatremia

CCF©2010

FIGURE 1 ADApTED FROM INFORMATION IN ADROgUé hJ, MADIAs NE. hypONATREMIA. N ENgL J MED 2000; 342:1581–1589

Normal state. The extracellular uid is in osmotic equilibrium withthe intracellular uid, including that o the brain cells, with no netmovement o water across the plasma membrane.

Acute hyponatremia. I the extracellular uid suddenly becomeshypotonic relative to the intracellular uid, water is drawn into thecells by osmosis, potentially causing cerebral edema.

Adaptation. Over the ensuing ew days, brain cells pump outosmoles, frst potassium and sodium salts and then organic osmoles,establishing a new osmotic equilibrium across the plasma mem-brane and reducing the edema as water moves out o the cells.

Overly aggressive therapy with hypertonic saline ater adapta-tion has occurred raises the serum sodium level to the point that theextracellular uid is more concentrated than the intracellular uid,drawing more water out o the brain cells and causing the syndromeo osmotic demyelination.

Osmoles

HYPONATREMIA





Assess the patient’s volume statusto determine the proper initial treatmentI s wh h-sl hwh d d ug h wh h-

c sl, h l s bsd clcl d lb ssss xcl-lul fud vlu sus, cludg s usdu su (TABLE 3).3 Ths wll bdscussd uh blw.

Check urine osmolality to assessor hyponatremic statesin which urinary dilution is intactMsug u sll s usul s-cg whh hc s kg l dlu u (< 100

Os/kg). I h , h cus h h- b xcssv w k, -s ss, lw slu k. I dd,s wh hvlc h hv l dlu u s wh sc vus fuds.

Th su sdu cc -us l h udlg cus s l-d (g, xcssv fud k s sd).I h sus sgs ss, hsc usull b cclshd whu ddlh wh vus fuds dcs,hb vdg h sk vcc.

Search or causeso rapidly correctable hyponatremiaI h s du svl - udlg cuss, vsdl c h udlg cus hs bld (TABLE 4). Exls: scgw k s wh schgclds, dscug hzd ducs,lshg dld fud vlu, sgdsss (DDAVP), d gvg glucc-cd lc hs wh glucc-cd-dc.

■ TREATING HYPONATREMIC PATIENTSWITH SERIOUS SIGNS OR SYMPTOMS

Ps wh h-sl hd sus sgs ss cbld (lhg, s dss, s-zus) d d l cc hsu sdu lvl, s hs s u dcl

gc.

C s g sk dvl-g cbl d h (TABLE 2).

O h h hd, s wh chch v ulkl swh sgs ss cbl d. Ic, wh chc h,c us b k vd vccbd h dd vs sv sgsd ss. I h cs whch wh chc h sswh sgs ss cbl d, hhc sl us us b sd ss s h sgs ss hv slvd.Fuh d chgs su sdu usb vdd.

Dug cc h, ss cull hgh sk scdl sd scd ud-lg bls cbl sc gul-. Ths clud s wh lchls,lu, hkl, d bus, dldl w hzd ducs.8 Thss shuld b d vgll

vl d cc dug .

TABLE 3

Initial treatment of hyponatremiaaccording to extracellular volume status

Hypervolemic Fluid restrictionSodium restrictionLoop diureticTreat underlying uid-retentive state (see text)

HypovolemicIntravenous isotonic salineDiscontinue diureticsReplace mineralocorticoids i defcient

EuvolemicFluid restriction

Loop diuretics plus salt tablets to replace urinary sodium lossesDemeclocycline (Declomycin)Vasopressin receptor antagonistsOral urea (not available in United States)Enhance solute intake i poor nutritionDiscontinue medications associated with syndrome o inappropriate

antidiuretic hormone secretion (SIADH)Treatment o underlying carcinoma i ADH-secreting tumorTreatment o underlying condition associated with SIADH

(eg, antibiotics or pneumonia)Treatment o endocrinopathy (eg, hypothyroidism)




Do not try

to correct

the serum

sodium to

‘normal’ values

■ INITIAL TREATMENT:REVERSE CEREBRAL EDEMA WITH 3% SALINE

Th gl h l, d hs cc- s vs cbl d.

Ps wh sus sgs ssshuld cv hc (3%) sl bu 1 L/kg/hu h s sv-l hus.8 Ths wh cc h-vl (s cgsv h lu) udlg cdvscul dss shuld lscv l duc d -wxc d v vlu vld h sl us. Ths g usu-ll ss h su sdu ccugh (usull b bu 1 l/L/hu) dcs cbl d d v s-s.

I s hvg cv szus shwg sgs b h, 3% s-l c b gv ll hgh bu 2 3 L/kg/hu v h s whus. A lv ch s l50-L blus 3% sl d ddl200 L gv v h subsqu 4 6hus.9

N sud hs cd h cc ds hs chs, d clcsshuld lws xcllul fud vl-u sus, ulgc sus, d su s-du lvls clsl d whhc sl.

A sv sgs d ss hvslvd, 3% sl s l dsc-ud d h s dbsd h ’s vlu sus dudlg cus h (s ds-

cuss blw).

■ NEXT, FIND THE APPROPRIATE RATEOF CORRECTION

A h l sus sgs sshv b ddssd wh hc sl,

g shuld cus lg h cc s wh chc h- h ukw du.

Al suds d scv husuds hv suggsd c gudls h c d gud c-c dug h vd sc dl sd.2

Clcs us cc hsu sdu “l” vlus. Alhughs wh cu h l- cl cc, h s ll v-

dc h sg h su sdu cc- cul b h 5 8 l/Ls dvgus. Th, cc shuldb judcus ll s.

Appropriate rates o correctionA c x cssus l suggsdh h su sdu lvl b sd b h 10 12 l/L dug h s24 hus , d b lss h 18l/L v 48 hus.2

Ps wh chc h dsgs ss cbl d shuldhv h sdu lvl sd vslw —s cd lss h 10l/L h s 24 hus.10 Aggssv -l cc h 1.5 2 l/hu h s 3 4 hus wh 3% sls dcd ul sus ss (szu,bud) slv, bu cc bd10 12 l/L h s 24 hus shuldb vdd. Hc sl h shuldusull b dscud wll b h susdu lvl hs s hs uch, vd cug s h sdu lvl hus hs sd.

Whl hc sl s bg usd,su sdu lvls shuld b chckd v1 2 hus. I sud 56 s whsv h (su sdu ≤ 105l/L),11 ulgc clcs wbsvd s wh chc h- whs su sdu ws ccd b lssh 12 l/L 24 hus b lss h 18l/L 48 hus wh h vg

cc su sdu 120

TABLE 4

Rapidly correctablehyponatremic states

Psychogenic polydipsia

Thiazide-diuretic-induced

Volume depletion

Desmopressin-induced

Glucocorticoid defciency

HYPONATREMIA





l/L ws lss h qul 0.55 l/L hu.

I the serum sodium concentration

has been overcorrectedDsss s cv vg dvsg dv vcc h-.12 I sud, dsss lwdh sdu cc b 2 9 l/L 14 20 s. N h s dvl-d sus dvs csqucs.

I dd, vus w (dxs5%) c b gv l cbwh dsss v vs xcssv cs su sdu.13 Suchh b csdd s wh

cu xc hc u d hvld chd su sdu cc- h s xcds h cdd gud chg.

Formulas or estimatingthe rate o correctionVus uls hv b dvsd s-g h chg su sdu cc- dug h.14

Th Adgué-Mds ul, hs cl usd, gvs s hw uch h su sdu ccwll s wh 1 L vus vus fudss gv (TABLE 5).15 Ths ul ls ccus h cs su sdu h kslc dug cc cc h-kl wh ssu. Rcl, hwv, scv sud16 ud h hs uludsd h chg su sdu 23 (74.2%) 31 s wh h- d wh hc sl. A lv s h Bsu-Lvqu, whch ks ccu ggu lsss. Alhugh s cub-s clcul, b cs.17

Alvl, s whu hv-l, h clc c clcul h u u xc w qud chv scc g su sdu dh su hul u w xc- dug quss ducd b usd(Lsx).8 Alhugh hslgc, hshd c b clcll cubs, -qug l hdlg u scs,

ccu cdg u uu, d d

g lb suls.Ull, hs hds sv l s s-

s h chg su sdu d d lc cul g lcls(v 1 2 hus dug cu h) dsdus ssss clcl sgs s-s sc dl sd.

■ PATIENTS WITH HYPONATREMIAAND NO SERIOUS SIGNS OR SYMPTOMS

General approachHc s whu sus sgs ss cbl d d quug h s h su sdu.

Ps wh chc sc h- cl cud clcl cc. As sul cbl d-, h c hv ssds su sdu lvls s lw s 115 120 l/L. Hwv, v h hv sus sgs ss cbl d,s s cl gu, lh-g, us, g bls, d usclcs d hv vdc ld s ucgv .18

I c cs-cl sud,18 ldl -s wh chc h ( s-u sdu cc 126 ± 5 l/L)

w lkl s h hsl

I inusing

3% saline,

monitor

serum sodium

every 1–2 hours

TABLE 5

How much will 1 liter of intravenous salineraise the serum sodium concentration?

Sodiuma + potassiumb in solution – serum sodium concentration

total body waterc + 1

a Sodium content o saline solutions:

513 mmol/L in 3% (hypertonic) saline

154 mmol/L in 0.9% (isotonic) salineb I any potassium is added. For example, i 20 mmol o potassium is added to 1 L o

isotonic saline, then this number would be 154 mmol + 20 mmol = 174 mmol.c Total body water:

0.60 × patient weight in kg (nonelderly male)

0.50 × patient weight in kg (nonelderly emale)

0.50 × patient weight in kg (elderly male)

0.45 × patient weight in kg (elderly emale)

ADApTED FROM ADROgUé hJ, MADIAs NE. hypONATREMIA. N ENgL J MED 2000; 342:1581–1589.COpyRIghT 2000 MAssAChUsETTs MEDICAL sOCIETy. ALL RIghTs REsERVED.




wh lls cd wh g-chd c-ls. Fuh lss suggsd hs shd kd s g d -, whch vd s s h su

sdu csd.Ah c sud19 d h ld

h ( su sdu cc- 132 l/L) ws ddl ss-cd wh h sk cu, v d-jus kw sc sk cs.

Ev wh h s d cuh s h su sdu lvl, hclc shuld scuz h dcl g- d vlbl clcl d ul uvsbl cuss w xcss. Ths clud gg ds hc

fuds (g, l u dxs 5% “k h v ”) dcsh cus ls ADH (g,slcv s uk hbs) h w xc (g, s-dl -f dugs). Th clcshuld ls sch udlg dgssh dsss w , such shhds, dl succ, cgs-v h lu, hc l lu.I h s du dc dss,cc hhds dl su-cc shuld sul w xc dv h su sdu.

I h cus h h s -dl , c b sd h bss ssss h ’s x-cllul fud vlu sus usg clclx d sul lbd such s h su uc cd ccd u sdu cc.3 TABLE 3 uls gl s h-sl h ccdg xcl-lul fud vlu sus.

O , hscl x l hs ssv d scc ssssg x-cllul fud vlu sus s whh.20,21 Ths hghlghs h -c s sus u sdud su uc cd d, wh ,sc vus sl chllg d-c ccul hvl.

I gl, s wh uvl d wh fud sc, d swh hvl gv sc sl.

Ps wh hvl c b dcul

, bu gl h scbd bhsdu d fud sc. L ducsc b gv xc wd sdu. Thzd ducs vdd,

s h u dlu d wsh. As shuld b d z h h udlg h-vlc dsd (cgsv h lu,chss, dvcd l lu). Vss-s c gss c ls b usd slcd css hvlc uvlch (s dscuss blw).

How to prescribe fuid restriction rationallyIdll, s shuld gs fud h h c xc u d s-

sbl lsss—hws, h su sdu ccu dcs.

W xc c b sd slu k d u sl. I h, 70-kg s wh cl dl slu -k bu 10 Os/kg d c udlu u sl 50 Os/Lc xc u 14 L u (700 Os/50Os/L) d. Hwv, whh sd ADH sc(SIADH) d xd u sll 700Os/kg wuld xc sl slu ld l 1 L u. Thus, fud k xcss hs vlu culd ws h-.

T xc w, u sdu lusu ssu us b lss h h susdu cc. I hs gd, h c-ss dg fud sc c ls bsd d h bss h ’su lcls.22

Increased solute intake

to augment water excretionI s whu hvl, slu -k c b csd ug w xc-.22 Ths c b chvd wh sl bls l u. Alhugh u c b cv, s cl usd bcus s vl-bl h Ud Ss d hs gs-sl lbl. I s whs u-l k s ld d wh cu gs fuds (such s, xl, ldl subssg d s) v - shuld b d cs slu k

wh hgh- ds suls.

Stop 3% saline

promptly once

severe signs

and symptoms

o cerebral

edema resolve

HYPONATREMIA





■ DRUGS TO INHIBIT VASOPRESSIN

Uul, s d dh hs sgs, s fud sc d u-lbl sl bls u c bc buds. I such scs, hc-lgc hb vsss-dd w- bs c b csdd usg hllwg gs. Demeclocycline (Dclc) and lithi-um hb h kd’s ss vss-s. Bcus lhu b hxc dhs uwd cs h cl vusss, dclccl hs bc h -d g. Gv dss 300 600 gwc dl, dclccl s w- xc, bu ks 1 2 wks h bg wkg.

Rl lu du dclccl hsb d s wh cclv dss.23 Dclccl c lscus hssv d s cd-cd chld d g w du bls b d l -. I dd, c b xsv d b cvd ull b s scls.

Vasopressin receptor antagonists (‘vaptans’)ADH, ls clld vsss, cs whvus c subs, cludg V1

(cusg vscsc, ll ggg-

, c sul, cdl - shss), V1b (cusg sc d-ccc h), d V2 (cusgw bs d ls v Wll-bd c d c VIII).

Dugs h blck V2 cs h lubul cs w xc, kg hcv s h s hcss (TABLE 6).24,25 Ths dugs x hquc c b cusg dcs -sc d s qu-2 ch-ls (“w s”) h cl cllcgduc b. As sul, h w -bl h cllcg duc s dcsd v h sc cculg ADH. Conivaptan (Vsl) s cbdV1-V2 gs h hs b vd h uvlc d hvl-c h. Cv hbs hcch P450 3A4 ss d hus c wh h dugs; h, s us hsb ld h 4 ds -vus ds h hsl sg.Th cdd dsg s l 20-gus v 30 us, llwd b c-uus uss 20 40 g/d. Dsgdjuss l d hc hv b wll dd. Tolvaptan (Ssc) s l slcvV2 gs h hs b sudd -s wh uvlc d hvlc h-

.26

Suds hv cludd s

Asymptomatic

patients with

hyponatremia

do not require

urgent

treatment

to acutely

increase serum

sodium

TABLE 6

Vasopressin antagonists for treating hyponatremia

TOLVAPTAN (SAMSCA) LIXIVAPTAN (VPA-985) SATAVAPTAN (AqUILDA) CONIVAPTAN (VAPRISOL)

Vasopressin receptor V2 V2 V2 V1a/V2

Administration Oral Oral Oral, intravenous Intravenous

Hal-lie (hours) 6–8 7–10 14–17 3.1–7.8

Metabolism Hepatic(CYP 3A4)

Hepatic(CYP 3A4)

Hepatic(CYP 3A4 90%)(CYP 2D6 10%)

Hepatic(CYP 3A4)

Dose 15–60 mgonce daily

50–100 mgtwice daily

5–25 mg once daily 20 mg in30 minutes, then20–40 mg/day

ADApTED FROM DECAUx g, sOUpART A, VAssART g. NON-pEpTIDE ARgININE-VAsOpREssIN ANTAgONIsTs: ThE VApTANs. LANCET 2008; 371:1624–163,COpyRIghT 2008, wITh pERMIssION FROM ELsEVIER.




wh cgsv h lu, chss, dSIADH. Alhugh lv hs bshw duc s hslz dh cgsv h lu, vs

su sdu, vll fud blc, d c-gsv ss.27 Tlv hs clb vd h uvlcd hvlc h.

A c sud hs cd h lg- cc lv 111 s v du g h 700ds.28 Whl h clcl bs chclv h hv b cll d-sd, hs sud shws h lvh c sul susd v su sdu cc whu

uccbl cs dvs vs.29

Lixivaptan (VPA-985), h l slc-v V2 c gs, s bg sudd s wh uvlc d hvlch.

Current role o vasopressin antagonistsCu suds vsss gss h h sg,hugh d cds dd su slw, cul cc h-. Ms suds suggs h hs gsvd slw, lbl css su sd-u. I lg sud s wh cgs-v h lu, su sdu s b h 12 l/L 24 hus w h 2% s.26

Nbl, css sc dlsd hv b d hs suds.Hwv, shuld b d h h wssd h hsl wh cls g su sdu lvls d dscu fud sc; h cdc vl dcc sdu b hgh usd cull d clcl suds. Clcsshuld d g sgs sl hs usd hs gus suds.

A s, h s ll xc whvsss gss hc -s wh sus sgs ss c-bl d, d s clcs sll vw 3%sl s h gld sdd hs s.

Vsss gss shuld b usd s wh hvlc h,du ccs bu V1 blckd cusg

hs d bu V2 blckd duc-

g w xc d wsg hvlu-dld s.

Rc clcl ls hv d hs xc csd hs

whl kg hs gs. Ths hghlghs hd su sdu dug -.

Ths gs xsv. Tlvcss bu $250 bl; cv,whch s dsd vusl, cs ll cus.

■ THERAPY IN SPECIFIC DISEASE STATES

Patients with hyponatremia and cirrhosisTh cus s w d sl

sc d judcus us l ducsd lds gss such s s-lc (Aldc).

Tlv hs b cv sgh su sdu lvl s wh c-hss,26 whl cv shuld b vdd s bcus vsdl V1c gs d s l cs ssc hdcs d sk v-cl bldg.30

As h sv chss css, hl cv h slv sl.

Patients with SIADHI s css, w sc s h -s h. Adqu ul kshuld ls b sssd s h ugh slus vlbl gg w xc. Al-hugh fud sc s usull cv, s c dh h lvl sc qud.

I css whch fud sc s -cv s w, dclcl c b usd gz ADH c d cs wxc. Sdu bls d l ducsc ls b usd, kg c vd h-vl duc-ducd sdu lsss.Th us lv s wh SIADHhs suld sh- css susdu.26 A c sud hs suggsd hhs c c b susd wh lg-,28 bu uh suds dd shw cl clcl b (g,vd ucg) gud h us

hs csl gs clcl cc.

Euvolemic and

hypervolemic

patients with

hyponatremia

should not

ingest any

more fuid

than they

can excrete

HYPONATREMIA





Patients with diuretic-induced hyponatremiaThzd ducs shuld b dscudd hvl d hkl shuld bccd wh sc sl d ssu

sul. As h hkl s c-cd d h duc c d hvl-c sulus ADH dsss, w xc- c cs dl, sulg bskchg su sdu.

Su sdu lvls shuld b clsld dug h vd vcc-. F hs s, us hc slshuld gll b vdd. Hc fu-d—g, hl-l (0.45%) qu-l(0.22%) sl v dsss— b-c css h l sgs h

vd vl d cc.

Patients with exercise-associatedhyponatremiaPs hghs sk xcs-sscdh clud hs wh dk uch fud dug lg-dsc c, whhv lw bd wgh, wh l, whxcs lg h 4 hus, d wh ussdl -f dugs.31 Thcus h s lkl ulc-l, wh xcssv w k culd whsdu lsss d d l xc w du ADH c d d -l dlu. T v xcs-sscdh, fud k shuld b ld 400 800 L/hu, wh h hgh dcdd lg hls d hcls.

Cssus cds suggs hs s wh ld h (susdu 130 135 l/L) shuld b dwh fud sc d clcl bsv,s sus w duss lds v- h su sdu lvl. Il,h fx vd sc sl ussshuld b vdd ulss cl sgs vludl s. Ivus sl hs

h l ws h hsc ADH. I dd, s hlswll hv d w h gss-l c h b blzd h c,

sulg wsg h.32

I hls wh sv h (s-u sdu < 120 l/L) scxcs-sscd h (lhg,s dss, szus), hcsl s h chc. O -cl suggss gvg 100 L 3% sl v10 us h ld, llwd b s hsl.33

■ SUMMARY POINTS

• H s c lcl ds-d h s s sv qusug h wh hc sl cc cbl d.

• I s whu sus sgs s-s cbl d, c bsv-s suggs h b clcll - slg lg lducgv dsuc d ss-c wh sk b cu.

• Mull sgs vlblccdg h udlg xcllulfud vlu sus d cus h-. Ths clud fud d sdusc d ug uw xc wh vus uld hclgc sgs. Th svl h cluds gs hvsss V2 c wh clss quc gs kw s vs.

• Th c b sus ulgc ju s-scd wh vl d cc chc h udcc cu sc h.

• Clcs us b l wh h d-ls ch h s d hv c h c culg dug . ■

Patients oten

do not adhere

to fuid

restriction

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ADDRESS: Benjamin J. Freda, DO, Renal Division, Baystate Medical Center,100 Wason Avenue, Suite 200, Springfeld, MA 01108; e-mail benjamin.

[email protected].

HYPONATREMIA

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