Clinical

DIMENSION

Management of Intracranial
Pressure: Part I
Pharmacologic Interventions
Tara L. Sacco, MS, RN, CCRN-K, AGCNS-BC, ACCNS-AG;
Samantha A. Delibert, PharmD, BCCCP

Dangerous, sustained elevation in intracranial pressure (ICP) is a risk for

any patient following severe brain injury. Intracranial pressure elevations
that do not respond to initial management are considered refractory to
treatment, or rICP. Patients are at significant risk of secondary brain
injury and permanent loss of function resulting from rICP. Both
nonpharmacologic and pharmacologic interventions are utilized to
intervene when a patient experiences either elevation in ICP or rICP. In
part 1 of this 2-part series, pharmacologic interventions are discussed.
Opioids, sedatives, osmotic diuretics, hypertonic saline solutions, and
barbiturates are drug classes that may be used in an attempt to
normalize ICP and prevent secondary injury. Nursing care of these
patients includes collaboration with an interprofessional team and is
directed toward patient and family comfort. The utilization of an
evidence-based guideline for the management of rICP is strongly
encouraged to improve patient outcomes.
Keywords: Intracranial pressure, Neurologic injury, Pharmacology
[DIMENS CRIT CARE NURS. 2018;37(3):120/129]

U.V. is a 31-year-old woman admitted to the neurologic
intensive care unit following a traumatic brain injury
(TBI) as the result of being struck by a car. U.V."s head
computed tomography scan revealed left-sided frontal-
parietal contusions, a subarachnoid hemorrhage, and
a basilar skull fracture. At the scene, U.V."s Glasgow Coma
Scale score was 3, and her left pupil was 7 mm and non-
reactive. She was intubated and brought to the trauma
center. On evaluation, she received mannitol 100 g once
prior to surgical intervention. She arrived to the intensive
care unit status post a left hemicraniectomy and intracra-
nial pressure (ICP) monitor placement. She is mechanically
ventilated, with her pain and sedation needs being treated
with propofol and fentanyl infusions. U.V."s opening ICP
was 45 mm Hg and decreased to 18 mm Hg postopera-
tively; however, on postinjury day 1, her ICP has been
sustained at greater than 25 mm Hg. Her Glasgow Coma
Scale score has ranged from a 3 to 8, and she has not
followed commands. Her ICP has been managed with
mannitol and 3% sodium chloride. However, her serum
sodium and osmolality levels have risen to the point where
she can no longer receive these mediations. A barbiturate
coma is being discussed.
It is apparent from this case study that patients with
neurologic injuries are at high risk of elevated ICP. In
severe cases, elevated ICP becomes refractory to treatment.

120 Dimensions of Critical Care Nursing Vol. 37 / No. 3 DOI: 10.1097/DCC.0000000000000293

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When this occurs, the patient requires complex management
by an interprofessional team utilizing both nonpharmacologic
and pharmacologic interventions. The prevention of second-
ary brain injury related to elevated and refractory ICP (rICP) is
paramount in the care of the neurocritical care patient. The
goal of this article is to present the pharmacologic interven-
tions available for the treatment of elevated ICP and rICP.
NEUROLOGIC INJURIES
Mass lesions, including brain tumors and abscesses,1-3 TBI
from blunt or penetrating mechanisms,1-7 and both ischemic
and hemorrhagic stroke can cause elevations in ICP.2,3,5,6
Further, inflammatory conditions typically related to in-
fections, such as meningitis or encephalitis, may cause
neurologic injury and raise ICP.1-3 Lastly, ICP elevation
from anoxia and hepatic encephalopathy are considered
metabolic inuries.1,3 Hydrocephalus, which may result from
any of the aforementioned conditions, also contributes to
ICP elevation.1-3 Mass lesions, TBI, stroke, and inflam-
matory and metabolic conditions can contribute to the
development of cerebral edema, furthering the sequelae
of ICP elevation.
Cerebral edema is swelling within the brain, thus
increasing the size of brain tissue. 2 There are generally
3 types of cerebral edema: vasogenic, cytotoxic, and
interstitial. Each type can occur simultaneously, in both
a localized or diffuse manner.3 Disruption in the blood-
brain barrier, often the result of vessel damage, increases
capillary permeability and leads to vasogenic cerebral
edema,2,8 where fluid accumulates in the extracellular
spaces within the brain. The most common causes of
vasogenic cerebral edema include TBI, surgical inter-
vention, mass lesions, and inflammatory mechanisms.2,3
When a patient develops cytotoxic cerebral edema, fluid
gathers in the intracellular space.2 Any cause of neuronal
hypoxia and resultant anaerobic respiration can lead to
cytotoxic cerebral edema.2,3,8 Alterations in cerebrospinal
fluid (CSF) hydrostatic pressures, related to hydrocephalus,
lead to interstitial cerebral edema. Regardless of the type
and cause, the processes resulting in cerebral edema occur
immediately following neurologic injury and continue for
up to and beyond 72 hours postinsult.3
Pathophysiology
Intracranial pressure is normally less than 15 mm Hg, with
an elevation considered anything sustained at greater than
20 to 25 mm Hg.1,9,10 There are 3 components within the
rigid skull: blood (arterial and venous), CSF, and brain
tissue. In order to maintain a normal ICP, these 3 compo-
nents must be in balance; however, neurologic insults can
result in an increase in 1 or more component.2,3,8-10 Under
normal circumstances, the increase in one component
will lead to a decrease in the others as the brain attempts
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Management of Intracranial Pressure
to compensate to maintain normal intracranial volume.
This concept is known as the Monro-Kellie doctrine.1,2,9,10
Compensatory mechanisms include displacement or
reabsorption of CSF, compression of the venous system,
and shunting of blood out of the venous sinuses.2,3,7 When
these compensatory mechanisms begin to fail, ICP rises,
ultimately compromising tissue perfusion.9,10
In order to appropriately perfuse the brain with oxygen
and glucose, 15% to 20% of the body"s cardiac output is
dedicated to cerebral blood flow (CBF). Cerebral blood
flow is measured indirectly by cerebral perfusion pressure
(CPP), calculated as mean arterial pressure minus ICP.9
To meet metabolic demands, the size of the cerebral vas-
cular bed is able to change. This function is referred to as
autoregulation.2,6,8 Vasodilation will increase CBF to meet
increased demands, whereas vasoconstriction decreases
CBF when demands are lessened. Vasodilation also allows
for the removal of wastes that result from cellular me-
tabolism.2 These compensatory mechanisms function well
in the uninjured brain; however, in the context of severe
neurologic injury, they may be compromised.6 As ICP
rises, CBF decreases, causing vasodilation to meet metabolic
demands. Unfortunately, this compensatory mechanism
increases arterial volume, which cannot be accommodated
within the rigid skull, and further elevation in ICP can
result.9 As this continues to occur, the brain becomes
ischemic, and autoregulation fails.2
A marker of how well the brain can accommodate ICP
elevation is referred to as compliance or the ‘‘Ichange
in pressure resulting from a change in volume.’’3(p213)
Because of compliance, the patient may be able to tolerate
increases in brain volume. Similar to the brain"s ability to
autoregulate, the extent of compliance is limited. When
these mechanisms are depleted, further elevation in ICP
occurs.3 The patient may exhibit a multitude of symptoms
related to ICP elevation, which can be found in Table 1.
Significant patient complications result from compensatory
mechanism failure.
Complications
Because health care providers are often unable to intervene
to prevent the primary brain injury, the focus of treatment
and management is to prevent secondary brain injury due
to cerebral edema, elevation in ICP, hypoperfusion, and
compensatory failure.9,11 Hypotension and hypertension,
hypoxia, hypercapnia, fever, hypoglycemia and hypergly-
cemia, hyponatremia, seizure, vasospasm, excessive release
of excitatory neurotransmitters, and ICP elevation are all
plausible causes of secondary brain injury.5,7,12,13 When
CBF is affected, the inflammatory response is activated,
leading to further metabolic derangements, ischemia, and
cellular death.4 Neuronal cells are forced into anaerobic
respiration as a result of hypoxia, and normal cellular
May/June 2018 121
 Management of Intracranial Pressure
TABLE 1 Symptoms of Elevated Intracranial
Pressure
Early Late
Headache Further change in LOC (obtunded)
Emesis Further decrease in GCS score
Change in LOC Pupillary dilation (ipsilateral or bilateral)
Decreased GCS score Compromised pupillary reaction
Irritability Hypertension
Pupillary changes Respiratory compromise
Cranial nerve dysfunction Cushing triad (ominous)
Visual disturbance Bradycardia
Seizure Systolic hypertension/wide pulse pressure
Irregular respirations
Abbreviations: GCS, Glasgow Coma Scale; LOC, level of consciousness.
Sources: Inoue,1 2010; Marcoux,3 2005.
functions are no longer effective. Cell membranes break
down, resulting in alterations in intracellular and extracellu-
lar sodium, potassium, and calcium levels. The consequence
is furthered cerebral edema and thus worsening of ICP.2
Uncontrolled elevation in ICP will cause cerebral
hypoperfusion and hypoxia, leading to further tissue
ischemia8,9 and worsening secondary injury. In severe
cases, this results in cerebral herniation and brain death.1,9
When a patient"s ICP is sustained at greater than 25 mm
Hg despite initial interventions, it is considered rICP.9,12,14
The risk of death has been reported to be 4 to 5 times
higher in those who experience rICP compared with those
who do not.14 Efforts to decrease ICP and the severity of
secondary neurologic injury are critical to the care of this
subset of patients.3,5,13
NEUROLOGIC MONITORING
Not everyone who experiences a brain injury will require
invasive ICP monitoring. The Brain Trauma Foundation
recommends that ICP and CPP monitoring be imple-
mented in patients following severe TBI to reduce inpatient
mortality.15 Devices utilized to monitor ICP include
subarachnoid, subdural, epidural, and intraparenchymal
bolts or external ventricular drains (ventriculostomies).
These devices include a fiber-optic catheter and external
transducer that transmits the patient"s ICP to a monitoring
system. Intracranial pressure monitoring via a ventriculostomy
has the additional ability to drain CSF and blood, which
in turn decreases ICP.1,6,8,10,14 Once the appropriate ICP
monitor is placed, both ICP and CPP can be monitored
continuously for abnormalities. When the ICP is elevated
at greater than 20 to 25 mm Hg, CPP should be maintained
between 60 and 70 mm Hg.10,12,15 Cerebral perfusion
122 Dimensions of Critical Care Nursing Vol. 37 / No. 3
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pressures of less than 50 mm Hg indicate decreased per-
fusion to the brain with potential ischemia and tissue death,2,8
whereas CPP of greater than 70 mm Hg may be associated
with poor outcome and respiratory compromise.15 Both
ICP and CPP values should be utilized to direct therapy to
ensure adequate cerebral perfusion and decreased second-
ary brain injury risk.4,8 To do so, multiple pharmacologic
interventions for ICP and rICP are available.
ELEVATED ICP: INITIAL PHARMACOLOGIC
MANAGEMENT
Initial pharmacologic management for ICP elevation
includes interventions for pain and agitation and the use
of osmotic diuretics and hypertonic saline (HTS). Each
therapy can effectively reduce ICP to normal ranges but is
not without risk. Knowledge of each intervention, includ-
ing assessment parameters, mechanism of action, ap-
propriate dosing, expected pharmacokinetics, and adverse
effects, is required for appropriate patient management.
Medication, mechanism of action, dosing/administration,
major adverse effects, and nursing considerations are found
in Table 2.
Analgesia and Sedation
Any noxious stimulus has the potential to increase ICP,1,2,10,15
and therefore, treatment aimed at their reduction is
warranted.7,14 Medications used to manage pain and
agitation in this population include intravenous opioids
(fentanyl, remifentanil) and intravenous anxiolytics (ben-
zodiazepines, propofol).
OPIOIDS
Fentanyl and remifentanil are the 2 most commonly used
continuous intravenous drips for the treatment of pain and
thus ICP. These medications act on opioid receptors in the
central nervous system and the gastrointestinal tract,13
producing pain relief.9 The onset of action for fentanyl
is immediate with a duration of action of 30 minutes to
1 hour and a half-life between 2 and 4 hours.16 Although
it has been reported that opioids can increase CBF and
potentially ICP,13 Colton et al17 reported that ICP decreased
in trauma patients after 2 hours with dose escalations of
continuous fentanyl drips. The fentanyl dose reported in
this study ranged between 25 to 550 2g/h,17 although
typical doses do not exceed 300 2g/h. No dose adjustment
is required for renal and hepatic impairment; however,
elderly patients may be more sensitive to the effects of
fentanyl.16 Remifentanil"s onset of action is 1 to 3 minutes,
with duration of 3 to 10 minutes and a half-life of 10 to
20 minutes, allowing for this drug to be rapidly titrated.
Dosages of remifentanil are recommended between 0.5
to 15 2g/kg per hour. As with fentanyl, there are no dose
adjustments required for renal or hepatic impairment.
 TABLE 2 Medication Information
Medication Mechanism of Action Dosing/Administration Adverse Effects Nursing Considerations

Opioids Bind to opioid receptors, providing pain Fentanyl: IV continuous drip 25-550 2g/h; Both: CNS depression Monitor: vital signs, ICP
Fentanyl relief and respiratory depression typically no greater than 300 2g/h Respiratory depression Neurologic exam
Remifentanil Remifentanil: IV continuous drip Hypotension Pain scores
0.5-15 2g/kg per hour Constipation Mechanical ventilation
Remifentanil: bradycardia Bowel regimen
Sedatives Benzodiazepines: bind to GABA receptors Benzodiazepines: midazolam IV loading dose Benzodiazepines: CNS depression Monitor: vital signs, ICP
Benzodiazepines producing anxiolysis, sedation, amnesia; 0.5-4 mg every 5-15 min until adequate Respiratory depression Neurologic exam
Midazolam also an antiepileptic sedation reached Delirium Sedation scores
Midazolam: metabolite accumulation Mechanical ventilation
Midazolam IV continuous infusion
Hypotension
0.02-0.1 mg/kg per hour

Nonbenzodiazepine Propofol: binds to GABA receptors; sedative Propofol: begin IV continuous drip at Propofol: propofol-related Propofol: monitor vital signs, ICP
Propofol hypnotic effects with CNS depression 5 2g/kg per minute infusion syndrome Neurologic exam
Rapidly titrate by 5-10 2g/kg per minute until Hypotension Pain scores
adequate sedation reached Bradycardia Labs: triglycerides, lactate, CK, myoglobin
Maintenance continuous drip dose Respiratory depression Mechanical ventilation
5-50 2g/kg per minute Change IV tubing every 12 h

Osmotic diuretics Osmotic effects: decreases water in brain IV bolus dosing 0.25-1 g/kg every 4-6 h Hypotension Monitor: vital signs, ICP
Mannitol tissue, intracellular, and interstitial space AKI Neurologic exam
to decrease ICP Hyperkalemia I & O electrolytes every 4-6 h
Rheologic effects: plasma expansion, decreased Rebound ICP elevation Serum osmolarity every 4-6 h;
hematocrit, increased RBC deformability, goal e320 mOsm/L

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decreased blood viscosity to increase CBF Administer through an inline filter
Diuretic effects: Changes the osmotic gradient
in the kidney to decrease water reabsorption,
leading to excretion in urine

May/June 2018
(continues)
Management of Intracranial Pressure

123
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TABLE 2 Medication Information, Continued
Medication Mechanism of Action Dosing/Administration Adverse Effects Nursing Considerations

Dimensions of Critical Care Nursing

Hypertonic saline Change the osmotic gradient by increasing sodium G23.4%: Bolus infusions volume varies by AKI Monitor: vital signs, ICP
Concentrations: and osmolarity concentration, give over 30 min or more
Management of Intracranial Pressure

Pulmonary edema Neurologic exam

G23.4% Decreases water in brain tissue, intracellular, and 23.4%: 30-60 mL over 20 min
Hypernatremia I & O electrolytes every 4-6 h; sodium goal
23.4% interstitial space to decrease ICP Hypokalemia 155-160 mEq/L
Rheologic effects: plasma expansion and RBC Acidosis Serum osmolarity every 4-6 h, goal

Vol. 37 / No. 3
deformability to increase CBF Phlebitis/necrosis 350-360 mOsm/L
Rebound ICP Central line preferred
23.4% Concentration may be administered only
by a provider, check nursing practice act

Barbiturates Sedative/hypnotic that decreases metabolic IV loading dose 10 mg/kg over 1 h, Hypotension Monitor: vital signs, ICP
Pentobarbital demand, CBF, and ICP followed by 5 mg/kg per hour  3 h, Decreased peristalsis EEG for burst suppression
followed by an IV continuous drip CNS depression Pentobarbital levels: 3%-4% target
1-4 mg/kg per hour
Respiratory depression Mechanical ventilation
Do not infuse faster than 50 mg/min Will be unable to perform neurologic and
pupillary examinations

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Abbreviations: AKI, acute kidney injury; CBF, cerebral blood flow; CK, creatinine kinase; CNS, central nervous system; GABA, +-aminobutyric acid; I & O, intake and output; ICP, intracranial pressure; IV, intravenous; RBC, red blood cell.

However, doses for elderly patients should be decreased
by 50% compared with younger adults.18
The precautions and adverse effects for fentanyl and
remifentanil are similar. Both can cause central nervous
system and respiratory depression, gastrointestinal effects
(nausea, vomiting, constipation), and hypotension.16,18
Additional adverse effects of remifentanil include bradycardia
and heart block,18 whereas prolonged use of fentanyl can
lead to drug dependence.16
There are many nursing considerations related to the
administration of opioid analgesics. Patients with ICP
elevations and those receiving continuous opioid drips
require appropriate airway management with mechanical
ventilation. Continuous monitoring of vital signs, includ-
ing ICP and CPP, is warranted. By nature of their disease
states, these patients already display central nervous system
dysfunction, and therefore astute neurologic assessments
are required. Further, a bowel regimen should be in place to
prevent gastrointestinal complications. The 2013 Society of
Critical Care Medicine (SCCM) Pain, Agitation, and
Delirium guideline outlines specific recommendations for
pain management in critically ill patients. According to the
SCCM, pain should be routinely monitored with a valid and
reliable tool.19 In addition, an analgesia-first methodology
should be incorporated, meaning that pain is treated prior to
agitation, as this may be a symptom of underlying pain.20
Communication with the patient and family is an important
component of care and can reduce noxious stimuli and stress.10
BENZODIAZEPINES AND PROPOFOL
Similarly to analgesia, sedation decreases ICP and the
stress response triggered after brain injury.9 Intracranial
metabolism can also be decreased using sedative agents.
Benzodiazepines are commonly used for sedation in this
patient population,2 with midazolam being the most
commonly used benzodiazepine for continuous sedation.
This medication is protein bound and lipid soluble, allowing
it to cross the blood-brain barrier.13,21 Midazolam binds
to +-aminobutyric acid (GABA) receptor sites, leading to
anxiolysis at lower doses and sedation, amnesia, and anti-
epileptic properties at higher doses.21 Midazolam doses
are recommended to be an initial bolus dose of 0.5 to 4 mg,
repeated every 5 to 15 minutes until the patient is adequately
sedated. An infusion is then started at a rate of 0.02 to
0.1 mg/kg per hour.22 Further, this medication can be rapidly
titrated because of a short onset of action (2-5 minutes)
and duration of action (2-4 hours),21 allowing for expe-
dited patient comfort and neurologic examination.2
Propofol is an alternative option to benzodiazepine
use for patients with intracranial injury. This medication
is a sedative/hypnotic that also crosses the blood-brain
barrier with a rapid onset of action.2 It is thought that
propofol works on GABA receptors, causing central nervous
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Management of Intracranial Pressure
system depression,21,23 amnesia, anxiolysis, muscle relax-
ation, and antiepileptic effects.21 Typical propofol dosing
regimens begin at 5 2g/kg per minute, with rapid titration
of 5 to 10 2g/kg per minute until the patient is adequately
sedated. Maintenance doses of 5 to 50 2g/kg per minute
are recommended.23 Similar to the effects of opioids, Colton
et al17 reported that dose escalations of propofol led to
ICP decreases for 2 hours following administration. An
added benefit of propofol use is a decrease in vascular
resistance, which can be neuroprotective13 and decreases
intracranial metabolism.10 This medication has a very rapid
onset and short duration of action, 9 to 51 seconds and 3 to
10 minutes respectively,23 allowing for rapid titration and
frequent neurologic evaluation.
There are major adverse effects to both benzodiaze-
pine and propofol use. The metabolites of benzodiazepines
can accumulate, leading to ongoing sedation and impeded
neurologic examination.2 Metabolite accumulation oc-
curs more commonly following long infusion duration
and in patients with renal or hepatic impairment; drug
tolerance may be a problem.21 High doses of midazolam
can also lead to hypotension and subsequent reduction in
CPP.13 Respiratory depression and central nervous
system depression are both common with benzodiazepine
use.21 Lastly, benzodiazepine use has been linked to the
development of delirium in critical care patients.20,21
The most concerning adverse effect of propofol is
propofol-related infusion syndrome (PRIS), which oc-
curs when the medication is infused at high doses and is
manifested by metabolic acidosis, rhabdomyolysis, dys-
rhythmias, and cardiac arrest.13,23 Patients at higher risk
of PRIS are those with sepsis, respiratory compromise,
and severe brain injury.23 To facilitate early detection of
PRIS, triglyceride, lactate, creatinine kinase, and myoglobin
levels should be monitored.21 Hypotension, bradycardia,
and respiratory depression are other common adverse
effects associated with propofol use. Another disadvantage
of propofol infusion is that vials and intravenous tubing
need to be discarded after 12 hours,21,23 because of the
risk of bacterial contamination.21
The nursing considerations related to the administra-
tion of sedatives are similar to those related to opioids and
include reduction of noxious stimuli, airway management,
continuous vital sign monitoring, and close neurologic
assessment. According to the Pain, Agitation, and Delir-
ium guideline, patient agitation levels should be monitored
using a valid and reliable tool. A nonbenzodiazepine sedative,
such as propofol, is preferred over benzodiazepines because
of the risk of delirium.19 Although the SCCM recommends
light sedation,19 in patients with elevated ICP and those
likely to develop rICP, deeper sedation may be necessary.
Ongoing communication with the patient and family is
supported to reduce noxious stimuli and stress.10
May/June 2018 125
 Management of Intracranial Pressure
Osmotic Diuretics
Osmotic diuretics, namely, mannitol, have been widely
used for the management of elevated ICP. This medica-
tion works by pulling water out of the brain tissue and
the intracellular and interstitial spaces. The medication
crosses the blood-brain barrier, enters the vasculature, and
is removed from the cranial vault, decreasing ICP.8,12 As
fluid enters the vasculature, plasma expands. Subsequently,
rheologic effects occur: hematocrit and blood viscosity
decrease, and red blood cells become more deformable.
Each of these effects increases CBF and oxygenation.2,3,7,8,15,24
The diuretic effects of mannitol occur in the kidney; an
osmotic gradient develops, decreasing water reabsorption
and leading to water excretion in urine.8,24 This diuretic
effect may continue for hours after the mannitol dose.7 The
onset of action of mannitol is 15 to 20 minutes with duration
of 1 to 5 hours12; however, reduction in ICP may occur for
1.5 to 6 hours.24 Mannitol should be administered as an
intravenous bolus, through an in-line filter; recommended
doses are between 0.25 and 1 g/kg8 every 4 to 6 hours.3
Related to the osmotic and diuretic effects of mannitol;
hypotension, acute kidney injury (AKI), hyperkalemia,
and rebound elevation in ICP are noted to be adverse
effects. The mechanism behind rebound elevation in ICP is
unclear,12 although this may occur when the blood-brain
barrier has been compromised because of neurologic injury,
changing the normal osmotic gradient, and allowing for
mannitol accumulation within the brain.8,12,13 The other
potential cause is related to the diuretic effects of mannitol,
which may lead to hypovolemia,12 intravascular dehydra-
tion, hypotension, and a reduction in CPP.4 Because of
adverse renal effects, mannitol is contraindicated in those
with preexisting renal dysfunction24; use of mannitol for
ICP management in this population is cautioned and a
risk-versus-benefit discussion is warranted.
Nursing considerations related to mannitol administra-
tion include monitoring intake and output, electrolytes and
serum osmolarity and osmolar gap, and hemodynamics.12,25
Strict monitoring of intake and output is important, with
euvolemia being the target when a patient requires mannitol
for ICP reduction.2 To avoid hypovolemia, fluid replace-
ment may be necessary.8 Alterations in potassium, sodium,
and chloride can occur, and therefore blood chemistries
must be monitored frequently. Serum osmolarity and os-
molar gap must also be monitored closely. Serum osmolarity
is determined by the concentrations of solutes in serum,
whereas osmolar gap is the difference between measured and
calculated osmolarity.26 Mannitol doses should be withheld
if the patient"s osmolarity reaches 320 mOsm/L or higher
or an osmolar gap greater than 20 in order to prevent
AKI.3,8,12,24,25 Laboratory monitoring is recommended
every 4 to 6 hours.2 Ongoing monitoring of hemodynamics
is essential, as hypovolemia can lead to hypotension.10
126 Dimensions of Critical Care Nursing Vol. 37 / No. 3
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Hypertonic Saline
Hypertonic saline is used to manage both elevated ICP and
rICP. Also used for its osmotic effects, HTS increases serum
sodium levels and serum osmolarity, which pulls water
from the brain tissue and intercellular and interstitial spaces
across the blood-brain barrier.7,8,11-13,27 Hypertonic saline
administration also causes a rheologic effect.8,15,27 An
additional benefit of HTS is an increase in intravascular
volume and cardiac function.3,8,11,27 Although changes in
osmolarity can cause diuresis; the mechanism is much
different than that of mannitol. Hypertonic saline stimulates
atrial natriuretic peptide release, leading to both diuresis
and natriuresis.8 Concentrations vary from 2% to 23.4%
saline8,11,12; the higher the concentration, the greater the
osmotic effect.8 The lower concentrations of HTS are more
frequently given by intravenous bolus for ICP elevation.11
Hypertonic saline administration has caused renal
failure, pulmonary edema, hypernatremia, hypokalemia,
acidosis, phlebitis/tissue necrosis, and rebound ICP eleva-
tion.12 Similarly to mannitol, HTS increases serum osmo-
larity, which can lead to AKI. When HTS is administered,
hypokalemia and acidosis transiently occur, often lasting
1 hour following administration. As fluid moves from the
brain and into the intravascular space, pulmonary edema
may result.12 Patients with underlying cardiac or pulmonary
conditions are at higher risk of experiencing pulmonary
edema with HTS administration.12 Elevation of sodium and
subsequently chloride may result in hyperchloremic acidosis
following administration.8 The risk of phlebitis and tissue
necrosis is higher with HTS than with isotonic solutions;
historically, this medication has been administered via
central line.8,11,12,28 However, a recent retrospective cohort
study indicated that administration of 3% HTS via
peripheral intravenous line can be done safely, and a central
line may not be required at rates up to 75 mL/h.28 Lastly,
rebound ICP elevation can occur when serum sodium
levels return to baseline12 or if an accumulation of sodium
in extracellular spaces alters the osmotic gradient.8 If the
patient experiences a rebound ICP elevation, repeating a
dose of HTS may be necessary.12
Monitoring intake and output, serum osmolarity, blood
chemistries, and vital signs is essential when administering
HTS. As with mannitol, the goal is to maintain euvolemia.3
In order to prevent AKI, the maximum recommended serum
osmolarity level for HTS is 350 to 360 mOsm/L. Hypertonic
saline administration may also cause hypernatremia; the
maximum recommended serum sodium level in this patient
population is 155 to 160 mEq/L.12 Vital signs, including ICP
and CPP, should be monitored continuously.
Patient Evaluation
The patient"s physiologic parameters will indicate the ef-
fectiveness of initial interventions implemented to decrease

ICP. Ideally, patient response will include a decrease in ICP,
maintenance or increase in CPP, and hemodynamic stability.
Further, the patient should be maintained euvolemic, with
laboratory values within normal limits or within the
parameters of treatment, and free of pain and agitation. In
the event that the patient"s ICP remains elevated despite initial
interventions or meets the criteria described in Table 3,
management of rICP begins.
ELEVATED ICP: REFRACTORY
PHARMACOLOGIC MANAGEMENT
Hypertonic Saline
Hypertonic saline in concentrations of 23.4% is used in
the management of rICP and impending cerebral hernia-
tion. This concentration is delivered in bolus doses of 30
to 60 mL30,31 and is administered over 20 minutes,30 as
compared with other concentrations of HTS, which may
be administered over 30 minutes to multiple hours11,32;
23.4% saline is administered by a provider because of the
significant risks of rapid administration30 and must be
given via central line.11,32 Institutional policy should guide
provider administration of 23.4% saline, and providers
may be considered attending physicians, fellows, or ad-
vanced practice providers. In some cases, the administration
of 23.4% saline has been noted to reverse transtentorial
herniation.30 The successful reduction in ICP and impact
on herniation is related to the same mechanisms of HTS
described previously: changes in the osmotic gradient pulling
fluid from the brain tissue.
Because this concentration is given by a rapid intra-
venous bolus, there is a risk that sodium levels will rise too
quickly, resulting in central pontine myelinolysis.3,8,12,32
This syndrome most frequently occurs if underlying
hyponatremia is corrected too rapidly8 or as a result of
precipitous changes in serum osmolarity.3 When this occurs,
the nerves within the pons demyelinate,8,12 resulting
in lethargy,8 quadriplegia,8,12 and long-term ventilator
dependence.8 Fortunately, central pontine myelinolysis
has rarely been reported after the administration of HTS
for the management of elevated ICP.30 Administration of
TABLE 3 Refractory Intracranial Pressure
(ICP) Criteria
ICP Sustained at 925 mm Hg Despite Initial Interventions or
Closed Skull Open Skull
ICP 925 mm Hg for 30 min ICP 915 mm Hg for 15 min
ICP 930 mm Hg for 15 min ICP 920 mm Hg for 10 min
ICP 940 mm Hg for 1 min ICP 930 mm Hg for 1 min
Sources: Bader et al, 2005; Censullo and Sebastian,14 2003; Eisenberg et al,29 1998.
9
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Management of Intracranial Pressure
23.4% saline may also cause immediate, but transient,
hypotension and decreased hemoglobin levels.30 Decreased
systemic vascular resistance or a vagal effect likely accounts
for the drop in blood pressure. Increased blood pressure
and cardiac contractility often follow this adverse effect.33
The changes in serum osmolarity following adminis-
tration are likely to disrupt red blood cell membranes,
resulting in decreased serum hemoglobin levels.30 Nursing
care and monitoring following administration of
23.4% saline are similar to those described for lower
saline concentrations.
Barbiturates
A barbiturate coma may be induced for the management
of rICP. Working in the reticular formation, barbiturates
are sedative/hypnotics and inhibit nerve impulses from
reaching the cortex,2 reducing cerebral metabolic demand
and CBF.2,9,13,34 When CBF decreases, ICP also decreases.2,34
The most commonly used barbiturate is pentobarbital,
with an onset of action within 5 minutes and duration of
15 to 45 minutes.34 Administration includes a loading
dose followed by a continuous infusion.12 The typical dosing
regimen is 10 mg/kg over 1 hour followed by 5 mg/kg per
hour for 3 hours, then initiating a continuous drip at 1 to
4 mg/kg per hour.14,34 Doses should not be administered
faster than 50 mg/min.34 The medication is then rebolused
and titrated based on ICP and physiologic parameters.
Adverse effects of pentobarbital include hypotension,
myocardial depression, vasodilation,9,12 decreased peri-
stalsis, and respiratory effects.12 Hypotension may result
in reduction of CPP; vasopressors may be indicated to
counter this effect.12,14,34 Barbiturates are respiratory
depressants. As such, induction of a barbiturate coma
requires the patient to be mechanically ventilated.14
Nursing care for the patient in a barbiturate coma
includes monitoring vital signs and electroencephalogram
(EEG) waveform.9 Pentobarbital levels may be monitored,9
with the appropriate laboratory capabilities. Blood pres-
sure, heart rate, ICP, and CPP should be monitored con-
tinuously. Invasive or minimally invasive hemodynamic
monitoring may be considered. Burst suppression (Figure),
as noted on the EEG waveform, indicates that the dose of
barbiturate is effective.9 Pentobarbital doses should be
titrated based on both EEG waveform and ICP; it may be
reasonable to titrate to pentobarbital levels.9 Burst sup-
pression and serum levels do not always correlate,12 and
therefore serum levels may not be a reasonable parameter
for titration. It is important to note that inducing a barbi-
turate coma will result in the inability to perform neuro-
logic assessments as the patient will be unresponsive and
unable to move. Pupillary dilation may also occur because
of the barbiturate infusion; thus, pupil size and reactivity
cannot be considered a reliable assessment tool.7,12 Because
May/June 2018 127
 Management of Intracranial Pressure
Figure. Electroencephalogram (EEG) with demonstration of burst suppression. Electroencephalogram demonstrates barbiturate-induced burst
suppression pattern. The 27-second EEG epoch demonstrates 2 periods of bursts separated by a 10-second period of cerebral inactivity.
of a long half-life elimination and accumulation of the
medication, once a pentobarbital coma is stopped, it can
take days for the medication to be completely removed
from the patient"s system.14
Patient Evaluation
Ideally, when these interventions are implemented, the
patient"s physiologic parameters will improve. Once a
barbiturate coma has been induced, if the patient"s ICP is
sustained at less than 20 mm Hg for at least 48 hours,
and if the interprofessional team determines it is appro-
priate, pentobarbital may be weaned.14 The half-life of
pentobarbital can range from 15 to 50 hours14,34; thus,
the weaning process is slow. The risk during this time is
that the patient may exhibit rebound ICP or seizure activity.
In the event this occurs, the coma may be reinduced.14
These measures are intended to be lifesaving immediately
after the injury. Patient functional outcomes will vary on
a case-by-case basis, and unfortunately ongoing neurologic
deficits and patient death are still possibilities, despite
aggressive rICP management.
CONCLUSION
The management of rICP is complex. It is likely that the
most critical and unstable patients with brain injuries will
128 Dimensions of Critical Care Nursing Vol. 37 / No. 3
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
require several, if not all, of the interventions described
previously. In addition to the pharmacologic management
described, each patient requires astute nursing care. Patient
care activities should be clustered to decrease stimuli.14
Many patients will require surgical intervention, ventilator
support, and other nonpharmacologic therapies, which
will be discussed in part 2 of this series. Elevated ICP may
lead to very subtle changes that the bedside nurse should
be equipped to recognize and address with the interprofes-
sional team.1 Regardless of the type of interventions
performed, the goals of care are to maintain oxygenation
and perfusion to the injured brain.8 Experiencing a brain
injury is a life-altering event for both the patient and the
family. Nursing care directed to the patient"s condition and
well-being and that to the family are important consid-
erations.7 Use of an evidence-based protocol for the
management of rICP is strongly recommended to provide
structure to the complex management of these critically
ill patients.
Acknowledgments
The authors thank Dr Olga Selioutski, DO, assistant pro-
fessor of neurology and associate director, Critical Care
Neurophysiology Monitoring, Strong Epilepsy Center,
University of Rochester Medical Center, New York.

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ABOUT THE AUTHORS
Tara L. Sacco, MS, RN, CCRN-K, AGCNS-BC, ACCNS-AG, is visiting
assistant professor, Wegmans School of Nursing, St John Fisher
College, Rochester, New York; clinical nurse specialist, Adult Critical
Care Nursing, University of Rochester Medical Center, New York; and
PhD student, College of Nursing, Villanova University, Pennsylvania/
Jonas Scholar Cohort 2016Y2018. Her research interests include quality
improvement, critical care nursing, and nursing workforce support,
specifically regarding compassion satisfaction and compassion fatigue.
She is a member of the American Association of Critical-Care Nurses,
Sigma Theta Tau International, and the Society of Trauma Nurses.
Samantha A. Delibert, PharmD, BCCCP, is neuromedicine ICU clinical
pharmacy specialist, University of Rochester Medical Center, New York.
She is a memeber of the Neurocritical Care Society, The Society of
Critical Care Medicine, and the American College of Clinical Pharmacy.
The authors have disclosed that they have no significant relationship with, or
financial interest in, any commercial companies pertaining to this article.
Address correspondence and reprint requests to: Tara L. Sacco, MS,
RN, CCRN-K, AGCNS-BC, ACCNS-AG, Wegmans School of Nursing,
St John Fisher College, 3690 East Ave, Rochester, NY14620 (tsacco@sjfc.edu).
Copyright B 2018 Wolters Kluwer Health, Inc. All rights reserved.
May/June 2018 129