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Intravenous Hypertonic Sodium Chloride - Adult/Pediatric - Inpatient

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1
Intravenous Hypertonic Sodium Chloride – Adult/Pediatric –
Inpatient
Clinical Practice Guideline
Target Population:
Adult and pediatric inpatients using intravenous hypertonic sodium
chloride.
CPG Contact:
Name: Philip Trapskin, Manager, Drug Policy Program
Phone Number: 608-263-1328
Email address: PTrapskin@uwhealth.org
Guideline Author(s):
Jennifer Ng, PharmD
Carin Bouchard, PharmD
Matt Wolf, PharmD
Coordinating Team Members:
Sara Shull, PharmD, MBA
Review Individuals/Bodies:
Josh Medow, MD
UW Health Pharmacy and Therapeutics Committee
Committee Approvals/Dates:
UW P&T Committee/June 2013
UW P&T Committee/June 2006
Release Date:
June 2013
June 2015 – Interim Update (administration instructions refer to IV
Administration Clinical Practice Guidelines)
Next schedule review:
June 2015
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

2
Clinical Practice Guideline (CPG)
Executive Summary
Guideline Title:
Intravenous Hypertonic Sodium Chloride – Adult and Pediatric – Inpatient – Clinical Practice
Guideline
Guideline Overview
These clinical practice guidelines are intended to guide clinicians in the use of hypertonic saline in
adult and pediatric patients. Graded recommendations for indications, dosing, administration,
and precautions for use are included.
Practice Recommendations
1. Hyponatremia
1.1. Indications
1.1.1. Management of symptoms of severe hypotonic hyponatremia (Class I, Level of
Evidence A).2,22,23
1.1.2. Management of severe sodium chloride depletion when rapid electrolyte restoration is
essential due to ongoing sodium losses (Class I, Level of Evidence A). 2,22
1.1.3. Inappropriate use includes treatment of asymptomatic hyponatremia without ongoing
losses (Class III, Level of Evidence A).23
1.2. Dose
1.2.1. An initial goal serum sodium concentration must be established.
1.2.1.1. Symptoms of severe hyponatremia: goal of 120 mmol/L initially followed by
slower correction to approximately 130 mmol/L over the following several days.
Initial goal serum sodium level should be lower if the baseline serum sodium is
<100 mmol/L.22
1.2.2. Calculate sodium deficit for patients with hyponatremia (Class I, Level of Evidence
A):2,22,24
1.2.2.1. Calculate Ideal Body Weight
1.2.2.1.1. Males (kg) = 50 kg + [2.3 kg X (each inch over 5 feet)].
1.2.2.1.2. Females (kg) = 45.5 kg + [2.3 kg X (each inch over 5 feet)].
1.2.2.2. Calculate Total Body Water (TBW)
1.2.2.2.1. Nonelderly (<65 yrs) males TBW (L)= 0.6 X IBW
1.2.2.2.2. Nonelderly (<65 yrs) females and elderly (≥65 yrs) males TBW (L)= 0.5 X
IBW
1.2.2.2.3. Elderly (≥65 yrs) females TBW (L)= 0.45 X IBW
1.2.2.3. Calculate Serum Sodium Deficit
1.2.2.3.1. Target serum sodium concentration (mmol/L) – actual serum sodium
concentration (mmol/L)
1.2.2.4. Calculate Amount of Sodium Chloride Required (mmol)
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
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3
1.2.2.4.1. Serum sodium deficit (mmol/L) X TBW (L)
1.2.2.5. See Appendix A for additional useful calculations
1.2.3. Available intravenous sodium chloride solutions for treating hyponatremia:
Table 1. Intravenous Sodium Chloride Solutions
Solution Solution Na+ (mmol/L) Tonicity (mOsm/L)
3% Sodium Chloride 513 1026
1.8% Sodium Chloride 308 616
0.9% Sodium Chloride 154 308
0.45% Sodium Chloride 77 154
1.3. Administration - Refer to UW Health Adult and Pediatric IV Administration Clinical Practice
Guidelines for appropriate rate of administration and level of care required
1.3.1. Sodium chloride 3% is a UWHC Level 3 medication which designates the nursing
1.3.2. A central line is preferred for administration of 3% sodium chloride to avoid
thrombophlebitis/extravasation. A central line is not required for 1.8% sodium chloride
(Class I, Level of Evidence A).25
1.3.3. In adult patients: Correction of symptomatic hyponatremia should occur at a rate that
reverses the symptoms of hyponatremia, but should not be so rapid as to cause
neurologic damage.22 To help avoid possible myelinolysis and neurologic damage
especially in the chronically hyponatremic individuals,5 the rate of administration of
hypertonic sodium chloride should ideally be strictly controlled so that the serum
sodium concentration is raised at the rate at which it fell (Class I, Level of Evidence
A).2,22,23
1.3.3.1. Acute onset of hyponatremia (<48 hours): raise serum sodium by 1 to 2
mmol/L/hr in the first 2 to 3 hours until symptoms abate (Class I, Level of
Evidence A).2,22,23
1.3.3.2. Chronic onset of hyponatremia (>48 hours or hyponatremia of unknown
Duration): raise serum sodium by no more than 0.5 mmol/L/hr in the first 2 to 3
hours until symptoms abate (Class I, Level of Evidence A).23,26
1.3.3.3. The maximum recommended rate of correction is ≤8 mmol/L/24 hrs (Class I,
Level of Evidence A).2,22
1.3.3.4. A typical initial rate of infusion of 3% sodium chloride is approximately 15 to 80
mL/hr (1mL/kg/hour) for 2 to 3 hours (Class I, Level of Evidence A).22
1.3.3.5. The concurrent use of a loop diuretic (e.g. furosemide) is usually applied in
nonhypovolemic patients to mandate free water excretion and to avoid treatment
induced expansion of the extracellular fluid volume (Class I, Level of Evidence
A).2,22,23
1.3.3.6. Vasopressin antagonists are non-formulary at UWHC (e.g. tolvaptan,
conivaptan).
1.3.4. In pediatric patients: Correction of symptomatic hyponatremia should occur at a rate
that reverses the symptoms of hyponatremia and restores any intravascular fluid
deficits but should not be so rapid as to cause neurologic damage.22 To help avoid
possible myelinolysis and neurologic damage especially in the chronically
hyponatremic individuals,5 the rate of administration of hypertonic sodium chloride
should ideally be strictly controlled so that the serum sodium concentration is raised at
the rate at which it fell (Class I, Level of Evidence A).2
Hyponatremic seizures are a medical emergency and must be treated with HTS
solution. In this situation, the serum sodium can be raised by as much as 4-8 mmol/L
in the first hour or until the seizure activity ceases. Following this, the rate of 3% HTS
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

4
solution infusion should raise the plasma sodium by about 1 mmol/L per hour until
either: 1) the patient is alert and seizure free; 2) the plasma sodium has increased by
20 mmol/L or 3) a serum sodium of about 125-130 mmol/L has been achieved,
whichever occurs first (Class I, Level of Evidence A).27
1.3.4.1. Assuming body water is 50% of weight, 1 mL/kg of 3% sodium chloride will
increase the serum sodium concentration by 1 mmol/L.27
1.3.5. The recommended indications for stopping rapid correction are:22
1.3.5.1. Cessation of life threatening manifestations (Class I, Level of Evidence A).2,22,23
1.3.5.2. Moderation of severe symptoms such as seizure, severe obtundation, coma, or
respiratory arrest (Class I, Level of Evidence A).2,22,23
1.3.5.3. Serum sodium concentration of 120 mmol/L or lower if the baseline serum
sodium was <100 mmol/L (Class I, Level of Evidence A).22
1.3.6. Serum sodium and serum potassium levels should be monitored every 1 to 4 hours
during therapy (1 to 2 hours during initial increased rates of therapy). Ongoing
gastrointestinal and/or urinary losses associated with diarrheal, cerebral, or
nephrogenic sodium wasting syndromes should be monitored closely as well (Class I,
Level of Evidence A).2,22,23
2. Elevated Intracranial pressure (ICP)
2.1. Indications
2.1.1. Management of life threatening intracranial hypertension with clinical/radiologic
evidence of elevated ICP (>20 – 25 mmHg) secondary to brain edema (Class I, Level
of Evidence A).7,9,14,20,28
2.1.1.1. Patient with elevated ICP values as defined by an ICP monitor.
2.1.1.2. Cerebral edema or mass effect.
2.1.2. Inappropriate use includes treatment of increased ICPs in patients with elevated
sodium levels (Class IIb, Level of Evidence B).7,29
2.1.2.1.1. Serum Na+ >160 mmol/L* and/or serum Osmol >360 mOsm/L (*upon
weighing risk and benefits of therapy, practitioners may wish to exceed
serum Na+ of 160 mmol/L to control ICP; however, there is an increased
risk for renal failure).
2.2. Dose
2.2.1. In adult patients: The goal serum sodium concentration is 150 to 160 mmol/L (Class
I, Level of Evidence B).7,30,31
2.2.1.1. Goal of hyperosmolar therapy for cerebral edema is to maintain serum
osmolality levels in the 300 to 320 mOsm/L range, with allowance of the serum
osmolality to reach 360 mOsm/L (Class I, Level of Evidence B).7
2.2.2. In pediatric patients: The goal is to maintain ICP <20 mmHg, with allowance of the
serum osmolality to reach 360 mOsm/L (Class I, Level of Evidence A).32,33
2.2.3. Available sodium chloride solutions for the treatment of elevated ICP:
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

5
Table 2. Intravenous Sodium Chloride Solutions
Solution Solution Na+ (mmol/L) Tonicity (mOsm/L)
7.5% Sodium Chloride (bolus only) 1274 2548
3% Sodium Chloride 513 1026
1.8% Sodium Chloride 308 616
0.9% Sodium Chloride 154 308
0.45% Sodium Chloride 77 154
2.3. Administration –
2.3.1. Refer to UW Health Adult and Pediatric IV Administration Clinical Practice Guidelines
for appropriate rate of administration and required level of care.
2.3.2. Sodium chloride 7.5% may only be initiated by a Neurosurgery ICU attending/chief or
Pediatric ICU attending/chief who is directly involved in the primary care of the patient
or in a consultative manner by another attending.
2.4. Preparation
2.4.1. All doses of sodium chloride 7.5% will be patient specific and prepared and dispensed
from the central pharmacy with a maximum volume of 250mL per dose
2.4.2. In adult patients:
2.4.2.1. Sodium chloride 1.8% or 3% - Initiate infusion at 1 to 2 mL/kg/hr (administration
rate range: 75 to 150 mL/hr). A 250 mL bolus over 30 minutes may be
administered if more aggressive therapy is desired (Class I, Level of Evidence
B).7,9,11,12
2.4.2.2. Sodium chloride 7.5% - A 2 mL/kg bolus over 30 minutes may be administered if
more aggressive therapy is desired (Class IIb, Level of Evidence B).15-17 Single
bolus doses are limited to a total volume of 250 mL.13,18
2.4.3. In pediatric patients:
2.4.3.1. Sodium chloride 3% - Administer 3% sodium chloride infusion in a range
between 0.1 and 1 mL/kg/hr (Class I, Level of Evidence A).32 A 3 to 5 mL/kg
bolus may be given over 30 minutes if more aggressive therapy is desired
(Class IIa, Level of Evidence B).34 Sodium chloride 1.8% may be used in place
of 3% sodium chloride (Class IIa, Level of Evidence C).
2.4.3.2. Sodium chloride 7.5% - Dose has not been established. Use may be approved
by pediatric ICU attending/chief (Class III, Level of Evidence C).
2.4.4. A central line is preferred for administration of 3% sodium chloride and 7.5% sodium
chloride boluses to avoid thrombophlebitis/ extravasation (Class I, Level of Evidence
A).25
3. Monitoring
3.1. During therapy de-escalation and discontinuation, caution must be taken to avert rebound
hyponatremia and cerebral edema. Consider weaning HTS therapy over 24 to 48 hours
(Class I, Level of Evidence B).7
3.2. Serum sodium every 1 to 8 hours with monitoring occurring every 1 to 4 hours during initial
increased rates of therapy (Class I, Level of Evidence A).2,7,22,23
3.3. Other electrolytes including potassium, bicarbonate, chloride and magnesium, and
parameters of renal function including BUN and serum creatinine levels. Measurement of
ongoing sodium losses in the urine should be monitored as well if cerebral salt-wasting
syndrome is a consideration (Class I, Level of Evidence A).2,7,22,23
3.4. Fluid balance such as intake and output (Class I, Level of Evidence A).2,7,22,23
3.5. Acid-base balance (Class I, Level of Evidence A).2,7,22,23
3.6. Symptoms of hyponatremia (Class I, Level of Evidence A).2,7,22,23
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6
3.7. Neurologic symptoms associated with myelinolysis: mutism, dysarthria, lethargy, affective
changes, spastic quadriparesis, pseudobulbar palsy, papillary and oculomotor
abnormalities, depressed level of consciousness, ataxia, irregular behavior, and movement
disorders (Class I, Level of Evidence A).2,4,7,22,23
3.8. Intracranial pressure monitor if used for intracranial hypertension (Class I, Level of
Evidence B).7
3.9. With continued therapy for the treatment of elevated ICP, chest radiographs are
recommended at least once daily to look for evidence of pulmonary edema. (Class I, Level
of Evidence B).7
4. Cautions/Warnings
4.1. Too rapid of serum sodium correction and/or over-correction to hypernatremia can lead to
myelinolysis and permanent neurologic damage (Class III, Level of Evidence A).4
4.1.1. The risk of myelinolysis is higher for patients with chronic hyponatremia (Class III,
Level of Evidence A).5,32
4.2. Use with caution in patients with congestive heart failure, pulmonary edema, cirrhosis of the
liver, renal failure, urinary tract obstruction or in any clinical state in which there exists
edema and sodium retention (Class I, Level of Evidence A).2,7,22,23
4.3. The risk of thrombophlebitis/extravasation exists with use of hypertonic solutions. A central
line preferred for administration of 3% sodium chloride and 7.5% sodium chloride boluses
(Class I, Level of Evidence A).25,34
5. Drug Interactions
5.1. Use caution in patients receiving drugs that can cause sodium retention or increase water
clearance (e.g. corticosteroids and mannitol) (Class IIb, Level of Evidence C).
5.2. Use caution in patients receiving drugs that contain high amounts of sodium (e.g. nafcillin,
ampicillin, sodium polystyrene sulfonate) as well as other potentially hidden sources of
sodium (enteral feeds and total parenteral nutrition) (Class IIb, Level of Evidence C).
New Recommendations
The May 2013 revision included recommendations to add 7.5% HTS bolus for the treatment of
elevated intracranial pressure in adults.
Pertinent UWHC Policies & Procedures
1. UWHC Adult IV Administration Guidelines
2. UWHC Pediatric IV Administration Guidelines
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

7
Intravenous Hypertonic Sodium Chloride – Adult and Pediatric – Inpatient – Clinical Practice
Guideline
A. Scope
1. Guidance for the use of intravenous hypertonic sodium chloride in UWHC adult and pediatric
inpatients.
B. Methodology
1. A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology (Figure 1)
has been used to assess the Quality and Strength of the Evidence in this Clinical Practice
Guideline.1
Figure 1. Quality of Evidence and Strength of Recommendation Grading Matrix
C. Introduction
Hyponatremia, defined as serum sodium concentrations <135 mmol/L, is a common electrolyte
disorder that requires careful management.2 In general, hyponatremia represents a relative imbalance
between free water and existing sodium stores in which the sodium deficit exceeds the free water
deficit. It is important to understand the underlying pathophysiologic basis of hyponatremia to provide
effective treatment. Most often, treatment involves limiting the free water intake or, in cases of
dehydration, restoring the intravascular volume with normal saline. However, circumstances exist
where infusion of hypertonic sodium chloride (HTS) solutions may be appropriate.3
The decision to infuse HTS should not be taken lightly. Infusions should be reserved only for patients
with symptoms of severe hyponatremia.3 Consequences of rapid and/or overcorrection of serum
sodium levels with HTS can lead to myelinolysis (demyelination of the pons and extrapontine areas of
the brain) and permanent neurologic damage.4
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8
Nevertheless, acute, symptomatic, severe hyponatremia is a serious medical condition that may lead
to changes in brain cell volume which ultimately may lead to seizures, brain herniation, death, or
irreversible brain damage.5 Symptoms are generally neurologic in nature. Malaise, weakness, and
nausea are commonly the earliest findings when sodium concentrations fall below 125 to 130 mmol/L
followed by headache, lethargy, muscle cramps, restlessness, encephalopathy, respiratory failure,
arrhythmias and obtundation. Severe symptoms such as seizure, coma, respiratory arrest and
death can occur when serum sodium concentrations reach <115 to 120 mmol/L.6
In addition to management of hyponatremia, HTS has demonstrated efficacy in the management of
elevated intracranial pressure (ICP). Elevated ICP is encountered frequently in patients requiring
neurologic intensive care.7 The Brain Trauma Foundation recommends treating elevated ICP above
20 to 25 mmHg. Elevated ICP (>20 mmHg) may reduce cerebral blood flow, thus resulting in
significant morbidity.8 Recently, HTS has been introduced as an option for treating elevated ICP. HTS
exerts its effect primarily through establishing an osmotic gradient between intravascular spaces and
the cerebral tissue. This allows water to move from the cerebral intracellular and interstitial spaces
into the capillaries, thereby reducing cerebral water content and the ICP.9
There is no consensus on the most optimal route or concentration of HTS for treatment of elevated
ICP, because all concentrations, administered via bolus or continuous infusion, appear to
demonstrate favorable effects on ICP.9-21 In order to minimize the risk associated with use of
concentrated electrolytes, only 3% and 7.5% HTS are available at UWHC.
D. Recommendations
1. Hyponatremia
1.1. Indications
1.1.1. Management of symptoms of severe hypotonic hyponatremia (Class I, Level of
Evidence A).2,22,23
1.1.2. Management of severe sodium chloride depletion when rapid electrolyte restoration is
essential due to ongoing sodium losses (Class I, Level of Evidence A). 2,22
1.1.3. Inappropriate use includes treatment of asymptomatic hyponatremia without ongoing
losses (Class III, Level of Evidence A).23
1.2. Dose
1.2.1. An initial goal serum sodium concentration must be established.
1.2.1.1. Symptoms of severe hyponatremia: goal of 120 mmol/L initially followed by
slower correction to approximately 130 mmol/L over the following several days.
Initial goal serum sodium level should be lower if the baseline serum sodium is
<100 mmol/L.22
1.2.2. Calculate sodium deficit for patients with hyponatremia (Class I, Level of Evidence
A):2,22,24
1.2.2.1. Calculate Ideal Body Weight
1.2.2.1.1. Males (kg) = 50 kg + [2.3 kg X (each inch over 5 feet)].
1.2.2.1.2. Females (kg) = 45.5 kg + [2.3 kg X (each inch over 5 feet)].
1.2.2.2. Calculate Total Body Water (TBW)
1.2.2.2.1. Nonelderly (<65 yrs) males TBW (L)= 0.6 X IBW
1.2.2.2.2. Nonelderly (<65 yrs) females and elderly (≥65 yrs) males TBW (L)= 0.5 X
IBW
1.2.2.2.3. Elderly (≥65 yrs) females TBW (L)= 0.45 X IBW
1.2.2.3. Calculate Serum Sodium Deficit
1.2.2.3.1. Target serum sodium concentration (mmol/L) – actual serum sodium
concentration (mmol/L)
1.2.2.4. Calculate Amount of Sodium Chloride Required (mmol)
1.2.2.4.1. Serum sodium deficit (mmol/L) X TBW (L)
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
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9
1.2.2.5. See Appendix A for additional useful calculations
1.2.3. Available intravenous sodium chloride solutions for treating hyponatremia:
Table 1. Intravenous Sodium Chloride Solutions
Solution Solution Na+ (mmol/L) Tonicity (mOsm/L)
3% Sodium Chloride 513 1026
1.8% Sodium Chloride 308 616
0.9% Sodium Chloride 154 308
0.45% Sodium Chloride 77 154
1.3. Administration
1.3.1. Refer to UW Health Adult and Pediatric IV Administration Clinical Practice Guidelines
for appropriate rate of administration and level of care required.
1.3.2. A central line is preferred for administration of 3% sodium chloride to avoid
thrombophlebitis/extravasation. A central line is not required for 1.8% sodium chloride
(Class I, Level of Evidence A).25
1.3.3. In adult patients: Correction of symptomatic hyponatremia should occur at a rate that
reverses the symptoms of hyponatremia, but should not be so rapid as to cause
neurologic damage.22 To help avoid possible myelinolysis and neurologic damage
especially in the chronically hyponatremic individuals,5 the rate of administration of
hypertonic sodium chloride should ideally be strictly controlled so that the serum
sodium concentration is raised at the rate at which it fell (Class I, Level of Evidence
A).2,22,23
1.3.3.1. Acute onset of hyponatremia (<48 hours): raise serum sodium by 1 to 2
mmol/L/hr in the first 2 to 3 hours until symptoms abate (Class I, Level of
Evidence A).2,22,23
1.3.3.2. Chronic onset of hyponatremia (>48 hours or hyponatremia of unknown
Duration): raise serum sodium by no more than 0.5 mmol/L/hr in the first 2 to 3
hours until symptoms abate (Class I, Level of Evidence A).23,26
1.3.3.3. The maximum recommended rate of correction is ≤8 mmol/L/24 hrs (Class I,
Level of Evidence A).2,22
1.3.3.4. A typical initial rate of infusion of 3% sodium chloride is approximately 15 to 80
mL/hr (1mL/kg/hour) for 2 to 3 hours (Class I, Level of Evidence A).22
1.3.3.5. The concurrent use of a loop diuretic (e.g. furosemide) is usually applied in
nonhypovolemic patients to mandate free water excretion and to avoid treatment
induced expansion of the extracellular fluid volume (Class I, Level of Evidence
A).2,22,23
1.3.3.6. Vasopressin antagonists are non-formulary at UWHC (e.g. tolvaptan,
conivaptan).
1.3.4. In pediatric patients: Correction of symptomatic hyponatremia should occur at a rate
that reverses the symptoms of hyponatremia and restores any intravascular fluid
deficits but should not be so rapid as to cause neurologic damage.22 To help avoid
possible myelinolysis and neurologic damage especially in the chronically
hyponatremic individuals,5 the rate of administration of hypertonic sodium chloride
should ideally be strictly controlled so that the serum sodium concentration is raised at
the rate at which it fell (Class I, Level of Evidence A).2
Hyponatremic seizures are a medical emergency and must be treated with HTS
solution. In this situation, the serum sodium can be raised by as much as 4-8 mmol/L
in the first hour or until the seizure activity ceases. Following this, the rate of 3% HTS
solution infusion should raise the plasma sodium by about 1 mmol/L per hour until
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

10
either: 1) the patient is alert and seizure free; 2) the plasma sodium has increased by
20 mmol/L or 3) a serum sodium of about 125-130 mmol/L has been achieved,
whichever occurs first (Class I, Level of Evidence A).27
1.3.4.1. Assuming body water is 50% of weight, 1 mL/kg of 3% sodium chloride will
increase the serum sodium concentration by 1 mmol/L.27
1.3.5. The recommended indications for stopping rapid correction are:22
1.3.5.1. Cessation of life threatening manifestations (Class I, Level of Evidence A).2,22,23
1.3.5.2. Moderation of severe symptoms such as seizure, severe obtundation, coma, or
respiratory arrest (Class I, Level of Evidence A).2,22,23
1.3.5.3. Serum sodium concentration of 120 mmol/L or lower if the baseline serum
sodium was <100 mmol/L (Class I, Level of Evidence A).22
1.3.6. Serum sodium and serum potassium levels should be monitored every 1 to 4 hours
during therapy (1 to 2 hours during initial increased rates of therapy). Ongoing
gastrointestinal and/or urinary losses associated with diarrheal, cerebral, or
nephrogenic sodium wasting syndromes should be monitored closely as well (Class I,
Level of Evidence A).2,22,23
2. Elevated Intracranial pressure (ICP)
2.1. Indications
2.1.1. Management of life threatening intracranial hypertension with clinical/radiologic
evidence of elevated ICP (>20 – 25 mmHg) secondary to brain edema (Class I, Level
of Evidence A).7,9,14,20,28
2.1.1.1. Patient with elevated ICP values as defined by an ICP monitor.
2.1.1.2. Cerebral edema or mass effect.
2.1.2. Inappropriate use includes treatment of increased ICPs in patients with elevated
sodium levels (Class IIb, Level of Evidence B).7,29
2.1.2.1.1. Serum Na+ >160 mmol/L* and/or serum Osmol >360 mOsm/L (*upon
weighing risk and benefits of therapy, practitioners may wish to exceed
serum Na+ of 160 mmol/L to control ICP; however, there is an increased
risk for renal failure).
2.2. Dose
2.2.1. In adult patients: The goal serum sodium concentration is 150 to 160 mmol/L (Class
I, Level of Evidence B).7,30,31
2.2.1.1. Goal of hyperosmolar therapy for cerebral edema is to maintain serum
osmolality levels in the 300 to 320 mOsm/L range, with allowance of the serum
osmolality to reach 360 mOsm/L (Class I, Level of Evidence B).7
2.2.2. In pediatric patients: The goal is to maintain ICP <20 mmHg, with allowance of the
serum osmolality to reach 360 mOsm/L (Class I, Level of Evidence A).32,33
2.2.3. Available sodium chloride solutions for the treatment of elevated ICP:
Table 2. Intravenous Sodium Chloride Solutions
Solution Solution Na+ (mmol/L) Tonicity (mOsm/L)
7.5% Sodium Chloride (bolus only) 1274 2548
3% Sodium Chloride 513 1026
1.8% Sodium Chloride 308 616
0.9% Sodium Chloride 154 308
0.45% Sodium Chloride 77 154
2.3. Administration
2.3.1. Refer to UW Health Adult and Pediatric IV Administration Clinical Practice Guidelines
for appropriate rate of administration and level of care required.
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

11
2.3.2. Sodium chloride 7.5% may only be initiated by a Neurosurgery ICU attending/chief or
Pediatric ICU attending/chief who is directly involved in the primary care of the patient
or in a consultative manner by another attending.
2.4. Preparation
2.4.1. All doses of sodium chloride 7.5% will be patient specific and prepared and dispensed
from the central pharmacy with a maximum volume of 250mL per dose
2.4.2. In adult patients:
2.4.2.1. Sodium chloride 1.8% or 3% - Initiate infusion at 1 to 2 mL/kg/hr (administration
rate range: 75 to 150 mL/hr). A 250 mL bolus over 30 minutes may be
administered if more aggressive therapy is desired (Class I, Level of Evidence
B).7,9,11,12
2.4.2.2. Sodium chloride 7.5% - A 2 mL/kg bolus over 30 minutes may be administered if
more aggressive therapy is desired (Class IIb, Level of Evidence B).15-17 Single
bolus doses are limited to a total volume of 250 mL.13,18
2.4.3. In pediatric patients:
2.4.3.1. Sodium chloride 3% - Administer 3% sodium chloride infusion in a range
between 0.1 and 1 mL/kg/hr (Class I, Level of Evidence A).32 A 3 to 5 mL/kg
bolus may be given over 30 minutes if more aggressive therapy is desired
(Class IIa, Level of Evidence B).34 Sodium chloride 1.8% may be used in place
of 3% sodium chloride (Class IIa, Level of Evidence C).
2.4.3.2. Sodium chloride 7.5% - Dose has not been established. Use may be approved
by pediatric ICU attending/chief (Class III, Level of Evidence C).
2.4.4. A central line is preferred for administration of 3% sodium chloride and 7.5% sodium
chloride boluses to avoid thrombophlebitis/ extravasation (Class I, Level of Evidence
A).25
3. Monitoring
3.1. During therapy de-escalation and discontinuation, caution must be taken to avert rebound
hyponatremia and cerebral edema. Consider weaning HTS therapy over 24 to 48 hours
(Class I, Level of Evidence B).7
3.2. Serum sodium every 1 to 8 hours with monitoring occurring every 1 to 4 hours during initial
increased rates of therapy (Class I, Level of Evidence A).2,7,22,23
3.3. Other electrolytes including potassium, bicarbonate, chloride and magnesium, and
parameters of renal function including BUN and serum creatinine levels. Measurement of
ongoing sodium losses in the urine should be monitored as well if cerebral salt-wasting
syndrome is a consideration (Class I, Level of Evidence A).2,7,22,23
3.4. Fluid balance such as intake and output (Class I, Level of Evidence A).2,7,22,23
3.5. Acid-base balance (Class I, Level of Evidence A).2,7,22,23
3.6. Symptoms of hyponatremia (Class I, Level of Evidence A).2,7,22,23
3.7. Neurologic symptoms associated with myelinolysis: mutism, dysarthria, lethargy, affective
changes, spastic quadriparesis, pseudobulbar palsy, papillary and oculomotor
abnormalities, depressed level of consciousness, ataxia, irregular behavior, and movement
disorders (Class I, Level of Evidence A).2,4,7,22,23
3.8. Intracranial pressure monitor if used for intracranial hypertension (Class I, Level of
Evidence B).7
3.9. With continued therapy for the treatment of elevated ICP, chest radiographs are
recommended at least once daily to look for evidence of pulmonary edema. (Class I, Level
of Evidence B).7
4. Cautions/Warnings
4.1. Too rapid of serum sodium correction and/or over-correction to hypernatremia can lead to
myelinolysis and permanent neurologic damage (Class III, Level of Evidence A).4
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12
4.1.1. The risk of myelinolysis is higher for patients with chronic hyponatremia (Class III,
Level of Evidence A).5,32
4.2. Use with caution in patients with congestive heart failure, pulmonary edema, cirrhosis of the
liver, renal failure, urinary tract obstruction or in any clinical state in which there exists
edema and sodium retention (Class I, Level of Evidence A).2,7,22,23
4.3. The risk of thrombophlebitis/extravasation exists with use of hypertonic solutions. A central
line preferred for administration of 3% sodium chloride and 7.5% sodium chloride boluses
(Class I, Level of Evidence A).25,34
5. Drug Interactions
5.1. Use caution in patients receiving drugs that can cause sodium retention or increase water
clearance (e.g. corticosteroids and mannitol) (Class IIb, Level of Evidence C).
5.2. Use caution in patients receiving drugs that contain high amounts of sodium (e.g. nafcillin,
ampicillin, sodium polystyrene sulfonate) as well as other potentially hidden sources of
sodium (enteral feeds and total parenteral nutrition) (Class IIb, Level of Evidence C).
E. Internal References
1. UWHC Adult IV Administration Guidelines
2. UWHC Pediatric IV Administration Guidelines
F. External References
1. Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC, Jr. Scientific evidence underlying the
ACC/AHA clinical practice guidelines. JAMA. Vol 301. United States2009:831-841.
2. Palmer BF, Gates JR, Lader M. Causes and management of hyponatremia. Ann Pharmacother.
Nov 2003;37(11):1694-1702.
3. Culpepper RM, Clements BD, Pence SR. Hypertonic saline: patterns of and guidelines for use.
South Med J. Dec 1994;87(12):1203-1207.
4. Laureno R, Karp BI. Myelinolysis after correction of hyponatremia. Ann Intern Med. Jan 1
1997;126(1):57-62.
5. Oh MS, Kim HJ, Carroll HJ. Recommendations for treatment of symptomatic hyponatremia.
Nephron. 1995;70(2):143-150.
6. Al-Salman J, Kemp D, Randall D. Hyponatremia. West J Med. May 2002;176(3):173-176.
7. Bhardwaj A, Ulatowski JA. Cerebral Edema: Hypertonic Saline Solutions. Curr Treat Options
Neurol. Jul 1999;1(3):179-188.
8. The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint
Section on Neurotrauma and Critical Care. Use of mannitol. J Neurotrauma. Jun-Jul 2000;17(6-
7):521-525.
9. Qureshi AI, Suarez JI, Bhardwaj A, et al. Use of hypertonic (3%) saline/acetate infusion in the
treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain.
Crit Care Med. Mar 1998;26(3):440-446.
10. Mortazavi MM, Romeo AK, Deep A, et al. Hypertonic saline for treating raised intracranial
pressure: literature review with meta-analysis. J Neurosurg. Jan 2012;116(1):210-221.
11. De Vivo P, Del Gaudio A, Ciritella P, Puopolo M, Chiarotti F, Mastronardi E. Hypertonic saline
solution: a safe alternative to mannitol 18% in neurosurgery. Minerva Anestesiol. Sep
2001;67(9):603-611.
12. Huang SJ, Chang L, Han YY, Lee YC, Tu YK. Efficacy and safety of hypertonic saline solutions in
the treatment of severe head injury. Surg Neurol. Vol 65. United States2006:539-546; discussion
546.
13. Oddo M, Levine JM, Frangos S, et al. Effect of mannitol and hypertonic saline on cerebral
oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension.
J Neurol Neurosurg Psychiatry. Vol 80. England2009:916-920.
14. Kamel H, Navi BB, Nakagawa K, Hemphill JC, 3rd, Ko NU. Hypertonic saline versus mannitol for
the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit
Care Med. Mar 2011;39(3):554-559.
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Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org

13
15. Vialet R, Albanese J, Thomachot L, et al. Isovolume hypertonic solutes (sodium chloride or
mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5%
saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med. Jun 2003;31(6):1683-1687.
16. Cottenceau V, Masson F, Mahamid E, et al. Comparison of effects of equiosmolar doses of
mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury. J
Neurotrauma. Oct 2011;28(10):2003-2012.
17. Alsharkasy M, Altouny A, Elshatoury H, Ewila H. Comparison between Mannitol 20% and
hypertonic saline 7.5% for cerebral resuscitation in severely head injured patients with intra-
cranial hypertension. Int J Health Sci (Qassim). Jul 2011;5(2 Suppl 1):36-37.
18. Bulger EM, May S, Brasel KJ, et al. Out-of-hospital hypertonic resuscitation following severe
traumatic brain injury: a randomized controlled trial. JAMA. Vol 304. United States2010:1455-
1464.
19. Suarez JI, Qureshi AI, Bhardwaj A, et al. Treatment of refractory intracranial hypertension with
23.4% saline. Crit Care Med. Jun 1998;26(6):1118-1122.
20. Rockswold GL, Solid CA, Paredes-Andrade E, Rockswold SB, Jancik JT, Quickel RR. Hypertonic
saline and its effect on intracranial pressure, cerebral perfusion pressure, and brain tissue
oxygen. Neurosurgery. Vol 65. United States2009:1035-1041; discussion 1041-1032.
21. Ware ML, Nemani VM, Meeker M, Lee C, Morabito DJ, Manley GT. Effects of 23.4% sodium
chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a
preliminary study. Neurosurgery. Vol 57. United States2005:727-736; discussion 727-736.
22. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. May 25 2000;342(21):1581-1589.
23. Vaidya C, Ho W, Freda BJ. Management of hyponatremia: providing treatment and avoiding
harm. Cleve Clin J Med. Vol 77. United States2010:715-726.
24. Adrogue HJ, Madias NE. Aiding fluid prescription for the dysnatremias. Intensive Care Med. Mar
1997;23(3):309-316.
25. Zimmet SE. The prevention of cutaneous necrosis following extravasation of hypertonic saline
and sodium tetradecyl sulfate. J Dermatol Surg Oncol. Jul 1993;19(7):641-646.
26. Ellis SJ. Severe hyponatraemia: complications and treatment. QJM. Dec 1995;88(12):905-909.
27. Moritz ML, Ayus JC. Preventing neurological complications from dysnatremias in children. Pediatr
Nephrol. Dec 2005;20(12):1687-1700.
28. Forsyth LL, Liu-DeRyke X, Parker D, Jr., Rhoney DH. Role of hypertonic saline for the
management of intracranial hypertension after stroke and traumatic brain injury.
Pharmacotherapy. Apr 2008;28(4):469-484.
29. Paredes-Andrade E, Solid CA, Rockswold SB, Odland RM, Rockswold GL. Hypertonic saline
reduces intracranial hypertension in the presence of high serum and cerebrospinal fluid
osmolalities. Neurocrit Care. Oct 2012;17(2):204-210.
30. Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes.
J Neurol Neurosurg Psychiatry. Vol 75 Suppl 3. England2004:iii22-28.
31. Thongrong C, Kong N, Govindarajan B, Allen D, Mendel E, Bergese SD. Current Purpose and
Practice of Hypertonic Saline in Neurosurgery: A Review of the Literature. World Neurosurg. Feb
9 2013.
32. Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of
severe traumatic brain injury in infants, children, and adolescents. Chapter 11. Use of
hyperosmolar therapy in the management of severe pediatric traumatic brain injury. Pediatr Crit
Care Med. Jul 2003;4(3 Suppl):S40-44.
33. Dominguez TE, Priestley MA, Huh JW. Caution should be exercised when maintaining a serum
sodium level >160 meq/L. Crit Care Med. Vol 32. United States2004:1438-1439; author reply
1439-1440.
34. Brenkert TE, Estrada CM, McMorrow SP, Abramo TJ. Intravenous hypertonic saline use in the
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G. Benefits/Harms of Implementation
Implementation of this guideline calls for the creation of a 7.5% HTS ERx in Health Link. Due to the
high-alert status of the medication, 7.5% HTS requires special storage, handling, and check systems
to prevent potentially fatal errors. All doses of 7.5% HTS will be patient specific and prepared and
dispensed from the central pharmacy utilizing 2.5mEq/mL NaCl.
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14
H. Implementation Strategy
The guideline was reviewed by pharmacy staff and then sent to adult and pediatric physicians for
review. After pharmacy and physician review, the guideline will be presented to the P & T committee
for approval.
I. Implementation Tools/Plan –
1. A request will be sent to the Drug Product Supply and Selection Committee for approval
2. Health link will have to be updated to include ERx for 7.5% HTS.
J. Disclaimer
This Clinical Practice Guideline provides an evidence-based approach for treatment of .
It is understood that occasionally patients will not match the conditions considered in the guideline.
Copyright © 2013 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/2013CCKM@uwhealth.org