Fluids and Hypernatremia

Kathryn Rice PharmD, BCPS

[email protected]
February 3, 2020
PHA5370 Renal
Objectives
• Discuss body water and electrolyte composition
• Differentiate between the different intravenous fluids, their
osmolarity and distribution within the extracellular and
intracellular compartments
• Calculate individualized daily fluid requirements
• Develop a pharmacotherapy plan for fluid management
• Describe the background of sodium and the importance of
homeostasis
• Differentiate the causes of hypernatremia
• Develop a pharmacotherapy plan for a patient with hypernatremia
Recommended Reading
• DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey
LM. Pharmacotherapy: A Pathophysiologic Approach, 10th
Edition; McGraw-Hill; ISBN 9781259587481.
• Chapter 49
• Adrogue HJ, Madias NE. Hypernatremia. NEJM.
2000;342(20):1493-1499.
Body Water Compartments
• Body water
• Men: 50-60% of lean body weight (LBW)
• Women: 45-55% of lean body weight (LBW)
• Neonates: 80%
• Total body water (TBW)
• Men: 0.6 * LBW
• Women: 0.5 * LBW
Body Water Compartments
• TBW distribution
• 2/3 intracellular space
• 1/3 extracellular space
• ¾ interstitial space
• ¼ intravascular space
http://slideplayer.com/slide/10536501/
 Water Distribution
• Capillary wall
• Separates interstitial fluid from
plasma
• Plasma proteins
• Primary osmoles that affect water
distribution between interstitium
and plasma

https://www.biochemden.com/plasma-proteins/
https://upload.wikimedia.org/wikipedia/commons/6/62/0307_Osmosis.jpg
Water Distribution
• Water travels freely across cell membranes
• Moves across membrane from area of low osmolality to high osmolality
• Net water movement stops when osmotic equilibrium occurs
• Cell membrane
• Only selectively permeable to solutes
• Impermeable solutes are osmotically active
• Can exert osmotic pressure which dictates distribution of water between fluid
compartments
• Fluid compartments: each contains a major osmotically active
solute
• Intracellular space: potassium
• Extracellular space: sodium
Electrolyte Composition
• Intracellular compartment: major ions
• Potassium
• Magnesium
• Phosphate
• Extracellular compartment: major ions
• Sodium
• Chloride
• Bicarbonate
http://anatomyandphysiologyi.com/wp-content/uploads/2013/11/electrolyte-composition.jpg
Plasma Osmolality
• Osmolality = # of particles / kg water (mOsm/kg)
• Determined by the number of particles in solution
• Not particle size or valence
• Osmolality of body fluid maintained between 280-295 mOsm/kg
• Nondissociable solutes generate 1 mOsm/mmol of particles
• Glucose
• Albumin
• Dissociable salts produce 2 mOsm/mmol of salt
• NaCl
• Plasma osmolality reflects osmolality of total body water
• All body fluid compartments are iso-osmotic
Plasma Osmolality
• Serum osmolality = (2 × Na + (BUN / 2.8) + (glucose / 18)
• Equation predicts measured plasma osmolality within 5-10 mOsm/kg
• Osmole gap
• Measured and calculated values differ by > 10 mOsm/kg
• Signifies presence of unidentified particles
• Used to detect presence of certain substances which have high osmolality
• Ethanol, methanol, ethylene glycol
• Increase in plasma osmolality
• Causes osmotic shift of fluid into the plasma and out of the cells
• Results in cellular shrinking due to dehydration
• Decrease in plasma osmolality
• Causes osmotic shift of fluid into the cells and out of the plasma
• Results in cellular swelling due to over-hydration
Osmoregulation
• Hypothalamus
• Osmoreceptors detect changes in plasma tonicity
• Regulates vasopressin aka antidiuretic hormone (ADH) release
• Plasma tonicity < 280 mOsm/kg
• Due to water ingestion: ADH release inhibited  water not reabsorbed in
collecting duct  large volume of dilute urine excreted
• Plasma tonicity > 295 mOsm/kg
• ADH released, thirst stimulated  increase water reabsorption  small
volume of concentrated urine excreted
• Urine osmolality variance
• Volume excreted depends on solute load to be excreted and urine osmolality
 ADH
• Produced in the
hypothalamus in
response to low
blood volume and /
or hyperosmolality
• Stimulates
receptors located
in the collecting
duct of the kidney
which cause free
water absorption
http://cnx.org/content/col11575/1.1/
 ADH
• Osmoreceptors
shrink in hypertonic
serum and increase
action potential firing
rate and
vasopressin (VP)
release from axon
terminals
• Osmoreceptors
swell in hypotonic
serum and decrease
VP release
Kidney International. 2012;82:1051-1053.
https://classconnection.s3.amazonaws.com/33/flashcards/602033/jpg/adh_mechanism_of_action1316763669712.jpg
Osmoregulation
• Amount of daily water intake includes:
• Volume of water ingested = sensible intake
• Water content of ingested food
• Metabolic production of water = insensible intake
• Homeostasis
• Water intake equal to amount of water excreted by the kidney and GI
tract = sensible loss
• Plus water lost from the skin and respiratory tract = insensible loss
Adult Fluid Requirements
• When determining the fluid needs of a patient, the clinician should
consider:
• Correction of fluid imbalances
• Maintenance fluid requirements
• Replacement of ongoing fluid losses
• Maintenance fluid
• Volume of daily fluid intake that replaces the insensible losses and also allows
excretion of urinary waste products in a volume of urine that is of an
osmolarity similar to plasma
• Maintenance fluid needs can be estimated using several methods
• The simplest method uses 30 to 35 mL/kg/day
• Another method is to provide 1500 mL for the first 20 kg of body weight plus
an additional 20 mL/kg for actual weight beyond the initial 20 kg
Daily Fluid Requirements
• Pediatric
• < 10 kg:
• 100 mL/kg
• 10-20 kg:
• 1000 mL + 50 mL/kg for excess weight > 10kg
• > 20 kg:
• 1500 mL + 20 mL/kg for excess weight > 20 kg
• Adult
• 1500 mL + 20 mL/kg for excess weight > 20 kg
• Quick adult average: 30-35 mL/kg/day
Daily Fluid Requirement: Calculation
• What is the estimated daily fluid requirement for a 49-year-old
female patient who weighs 71 kg?
• Quick adult average: 30-35 mL/kg/day

• What would be the hourly rate for a continuous maintenance fluid infusion
for this patient?

• What is the estimated daily fluid requirement for a 16 kg pediatric

patient?
• 1000 mL + 50 mL/kg for excess weight > 10kg

• What would be the hourly rate for a continuous maintenance fluid infusion
for this patient?
 Fluid Balance for 70 kg Adult

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%20101.htm
Volume Regulation
• Sodium almost exclusively in ECF
• Amount of total body sodium determines extracellular volume (ECV)
• Changes in effective circulating volume are sensed by various
receptors
• Intrathoracic volume receptors
• Baroreceptors in the carotid sinus and aortic arch
• Afferent arteriole in the glomerulus
• Volume changes
• Decreased volume  ADH released, RAAS activation
• Increased volume  RAAS suppression
Intravenous Fluids
• Maintenance = crystalloids • Resuscitation = crystalloids
• Goal is to preserve the or colloids
extracellular volume while • Goal is to produce a
maintaining a normal electrolyte predictable and sustained
balance increase in intravascular
• Appropriate maintenance fluid volume
provides an adequate quantity of
both water and electrolytes to
ensure good tissue perfusion
without causing complications
related to fluid overload or volume
depletion
• Also prevents the development of
hyponatremia, hypernatremia, and
other electrolyte imbalances
Intravenous (IV) Fluids:
Crystalloids
• Use:
• Resuscitation fluids (mainly)
• Maintenance fluids (occasionally
• 0.9% Sodium Chloride (Normal Saline, NS)
• Na+ and Cl- do not flow freely across membranes
• Remains in extracellular space
• Intravascular: 25%
• Interstitial: 75%
• Lactated Ringers (LR or RL)
• Similar to 0.9% NaCl
• Also contains lactate, K+, and Ca2+
Intravenous (IV) Fluids:
Crystalloids
• Use: maintenance fluids ONLY
• 5% Dextrose in Water (D5W)
• Metabolism: dextrose  H2O + CO2
• “Free water”
• Flows freely across membranes
• Avoid in patients with elevated intracranial pressure (ICP)
• 0.45% NaCl (Half-normal saline, 1/2NS)
• Typical maintenance fluid (with KCl)
 Intravenous Fluids: Crystalloids

DiPiro et al. Chapter 49

http://slideplayer.com/slide/10536501/
Intravenous (IV) Fluids:
Colloids
• High-molecular weight solutions, draw fluid into the
intravascular compartment via oncotic pressure (pressure
exerted by plasma proteins not capable of passing through
membranes on capillary walls)
• Plasma expanders, as they are composed of macromolecules and are
retained in the intravascular space
• Colloids:
• Albumin
• Dextran
• Hetastarch (Hespan)
• Tetrastarch (Voluven)
 Intravenous (IV) Fluids:
Colloids
• Human albumin 5% in saline is considered to be the reference
colloidal solution
• 5% albumin (50 g/L)
• 500 mL IV = 500 mL intravascular volume replacement
• “Iso-oncotic”
• 25% albumin (250 g/L)
• 100 mL IV = 500 mL intravascular volume replacement
• Causes fluid redistribution: oncotic pressure pulls fluid into the vascular space
• “Hyper-oncotic”

NEJM. 2013;369:1243-1251.
 Intravenous (IV) Fluids:
Colloids
• Patient who would benefit
from colloid administration

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Intravascular Volume Depletion
• Signs / symptoms of volume • Assess volume status
depletion • Select replacement fluid after
• Hypotension (SBP < 80 mm Hg) examination of serum sodium
• Tachycardia (HR > 100 beats/minute) concentration
• Orthostatic changes in HR or BP • Crystalloids are the fluid of choice
• Dizziness for initial resuscitation and
• Dry mucous membranes subsequent intravascular volume
• Decreased skin turgor replacement
• Increased BUN / SCr ratio > 20:1 • May use either balanced crystalloids
(LR) or saline for fluid resuscitation
• Decreased UOP, concentrated urine
• Improvement in HR and BP after a
500- to 1000-mL fluid bolus
 Resuscitation Fluids

https://www.nejm.org/doi/story/10.1056/feature.2013.09.11.14
Distribution of Intravenous Fluid
Body Water Compartments
• TBW distribution
• 2/3 intracellular space
• 1/3 extracellular space
• ¾ interstitial space
• ¼ intravascular space
 Maintenance Fluids

Modified from NEJM. 2015;373:1350-60.

IV Fluid Osmolarity
• Hypotonic fluid with osmolarity <150 mOsm/L
• Causes fluid to shift from extracellular to intracellular compartment
• Results in cellular over hydration and swelling
• RBC swelling  cell rupture (hemolysis)
• Brain cells can swell  cerebral edema and herniation
• Most likely to occur with hyponatremia

• Isotonic fluid
• Will not result in fluid shift between compartments
• Osmolarity similar to plasma
• Hypertonic fluid
• Causes fluid to shift from intracellular to extracellular compartment
• Results in cellular dehydration and shrinkage
Maintenance Fluids
• IV maintenance fluids
• Indicated for patients who are NPO
• Balance fluid losses
• Prevent dehydration
• Maintain normal fluid and electrolyte balance
• Administer as continuous infusion
• Peripherally or centrally
• Calculate patient specific fluid requirements
• Account for patients with excess fluid loss
• Adjust based on individual input, output and approximate insensible loss
• Common maintenance fluid
• D5W1/2NS + 20-40 mEq KCl per liter
Edema
• Clinically detectable increase in interstitial fluid volume
• Formation requires increased interstitial volume of ~2.5 – 3 L
• Typically due to heart, kidney, or liver failure
• May develop secondary to rapid decrease in serum albumin +
excess fluid intake
• e.g. burns, trauma
• Quantified based on area of involvement
Edema Presentation
• Jugular venous distention (JVD)
• Location
• Feet or pretibial area of ambulatory patients
• Pre-sacral area of bed-bound patients
• Pulmonary edema heard by “crackles”/”rales” upon auscultation
• “Pitting” edema
• Depression when pressure is placed several seconds over a bony
prominence and does not rapidly refill
• Severity rated based on depth of pit
• 1+, 2+, 3+, or 4+
 Diagnosis: Peripheral Edema
• Peripheral edema / pitting edema

https://www.healthline.com/health/pitting-edema#symptoms
 Pitting Edema

Mosby's Medical Dictionary, 9th edition. © 2009, Elsevier.

http://jmabrey.blogspot.com/2015/05/
Edema Treatment
• Treat underlying disease
• Restrict fluid and sodium intake
• Diuretics
• Loop: most common
• May add on thiazide or distal acting diuretic if refractory to loop
monotherapy
• HCTZ
• Spironolactone
• Metolazone
Sodium
• Circulatory system
• Brain
Hypernatremia
Background and Etiology
• [Na+] > 147 mEq/L
• Causes
• Decreased water intake
• Loss of hypotonic fluid
• Diabetes insipidus
• Medications
• Mineralocorticoid excess
• Assessed based upon volume status
• Hypovolemic
• Euvolemic
• Hypervolemic
NEJM. 2000;342(20):1493-1499.
NEJM. 2000;342(20):1493-1499.
Hypernatremia Presentation
• Mild • Other symptoms: depend on etiology
• Lethargy • Postural hypotension
• Weakness • Tachycardia
• Confusion • Dry mucous membranes
• Restlessness, irritability • Diminished skin turgor
• Moderate • Reduced or increased UOP
• Twitching
• Severe/late
• Seizures
• Coma
• Intracerebral hemorrhage
• Death (usually with > 160 mEq/L)
Hypernatremia Comparison
Characteristics Hypovolemic Euvolemic Hypervolemic

H2O and Na+ H2O loss >> Na+ loss H2O loss only Na+ gain > H2O gain

Causes Renal: osmotic diuresis, diuretic Congenital or acquired Sodium overload (e.g.
use, high output acute tubular Diabetes Insipidus (DI); sodium bicarbonate, salt
necrosis Nephrogenic DI tablets)
Effect on TBW   

Effect on TBNa   

Presentation Orthostasis, hypotension, Depends on severity: Peripheral + pulmonary

tachycardia, dry mucous seizures, lethargy edema, variable BP
membranes
Hypovolemic Hypernatremia:
Free Water Deficit
• Free water deficit is used to assess the amount of water replacement needed to
correct hypernatremia
• Calculation is based on actual body weight, so it may be incorrect in patients with significant
weight gain or loss (especially from fluid sources)

Water deficit volume (L) =

(total body water %) × weight in kg × [1 - (140 / serum sodium)]

• For total body water %

• 0.6 for men 65 years and younger and for children
• 0.5 for women 65 years and younger and for men older than 65 years
• 0.45 for women older than 65 years

• Online calculator
• http://www.nephromatic.com/water_deficit.php
Free Water Deficit Correction
• Do not want to correct the free water deficit too quickly
• Calculation is based on a conservative correction rate of 0.5 mEq/L/hr
to avoid cerebral edema, but this might still be too aggressive for some
patients

Hours to correct = (serum sodium – 140) / 0.5

Free Water Deficit: Calculation
• What is the free water deficit for a 39-year-old male patient who
weighs 88 kg and has a serum sodium level of 153?

• Bm = body mass in kg

• What is the minimum number of hours needed to correct his

free water deficit?
• Hours to correct = (serum sodium – 140) / 0.5
Hypovolemic Hypernatremia:
Pharmacotherapy
• Initial treatment with 0.9% sodium chloride (normal saline, NS)
until intravascular volume restored
• Initial infusion rate of 200 to 300 mL/h for most adults
• Transition to hypotonic fluid (usually 0.45% sodium chloride) to
correct water deficit once blood pressure and heart rate
normalized
• Must calculate rate of maintenance fluids based on serum sodium level
• Do not drop the serum sodium by more than 10 mEq/L/day
• Newer publications recommend no more than 6-8 mEq/L/day
Euvolemic Hypernatremia:
Diabetes Insipidus
• Disorder caused by insufficient secretion of vasopressin by the
pituitary gland or by a failure of the kidneys to respond to
circulating vasopressin
• Nephrogenic
• Kidney not responsive to ADH
• Central
• Hypothalamus not producing ADH
• Diabetes (definition): secretion and excretion of excessive
amounts of urine
• Diabetes mellitus = insulin deficiency
• Diabetes insipidus = vasopressin deficiency
DiPiro et al. Chapter 49
Euvolemic Hypernatremia:
Diabetes Insipidus
• Characterized by the excretion of large amounts of hypotonic
urine in the presence of high or normal serum sodium
• Urine output > 3 liters in 24 hours and urine osmolality < 300 mOsm/kg
• Symptoms: polyuria, polydipsia
• Pharmacotherapy
• Central
• Administer desmopressin acetate
• Brand: DDAVP
• Synthetic analogue of the antidiuretic hormone arginine vasopressin
• Nephrogenic
• HCTZ 25 mg PO q12-24h and sodium restriction (2000 mg/day)
 Desmopressin (DDAVP):
Dosing
• IV, SQ
• 2 to 4 mcg daily (0.5 to 1 mL) in 2 divided doses
• One-tenth (1/10) of the maintenance intranasal dose.
• Intranasal (100 mcg/mL nasal solution)
• 10 to 40 mcg daily (0.1 to 0.4 mL) as a single dose or
divided 2 to 3 times daily.
• Most adults require 10 mcg (0.1 mL) twice daily
• Oral
• Start at 0.05 mg twice daily
• Range: 0.1 to 1.2 mg divided 2 to 3 times daily
• Total daily dose should be increased or decreased as
needed to obtain adequate antidiuresis
http://online.lexi.com/lco/action/home
https://www.drugs.com/drp/ddavp-injection-4-mcg-ml.html
Hypervolemic Hypernatremia
• Sodium and fluid overload (but gain of more sodium than water)
• Treatment: D5W + furosemide 20 to 40 mg IV q6h
• Facilitate excretion of excess sodium
Hypernatremia Comparison
Characteristics Hypovolemic Euvolemic Hypervolemic

H2O and Na+ H2O loss >> Na+ loss H2O loss only Na+ gain > H2O gain

Causes Renal: osmotic diuresis, diuretic Congenital or acquired Sodium overload (e.g.
use, high output acute tubular Diabetes Insipidus (DI); sodium bicarbonate, salt
necrosis Nephrogenic DI tablets)
Effect on TBW   

Effect on TBNa   

Presentation Orthostasis, hypotension, Depends on severity: Peripheral + pulmonary

tachycardia, dry mucous seizures, lethargy edema, variable BP
membranes
Hypernatremia Treatment
• Management of underlying cause
• Reduce serum sodium at 1 mEq/L/hour in patients who
developed hypernatremia over a period of hours
• Reduce serum sodium at a maximal rate of 0.5 mEq/L/hour in
patients with hypernatremia for a longer or unknown duration
• Target a decrease of no more than 10 mEq/L/day
• Newer publications recommend no more than 6-8 mEq/L/day
• Administer hypotonic fluids via the oral (pure water) or
intravenous route (0.2% saline, 0.45% saline)
• 5% dextrose in water may cause serum sodium to drop too rapidly –
may also cause osmotic diuresis
NEJM. 2000;342(20):1493-1499.
Patient Case: LM
• LM is a 62-year-old man sent to the emergency room from the
nursing home for altered mental status.
• Patient nonverbal and listless in the ER, so history obtained from
nurse at nursing home.
• Patient has dementia at baseline. At baseline he is responsive,
takes oral medications crushed in applesauce and is continent of
bowel and bladder.
• Over the last few weeks, he has become less responsive and
increasingly incontinent of urine, requiring placement of a foley
catheter
• Decreased oral intake for the past 2 weeks, and “has not been
eating for the past 2 days.”
Patient Case: LM
• Medical history
• Dementia
• Diabetes mellitus type 2 – diet controlled
• Hyperlipidemia
• Hypertension
• Home medications
• Amlodipine 5 mg PO q24h
• Aspirin 81 mg PO q24h
• Docusate 100 mg PO q24h
• Lisinopril 20 mg PO q24h
• Pravastatin 40 mg PO qhs
• Quetiapine 12.5 mg PO qhs
Patient Case: LM
• No known drug allergies • On physical exam
• Height = 67” • Oral mucosa dry
• Foley catheter in place. Dark
• Weight = 57.2 kg yellow urine in foley bag.
• Temperature = 38.8 C • Opens eyes to voice and
painful stimuli
• Blood pressure = 131/76
• Heart rate = 106
• Respiratory rate = 20
Patient Case: LM - Labs
Patient Case:
LM - Labs
Patient Case: LM - Labs
Patient Case: LM
• Diagnosis:
1. Profound dehydration
2. Hypernatremia (secondary to #1)
3. Urinary tract infection
• Empirically started on cefepime 1 g IV q12h
• Changed to cephalexin 500 mg PO q12h once sensitivity results back
4. Altered mental status (secondary to #2 and #3)
Patient Case: LM
• What is LM’s daily fluid requirement?
• Quick adult average: 30-35 mL/kg/day
• 1716 mL (71 mL/h) – 2002 mL (83 mL/h) fluid per day
• What is LM’s water deficit?

• 5.5 L
• What is the minimum number of hours needed to correct his
free water deficit?
• Hours to correct = (serum sodium – 140) / 0.5
• 54 h
Patient Case: LM
• If we were to begin 0.45% normal saline maintenance fluids for LM, how
much would 1 liter lower his serum sodium level?
• 2.5 mEq/L
• What infusion rate (in mL/h, round down to the nearest whole number) of
0.45% normal saline will lower LM’s serum sodium by 8 mEq/L in a 24
hour period?
• 3200 mL / 24 h = 133 mL/h
• How long will it take to replace LM’s free water deficit if we infuse 0.45%
normal saline at this rate?
• Daily requirements = 71 to 83 mL/h
• 133 mL/h – 71 mL/h = 62 mL/h
• Fluid deficit of 5500 mL / 62 mL/h = 89 hours
• 133 mL/h – 83 mL/h = 50 mL/h
• Fluid deficit of 5500 mL / 50 mL/h = 110 hours
Height = 67”
Weight = 57.2 kg

NEJM. 2000;342(20):1493-1499.
Patient Case: LM - Labs
 Questions?

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Patient Case: FW
• FW is a 72-year-old male sent to the emergency room on
12/31/18 from the nursing home due to progressive weight loss,
dysphagia and altered mental status
• History obtained from his daughter, who says that he has been in a
steady decline over the past month with decreased oral intake (holds
food in his mouth without swallowing) and a 14 pound weight loss
• Daughter is concerned the patient might be having a stroke
• Patient made nothing by mouth (NPO) on admission and
speech therapy was consulted for a swallowing study
• Height = 68”
• Weight = 67.5 kg
Patient Case: FW
Patient Case: FW
• Using the 35 mL/kg/day adult average estimation, calculate
FW’s daily fluid requirement.
• 2362.5 mL/day
• What would be the maintenance fluid infusion rate per hour (mL/h,
rounded to the nearest whole number) to provide that amount of fluid in
a 24 hour period?
• 98 mL/h
• Calculate FW’s water deficit, using the admission sodium level
of 156 and the correction factor of 0.5 for an elderly man.
• 3.46 L
Patient Case: FW
• If we were to begin 0.45% normal saline maintenance fluids for FW,
how much would 1 liter lower his serum sodium level?
• Lowers serum sodium by 2.27 mEq/L
• What infusion rate (in mL/h, round down to the nearest whole number)
of 0.45% normal saline will lower FW’s serum sodium by 8 mEq/L in a
24 hour period?
• 146 mL/h, or 3524 mL in a 24 hour period
• Would this maintenance fluid and infusion rate be appropriate for FW?
• Yes, it provides his daily estimated fluid needs plus approximately an
additional 1160 mL per day to replace his free water deficit without lowering
his serum sodium level too quickly. With this fluid at this rate, his free water
deficit should be replaced within 3 days. At that time, the maintenance fluid
rate can be decreased to 98 mL/h to provide his daily estimated needs