Edelman-derived quantification of dyselectrolytemias.
Equation-based monitoring of hyponatremia therapy with a focus on safely and predictably increasing sodium as per guideline advice using a strategy involving desmopressin administration in severe hyponatremias, especially those patients at risk of becoming overcorrectors. Explanation of risk factors responsible for overshooting when correcting hyponatremia. Adrogue-Madias, Barsoum, Nguyen-Kurtz equations are explained and proven to be of help at least conceptually when attempting to have a desmopressin-guided therapy in hyponatremia. All recommendations are done in accordance with European and American guidelines published in 2013 and 2014.
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Quantitative Approach to Managing Dysnatremias
1. Quantitative Approach in Dysnatremias
- a complementary tool for the busy intensivist -
13th November 2015
2. Assigning a context
๏ง Define the determinants(โindependentโ variables) of plasma water sodium
๏ง Define the physiological basis of sodium-related transport(e.g. Laytonโs math-models of urine
concentrating mechanism, mammalian transporters, Gibbs-Donnan equilibrium,
intercompartmental dynamics-Hahnโs fluid distribution kinetics)
๏ง Describe the generation of dysnatremias in terms of plasma water sodium determinants
๏ง Classification, etiology and pathophysiology of dysnatremias
๏ง Incidence, short and long-term prognosis of dysnatremias
๏ง Clinical/pathological frame and implications of dysnatremias
๏ง Diagnosis (differential) of dysnatremias (e.g. the never ending debate about CSW(Maesakaโs
RSW) vs SIADH โ Sternโs salt โwantingโ syndromes)
๏ง Describe cell-volume related physiology and its clinical implications
๏ง Build a quantitative-based framework to treat/prevent dysnatremias
๏ง Devise new monitoring frameworks(e.g. trending the urinary uric fractional excretion
according to Maesakaโs algorithm to better delineate between SIADH-RSW)
3. Narrowing the context to hyponatremia
๏ง Define the rules, pitfalls, risk factors inherent to hyponatremia correction
๏ง Describe classical ill-derived equations to prevent/amend overcorrection and/or
perform/guide correction
๏ง Provide a quantitative, physiologically โ derived, still perfectible equation(โmaster equationโ
or maybe just โintractable abracadabraโ J Appl Physiol 101: 692โ694, 2006) for understanding
plasma water sodium determinants
๏ง Describe the shortcomings of equation-based ways to manage hyponatremias
๏ง Describe a case naturally resembling a beaker - meant to be the ideal patient to be dealt with
when using an equation-based management
๏ง Provide a solution whereby at least severely hyponatremic patients at high risk of
overcorrection-related complications might benefit from being artificially, temporarily
transformed into human beakers
5. Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations-2013
Joseph G. Verbalis, Steven R. Goldsmith, Arthur Greenberg, Cynthia Korzelius, Robert W. Schrier, Richard H. Sterns, Christopher J. Thompson. The American Journal of Medicine (2013) 126, S1-
S42
Clinical practice guideline on diagnosis and treatment of hyponatraemia โ 2014
Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert
Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen and Evi Nagler on behalf of the Hyponatraemia Guideline Development Group. European Journal of Endocrinology (2014) 170, G1โ
G47; Intensive Care Med. 2014 Mar;40(3):320-31; Nephrol Dial Transplant. 2014 Apr;29 Suppl 2:i1-i39
๏ง most common disorder of electrolytes occurring in
15%-30% of acutely or chronically hospitalized
patients โ Madias et al; Am J Med. 2006; 119:S30-
S35
๏ง severe hyponatremia(serum [Naรพ] <125 mmol/L)
more than doubled the risk of in-hospital mortality
(RR 2.10; P <.001) in an ICU with a overall mortality
rate of 37.7% - Bennani et al; Rev Med Interne.
2003;24:224-229
๏ง Dissenting results as to whether chronic
hyponatremia is just a marker of the underlying
disease severity or is itself a risk factor - Chawla,
Sterns et al; Clin J Am Soc Nephrol. 2011
May;6(5):960-5
๏ง Overall, chronic hyponatremia, not in the least
inconsequential, indirectly is proven to be a cause
of increased morbidity and mortality - Kinsella et
al; Clin J Am Soc Nephrol. 2010;5:275-280
๏ง Classification according to biochemical and clinical
severity
๏ง In terms of overall severity and therapeutic
management, the clinical picture will override the
biochemical one
๏ง Defining target /aim and limit concepts
๏ง Always aiming for the smallest increase needed to
effect a clinical improvement
๏ง Low treshold for searching other explanations in
view of the low specificity of hyponatremia
associated symptoms
๏ง Focus on defining acute versus chronic given the
risks related to brain volume autoregulation
๏ง Low treshold for positing chronic instead of acute
with less than severe symptoms
๏ง Greatly limiting the aim for acute hyponatremia-4
to 6 mmol/l/first 6h
๏ง Setting a common aim of 4-6mmol/l /24h for acute
and chronic states but with a different time-scale
๏ง Setting a limit at 8-10mmol/l/24h
๏ง Describe high risk ODS patients
๏ง Describe management for preventing ODS
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6. Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations-2013
Joseph G. Verbalis, Steven R. Goldsmith, Arthur Greenberg, Cynthia Korzelius, Robert W. Schrier, Richard H. Sterns, Christopher J. Thompson. The American Journal of Medicine (2013) 126, S1-
S42
Clinical practice guideline on diagnosis and treatment of hyponatraemia โ 2014
Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert
Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen and Evi Nagler on behalf of the Hyponatraemia Guideline Development Group. European Journal of Endocrinology (2014) 170, G1โ
G47; Intensive Care Med. 2014 Mar;40(3):320-31; Nephrol Dial Transplant. 2014 Apr;29 Suppl 2:i1-i39
six a day makes sense for safety; so six in six hours for severe sxโs and stop
Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010;56:774-779
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๏ง Adrogue HJ, Madias NE. The challenge of hyponatremia. J Am Soc
Nephrol. 2012
๏ง Arampatzis S, Frauchiger B, Fiedler GM, et al. Characteristics,
symptoms, and outcome of severe dysnatremias present on hospital
admission. Am J Med. 2012
7. Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations-2013
Joseph G. Verbalis, Steven R. Goldsmith, Arthur Greenberg, Cynthia Korzelius, Robert W. Schrier, Richard H. Sterns, Christopher J. Thompson. The American Journal of Medicine (2013) 126, S1-
S42
Clinical practice guideline on diagnosis and treatment of hyponatraemia โ 2014
Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert
Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen and Evi Nagler on behalf of the Hyponatraemia Guideline Development Group. European Journal of Endocrinology (2014) 170, G1โ
G47; Intensive Care Med. 2014 Mar;40(3):320-31; Nephrol Dial Transplant. 2014 Apr;29 Suppl 2:i1-i39
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๏ง Hypokalemia#Hyperkalemia
๏ง Alcoholism
๏ง Malnutrition
๏ง Contextual SIADH
๏ง Hypoxemia
๏ง Low solutes(e.g.beerpotomania)#urea
๏ง Corticoid deficiency-after substitution
๏ง Hypothyroidism-after substitution
๏ง Serum sodium<105mmol/l
๏ง Advanced liver disease
โบacute water diuresis(EFWC) is most often responsible for overcorrectionโ
Mohmand et al,Clin J Am Soc Nephrol 2: 1110โ1117, 2007
8. Reasons behind large positive EFWC
- contextual SIADH or non-osmotic induced ADH secretion-
๏ง Undiagnosed hypovolemia is the most common feature of
overcorrectors
๏ง Unpredictable time-dependent stimulation due to thiazide,
SSRI โบ
๏ง Stress,pain, exercise - related but in this case without
consequences due to the acute nature
๏ง Hypothiroidism induced ADH-secretion(indirectly-low EABV)
๏ง Glucorticoid deficiency induced ADH suppression failure
sAntidepressants
SSRIs
Tricyclic
MAOI
Venlafaxine
Anticonvulsants
Carbamazepine
Sodium valproate
Lamotrigine
Antipsychotics
Phenothiazides
Butyrophenones
Anticancer drugs
Vinca alkaloids
Platinum compounds
Ifosfamide
Melphalan
Cyclophosphamide
Methotrexate
Pentostatin
Antidiabetic drugs
Chlorpropamide
Tolbutamine
Miscellaneous
Opiates
MDMA (XTC)
Levamisole
Interferon
NSAIDs
Clofibrate
Nicotine
Amiodarone
Proton pump
inhibitors
Vasopressin
analogues
Desmopressin
Oxytocin
Terlipressin
Vasopressin
9. Urea as a protector and therapeutic strategy
- lessons from the elasmobranchs -
๏ง Sharks are osmoconformers
๏ง Have a low adaptability to outer osmolarity variation but still much higher than
predicted (high urea, high K)
๏ง Urea has been proven to be a true antioxidant - Novel cardiac protective eโฌffects of
urea: from shark to rat, Wang et al, Br. J. Pharmac., 1999
๏ง Urea is known to act as a cryoprotector in amphibians - Cryoprotection by urea in
terrestrially hibernating frog, Constazo, J Exp Biol 2005; Urea loading enhances
freezing survival and postfreeze recovery in a terrestrially hibernating frog,
Constazo J Exp Biol 2008
400mOsm
1000mOsm/kg
Na
280 m0sm
K
7-14 m0sm
10. Urea as a protector and therapeutic strategy
- icu beginnings -
EFWC = Vu ร (๐ โ
๐ผ ๐ต๐จ + ๐ผ ๐ฒ
๐ท ๐ต๐จ
))
Vu =
๐๐๐๐๐๐ ๐๐๐๐๐๐๐๐๐
๐ผ๐๐๐
๏ง Decaux, Soupart; Nephrol Dial Transplant (2007)
22: 1856โ1863
๏ง Decaux, Soupart, Critical Care 2010
๏ง Decaux, Soupart; Nephron. 1993;63(4):468-70
๏ง Decaux, Musch; Clin J Am Soc Nephrol 3: 1175โ
1184, 2008.
๏ง Soupart, Decaux; Clin J Am Soc Nephrol 7: 742โ
747, 2012
๏ง Reeth, Decaux; Clinical Science (1989) 77,35 1-
355
๏ง Soupart, Decaux; Nephrol Dial Transplant (2007)
22: 1856โ1863
๏ง Decaux, J.L.Vincent; Annals of Intensive Care
2012
๏ง Decaux, Soupart, Kidney International (2015) 87,
323โ331; Urea minimizes brain complications
following rapid correction of chronic
hyponatremia compared with vasopressin
antagonist or hypertonic saline
โOnly a pathetic oaf would suggest anything so ludicrous. Putting back into the
body the final waste product of protein metabolism could only be deleterious!โ
1950 (from Rocque, Neurosurgery 2012; 70: 1049โ1054)
11. Urea as a protector and therapeutic strategy
- context-sensitive osmolar effectiveness -
ฯ=0.5
ฯ=0.5
Sterns et al,Kidney International (2015) 87, 268โ270
12. A tribute to the forerunners of urea treatment
1892
Friedrich W., Magy.orv.Arch.1:400-415,1892
Manucher J. Javid, MD.
1925
Crawford, Arch Intern Med (Chic).
1925อพ36(4):530541
Heart failure-
diuretic
The 1950โs
Manucher and Settlage
See review - Neurosurgery 70:1049โ1054, 2012
ICP
management
1960s-
1970s
1980-
Guy Decaux, Alain Soupart
Belgium, Erasme
hNa+
management
13. ๏ง Know the cause, the subtype(e.g.pseudohyponatremia, hyperosmolar hypertonic
hyponatremia, RSW vs SIADH) or the probable course after having begun
correction(underlying hypovolemia )
๏ง Frequently monitoring(plasma as well as urine Na, K; urine flow, total balance; even hourly
basis) with a limited possibilty for now to have a quasicontinuous urinary flow and electrolyte
monitoring(K.I.N.G. system, Italy-Milan, P.Caironi)
๏ง Judicious use of equation based-forecasting(Adrogue-Madias, Barsoum-Levine, EFWC-
approach or the tonic balance approach, sodium deficit formula)
๏ง Targeting normal-high potassium(4.5-5.5 mmol/l)
๏ง Use urea in selected cases(e.g. euvolemic hyponatremia-SIADH)
๏ง Avoid vaptans for chronic hyponatremia management
๏ง Prompt counteraction of overcorrection(D5W, half normal saline, oral water input,
desmopressin) +/- CSโบ
Classical approach to minimize the risk of
overcorrection
Soichi Oya et al,Neurology November
27, 2001 vol. 57 no. 10 1931
14. Equation-driven correction of hNa+
๐ต๐ ๐ ๐๐ = (๐ต๐ ๐๐๐ โ ๐ต๐๐๐ ๐๐๐) ร ๐ป๐ฉ๐พ
๐ต๐ ๐=
๐ฝ๐๐๐๐๐ร(๐ต๐๐๐๐+๐ฒ๐๐๐) + ๐ป๐ฉ๐พร๐ต๐ ๐
๐ป๐ฉ๐พ+๐ฝ๐๐๐๐๐
๐ต๐ ๐=
๐ฝ๐๐๐๐๐๐๐ร ๐ต๐๐๐๐๐๐+๐ฒ๐๐ ๐๐๐ โ๐ฝ๐๐ ๐๐๐ร ๐ต๐ ๐๐๐+๐ฒ๐๐๐ + ๐ป๐ฉ๐พร๐ต๐ ๐
๐ป๐ฉ๐พ+โ๐ฝ๐๐
๐ต๐ ๐ =
๐ต๐ ๐ ร ๐ป๐ฉ๐พ
๐ป๐ฉ๐พ โ ๐ฌ๐ญ๐พ๐ช
Halperinโs tonicity balance โ reply to EFWC
approach. Undistinguishable from BL.
Sodium deficit formula
Adrogue-Madias
Barsoum-Levine
Electrolyte free water formula
EFWC = Vu ร (๐ โ
๐ผ ๐ต๐จ +
๐ผ ๐ฒ
๐ท ๐ต๐จ
)
Simplicity should have been the ultimate sophistication
+
Na1 =
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ ๐
Na2 =
๐ต๐ ๐+๐ฒ๐+โ(๐ต๐+๐ฒ)
๐ป๐ฉ๐พ ๐+โ๐ป๐ฉ๐พ
Na2 =
(๐ต๐ ๐ร๐ป๐ฉ๐พ ๐)+โ(๐ต๐+๐ฒ)
๐ป๐ฉ๐พ ๐+โ๐ป๐ฉ๐พ
๏ง The orange equations are all derived from the blue one
๏ง The blue equation is itself a marked oversymplification of
another one which weโll deal with later(Edelman-derived by
Nguyen and Kurtz)
๏ง Orange SDF psupp. that โTBW=0 โ TBWsensibility is actually high
and does not suit as a model for 99.9% of all path. states
๏ง Orange AM does not take into account anything but the
infusate. If output is large, then it would be futile to use it.
๏ง Orange BL seems identical to the blue one. Indeed it is if you
discard e.g. metabolic water. Output refers to urine, drains,
vomiting etc. whilst input refers to iv, oral.
๏ง The numerator Nae+Ke stands for total exchangeable sodium
and potassium which by definition (1958) is the sum of total
osmotically active as well as inactive sodium and potassium.
This sheds doubt on the blue equation(and therefore on all the
other) as Na(osm. active) cannot be the result of smth inactive.
๏ง Orange EFWC psupp. that the kidney is the single most
important determinant of Nap. What if there is no urine output?
๏ง Tzamaloukas et al, J Am Heart Assoc. 2013.
๏ง Lindner et al, Nephrol Dial Transplant (2008) 23: 3501โ3508
๏ง Nguyen, Kurtz, Clin Exp Nephrol (2004) 8:12โ16
๏ง Nguyen, Kurtz, Clin Exp Nephrol (2005) 9:1โ4
๏ง Barsoum, Levine, Nephrol Dial Transplant (2002) 17:1176-1180
๏ง Adrogue, Madias, J Am Soc Nephrol 23: 1140โ1148, 2012
๏ง Halperin et al, Crit Care Clin 18 (2002) 249 โ 272
๏ง Halperin et al, ICM Volume 27, Issue5/May 2001
16. Understanding Nae+Ke
- 1958 -
๏ง 98 patients were studied with โmaximum heterogeneity in clinical and
metabolic status to to assure that any correlations between body composition
and serum electrolyte concentrations would have general validityโ
๏ง Isotope administration Na34 and K42
๏ง D2O administration
๏ง Regression equations obtained by least squares method
๏ง Equilibrium time is never straightforward-main issue
22. Edelmanโs results
- 1958 -
๏ง Nap is a reflection of the ratio between the sum of monovalent cations (Na and K) and
TBW โ the slope is ~1
๏ง The y-intercept (Na for a ratio=0) โprobably is a measure of the quantity of osmotically
inactive exchangeable sodium and potassium per unit of body water.โ
23. Edelman revisited
Nguyen, Kurtz
What do the slope and the y-
intercept stand for in terms
of physiological significance?
Comprehensive
mathematical description of
factors determining Nap
Appreciation of the fact that
the slope as well as the y-
intercept might be variable
in certain disease states
Multiple equations derived
to serve particular issues e.g.
definition of an isonatric
urine
๏ง Still perfectible in
terms of
mathematical
manipulation of
physiological
parameters
๏ง Disease states
might be
characterized by
activation of
inactive pools or
vice versa(resistant
Na-HTN) # Nguyen
et al. J Appl Physiol
102: 445โ447,
2007.
While there is still uncertainty regarding the 95% conf.interval of the slope and
y-intercept, the Nguyen&Kurtz formula โis worth oneโs saltโ (J Appl Physiol
100: 1105โ1106, 2006;) as it highlights all Na-determinants.
Ring, Troels, J Appl
Physiol 101: 692โ
694, 2006
INTRACTABLE
ABRACADABRA
Denmark, Aalborg
Dorrington, J Appl
Physiol 104: 569,
2008
PROOF or SPOOF
UK, Oxford
www.soapoperadigest.com
โThe truth is in the spoofโ
Napw =
๐ฎ
๐ฃ
ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
-
๐ฎ
๐ฃ
ร
๐ต๐ ๐๐๐ ๐๐๐๐๐๐๐๐+๐ฒ ๐๐๐ ๐๐๐๐๐๐๐๐
๐ป๐ฉ๐พ
โ
๐ถ๐๐๐ฐ๐ช๐ญ+๐ถ๐๐๐ฌ๐ช๐ญ
๐ป๐ฉ๐พ
+ ๐ฒ๐๐ +
๐ถ๐๐๐๐ ๐๐
๐ฝ ๐๐
Napw = ๐. ๐๐ ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
- 25.6
24. Edelman revisited
Nguyen, Kurtz
โThe truth is in the spoofโ
Napw =
๐ฎ
๐ฃ
ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
-
๐ฎ
๐ฃ
ร
๐ต๐ ๐๐๐ ๐๐๐๐๐๐๐๐+๐ฒ ๐๐๐ ๐๐๐๐๐๐๐๐
๐ป๐ฉ๐พ
โ
๐ถ๐๐๐ฐ๐ช๐ญ+๐ถ๐๐๐ฌ๐ช๐ญ
๐ป๐ฉ๐พ
+ ๐ฒ๐๐ +
๐ถ๐๐๐๐ ๐๐
๐ฝ ๐๐
Napw = ๐. ๐๐ ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
- 25.6
๏ง G=correction factor as dictated
by Gibbs-Donnan equilibrium
(1.04)
๏ง ฮ=average osmotic coeffiecient
of osmotic salts(0.93)
๏ง Nae, Ke=total exchangeable
cations(osm. Active + inactive)
๏ง Osm = osmoles non Na, non K
๏ง Pw=plasma water
๏ง ICF=intracellular fluid
๏ง ECF=extracellular fluid
(PW+ISF)
Nap = ๐. ๐๐ ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
- 23.8Plasma has 93% water
๏ง
๐ฎ
๐ฃ
๏ง
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
๏ง
๐ต๐ ๐๐๐ ๐๐๐๐๐๐๐๐+๐ฒ ๐๐๐ ๐๐๐๐๐๐๐๐
๐ป๐ฉ๐พ
๏ง
๐ถ๐๐ ๐ฐ๐ช๐ญ+๐ถ๐๐๐ฌ๐ช๐ญ
๐ป๐ฉ๐พ
๏ง ๐ฒ ๐๐
๏ง
๐ถ๐๐๐๐ ๐๐
๐ฝ ๐๐
๏ง Increase
๏ง Increase
๏ง Decrease
๏ง Increase
๏ง Decrease
๏ง decreaseโฒ
๏ง With all parameters left
unchanged except for
๐ต๐ ๐๐๐ ๐๐๐๐๐๐๐๐+๐ฒ ๐๐๐ ๐๐๐๐๐๐๐๐
๐ป๐ฉ๐พ
,
increasing this one will
translate into cation
inactivation and thereby a
plasma sodium decrease
๏ง OsmECF + OsmICF (Ca2+,Mg2+ ,
organic cations, glucose etc)=
OsmISF + OsmPW + OsmICF OsmPW
will oppose the other two but
mass balance will eventually
favor a direct proportionality :
Napw versus
๐ถ๐๐ ๐ฐ๐ช๐ญ+๐ถ๐๐ ๐ฌ๐ช๐ญ
๐ป๐ฉ๐พ
25. Unforseen theoretical implications
Defining the role of albumin infusion
in cirrhosis-associated hyponatremia
Nguyen, Am J Physiol Gastrointest Liver Physiol
307: G229โG232, 2014
๏ง โwe have demonstrated for the first time that
changes in the [Alb] can directly lead to changes in
the [Na] due to the effect of Gibbs-Donnan
equilibrium. Our findings demonstrated that, for
each 1 g/dl increase in the plasma [Alb], plasma [Na]
is expected to increase by 1 mmol/l due to the Gibbs-
Donnan effectโ
26. Unforseen clinical implications
โFluid overconsumption or retention of a moderate fluid overload is the
โeasiestโ way to induce EAH. Loss of the electrolytes sodium and potassium
can be significant over time and in hot weather, and should be considered in
post-event rehydration. The most effective treatment of hyponatraemia
associated to exercise would be to induce excretion of EFWโ
27. More than eleven equations
Nguyen et al, Kidney International, Vol. 68
(2005), pp. 1982โ1993
just keep in mind that people cannot be beakers1
28. Numerators as well as denominators
- how to assess them both simultaneously -
+100
mmol
NaCl
1M
cation challenge test
Assess carefully any other โV and
โE over the next 10-15 minutes
Adrogue and Madias, J Am Soc Nephrol 23:
1140โ1148, 2012
Draw blood test, measure Nap1
Draw blood test, measure Nap2
Solve the 2
unknowns
Solve for (Nae+Ke) and TBW1
Use the values for further predictionsjust keep in mind that people cannot be beakers2
HOW MUCH?
Nap2 = ๐. ๐๐ ร
๐ต๐ ๐+๐ฒ๐+๐๐๐
๐ป๐ฉ๐พ ๐+๐.๐
- 23.8
Nap1 = ๐. ๐๐ ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ ๐
- 23.8
29. Do they work?
๏ง 66 patients, 681 patient-days(194 hypernatraemic)
๏ง Excellent output-input balance
๏ง Day-per-day change in plasma sodium concentration
๏ง Results are definitely not to be expanded to hyponatremic patients as per authorโs conclusions
30. ๏ง all four formulae were inaccurate in the clinical setting for different reasons
๏ง although there is a good correlation between the predicted and actual changes for the whole group, the formulae were
unable to predict changes in the serum sodium level in the individual patient and thus are not without risk in practice
๏ง the analysis of major pathophysiological mechanisms (extrarenal and renal losses of electrolyte-free water, volume
status, etc) that contributes to hypernatraemia was more important for therapy guidance than all the proposed formulae
(see Halperin, Crit Care Clin 2002; 18:249โ272)
just keep in mind that people cannot be beakers3
32. Some think they do
EFWC = Vu ร (๐ โ
๐ผ ๐ต๐จ + ๐ผ ๐ฒ
๐ท ๐ต๐จ
))
โEFWC
33. Are they really spoof or intractable abracadabra?
Napw =
๐ฎ
๐ฃ
ร
๐ต๐ ๐+๐ฒ๐
๐ป๐ฉ๐พ
-
๐ฎ
๐ฃ
ร
๐ต๐ ๐๐๐ ๐๐๐๐๐๐๐๐+๐ฒ ๐๐๐ ๐๐๐๐๐๐๐๐
๐ป๐ฉ๐พ
โ
๐ถ๐๐๐ฐ๐ช๐ญ+๐ถ๐๐๐ฌ๐ช๐ญ
๐ป๐ฉ๐พ
+ ๐ฒ๐๐ +
๐ถ๐๐๐๐ ๐๐
๐ฝ ๐๐
๐ต๐ ๐=
๐ฝ๐๐๐๐๐ร(๐ต๐๐๐๐+๐ฒ๐๐๐) + ๐ป๐ฉ๐พร๐ต๐ ๐
๐ป๐ฉ๐พ+๐ฝ๐๐๐๐๐
๐ต๐ ๐=
๐ฝ๐๐๐๐๐๐๐ร ๐ต๐๐๐๐๐๐+๐ฒ๐๐๐ ๐๐ โ๐ฝ๐๐ ๐๐๐ร ๐ต๐ ๐๐๐+๐ฒ๐๐๐ + ๐ป๐ฉ๐พร๐ต๐ ๐
๐ป๐ฉ๐พ+โ๐ฝ๐๐
โบacute water diuresis (EFWC) is most often responsible for overcorrectionโ
Mohmand et al, Clin J Am Soc Nephrol 2: 1110โ1117, 2007
Spasovski et al, European Journal of Endocrinology (2014) 170, G1โG47
Verbalis et al, The American Journal of Medicine (2013) 126, S1-S42
just keep in mind that people cannot be
beakers
4
34. โบacute water diuresis (EFWC) is most often responsible for overcorrectionโ
Mohmand et al, Clin J Am Soc Nephrol 2: 1110โ1117, 2007
Spasovski et al, European Journal of Endocrinology (2014) 170, G1โG47
Verbalis et al, The American Journal of Medicine (2013) 126, S1-S42
People actually can be turned into human
beakers.
๏ง Sterns, Kidney International
(2009) 76, 587 โ 589
๏ง Kengne, Kidney International
(2009) 76, 614โ621
Predictable,
constant UO
and Uosm.
Overcorrection of hNa+ is a medical emergency
- lessons learned from rats -
35. โบacute water diuresis (EFWC) is most often responsible for overcorrectionโ
Mohmand et al, Clin J Am Soc Nephrol 2: 1110โ1117, 2007
Spasovski et al, European Journal of Endocrinology (2014) 170, G1โG47
Verbalis et al, The American Journal of Medicine (2013) 126, S1-S42
36. Human Beakers
Desmopressin 2-4mcg/6h
๐ต๐ ๐=
๐ฝ๐๐๐๐๐ร(๐ต๐๐๐๐+๐ฒ๐๐๐) + ๐ป๐ฉ๐พร๐ต๐ ๐
๐ป๐ฉ๐พ+๐ฝ๐๐๐๐๐
๐ต๐ ๐=
๐ฝ๐๐๐๐๐๐๐ร ๐ต๐๐๐๐๐๐+๐ฒ๐๐๐ ๐๐ โ๐ฝ๐๐ ๐๐๐ร ๐ต๐ ๐๐๐+๐ฒ๐๐๐ + ๐ป๐ฉ๐พร๐ต๐ ๐
๐ป๐ฉ๐พ+โ๐ฝ๐๐
Preemtively or as a rescue therapy
Rochester General Hospital, Professor Richard Sterns
Control UO and UOsm
39. Clinical practice guideline on diagnosis and treatment of hyponatraemia โ 2014
Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert
Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen and Evi Nagler on behalf of the Hyponatraemia Guideline Development Group. European Journal of Endocrinology (2014) 170, G1โ
G47; Intensive Care Med. 2014 Mar;40(3):320-31; Nephrol Dial Transplant. 2014 Apr;29 Suppl 2:i1-i39
๏ง Frequent monitoring of UO, Nap, urinary electrolytes
๏ง Use of 3% and less often higher than that
๏ง Use of desmopressin 1-4mcg/6-8h preemtively
๏ง Treat overcorrection as a medical EMERGENCY
๏ง Eventually use D5W or 0.45 saline
๏ง Use the 6 rule as an aim and limit the increase to 8-10mmol/24h
๏ง Have a low treshold to declare at risk of ODS
๏ง Have a low treshold to search for other explanations related to supposedly hyponatremia-
symptoms especially in case of moderate-mild hNa (biochemically)
๏ง Search for causes of โcontextual SIADHโ
๏ง May use an equation based management as long as frequent monitoring and clinical
judgement + physiological reasoning are not curtailed
๏ง Avoid using vaptans โ unpredictable behavior
๏ง Potassium will increase Nap as per Edelman equation โ fatal case review see Berl et al,
American Journal of Kidney Diseases, Vol 55, No 4 (April), 2010: pp 742-748
๏ง In case of overcorrection you may use CS but primordial is reversing the Na increase
Controlled hyponatremia correction
- Sternsโ management -
๏ง Sterns, Clin J Am Soc Nephrol 3: 331-336, 2008
๏ง Sterns, Kidney International (2009) 76, 587 โ 589
๏ง Kengne, Kidney International (2009) 76, 614โ621
๏ง Sterns, Am J Kidney Dis 56:774-779. 2010
Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations-2013
Joseph G. Verbalis, Steven R. Goldsmith, Arthur Greenberg, Cynthia Korzelius, Robert W. Schrier, Richard H. Sterns, Christopher J. Thompson. The American Journal of Medicine (2013) 126, S1-
S42