"SODIUM and water: the CONDIMENT for fluid - CSHP

Learning Objectives
"SODIUM and water: the
CONDIMENT for fluid balance
in your patient"

Upon the completion of this session, the
learner will be able to:

Edward C. Dillon,
BA.,BSc.,BSc.Pharm.,ACPR., PharmD

Clinical Pharmacotherapy Specialist - ICU
Surrey Memorial Hospital
Fraser Health Authority
LMPS

Estimate the amount of total body water in
each of the following compartments: ICF,
ECF, ISF & IVF
List how many mOsm/L are provided by D5W,
NS, LRS & Plasmalyte
Calculate a Na & Water deficit
Apply a systematic process & effectively
assess hyponatremia in patient care & list one
pathological etiology
1
Personal Disclosures
2
Distribution of Total Body Water

I have no disclosures to report

Adult total body water (TBW) = 60% of
lean body weight (45-75%)
Intracellular fluid = 67% (2/3 TBW)
Extracellular fluid = 33% (1/3 TBW)

Chumlea WC et al. (1999) Kidney
Internat
3
Distribution of Total Body Water

New born body weight = 75-85% water
After puberty, % of water per kg
decreases with age as adipose tissue
increases with age

70 kg male has ~ 42 L of body water
Guyton & Hall Textbook of Medical
Physiology (2010)
5
4
Distribution of Total Body Water

Adult males have 50-65% body water by LBW
Adult females have 45-55% body water by
LBW
Interstitial fluid = 25% (75% ECW)
Intravascular fluid = 8% (25% ECW)
Water passes freely between the ICF & ECF
compartments
Each compartment is selectively permeable to
different solutes

K is major osmotically active cation in ICF (Mg, Na)
Na is major osmotically active cation in ECF (K, Ca,
Mg)
Solutes exert osmotic pressure to drive water
from low concentration gradients to higher
gradients
Guyton & Hall Textbook of Medical
Physiology (2010)
6
Fluid Losses

The Average 70 kg person looses 2.5
L/day:
Urine – 1500 mL
Skin – 400 mL
Air Expirations – 400 mL
Feces – 200 mL
Guyton & Hall Textbook of Medical
Physiology (2010)
7
Fluid Gains
Assessment of Hydration status

Gain water in three ways:
Fluids
Food
Oxidation of hydrogen in food

Symptoms of depletion appear when 15%
(525 mL) of blood volume is lost or shifts
out of the intravascular space
Subjective symptoms:

Guyton & Hall Textbook of Medical
Physiology (2010)
Dry MM
< skin turgor
Dizziness
Orthostatic changes in BP & HR
Washington Manual of Critical Care
(2012)
9
Assessment of Hydration status
Objective changes:

Water Deficit:

Tachycardia
Hypotension (SBP < 90 mm Hg)
BUN/Cr ratio > 0.08:1
< urine output
Calculated water deficit

Washington Manual of Critical Care
(2012)
11
10
Assessment of Hydration status

8
Vd (water) x LBW x (Existing
[Na]/140 -1)
0.5 L/kg (male) x 70 kg x (160/140 1)
5 L (male)
Vd (female) = 0.4 L/kg
LBW = kg; [Na] = mM/L
12
Crystalloids
Replacement Fluids

Replete the IVS to improve cardiac
function & organ perfusion
Given centrally @ rapid rates for
resuscitation
Crystalloids: D5W, NS, LRS, Plasmalyte
Colloids: Plasma, ALB
Solution (L)
Na
Cl
K
Ca
Mg
Lact
Acet
Gluc
D5%W
Dex
pH
Osm
Cost
50
5
278
1.34
100
4.3
33
504
1.89
3.3%D0.3%NS
51
5.2
263
1.48
0.9%NaCl
154 154
5.7
308
1.26
3% NaCl
513 513
5
1026
1.28
LRS
130 109
4
6.5
274
1.44
Plasmalyte A
140
5
7.4
294
6.95
D10%W
51
98
3
28
1.5
27
23
13
14
Crystalloids

Crystalloid Fluid Resuscitation
Contains water, Na, Cl &/or dextrose
LRS also contains lactate, K & Ca
Plasmalyte also contains K, Mg, Acetate &
Gluconate
Na & Cl remains only in the ECF & does
not freely cross into the cells (ICF)
For NS, LRS & Plasmalyte: 100% of the
volume distributes into the ECF (75% in
the ISF & 25% in the IVF)
Washington Manual of Critical Care
(2012)

Initial bolus:

Adults: 500 – 1000 mL & up to 30 mL/kg of NS
or LRS
Maintenance infusion:

> 20 kg: 1500 mL + 20 mL/kg per kg> 20 kg/d
> 50 kg: 20-40 mL/kg/day
Washington Manual of Critical Care
(2012)
15
D5W Fluid Resuscitation

Knowledge Test #1
Dextrose 5% Water (D5W) – considered
“free water” metabolized to H20 + CO2

Free water crosses into all compartments

67% into ICF/33% into ECF (75% in ISF + 25% in
IVF)
Equivalent to enterally-administered water
Consider clinical impact of glucose (DM)
Consider clinical impact of free water
expansion for over hydrated pts (CHF,
cerebral edema)
Washington Manual of Critical Care
(2012)
16
How much volume of a 2-litre bolus of
0.9% NaCl will stay in the intravascular
compartment?
1.
2.
3.
4.
5.
17
160 mL
250 mL
500 mL
600 mL
1500 mL
18
Knowledge Test #2
Colloids
How much volume of a 2-litre bolus of
D5W will stay in the intravascular
compartment during fluid resuscitation?

1.
2.
3.
4.
5.
Colloid (L)
160 mL
250 mL
500 ml
600 mL
1500 mL
Na
Cl
K
Ca Mg Dex pH Osm OP VE Cost/L
Plasma
140 100
ALB 5%
145 145
7
ALB 25%
145 145
7
4
1
5
7.4 285
N/A
292 25 80% 137.28
400
297 110 % 686.40
19
20
Colloids
Colloids

Very large molecules that do not cross
capillary membranes (IVS)
Used mainly for intravascular expansion in
patients that are euvolemic or hypervolemic
(ascites; pleural effusion)
May cause major fluid shifts due to oncotic
pressure gradient

Concerns: allergic rxn, impaired coagulation,
renal damage, more costly

Increase IVV
can be stored up to a year
From whole blood when RBC no longer viable
Useful for hypoproteinemia & maintaining oncotic
pressure
Administer < 10 mL/kg/h
21
Colloid

Useful for treating coagulation defects
Increase IVV
Frozen: colloids

Desirable for redistribution of fluids
Washington Manual of Critical Care
(2012)
Plasma:
Two types: fresh frozen or frozen
Fresh frozen: colloids & active clotting factors
Bartels K et al. Crit Care (2013)
22
Crystalloid & Colloid distribution
Albumin 5% or 25% (NS)

natural protein indicated for:
Dose:

volume expansion (VE) & oncotic deficit (OD)
VE: depends on hemodynamic response < 2 g/kg/d
OD: Determine TSA (d) – TSA (m) x IVV (50 mL/kg) x 2
60% in the EVF
t1/2 = 20 days in plasma
produces 80% of oncotic pressure
Draws 3.5 - 5 x its volume into the IVS within 30 min
effect lasts about 24-48 hours
stays within the intravascular space unless the capillary permeability is
abnormal
5% solution- isooncotic; 10% and 25% solutions – hyperoncotic
25 g/L is estimated to prevent peripheral edema
Side Effects- volume overload, fever (pyrogens in albumin), defects of
hemostasis
Bartels K et al. Crit Care (2013)
23
IV Fluid
Infused Volume
(mL)
Intravascular
expansion (mL)
Sodium content
(mEq)
0.45% NaCl
0.9% NaCl
3% NaCl
LRS
D5W
ALB 5%
ALB 25%
1000
1000
1000
1000
1000
500
100
183
250
250
250
100
500
500
77
154
513
130
0
72.5
14.5
24
Osmolality

Osmolality Calculation
Osmolality (mOsmol/kg) = Osmoles of
solute per kg solvent
Osmolarity (mOsmol/L) = Osmoles of
solute per litre solvent
Plasma osmolality reference range: 275295 mOsmol/kg

> osmolality Î cellular dehydration/shrinkage
< osmolality Î cellular over hydration/swell

Plasma Osmolality (mOsmol/kg) = 2 x [Na] +
[Glu] + [BUN]
[Na] = Sodium = mEq/L or mMol/L
[Glu] = Glucose = mMol/L
[BUN] = Blood Urea Nitrogen = mMol/L
D5W = 5 g/100 mL Î 278 mOsm/L
0.9% NS = 154 mM/L Na Î 308 mOsm/L
25
26
Osmoregulation

Isotonic fluids do not shift fluids between
compartments: osmolarity = plasma
Hypotonic fluids shift the water from the EC
space to the IC space

Cellular over hydration/swelling

Volume regulation

RBC rupture = hemolysis
Brain cells swell = cerebral edema
Hypertonic fluids shift water from the IC space
to the EC space

The serum Na concentration is determined
by the amount of EC water relative to the
amount of Na in the body
Water is regulated by two mechanisms:

Cellular dehydration/shrinkage
Thirst – osmoreceptive neurons regulate the
intake of free water
Vasopressin – released from pituitary gland to
> water reabsorption in distal tubule of
nephron & concentrate urine
27
28
Sodium

Na is the major cation of the ECF; responsible
for ECF volume regulation & osmotically
determining water distribution in the body

Sodium

Major determinant of membrane potential to actively
transport molecules across cell membranes

Kidney has major role in regulating Na balance

Na - [135-145 mM/L]
Increases in: dehydration; reduced water
intake; Diabetes Insipidus
Decreases in: severe burns; vomiting; diabetic
acidosis;
Aldosterone (> [Na]); natriuretic hormone (< [Na])
[Na] urine > 20 mM/L = renal excretion
[Na] urine < 20 mM/L = other pathways of Na
excretion
Washington Manual of Critical Care
(2012)
29
30
Sodium
Hyponatremia
Serum [Na] is a more
reliable indicator of
the patient’s fluid
status rather than Na
balance
Koda-Kimble & Young's Applied
Therapeutics 10th ed. (2013)

Most common electrolyte disorder
[Na]
120-125
Symptoms
Nausea, weak
115-120
Lethargy, h/a
< 115
Seizure, coma
Washington Manual of Critical Care
(2012)
31
Hyponatremia
Hyponatremia

Hypervolemia
Hyponatremia
Measured Osmolality?
2[Na]+[Glu]+[BUN] = 275-295 mOs/kg H20

Euvolemia
Three options:

Hypovolemia

hyperosmolal
Euosmolal
Hypoosmolal
Koda-Kimble & Young's Applied
Therapeutics (2013)
33
Hyponatremia

32
34
Hyponatremia
HyperOsmolal

DKA
EuOsmolal
pseudo-hyponatremia
hyperproteinemia)
> [Glu] 5.5 mM/L Î [Na] < 1.6 mM/L
Symptoms: confusion, collapse neck veins,
tachycardia, hypotension, dehydration,
orthostasis, oliguria, U[Na]<20 mEq/L
Treat underlying cause
Insulin & NS

(hyperlipidemia &
Usually asymptomatic
Treat underlying cause
Diet
Exercise
Statins

35
36
Pseudo-Hyponatremia

C
140 mM/1000 mL
A
140 mM/960 mL
1000 mL
Pseudo-Hyponatremia
=A/V
=A/1000 mL
= 140 mM
= 0.1458 mM/mL
= 145.8 mM
C=A/V
C=(0.1458
mM/mL x 920 mL)/1000 mL
C=134.1 mM/L
<
5% change => hyponatremia
37
38
Hyponatremia
Hyponatremia

HypoOsmolal

Volume status?

Hypo-Osmolal
Hypervolemic

Three options:
Hypervolemic
Euvolemic
Hypovolemic
CHF; Nephrotic Syndrome; Cirrhosis; Ascites

Symptoms: JVD, HJR, ascites, U [Na] < 20 mEq/L,
edema
Treat underlying cause
Fluid restriction
Medications
39
40
Hyponatremia
Hyponatremia

HypoOsmolal
Hypovolemic
Euvolemic

Syndrome of Inappropriate Anti-Diuretic
Hormone (SIADH) secretion

HypoOsmolal
diuretic, vomiting; diarrhea; fever

Asymptomatic
Endocrine disorders, stress, pain
U [Na] > 20 mEq/L; U Osm > 300 mOsmol/kg
Drug-induced Î discontinue drug (carbamazepine,
cyclophosphamide, vincristine)
Fluid restriction; NaCl 3%; furosemide
Vasopressin receptor antagonists

41
Other symptoms: confusion, lethargy, collapse neck
veins, dehydration, tachycardia, hypotension,
orthostasis, oliguria, acid-base & other electrolyte
disorders, [Na] < 20 mM/L, U Osm > 600 mOsm/kg,
weakness
Treat the underlying cause
Add or stop medication
Fluid resuscitation with NS (or 3% NaCl if indicated
by Na deficit)
42
Hypertonic Saline
Overall Treatment of Hyponatremia

Identify & treat the underlying cause to allow
the body to correct the hyponatremia
Correct the serum [Na] by no more than 10
mEq/day
Euvolemic & hypervolemic hyponatremia is
treated with fluid restriction (800-1200 mL/day)

+/- vasopressin antagonists

Hypovolemic hyponatremia managed with fluid
resuscitation & Na
Washington Manual of Critical Care
(2012)
3% NaCl

43
Spasovski G et al. (2014)
Vasopressin antagonists

> U/O Î > net fluid loss
< U osmolality
Restores serum [Na]
Numerous DI Î CYP3A4 inhibition
> serum [Na] > 5 mEq/L without symptom
improvement
Monitor: [Na], BP, wt, U output, I/O
Conivaptan IV, tolvaptan po

Na deficit (mM) = Vd for Na (gender) x IBW x Na
deficit mM/L (Na desired-Na serum)
Vd (male)=0.6 L/kg; Vd (female)=0.5L/kg; Na
desired = 125 mM/L
0.6 L/kg x 70 kg x (125-120 mM/L)
210 mM
45
46
Sodium Correction
Corrected [Na] for hyperglycemia

44
Sodium Deficit
MOA: block V2 receptors Î free water excretion
without the loss of serum electrolytes

[Na] < 115 mM/L
Central line administration @ 1-2 mL/kg/h (150 mL)
Q20min prn x 2 until symptoms resolve or [Na] > 5
mM/L
Check [Na] after 1 h & q4h while on NaCl 3%
Limit [Na] increase < 10 mM/L/24h day 1
Limit [Na] increase < 8 mM/L/24h on other days
Stop NaCl 3% administration if [Na] > 130 mM/L
Complications include: osmotic demyelination
syndrome (too rapid correction), hypernatremia,
hypokalemia, hypotension
Corrected [Na] (mM/L) = serum [Na] +
(0.23 x serum [Glu])
For every 5.5 mM/L increase in [Glu] Î
[Na] decreases by ~ 1.6 mM/L up to [Glu]
< 22 mM/L
> 22 mM/L [Glu]: For every 5.5 mM/L
increase in [Glu] Î [Na] decreases by ~
2.4 mM/L
47

Infusate rate (mL/h)= [1000 x serum [Na]
change/h x ((Vd x wt) + 1)/(IV [Na] + IV [K] –
serum [Na])]
Serum [Na] change per litre=(IV [Na] + IV[K] –
serum [Na])/((Vd x wt) + 1 )

Vd= 0.6 L/kg adult male
Vd= 0.5 L/kg for adult female or elderly male
Vd=0.45 L/kg for elderly female
IV [Na] = 513 mM/L for 3% NaCl; 154 mM/L for NS;
130 mM/L for LRS (+ 4 mM/L K)
48
Hypernatremia
Hypernatremia

[Na] > 145 mM/L (acute < 24 h)
When thirst or access to water impaired

Hypervolemic:

Altered mental status
Intubated
Infants or elderly or physically challenged

Euvolemic:

Water loss or over-correction of hyponatremia
Prevention: 1) ADH release Î 2) thirst
Symptoms: confusion, fatigue, lethargy, tremor,
seizures, coma, death

TPN, NaCl 3%, NaHCO3
Adrenal tumors
Extrarenal: tachypnea, fever
Renal: DI
Compromised fluid intake
Hypovolemic:

GI: vomiting, diarrhea
Skin: burns, sweating
Renal: RF, diuretics, osmotic diuresis
49
50
Hypernatremia
Hypernatremia

chronic hypernatremia: neurons increase
uptake of solutes & lytes to minimize
osmotic shifts between ECF & ICF
The uptake maintains brain volume wnl Î
prevents cerebral dehydration
Treatment:

Replace water deficit over 48 – 72 h
Decrease [Na] by no more than 10 mM/day
First line treatment: po free water &/or IV
D5W
If hypotensive: use NS to restore tissue
perfusion
For significant water & Na losses & no
hypotension use 0.45% NaCl
51
52
Learning Objectives
Summary: Managing Na Disorders

Determine the cause
Determine osmolality (hyponatremia)
Correct [Na] for any hyperglycemia
Calculate water deficit or surplus
Select appropriate replacement solution
Upon the completion of this session, the
learner will be able to:

Washington Manual of Critical Care
(2012)
53
Estimate the amount of total body water in
each of the following compartments: ICF,
ECF, ISF & IVF
List how many mOsm/L are provided by D5W,
NS, LRS & Plasmalyte
Calculate a Na & Water deficit
Apply a systematic process & effectively
assess hyponatremia in patient care & list one
pathological etiology
54
References
References

Clinical Practice Guidelines on Diagnosis & Treatment of
Hyponatremia. European J of Endocrinology (2014) 170: G1-G47
Lau AH et al., Fluid & Electrolyte Disorders. Koda-Kimble & Young’s
Applied Therapeutics. 10th Ed. Aldredge BK et al. (eds) (2013) 188 216
Verbalis JG et al. Diagnosis, evaluation, and treatment of
hyponatremia: expert panel recommendations. Am J Med. (2013)
126: S1–S42
Washington Manual of Critical Care. Second edition. Kollef I et al.
(eds). Lippincott, Williams & Wilkins (2012) 178-208
Rhoda KM et al., Fluid & Electrolyte management: putting a plan in
motion. J Parent Enteral Nutr (2011) 35: 675-685
Wald R et al. Impact of hospital-associated hyponatremia on
selected outcomes. Arch Intern Med. (2010) 170:294–302.
Sterns RH et al., Treating profound hyponatremia: a strategy for
controlled correction. Am J Kidney Dis. Elsevier Inc.; (2010) 56:774–
9.

Sterns RH et al., The treatment of hyponatremia. Semin Nephrol.
Elsevier Inc.; (2009) 29:282–99.
Verbalis JG et al., Hyponatremia treatment guidelines 2007: Expert
panel recommendations. American J of Medicine (2007) 120: S1-S21
Kraft MD et al.; Treatment of electrolyte disorders in adult patients
in the intensive care unit. Am J Health-Sys Pharm (2005) 1663-1681
Chua M et al., Prognostic implications of hyponatremia in elderly
hospitalized patients. Arch Gerontol Geriatr. (2007) 45:253–8.
Lien Y-HH et al. Hyponatremia: clinical diagnosis and management.
Am J Med. (2007) 120:653–8.
Androgue HJ et al. Hyponatremia. N Engl J Med (2000) 342:15811589
Chumlea WC et al., Total body water data for white adults 18 to 64
years of age: The Fels Longitudinal Study. Kidney
International (1999) 56, 244–252
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Case #1

Case #2
Patient R.M, 73 yo male
Wt = 70 kg; ht= 5’10”
Na = 108 mM/L (135–145)
K = 3.8 mM/L (3.5–5)
Cl = 78 mM/L (90–110)
HC03 = 22 mM/L (20–30)
BUN = 11.2 mM/L (5-9)
SCr = 110 mcM/L (90–140); eGFR 46 mL/min
BG = 7.6 mM/L (3.5-6)
Cc: N & V, muscle pain & weakness, confusion,
hostility, anxiety, one witnessed seizure

57
Case #3

RT is a 65 y/o, F, 5’ 7”, 78 kg brought to the emergency department
from home due to increased shortness of breath and lethargy.
Past Medical History: CHF – LVEF 30%; Afib; HTN; T2DM
Medication List: Warfarin 4mg PO daily; Metoprolol 50mg PO BID;
Ramipril 5mg PO daily; Furosemide 40mg PO daily; Metformin
1000mg PO BID; Glyburide 5mg PO daily; Calcium 500mg PO BID;
Vitamin D 2000 units PO daily;
Relevant Exam: Moderate distress, Temp: 36.8, BP: 111/72, HR: 92
irregular laboured breathing with crackles, orthopnea, JVP: 10cm
ASA; CXR: bilateral pleural effusions, cardiomegaly and interstitial
pulmonary infiltrates; 3+ edema bilateral to legs, obese with recent
weight gain of 4kg this week
Labs: WBC=8.9; Neut=7.2; Hb=112; Na=115; K=4.2; Cl=80;
HCO=31; BUN=8; SCr= 92; BG=9.8; Plasma OSM=260;
BNPNT=16500; TROP=0.08; Urine Na=5;
59
DR is a 75 y/o M, 6’ 1”, 72 kg admitted to the medicine ward for failure to
thrive. Previously he was admitted for an acute exacerbation of COPD and
discharged with a short course of prednisone and moxifloxacin 7 days ago.
About 3 days ago he started to have loose stools and has become
increasingly weak, feeling like he can never be more than a few minutes
from the bathroom.
Past Medical History: COPD; Hypertension; Gout; BPH
Medication List: Prednisone 40mg PO daily (stopped 5 days ago);
Moxifloxacin 400mg PO daily (stopped 3 days ago); Fluticasone/Salmeterol
250/25mcg – 2 puffs BID; Salbutamol 100mcg – 2 puffs PO QID PRN;
Hydrochlorothiazide 25mg PO daily; Ramipril 5mg PO daily; Allopurinol
300mg PO daily; Tamsulosin 0.4mg PO HS;
Relevant Exam: Mild distress, Temp: 37.8, BP: 133/82 supine 101/62
standing, HR: 105p; JVP: not identified, 5 loose BM yesterday and 2 this
morning, abdominal tenderness
Labs: WBC=22; Neut=18; Hb=142; Plts=398; Na=116; K=3.2; Cl=96;
HCO3=16; BUN=22; SCr=185; eGFR= 26; BG=6.9;
58

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