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EM Critical Care
UNDERSTANDING AND CARING FOR
CRITICAL ILLNESS IN EMERGENCY MEDICINE
Therapeutic Uses Of Hypertonic
Saline In The Critically Ill
Emergency Department Patient
Author
Jeffrey A. Holmes, MD
Attending Physician, Maine Medical Center, Portland, ME;
Assistant Professor, Tufts University School of Medicine,
Boston, MA
Peer Reviewers
Abstract
David Callaway, MD, MPA
Hypertonic saline is defined as any crystalloid solution containing
more than 0.9% saline. The administration of hypertonic saline has
been studied alone as well as in combination with colloid solutions
(most commonly dextran). Its many theoretical advantages (including small-volume resuscitation, reduction of intracranial pressure,
improved hemodynamics, and improved microcirculation and immunomodulation) have prompted research into its use as a resuscitative fluid for a variety of critically ill patients. The 2 patient cohorts
most frequently studied are patients with traumatic brain injury and
trauma patients with hemorrhagic shock. Hypertonic saline has been
shown to be safe and efficacious in decreasing intracranial pressure
and improving hemodynamics with few adverse effects, but there
are no prospective human trials demonstrating improved clinical
outcomes for these patients. Hypertonic saline has been shown to
be a valuable therapy for the treatment of severe hyponatremia in
patients with signs of cerebral edema, but treatment guidelines are
based mostly upon expert consensus and are not well defined. This
review examines the evidence on the use of hypertonic saline for the
treatment of patients with traumatic brain injury and secondary intracranial hypertension, trauma patients in hemorrhagic shock, and
patients with severe hyponatremia.
Editor-in-Chief
Volume 3, Number 1
Associate Professor, Emergency Medicine, Carolinas Medical
Center, Charlotte, NC
Catherine A. Gogela Carlson, MD
Critical Care Medicine Fellow, Departments of Critical Care
Medicine and Emergency Medicine, University of Pittsburgh
Medical Center, Pittsburgh, PA
CME Objectives
Upon completion of this article, you should be able to:
1.
2.
3.
4.
Describe the theoretical advantages of using hypertonic
saline over traditional crystalloid solutions for the
treatment of traumatic brain injury.
Describe the practical and theoretical advantages of
using hypertonic saline over traditional resuscitative
crystalloid solutions for traumatic hemorrhagic shock.
Recognize the signs of cerebral edema secondary to
severe hyponatremia.
Describe the use of hypertonic saline in the treatment
of severe hyponatremia while avoiding overrapid
correction of sodium levels.
Prior to beginning this activity, see the back page for faculty
disclosures and CME accreditation information.
Andy Jagoda, MD, FACEP
Julie Mayglothling, MD
Professor and Chair, Department
Assistant Professor, Department
of Emergency Medicine, Mount
of Emergency Medicine,
Sinai School of Medicine; Medical
Department of Surgery, Division
Lillian L. Emlet, MD, MS, FACEP
Director, Mount Sinai Hospital, New
of Trauma/Critical Care, Virginia
Assistant Professor, Department of
York, NY
Commonwealth University,
Critical Care Medicine, Department
Richmond, VA
of Emergency Medicine, University
of Pittsburgh Medical Center;
William A. Knight, IV, MD
Program Director, EM-CCM
Assistant Professor of Emergency Christopher P. Nickson, MBChB,
Fellowship of the Multidisciplinary
Medicine, Assistant Professor
MClinEpid, FACEM
Associate Editor
Critical Care Training Program,
of Neurosurgery, Emergency
Senior Registrar, Intensive Care
Pittsburgh, PA
Medicine Mid-Level Program
Scott Weingart, MD, FACEP
Unit, Royal Darwin Hospital,
Medical Director, University of
Associate Professor, Department of
Darwin, Australia
Cincinnati College of Medicine,
Emergency Medicine, Mount Sinai Michael A. Gibbs, MD, FACEP
Cincinnati, OH
School of Medicine; Director of
Professor and Chair, Department
Jon Rittenberger, MD, MS, FACEP
Emergency Critical Care, Elmhurst
of Emergency Medicine, Carolinas
Assistant Professor, Department
Hospital Center, New York, NY
Medical Center, University of North Haney Mallemat, MD
of Emergency Medicine,
Carolina School of Medicine,
Assistant Professor, Department
University of Pittsburgh School
Chapel Hill, NC
of Emergency Medicine, University
of Medicine; Attending Physician,
Editorial Board
of Maryland School of Medicine,
Emergency Medicine and Post
Benjamin S. Abella, MD, MPhil,
Baltimore, MD
Robert Green, MD, DABEM,
Cardiac Arrest Services, UPMC
FACEP
Presbyterian Hospital, Pittsburgh,
FRCPC
Assistant Professor, Department
Evie Marcolini, MD, FAAEM
PA
Professor, Department of
of Emergency Medicine and
Assistant Professor, Department of
Anaesthesia, Division of Critical
Department of Medicine /
Emergency Medicine and Critical
Care Medicine, Department of
Section of Pulmonary Allergy
Care, Yale School of Medicine,
Emergency Medicine, Dalhousie
and Critical Care, University of
New Haven, CT
University, Halifax, Nova Scotia,
Pennsylvania School of Medicine;
Canada
Clinical Research Director,
Robert T. Arntfield, MD, FACEP,
FRCPC, FCCP
Assistant Professor, Division
of Critical Care, Division of
Emergency Medicine, Western
University, London, Ontario,
Canada
Center for Resuscitation Science,
Philadelphia, PA
Emanuel P. Rivers, MD, MPH, IOM
Vice Chairman and Director
of Research, Department of
Emergency Medicine, Senior
Staff Attending, Departments of
Emergency Medicine and Surgery
(Surgical Critical Care), Henry
Ford Hospital, Clinical Professor,
Department of Emergency
Medicine and Surgery, Wayne State
University School of Medicine,
Detroit, MI
Isaac Tawil, MD, FCCM
Assistant Professor, Department
of Anesthesia and Critical Care /
Department of Emergency Medicine,
Director, Neurosciences ICU,
University of New Mexico Health
Science Center, Albuquerque, NM
Research Editor
Amy Sanghvi, MD
Department of Emergency
Medicine, Mount Sinai School of
Medicine, New York, NY
Case Presentations
Your shift is just beginning when you are notified that
EMS is bringing in a 20-year-old male patient who was
struck by a motor vehicle. As your team assembles, you
notify the CT scanner and ask him to keep it open and
available. When the patient arrives, you find that he
has decorticate posturing, a large scalp hematoma, and
multiple facial fractures. After you intubate him via
RSI and complete your initial assessment, he is quickly
wheeled over to CT. His head CT shows a large epidural
hematoma with 10 mm of midline shift. His abdominal
CT reveals a splenic laceration with active extravasation.
You begin your interventions to manage the patient’s elevated intracranial pressure and arrange transport to the
nearest Level 1 trauma center. As you hear the helicopter
landing, you notice that the patient’s pupils have become
asymmetric. You ask yourself, “Which would be better to
control the patient’s intracranial hypertension: mannitol
or hypertonic saline?”
A short time later, EMS wheels a first-time marathon
runner into the critical care bay. She was witnessed to
have collapsed at mile 22 with seizure-like activity of 1
minute duration. She is currently postictal with a normal
fingerstick blood glucose. Her vital signs are as follows:
heart rate of 118 beats per minute, respiratory rate of 24
breaths per minute, blood pressure of 138/90 mm Hg,
rectal temperature of 38.3°C, and oxygen saturation of
98% on a nonrebreather mask. You wonder if she might
have suffered a heat stroke. Her temperature is elevated
— but not enough to cause a seizure. Besides her continued altered mental status, she has an otherwise normal
exam. You send her off to the CT scanner to look for acute
intracranial pathology. As her scan is completed and the
results are confirmed by the radiologist as unremarkable,
the lab calls back with a critical value: her serum sodium
is 109 mEq/L. The nurse calls out to you from the scanner, “Doc, she’s seizing again!”
Introduction
Hypertonic saline (HTS), which is defined as any
crystalloid solution containing more than 0.9%
saline, has a potentially important role in the treatment of several life-threatening conditions seen
in the emergency department (ED). With respect
to the trauma patient, HTS has unique properties
that may make it an ideal resuscitative fluid for the
most common causes of traumatic death: central
nervous system injury, exsanguination, and organ
failure.1 (See Table 1.) It has been shown to reduce
intracranial pressure (ICP) in patients with traumatic brain injury (TBI) and may have an immunomodulatory effect that further reduces neuronal
damage and multiple-organ failure.2-7 HTS may
also improve hemodynamics and microcirculation,
resulting in improved resuscitation in hemorrhagic
shock.8-10 Compared to traditional crystalloid solu-
EMCC © 20132
tions (normal saline or lactated Ringer’s solution),
a smaller volume of HTS is required to improve
hemodynamic stability in hypotensive patients.11
This has many practical advantages for the military
and for other austere environments that preclude
carrying a large volume of fluid for the purpose of
resuscitation.12
HTS also has an important role in the treatment
of severe hyponatremia. While hyponatremia in the
ED is typically chronic and requires no immediate
intervention, acute severe hyponatremia can cause
significant morbidity and mortality. Appropriate recognition and treatment with HTS can help prevent
devastating sequelae from both the hyponatremia
itself and its overaggressive treatment.
This issue of EMCC examines the evidence supporting the use of HTS for the treatment of patients
with TBI with elevated ICP, trauma patients in hemorrhagic shock, and patients with severe hyponatremia.
Critical Appraisal Of The Literature
A literature search was performed using Ovid MEDLINE®, PubMed, and EMBASE from 1990 to the
present. The area of focus was the use of HTS in the
treatment of TBI, hypovolemic shock, and severe hyponatremia. Search terms included hypertonic saline,
traumatic brain injury, intracranial hypertension, shock,
hypovolemic shock, hemorrhagic shock, and hyponatremia. Over 300 articles were retrieved and provided
background for further literature review. The Cochrane Database of System­atic Reviews, Eastern Association for the Surgery of Trauma (EAST) Guidelines, Western Trauma As­sociation (WEST) Guidelines, American College of Emergency Physicians
Clinical Policies, National Neurotrauma Society,
National Brain Trauma Foundation, Neurosurgical
Society of America, Annals of Emergency Medicine’s
Evidence-Based Emergency Medicine reviews, and
National Guideline Clearing­house (www.guideline.
gov) were also searched. All HTS solutions were
incorporated, with solutions ranging from 1.6% to
30%, including those mixed with colloids.
The literature on the use of HTS for resuscitation of trauma patients is difficult to interpret due to
several confounding variables. For instance, studies
Table 1. The Causes Of Death Following
Trauma1
Acute
(< 2 d)
Early
(3-7 d)
Late
(> 7 d)
Central nervous system
40%
64%
39%
Blood loss
55%
9%
0%
Multiple organ dysfunction
1%
18%
61%
Other
4%
8%
0%
www.ebmedicine.net • Volume 3, Number 1
Comparison Of Hypertonic Saline To
Mannitol
have used varied concentrations of HTS (from 2% to
7.5%), have used varied methods of HTS administration (bolus as well as maintenance drips), and have
included nontrauma patients in their study groups.
In addition, the results from some clinical trials
comparing HTS to mannitol can be deceiving, as
they do not use equiosmolar doses of HTS. This difference may make HTS appear more effective than
mannitol, where the primary effect could arguably
be attributed to the higher osmotic load. Lastly, most
studies only demonstrate significance in surrogate
physiologic markers rather than meaningful clinical outcomes. For these reasons, current treatment
guidelines for the use of HTS in trauma resuscitation
are based largely upon expert opinion.
The literature on the use of HTS to treat patients with severe hyponatremia is weak and mostly
comprised of retrospective studies. Few prospective
studies have been done, and treatment guidelines
are based mostly upon expert consensus.
Despite the lack of evidence for any mortality
benefit,22 mannitol is currently considered to be the
gold standard for osmotic therapy in the treatment
of acute intracranial hypertension, and it is endorsed
by the Brain Trauma Foundation’s most recent
guidelines for the management of severe TBI.23
However, HTS is being increasingly investigated as
an alternative. Several retrospective studies have
suggested that HTS might be effective in reducing
intracranial hypertension that is refractory to the
use of mannitol.24,25 Only a few rigorous prospective studies have compared the effectiveness of HTS
or HTS combined with dextran to mannitol in ICP
reduction. Kamel et al performed a meta-analysis
of randomized clinical trials comparing HTS and
mannitol for reduction of ICP.26 Only studies that
administered equiosmolar doses in human subjects
undergoing quantitative ICP measurements were
included in this meta-analysis. Five trials comprising 112 patients with 184 episodes of intracranial
hypertension were included. Despite small sample
sizes and mild heterogeneity (mostly due to different formulations of HTS), they found that HTS was
more effective than mannitol for the treatment of intracranial hypertension. In 2007, a Cochrane review
assessed the effects of mannitol therapy for acute
TBI compared to other treatment regimens. Only 1
trial was found that directly compared mannitol to
HTS.27 In this study, which was performed by Vialet
et al, it was suggested that mannitol therapy for
intracranial hypertension may have a detrimental
effect on mortality when compared to HTS therapy
(relative risk for death = 1.25; 95% confidence
interval, 0.47-3.33).28 Unfortunately, this study was
too small to make valid conclusions, as there were
only 20 patients in each arm. In 2011, Cottenceau
performed a multicenter prospective study on 47
severe TBI patients in intensive care units (ICUs).29
Patients were randomized to equiosmolar doses of
20% mannitol (4 mL/kg) or 7.5% HTS (2 mL/kg).
Both treatment arms effectively reduced ICP. There
was a trend toward HTS being significantly stronger
and of longer duration than mannitol; however, this
difference was not statistically significant. There
were no reported significant adverse events or differences in neurologic outcome at 6 months between
the groups. While these studies suggest that HTS is a
safe and effective alternative to mannitol for treating
intracranial hypertension, there is limited evidence
to support any superior efficacy or improved patient
outcomes, and a large randomized controlled trial
comparing mannitol and HTS is needed.
Traumatic Brain Injury
Although the primary injury to the brain occurs
at the time of impact, subsequent compromise of
cerebral perfusion can extend the primary injury
and create a secondary injury. Current therapy in
the prehospital setting and the ED aims to minimize secondary injury by supporting systemic
perfusion, reducing ICP, and optimizing cerebral
perfusion pressure (CPP). The interventions to
decrease intracranial hypertension that have
historically been used in the ED include: head
of bed elevation, supporting systolic blood pressure (SBP) > 90 mm Hg, preventing hypoxia, and
ensuring normocapnic ventilation. Additionally,
for patients with signs of impending herniation
(such as asymmetric pupillary response, dilated
and unreactive pupils, motor posturing, or rapid
neurologic decline), osmotic agents (such as mannitol or HTS) should be administered.
Intracranial Pressure Reduction
Many trials have shown administration of HTS to
be an effective method to reduce ICP for the braininjured patient. Five case control studies have shown
that HTS alone or with a colloid reduces ICP in
both adult and pediatric patients with TBI.13-17 Five
randomized controlled studies also compared HTS
to mannitol,18,19 isotonic crystalloid, or hypotonic
crystalloid20,21 and found HTS to be effective in reducing intracranial hypertension secondary to both
traumatic and nontraumatic causes. Most studies
used bolus dosing rather than continuous infusion
and varied the solution concentration from 1.8% to
10% with and without colloids.
www.ebmedicine.net • Volume 3, Number 1
3
EMCC © 2013
Clinical Outcome
Few studies have examined how the use of HTS may
affect mortality or long-term neurological disability
for patients with TBI. In 2008, Bunn and colleagues
performed a Cochrane review to determine whether
the use of HTS decreases mortality in patients with
hypovolemia with and without head injuries.30 They
found only 1 trial that specifically studied whether
prehospital resuscitation with intravenous (IV)
HTS improves long-term neurological outcome in
patients with severe TBI compared to resuscitation
with crystalloid solutions.31 There was no difference in survival or neurologic outcome at 6 months
between the 2 groups.
Shortly after the Cochrane review by Bunn
et al, the National Institutes of Health sponsored
the largest and most important study to date with
respect to these outcomes. This multicenter randomized double-blind placebo-controlled trial
enrolled 1331 patients from the prehospital setting.32 Patients with concomitant hypotension were
excluded. Patients were randomized to receive a
250-mL prehospital bolus of 7.5% HTS, 7.5% HTS
with 6% dextran 70, or normal saline and were followed for 6 months. The study was stopped after
an interim analysis determined that HTS provided
no improvement in either mortality or neurologic
outcome and that enrolling new patients would not
change the outcome of the study.
In 2011, Tan et al conducted a systematic literature review to investigate whether the infusion of
HTS or colloid solutions results in better outcomes
than standard isotonic crystalloid solutions for
patients with TBI. They identified 9 randomized
controlled trials and 1 cohort study that examined
the effects of infusion of hypertonic solutions (with
or without the addition of colloids) for prehospital volume resuscitation.33 Studies that included
patients who had sustained a TBI, with and without
other injuries, were included in the review. None of
these trials reported better survival and functional
outcomes with HTS compared to the use of standard
isotonic crystalloid solutions.
In 2007, the Brain Trauma Foundation, in conjunction with the American Association of Neurological Surgeons and the Congress of Neurological
Surgeons, published guidelines regarding the use of
hyperosmolar therapy for the management of severe
TBI. The guideline authors only examined literature
on adult human hospitalized patients. The major
outcomes they reviewed included reduction in ICP,
changes in CPP, changes in cerebral blood flow, and
long-term morbidity and mortality. They concluded
that the current evidence is not strong enough to
make recommendations on the use, concentration,
or method of administration of HTS in traumatic
intracranial hypertension.23 Until more conclusive
evidence regarding the use of HTS for ICP manage-
EMCC © 20134
ment for patients with severe TBI emerges, future
guidelines are unlikely to be different from the current guidelines.
Traumatic Brain Injury With Concurrent
Hypotension
Trauma patients with TBI often have accompanying
injuries that lead to hypotension. Volume resuscitation in this patient population can be challenging, as
the isotonic crystalloid solutions that are traditionally used to restore end-organ perfusion and prevent
secondary anoxic brain injury could, theoretically,
exacerbate cerebral edema. It would seem intuitive that these patients would be an ideal cohort to
benefit from HTS. Unfortunately, there is no strong
evidence to support this. One multicenter trial using 7.5% HTS with dextran suggested a mortality
benefit in hypotensive patients who sustained a TBI.
However, the strength of this conclusion is weak, as
the improvement was in comparison with predicted
survival, not a direct comparison with the control
group.34 Wade et al performed a manufacturer-supported cohort analysis of 223 patients with TBI and
hypotension from 6 previous prospective randomized double-blind trials. These trials compared 7.5%
HTS with dextran versus a “standard-of-care isotonic crystalloid” (usually lactated Ringer’s). They
showed a trend toward survival until discharge
(38% vs 27%; P = 0.08).35 Cooper et al from Australia
performed a double-blind randomized controlled
trial focusing on the effect of prehospital resuscitation with 7.5% HTS on neurologic outcomes in
patients with severe TBI and an SBP < 100 mm Hg.31
A total of 229 patients were enrolled. Though there
was no significant neurologic difference between
the groups at 6 months, there was a trend toward
survival in the HTS group (55% for the HTS group
and 47% for the control group; P = 0.25). While these
studies show promise for the treatment of the hypotensive TBI patient with HTS, it is difficult to draw
definitive conclusions from such small sample sizes.
Summary Of The Use Of Hypertonic Saline
In Severe Traumatic Brain Injury
Although the strength of the current literature is
weak, it suggests that HTS is as effective as mannitol for treating intracranial hypertension from TBI.
Currently, there is no convincing evidence to suggest
that osmotic therapy (whether HTS or mannitol) results in improved long-term neurologic outcome or
overall mortality benefit. HTS may be an acceptable
alternative to mannitol, and indications for its use by
the emergency physician would include significantly
deteriorating neurologic status or signs of herniation. While there is no agreement as to the dose or
concentration of HTS to use, most studies administered a 250 mL bolus of 7.5% HTS with dextran. www.ebmedicine.net • Volume 3, Number 1
who received HTS with dextran had better survival
than predicted by trauma scores.41
Bunn and colleagues performed a Cochrane review to determine whether HTS decreases mortality in patients with hypovolemia from causes other
than hemorrhage. Their search included randomized trials comparing isotonic and near-isotonic
crystalloid solutions to HTS in patients with trauma, with burns, or who were undergoing surgery.
Fourteen trials with a total of 956 participants were
included in the meta-analysis. They concluded that
the confidence intervals for relative risk were wide,
and no conclusions could be drawn about a mortality benefit.30
In 2011, a multicenter double-blind randomized
controlled trial sponsored by the National Institutes
of Health examined whether the effect of 7.5% HTS
(with and without 6% dextran 70) compared to
normal saline improved mortality in hypotensive
blunt and penetrating trauma patients.48 This study,
which included 853 patients, is the largest study to
date. Patients were randomized to receive a 250-mL
prehospital bolus of 7.5% HTS with dextran 70, 7.5%
HTS, or normal saline. Like the previously mentioned National Institutes of Health TBI study, it was
terminated early by the Data and Safety Monitoring
Board after they found that patients who received
HTS and did not receive blood transfusions in the
first 24 hours had a higher mortality (HTS with
dextran: 10%; HTS: 12.2%; normal saline: 4.8%). The
authors of this study offered 2 possible explanations
for this early mortality. The first is that the patients
treated with HTS had a higher rate of early hemorrhage (possibly precipitated by the HTS). However,
if increased bleeding was the primary mechanism
for earlier mortality, one would anticipate higher
mortality among penetrating rather than blunt
trauma patients; the opposite effect was seen in this
study. Moreover, those patients requiring emergent
hemorrhage control who received hypertonic fluids
did not have an increase in mortality. The other,
more likely, explanation is that the administration
of HTS caused a change in physician behavior that
delayed the recognition of shock and subsequent
transfusion. It is unclear whether any of these early
deaths were preventable, as there was no overall difference in the 28-day survival between the groups.48
Hypotensive Trauma Patients
For the trauma patient in hemorrhagic shock, the
choice and amount of resuscitative fluids are issues
of continued debate. Current Advanced Trauma Life
Support® guidelines recommend treating patients
in hemorrhagic shock by infusing 2 L of isotonic
or near-isotonic crystalloid solutions, followed by
blood products. However, in the last decade, 2 major
concepts have challenged this approach. The first
is the concept of “hypotensive resuscitation” (ie,
the premise that resuscitation to “normal” blood
pressures may increase bleeding at a site of uncontrolled hemorrhage). The second is the use of HTS
as an alternative resuscitative fluid. It is cheap, is
portable, improves microcirculation, and has immunomodulatory properties. It allows “small volume”
resuscitation (4 mL/kg) in austere environments and
empowers a single medic to treat multiple combat
casualties. The 1999 Institute of Medicine report on
resuscitation of combat casualties recommended
HTS with dextran as the optimal resuscitation fluid
in that environment.36 HTS may also have practical
advantages for civilian emergency medical services.
Due to short transport times, restoration of mean
arterial pressure (MAP) for patients with TBI is difficult with traditional crystalloid solutions. HTS with
dextran administered by prehospital providers may
restore MAP more quickly and reduce the potential
for secondary neurologic injury in TBI patients.
In 1980, de Felippe et al reported astonishing results of survival in 11 of 12 patients with
refractory hemorrhagic shock who were treated
with HTS.37 That same year, researchers from the
University of Sao Paulo published the first animal
study on the use of HTS.38 They subjected dogs to
hemorrhagic shock and reported that 7.5% sodium
chloride (NaCl) infused in a volume equal to only
10% of shed blood volume rapidly restored blood
pressure.38 These initial studies prompted several
subsequent trials to evaluate the use of HTS for the
treatment of hemorrhagic shock.
From 1987 to 2011, there were 10 randomized controlled trials comparing the use of HTS to
isotonic crystalloid solutions in hypotensive trauma
patients.34,39-47 Many of these trials had very low patient numbers and compared bolus therapy of 7.5%
HTS with dextran to 7.5% HTS or normal saline,
followed by standard resuscitation with crystalloids
and blood products, if necessary. Most of the trials
found that 7.5% HTS with dextran increased MAP
more than a similar volume of isotonic crystalloid
solution. No significant side effects were noticed.
Unfortunately, no studies showed an overall mortality benefit. In post-hoc analysis, some studies
showed mortality difference in certain subgroups,
such as those requiring surgery40 or when MAP was
< 70 mm Hg.39 Vassar et al remarked that, while
there was no difference in overall mortality, patients
www.ebmedicine.net • Volume 3, Number 1
Summary Of The Use Of Hypertonic Saline
In Hypotensive Trauma Patients
HTS improves hemodynamics for trauma patients
in hemorrhagic shock. Small-volume resuscitation
may make HTS an ideal crystalloid solution for
combat casualty situations. Most studies on the
use of HTS in hypotensive trauma patients administered a 250-mL bolus of 7.5% HTS with dextran.
While small trials suggest that there may be some
subsets of patients who may benefit from the use of
5
EMCC © 2013
HTS (eg, those requiring surgery or patients with
SBP < 70 mm Hg), there is currently no strong evidence to support its use in hypotensive trauma patients. Further, it may worsen mortality in patients
who do not receive blood transfusions in the first
24 hours, as it may delay the recognition of shock
and subsequent transfusion.
Severe Hyponatremia
Hyponatremia (defined as a serum sodium concentration < 135 mEq/L) is one of the most common
disorders of electrolytes in clinical practice, occurring in up to 30% of both acutely and chronically
hospitalized patients.49 The majority of patients
who present to the ED with hyponatremia do not
require emergent management; however, patients
who present with severe hyponatremia need immediate attention and an appropriate rate of correction
to prevent devastating neurologic deficits or even
death. Recognizing and appropriately instituting
treatment is critical for this life-threatening electrolyte emergency.
Brain Adaptation And Osmotic
Demyelination Syndrome
To understand the reasoning behind the recommended guidelines for treating severe hyponatremia
(including the pitfalls of overly rapid correction), it
is necessary to review how the brain adapts to hyponatremia and the time course over which this occurs.
Brain adaptation to hyponatremia begins fairly
quickly after an acute fall in serum sodium and is
complete within 2 days.50 Initially, water moves
from the hyposomolar extracellular compartment
to the relatively hyperosmolar cells. There is a loss
of interstitial sodium and water in the cerebrospinal
fluid due to increased hydraulic pressure. Within
hours, intracellular potassium, sodium, and organic
solutes are pumped out of the cell. This adaptation
helps reduce the severity of neurologic symptoms
and the risk of cerebral edema. Once adaptation is
complete, however, the neurons are hyposmolar
and, if exposed to excess sodium (as may occur during overcorrection of the hyponatremia), are prone
to suffering cellular injury; this is termed osmotic
demyelination syndrome (ODS). (See Figure 1.)
ODS is an irreversible or only partially reversible neurologic injury that may include dysarthria,
dysphagia, paraparesis or quadriparesis, behavioral
disturbances, lethargy, confusion, obtundation,
or coma. The most important risk factors for the
development of ODS include the serum sodium
concentration at presentation, the duration of hyponatremia, and the rate of correction. While no rate of
correction is totally protective, ODS can usually be
avoided by limiting correction of chronic hyponatremia (ie, hyponatremia lasting > 48 h) to no more
EMCC © 20136
than 10 to 12 mEq/L in 24 hours.51 Certain patients
may be at a particularly high risk of ODS secondary to underlying abnormalities in cerebral osmotic
regulation. These include patients with alcoholism,
malnutrition, hypokalemia, and burns as well as
elderly women on diuretics.52
Considerations For The Treatment Of Severe
Hyponatremia
When considering whether or not to treat hyponatremia with HTS, 3 questions must first be answered:
1. Does the patient’s corrected serum sodium correspond to his clinical picture?
2. Does the patient have severe neurologic symptoms (eg, coma, seizure, focal neurologic examination) that warrant treatment with HTS?
3. Is the duration of hyponatremia acute or chronic?
The corrected serum sodium should correlate
with the patient’s neurologic symptoms. Most
patients with severe neurologic symptoms from hyponatremia have serum sodium levels < 115 mEq/L.
If a patient’s serum sodium level does not correlate
with his neurologic symptoms, consider an alternative etiology for their presentation (such as toxicological, infectious, or metabolic).
Patients who present with acute severe hyponatremia (ie, hyponatremia for < 48 h) have had
little time for their brain to adapt and are more
prone to cerebral edema, but they are less likely to
develop ODS with rapid correction. These patients
usually present with seizures, encephalopathy, or
focal neurologic signs. The most common clinical
scenario an emergency physician might encounter
is water intoxication that is secondary to psychosis, ecstasy use, or endurance sports (such as
marathon running).
Patients with chronic hyponatremia (ie, hyponatremia lasting > 48 h) have had time for their brain
to adapt, are less prone to cerebral edema, and are
more likely to develop ODS with rapid correction.
These patients generally present with only mild neurologic symptoms (such as gait disturbances, confusion, lethargy, and nausea). Sometimes, the duration
of hyponatremia is not known. In this setting, it is
safest to assume that the patient has chronic hyponatremia and to treat accordingly.
Patients who have only mild symptoms of
hyponatremia (eg, confusion) are unlikely to have
severe neurologic sequelae from their hyponatremia,
if treated conservatively. Only patients with severe
neurologic symptoms such as coma, seizure, or focal
neurologic signs warrant treatment with HTS.
Treatment Of Severe Hyponatremia
Optimal treatment strategies with HTS for severe
hyponatremia are based on expert consensus and
are not well defined. (See Table 2 on page 8.) There
www.ebmedicine.net • Volume 3, Number 1
is no study that compares the efficacy and safety of
different treatment regimens. Therefore, patients
treated with HTS should have frequent neurologic
checks and measurement of serum sodium levels
every 1 to 2 hours.
The initial goal of treating hyponatremic patients with severe neurological symptoms is to
reverse the cerebral edema with 3% HTS. Perhaps
the easiest method of administration was developed
by the Second International Exercise-Associated
Figure 1. The Danger Of Overly Aggressively Correction Of Hyponatremia
Normal state. The extracellular fluid is in osmotic equilibrium with the intracellular
fluid, including that of the brain cells, with no net movement of water across the
plasma membrane.
Osmoles
water
Acute hyponatremia. If the extracellular fluid suddenly becomes hypotonic relative
to the intracellular fluid, water is drawn into the cells by osmosis, potentially causing cerebral edema.
water
water
water
Adaptation. Over the ensuing few days, brain cells pump out osmoles, first potassium and sodium salts and then organic osmoles, establishing a new osmotic
equilibrium across the plasma membrane and reducing the edema as water
moves out of the cells.
Osmoles
water
water
water
water
Overly aggressive therapy with hypertonic saline after adaptation has occurred
raises the serum sodium level to the point that the extracellular fluid is more concentrated than the intracellular fluid, drawing more water out of the brain cells and
causing the syndrome of osmotic demyelination.
water
water
www.ebmedicine.net • Volume 3, Number 1
Reprinted from: Vaidya C, Ho W, Freda BJ. Management of hyponatremia: Providing treatment and avoiding harm. Cleve Clin J Med 2011; 77:715-726. Reprinted
with permission. Copyright © 2011 Cleveland Clinic Foundation. All rights
reserved.
7
EMCC © 2013
Consensus Development conference.53 They recommend that any athlete with severe hyponatremia
and encephalopathy be treated immediately with
a bolus infusion of 100 mL of 3% NaCl to acutely
reduce brain edema. Two additional 100-mL boluses
of 3% NaCl should be repeated at 10-minute intervals if there is no clinical improvement. This would
translate to 6 mL/kg of 3% NaCl for a 50-kg woman,
which is enough to raise the serum sodium concentration by 5 to 6 mEq/L. While this guideline was
developed to treat those with exercise-associated
hyponatremia, it is probably a reasonable regimen to
extrapolate to all patients with severe hyponatremia,
regardless of etiology or duration.
After the initial treatment with HTS to address
the serious signs and symptoms of hyponatremia,
the subsequent rate of correction should be closely
monitored. The goal is not to correct the patient’s
serum sodium to “normal” values. For patients with
either chronic hyponatremia or hyponatremia of
an unknown duration, an expert panel suggested a
correction of no more than 10 to 12 mEq/L during
the first 24 hours of treatment.51 They also suggested
that, due to a sometimes unexpected “autocorrection” during the course of treatment, it may be best
to aim for undercorrection (more near the rate of 8
mEq/L/d). It is important to emphasize that these
recommendations were derived from relatively
small numbers of patients and that they only give an
estimate of reasonable correction rates.
Going Deeper: How Hypertonic Saline Works
Intracranial Pressure Effects
As mentioned previously, the primary goals of
managing a patient with TBI are to reduce cerebral edema, decrease ICP, and improve CPP. While
mannitol has historically been considered the drug
of choice for acute intracranial hypertension, it has
some drawbacks.54 First, it is believed that the blood-
Table 2. Recommended Steps For The
Treatment Of Severe Hyponatremia53
1.
2.
3.
4.
5.
6.
Determine whether the patient’s corrected serum sodium value
explains his clinical condition.
Assess for severe neurologic signs suggesting cerebral edema
(seizures, coma, focal neurologic signs).
Assess the patient’s duration of hyponatremia. Patients with
chronic hyponatremia (duration > 48 h) are at a higher risk of
developing ODS from overrapid correction.
Administer an IV bolus of 100 mL of 3% HTS. Repeat twice over
10-minute intervals, if needed.
Monitor serum sodium every 1-2 hours.
The serum sodium should not be raised more than 10-12
mEq/L/d.
Abbreviations: HTS, hypertonic saline; IV, intravenous; ODS, osmotic
demyelination syndrome.
EMCC © 20138
brain barrier may be compromised in TBI, leading to
accumulation of mannitol in already edematous tissue, which ultimately causes an increase in cerebral
edema and ICP. Additionally, mannitol is an osmotic
diuretic and may cause hypotension, which worsens
secondary brain injury.
HTS has the theoretical potential to improve both
CPP and intracranial hypertension without the deleterious effects of mannitol. The primary effect by which
HTS reduces ICP is by setting up an osmotic gradient
across an intact blood-brain barrier and dehydrating brain tissue in the mostly uninjured portions.55 It
is more attractive than mannitol as a hyperosmotic
therapy, as it is less permeable across an intact bloodbrain barrier and has a higher osmotic gradient in the
vascular compartment.8,9 Because the osmotic effect
of HTS alone is transient, it is usually combined with
a colloid (hydroxyethyl starch or dextran). This may
prolong the clinical effect by 2 to 4 hours.56
Hemodynamic And Microcirculatory Effects
Isotonic crystalloid solutions currently predominate
over all other resuscitative fluids for the hypotensive
trauma patient. When NaCl or lactated Ringer’s
is given, it is rapidly redistributed throughout the
entire extracellular space with no preference for the
vascular space. Ultimately, only 10% to 20% of the
infused isotonic crystalloid remains in the circulation.57-59 This can necessitate large volumes of fluid
for resuscitation, potentially worsening hemorrhage
and neuronal injury. (See Figure 2.)
In contrast, HTS allows for resuscitation with
smaller volumes (4 mL/kg of 7.5% NaCl). The
osmotic effect is immediate, and it can increase the
intravascular volume by as much as 4 times the
infused volume within minutes of infusion.60 That
said, it is most likely an oversimplification to consider HTS as a potential treatment for TBI and shock
solely from its actions as an osmotic agent. Fortunately, there are many rheological effects by which it
may improve microcirculation, including decreasing
blood viscosity, endothelial cell edema, and capillary resistance via dehydration of erythrocytes.8-10
Hypertonicity also has a direct relaxant effect on the
vascular smooth muscle with resultant arteriolar
vasodilation.2 Last but not least, the optimization
of blood flow and CPP is supported by the effect of
HTS on increasing the MAP.
Immunologic Effects
One of the more intriguing aspects of HTS is its
potential to modulate the immune system in the
trauma patient. It is well known that dysfunctional
activation of the immune system after traumatic
injuries and other shock states can cause subsequent tissue and organ injury.61 Basic science studies have confirmed that HTS has marked effects on
the immune system.2 It has been shown to blunt
www.ebmedicine.net • Volume 3, Number 1
One obvious potential complication of HTS is
sequelae from unintended iatrogenic-induced hypernatremia (other than ODS). A retrospective analysis
of more than 600 neurointensive care unit patients
examined upper threshold values of hypernatremia.
Unless serum sodium values exceeded 160 mEq/L,
no worse outcomes were detected. This is well
beyond the value that would commonly be reached
after initial treatment in the ED.62
ODS is arguably the most-feared complication
from the administration of HTS. Fortunately, it is
rare and generally only associated with chronic
hyponatremic patients who undergo overrapid
correction. There is little evidence from the current
literature to support the fear of ODS from treating
patients with TBI or hemorrhagic shock with HTS.
However, since ODS is a devastating condition, caution should still be exercised when using HTS in a
patient who may have chronic hyponatremia (such
as an alcoholic patient or a patient with congestive
heart failure).
In head-injured patients whose blood-brain
barrier is disrupted, the potential exists for HTS
to permeate into the injured tissue, raising water
content, increasing ICP, and exacerbating brain
damage.11 The majority of studies do not report this
neutrophil activation, modify cytokine production,3
and augment T-cell function.4,5 In animal models, it
decreases hemorrhage-induced neutrophil activation
and is protective against acute lung injury.6,7 To date,
no clinical studies have been conducted that demonstrate a patient-oriented benefit from these immunomodulation properties.
Adverse Effects
As a resuscitative fluid, HTS is cheap, does not
transmit infection, and is unlikely to provoke an
anaphylactic reaction. It has a strong safety record
based on previous clinical trials and reported use.
However, it is worthy to note that the patients at the
highest risk of being harmed by HTS (such as those
with heart failure, pulmonary edema, and kidney
failure) were often excluded from these trials.
The largest randomized controlled trial of HTS
and TBI (which included 1331 patients) did not
find a statistically significant difference in the rate
of adverse events between the treatment groups,
although they did describe a not statistically significant trend toward a higher nosocomial infection rate
in the HTS groups. Importantly, they observed no
increase in progression of intracranial hemorrhage in
the hypertonic fluid groups.32
Figure 2. Distribution Of Crystalloid Solution Administration
A. Distribution of isotonic crystalloids (3000 mL isotonic solution)
Extracellular
Interstitial
Intracellular
IV isotonic crystalloids (isotonic NaCl solution, lactated Ringer’s
solution) diffuse throughout the extracellular space and do not
(normally) enter the cells. Therefore, the majority of the 3000 mL
of an IV isotonic NaCl solution will be distributed in the extracellular compartment, with three-quarters (2250 mL) entering the
interstitial space and one-quarter (750 mL) remaining in the
intravascular space. Although this intravascular volume gain is
not insignificant, the majority of infused fluid enters the interstitial
space, promoting edema.
Intravasculature
3000 mL
2250 mL
750 mL
B. Distribution of hypertonic crystalloids (250 mL of 7.5% NaCl)
Extracellular
Interstitial
H 20
Intracellular
Hypertonic crystalloids infused into the circulation actually draw
body water from the large reservoirs of the intracellular and
interstitial compartments into the vessels. This shift dramatically
increases blood volume by many times the actual volume infused.
Intravasculature
2000 mL
H 20
Abbreviations: H2O, water; IV, intravenous; NaCl, sodium chloride.
Adapted from: Johnson AL, Criddle LM. Pass the salt: indications for and implications of using hypertonic saline. Crit Care Nurse. 2004.24(5):36-44.
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9
EMCC © 2013
finding. These effects are more likely to be secondary
to changes in serum osmolality.63
Table 3 summarizes the adverse effects of HTS
as well as its benefits.
Tools And Techniques: Practical
Considerations For Hypertonic Saline
HTS for the trauma patient with TBI and/or hemorrhagic shock is most often infused as a single 250-mL
IV bolus of 7.5% NaCl solution with 60% dextran 70.
An alternative weight-based bolus of 4 mL/kg has
also been used.
The military has examined the intraosseous
route as an alternative method for infusing resuscitation fluids for the treatment of hemorrhagic shock
in animals. It appears to be as effective in restoring
MAP as the IV route,64-66 and no short- or long-term
major tissue damage was observed. Caution should
still be exercised, however, as extravasated hypertonic fluid has the potential to cause tissue necrosis.
This may have accounted for 1 study reporting tibial
necrosis 2 days after the infusion of HTS with dextran into dehydrated pigs.67
For the treatment of severe hyponatremia, 100
mL of 3% HTS saline should be given as an IV bolus.
This should raise the serum sodium concentration
by 2 to 3 mEq/L. Be careful, as the serum sodium
may autocorrect and rise faster than expected. Some
experts suggest a target increase of no more than 8 to
10 mEq/L/d.
Due to the high osmolarity of HTS, infusion
through a central line is preferred to minimize phlebitis.68 Most studies used a 7.5% HTS solution, which has
an osmolarity of 2567 mOsm/L. The usual maximum
recommended osmolarity infused via a peripheral IV
line is 900 mOsm/L. For this reason, when central access is not available, it is advisable to administer HTS
through a large-bore peripheral IV line.
Table 3. Proposed Benefits And Adverse
Effects Of Hypertonic Saline
Benefits
Adverse Effects
•
•
•
•
• Theoretical risk of ODS
• ‘Rebound’ increase in ICP
• Elevating MAP and worsening bleeding in patients with
uncontrolled hemorrhage
Inexpensive
Reduces ICP
Improves CPP
Improves hemodynamics
and microcirculation
• Immunomodulation
• Vasoregulation
• Small-volume resuscitation
Abbreviations: CPP, cerebral perfusion pressure; ICP, intracranial
pressure; MAP, mean arterial pressure; ODS, osmotic demyelination
syndrome.
EMCC © 201310
Clinical Course In The ED
Stabilization
After an osmotic agent has been administered to a
TBI patient with an asymmetric pupillary response,
dilated and unreactive pupils, motor posturing, or
rapid neurologic decline, the focus should be on
reducing ICP and optimizing CPP. This includes
head of bed elevation, supporting MAP > 90 mm
Hg, preventing hypoxia, and obtaining immediate
neurosurgical consultation.
For the trauma patient in shock who has stabilized after fluid resuscitation, further evaluation
(including ultrasound, plain films, and computed
tomography) should be used to pursue the cause for
the patient’s hypotension.
For the hyponatremic patient whose neurologic
symptoms have stabilized, you can reduce the risk
of overrapid correction by not administering additional infusions of HTS. Careful monitoring of the
serum sodium level should be performed every 2 to
3 hours.
Deterioration
The administration of an osmotic agent for severe
TBI is only a temporizing measure while further diagnostic procedures or interventions are performed.
If a patient continues to show signs of deterioration,
efforts to reduce ICP and optimize CPP should be
maximized. Immediate neurosurgical consultation
is essential, as refractory intracranial hypertension
may require urgent neurosurgical intervention.
For the trauma patient in refractory shock, resuscitation should continue with packed red blood
cells. For patients with penetrating trauma and
ongoing hemorrhage, an SBP of 80 to 90 mm Hg
may be a more optimal resuscitation endpoint until
definitive hemorrhage control can be achieved.69
Continue an aggressive search for both hemorrhagic causes (external bleeding, hemothorax, hemoperitoneum, pelvic fracture, long bone fracture)
and nonhemorrhagic causes (tension pneumothorax, pericardial tamponade, myocardial contusion,
spinal cord injury, coincident medical event such as
gastrointestinal bleeding). Focus on etiologies that
are immediately correctable in the ED (eg, tension
pneumothorax), and obtain immediate consultation
by a trauma surgeon.
For the hyponatremic patient whose neurologic
symptoms persist or worsen, an additional 100-mL
bolus of 3% HTS can be repeated 1 or 2 more times
at 10-minute intervals. This will usually be effective at terminating the seizures. If seizures continue,
standard anticonvulsant therapy may also be administered but should not distract the provider from
treating the primary cause.
www.ebmedicine.net • Volume 3, Number 1
This begs the question: Does the use of HTS
work against this new resuscitative strategy? As
discussed previously, HTS has been shown to increase MAP more than a similar volume of isotonic
crystalloid solution, and some animal studies of
uncontrolled hemorrhage have raised concern for increased bleeding after administration of HTS.71-75 In
the largest study to date evaluating HTS for trauma
patients in hemorrhagic shock, the HTS group had a
higher earlier mortality and lower admission hemoglobin,48 which might have been caused by the artificially high MAP hiding the fact that the patient has
organ hypoperfusion and delaying the recognition
of shock by the emergency physician (and thereby
delaying subsequent transfusion).
Special Circumstances
Pediatric Patients With Traumatic Brain
Injury
Like many areas of pediatric critical care, the majority of evidence for using HTS to treat severe TBI in
children is extrapolated from the adult literature.
There have been few rigorous prospective studies examining the effect of HTS for severe TBI in
children. Fisher et al performed a randomized
controlled crossover study of 18 children with severe
TBI and compared bolus dosing of 3% HTS with normal saline.20 They reported that HTS was associated
with a lower ICP and a reduced need for additional
interventions (thiopental and hyperventilation) to
control ICP. Simma et al prospectively randomized
35 consecutive pediatric patients with severe TBI to
receive either lactated Ringer’s solution or 1.7% HTS
for 72 hours.21 All patients subsequently received
ICP monitors, and their ICU courses were compared.
While there was no significant difference in survival rate, patients treated with HTS had a shorter
length of ICU stay and required fewer interventions
to maintain ICP control. These studies suggest that
HTS is promising for the treatment of severe TBI
in children, but the strength of their conclusions is
limited due to small sample sizes.
The pediatric section of the Society of Critical
Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies published
guidelines in 2012 for the treatment of the pediatric
patient with severe TBI.70 They cited 2 pediatric
studies20,21 as evidence for the use of HTS and adapted adult severe TBI guidelines. They recommended
that HTS be considered for the treatment of pediatric
TBI associated with elevated ICP (Level II evidence).
While they recognized that there was insufficient
evidence to recommend specific concentrations or
doses, they recommended bolus dosing between 6.5
and 10 mL/kg of 3% HTS.
Hypertonic Saline For Sepsis
Due to its various effects at the systemic, organ, and
microcirculatory levels, HTS appears to be a promising therapy in sepsis for improving tissue oxygenation and patient outcomes. To date, there are few
prospective human trials that have studied HTS as
a resuscitative fluid in sepsis. Those that have been
performed showed an improvement in physiologic
endpoints with HTS (increased cardiac output, decreased systemic vascular resistance, and increased
pulmonary capillary wedge pressure), but they did
not measure clinical outcomes.76-78
It is also theorized that, because of its immunomodulatory effects, HTS may help prevent the
development of multiple organ failure in the septic
patient. Thousands of patients with sepsis have
been entered into various studies where different
inflammatory mediators were blocked or modulated in the hope that HTS might alter outcome.
Unfortunately, none of these have proven successful, and this author believes that it is doubtful that
HTS will prove to have a beneficial patient effect
secondary to these properties.
Disposition
Controversies And Cutting Edge
Patients with a TBI requiring hyperosmolar therapy
will most likely require neurosurgical specialists
and transfer to either the ICU or the operating
room for urgent neurosurgical intervention. Transfer from community hospitals should be performed
in the most expeditious method available. (For
a review of critical care transport, see Volume 2,
Number 4 of EMCC: “Air Transport Of The Critically Ill Trauma Patient.”)
Trauma patients with hemorrhagic shock will
likely require a surgical intervention in the operating
room for definitive hemorrhage control. If a patient
initially presents at a community hospital, transfer
should begin as soon as the initial life threats are
addressed. Transfer should not be delayed for any
additional imaging.
Hypertonic Saline And Hypotensive
Resuscitation
In trauma patients, restoring intravascular volume
and blood pressure in an attempt to achieve normal
systemic pressure may cause further blood loss,
dilutional coagulopathy, and increased mortality. This has led to an increasing emphasis on the
concept of hypotensive resuscitation (ie, lowering
resuscitation endpoints to an SBP of 80 to 90 mm Hg
until definitive hemorrhage control can be achieved).
This strategy has been shown to improve mortality for patients with penetrating trauma.69 While
it is tempting to hope for a similar benefit in blunt
trauma patients, the current literature has not demonstrated this.
www.ebmedicine.net • Volume 3, Number 1
11
EMCC © 2013
Patients with severe hyponatremia requiring
HTS administration should be admitted to an ICU.
Summary
HTS has been shown to be safe and effective for
reducing ICP and improving hemodynamics for the
trauma patient in hemorrhagic shock. Currently, no
convincing data show any improvement in clinical
outcomes. HTS is an important therapy for patients
with severe hyponatremia with signs of cerebral
edema. A bolus of 100 mL of 3% saline is a reasonable start and may be repeated twice over 10-minute
intervals to abate neurologic symptoms. Correction
of a patient’s serum sodium < 10 to 12 mEq/L in
the first 24 hours is unlikely to precipitate ODS. The
theoretical benefits of HTS raise the possibility of its
use as a therapy for other critically ill patients; however, little data exist to make any recommendations.
Case Conclusions
You were worried about the motor vehicle accident patient’s worsening mental status and signs of herniation.
Based on the available evidence indicating that HTS
with dextran is as effective as mannitol to reduce ICP
(and the fact that it may help support this patient’s systemic pressure and CPP during helicopter transport if
his splenic laceration continues to bleed), you decided to
infuse 250 mL of 7.5% HTS with dextran. Fortunately,
his neurologic status did not deteriorate any further, and
he was quickly transferred to the nearest Level 1 trauma
center, where he underwent acute decompression for his
epidural hematoma and angiography embolization for
his splenic laceration.
Based on your second patient’s history and sodium
level, you quickly determined that she had suffered
exercise-associated hyponatremia. It was acute in onset,
and, because of her seizures, you determined that she most
likely had cerebral edema. After intubation, you administered 100 mL of 3% HTS. She had no continued seizures
and was transferred to the ICU. Her repeat serum sodium
1 hour later had increased by 4 mEq/L. After a short stay
in the ICU, she was discharged home with a normal neurologic status.
Must-Do Markers Of Quality Care
• Avoid secondary brain injury caused by hypotension and hypoxia.
• Reduce ICP and maximize CPP by using head
of bed elevation, supporting SBP > 90 mm Hg,
preventing hypoxia, and using normocapnic
ventilation.
• Administer osmotic agents to patients with signs
of impending herniation (asymmetric pupillary
response, dilated and unreactive pupils, motor
posturing, or rapid neurologic decline).
EMCC © 201312
• Recognize neurologic signs of cerebral edema
secondary to hyponatremia (seizures, encephalopathy, or focal neurologic signs).
• Do not try to correct the patient’s serum sodium
level to “normal” values.
• Avoid overcorrection of chronic hyponatremia
or undercorrection of acute symptomatic hyponatremia, as these can lead to serious neurologic injury.
• Do not increase a patient’s serum sodium by
more than 10 to 12 mEq/L/d, as this may precipitate ODS.
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in the study, will be included in bold type following
the ref­erence, where available. In addition, the most
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tonic solutes (sodium chloride or mannitol) in the treatment
of refractory posttraumatic intracranial hypertension: 2 mL/
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4. In order to reduce the risk of ODS in patients
with chronic hyponatremia, the recommendation is to limit correction to:
a. < 20 to 24 mEq/L in 24 hours
b. < 20 to 24 mEq/L in 48 hours
c. < 6 to 8 mEq/L in 24 hours
d. < 10 to 12 mEq/L in 24 hours
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5. Patients with severe hyponatremia for < 48
hours can present with seizures, encephalopathy, or focal neurologic signs and are:
a. Less prone to cerebral edema but more likely to develop ODS with rapid correction
b. Less prone to cerebral edema and less
likely to develop ODS with rapid correction
c. More prone to cerebral edema but less likely
to develop ODS with rapid correction
d. More prone to cerebral edema and more likely to develop ODS with rapid correction
6. Current recommendations are that any athlete
with severe hyponatremia and encephalopathy
be treated immediately with a bolus infusion
of:
a. 500 mL of 3% NaCl followed by 2 additional 100-mL boluses of 3% NaCl repeated at 10-minute intervals if there is no improvement.
b. 100 mL of 3% NaCl followed by 2 additional 100-mL boluses of 3% NaCl repeated at 10-minute intervals if there is no improvement.
c. 100 mL of 3% NaCl followed by 1 additional 100-mL bolus of 3% NaCl repeated after 10 minutes if there is no improvement
d. 100 mL of 1.5% NaCl followed by 2 additional 100-mL boluses of 1.5% NaCl repeated at 10-minute intervals if there is no improvement.
1. In regards to the evidence for the use of HTS in
patients with TBI:
a. The evidence is strongly in support of a dextran and HTS admixture over mannitol.
b. The evidence is strongly in support of mannitol over HTS solutions.
c. The evidence, as of yet, has not shown improved mortality outcomes with HTS.
d. The evidence has shown that HTS clearly worsens mortality.
2. With regard to the evidence for the use of HTS
in patients with TBI and concurrent hypotension:
a. HTS is recommended for all patients with TBI and concurrent hypotension.
b. HTS may be of use in some populations, such as combat casualty resuscitations.
c. HTS improves mortality in patients who do not receive blood transfusions in the first 24 hours.
d. HTS improves mortality in patients who require surgery.
3. ODS is characterized by:
a. Cellular injury after adaptation to acute hyponatremia when the neurons are hyposmolar and are subsequently exposed to excess sodium
b. Cellular injury after adaptation to acute hyponatremia when the neurons are hyperosmolar and are subsequently exposed to excess sodium
c. Initial cerebral edema that results from acute hyponatremia
d. Initial cerebral edema that results from acute hypernatremia
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