Overview of

Fluid and
Electrolyte
Maintenance
Mallory Turner, Pharm.D., BCPS
AAHP Fall Seminar
October 9, 2015
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Disclosure
• I have no relevant financial relationships to disclose.

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Pharmacist Objectives
• Discuss the distribution of total body fluid, and apply this concept
towards the management of a patient's fluid replacement.
• Recommend an appropriate intravenous fluid regimen based on a
patient's clinical characteristics.
• Develop an effective electrolyte replacement plan based on a
patient's clinical status and electrolyte abnormalities.
• Identify appropriate clinical situations for the use of hypertonic and
hypotonic saline, and recommend monitoring parameters to ensure
the safe use of these intravenous fluids.

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Technician Objectives
• Recognize appropriate precautions to be taken while compounding
intravenous electrolyte replacement products, including hypotonic
and hypertonic saline.
• Delineate the differences between colloid and crystalloid fluids, and
recall appropriate instances for their use.
• Identify common intravenous fluid regimens and describe
appropriate dosages and concentrations for electrolyte additives.
• Identify common units and calculations involved in compounding
electrolyte replacement products.

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Fluid Management

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Fluid Distribution
• Total body fluid (TBF)
 Estimated as ~60% of lean body weight (LBW) in males
 Estimated as ~50% of LBW in females

• TBF further divided

 Intracellular (IC) space 60% of TBF
 Enclosed by the cell membrane
 Extracelllular (EC) space 40% of TBF
 Interstitial space 75% of EC fluid
 Intravascular space 25% of EC fluid
 Plasma ~3L
 Red blood cells ~2L fluid

• Distribution in the body determines distribution of intravenous (IV) fluids

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Fluid Distribution
Total Body Fluid
Extracellular

Cell Membrane
Total Body Fluid
Intracellular
60% TBF
Extracellular
Interstitial Fluid
75% EC

40% TBF
Capillary Membrane
Intravascular Fluid
25%

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Fluid Compartments

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Osmotic Equilibrium
• Osmotic pressure
 Created by concentration of ions/electrolytes in each compartment
 Responsible for containing water in each space, keeps volume constant

• Osmolality
 Number of particles per kilogram of water

• Osmotic Equilibrium
 Water moves across the cell membrane from of region of low osmolality to one of
higher osmolality

• Plasma osmolality
 Normal value: 280-300 mOsm/kg

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Acute Fluid Resuscitation
• Intravascular fluid depletion can occur as a result of shock
 Associated with reduced cardiac function and organ hypoperfusion
 Signs and symptoms usually occur when ~15% (750mL) of blood volume is lost or shifts
out of intravascular space

• Signs and Symptoms of intravascular volume depletion

 Tachycardia
 Hypotension
 Orthostatic changes in HR or BP
 Increased BUN/Scr ration >10:1
 Dry mucous membranes
 Decreased skin turgor
 Reduced urine output
 Dizziness
 Improvement after a 500- or 1000-mL fluid bolus

• Fluid resuscitation is indicated in patients exhibiting signs and

symptoms
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Acute Fluid Resuscitation
• Goal: restore intravascular volume and prevent organ hypoperfusion

• Crystalloids recommended as a rapid infusion

 NS or LR typically used
 LR preferred in surgery and trauma patients
 LR has more physiological amount of Cl than NS

• Crystalloids vs Colloids
 No difference has been shown in time to resuscitation or outcomes
 Colloids: higher cost, some adverse effects

• Selective instances to consider colloids (controversial)

 4-6L crystalloid fluid resuscitation has failed or caused significant edema
 Patients with albumin <2.5mg/dL who have required a large volume already
 Albumin + diuretics for patients with clinically significant edema and low albumin

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Maintenance Fluid Replacement
• Indicated in patients unable to tolerate oral fluids
• Goal: prevent dehydration and maintain normal fluid/electrolyte
balance
• Administered as continuous infusions through peripheral or central
lines
• Example maintenance fluid
 D5W with 0.45% NaCl with 20-40mEq of KCl per liter

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Maintenance Fluid Replacement
• Calculations to determine daily volume needed in children and adults
 Administer 100mL/kg for the first 10kg of weight, then 50mL/kg for the next 10-
20kg, plus 20mL/kg for every kilogram greater than 20kg
OR
 Administer 20-40ml/kg/day (adults only)

• Adjust fluids according to individual patient’s input, output, insensible

losses

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Commonly Used IV Fluids
Crystalloids
• Crystalloids
 Normal saline, Lactated Ringer’s, Normosol-R
 Contain water, sodium, chloride, and additional electrolytes
 Hypertonic and hypotonic crystalloid options

• Normal Saline (0.9% sodium chloride)

 Advantages
 Low risk for adverse reactions
 Disadvantages
 Freely distributes across vascular barrier
 Risks of hypernatremia and hyperchloremic metabolic acidosis

• Additional Considerations
 Duration 1-4 hours
 Isotonic

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Commonly Used IV Fluids
Crystalloids
• Lactated Ringers (or Ringers Lactate)
 Advantages
 Low risk for adverse reactions
 Disadvantages
 Freely distribute across the vascular barrier
 Risk of respiratory acidosis due to CO2 accumulation
 Risk for hyperkalemia (4mEq/L of potassium)
 Impaired metabolism of lactate to bicarbonate in patients with severe liver disease

• Additional Considerations
 Duration of action 1-4 hours
 Considered equally effective as NS
 Not recommended in hemorrhagic shock or brain trauma
 Traditionally preferred in surgical patients
 Contains sodium chloride, sodium lactate, potassium chloride, calcium chloride

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Commonly Used IV Fluids
Crystalloids
• 5% Dextrose in Water (D5W)
 “Free water”: metabolized to water and carbon dioxide
 Water crosses any membrane in the body
 60% into the IC space and 40% to the EC space

• Hypotonic
 Isotonic in bag but becomes hypotonic when metabolized to free water

• Additional Considerations
 Not preferred for fluid resuscitation
 50 grams of dextrose per liter
 Not recommended in patients with neurologic injury or elevated intracranial
pressure

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Commonly Used IV Fluids
Colloids
• Colloids
 PRBCs, albumin, dextran, hetastarch
 Too large to cross capillary membrane
 Provide significant volume increase because they remain in intravascular space

• Controversial use
 Albumin showed no mortality benefit over NS (SAFE trial)
 Hydroxyethyl starch no longer recommended due to adverse effects
 Expensive compared to crystalloids
 Higher risk of adverse and allergic reactions

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Commonly Used IV Fluids
Colloids
• Albumin (5% and 25% formulations)
 Advantages
 Colloids provide greater volume expansion than equal volumes of crystalloids
 Disadvantages
 Potential for allergic reactions
 Potential for transmission of infection
 Hyperoncotic albumin may cause kidney damage
 Expensive

• Additional Considerations
 Natural colloid (blood product)
 Duration of action 12-24 hours
 5% albumin is iso-oncotic, 25% albumin is hyperoncotic

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Commonly Used IV Fluids
Colloids
• Dextran
 Advantages
 Provides greater volume expansion than equal volumes of crystalloids
 Disadvantages
 High risk for adverse reactions
 Potential for allergic reactions or anaphylactoid reactions
 Impairs hemostasis
 May cause kidney damage

• Additional Considerations
 Artificial colloid
 Duration of action 1-2 hours
 Use for fluid resuscitation has fallen out to favor due to risk of adverse reactions

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Commonly Used IV Fluids
Colloids
• Hydroxyethyl starch (HES)
 Advantages
 Provides greater volume expansion than equal volumes of crystalloids
 May modulate inflammation
 Disadvantages
 Potential for anaphylactoid reactions
 May accumulate in tissues and cause prolonged itching
 May impair platelet function and/or cause kidney damage
 Expensive

• Additional Considerations
 Synthetic colloid
 Duration of action up to 36 hours
 Hyperoncotic (6%)
 Larger molecular weight than albumin
 Not recommended in patients with severe sepsis (increased mortality, bleeding)

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 Composition of Commonly Used
Intravenous Replacement Solutions
Na Cl Distribution Distribution Free
Solution Dextrose Tonicity
(mEq/L) (mEq/L) (% ECF) (% ICF) water/L
D5W 5g/100mL 0 0 Hypotonic 40 60 1000ml
0.45%
0 77 77 Hypotonic 73 37 500mL
NaCl
0.9%
0 154 154 Isotonic 100 0 0mL
NaCl
3% NaCl 0 513 513 Hypertonic 100 0 -2331mL
Hypotonic
LR 0 130 109 100 0 0mL
(slightly)

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 IV Fluid Distribution
Intravenous Fluid Infused Volume (mL) Equivalent Intravascular
Volume Expansion (mL)
NS 1000 250
LR 1000 250
Normosol-R 1000 250
D5W 1000 100
Albumin 5% 500 500
Albumin 25% 100 500
Hetastarch 6% 500 500

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Electrolyte Replacement

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Electrolyte Composition
Total Body Fluid

Intracellular Extracellular
Compartment Compartment

• Potassium • Sodium
• Magnesium • Chloride
• Phosphate • Bicarbonate
• Calcium

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Disorders of Sodium
• Normal range 135 – 145 mEq/L
• Role in the body
 Sodium in the ECF determines the tonicity of the ECF
 Directly affects the distribution of water between EC and IC compartments
 Sodium concentration is the ratio of Na:H2O (not absolute amount of either)
 Sodium level does not indicate whether abnormality is due to increase in the total
amount of Na, H2O, or both

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 Hyponatremia
• Sodium concentration <135 mEq/L
• Most common electrolyte abnormality
• Significant morbidity and mortality
• Signs and symptoms
 Clinically do not appear until sodium <125 mEq/L
 Acute: cerebral edema, seizures, increased mortality risk
 Chronic: N/V, confusion, personality changes, neurologic dysfunction, gait
disturbances, seizures

Serum sodium (mEq/L) Clinical manifestations

120-125 Nausea, malaise
115-120 HA, lethargy, obtundation, unsteadiness, confusion
<115 Delirium, seizure, coma, respiratory arrest, death
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Types of Hyponatremia
Hypovolemic Euvolemic Hypervolemic
Hypotonic Hypotonic Hypotonic
Hyponatremia Hyponatremia Hyponatremia
Description Deficit of both Na Normal total body Caused by excess Na
and fluid, but total Na with excess and fluid, but fluid
Na is decreased more fluid volume excess predominates
than TBW (dilutional)
Example Fluid loss, third SIADH, HF, cirrhosis,
spacing, renal loss medications nephrotic syndrome
Treatment Fluid resuscitation Treat cause Na and water
Fluid restriction restriction
Vasopressin Treat underlying
receptor cause
antagonists Vasopressin receptor
antagonists
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Principles of Hyponatremia Correction
• AVOID overly rapid increases in serum sodium (>10-12 mEq/L in 24 hours)

• Treat underlying cause

• Chronicity of hyponatremia impacts the rate at which correction should be

undertaken

• Transient or permanent brain dysfunction may result from overly rapid

correction of hyponatremia
 Osmotic demyelination syndrome

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3% Sodium Chloride Infusion
• High alert medication
• Administration
 Symptomatic hyponatremia: infusion rate 1-2ml/kg/hour
 Central IV access (osmolarity >900mOsm/L)
 If peripheral IV must be used (emergency), monitor for phlebitis
 Monitor serum sodium changes every 1-4 hours depending on symptom severity

• Complications
 Osmotic demyelination syndrome
 Hypokalemia
 Hyperchloremic acidosis
 Hypernatremia
 Heart failure
 Coagulopathy
 Hypotension

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Hypernatremia
• Sodium level >145mEq/dL
• Hypertonic state resulting in cellular dehydration
• Commonly observed in patients without thirst response
• High mortality rates if serum sodium >160mEq/dL (~60-75%)
• Signs and symptoms
 Thirst, dry mucous membranes, decreased skin turgor, acute weight loss, weakness,
lethargy, restlessness, irritability, confusion, hallucinations, ICH, coma, seizures,
death

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Types of Hypernatremia
Hypovolemic Euvolemic Hypervolemic
Hypernatremia Hypernatremia Hypernatremia
Description Water loss Water loss only Sodium gain
exceeds sodium exceeds water
loss gain
Example Insensible losses DI Sodium overload,
exceed intake mineralicorticoid
excess
Treatment 0.9%NS until VS Free water Free water
stable, then free replacement, replacement with
water vasopressin loop diuretic, HD

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Hypernatremia
• Treatment
 Depends on cause: too little water or too much sodium

• Rapid correction is NOT indicated

 Results in cerebral edema, seizures, neurologic damage, death
 Do not exceed a change of greater than 10mEq/day

• Hypovolemic Hypernatremia
 NS adminstered to correct ECF volume
 Then hypotonic solution to correct H2O deficit

• Euvolemic hypernatremia
 Hypotonic solution
 Treatment for DI if indicated

• Hypervolemic hypernatremia
 Goal: to remove sodium from the body
 Diuretics (loops) and hypotonic solution (D5W)

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Disorders of Potassium
• Normal range: 3.5 – 5 mEq/L
• Intracellular ion
 Most abundant cation in the body
 98% in intracellular compartment, 2% in extracellular space

• Role in the body

 Cellular synthesis and metabolism, action potential across cell membrane,
neuromuscular activity, cardiac conduction

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Hypokalemia
• Potassium level < 3.5 mEq/L
 Mild: 3 – 3.5 mEq/L
 Moderate : 2.5 – 3 mEq/dL
 Severe: < 2.5 mEq/L

• Causes
 GI loss
 Medications
 Metabolic acidosis
 Hypomagnesemia

• Signs and Symptoms

 Mild: asymptomatic
 Moderate to severe: muscle weakness, cramping, ileus, EKG changes, cardiac
arrhythmias

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Hypokalemia Treatment
• Potassium level 3.5 – 4 mEq/L
 Increase dietary intake of potassium rich foods

• Potassium level 3 – 3.5 mEq/L

 PO potassium supplementation in patients with cardiac conditions or on digoxin

• Potassium level <3 mEq/L

 IV infusion recommended

• Correct hypomagnesemia first

 Low magnesium impairs the function of the Na-K-ATPase pump
 Impairment results in increased renal excretion of potassium

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 Hypokalemia Treatment
Plasma K+ Treatment Comments
(mEq/L)
3-3.5 Oral KCl 60-80 mEq/day if no signs or Doses >60mEq should be
symptoms divided to avoid GI effects
Recheck K+ daily
2.5-3 Oral KCl 120 mEq/day or IV 60-80 mEq Monitor K+ (i.e. 2 hours post-
administered at 10-20mEq/hour if signs or infusion)
symptoms
2-2.5 IV KCl at 10-20mEq/hour Consider continuous ECG
monitoring
<2 IV KCl at 20-40mEq/hour Consider continuous ECG
monitoring

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 Potassium IV Administration
General Med-Surg Areas ICU/Telemetry Beds

Rate Not to exceed 10mEq/hour Recommended: 10mEq/hour

Max rate: 20mEq/hour

Concentration Not to exceed 10mEq/50mL 20mEq/50mL (central line)

Notes Rates >10mEq/hour must be

monitored

KCl: Never to be administered IV Push!

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Hyperkalemia
• Potassium level >5.5 mEq/L
 Mild: potassium level 5.5 – 6 mEq/L
 Moderate: potassium level 6.1 – 6.9 mEq/L
 Severe: potassium level > 7 mEq/L

• Causes
 Renal failure, acidosis, red cell hemolysis, overcorrection, medications, salt
substitutes, traumatic injury (MVC), adrenal insufficiency

• Signs and Symptoms

 EKG changes
 Peaked T waves, depressed ST segment, disappearance of P wave, widened QRS complex
 Additional
 Muscle weakness, paresthesias, GI hypermotility, paralysis

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Hyperkalemia Treatment
• Treatment Goals
 Reverse cardiac effects immediately
 Redistribute potassium from extracellular space into the cell
 Eliminate potassium from the body
 Additionally: treat underlying cause and stop excess intake or medications

• Treatment
 Calcium gluconate
 Insulin and glucose
 Β2-agonists
 Sodium bicarbonate
 Sodium polystyrene sulfonate
 Loop diuretics
 Dialysis

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Disorders of Magnesium
• Normal Range: 1.5 – 2.2 mEq/L
• Role in the body
 Intracellular ion predominantly
 Found in bone and muscle

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Hypomagnesemia
• Magnesium level <1.4 mEq/L
• Causes
 Reduced intake, reduced absorption, increased loss, drug-induced
 Often due to other electrolyte abnormalities

• Signs and Symptoms

 Neuromuscular: tremor, hyperactive reflexes, seizures
 Cardiac: arrhythmias (ventricular fibrillation, Torsades de Pointes)

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Hypomagnesemia Treatment
• PO, IV infusion, or IM

• PO
 Magnesium containing antacids or laxatives
 Magnesium oxide
 SE: diarrhea

• IV infusion
 Magnesium sulfate
 Dose depends on the depletion 8-12 g (1 gram = 4 mEq)
 Standard infusion rate: 1-2 grams/hour

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Hypermagnesemia
• Magnesium level: > 2.2 mEq/L
• Causes
 Renal failure (acute vs chronic), elderly, adrenal insufficiency, hypothyroidism,
lithium

• Signs and Symptoms

 Asymptomatic < 4 mEq/L
 Weakness, N/V, hypotension, respiratory depression, muscle paralysis, coma,
cardiac arrhythmias

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Hypermagnesemia Treatment
• Reduce magnesium intake

• Enhance magnesium excretion

 Loop diuretics

• Antagonize physiologic effects of magnesium

 IV calcium – antagonizes neurological and cardiovascular effects of magnesium

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Disorders of Phosphorous
• Normal range: 2.5 – 4.5 mg/dL
• Role in the body
 Intracellular ion
 Cell membrane function, DNA/RNA/proteins, part of energy molecule (ATP), RBC
function, bone mineral

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Hypophosphatemia
• Phosphate < 2.6 mg/dL
• Causes
 Decreased GI absorption, increased urinary excretion, redistribution

• Signs and Symptoms

 Neurological: irritability, neuropathy, seizures, coma
 Musculoskeletal: weakness, atrophy, rickets, osteomalacia
 Cardiopulmonary: CHF, respiratory failure
 Hematologic: hemolysis, anemia

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Hypophosphatemia Treatment
• Mild to moderate hypophosphatemia
 Usually asymptomatic
 PO phosphorous replacement

• Severe hypophosphatemia
 IV phosphorous 15-30mmol (0.5 – 0.75 mmol/kg of IBW)
 Max IV rate 7.5 mmol/hour
 Monitor q6hours for up to 72 hours

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Hyperphosphatemia
• Phosphate > 4.5 mg/dL
• Causes
 Chronic kidney disease or hypoparathyroidism

• Signs and Symptoms

 Generally asymptomatic
 Hypocalcemia, ECG changes, and paresthesias can occur

• Treatment
 Limit intake of phosphorous
 Phosphate binding agents
 Dialysis
 Replace calcium if patient is also hypocalcemic

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Disorders of Calcium
• Normal range: 8.5 – 10.5 mEq/dL (ionized calcium 1.1 – 1.3 mmol/L)
• Distribution
 Extracellular fluid contains <1% of calcium, 99% of total body stores is in skeletal
bone
 Half of calcium in EC fluid is bound to albumin and other plasma proteins
 Ionized calcium (unbound) is the active form
 Ionized calcium is regulated by parathyroid hormone, phosphorous, vitamin D and
calcitonin

• Role in the body

 Bone mineral, blood coagulation, membrane excitability, muscle contraction, neuron
activation

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Hypocalcemia
• Total serum calcium level <8.5 mg/dL
• Ionized calcium level <1.1 mmol/L
• Causes
 Post-operative hypoparathyroidism, vitamin D deficiency, renal failure,
malnutrition, medications, hyperphosphatemia

• Signs and Symptoms

 Neuromuscular: paresthesias, muscle cramps, tetany, laryngeal spasm
 Cardiovascular: prolonged QT interval, arrhythmias, bradycardia, hypotension
 Dermatologic: hair loss, brittle nails, eczema
 CNS: depression, anxiety, memory loss, confusion, hallucinations, seizures

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Hypocalcemia Treatment
• Acute hypocalcemia
 IV calcium (calcium chloride or calcium gluconate)
 200-300mg of elemental calcium
 Monitor calcium q4-6 hours during IV therapy
 Treat underlying disorder

• Chronic hypocalcemia
 Oral calcium supplementation
 Oral vitamin D supplementation

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Hypercalcemia
• Serum calcium >10.5mg/dL
• Ionized calcium >1.3 mmol/L
• Causes
 Usually due to malignancy, hyperparathyroidism

• Signs and Symptoms

 Muscle weakness, anorexia, N/V, constipation, ventricular arrhythmias, lethargy,
depression, psychosis, coma

• Treatment
 Beyond the scope of this discussion
 ECG changes: volume expansion, loop diuretics, HD
 Treat underlying disorder

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