Download Sodium: Conspicuous by its Absence

SODIUM
CONSPICUOUS BY ITS ABSENCE
Larry Krevolin D.O. FASH
Clinical Nephrology Associates
Drexel University College of Medicine
1
Epidemiology of Hyponatremia (<130 mEq/L)
in a Study at a General Hospital
• Daily incidence and prevalence of ~1% and
2.5%, respectively
• 67% of all hyponatremia cases were hospitalacquired
• Mean minimal serum [Na+] was approximately
125 mEq/L
• Values <120 mEq/L were observed in 12% of
hyponatremic patients
Anderson RJ et al. Ann Intern Med. 1985;102:164-168.
2
Total, Admission, and Hospital-Acquired
Hyponatremia in Acute Hospital Care
50
Total
40
Occurrence (%)
42.6
Admission
Hospital-acquired
28.2
30
20
14.4
10
6.2
1.2
0.5
0.7
2.5
3.7
0
Na < 116
Na < 126
Na < 136
Serum [Na+] (mEq/L)
Data are from the Tan Tock Seng Hospital in Singapore, and are based on 303,577 samples from 120,137 patients available
for analysis.
Hawkins RC. Clin Chim Acta. 2003;337(1-2):169-172.
3
4
Hyponatremia Associated Mortality
5
Hyponatremia And Mortality
6
Hyponatremia Associated Mortality
7
Risk Factors for Hyponatremia
Selected Conditions1
Selected Drug Classes
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Congestive Heart Failure
Cirrhosis
SIADH
Very young or very old age
Adrenal insufficiency
Hypothyroidism
Renal dysfunction
Central nervous system
impairment
• Surgery or injury
Diuretics1,2
NSAIDs1,2
Opiate derivatives1,2
Antidepressants1,2
Antipsychotics1,2
Antiepileptic agents1,2
Anticancer agents1,2
Antihypertensive agents2
Proton-pump inhibitors2
[Na+] <135 mEq/L3
NSAIDS = nonsteroidal anti-inflammatory agents, SIADH = syndrome of inappropriate antidiuretic hormone.
1. Adrogué HJ. Am J Nephrol. 2005;25:240-249. 2. Liamis G et al. Am J Kidney Dis. 2008;52:144-153.
3. Ellison DH, Berl T. N Engl J Med. 2007;356:2064-2072.
8
Epidemiology of Hyponatremia (<130 mEq/L)
in a Study at a General Hospital (cont’d)
9%
5%
34%
16%
17%
Normovolemia
Hypovolemia
Edema
Hyperglycemia
Renal Failure
Error
19%
N = 196
Anderson RJ et al. Ann Intern Med. 1985;102:164-168.
9
Hyponatremia Is Common in the ICU
Hyponatremia
(Na+ ≤ 134 mEq/L)
(n=29),
29.6%
Patients admitted
consecutively to ICU (n=98)
DeVita MV et al. Clin Nephrol. 1990;34(4):163-166.
10
Special Considerations in the ICU1,2
• Administration of intravenous fluid is common
• Ventilated and sedated patients
– Signs and symptoms may not be observable
– Reduced access to free water
• Reliance on nutritional support
• Serious underlying disease
• Non-osmotic stimuli for vasopressin release
–
–
–
–
Nausea
Pain
Narcotics
Stress
1. Lee JW. Electrolyte Blood Press. 2010;8(2):72-81; 2. Rosner MH, Ronco C. Contrib Nephrol. 2010;165:292-298.
11
12
13
Risk Factors for ICU-Acquired
Hyponatremia
Serum [K+]
3.5–5.0 mmol/L
(P<0.001)
>5.0 mmol/L
(P=NS)
<3.5 mmol/L
Temperature
35.0–37.3 °C
>37.3 °C
(P=0.005)
<35.0 °C
(P=0.008)
Glucose (each additional 1 mmol/L)
(P<0.001)
Minimum Glasgow Coma Scale (each additional unit)
(P<0.001)
(P<0.001)
Day of ICU stay (each additional log unit day)
(P<0.001)
APACHE II score (each additional unit)
Admitting diagnosis category
Surgical
(P=0.017)
(P=0.012)
Neurological/trauma
Medical
(P=0.004)
Age (each 10 year increase)
0.5
ICU-acquired hyponatremia (serum [Na+] <133 mEq/L)
was identified in 917 (11%) patients.
Stelfox HT et al. Crit Care. 2008;12(6):R162.
1
1.5
2
2.5
Favors development of ICU-acquired hyponatremia
Odds Ratio (95% CI)
14
The Cost Associated With Hyponatremia
in the United States
• The estimated direct cost of treating hyponatremia ranges
between $1.6 billion and $3.6 billion per year1
– Based on inpatient hospital discharge data, published literature,
and an expert consensus panel, from a 2006 article
• One-year medical costs for patients with normal serum [Na+]
were $9,257 versus $19,215 for patients with hyponatremia2
– Based on data from a large managed care database involving
more than 162,000 patients
• In hospitalized patients, the increase in costs attributable to
hyponatremia was $2,2893
– Based on data from 198,281 patients in a database comprising
39 hospitals
1. Boscoe A et al. Cost Eff Resour Alloc. 2006.31;4:1-11.
2. Shea AM et al. J Am Soc Nephrol. 2008;19(4):764-770.
3. Zilberberg MD et al. Curr Med Res Opin. 2008;24(6):1601-1608.
15
Hyponatremia Treatment:
“Unsafe At Any Speed”
“Be quick but don’t hurry”
John Wooden
16
Hyponatremia: A Disorder Of Water
Serum [Na+] ~
Acknowledge Communication by R. H. Sterns.
Verbalis JG et al. Am J Med. 2007;120(11 suppl 1):S1-S21.
Na+E + K+E
Body water
17
Body Fluid Distribution
18
Volume Regulatory Hypothesis
 Extracellular Fluid
Volume
Low Output Cardiac Failure,
Pericardial Tamponade,
Constrictive Pericarditis
 Oncotic Pressure
and/or
Capillary Permeability
 Cardiac Output
Activation of Ventricular
and Arterial Receptors
Non-osmotic
Vasopressin
Simulation
Renal Water
Retention
Stimulation of Sympathetic
Nervous System
Activation of the
Renin-AngiotensinAldosterone System
Peripheral and Renal
Arterial Vascular Resistance
Renal Sodium
Retention
Maintenance of Arterial
Circulatory Integrity
19
Sodium And Water Retention With Plasma
Volume Expansion In Edematous Disorders
Normal
Venous
and
Capillary
(85%)
Normal
Arterial
Underfilling Cardiac Output
Arterial (15%)
20
21
Cardiac Failure
Diminished Distal Sodium and Water Delivery to Sites of Action
of Vasopressin, Aldosterone and Atrial Natriuretic Peptide
Reabsorption
Distal Na and
H2O Delivery
PROXIMAL
TUBULE
CORTICAL
COLLECTING
DUCT
 Vasopressin
 Aldosterone
OUTER MEDULLA
COLLECTING
DUCT
INNER MEDULLA
COLLECTING
DUCT
 Vasopressin
 Aldosterone
 Vasopressin
 Atrial Natriuretic Peptide
22
23
24
25
Role of Vasopressin in the
Pathophysiology of Hyponatremia
• Peptide hormone composed of
9 amino acids
• Synthesized within the
supraoptic and paraventricular
nuclei of the hypothalamus
– Transported from the
hypothalamus via nerve tracts
to the neural lobe of the
pituitary, where it is released
into circulation
• Regulates urinary water
excretion
Verbalis JG, Berl T. Disorders of water balance. In: Brenner BM. Brenner and Rector's The Kidney. 8th ed. Philadelphia, PA:
Saunders; 2007:chap 13.
26
Vasopressin V1a Receptor Subtype
V1a Sites of Action
• Vascular smooth muscle
• Platelets
• Brain
• Hepatocyte
• Uterine muscle
• Adrenal gland
Physiologic Effects
• Vasoconstriction
• Myocardial hypertrophy
• Platelet aggregation
• Memory, BP and HR regulation, other*
• Glycogenolysis
• Uterine constriction
• Aldosterone and cortisol secretion
*Stress adaptation, social recognition, circadian rhythmicity, temperature regulation.
Decaux G et al. Lancet. 2008;371:1624-1632.
27
Vasopressin V1b Receptor Subtype
V1b Sites of Action
• Anterior pituitary
• Brain
• Pancreas
Physiologic Effects
• Release of ACTH/
β-endorphins
• Stress adaptation
• Insulin release
ACTH = adrenocorticotropic hormone.
Decaux G et al. Lancet. 2008;371:1624-1632.
28
Vasopressin V2 Receptor Subtype
V2 Sites of Action
• Renal collecting ducts (primary)
• Pneumocytes
• Vascular endothelium
• Vascular smooth muscle
Physiologic Effects
• Free water resorption
• Stimulation of sodium resorption
• Release of von Willebrand factor
and factor VIII
• Vasodilation
Decaux G et al. Lancet. 2008;371:1624-1632.
29
Effect of Vasopressin on
Renal Water Handling
Modified from Mayinger B, Hensen J. Exp Clin Endocrinol Diabetes. 1999;107:157-165.
30
31
Nonosmotic Stimuli for Vasopressin
Nausea
Medications
Pain/
stress
Tumors
Pulmonary
diseases
CNS
diseases
Hypovolemia
Freda BJ et al. Cleve Clin J Med. 2004;71(8):639-650.
32
Mechanisms of Drug-Induced
Hyponatremia
 Hypothalamic Production
of Vasopressin
•
•
•
•
•
 Vasopressin Effect at
Renal Tubule Level
• Antidiabetic drugs
(chlorpropamide, tolbutamide)
• Antiepileptics (carbamazepine,
lamotrigine)
• IV cyclophosphamide
• NSAIDs
Antidepressants (TCAs, SSRIs, MAOIs)
Antipsychotics (phenothiazines, haloperidol)
Antiepileptics (carbamazepine, valproic acid)
Antineoplastic agents
Opiates
Alter Na/H2O Homeostasis
• Thiazide diuretics/indapamide
• Amiloride
• Loop diuretics
MAOIs = monoamine oxidase inhibitors; NSAIDs = nonsteroidal antiinflammatory drugs; SSRIs = selective serotonin
reuptake inhibitors; TCAs = tricyclic antidepressants.
Adapted from Liamis G et al. Am J Kidney Dis. 2008;52(1):144-153.
33
Proposed Mechanisms of
Thiazide-Induced Hyponatremia
• Impair urinary dilution at distal convoluted tubule
•  ADH due to  volume
• Excess total body loss of solutes (K, Na) relative to
H2O losses
• Coexisting hypokalemia leading to cation exchange
(K leaves cells and Na moves into cells to preserve
electroneutrality)
• Stimulate thirst
• Excessive ADH secretion
• Magnesium depletion
Adapted from Liamis G et al. Am J Kidney Dis. 2008;52(1):144-153.
34
Characteristics of
Thiazide-Induced Hyponatremia
• In an observational study, thiazide-induced hyponatremia
occurred in 13.7% of treated patients1
• Thiazides implicated in 26% of hyponatremic subjects2
• Thiazides used in 75% of hospitalized hypertensive
patients, in a retrospective analysis3
• Risk factors4
–
–
–
–
Increasing age
Female sex
Low body weight
Increased incidence in summer5
1. Clayton JA et al. Br J Clin Pharmacol. 2006;61(1):87-95. 2. Bissram M et al. Intern Med J. 2007;37(3):149-155.
3. Sharabi Y et al. J Hum Hypertens. 2002;16(9):631-635. 4. Chow KM et al. J Natl Med Assoc. 2004;96(10):1305-1308.
5. Gross P, Palm C. Nephrol Dial Transplant. 2005;20(11):2299-2301.
35
Diuretic Therapy
36
SSRI-Induced Hyponatremia
• Incidence of SSRI-induced hyponatremia varies from
0.5% to 32%1-3
• Most cases occur within first few weeks of therapy1-3
– Normal sodium levels typically achieved within 2 weeks after
drug discontinuation
• Risk factors1,2
–
–
–
–
Older age
Concomitant diuretic use
Low body weight
Lower baseline serum [Na+]
1. Liamis G et al. Am J Kidney Dis. 2008;52(1):144-153.
2. Jacob S, Spinler SA. Ann Pharmacother. 2006;40(9):1618-1622.
3. Bouman WP et al. Int J Geriatr Psychiatry. 1998;13(1):12-15.
37
Common Symptoms Associated
With Hyponatremia
Serum [Na+] 130-135 mEq/L1,2
•
•
•
•
•
•
•
•
•
Asymptomatic
Headache
Nausea
Vomiting
Fatigue
Confusion
Anorexia
Muscle cramps
Depressed reflexes
Serum [Na+] 120-130 mEq/L1,2
•
•
•
•
•
•
•
•
•
Malaise
Unsteadiness
Headache
Nausea
Vomiting
Fatigue
Confusion
Anorexia
Muscle cramps
1. Bagshaw SM et al. Can J Anesth. 2009;56:151-161.
2. Ghali JK. Cardiology. 2008;111:147-157.
Serum [Na+] <120 mEq/L1,2
•
•
•
•
•
•
•
Headache
Restlessness
Lethargy
Seizures
Brainstem herniation
Respiratory arrest
Death
38
Acute Hyponatremia (<36-48 hrs):
Severe Osmotic Cerebral Edema
39
Brain Volume Adaptation
With Hyponatremia
Reprinted from Adrogué HJ, Madias NE. N Engl J Med. 2000;342:1581-1589.
40
Cellular Mechanisms Underlying Volume
Regulatory Losses Of Brain Electrolytes
normal cell volume
(isotonic ECF)
increased cell volume
(hypotonic ECF)
Image provided by J. Verbalis; Personal research, J. Verbalis.
41
Reduction of Brain Organic Osmolytes
After 14 Days of Sustained Hypoosmolality
Brain Osmolyte Content
(mmol/kg DBW)
60
Normonatremic control rats (n=15)
Sustained hyponatremic rats (n=21)
50
40
*
30
*
20
10
0
*
*
Inositol
Glutamate Glutamine
*
Taurine
Creatine
GPC
Urea
*P< 0.01 compared to normonatremic control rats.
Verbalis JG, Gullans SR. Brain Res. 1991; 567:274-282.
42
Brain Volume Regulation
1. true loss of
brain solute
2. can reduce or
eliminate brain
edema despite
severe
hypoosmolality
3. time dependent
process
THIS IS NOT A NORMAL BRAIN!
Gullans & Verbalis Ann Rev Med 44:289-301, 1993
43
Falls Are a Common Symptom of Chronic
“Asymptomatic” Hyponatremia
44
Hyponatremia Induced Ambulatorty
Dysfunction
45
Hyponatremia Induced Osteopenia
46
Hyponatremia Induced Osteopenia
47
Volume Status and Common Etiologies
of Major Classes of Hyponatremia
Hypervolemic
Euvolemic
Hypovolemic
Volume status
Total body water
Total body sodium
Unchanged
Extracellular fluid
Greatly increased
Edema
Present
Absent
Absent
Etiologies
Congestive heart
failure
Cirrhosis
Nephrotic syndrome
Acute/chronic renal
failure
SIADH
- Drugs (antidepressants,
antipsychotics,
barbiturates, nicotine,
NSAIDs, morphine,
vincristine)
- Physical/emotional stress
Glucocorticoid deficiency
Diuretic excess
Mineralocorticoid deficiency
Salt-losing nephritis
Osmotic diuresis
Ketonuria
Bicarbonaturia
Vomiting or diarrhea
(extrarenal origin)
Third-spacing (ie, burns,
pancreatitis)
Adapted from Douglas I. Cleve Clin J Med 2006;73(suppl 3):S4-S12, Copyright © 2006 The Cleveland Clinic Foundation with permission; adapted from data in Schrier R.
The patient with hyponatremia or hypernatremia. In: Schrier RW, ed. Manual of Nephrology. 5th ed. Philadelphia PA: Lippincott Williams & Wilkins;2000:21-36, and Craig S.
48
Hyponatremia. eMedicine Web site. Updated January 20, 2005. Available at http://www.emedicine.com/emerg.topic275.htm. Accessed April 13, 2005.
Hypotonic Hyponatremia
49
Role of Vasopressin in
Edematous Disorders
Cirrhosis
CHF
↓ Cardiac
output
↓ Peripheral
Arterial Underfilling
Stimulation of Arterial Baroreceptors
vascular
resistance
due to
splanchnic
vasodilation
Nonosmotic Release of Vasopressin
Impaired Water Excretion
Hypervolemic Hyponatremia
Janicic N, Verbalis JG. Endocrinol Metab Clin North Am. 2003;32:459-481.
50
Cardio-Renal Axis
Natriuretic Peptide
System
• Natriuretic
• Diuretic
• Vasodilating
RAAS and AVP
• Sodium and water
retaining
• Vasoconstricting
• Renin and
aldosterone
inhibiting
51
The Cardio-Renal Syndrome
• Decreased cardiac
performance
• Neurohormonal
activation
• Increased water
and Na+ retention
(Congestion)
• Impaired renal
function
• Decreased renal
perfusion
52
Role of Vasopressin in HF
Cardiac
Output
Hypervolemic
hyponatremia
Arterial
Underfilling
Stimulation of
arterial
baroreceptors
Impaired
water
excretion
Nonosmotic release
of vasopressin
Janicic N, Verbalis JG. Endocrinol Metab Clin North Am. 2003;32(2):459-481.
Schrier RW, Ecder T. Mt Sinai J Med. 2001;68(6):351-361.
53
Neuroendocrine Activation in HF
Schrier RW, Abraham WT. N Engl J Med. 1999;341(8):577-585.
54
55
56
57
Role of Vasopressin in Liver Failure
Splanchnic
vasodilatation
Arterial
Underfilling
Hypervolemic
hyponatremia
Stimulation of
arterial
baroreceptors
Impaired
water
excretion
Nonosmotic release
of vasopressin
Adapted from Janicic N, Verbalis JG. Endocrinol Metab Clin North Am. 2003;32(2):459-481.
58
59
60
61
62
Essential Criteria for Diagnosis of SIADH
1
 Effective osmolality of the ECF
– Posm <275 mOsmol/kg H2O
2
Inappropriate urinary concentration
3
Clinical euvolemia
– Uosm >100 mOsmol/kg H2O with normal renal function at
some level of hypoosmolality
– No signs of hypovolemia (orthostasis, tachycardia,  skin
turgor, dry mucous membranes) or hypervolemia
(subcutaneous edema, ascites)
4
5
Elevated urinary sodium excretion despite normal salt and
water intake
No other potential causes of euvolemic hypoosmolality
(eg, hypothyroidism, hypocortisolism, diuretic use)
Posm = plasma osmolality; Uosm = urinary osmolality.
Janicic N, Verbalis JG. Endocrinol Metab Clin North Am. 2003;32(2):459-481.
63
SIADH Can Be Common in the ICU
98 patients admitted consecutively to ICU
Hyponatremia (Na ≤134 mEq/L)
(n=29), 29.6%
No further study
(n=10)
Serum and urine data
(n=12)
No serum hypoosmolality
(n=2)
Serum hypoosmolality
(n=10)
Urine not maximally dilute
Urine [Na+] >30 mEq/L
SIADH
ICU = intensive care unit.
DeVita MV et al. Clin Nephrol. 1990;34(4):163-166.
64
Special Considerations in the ICU1,2
• Administration of intravenous fluid is common
• Ventilated and sedated patients
– Signs and symptoms may not be observable
– Reduced access to free water
• Reliance on nutritional support
• Serious underlying disease
• Non-osmotic stimuli for vasopressin release
–
–
–
–
Nausea
Pain
Narcotics
Stress
1. Lee JW. Electrolyte Blood Press. 2010;8(2):72-81; 2. Rosner MH, Ronco C. Contrib Nephrol. 2010;165:292-298.
65
Vasopressin Levels Inappropriately
Elevated in Patients With SIADH
Plasma Vasopressin (pg/mL)
50
30
10
NORMAL
RANGE
8
6
4
2
240
250
260
270
280
290
300
310
320
Plasma Osmolality (mOsmol/kg)
Adapted with permission from Zerbe R et al. Annu Rev Med. 1980;31:315-327.
66
Vasopressin Secretion In SIAD
67
Cerebral Salt Wasting vs SIADH
CSW
SIADH
Head injury or neurosurgical procedures
Numerous etiologies
Disruption of neural input to the kidney
OR
CNS-induced release of a natriuretic factor
Excessive AVP release
Reductions in proximal sodium reabsorption
and renin release
Renal water reabsorption
Contraction of ECF volume
Expansion of ECF volume;
Normal or slightly increased intravascular volume
Manage with sodium and volume
replacement
Manage with fluid restriction and/or
aquaresis
CSW = cerebral salt wasting
Palmer BP. Semin Nephrol. 2009;29(3):257-270; Verbalis JG et al. Am J Med. 2007;120(11 suppl 1):S1-S21.
68
69
SIADH vs. Cerebral Salt Wasting
70
“We can’t figure it out. Mind if we call in a quack?”
71
Assessing Effective Arterial Blood
Volume
Physical Examination
• Orthostatic changes
(pulse, BP)
• Jugular venous distention
• Skin turgor
• Dry mucous membranes
•
•
•
•
Sunken eyes
Edema
Ascites
Pulmonary congestion
Laboratory
•
•
•
•
BUN/creatinine
Albumin
Hematocrit
Uric Acid
Palmer BF. J Hosp Med. 2010;5(suppl 3):S1-S7.
Palmer BF et al. Ann Pharmacother. 2003;37:1694-1702.
Douglas I. Cleve Clin J Med. 2006;73(suppl 3):S4-S12.
• Urine electrolytes:
- Na+K+Cl- Creatinine
- Fractional excretion of sodium
72
Laboratory Assessment of Hyponatremia
Parameter
Normal Value
Serum osmolality
275–290 mOsm/kg H2O
Urine osmolality
50–1200 mOsm/kg H2O
Urine sodium
<20 mEq/L (low effective circulating volume
states)
>20–40 mEq/L (euvolemic patients without
decreased effective circulating volume)
Plasma glucose
Serum Na  1.6–2.4 mmol/L for every 100 mg/dL 
in glucose > 100 mg/dL
Adrenal and thyroid
function tests
Vary by laboratory
Serum uric acid, BUN
Vary by laboratory
Freda BJ et al. Cleve Clin J Med. 2004;71(8):639-650.
73
Hyponatremia In Adrenal Disease
74
Urinary Indices In Hyponatremia
75
HYPOTONIC HYPONATREMIA
76
Causes Of SIAD
77
78
79
Treating Chronic Hyponatremia
• Limited correction may avoid iatrogenic
neurologic injury
– <10 mEq/L per 24 h
– <18 mEq/L per 48 h
– <20 mEq/L per 72 h
• To maximize patient safety, goals of therapy
should be more modest
– 6–8 mEq/L per 24 h
– 12–14 mEq/L per 48 h
– 14–16 mEq/L per 72 h
Sterns R et al. Semin Nephrol. 2009;29:282-299.
80
Patients at Risk for ODS
• Chronic hyponatremia
• Alcoholism
• Malnutrition
• Liver disease
• Burns
• Hypokalemia
• Serum Na 105 mEq/L
Kumar S, Berl T. Lancet. 1998;352(9123):220-228.
Sterns RH et al. Am J Kidney Dis. 2010;56(4):774-779.
81
82
83
Management Of SIAD
84
85
Formula To Manage Absolute
Hyponatremia
86
Sodium Infusion
87
Saline Infusions In Hyponatremia
88
Water Restriction In Hyponatremia
89
TLV Alone
TLV + Furosemide
TLV Alone
TLV + HCTV
Furosemide Alone
Baseline (Day–1)
HCTZ Alone
Baseline (Day–1)
5000
5000
4500
4500
4000
4000
Cumulative Urine Excretion (mL)
Cumulative Urine Excretion (mL)
Mean Cumulative Urine Excretion
for 24 Hours
3500
3000
2500
2000
1500
1000
500
3500
3000
2500
2000
1500
1000
500
0
0
0
4
8
12
Time (h)
16
20
24
Shoaf SE et al. J Cardiovasc Pharmacol. 2007;50(2):213-22.
0
4
8
12
Time (h)
16
20
24
90
Mean 24-hour Urinary Excretion
of Sodium
6
350
Baseline
TLV alone
Diuretic alone
TLV + Diuretic
300
250
200
150
100
50
TLV alone
Furosemide alone
TLV + Furosemide
4
Change From Baseline in Plasma Na+ (mEq/L)
24-Hour Urine Excretion of Sodium (mEq)
A
2
0
-2
-4
0
4
8
12
6
16
20
24
TLV alone
HCTZ alone
TLV + HCTV
4
2
0
-2
-4
0
Furosemide
HCTZ
0
4
8
12
16
20
24
Time (h)
Shoaf SE et al. J Cardiovasc Pharmacol. 2007;50(2):213-22.
91
Mean Free Water Clearance
8
8
TLV alone
Furosemide alone
TLV + Furosemide
Free Water Clearance (mL/min)
6
TLV alone
HCTZ alone
TLV + HCTZ
6
4
4
2
2
0
0
*
-2
-2
1
2
3
4
Time Post-dose (h)
Shoaf SE et al. J Cardiovasc Pharmacol. 2007;50(2):213-22.
1
2
3
4
Time Post-dose (h)
92
2013 ACCF/AHA Guideline for the Treatment
of Hyponatremia in Heart Failure
93
Extracorporeal Therapy In Dilutional
Hyponatremia
94
‘’If you don’t know where you are going, you will end up
someplace else”
Yogi Berra
95