82
Journal of Neuroscience Nursing
Pharmacologic Management of Paroxysmal
Sympathetic Hyperactivity After Brain Injury
Sophie Samuel, Teresa A. Allison, Kiwon Lee, Huimahn A. Choi
ABSTRACT
Downloaded from http://journals.lww.com/jnnonline by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 05/24/2021
Paroxysmal sympathetic hyperactivity (PSH) is a result of acute brain injury that has been well known for
many decades. However, the evidence for management of PSH is almost entirely anecdotal in nature.
We reviewed case reports or series of pharmacotherapy management of PSH. These studies mentioned
treatment options, but few studies exist to guide treatment strategies. For many years, the syndrome was
not clearly understood; therefore, the therapy has focused on control of symptoms. In 2014, a Steering
Committee came together to develop a conceptual definition and produced a consensus set of diagnostic
criteria. Although understanding the diagnostic criteria is very well needed in management of patients
with PSH, pharmacologic management is also crucial. Data describing the drug choices, dosing, and
duration of therapy are also sparse. Recognition of appropriate medications is important because PSH is
associated with morbidity, longer hospitalization, delaying transfer to rehabilitation units, and increasing
cost. In this review article, we discussed the common medications used in the treatment of PSH. Treatment
should target symptom abortion, prevention of symptoms, and refractory treatment. Symptom-abortive
medications are indicated to control discrete breakthrough episodes, using medications such as morphine and
short-acting benzodiazepines. Other medications used for prevention of symptoms and refractory treatment
include long-acting benzodiazepines, nonselective "-blockers, !2 agonists, opioids, and GABA agonists.
The mechanisms by which these agents improve symptoms of PSH remain speculative. However, a
combination of medications from different classes seems the most effective approach in managing PSH
symptoms. There is wide variability in clinical practice with regard to drug choices, dosing, and duration of
therapy. Future research needs to be conducted using the new PSH assessment measure to appropriately
apply drug management.
Keywords: autonomic storming, brain injury, central autonomic dysfunction, dysautonomia crises,
paroxysmal sympathetic hyperactivity
P
aroxysmal sympathetic hyperactivity (PSH) is
a syndrome associated with brain injury and is
characterized by hypertension, tachypnea, hyperthermia, diaphoresis, and dystonic posturing because
of uncontrolled episodes of unbalanced sympathetic
surges (Baguley et al., 1999). The syndrome has been
recognized since the mid-1950s, and numerous terms
have been used to describe this syndrome (Baguley
et al., 2014). As of September 2014, a Steering
Questions or comments about this article may be directed to
Sophie Samuel, PharmD BCPS, at Sophie.samuel@memorial
hermann.org. She is a Pharmacist, Department of Pharmacy,
Memorial Hermann-Texas Medical Center, Houston, TX.
Teresa A. Allison, PharmD BCPS, is a Pharmacist, Department of
Pharmacy, Memorial Hermann-Texas Medical Center, Houston, TX.
Kiwon Lee, MD, is a Physician, Department of Neurosurgery and
Neurology, The University of Texas Medical School at Houston,
Houston, TX.
Huimahn A. Choi, MD, is a Physician, Department of Neurosurgery
and Neurology, The University of Texas Medical School at Houston,
Houston, TX.
The authors declare no conflicts of interest.
Copyright B 2016 American Association of Neuroscience Nurses
DOI: 10.1097/JNN.0000000000000207
Committee group including clinical specialties of critical
care medicine, neurology, neurosurgery, nursing, occupational therapy, and rehabilitation medicine from
Australia, Europe, and United States came together to
develop a conceptual definition and produced a consensus set of diagnostic criteria (Baguley et al., 2014).
The term ‘‘paroxysmal sympathetic hyperactivity’’ or
PSH has been adapted and replaced previous terms
used to describe the syndrome, such as episodic autonomic instability, dysautonomia, autonomic dysregulation, central autonomic dysfunction, paroxysmal
autonomic instability with dystonia, sympathetic
storming, autonomic storming, dysautonomic crises,
and diencephalic fits (Baguley et al., 2014; Perkes,
Menon, Nott, & Baguley, 2011). The absence of a
unified diagnostic criterion has severely hindered the
ability to advance research of treatment options. The
prevalence of PSH has been reported from 7.7%
to 33% of patients admitted to the intensive care
unit, reflecting the differences in patient populations (Fearnside, Cook, McDougall, & McNeil, 1993;
Perkes et al., 2011). Delayed recognition of the disease leads to unnecessary diagnostic work-up and
inappropriate use of medications, which can further
prolong hospitalization. In addition, uncontrolled
Copyright © 2016 American Association of Neuroscience Nurses. Unauthorized reproduction of this article is prohibited.
Volume 48
symptoms can lead to secondary brain injury from
hypertension, hyperthermia, cardiac damage, and
even death.
The cause of brain injury is an important risk factor
for the development of PSH. Most reported cases of
PSH result from traumatic brain injury TBI (79.4%),
followed by hypoxic brain injury (9.7%) and stroke
(5.4%) (Perkes, Baguley, Nott, & Menon, 2010).
Significant risk factors for developing PSH after
acute brain injury include the severity of the initial
brain injury, younger age, and male gender (Perkes
et al., 2010).
Most agree that PSH is caused by a functional disconnection leading to unbalanced activation of brainstem systems controlling the autonomic nervous
system. Damage to numerous brain regions has been
implicated in the pathogenesis of the disease (Carmel,
1985; Pranzatelli, Pavlakis, Gould, & De Vivo, 1991).
PSH can be caused by different mechanisms of injury in different locations, explaining the variability
in symptoms and severity. Regardless of the lesion
location, the final common pathway is an imbalance
of adrenergic outflow. More detailed reviews of the
pathobiology of PSH have been published (Choi, Jeon,
Samuel, Allison, & Lee, 2013).
Often, PSH is only recognized once the patient is
weaned off of continuous intravenous sedation and
begins to awaken. Usually, it occurs in patients with
a depressed mental status, and episodes are associated
with worsening mental status (Choi et al., 2013). The
clinical manifestations of PSH include presence of
episodic increases in heart rate, blood pressure, respiratory rate, temperature, diaphoresis, and posturing
activity (Baguley et al., 2014). Episodes of exacerbation may last from minutes to hours and can
occur several times a day or in refractory cases nearly
continuously (Fernandez-Ortega et al., 2012; Rossitch
& Bullard, 1988; Srinivasan, Lim, & Thirugnanam,
2007). It may persist into the rehabilitation phase
and last weeks to months after the injury. In severe
cases, it may persist for years (Baguley, Heriseanu,
Nott, Chapman, & Sandanam, 2009; Fernandez-Ortega
et al., 2012).
Clinical suspicion and careful examination are of
paramount importance in the detection of PSH. The
overlapping symptoms of PSH with other neurologic
sequelae of acute brain injury as well as other conditions make the diagnosis difficult and can only be
made after excluding other causes for symptoms. Infections, sepsis, pain, opiate withdrawal, agitation, and
seizures are all diagnoses that have overlapping clinical
presentations that need to be excluded to diagnose
PSH. Some of these diagnoses can coexist with PSH
and in fact can trigger episodes resulting in complicating the management of PSH.
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Previous terms used to describe PSH
include: storming, sympathetic
storming, dysautonomic crises,
and autonomic fits.
Although multiple proposed diagnostic criteria overlap significantly in descriptive ways, consensuses regarding specifics of timing, severity, and number of
episodes have been described (Baguley et al., 2014).
To help with the diagnosis of PSH, the current literature has recommended the use of an assessment tool.
The assessment measure is a diagnostic tool that has
two components, one addresses the probability of
the diagnosis and another assesses the severity of
the clinical features (Table 1). The process requires
addition of the two components, which will help
estimate the likelihood of diagnosis and severity of
the PSH. The assessment tool is designed to assess
patients in a daily basis during intensive care unit stay
and throughout rehabilitation. The availability of diagnostic criteria should hopefully alleviate delaying recognizing of symptoms and medical management.
TABLE 1.
Paroxysmal Sympathetic
Hyperactivity Assessment Tool
Diagnosis Likelihood Tool
Clinical Features Scale
Clinical features occur
simultaneously
Heart rate
Episodes are paroxysmal
in nature
Respiratory rate
Sympathetic overreactive to
normally nonpainful stimuli
Systolic blood pressure
Features persist Q3
consecutive days
Temperature
Features persist Q2 weeks
after brain injury
Sweating
Medication administered to
decrease sympathetic features
Posturing during
episodes
Q2 episodes daily
Absence of parasympathetic
features during episodes
Absence of other presumed
cause of features
Antecedent acquired
brain injury
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TABLE 2.
Medications Used for Treatment of Paroxysmal Sympathetic Hyperactivity
Medication
Location of Action
Proposed Mechanism
Baclofen
Centrally
GABAB agonist
Pain, clonus, rigidity
Benzodiazepines
Centrally
GABAA agonist
Agitation, hypertension,
tachycardia, posturing
Bromocriptine
Centrally at hypothalamus
Dopamine agonist
Dystonia, fever, posturing
Clonidine
Centrally decreased
sympathetic outflow
!2 agonist
Hypertension
Dantrolene
Peripherally
Calcium ion blocker
Muscle rigidity, posturing
Dexmedetomidine
Centrally
!2 agonist
Hypertension, agitation, tachycardia
Gabapentin
Centrally
GABA agonist
Spasticity, allodynic response
Intrathecal baclofen
Centrally
GABAB agonist
Pain, clonus, rigidity
Morphine
Centrally medullary vagal
nuclei and peripherally
2-opiate agonist
Tachycardia, peripheral
vasodilation, allodynic response
Propranolol
Peripherally decreasing
effect of catecholamine
"-blocker
Hypertension, tachycardia, fever
Because of the significance of unrecognized and
undertreated symptoms, it is important that all members of the healthcare team caring for the patient be
familiar with the syndrome and its clinical manifestations. In addition, clinicians must be aware of the pharmacological options for controlling the symptoms.
Treatment
Management of PSH requires a combination of pharmacological as well as nonpharmacological treatment
modalities. Treatment is often challenging because of
the complexity of the disease. In addition, with few
prospective studies available, management is guided
predominantly by case reports and case series utilizing
different medications and treatment strategies. Because
the etiology of the disease is not clearly understood,
therapy has focused on control of symptoms. Medical
treatments for PSH include opioids, "-blockers, dopamine agonists, !2-agonists, GABAergic agents, benzodiazepines, gabapentin, and muscle relaxants (Table 2).
The mechanisms by which these agents improve
symptoms of PSH remain speculative; however, a
combination of medications from different classes
seems the most effective approach in managing PSH
symptoms (Blackman, Patrick, Buck, & Rust, 2004).
Optimizing outcomes with these medications and minimizing side effects, such as sedation, is the goal but
can be a challenge. Ideally, the appropriate approach
to preventing side effects can be done by using shortacting medications, choosing the appropriate regimen, and avoiding medications that fail to control
the symptoms.
Pharmacologic management of PSH focuses on three
treatment approaches: symptom abortion, prevention
Symptoms Treated
of symptoms, and refractory treatment. Symptomabortive medications are indicated to control discrete
breakthrough episodes. These medications have a
rapid onset of action with a short half-life. The targets
of the abortive medications usually depend on the
predominant symptoms: treating hyperthermia with
antipyretics, agitation with sedation, and hypertension
with antihypertensive agents. Morphine and shortacting benzodiazepines are first-line treatment options
for this indication because of their efficacy. Symptom
resolution should be immediate, and side effects from
medications, such as sedation, are reduced given the
short half-life of the medications.
Scheduled symptom preventative medications
should be initiated to decrease the frequency and intensity of episodes. These medications include nonselective "-blockers, !2-agonists, bromocriptine,
baclofen, gabapentin, and long-acting benzodiazepines
such clonazepam.
Refractory PSH, in which symptoms do not respond to treatment, can lead to secondary brain injury
from hypertension, hyperthermia, or cardiac damage
and even death. Intravenous medications and/or continuous intravenous medications such as benzodiazepines, propofol, opioids, or dexmedetomidine drips
should be administered.
Nonselective "-Receptor Blockers
Signs and symptoms of PSH include hypertension,
tachycardia, diaphoresis, and hyperpyrexia, of which
"-blockers are the mainstay of treatment (Bullard, 1987;
Sneed, 1995). Additional manifestations of PSH,
including diaphoresis and dystonic posturing, have
also been shown to respond to "-blockers (Rabinstein
Copyright © 2016 American Association of Neuroscience Nurses. Unauthorized reproduction of this article is prohibited.
Volume 48
& Benarroch, 2008). Propranolol, a competitive nonselective "-blocker, is an ideal drug for controlling
symptoms of PSH because of its broad actions (Bullard,
1987; Sneed, 1995). Treatment of hypertension and
tachycardia because of PSH after brain injury using
propranolol versus hydralazine was examined in six
head injury-related patients. Both drugs effectively
normalized blood pressure. In addition to blood pressure control, the propranolol group further deceased
heart rate by 21%, cardiac index by 26%, left cardiac
work by 35%, pulmonary venous admixture by 15%,
and oxygen consumption by 18%. In contrast, hydralazine increased heart rate by 30%, cardiac index by
49%, left cardiac work by 21%, and pulmonary venous
admixture by 53%. In this small study, propranolol
appeared to be a useful agent in patients with PSH
after brain injury (Robertson, Clifton, Taylor, &
Grossman, 1983). Selective "-blockers, such as metoprolol, have not been shown to improve symptoms of
PSH when used alone. Do, Sheen, and Bromfield
(2000) discussed a case report of a 21-year-old, s/p
motor vehicle collision, who initially presented comatose and was treated with metoprolol 25 mg three times
daily for management of PSH with no improvement.
The patient was then switched to labetalol 100 mg
twice daily, which in turn led to reduction in the
frequency of events to about once a day. An increased
dose of labetalol to 200 mg twice daily markedly decreased the paroxysmal sympathetic storm over several days. At the time of discharge, the patient was
returned to his preadmission baseline (Do et al.,
2000). This study suggested that B1 antagonism alone
is not sufficient to suppress symptoms. In contrast,
the additional effect on alpha receptor from labetalol
might have improved the outcome. Recently, a large
cohort study reported the benefit of propranolol as
the preferred "-blocker agent to use to decrease the
incidence of secondary injury and to improve mortality outcome in patients with TBI experiencing
PSH (Schroeppel et al., 2014).
In addition to its cardiovascular effects, propranolol has been shown to decrease the hyperthermic
response to brain injury (Robertson et al., 1983). The
use of propranolol was evaluated in three patients
with severe TBI secondary to motor vehicle accidents
who presented with decorticate posturing and symptoms of autonomic dysfunction, manifested by tachycardia and profuse sweating. Each patient developed
high fevers ranging from 38.9-C to 40.6-C during
their stay in the hospital. Patients received propranolol 20Y30 mg every 6 hours and reduced the
temperature by at least 1.5-C within 48 hours. When
weaning from propranolol was attempted, an increase
in temperature reoccurred within 3 days (Meythaler
& Stinson, 1994).
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Alpha2-Receptor Agonist
Clonidine, a presynaptic !2-receptor agonist, has
been used to manage hypertension and tachycardia
(Lowenthal, Matzek, & MacGregor, 1988). Because
increased blood pressure due to excitation of the
sympathetic nervous system is one of the major features of PSH, clonidine is often used as a first-line
agent for managing these symptoms. Clonidine use
in PSH was described by Payen and colleagues, to
be effective in reducing circulating plasma levels of
catecholamine resulting in controlled blood pressure
and heart rate (Payen, Quintin, Plaisance, Chiron, &
Lhoste, 1990). However, clonidine use as monotherapy is ineffective in controlling the other manifestation of PSH increasing the need for more than one
agent with different mechanism of actions (Baguley,
Heriseanu, Felmingham, & Cameron, 2006).
Dexmedetomidine, an alternative continuous infusion !2-receptor agonist, is widely used in intensive
care units. Its advantage over other continuous sedatives is that it may be used in patients not dependent
on mechanical ventilation. A recent case report showed
that it may be effective for the management of PSH
symptoms, and given its favorable effects on heart rate,
blood pressure, and agitation, it is an attractive option
to clonidine when an intravenous agent is required
(Goddeau, Silverman, & Sims, 2007).
Opioid Receptor Agonist
Morphine is a potent 2-opioid receptor agonist. Although morphine’s analgesic action is helpful, the
benefit from this drug probably results from increasing the production of cholinergic effects and inducing the release of histamine, making it a good agent
for the management of tachycardia and hypertension (Boeve, Wijdicks, Benarroch, & Schmidt, 1998;
Bullard, 1987; Ko, Kim, Lee, Bae, & Yoon, 2010).
Morphine is often used as an abortive medication to
control breakthrough episodes. It can also be used as
a scheduled dose and converted to an oral agent, such
as oxycodone, for maintenance therapy.
Dopamine Receptor Agonist
Bromocriptine is a synthetic dopamine agonist; however, the mechanism by which resolution of symptoms including hyperpyrexia and dysautonomia are
achieved is unclear (Russo & O’Flaherty, 2000). The
clinical similarities between PSH and neuroleptic malignant syndrome (NMS) have led to its use in PSH.
The role of bromocriptine in management of PSH was
described in a case report in a child with severe TBI
from motor vehicle collision. Because of a history of
severe asthma, the use of propranolol was contraindicated. Patient’s symptoms were initially managed
Copyright © 2016 American Association of Neuroscience Nurses. Unauthorized reproduction of this article is prohibited.
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with morphine and midazolam. On day 5, clonidine
was added to control hypertension. Because the episodes persisted, bromocriptine was initiated on day 9,
which abated the symptoms including hyperpyrexia,
24 hours after starting bromocriptine. Bromocriptine
has shown to be an effective alternative treatment in
management of PSH (Russo & O’Flaherty, 2000).
Although it does not appear to work well as monotherapy, its usefulness has been reported in combination therapy with morphine (Bullard, 1987).
GABA Receptor Agonist
Baclofen, a GABAB receptor agonist, is indicated for
treatment of spasticity associated with PSH and to
improve mobility. It decreases the number and severity
of spasms, thus relieving associated pain, clonus, and
muscle rigidity. In cases where dysautonomia or
posturing persists, the use of intrathecal infusion of
baclofen (ITB) has been reported (Becker, Benes,
Sure, Hellwig, & Bertalanffy, 2000; Cuny, Richer, &
Castel, 2001). These studies have shown a dramatic
immediate improvement and efficient control of spasm
(965%) and tone (980%) (Dario & Tomei, 2004).
Concerns with using ITB include an increase risk in
cerebral spinal fluid leak and infection as well as mechanical problems with the catheter or pump. Occasionally, anatomic anomalies or spinal fusion makes
placement of the intrathecal catheter difficult. Intraventricular baclofen has been shown to be a safe
alternative to ITB (Rocque & Leland Albright, 2012).
Although the use of oral baclofen might be preferred,
the use of high-dose oral baclofen did not reduce the
frequency of spasticity in the traumatic spinal-cordinjured patients (Hinderer et al., 1990).
Gabapentin, an analog of GABA, was originally
developed as an anticonvulsant. However, it may be
more useful in the management of painful neuropathies, spasticity, and tremor (Dworkin et al., 2007;
Zesiewicz et al., 2011). Because of a similar mechanism of action, it is considered an alternative to oral
baclofen. However, its use has not been evaluated as
monotherapy or compared with baclofen in a clinical
trial. Baguley, Heriseanu, Gurka, Nordenbo, and
Cameron, (2007) reported a case on a patient started
on ITB 2 months after admission. ITB markedly reduced
tone and dysautonomic features while at rest, but when
stimulated, patient continued to experience dysautonomic
episodes specifically with muscle stretches and ranging
of joints. Patient was then started on gabapentin 300 mg
three times daily for suspected neuropathic pain syndrome. The addition of gabapentin in this patient immediately decreased dysautonomia, pain, improved
outcome in sleep, and agitation. The sedative properties of gabapentin may have contributed to less agitation (Baguley et al., 2007).
Benzodiazepines, GABAA receptor agonists, have
been used with some success in management of symptoms such as tachycardia and hypertension (Baguley
et al., 2004; Blackman et al., 2004; Rabinstein &
Benarroch, 2008). The concern with benzodiazepines
is the possibility of worsening neurological functioning in newly injured brain (Lazar, Fitzsimmons,
Marshall, Mohr, & Berman, 2003). In addition, sudden withdrawal may result in seizures and worsening
of PSH symptoms; therefore, careful drug tapering
is recommended to avoid complications. Short-acting
benzodiazepines are preferable for patients experiencing breakthrough episodes. These agents can be converted to longer-acting agents to decrease the bouts of
hyperactivity. Clonazepam, diazepam, and lorazepam
are widely used for the treatment of dystonia and
spasticity (Pranzatelli et al., 1991; Rossitch & Bullard,
1988; Sneed, 1995).
Ryanodine Receptor Antagonist
Dantrolene has been reported in case studies where
dystonia or posturing continues to persist. Dantrolene
acts directly on skeletal muscle, decreasing the force
of contraction by interfering with release of calcium
ion from sarcoplasmic reticulum. Dantrolene can possibly be effective for the amelioration of dystonic posturing, but the risk of causing hepatotoxicity can limit
its use (Baguley et al., 1999; Chan, 1990; Rossitch &
Bullard, 1988). Monitoring liver function tests while
on dantrolene might help prevent hepatic failure.
Dopamine Receptor Antagonist
Failure to control symptoms of PSH can be distressing to healthcare professionals and families. Persistent
symptoms have led practitioners to use dopamine antagonists such as chlorpromazine and haloperidol,
leading to reports of exacerbation of cognitive deficits,
psychosis, and NMS (Sandel, Olive, & Rader, 1993;
Wilkinson, Meythaler, & Guin-Renfroe, 1999). NMS
typically consists of autonomic instability, hyperpyrexia, posturing, and cognitive changes, which resemble the symptoms of PSH or can be side effects from
the dopamine antagonists. At this time, dopamine
antagonists cannot be recommended for use in PSH
because of possible worsening of symptoms.
An Algorithm for Pharmacologic
Management of PSH
Effective clinical management of PSH requires a
firm understanding of the appropriate drug choices
for the given symptoms, dosing, and duration of drug
therapy. Given the complexity of the disease with
presence of symptoms, standardized clinical management protocols are essential for optimal patient care.
Copyright © 2016 American Association of Neuroscience Nurses. Unauthorized reproduction of this article is prohibited.
Volume 48
Nonetheless, the lack of well-designed studies continues to be challenging in creating effective guidelines. In our institution, we have created a treatment
approach in how to pharmacologically manage patients with PSH. Our primary goal is to avoid overmedicating patients or treating symptoms with
medications that might worsen the situation, such as
treating with dopamine antagonists. We included the
clinical presentations of PSH: heart rate, respiratory
rate, systolic blood pressure, temperature, sweating,
and posturing during episodes. We then divided the
appropriate medications based on the symptoms presented (Fig 1).
Nonpharmacologic treatment modalities play a
pivotal role in conjunction with pharmacologic therapies. When symptoms are triggered by minimal external stimuli, such as touching, turning, or endotracheal
tube suctioning, every effort should be applied to recognize and minimize the cause of PSH symptoms. Other
symptoms, such as sepsis, infection, encephalitis, or
alcohol or drug withdrawal, should be ruled out.
Symptom-abortive medications are indicated to
administer as soon as episodes are identified. These
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medications have a rapid onset of action with a short
half-life. Symptom resolution should be immediate,
and side effects from medications such as sedation
should be reduced given the short half-life of the
drugs. Although there is no definitive evidence indicating which abortive medication to initiate first,
combination therapy might be warranted to prevent
ongoing episodes. If symptoms persist, preventative
medications should be scheduled preferably with
the first agent that controlled the episodes. In cases
where dystonia or posturing continues to persist with
or without the presence of other symptoms, drugs
such as benzodiazepines, gabapentin, and dantrolene
should be considered. Because of a long onset of
action, symptom resolution cannot be achieved
quickly with gabapentin or baclofen. However, early
introduction of these agents will help alleviate further
complications, namely, delaying rehabilitation and
transferring patient from intensive care unit. In the
presence of refractory PSH, use of intravenous medications and/or continuous intravenous medication, namely, benzodiazepines, propofol, opioids, or
dexmedetomidine drips, might be required.
FIGURE 1 Management of Paroxysmal Sympathetic Hyperactivity
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Implications for Practice
Training, with a focus on recognition of signs and
symptoms of PSH, should include intensive care
nurses who are consistently at the bedside with the
patient. Symptoms can pose a challenge for the bedside nurse, while managing severe storming episodes,
administrating medications, and educating the family.
Early recognition of PSH might alert nurses in the
role of moderator to intervene sooner and help guide
in choosing appropriate medications.
Conclusion
Early recognition and treatment of PSH may contribute to reducing length of stay as well as decreasing
mortality associated with PSH. The availability of consensus on conceptual definition, nomenclature, and diagnostic criteria is a promising development that will
pave the way to having a better pharmacologic management of PSH. Future studies should incorporate the use
of PSH assessment measure to eventually guide practitioners to effective drug choices, doses, and duration.
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