The Journal of Emergency Medicine, Vol. 54, No. 4, pp.

447–457, 2018
Published by Elsevier Inc.
0736-4679/$ - see front matter

https://doi.org/10.1016/j.jemermed.2017.12.049

Clinical Reviews
in Emergency Medicine

APPROACH TO THE AGITATED EMERGENCY DEPARTMENT PATIENT

Michael Gottlieb, MD, RDMS,* Brit Long, MD,† and Alex Koyfman, MD‡
*Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois, †Department of Emergency Medicine, San Antonio
Military Medical Center, Fort Sam Houston, Texas, and ‡Department of Emergency Medicine, The University of Texas Southwestern Medical
Center, Dallas, Texas
Reprint Address: Brit Long, MD, Department of Emergency Medicine, San Antonio Military Medical Center, 3841 Roger Brooke Dr., Fort Sam
Houston, TX 78234

, Abstract—Background: Acute agitation is a common INTRODUCTION

occurrence in the emergency department (ED) that requires
rapid assessment and management. Objective: This review
provides an evidence-based summary of the current ED
evaluation and management of acute agitation. Discussion:
Acute agitation is an increasingly common presentation to
the ED and has a broad differential diagnosis including
metabolic, neurologic, infectious, toxicologic, and psychiat-
ric etiologies. Missed diagnosis of a dangerous etiology of
the patient’s agitation may result in severe morbidity and
mortality. Assessment and management of the agitated pa-
tient should occur concurrently. Focused history and phys-
ical examination are recommended, though control of the
patient’s agitation may be required. All patients should
receive a point-of-care glucose test, with additional testing
depending upon the specific patient presentation. Initial
management should involve verbal de-escalation techniques,
followed by pharmacologic interventions, with physical re-
straints reserved as a last resort. Pharmacologic options
include first-generation antipsychotics, second-generation
antipsychotics, benzodiazepines, and ketamine. Finally, the
management of pediatric, pregnant, and elderly patients
warrants special consideration. Conclusion: Acute agitation
is an important presentation that requires prompt recogni-
tion and treatment. A focused and thorough examination
coupled with appropriate management strategies can assist
emergency clinicians to safely and effectively manage these
patients. Published by Elsevier Inc.
, Keywords—agitation; psychosis; delirium; control;
benzodiazepine; antipsychotic; ketamine; physical restraint
Background
Altered mental status accounts for 5–10% of emergency
department (ED) patient visits (1–4). Among these
patients, a subset present with acute agitation. The
etiology can vary widely, including medical, substance-
induced, and psychiatric causes (4–10). These patients
may harbor major illnesses with the potential for
significant morbidity or mortality if not diagnosed and
managed, while rapidly controlling their agitation
(4–6,9).
As a result of this agitation, patients may present a risk
to themselves or others (5,6,11). Almost 50% of medical
providers will be a victim of violence during their career
(5,6,12,13). A survey of physicians found that 73% were
threatened in the workplace, and 36% were assaulted
during residency (14). This survey also found that two-
thirds of physicians received minimal or no formal
training in the management of the agitated patient (14).
Additional studies suggested that only 20–40% of hospi-
tals possess a formal training program for the manage-
ment of combative patients (15–17).
These studies reflect the need for further education on
this condition. This review seeks to provide physicians
with an overview of the clinical features, differential
diagnosis, emergency medicine evaluation, and manage-
ment of the acutely agitated patient in the ED.

RECEIVED: 13 December 2017;

ACCEPTED: 17 December 2017

447
448 M. Gottlieb et al.

METHODS Table 1. Dangerous Causes of Agitation

System Etiology
Authors searched PubMed and Google Scholar for arti-
cles using a combination of the keywords ‘‘agitated,’’ Metabolic/endocrine Electrolyte abnormalities (e.g., sodium,
calcium, magnesium, potassium,
‘‘sedation,’’ ‘‘psychiatric,’’ and ‘‘emergency.’’ The litera- phosphate)
ture search was restricted to studies published in En- Hypoglycemia
glish. Authors reviewed all relevant articles and Hyperglycemia (eg, DKA/HHNK)
Hypoxia
decided which studies to include for the review by Hypercarbia
consensus. A total of 126 articles were selected for in- Renal or liver failure
clusion in this review. Thyrotoxicosis
Myxedema coma
Nutritional deficiency (e.g., Wernicke’s,
DISCUSSION vitamin B12 deficiency)
Infection Sepsis
Differential Diagnosis Systemic infections
Fever-related delirium
Neurologic Head injury
Agitation can encompass a wide variety of findings, and a Stroke
patient’s agitation may be secondary to a dangerous med- Intracranial mass
ical condition rather than primary psychosis (4–6). Drug Intracranial hemorrhage
CNS infection (e.g., meningitis,
and alcohol intoxication are the most common diagnoses encephalitis, abscess)
in the ED (4–7,18–22). Other conditions that may result Seizure
in agitation are shown in Table 1 (4–7,18–22). These Dementia
Toxicological Anticholinergic intoxication
conditions require rapid diagnosis and management. Stimulant intoxication
Steroid psychosis
Clinical Features and Evaluation Antibiotic reaction
Other drug reaction
Carbon monoxide toxicity
Emergency physicians should assess for the cause of the Alcohol intoxication or withdrawal
agitation when this can be completed safely (Table 1). If Toxic alcohols
Serotonin syndrome
possible, initial assessment and de-escalation should Neuroleptic malignant syndrome
occur at the same time. It may be necessary to calm or Other conditions Shock (e.g., hypovolemic, cardiogenic,
sedate the patient first to avoid harm to the patient or pro- distributive, obstructive)
Burn
viders. However, after this, it is important to rapidly Hypothermia
perform a focused history and physical examination, Hyperthermia
assessment of vital signs, and obtain any relevant labora- Psychiatric Psychosis
Schizophrenia
tory or imaging tests (5,6,18–21). Paranoid delusions
The patient evaluation should include obtaining the Personality disorder
history, performing a focused physical examination, and
assessing the degree of patient agitation. One of the first DKA = diabetic ketoacidosis; HHNK = hyperosmotic hyperglyce-
mic nonketotic state; CNS = central nervous system.
determinations is whether delirium or excited delirium
is present. Delirium may be an underlying component
of the patient’s agitation. Delirium is an organic condition Excited delirium is a subset of delirium presenting
associated with a global disturbance in cognition, atten- as an acute agitated state (11,30). It is marked by
tion, or consciousness. It develops abruptly and fluctuates delirium and agitation (e.g., fear, violence, shouting,
over time (18,21–25). Close to 40% of elderly patients in hyperactivity, panic), followed by sudden cessation and
the ED may demonstrate alteration in mental status, with respiratory compromise, leading to death (11,30–33).
25% demonstrating delirium (21,22,26). Patients can Hyperthermia is typically present, as is exaggerated
present with disturbances in the sleep/wake cycle and strength (11,30–33). Nearly two-thirds of patients die at
alteration in consciousness ranging from coma to the scene or prior to transport (11,30–33).
hyperactive agitation (21–25). Delirium may also Chronic cognitive impairment may also contribute to
present with shifting attention, difficulty following agitation. Patients with dementia, developmental
commands, and trouble with concentration (5,6,21–25). disability, or severe brain injury may display agitation
Agitation is not always present in delirium, with only and confusion in unfamiliar settings (21).
one-third of cases demonstrating agitation (26). Delirium History should be obtained from the patient, emer-
itself is a medical emergency, with hospital mortality gency medical services personnel, family, witnesses,
rates approaching 33% (25–29). and caregivers (5,6,9). One study found that the history
Approach to the Agitated ED Patient
alone was 94% sensitive for detecting the etiology for
agitation (22). When asked directly, the patient may pro-
vide a different reason for being brought to the ED other
than family members, police, or others accompanying the
patient (5,21). It is important to determine the true issue
for the crisis, as well as the specific time frame and
recent stressors or exacerbating factors. If able, the
patient can provide valuable information, and the
clinician should take time to listen to the patient
history. Baseline mental status, history of prior
psychiatric illness and hospitalizations, prior violent
episodes, and functional status are important factors in
assessment of the agitated, altered patient (5,6,18,21).
Acute factors such as substance use, oral intake, fevers,
trauma, ingestion, withdrawal, and presence of systemic
disease should be assessed (4–7,18,21). A prior history
of immunocompromised state, cancer, or neurologic
disease (e.g., stroke, multiple sclerosis) can suggest a
medical etiology (5,18,21,22).
Examination requires close assessment of patient he-
modynamics, core temperature, and cardiopulmonary
and neurologic systems (4–7,18). Medical and surgical
causes for the patient’s alteration include infection,
trauma, and focal neurologic deficits. The examination
should assess for findings consistent with these
conditions. Other findings such as abnormal vital signs
or physical examination, age older than 45 years with
new-onset agitation, neck stiffness, fever, signs of drug
intoxication or withdrawal, focal neurologic deficit,
decreased awareness or confusion, evidence of trauma
(contusion or bleeding), palpitations, clonus, vomiting,
diarrhea, visual hallucinations, and tremors are also sug-
gestive of a medical etiology (Table 2) (4–8,18–21).
A focused examination of the patient’s mental status is
recommended if able, focusing on the patient’s behavior,
appearance, affective state, thought process, presence of
Table 2. Concomitant Findings Requiring Further
Evaluation
Symptoms Signs
Memory loss, disorientation, Abnormal vital signs
confusion Evidence of trauma
Severe headache Abnormal neurologic
Muscle stiffness, weakness examination (e.g., asymmetric
Heat intolerance, chills pupils, focal weakness,
Weight loss, unintentional seizure, slurred speech,
Psychosis new in onset incoordination)
Shortness of breath/chest pain Cardiopulmonary abnormality
Abdominal symptoms Evidence of toxidrome (e.g.,
(including vomiting and sympathomimetic,
diarrhea) anticholinergic, serotonin
syndrome)
Evidence of withdrawal state
(e.g., alcohol,
benzodiazepines)
Age > 45 years
449
suicidal or homicidal ideations, attention, psychosis,
awareness, judgment and insight, executive functions,
and reliability (18,21). Cognitive abilities can be
evaluated using the Folstein Mini Mental State
Examination or the Brief Mental Status Examination
(34,35). If not already obtained, past psychiatric history
including prior psychiatric conditions, hospitalizations,
family history, prior suicidal attempts, substance use,
current stressors, social support system, and living
situation can assist clinicians (18,21).
Agitation Scales
Several scales are available to assess the patient’s level of
agitation. Scales include the Behavioural Activity Rating
Scale (Table 3), Overt Agitation Severity Scale, and
Overt Aggression Scale (4–6,36–38). Other scores
primarily evaluated for sedation may also be used for
agitation, including the Richmond Agitation-Sedation
Scale and the Sedation-Agitation Scale (39,40). For
sedation in critically ill patients, the Richmond
Agitation-Sedation Scale and the Sedation Agitation
Scale are the most valid and reliable subjective scoring
systems (41). However, their use for agitation in the ED
may not be as reliable. The Behavioural Activity Rating
Scale is rapid and reliable for the ED, with scores $ 5
associated with agitation (18,21,36). Additionally,
unlike other agitation scales, this score does not require
the patient to answer questions, which can be
challenging in many patients when acutely agitated
(5,18).
Laboratory Testing and Imaging
The most important initial test in an acutely agitated pa-
tient is a rapid point-of-care glucose level. Hypoglycemia
can present with a myriad of symptoms, and agitation is a
well-known presentation. In addition, all women of child-
bearing age should have a pregnancy test performed. As
patients may not be cooperative with a urine pregnancy
test, serum pregnancy testing should be strongly
Table 3. BARS Assessment for Agitation
Points Characteristic
1 Difficult or unable to rouse
2 Asleep but can respond to verbal/physical contact
3 Appears sedated, drowsy
4 Normal level of activity, quiet and awake
5 Signs of overt activity (physical or verbal), but calms with
instruction
6 Continuously or extremely active, not yet requiring
restraint
7 Violent, requiring restraint
BARS = Behavioural Activity Rating Scale.
450
considered. In addition, an electrocardiogram (if
possible), basic metabolic panel, hepatic function studies,
ethanol level, and thyroid studies may be considered,
especially when abnormal physical examination findings
are present or the patient does not have a prior psychiatric
history. If patients demonstrate significant psychomotor
agitation, a creatinine kinase level should be considered
to assess for rhabdomyolysis. When there is concern for
an intracranial abnormality causing symptoms, a noncon-
trast computed tomography of the head should also be ob-
tained.
Nonpharmacologic Interventions
Prior to giving any sedative agents, providers should
begin with verbal de-escalation techniques (6,42–45).
These may include offering environmental changes,
food, or other comfort measures (42,43,45). It is
important to bring the patient to a quiet and safe
location, devoid of other patients, medical supplies, or
loose objects, which may become potential weapons in
the hands of the patient (6,43,45,46). When possible,
larger rooms are preferable, as they may make patients
feel less trapped (6,46). Additionally, decreasing the
ambient noise, dimming the lights, and adjusting the
temperature may further calm patients (6). The ability
of patients to consider and weigh these options can sug-
gest how cooperative the patient may be (6). Furthermore,
if medication is necessary, this may also increase the like-
lihood that the patient will cooperate with oral dosing or
facilitate the injection. An excellent summary of de-
escalation techniques for the emergency provider is pro-
vided by Richmond et al. (45).
Pharmacologic Interventions
If verbal de-escalation is ineffective, medications may be
required (Table 4). Note that the goal of pharmacologic
Table 4. Medications for the Treatment of the Agitated
Patient
Type of Medication Available Routes and Doses
Haloperidol p.o./i.m./i.v.: 5 mg (maximum: 20 mg over
24 h)
Risperidone p.o.: 2 mg (maximum: 6 mg over 24 h)
Olanzapine p.o./i.m./i.v.: 5–10 mg (maximum: 20 mg
over 24 h)
Ziprasidone i.m.: 10–20 mg (Maximum: 40 mg over
24 h)
Aripiprazole i.m.: 9.75 mg (Maximum: 30 mg over 24 h)
Lorazepam p.o./i.m./i.v.: 2 mg
Midazolam p.o./i.m./i.v.: 2 mg
Ketamine i.m.: 4–6 mg/kg; i.v.: 1–2 mg/kg
p.o. = per os (orally); i.m. = intramuscular; i.v. = intravascular.
M. Gottlieb et al.
agents should be to calm, rather than completely sedate
the patient (47). Medications may be given via the oral,
intramuscular, or intravenous route. When patients are
cooperative, the oral route is preferred, as it decreases
the potential for provider injury, while increasing the pa-
tient’s sense of autonomy (6,48). Multiple studies have
demonstrated that oral medications are as effective as
intramuscular medications for the treatment of acute
agitation (49–54). It is important to note that oral
medications are susceptible to diversionary tactics. If
this is a concern, dissolvable preparations should be
considered (6,55).
First-generation antipsychotic agents. Haloperidol is a
first-generation antipsychotic (FGA) commonly utilized
for the sedation of agitated patients, especially those
with a known psychiatric history. Haloperidol is a typical,
butyrophenone-type antipsychotic with a high affinity for
D2 receptors in the brain (44). It has a mean time to seda-
tion of 25–28 min, with a mean total sedation time of 84–
126 min (56,57). The most common side effects are
extrapyramidal symptoms (e.g., Parkinsonism, dystonia,
akathisia), which may be reduced with the concomitant
use of an anticholinergic agent (e.g., benztropine,
diphenhydramine) (44,58). There is also a risk of QTc
prolongation, which may be increased in patients taking
other QTc prolonging agents (44).
Second-generation antipsychotic agents. There has been
increasing literature evaluating the use of second-
generation (atypical) antipsychotics (SGA) in place of
more typical agents due to a better side-effect profile
(59–69). Additionally, some patients can experience
significant dysphoria after initiation of FGAs, and one
study demonstrated a significant patient preference for
SGAs over FGAs (70,71). Common SGAs include
olanzapine, ziprasidone, aripiprazole, and quetiapine.
These agents work at D2 receptors, similar to FGAs,
but also have affinity for several other sites, including
the 5-HT2A, histamine, norepinephrine, and a-2 recep-
tors (44).
When compared with FGAs, SGAs have demonstrated
similar overall efficacy (59,61,62). Wright et al.
demonstrated improved sedation in the olanzapine
group compared with the haloperidol group during the
first 45 min of treatment; however, this resolved by 1 h
(59). Both FGAs and SGAs demonstrated low rates of
adverse events (59,61,62). Although all antipsychotic
medications have a risk of QTc prolongation, this
occurs much less commonly with the SGAs and is very
rare with the agents commonly used in the ED (eg,
olanzapine, quetiapine, and risperidone) (72).
Although these medications are often given via the
oral or intramuscular route, the intravenous route has
Approach to the Agitated ED Patient
been suggested to be a safe alternative when available
(68,69). One study of intravenous olanzapine
demonstrated a very low rate of akathisia, QTc
prolongation on electrocardiogram, or allergic reactions
among a sample of 672 ED patients (68). Another study
identified no statistically significant difference in respira-
tory depression, intubation, QTc prolongation, or other
side effects among a sample of 784 patients receiving
either intravenous or intramuscular olanzapine (69).
Benzodiazepines. Benzodiazepines work directly at the
gamma-aminobutyric acid receptor to increase sedation.
There are several options, though lorazepam and mida-
zolam are the most common agents utilized in practice.
Lorazepam can be given via the intravenous, intramus-
cular, and oral routes. Midazolam can be given via the
intravenous, intramuscular, intranasal, rectal, and oral
routes. Midazolam has a mean time to sedation of 13–
18 min and a mean total sedation time of 82–105 min,
whereas lorazepam has a mean time to sedation of
32 min and a mean total sedation time of 217 min
(56,57). Although both are effective, some may prefer
midazolam due to its more rapid onset of action,
whereas others may favor lorazepam due to its longer
total sedation time. One study comparing ziprasidone
with midazolam found that midazolam had a more
rapid time to sedation, but required more doses of
rescue medications (73).
The combination of haloperidol with benzodiazepines
has been suggested to be superior to either agent alone,
with several studies demonstrating improved sedation
and no significant difference in adverse events between
groups (74–76). Additional studies have assessed
midazolam in combination with droperidol, noting
improved sedation in the combination group when
compared with either agent alone and no difference in
adverse events (63–65).
Ketamine. Ketamine is a sedative agent that works by in-
teracting with a variety of receptors, including N-methyl-
D-aspartate, nitric oxide synthase, and multiple opioid
receptors (77). Ketamine has an onset of action of
2–3 min with a duration of effect ranging from
5–30 min (77,78). Although initially utilized for
procedural sedation, recent literature has described the
use of ketamine to sedate the agitated patient.
One study described the use of ketamine for the
sedation of psychiatric patients requiring aeromedical
transportation over a 9-year period (79). The authors
found that the use of a ketamine-based protocol resulted
in a significantly lower rate of intubations in this high-
risk environment (79). However, the authors used retro-
spective data and comparator agents were not described.
Another prehospital study compared intramuscular
451
ketamine with intramuscular haloperidol and found keta-
mine was associated with a significantly faster time to
adequate sedation (5 min vs. 17 min) but had higher rates
of overall complications (49% vs. 5%) and intubations
(39% vs. 4%) (80). In the only prospective, comparative
study conducted in an ED setting, ketamine was
compared with haloperidol, benzodiazepines, or a combi-
nation of haloperidol and benzodiazepines and resulted in
a greater number of patients successfully sedated at 5, 10,
and 15 min (81). The rate of intubation was low in both
groups (81). Importantly, ketamine may lose its effect
much quicker than other agents, which may require re-
dosing or the addition of a different medication. Although
the administration of ketamine to patients with schizo-
phrenia has not been associated with long-term conse-
quences, it has been suggested to increase acute
agitation and is not recommended in this population for
acute management of agitation (82,83).
Physical Restraints
Although the use of physical restraints has declined over
the past several decades, they are still commonly used in
the acute setting, with studies suggesting their use in over
half of all acutely agitated patients (84–86). Restraints
were initially viewed as a mechanism to reduce injuries
to both patients and providers (6). However, the physical
act of placing the patient into restraints has been sug-
gested to account for a large proportion of agitation-
related injuries (6,87). Additionally, restraints do not
protect patients from all significant injuries. Continued
fighting against restraints can lead to muscle breakdown
and rhabdomyolysis (6,87). Moreover, there are
numerous studies describing deaths from asphyxiation,
strangulation, and chest compression due to restraint
use (87–90). Finally, one must consider the
psychological impact that physical restraints may have
on the patient (91,92).
Whenever possible, verbal de-escalation and patient
seclusion should be attempted first (6). If this is unsuc-
cessful, providers should consider one of the above phar-
macologic interventions prior to resorting to physical
restraints. Physical restraints should be reserved for pa-
tients who remain a danger to themselves and others
despite the above measures (6). The most common forms
of restraints are soft cloth and locked leather restraints
(93). Although cloth restraints are easier for health care
providers to place on the patient, they can tighten around
the distal extremity as patients move and may lead to
compromised circulation to the extremities (93). It is
important to secure the restraints to the frame of the
bed, rather than the side rails, which are mobile (93). Dur-
ing the restraint procedure, it is important to have a min-
imum of five people present to assist with placement (i.e.,
452
one person for the head and one person for each extrem-
ity). If all four extremities are to be restrained, the clini-
cian leading the team should ensure that one arm is fixed
to the gurney in the up position, whereas the other arm is
in the down position, to reduce the risk of patients gener-
ating enough force to overturn the gurney (93).
Regardless of whether restraints are used, verbal de-
escalation should continue, and the behavioral modifica-
tions necessary for restraint removal should be frequently
emphasized (6). The minimal restraints that are necessary
to protect the patient and others should be utilized, and
patients should be closely monitored by staff (93,94).
Efforts should be made to remove the restraints as soon
as possible. Although institutional protocols may vary,
the Centers for Medicare and Medicaid Services
dictates the time limits and regulations on the use of
restraints. The Centers for Medicare and Medicaid
Services states that patients should remain in constant
physical restraints for a period of no longer than 4 h for
an adult, 2 h for adolescents, and 1 h for children
younger than 9 years old (95).
Special Populations
Pediatric patients. ED visits for psychiatric or behavioral
crises in children have been increasing and now represent
approximately 5% of all pediatric visits (96). Children
may not be able to fully describe why they are agitated
and may even describe a ‘‘voice in my head’’ telling
them to hit or break objects or others around them (97).
Additionally, descriptions of hallucinations may be less
reliable in children (97). Therefore, it is particularly
important to gather information concerning precipitating
events, as well as any prior medical and psychiatric his-
tory and potential exposure to medications, from parents
and caretakers (97). Agitation may begin with tantrums or
acting defiantly, but can progress to fully aggressive
behavior and even physical violence (97). As with adults,
verbal de-escalation should be the first-line approach. In-
clusion of parents and caretakers may help facilitate this
by providing familiarity in a foreign environment. How-
ever, at times one or more family members may be the
source of or exacerbate the patient’s agitation. In the latter
case, they should be removed from the patient’s room.
When medications are necessary, the oral route should
be offered, as the pain associated with an injection may
exacerbate symptoms (97). If the child has a known psy-
chiatric disorder, it may be reasonable to give them an ex-
tra dose of their home medications (97). However, the
provider should be careful with giving new medications,
as pediatric patients react differently than adults (97). For
example, benzodiazepines can result in paradoxical agita-
tion in pediatric patients, particularly younger patients or
M. Gottlieb et al.
those with developmental delay (97). Diphenhydramine
has been suggested to be one of the safest agents, partic-
ularly in young children (97). Antipsychotics may also be
considered, but have a higher rate of extrapyramidal side
effects in younger patients (97,98). If an FGA is given
to a pediatric patient, it should be given with
diphenhydramine to reduce the risk of side effects.
Olanzapine has been suggested to be relatively safe in
pediatric patients, with minimal side effects among a
sample of 285 pediatric patients (99). There is minimal
literature on the use of restraints in pediatric patients.
As with adults, it is important to monitor the patient
closely and remove the restraints as soon as feasible. Pro-
viders should also be aware of the difference in restraint
guidelines for pediatric patients (e.g., 2 h for adolescents,
1 h for children < 9 years of age) (95).
Pregnant patients. Pregnancy can significantly compli-
cate psychiatric disorders. Previously well-managed psy-
chiatric disorders may worsen due to changes in
medication dosing, complete cessation of medication,
or the pregnancy itself (100–103). Additionally, the
selection of potential medications becomes more
limited (103). Risperidone should be the first-line agent
in pregnant patients, as it has no known teratogenic ef-
fects (104,105). Haloperidol has been suggested to be
relatively safe but is associated with a small increased
risk of fetal limb defects with prolonged use
(103,106–108). Benzodiazepines are also a relatively
safe adjunct in the acute setting (103). However, the pro-
longed use of benzodiazepines remains controversial,
with studies suggesting a possible association with major
malformations and cleft lip when taken during the first
trimester (109). Of note, this effect was observed only
in case-control studies, not cohort studies (109). Addi-
tionally, the risk rate was a difference of 5 cases per
10,000 births, leading some experts to suggest this as a
reasonable second-line agent (103,110). If longer-term
agents are required, valproic acid, lithium, and carbamaz-
epine should be avoided due to an increased risk of tera-
togenicity, especially in the first trimester (111–119).
Restraints should be avoided whenever possible, as
patients in the second or third trimester are at risk of
inferior vena cava compression (103). Should restraints
be necessary, it may be valuable to rotate the patient’s
body to the left lateral decubitus position or place a sup-
port under her right side to reduce the risk of inferior vena
cava compression.
Elderly patients. Elderly patients represent a unique sub-
set of the adult population because they have an increased
baseline incidence of medical illnesses and may respond
differently to interventions if baseline cognitive
Approach to the Agitated ED Patient
dysfunction is present. Medical disorders are more com-
mon in this subgroup, and one should evaluate for infec-
tious disorders and consider obtaining a noncontrast
computed tomography scan of the head to evaluate for
intracranial pathology (120,121). The effect of
medication interactions or incorrect intake due to
polypharmacy is another concern in this population
(121). Similar to the above patients, verbal de-
escalation should be attempted prior to the initiation of
chemical or physical restraints (120). Whenever possible,
family members and friends should be utilized to help
calm and reorient the patient should he or she become
more confused (120,122). When medications are
required, a lower dose should be used, with some
experts recommending using no more than half the
normal starting dose (6,120,121). Additionally, due to
the potential for decreased breakdown and excretion of
medications, titration should be slower than in younger
patients (121). Benzodiazepines should be avoided, as
their use in the elderly is associated with worse outcomes
(e.g., central nervous system depression, respiratory
depression, falls), even after a single dose (123–125).
Although the literature is limited, either FGAs or SGAs
are reasonable first-line pharmacologic agents (121).
However, one should be cognizant of the increased poten-
tial for QTc prolongation, as many elderly patients are on
concomitant medications that may interact with or pro-
long the QTc interval (46). If restraints are required, a
trial of discontinuation should be considered as soon as
the agitation resolves, as prolonged use of restraints has
been associated with an increased risk of adverse events
in this population (126).
CONCLUSION
Acute agitation is a common occurrence in the ED and re-
quires rapid assessment and management. Acute agita-
tion has a broad differential diagnosis that can include
metabolic, neurologic, infectious, toxicologic, and psy-
chiatric etiologies. All patients should receive a point-
of-care glucose test, with additional testing depending
upon the specific patient presentation. Initial manage-
ment should involve verbal de-escalation techniques, fol-
lowed by pharmacologic interventions, with physical
restraints reserved as a last resort. Pharmacologic options
include FGAs, SGAs, benzodiazepines, and ketamine.
The management of pediatric, pregnant, and elderly pa-
tients warrants special consideration. Acute agitation is
an important presentation that requires prompt recogni-
tion and treatment. A focused and thorough examination
coupled with appropriate management strategies can
assist emergency clinicians with effectively managing
these patients.
453
Acknowledgments—MG, BL, and AK conceived the idea for
this manuscript and contributed substantially to the writing
and editing of the review. This manuscript did not utilize any
grants, and it has not been presented in abstract form. This clin-
ical review has not been published, it is not under consideration
for publication elsewhere, its publication is approved by all au-
thors and tacitly or explicitly by the responsible authorities
where the work was carried out, and that, if accepted, it will
not be published elsewhere in the same form, in English or in
any other language, including electronically without the written
consent of the copyright holder. This review does not reflect the
views or opinions of the U.S. government, Department of De-
fense, U.S. Army, U.S. Air Force, or the San Antonio Uniformed
Services Health Education Consortium Emergency Medicine
Residency Program.
REFERENCES
1. Elie M, Rousseau F, Cole M, et al. Prevalence and detection of
delirium in elderly emergency department patients. CMAJ 2000;
163:977–81.
2. Hustey F, Meldon S. The prevalence and documentation of
impaired mental status in elderly emergency department patients.
Ann Emerg Med 2002;39:248–53.
3. Hustey F, Meldon S, Smith M, et al. The effect of mental status
screening on the care of elderly emergency department patients.
Ann Emerg Med 2003;41:678–84.
4. Kanich W, Brady W, Huff S, et al. Altered mental status: evalua-
tion and etiology in the ED. Am J Emerg Med 2002;20:613–7.
5. Nordstrom K, Zun LS, Wilson MP, et al. Medical evaluation and
triage of the agitated patient: consensus statement of the American
Association for Emergency Psychiatry Project BETA Medical
Evaluation Workgroup. West J Emerg Med 2012;13:3–10.
6. New A, Tucci VT, Rios J. A modern-day fight club? The stabiliza-
tion and management of acutely agitated patients in the emergency
department. Psychiatr Clin North Am 2017;40:397–410.
7. Dubin WR, Weiss KJ. Emergency psychiatry. In: Michels R,
Cavenar JD, Cooper AM, et al., eds. Psychiatry. Philadelphia: Lip-
pincott-Raven; 1997.
8. Han JH, Wilber ST. Altered mental status in older patients in the
emergency department. Clin Geriatr Med 2013;29:101–36.
9. Wilber ST, Ondrejka JE. Altered mental status and delirium.
Emerg Med Clin North Am 2016;34:649–65.
10. Joseph J, Kennedy M. Altered mental status in the elderly. In:
Mattu A, Grossman SA, Rosen PL, eds. Geriatric emergencies: a
discussion-based review. Hoboken, NJ: John Wiley & Sons;
2016:58–70.
11. Takeuchi A, Ahern TL, Henderson SO. Excited delirium. West J
Emerg Med 2011;12:77–83.
12. Schulte JM, Nolt BJ, Williams RL, et al. Violence and threats of
violence experienced by public health field-workers. JAMA
1998;280:439–42.
13. Al-Sahlawi KS, Zahid MA, Shahid AA, et al. Violence against
doctors: 1. A study of violence against doctors in accident and
emergency departments. Eur J Emerg Med 1999;6:301–4.
14. Schwartz TL, Park TL. Assaults by patients on psychiatric resi-
dents: a survey and training recommendations. Psychiatr Serv
1999;50:381–3.
15. Lavoie FW, Carter GL, Danzl DF, et al. Emergency department
violence in United States teaching hospitals. Ann Emerg Med
1988;17:1227–33.
16. Kansagra SM, Rao SR, Sullivan AF, et al. A survey of workplace
violence across 65 U.S. emergency departments. Acad Emerg Med
2008;15:1268–74.
454
17. McAneney CM, Shaw KN. Violence in the pediatric emergency
department. Ann Emerg Med 1994;23:1248–51.
18. American College of Emergency Physicians Clinical Policies Sub-
committee (Writing Committee) on the Adult Psychiatric Patient.
Clinical policy: critical issues in the diagnosis and management of
the adult psychiatric patient in the emergency department. Ann
Emerg Med 2017;69:480–98.
19. Lavoie FW. Consent, involuntary treatment, and the use of force in
an urban emergency department. Ann Emerg Med 1992;21:25–32.
20. Olshaker JS, Browne B, Jerrard DA, Prendergast H, Stair TO.
Medical clearance and screening of psychiatric patients in the
emergency department. Acad Emerg Med 1997;4:124–8.
21. Stowell KR, Florence P, Harman HJ, et al. Psychiatric evaluation
of the agitated patient: consensus statement of the American Asso-
ciation for Emergency Psychiatry Project BETA Psychiatric Eval-
uation Workgroup. West J Emerg Med 2012;13:11–6.
22. Caplan LR. Delirium: a neurologist’s view—the neurology of
agitation and overactivity. Rev Neurol Dis 2010;7:111–8.
23. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in crit-
ically ill patients: validation of the Confusion Assessment Method
for the Intensive Care Unit (CAMICU). Crit Care Med 2001;29:
1370–9.
24. Inouye SK, Van Dyck CH, Alessi CA, et al. Clarifying confusion:
the confusion assessment method: a new method for detection of
delirium. Ann Intern Med 1990;113:941–8.
25. Grover S, Kate N. Assessment scales for delirium: a review. World
J Psychiatry 2012;2:58–70.
26. Naughton BJ, Moran MB, Kadah H, et al. Delirium and other
cognitive impairment in older adults in the emergency department.
Ann Emerg Med 1995;25:751–5.
27. Inouye S, Rushing J, Foreman M, et al. Does delirium contribute to
poor hospital outcomes? A three-site epidemiologic study. J Gen
Intern Med 1998;13:234–42.
28. Pompei P, Foreman M, Rudberg M, et al. Delirium in hospitalized
older persons: outcome and predictors. J Gen Intern Med 1998;13:
234–42.
29. Dolan M, Hawkes W, Zimmerman S, et al. Delirium on hospital
admission in aged hip fracture patients: prediction of mortality
and 2-year functional outcomes. J Gerontol A Biol Sci Med Sci
2000;55:M527–34.
30. Sztajnkrycer MD, Baezz AA. Cocaine, excited delirium and sud-
den unexpected death. Emerg Med Serv 2005;34:77–81.
31. Wetli CV, Mash D, Karch SB. Cocaine-associated agitated
delirium and neuroleptic malignant syndrome. Am J Emerg Med
1996;14:425–8.
32. Wetli CV, Fishbain DA. Cocaine-induced psychosis and sudden
death in recreational cocaine users. J Forensic Sci 1985;30:873–80.
33. Ruttenber AJ, Lawler-Heavner J, Yin M, et al. Fatal excited
delirium following cocaine use: epidemiologic findings provide
new evidence for mechanisms of cocaine toxicity. J Forensic Sci
1997;42:25–31.
34. Folstein MF, Folstein SE, McHugh PR. ‘‘Mini-mental state’’: a
practical method for grading the cognitive state of patients for
the clinician. J Psychiatr Res 1975;12:189–98.
35. Kaufman DM, Zun L. A quantifiable, Brief Mental Status Exami-
nation for emergency patients. J Emerg Med 1995;13:449–56.
36. Kopecky HJ, Kopecky CR, Yudofsky SC. Reliability and validity
of the Overt Agitation Severity Scale in adult psychiatric inpa-
tients. Psychiatr Q 1998;69:301–23.
37. Silver JM, Yudofsky SC. The Overt Aggression Scale: overview
and guiding principles. J Neuropsychiatry Clin Neurosci 1991;3:
S22–9.
38. Swift RH, Harrigan EP, Cappelleri JC, et al. Validation of the be-
havioural activity rating scale (BARS): a novel measure of activity
in agitated patients. J Psychiatr Res 2002;36:87–95.
39. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-
Sedation Scale: validity and reliability in adult intensive care unit
patients. Am J Respir Crit Care Med 2002;166:1338–44.
40. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the
Sedation-Agitation Scale for adult critically ill patients. Crit
Care Med 1999;27:1325–9.
M. Gottlieb et al.
41. Robinson BRH, Berube M, Barr J, et al. Psychometric analysis of
subjective sedation scales in critically ill adults. Crit Care Med
2013;41(9 suppl 1):S16–29.
42. Gaynes BN, Brown CL, Lux LJ, et al. Preventing and de-escalating
aggressive behavior among adult psychiatric patients: a systematic
review of the evidence. Psychiatr Serv 2017;68:819–31.
43. Knox DK, Holloman GH Jr. Use and avoidance of seclusion and
restraint: consensus statement of the American Association for
emergency psychiatry project Beta seclusion and restraint work-
group. West J Emerg Med 2012;13:35–40.
44. Wilson MP, Pepper D, Currier GW, Holloman GH Jr, Feifel D. The
psychopharmacology of agitation: consensus statement of the
American Association for emergency psychiatry project Beta psy-
chopharmacology workgroup. West J Emerg Med 2012;13:26–34.
45. Richmond JS, Berlin JS, Fishkind AB, et al. Verbal de-escalation
of the agitated patient: consensus statement of the American Asso-
ciation for Emergency Psychiatry Project BETA De-escalation
Workgroup. West J Emerg Med 2012;13:17–25.
46. Somes J, Donatelli NS. Medicating the ‘‘out of control’’ older
adult. J Emerg Nurs 2016;42:75–7.
47. Zun L, Wilson MP, Nordstrom K. Treatment goal for agitation:
sedation or calming. Ann Emerg Med 2017;70:751–2.
48. Gault TI, Gray SM, Vilke GM, Wilson MP. Are oral medications
effective in the management of acute agitation? J Emerg Med
2012;43:854–9.
49. Currier GW, Simpson GM. Risperidone liquid concentrate and
oral lorazepam versus intramuscular haloperidol and intramus-
cular lorazepam for treatment of psychotic agitation. J Clin Psychi-
atry 2001;62:153–7.
50. Lejeune J, Larmo I, Chrzanowski W, et al. Oral risperidone plus
oral lorazepam versus standard care with intramuscular conven-
tional neuroleptics in the initial phase of treating individuals
with acute psychosis. Int Clin Psychopharmacol 2004;19:259–69.
51. Currier GW, Chou JC, Feifel D, et al. Acute treatment of psychotic
agitation: a randomized comparison of oral treatment with risper-
idone and lorazepam versus intramuscular treatment with haloper-
idol and lorazepam. J Clin Psychiatry 2004;65:386–94.
52. Kinon BJ, Ahl J, Rotelli MD, McMullen E. Efficacy of accelerated
dose titration of olanzapine with adjunctive lorazepam to treat
acute agitation in schizophrenia. Am J Emerg Med 2004;22:
181–6.
53. Hsu WY, Huang SS, Lee BS, Chiu NY. Comparison of intramus-
cular olanzapine, orally disintegrating olanzapine tablets, oral ris-
peridone solution, and intramuscular haloperidol in the
management of acute agitation in an acute care psychiatric ward
in Taiwan. J Clin Psychopharmacol 2010;30:230–4.
54. Lim HK, Kim JJ, Pae CU, et al. Comparison of risperidone orodis-
persible tablet and intramuscular haloperidol in the treatment of
acute psychotic agitation: a randomized open, prospective study.
Neuropsychobiology 2010;62:81–6.
55. Pascual JC, Pérez V, Martı́n JL, Safont G, Puigdemont D,
Alvarez E. Olanzapine orally-disintegrating tablet in severe psy-
chotic agitation: a naturalistic study. Actas Esp Psiquiatr 2007;
35:47–51.
56. Nobay F, Simon BC, Levitt MA, Dresden GM. A prospective,
double-blind, randomized trial of midazolam versus haloperidol
versus lorazepam in the chemical restraint of violent and severely
agitated patients. Acad Emerg Med 2004;11:744–9.
57. Isenberg DL, Jacobs D. Prehospital Agitation and Sedation Trial
(PhAST): a randomized control trial of intramuscular haloperidol
versus intramuscular midazolam for the sedation of the agitated or
violent patient in the prehospital environment. Prehosp Disaster
Med 2015;30:491–5.
58. Wirshing WC. Movement disorders associated with neuroleptic
treatment. J Clin Psychiatry 2001;62(suppl 21):15–8.
59. Wright P, Birkett M, David SR, et al. Double-blind, placebo-
controlled comparison of intramuscular olanzapine and intra-
muscular haloperidol in the treatment of acute agitation in
schizophrenia. Am J Psychiatry 2001;158:1149–51.
60. Meehan K, Zhang F, David S, et al. A double-blind, randomized
comparison of the efficacy and safety of intramuscular injections
Approach to the Agitated ED Patient
of olanzapine, lorazepam, or placebo in treating acutely agitated
patients diagnosed with bipolar mania. J Clin Psychopharmacol
2001;21:389–97.
61. Breier A, Meehan K, Birkett M, et al. A double-blind, placebo-
controlled dose-response comparison of intramuscular olanzapine
and haloperidol in the treatment of acute agitation in schizo-
phrenia. Arch Gen Psychiatry 2002;59:441–8.
62. Battaglia J, Lindborg SR, Alaka K, Meehan K, Wright P. Calming
versus sedative effects of intramuscular olanzapine in agitated pa-
tients. Am J Emerg Med 2003;21:192–8.
63. Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DC.
Intravenous droperidol or olanzapine as an adjunct to midazolam
for the acutely agitated patient: a multicenter, randomized,
double-blind, placebo-controlled clinical trial. Ann Emerg Med
2013;61:72–81.
64. Taylor DM, Yap CYL, Knott JC, et al. Midazolam-droperidol, dro-
peridol, or olanzapine for acute agitation: a randomized clinical
trial. Ann Emerg Med 2017;69:318–26.
65. Yap CYL, Taylor DM, Knott JC, et al. Intravenous midazolam-
droperidol combination, droperidol or olanzapine monotherapy
for methamphetamine-related acute agitation: subgroup analysis
of a randomized controlled trial. Addiction 2017;112:1262–9.
66. Centorrino F, Meyers AL, Ahl J, et al. An observational study of
the effectiveness and safety of intramuscular olanzapine in the
treatment of acute agitation in patients with bipolar mania or
schizophrenia/schizoaffective disorder. Hum Psychopharmacol
2007;22:455–62.
67. MacDonald K, Wilson M, Minassian A, et al. A naturalistic study
of intramuscular haloperidol versus intramuscular olanzapine for
the management of acute agitation. J Clin Psychopharmacol
2012;32:317–22.
68. Martel ML, Klein LR, Rivard RL, Cole JB. A large retrospective
cohort of patients receiving intravenous olanzapine in the emer-
gency department. Acad Emerg Med 2016;23:29–35.
69. Cole JB, Moore JC, Dolan BJ, et al. A prospective observa-
tional study of patients receiving intravenous and intramuscular
olanzapine in the emergency department. Ann Emerg Med
2017;69:327–36.
70. Lambert M, Schimmelmann BG, Karow A, Naber D. Subjective
well-being and initial dysphoric reaction under antipsychotic
drugs - concepts, measurement and clinical relevance. Pharmacop-
sychiatry 2003;36(suppl 3):S181–90.
71. Karow A, Schnedler D, Naber D. What would the patient choose?
Subjective comparison of atypical and typical neuroleptics. Phar-
macopsychiatry 2006;39:47–51.
72. Glassman AH, Bigger JT Jr. Antipsychotic drugs: prolonged QTc
interval, torsade de pointes, and sudden death. Am J Psychiatry
2001;158:1774–82.
73. Martel M, Sterzinger A, Miner J, Clinton J, Biros M. Management
of acute undifferentiated agitation in the emergency department: a
randomized double-blind trial of droperidol, ziprasidone, and mid-
azolam. Acad Emerg Med 2005;12:1167–72.
74. Battaglia J, Moss S, Rush J, et al. Haloperidol, lorazepam, or
both for psychotic agitation? A multicenter, prospective,
double-blind, emergency department study. Am J Emerg Med
1997;15:335–40.
75. Bieniek SA, Ownby RL, Penalver A, Dominguez RA. A double-
blind study of lorazepam versus the combination of haloperidol
and lorazepam in managing agitation. Pharmacotherapy 1998;
18:57–62.
76. Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with
haloperidol vs haloperidol alone on agitated delirium in patients
with advanced cancer receiving palliative care: a randomized clin-
ical trial. JAMA 2017;318:1047–56.
77. Linder LM, Ross CA, Weant KA. Ketamine for the acute manage-
ment of excited delirium and agitation in the prehospital setting.
Pharmacotherapy 2018;38:139–51.
78. Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect
of ketamine in man. Br J Anaesth 1981;53:27–30.
79. Le Cong M, Humble IA. Ketamine protocol and intubation rates
for psychiatric air medical retrieval. Air Med J 2015;34:357–9.
455
80. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ke-
tamine versus haloperidol for severe prehospital agitation. Clin
Toxicol (Phila) 2016;54:556–62.
81. Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Keta-
mine as a first-line treatment for severely agitated emergency
department patients. Am J Emerg Med 2017;35:1000–4.
82. Lahti AC, Koffel B, LaPorte D, Tamminga CA. Subanesthetic
doses of ketamine stimulate psychosis in schizophrenia. Neuro-
psychopharmacology 1995;13:9–19.
83. Lahti AC, Warfel D, Michaelidis T, Weiler MA, Frey K,
Tamminga CA. Long-term outcome of patients who receive keta-
mine during research. Biol Psychiatry 2001;49:869–75.
84. Cleary KK, Prescott K. The use of physical restraints in acute and
long-term care: an updated review of the evidence, regulations,
ethics, and legality. J Acute Care Phys Ther 2015;6:8–15.
85. Zun LS, Downey L. The use of seclusion in emergency medicine.
Gen Hosp Psychiatry 2005;27:365–71.
86. Downey LV, Zun LS, Gonzales SJ. Frequency of alternative to re-
straints and seclusion and uses of agitation reduction techniques in
the emergency department. Gen Hosp Psychiatry 2007;29:470–4.
87. Mohr WK, Petti TA, Mohr BD. Adverse effects associated with
physical restraint. Can J Psychiatry 2003;48:330–7.
88. Rubin BS, Dube AH, Mitchell EK. Asphyxial deaths due to phys-
ical restraint. A case series. Arch Fam Med 1993;2:405–8.
89. Evans D, Wood J, Lambert L. Patient injury and physical restraint
devices: a systematic review. J Adv Nurs 2003;41:274–82.
90. Berzlanovich AM, Schöpfer J, Keil W. Deaths due to physical re-
straint. Dtsch Arztebl Int 2012;109:27–32.
91. Gallop R, McCay E, Guha M, Khan P. The experience of hospital-
ization and restraint of women who have a history of childhood
sexual abuse. Health Care Women Int 1999;20:401–16.
92. Frueh BC, Knapp RG, Cusack KJ, et al. Patients’ reports of trau-
matic or harmful experiences within the psychiatric setting. Psy-
chiatr Serv 2005;56:1123–33.
93. Tadros A, Kiefer C. Violence in the emergency department: a
global problem. Psychiatr Clin North Am 2017;40:575–84.
94. Glezer A, Brendel RW. Beyond emergencies: the use of physical
restraints in medical and psychiatric settings. Harv Rev Psychiatry
2010;18:353–8.
95. Centers for Medicare and Medicaid Services. State Operations
Manual. Department of Health and Human Services; 2008. Available
at: https://www.cms.gov/Regulations-and-Guidance/Guidance/Tra
nsmittals/downloads/R37SOMA.pdf. Accessed December 3, 2017.
96. Grupp-Phelan J, Harman JS, Kelleher KJ. Trends in mental
health and chronic condition visits by children presenting
for care at U.S. emergency departments. Public Health Rep
2007;122:55–61.
97. Santillanes G, Gerson RS. Special considerations in the pediatric
psychiatric population. Psychiatr Clin North Am 2017;40:463–73.
98. Ratcliff SL, Meyer WJ 3rd, Cuervo LJ, Villarreal C, Thomas CR,
Herndon DN. The use of haloperidol and associated complications
in the agitated, acutely ill pediatric burn patient. J Burn Care Re-
habil 2004;25:472–8.
99. Cole JB, Klein LR, Strobel AM, Blanchard SR, Nahum R,
Martel ML. The use, safety, and efficacy of olanzapine in a Level
I pediatric trauma center emergency department over a 10-year
period. Pediatr Emerg Care 2017; https://doi.org/10.1097/
PEC.0000000000001231. [Epub ahead of print].
100. Altshuler LL, Hendrick V, Cohen LS. Course of mood and anxiety
disorders during pregnancy and the postpartum period. J Clin Psy-
chiatry 1998;59(suppl 2):29–33.
101. Yonkers KA, Vigod S, Ross LE. Diagnosis, pathophysiology, and
management of mood disorders in pregnant and postpartum
women. Obstet Gynecol 2011;117:961–77.
102. Viguera AC, Tondo L, Koukopoulos AE, Reginaldi D,
Lepri B, Baldessarini RJ. Episodes of mood disorders in
2,252 pregnancies and postpartum periods. Am J Psychiatry
2011;168:1179–85.
103. Aftab A, Shah AA. Behavioral emergencies: special consider-
ations in the pregnant patient. Psychiatr Clin North Am 2017;40:
435–48.
456
104. Ratnayake T, Libretto SE. No complications with risperidone
treatment before and throughout pregnancy and during the nursing
period. J Clin Psychiatry 2002;63:76–7.
105. Mackay FJ, Wilton LV, Pearce GL. The safety of risperidone: a
post-marketing study on 7684 patients. Hum Psychopharmacol
1998;13:413–8.
106. McCullar FW, Heggeness L. Limb malformations following
maternal use of haloperidol. JAMA 1975;231:62–4.
107. Iqbal MM, Aneja A, Rahman A, et al. The potential risks of
commonly prescribed antipsychotics: during pregnancy and lacta-
tion. Psychiatry (Edgmont) 2005;2:36–44.
108. Diav-Citrin O, Shechtman S, Ornoy S, et al. Safety of haloperidol
and penfluridol in pregnancy: a multicenter, prospective,
controlled study. J Clin Psychiatry 2005;66:317–22.
109. Dolovich LR, Addis A, Vaillancourt JM, Power JD, Koren G,
Einarson TR. Benzodiazepine use in pregnancy and major malfor-
mations or oral cleft: meta-analysis of cohort and case-control
studies. BMJ 1998;317:839–43.
110. Yonkers KA, Wisner KL, Stowe Z, et al. Management of bipolar
disorder during pregnancy and the postpartum period. Am J Psy-
chiatry 2004;161:608–20.
111. Wyszynski DF, Nambisan M, Surve T, et al., Antiepileptic drug
pregnancy registry. Increased rate of major malformations in
offspring exposed to valproate during pregnancy. Neurology
2005;64:961–5.
112. Jentink J, Loane MA, Dolk H, et al., EUROCATAntiepileptic Study
Working Group. Valproic acid monotherapy in pregnancy and major
congenital malformations. N Engl J Med 2010;362:2185–93.
113. Hernández-Dı́az S, Smith CR, Shen A, et al., North American
AED Pregnancy Registry. Comparative safety of antiepileptic
drugs during pregnancy. Neurology 2012;78:1692–9.
114. Correa-Villaseñor A, Ferencz C, Neill CA, Wilson PD,
Boughman JA. Ebstein’s malformation of the tricuspid valve: ge-
netic and environmental factors. The Baltimore-Washington Infant
Study Group. Teratology 1994;50:137–47.
M. Gottlieb et al.
115. Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML.
A reevaluation of risk of in utero exposure to lithium. JAMA 1994;
271:146–50.
116. Cohen LS. Treatment of bipolar disorder during pregnancy. J Clin
Psychiatry 2007;68(suppl 9):4–9.
117. ACOG Committee on Practice Bulletins-Obstetrics. ACOG Prac-
tice Bulletin: Clinical management guidelines for obstetrician-
gynecologists number 92, April 2008 (replaces practice bulletin
number 87, November 2007). Use of psychiatric medications dur-
ing pregnancy and lactation. Obstet Gynecol 2008;111:1001–20.
118. Rosa FW. Spina bifida in infants of women treated with carbamaz-
epine during pregnancy. N Engl J Med 1991;324:674–7.
119. Källén AJ. Maternal carbamazepine and infant spina bifida. Re-
prod Toxicol 1994;8:203–5.
120. Peisah C, Chan DK, McKay R, Kurrle SE, Reutens SG. Practical
guidelines for the acute emergency sedation of the severely
agitated older patient. Intern Med J 2011;41:651–7.
121. Aftab A, Shah AA. Behavioral emergencies: special consider-
ations in the geriatric psychiatric patient. Psychiatr Clin North
Am 2017;40:449–62.
122. Livingston G, Kelly L, Lewis-Holmes E, et al. Non-pharmaco-
logical interventions for agitation in dementia: systematic re-
view of randomised controlled trials. Br J Psychiatry 2014;
205:436–42.
123. Grymonpre RE, Mitenko PA, Sitar DS, Aoki FY, Montgomery PR.
Drug-associated hospital admissions in older medical patients. J
Am Geriatr Soc 1988;36:1092–8.
124. Kruse WH. Problems and pitfalls in the use of benzodiazepines in
the elderly. Drug Saf 1990;5:328–44.
125. Bogunovic OJ, Greenfield SF. Practical geriatrics: use of ben-
zodiazepines among elderly patients. Psychiatr Serv 2004;55:
233–5.
126. Castle NG, Mor V. Physical restraints in nursing homes: a review
of the literature since the Nursing Home Reform Act of 1987. Med
Care Res Rev 1998;55:139–70.
Approach to the Agitated ED Patient 457

ARTICLE SUMMARY
1. Why is this topic important?
The acutely agitated patient in the emergency depart-
ment (ED) can be common, and these patients require
rapid evaluation and management, including behavioral
control.
2. What does this review attempt to show?
This review seeks to provide an evidence-based evalu-
ation of the current ED assessment and management of
acute agitation.
3. What are the key findings?
Acute agitation is increasingly common in the ED, with
a wide range of etiologies including neurologic, infec-
tious, metabolic, toxicological, and psychiatric. Agitated
patients require rapid evaluation and management.
Focused history and physical examination are needed,
as well as rapid control of the patient’s agitation. Point-
of-care glucose test with additional testing depending on
the specific presentation is recommended. Management
should involve verbal de-escalation, followed by pharma-
cologic interventions. Physical restraints should be
reserved as a last resort. Pharmacologic options include
first-generation antipsychotics, second-generation anti-
psychotics, benzodiazepines, and ketamine. The manage-
ment of pediatric, pregnant, and elderly patients warrants
special consideration.
4. How is patient care impacted?
Acute agitation is a potentially life-threatening condi-
tion requiring immediate recognition and treatment.
Focused history and physical examination, along with
appropriate management strategies, can assist emergency
physicians in the safe and effective management of these
patients.