Fluids and electrolytes
Joel Topf, MD
Nephrology Attending
St. John Hospital

The lungs serve to maintain the composition of the
extracellular fluid with respect to oxygen and carbon
dioxide, and with this their duty ends. The responsibility for
maintaining the composition of this fluid in respect to other
constituents devolves on the kidneys. It is no exaggeration to
say that the composition of the body fluids is determined not
by what the mouth takes in but what the kidneys keep: they
are the master chemists of our internal environment. Which,
so to speak, they manufacture in reverse by working it over
some fifteen times a day. When among other duties, they
excrete the ashes of our body fires, or remove from the
blood the infinite variety of foreign substances that are
constantly being absorbed from our indiscriminate
gastrointestinal tracts, these excretory operations are
incidental to the major task of keeping our internal
environments in the ideal, balanced state.
Homer W. Smith From Fish to Philosopher

Answer:
The percentage of
admissions that get either:
IV fluids or
Diuretics

Question:
What is 100%

Answer:
The percentage of hospital
days that patients get
electrolytes drawn

Question:
What is 100%

Fluids and electrolyte issues are ubiquitous
34
132 108 106
4.4 17 3.8
The ability to screw up is ubiquitous

Fluids: Total body water

Ideal weight: Females: 45 kg
+ 2.3 kg for every inch over 5 feet
Males: 50 kg
Adjusted weight: ideal weight + 0.4 (actual body weight – ideal weight)

67% 25% 8%
28 L 11 L 3L
Blood volume = 5 L

Hemoconcentration
 Mr. Jones drank too
much and puked his RCVpre = RCVpost
guts out. RCV = IVV \" Hct
 On admission his hct is IVVpre \" Hct pre = IVVpost \" Hct post
65%. Up from a recent
hematocrit of 40%. 5L \" 0.40 = IVVpost \" 0.65
 How much water was 5L \" 0.40
= IVVpost
lost from his vascular 0.65
space? 3.1L = IVVpost
!

Intravenous fluids
Crystalloids
Dextrose Saline Ringers Plasma
Lactate expanders

Dextrose solutions
 The convention for naming dextrose
solutions is grams percent (g%)
 To convert this to conventional mg/dL
multiply the g% by 1,000
 Example
 D5W contains 5g of glucose per 100 mL or
 50 g per liter (200 Kcal/liter)
 The glucose concentration of D5W is
5,000 mg/dL

Dextrose solutions
 The glucose concentration in D5W is so
high to make the fluid isosmotic to plasma
 To convert from mg/dL to mmol/L
 Divide the mg/dL by the molecular weight of
glucose (180) to get mmol/dL
 Multiply by 10 to convert mmol/dL to mmol/L
5000 mg/dL 27.8 mmol/dL
277 mmol/L
180 mg/mmol 10 dL/L

Saline
 Isotonic saline is the primary fluid for
volume resuscitation
 Sodium concentration
154 mmol/L
 pH of 5.5
 When given in large volumes can cause a non-
anion gap (hyperchloremic) metabolic
acidosis
 Dilutional acidosis

Lactated ringers
 Contains Na, Cl, K,  The Contents
and Ca at physiologic  Sodium: 130 mmol/L
concentrations  Chloride: 109 mmol/L
 Do not use with  Lactate: 28 mmol/lL
hyperkalemia  Potassium: 4 mmol/L
 Do not use with  Calcium: 6 mg/dL
hypercalcemia
 Lactate is used to
supply alkali
 Do not use with lactic
acidosis
 pH=6.5

Dextrose Ringers Lactate
Saline Plasma expanders

Mr. Jones is down 1.9 L
How much D5W will it
23.75

take to replace the
intravascular volume?
 Dextrose distributes in
liters
proportion to total
body water.
 8% of TBW is
intravascular
 1.9/0.08 = 23.75 L

Mr. Jones is down 1.9 L
How much 0.9%
7.6

NaCl (or LR) will it
take to replace the
intravascular volume?
Saline distributes
liters

among extracellular
compartments.
 25% of ECC is
intravascular
 1.9/0.25 = 7.6 L

Mr. Jones is down 1.9 L
 How much
blood/albumin will it
1.9
take to replace the
intravascular volume?
 Blood/albumin is
liters
limited to the
intravascular space.
 1.9/1.0 = 1.9 L

Bicarbonate drips
 Do not add bicarb to
normal saline
 An amp of bicarb has
50 mmol Na per 50
mL (1000 mmol/L)
 Add bicarbonate to:
 D5W: 3-4 amps per liter
 0.45 NS: 1-2 amps per
liter
 Sterile water: 3-4 amps
per liter

Answer:
The percentage of
admissions that need both:
IV fluids and
Diuretics
Question:
What is very few?

Don’t give a drowning man a glass of water
 Don’t use IVF and diuretics
 Except
 Hypercalcemia
 Hyperkalemia

Proper use of diuretics: Loops
 Loop diuretics block the Na-K-2Cl co-transporter
in the thick ascending limb of the loop of Henle
 They block chloride in the tubular fluid from
binding
 So loop diuretics (like all diuretics except
spironolactone) must get from the blood into the
tubular fluid
 Secretion in the proximal tubule
 Secretion is dependent on renal function
 Must increase the dose as renal function deteriorates
 Age + BUN

Proper use of diuretics: Loops
 Loop diuretics block the Na-K-2Cl co-transporter
in the thick ascending limb of the loop of Henle
 They block chloride in the tubular fluid from
binding
 So the loop diuretic (like all diuretics except
spironolactone) must get from the blood into the
tubular fluid
 Secretion in the proximal tubule
 Secretion is dependent on renal function
 Must increase the dose as renal function deteriorates
 Age + BUN
 Cr x 20

Loop diuretic resistance
 Chronic use of loop diuretics results in
hypertrophy of distal convoluted tubule
 Increased distal reabsorption of sodium and
fluid attenuate diuretic response
 Addition of a thiazide diuretic can restore
loop sensitivity

Loop diuretic resistance
Mechanism of diminished Therapeutic
Situation response response
Impaired delivery to tubular
Renal failure Increased dose
fluid
Protein binding in the urine.
Nephrotic Syndrome Increased dose
Sodium avid nephron
Increased
Heart Failure Sodium avid nephron
frequency
Increased
Cirrhosis Sodium avid nephron
frequency

Furosemide drips
 High dose furosemide  Give 40-80 mg bolus of
causes furosemide
 Electrolyte abnormalities  Start infusion at 20
 Ototoxicity mg/hour
Volume depletion

 Titrate drip to desired
 In a meta analysis diuresis
Salvadore and Rey found  May need to repeat the
continuous infusions for loading doses when
CHF: titrating the drip
 More diuresis  Maximum of 40 mg/hr
 Less ototoxicity
 No change in electrolyte
abnormalities
Salvador DR, Rey NR, Ramos GC, Punzalan FE.
Cochrane Database Syst Rev. 2004;(1):CD003178

Proper use of diuretics: Thiazides
 Thiazide diuretics lose much of their
effectiveness with a GFR < 50 mL/min
 This can be overcome with higher doses
 50-100 mg of HCTZ with GFR 30-50
 200 mg of HCTZ with GFR < 30
 Metolazone (Zaroxolyn)
 2.5-20 mg daily
 Half-life is 2 days

Electrolyte Emergencies

Sodium is different
 Most ions must be regulated because of
direct effects of the ion.
 Arrhythmias from high (or low) potassium
 Weakness from high magnesium
 Tetany from low calcium
 Sodium is not like that.
 The problems with high or low sodium have little
to do with direct effects of the ion.
 Disregulation of sodium causes changes in cell
volume.

The movement of water in the body
 The movement of water into and out of
cells is governed by tonicity (sodium):
intracellular compartment extracellular compartment

Why we care about osmolality
 Alterations in cell size disrupt tissue
function.

Low sodium: hyponatremia
 Hyponatremia is defined as a sodium
concentration less than 135 mEq/L.
 Pseudohyponatremia is when the sodium
concentration is low (< 135) but
osmolality is high or normal.
 True hyponatremia is when both the
sodium and the osmolality are low.

Pseudohyponatremia:
high osmolality
 Elevated glucose (or
mannitol) raise
plasma tonicity which
draws water from the
intracellular
compartment diluting
plasma sodium.
Hillier TA, Abbott RD, Barrett EJ. Am J Med 1999; 106: 399-403.

Pseudohyponatremia:
high osmolality
 Correcting the sodium for hyperglycemia.
 Add 1.6 to the sodium for every 100 mg/dL the
glucose is over 100.
 Example: Na = 126 mEq/L. Glucose = 600 mg/dL:
 600 - 100 = 500. So the glucose is five 100’s over 100
 5 x 1.6 = 8
 126 + 8 =134
 True sodium equals 134 mEq/L
 To remember 1.6 think “Sweet 16”
 Underestimates true adjusted sodium

Pseudohyponatremia:
Normal osmolality
 Increased protein or lipids can cause a lab
error causing a falsely lowered sodium.
 Hyperlipidemia  TPN with lipids
 Hypercholesterolemia  IV immunoglobulin infusions

True hyponatremia:
water intake > water excretion
 Intake
 Psychogenic
polydipsia

True hyponatremia:
water intake > water excretion
 Intake
 Psychogenic
polydipsia
 Excretion
 Renal failure
 ADH
 SIADH
 CHF
 Volume depletion
 Cirrhosis
 Adrenal
insufficiency
 Hypothyroidism

Healthy
Kidneys
50
Na+
Dilute urine
Urine Osmolality
Na+
1200 Concentrated urine

Healthy Chronic ESRD or Absence of
Kidneys Kidney acute renal ADH: Diabetes
Disease failure insipidis
50 50
150
Urine Osmolality
150
300 Excess ADH:
isosthenuria
• SIADH
• CHF
• Volume depletion
600
900 900
1200

Excess ADH:
• SIADH
• CHF
• Volume depletion
600
Na+
Concentrated urine
900

Etiology of Hyponatremia: 3 steps
to generating dilute urine
1.Delivery of water to the
diluting segments of 100 50
the nephron.
2.Functional diluting 285
segments.
3.Collectingtubule
impermeable to water 1400
(lack of ADH)

Failure to Generate dilute urine
 Lack of water delivery
to the diluting
segments.
 Renal failure
 Volume deficiency
 Cirrhosis
 Heart failure
 Nephrotic syndrome

Failure to Generate dilute urine
 Ineffective solute
reabsorption in the
diluting segments:
 Thick ascending limb
of the loop of Henle
(TALH)
 Distal convoluted
tubule.
 Diuretics
 Non-oliguric ATN

Failure to Generate dilute urine
 Permeable collecting
ducts (ADH)
 Volume related ADH
 SIADH
 Drug induced
 Paraneoplastic
 CNS
 Pulmonary disease
 Adrenal insufficiency
 Hypothyroidism

Implications of hyponatremia

Adrogué and Madias NEJM 2000;342:1581.

The response to hyponatremia
Compensated chronic
hyponatremia is essentially
Low sodium concentration causes water to move into the cells.
In the brain this causes an increase in ICP.
asymptomatic.

The problem with compensation
interns
The starting point is after Sodium
compensation has reduced 134
108
the amount of intracellular
solute and the ICP
Now, an over-eager intern
sees the low sodium and starts
an infusion of 3% NaCl to
raise the sodium to normal.
The sodium draws water from
the inside of the cells causing
the brain to shrivel.
This causes osmotic brain
damage. Central pontine
myelinolysis. This is lethal.

Damned if you do. Damned if you don’t.
T. Berl
 Correction of sodium puts  Without treatment patients
patients at risk for OBD have cerebral edema.
To treat or not to treat? That is the question.

Damned if you do. Damned if you don’t.
T. Berl
 Correction of sodium puts  Without treatment patients
patients at risk for OBD have cerebral edema.
To treat or not to treat? That is the question.

Symptomatic vs. Asymptromatic
 Uncompensated,  Symptoms
symptomatic  Mental status changes
 Treat aggressively with 3%  Nausea
saline  Vomiting
 Critical care or nephrology  Headache
consult.  Movement abnormalities
 Compensated,  Seizures
asymptomatic  Hypoxia/respiratory failure
 Treat conservatively
 Water restriction
 Conivaptan / Tolvaptan
 Demeclocycline
 Lasix

Symptomatic vs. Asymptromatic
 Use the etiology of hyponatremia as a clue to
duration of hyponatremia
 Patients with long standing disease processes are
more likely to be chronic:
 SIADH
 CHF COMMON
 Cirrhosis
 Likely to cause acute hyponatremia:
 Psychogenic polydipsia
 Thiazide diuretics RARE
 Post-operative hyponatremia

Clock and calendar are
unreliable measures of chronicity

Chronic vs acute
Symptomatic vs Asymptomatic
Early aggressive therapy Late aggressive therapy Conservative therapy
 Prospectively collected case series of 53 postmenopausal women.
 Average duration of hyponatremia: 5.2 days
 All had severe neurologic symptoms.
Ayus JC, Arieff AI. JAMA 1999; 281: 2299-2304.

Conservative therapy for
asymptomatic hyponatremia
 Do no harm.
 Fluid restrict the patient.
 Check the urine Na plus K
 If it is greater than the serum Na,
furosemide may help.
 Speed limit
 0.5 mmol/L/hr
 No more than 12 mmol in the first day.

9.45 67.43
 151 consecutive euvolemic hyponatremic
patients admitted to through the ED
 Na from 115 to 132
 Excluded patients with CHF, acute
hyponatremia, or seizures
 N = 122
Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8.

Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8.

Introducing the vaptans
 Non-peptide vasopressin competitive antagonists
 Three vasopressin receptors
 V1a: Vasoconstriction
 V1b: Cortisol modulation
 V2: Water metabolism in the kidney
 Treatment of hyponatremia and heart failure

Conivaptan marketed as Vaprisol®
 First licensed ADH antagonist
 Dual V1a (vasopresssor) and
V2 (aquaporin) antagonist
 Licensed December 2005 for
the treatment of euvolemic
hyponatremia

Placebo Conivaptan 40mg/d
(n=21) (n=18)
Baseline sodium 124.3 mmol/l 123.6 mmol/l
Sodium at 48 hours 125.1 mmol/l 129.4 mmol/l
Sodium at 96 hours 126.7 mmol/l 130.0 mmol/l
Number with a Na rise
0 (0%) 7 (38.9%)
of ≥ 6 mmol/L at 48 hours
Number with a Na rise
6 (28.6%) 12 (66.7%)
of ≥ 6 mmol/L at 96 hours
9% of patients had overly rapid (>12 mmol/L in 24 hours)
correction of hyponatremia
Potent CYP3A4 inhibitor: Caution with ketoconazole,
itraconazole, clarithromycin, ritonavir and indinavir

Conivaptan
 No data in liver disease
 No current indication in
heart failure
 Lowers wedge pressure
 Increases urine output
 Corrects hyponatremia
JE Udelson, WB Smith, Et al. Circulation. 2001;104:2417.

Conivaptan
 Only available as an IV agent
 Requires continuous infusion
 20 mg loading dose over 30
minutes
 Then 20 mg over the rest of
the day
 40-80 as continuous infusion
for up to 96 hours

 Two identical studies SALT  Patients randomized to
1 (US Study) and SALT 2 placebo or tolvaptan
(European Study)  Dose was titrated from 15 mg
 Randomized double blind to a maximum of 60 mg to
bring the Na up to 135.
placebo controlled trial
Study drug was continued for
All patients had


30 days and then stopped.
hyponatremia due to:
 SIADH
 CHF
 Cirrhosis

Sodium 130-134 Sodium < 130

Acute symptomatic hyponatremia
 In patients with neurologic symptoms due
to hyponatremia: Use 3% NaCl.
 Increase sodium until symptoms abate or 6
mmol/L, which ever comes first.

12
Increase Na 12 mmol/L in the first 24 hours.

Change in sodium formula:
 The formula predicts serum
sodium following one liter of
any infusion.
$ Naiv # Nas '
 Works equally well in \"Na = % (
hyponatremia & TBW +1 )
 3% NaCl
Change in sodium following
 and hypernatremia one liter of any IVF.
 D5W
TBW = kg x 0.6
!
 In adults, using 3% NaCl the Na in 3% NaCl: 513
Na in 0.9% NaCl: 154
∆Na should be pretty close Na in 0.45% NaCl: 77
to 10 mmol/L per liter Na in 0.225% NaCl: 39
Adrogué and Madias NEJM 2000;342:1581.

Change in sodium formula:
Examples
 46 yo AA female 3 $ Na # Nas '
\"Na = % iv (
& TBW +1 )
days post-op from $ 513# 108 '
TAH develops \"Na = %
&( 65* 0.6) +1)
(
seizures and is \"Na = 10.125
unresponsive.
For every liter of 3% the Na will
Na = 108
1.

! rise 10.1 mmol/L
 Weight = 65 kg  So 1 mmol/L per 100 cc of 3%
2. Raise Na 6 mEq in 2 hours give
 You prescribe 3% 300 ml/hr for 2 hours or until
symptoms resolve.
NaCl 3. After that 50mL for 12 will
increase serum Na by 6 mmol/L to
get you to 12 mmol/L.
4. Check frequent serum Na, recheck
change in Na calc.

Change in sodium formula:
Limitations
 Under estimates
change in sodium $ Naiv # Nas '
\"Na = % (
 Assumes no urine & TBW +1 )
output Change in sodium following
 The greater the urine one liter of any IVF.
output the more TBW = kg x 0.6
inaccurate the formula !
Na in 3% NaCl: 513
 In 40% of people who Na in 0.9% NaCl: 154
overcorrect, there is Na in 0.45% NaCl: 77
documented diuresis Na in 0.225% NaCl: 39
 Assumes accurate
calculation of total
body water
Mohmand HK, Issa D, Et al. Abstract ASN 2006
Adrogué and Madias NEJM 2000;342:1581.

Fluids: Total body water

70 kg 100 kg
60% 45%
H2 O H2 O
Ideal weight: Females: 45 kg
+ 2.3 kg for every inch over 5 feet
Males: 50 kg
Adjusted weight: ideal weight + 0.4 (actual body weight – ideal weight)

Hyponatremia summary
 The primary issues:
 Is it true hyponatremia
 Check a spot glucose
 If it is true then:
 To treat or not to treat?
 Symptomatic: Treat with 3%
 Asymptomatic: fluid restrict
 Tolvaptan / Conivaptan
 Demeclocycline
 Lasix and /or salt tablets

Hypernatremia
 Hypernatremia is defined as a sodium > 145
mEq/L.
 Hypernatremia is associated with increased
hospital mortality.
 Patients who present with hypernatremia typically
get appropriate therapy.
 In patients who develop hypernatremia while
hospitalized don’t get therapy as often.

Causes of hypernatremia
 Water excretion exceeds Generation
water intake
 Two step process
 Generation
 Gain of sodium
 Loss of water
 Maintenance
 Inability to ingest water Maintenance
 Without both of these
processes there cannot be
hypernatremia.

Consequences and compensation

Treatment
 Provide water
 Enteral water is
preferred
 D5W results in
hyperglycemia
 Note on D5W, since
D5W distributes through
the total body water 1
liter of D5W increases
the intravascular space
by only 83 mL

The amount of fluid
 Use the change in sodium  TBW= kg x % body
formula to calculate the water
fluid volume.
 0.7 for well hydrated
Initial Na = 168 mmol/L young males
\"Na = iv
Na + K iv # Nas
TBW + 1
 0.6 for well hydrated
\"Na =
0 + 0 #168 young females
42 + 1
\"Na = 3.9 $ 4  reduce by 0.1 for:
 Obesity
 Each liter of D5 or free water
! lowers Na 4, so 6 liters will  Elderly
reduce the Na to 144.  Dehydration

Treatment
 For routine hypernatremia correct the fluid deficit
over 48 hours.
 Patients with DI have large ongoing free water
losses (200-300 mL/hr).
 Failing to account for these losses will result in a
failure to correct the hypernatremia.
 Many of these patients have poor perfusion.
 Treat the shock and compromised perfusion without
worrying about the Na.
 After perfusion is restored treat the hypernatremia.