Agitation: What Every Emergency Physician Should Know
Agitation: What Every Emergency Physician Should Know
Does this happen in your ED? About half-way through your shift, the triage nurse brings you a restraint order form and asks you to sign it. You ask what is going on and are told that EMS is bringing in a combative patient, so Security is going to meet them at the ambulance entrance to restrain the patient and they need an order to so do. We emergency physicians, in the interest of staff safety and patient flow, usually sign the order. As discussed in this review, we probably should not be quick in our response to the "please sign this order" request.
J. Stephan Stapczynski, MD, Editor
Introduction
"When I treat a psychoneurotic, for instance, a hysterical patient ... I am compelled to find explanations for the first symptoms of the malady, which have long since disappeared, as well as for those existing symptoms which have brought the patient to me; and I find the former problem easier to solve than the more exigent one of today." Sigmund Freud1
Most emergency physicians think of agitation as one of the simplest cases to treat. "Haldol 'em, Ativan 'em, and forget 'em" is a common approach in many emergency departments, reflecting a prevailing view that all agitation is best treated with haloperidol and a benzodiazepine. As atypical antipsychotics have become increasingly used in the acute setting, it is clear that although haloperidol still may have its place, newer antipsychotics now may be preferred over haloperidol in many instances. In fact, the old practice of over-sedation ("sedate them until they sleep") actually may delay disposition of these patients from the emergency department, and with just a few such psychiatric patients sleeping in precious emergency department beds, waiting times for the entire emergency department may increase. In some cases, non-pharmacologic methods of behavior control, such as a verbal de-escalation or limit setting, may be effective without exposing the patient to the side effects of butyrophenones, the medication class that includes haloperidol and droperidol.
It also is becoming clearer that not all agitation is the same. This creates a dilemma for the emergency physician. In addition to a bewildering array of new antipsychotics with which emergency physicians are expected to become familiar, EM physicians also are expected to accurately categorize different types of agitation with their accompanying appropriate treatments. Thyroid storm, hypoxia, hypoglycemia, alcohol withdrawal, and schizophrenia, all of which may cause agitation, have different origins, treatments, and dispositions.
This review discusses agitation, how to approach a patient with undifferentiated agitation in the emergency setting, the proper goal of sedation, treatment options for agitation, treatment options for intoxicated patients with agitation, and physical restraints. Since most EM physicians are already well trained on agitation from medical causes such as alcohol withdrawal or hypoxia, the focus of this review is instead on agitation of a psychiatric origin. It also provides an evidence-based guideline for using antipsychotic agents in the emergency department or acute care setting, and reviews several studies not included in the last ACEP clinical policy on medication of psychiatric patients.2
What Is Agitation?
Although most practitioners "know it when they see it," agitation is not a diagnosis but rather a symptom. In fact, it is actually a poorly defined symptom at best. Roughly speaking, agitation can be defined as a temporary disruption of the typical physician-patient collaboration that has unintended consequences for the staff or other patients.3 These consequences may arise because the staff or physicians are exposed to threatening or violent behavior or because it becomes difficult to treat other patients if an agitated patient is disrupting the entire emergency department. Importantly, however, agitation involves violence or the potential of violence, not just resistance to following physician instructions, such as staring or refusing treatment.3
Not surprisingly, since agitation is difficult to define, its prevalence is somewhat difficult to measure. Many studies, therefore, have either investigated staff perceptions of safety or instances of physical aggression. The National Emergency Department Safety Study, for instance, which surveyed staff at 69 U.S. emergency departments, documented that at least 25% of ED staff felt safe at work "sometimes," "rarely," or "never."4 In another study conducted at a medium-size university teaching hospital, university police had to respond an average of twice daily to violent incidents, with most cases occurring at night.5 Although allied health staff bear the brunt of violence, physicians are not immune.6-8 In a survey conducted by Anglin and colleagues, for instance, nearly 22% of residents reported being fearful of assault at work.7 Taken together, these studies indicate that physical aggression toward ED staff is likely a significant and under-reported problem, with nursing staff feeling the most vulnerable.4,9-10
Agitation and its extreme form, aggression, have a wide variety of causes. Many underlying disorders, including substance intoxication, substance withdrawal, electrolyte disturbances, thyroid dysfunction, brain injury, dementia, or psychiatric disorders such as schizophrenia, may cause agitation.11 Diagnoses of mental disorders in the emergency department are particularly likely. Approximately 3.6% of all visits to U.S. emergency departments in 2006 resulted in some sort of diagnosis of psychosis, although likely not all of these patients were agitated.12
One of the first crucial steps in treating agitation is a provisional diagnosis of its cause. Although it isn't always easy to distinguish between agitation of psychiatric and medical origin,13 practitioners generally should rule out organic causes of delirium first before assuming that the agitation is psychiatric in etiology.14 Physicians always should check both an oxygen saturation and a finger-stick glucose level, as these are easily correctable causes of agitation. Beyond this, there are a few guidelines that can help further distinguish between psychiatric and medical causes of agitation.11,14-16
Does the patient lack a previous psychiatric history?
Are there any features atypical for a psychiatric diagnosis? Psychotic patients, for instance, are almost always alert and oriented. Lethargy and confusion strongly suggest a medical cause.
Are vitals signs abnormal? Although agitated patients can have elevated heart rates, this should resolve as the agitation resolves. There should never be a fever or low blood pressure.
Are the symptoms waxing and waning? This suggests delirium.
Did the symptoms have a sudden onset?
Are there nonauditory hallucinations?
Does the patient have a heavy drinking history? If so, consider Wernicke's encephalopathy.
Has the patient recently started any new medications, particularly steroids or anticholinergics?
If any of these questions can be answered yes, the patient deserves a medical workup before attributing symptoms to psychiatric agitation. Keep in mind that patients with previous psychiatric illness also may decompensate quickly in the presence of infection or medical illness, and so even established psychiatric patients may require a medical workup.
On the other hand, several factors suggest agitation of psychiatric origin. These include patients with an established psychiatric diagnosis, medication noncompliance, and normal vital signs.17 Established psychiatric patients who are not improving on antipsychotics, however, still may warrant a further medical workup.
How Should an Agitated Patient Be Approached in the Emergency Setting?
All agitated patients in the emergency department should be approached the same way carefully. No matter what the circumstance, the goals of agitation treatment are to protect and calm the patient; protect and calm the staff; allow the patient's participation in care to whatever extent possible; and finally, to foster evaluation and disposition. These goals are not necessarily achieved in order, but all involve boundary-setting on the part of the physician and coordination among ED staff.
Although all patients with threatening behavior should be considered for both chemical and physical restraint, determining which patients are likely to become violent is not an easy task. Previous work has identified a number of factors that predispose patients to violence, including young age; male gender; lack of education; a past history of victimization or substance abuse; a personality disorder; command hallucinations or paranoid delusions; and poor impulse control or insight.18 These factors, however, are mostly unhelpful for predicting violence in the emergency setting where a patient's past medical history or past or current psychological state may not be known extensively.
A recent study on community violence, however, offers some guidance as to which patients should be considered at higher risk of violence.19 In this community study, a sample of 34,653 persons was assessed via face-to-face interviews with trained interviewers at two time points. Psychiatric history, including mental illness, history of violence, and substance use, was assessed at time 1. At time 2, about two years apart for most participants, individuals were asked about violence between time 1 and time 2. Researchers found that individuals with a previous history of violence were more likely to repeat violent acts. In fact, past violent acts were the strongest predictor of future violence. A serious mental health diagnosis, such as schizophrenia, bipolar disorder, or major depression, alone did not make individuals any more likely than others to commit violent acts. However, an individual with any combination of these variables, such as an individual with a history of violence and substance abuse, was at higher risk of future violence. An individual with all three factors (previous history of violence, substance abuse, and a serious mental illness) was at the highest risk to commit more violent acts.
In a study of violent crime rates in Swedish schizophrenics, Fazel et al. found a slightly increased tendency toward violent crime in schizophrenics without substance use when compared to the general population (OR = 1.2).20 However, schizophrenics with substance abuse were 4.4 times as likely to commit a violent crime.
What does this mean for the practicing emergency physician? Certainly, caution should be used in extrapolating any results from a community setting to an emergency department. However, these studies do offer some useful guidance. Any psychiatric patient who has a previous history of violence, such as one who had to be restrained by police officers or EMS prior to transport, should be assumed to be at higher risk of repeat violent acts in the emergency department. If this psychiatric patient is abusing alcohol or drugs in addition, then he or she may be presumed to be at the highest risk of repeat violence while in the hospital. Of course, patients who do not meet any of these criteria, and thus have a lower risk of violence, still may become violent, so clinicians should use their best professional judgment when approaching patients. Staff reports of any violent actions by patients should be taken seriously.
Approaching any agitated patient, especially one considered to be at high risk for violence, should be done with safety of the ED staff in mind. "Safety first" starts with planning even before agitated patients arrive at the ED, with preparations to place them in a separate room away from other patients. Potential weapons and sharp instruments should not be located in close proximity to the patient, and staff should have an easy way of notifying security if the need arises.21-22
Once an agitated patient arrives in the emergency department, all efforts should be made to ensure that the patient is physically comfortable.22 Limit-setting while bargaining with food and drink can be an effective way of defusing a potentially hostile situation.23 If possible, external stimuli such as loud noises should be decreased. For patients who remain agitated but can be assessed safely, verbal intervention is the preferred initial treatment.3 Interestingly, there is little experimental evidence on this point, such as what sorts of verbal techniques to employ and how long verbal intervention must be used to be effective. However, given that there are no side effects to patients from being "talked down," many emergency psychiatrists recommend at least a brief verbal intervention if this can be done safely.
In terms of talking to patients, there are few experimental studies to offer guidance on this point. However, most experts recommend that practitioners adopt a calm, dominant presence.17,21 Practitioners should start by asking why the patient is angry or upset, as well as set limits on acceptable behavior while in the emergency department.24 Voluntary oral medication may be useful at this stage (options for medication are discussed later).
For those patients whose behavior continues to deteriorate or who refuse medication, a show of force typically is recommended.3 This is often termed a "show of concern" instead of a "show of force," in order to reinforce the caring nature of the intervention. Again, there is little experimental evidence to offer guidance for EM physicians. However, it seems reasonable that having security officers close at hand will reinforce appropriate limits in the emergency department. If medication is needed, patients once again can be offered medication during a show of concern. If their behavior continues to deteriorate or they again refuse oral medication, IM or IV medication then should be administered.
The decision to force IM or IV medications often is made with little forethought. In general, emergency physicians must make a determination that a patient lacks the capacity to make decisions about his or her own care during the emergency department visit. Patients who cannot appreciate a situation or its consequences, such as those who are violent toward themselves, other patients, or staff, do not have decisional capacity.25 Simply being on a psychiatric hold generally is not grounds for forcing medication or procedures, unless the patient's illness makes it impossible for him or her to participate in his or her own care.
The choice of medication in most instances will be guided by the type of agitation. Agitation that is not psychiatric in origin generally should not be treated with antipsychotics. Hypoglycemia, for instance, should be treated with glucose, hypoxia with oxygen, and thyroid storm with appropriate beta-blockers and anti-thyroid medications, etc. Substance withdrawal typically is treated with benzodiazepines. The appropriate treatment for agitation resulting from alcohol intoxication, commonly encountered in emergency departments, is controversial and is discussed later. In general, placing an intoxicated patient in a quiet environment may have the fewest side effects of all.
If a patient's behavior continues to deteriorate, physical restraints are a last resort. In general, this means that the practitioner has been unable to establish any sort of therapeutic relationship with the patient other than by means of brute force. Restraints should be used sparingly, with as minimal force as possible, and only when necessary to protect the patient or staff.
What Is the Proper Goal of Sedation?
Many emergency physicians and staff think that the only properly sedated patient is one who is sleeping, despite multiple appeals from consensus-based expert reviews for "calming" instead of outright sedation.3,21,26 Current guidelines on sedation state that the proper goal of sedation is to calm patients and reduce the risk of violence, while still allowing them to participate in their own care as much as possible.3
More practically, however, patients who are not asleep are easier to obtain a disposition from the emergency department. Sleeping patients generally cannot be evaluated by consultants and so must be held for a length of time in the emergency department. Some research indicates that both waiting room times and length of stay for all emergency department patients increase in a step-wise fashion as the number of psychiatric holds in the emergency department increases. Thus, it is prudent to avoid over-sedating agitated patients as long as staff still can be protected from violence on the part of the patient.27
Is Haloperidol Really the Best Medicine?
There are a number of different options for chemical restraint in the emergency setting, with haloperidol plus lorazepam perhaps being the most common antipsychotic combination among U.S. emergency physicians.28
Haloperidol is a butyrophenone with primary activity at the dopamine 2 (D2) receptor. It has little activity at other receptor types and, as such, is considered a classical antipsychotic. Classical antipsychotics may be divided into low-potency (such as chlorpromazine) or high-potency (haloperidol, droperidol) according to the affinity for the drug at the D2 receptor. Although the exact mechanisms are yet to be understood, dopamine dysfunction is thought to be at the core of many of the clinical expressions of schizophrenia.29
Haloperidol has a number of properties that make it attractive for use in the emergency department. First is its long record of safety in emergency settings.30 The drug has minimal effects on vital signs, even if the patient is oversedated, meaning that patients are not likely to become hypotensive or suffer from respiratory depression with its use. It also has no anticholinergic activity and minimal interactions with other non-psychiatric medications.
On the negative side, haloperidol now carries a black-box warning about the risks of using it to treat dementia-related psychosis. It lengthens QT intervals and should be used cautiously in patients whose intervals are already prolonged or who are taking other QT-prolonging drugs. Finally, because of its action at the D2 receptor, which is located primarily in the basal ganglia, haloperidol may cause dystonic or other extrapyramidal reactions.
In the largest study of haloperidol in the emergency department, Battaglia and colleagues studied haloperidol and lorazepam in 98 psychotic agitated patients in five U.S. emergency departments.31 In this study, patients were randomly assigned to receive either IM lorazepam 2 mg, IM haloperidol 5 mg, or both in combination. Although all patients had a significant reduction in agitation, this reduction was more rapid in patients receiving the combination of haloperidol plus lorazepam. In addition, the number of extrapyramidal symptoms, defined as dystonia, hypertonia, or tremor, was highest in patients receiving haloperidol alone. Approximately 20% of this group experienced motor side effects, compared to 6% of patients who received the combination and 3% of patients who received lorazepam alone. Although the haloperidol plus lorazepam group spent more time sleeping, the authors concluded that if haloperidol is given, it should be given with lorazepam, since the combination was more effective with a lower risk of side effects. A Cochrane review in 2005, however, concluded that there was not enough evidence to recommend haloperidol plus lorazepam over another combination such as haloperidol plus promethazine without further research.32
Atypical antipsychotics, also called second-generation antipsychotics or SGAs, also act at the D2 receptor, but as a group, they have less affinity at this receptor.33 These medications target other receptors besides dopamine, including serotonin, histamine, and alpha-2 receptors. This means that patients who overdose with these medications can present with a variety of different signs and symptoms. Ziprasidone, for instance, has an affinity some 10 times higher for serotonin receptors than for D2 receptors.34 Olanzapine and quetiapine, on the other hand, have relatively high affinities for the histamine receptor. This fact makes these latter two medications relatively more sedating than others in the class. Olanzapine also targets the alpha-1 receptor, and case reports of hypotension have been reported with its use, especially if this medication is combined with benzodiazepines.35 In human volunteers taking therapeutic doses, atypical antipsychotics lengthened QT intervals, with ziprasidone being perhaps the worst offender. However, this prolongation generally is less severe than with classical antipsychotics such as haloperidol.36 No patient in this study developed a QTc > 500 msec. Whether this fact matters for long-term mortality in patients on daily therapy, however, recently has been called into question.37
With the exception of risperidone, there are no randomized controlled trials of atypical antipsychotics in the emergency department.38-49 Most research on atypical antipsychotics has been performed in recently hospitalized patients who are agitated.50-62 Available data from both settings indicate that each drug in the class is effective in reducing agitation when compared to placebo,63-64 is at least as calming as haloperidol in the studies that have directly compared it,39-40,43,46,48,50-52,59-60 and has a lower incidence of movement-related side effects compared to haloperidol alone.61-64 Many of these trials, however, are industry-sponsored.
Unfortunately, to date there have been no head-to-head trials of the atypical antipsychotics, and so the relative effectiveness of these drugs is unknown. However, several meta-analyses of these medications have been conducted. These analyses have limitations, as trials examining each medication generally have used different rating scales and definitions of efficacy. One meta-analysis of atypical antipsychotics by Citrome65 compared the response at two hours after the first injection of olanzapine, ziprasidone, aripiprazole, haloperidol, or lorazepam. This meta-analysis converted individual trials into number needed to treat (NNT), and then compared different second-generation antipsychotics (SGAs) on that common scale. When comparing in this manner, most SGAs appear equivalent in terms of efficacy. This does not, however, include aripiprazole, which has a slightly higher NNT than other SGAs. In addition, a randomized controlled trial of 301 hospitalized patients showed that, while effective against placebo, IM aripiprazole was similar in efficacy to IM lorazepam, although with a lower incidence of sedation.61 A third study showed that IM aripiprazole was as effective as haloperidol, although not as quickly sedating.50 For these reasons, aripiprazole cannot yet be recommended for use in the emergency department. Atypical antipsychotics that have been studied in the emergency department or acute settings, along with their recommended dosages, are listed in Table 1.
So what is the benefit of using atypical antipsychotics if they are of comparable efficacy to haloperidol? First, nearly every study that has compared haloperidol against an atypical antipsychotic has found a lower incidence of dystonic reactions with an atypical antipsychotic. This research, however, extends only to haloperidol alone.66-70 Few studies have examined haloperidol plus an anticholinergic or benzodiazepine as is typically utilized in the emergency department. Comparisons of atypical antipsychotics with the combination of haloperidol plus promethazine have shown similar rates of acute dystonias, although haloperidol plus promethazine studies were not double-blinded and so findings may be difficult to compare with randomized controlled trials.71-72 Second, at least one study has found a trend toward more rapid disposition with an atypical antipsychotic such as ziprasidone.45 A second study by Currier and colleagues described in the next section has found that treatment with an atypical antipsychotic such as risperidone calms patients just as effectively as haloperidol without oversedating them to the point of sleepiness.40 If patients are asleep, they cannot be evaluated effectively by psychiatry consultants, necessitating a psychiatric hold and prolonged ED time.
Do All Patients Have to Get a Shot?
Many emergency department physicians rely on IM injections for agitated patients, since intuitively, IM medication should work more rapidly than oral medication. This, however, may not be the case. In two studies, oral risperidone and oral lorazepam were effective as rapidly as IM haloperidol and IM lorazepam.39-40 In a randomized rater-blinded study conducted by Currier and colleagues (2004; an earlier study in 2001 was a convenience sample only), 162 patients who were agitated from active psychosis were randomly assigned either 2 mg risperidone plus 2 mg lorazepam PO or 5 mg haloperidol plus 2 mg lorazepam IM. At all time points, beginning 30 minutes after medication administration, PO medications were just as effective as IM medications. However, by 30 minutes, a significantly lower percentage of patients who received PO medication could not be evaluated because they were asleep (6%) compared to patients who received the IM injections (21%). This difference was even larger by 60 minutes (23% vs. 43%).
Although the study only included patients who were capable of giving informed consent, and thus capable of swallowing oral medications, the severity of illness was comparable between the two groups. The authors concluded that PO medication was just as effective as IM injections without oversedation. Given that the authors included emergency department patients in the study, this has implications for the treatment of agitated patients by emergency physicians. All patients who need medication should be considered for use of an oral medication first. If feasible, use of oral medications helps to maintain a therapeutic relationship since patients are not being forced to take medication against their will. It also protects staff who would have to restrain the patient and prevents accidental needlestick injuries.
How and When Should a Patient Be Restrained?
Restraint of a patient is encountered frequently in practice and has been reported in up to 3.7% of all patients in one urban ED.73-74 The decision to restrain a patient, although monumental in terms of the philosophical and legal implications, often is made with very little thought. The advantages to restraining a patient are obvious, in that it primarily protects staff from a violent patient and facilitates IM delivery of medications. In all 50 states, EM physicians are required by law to detain patients who are judged to be a danger to themselves or others.75
The disadvantages of restraint are many. Improperly applied restraints may cause injury to the patient.76-77 Philosophically, there are further disadvantages to restraints in that they do not allow the patient's participation in care.3 Ethically, restraints are equivalent to arrest in that they deprive a patient of liberty to leave a situation if desired.
Appropriate restraints generally are applied either in two points (upper extremities only) or four points (upper and lower extremities), since there may be a risk of asphyxiation with torso or posey restraints. Restraints generally should be applied with a minimum of force, which usually requires multiple individuals. Healthcare providers should make every attempt to avoid standing or sitting on a patient during application, and if weight force needs to be used, it should be applied for as short of a time as possible with careful monitoring of the patient's ventilatory status.17 Many physicians often wish to stand aside during forceful takedown of patients so as to maintain a therapeutic relationship as much as possible. Anecdotally, however, physician assistance during takedown may reassure staff and patients that these procedures will be done as gently as possible. This should only occur if the physician has been trained to assist in these procedures, as an untrained individual could place both the patient and restraining staff at risk for injury if they are not working together as a team.
Restraints also can be considered ethically problematic, since medication and restraint procedures must be used against the patient's wishes. Although controversial, the right of psychiatric patients to refuse forced treatment has been upheld by several courts.22 This does not apply when a patient lacks capacity in the emergent setting, but physicians always must be mindful to allow patient participation in care as much as possible. In general, restraints should be used only if the patient is extremely agitated or if the staff are in danger. Patient wishes should be overridden only if it is clearly in the patient's best interests, and such a conclusion should be clearly noted in the chart. Providers should be aware of current CMS regulations, which require evaluation by a healthcare provider within one hour for restrained patients. Physicians can delegate or verbally order restraints but are accountable for any actions taken under their license by other individuals.
Whether to restrain a patient who has not been chemically sedated is somewhat controversial and depends on many factors, including patient willingness to take medication, degree of agitation and perceived risk of violence, and the availability of trained personnel to assist in the restraint process. A patient willing to take oral medications voluntarily typically will not need restraint. But once the decision is made to treat a patient involuntarily with IM medications and restraint, the planning for successful execution must occur. Many physicians restrain the patient first, then deliver the IM or IV medication, and have even developed algorithms for this approach.78 Others attempt to hold down the patient, administer IM medication, and then continue with the restraint process if it still is deemed necessary. Most believe that if an agitated patient needs to be restrained, the patient then should be treated with chemical restraint. There have been deaths reported in highly agitated patients who received only physical restraint without subsequent chemical restraint,76-77 although death can occur in patients exhibiting signs of extreme agitation who have already received medical therapy. More importantly, it seems ethically inappropriate to leave a patient in physical restraints without administering calming medication. Thus, although patients sometimes may need to be physically restrained in order to receive medication, physical restraint almost always should be accompanied by chemical restraint as well.
Agitation Due to Alcohol Intoxication
One of the more controversial topics concerns treatment of the belligerent alcohol intoxicated patient. Alcohol abuse is a common problem in the emergency department, with an estimated 10-46% of visits related to this.79 In addition, alcohol can be, and often is, a factor in almost every type of injury, and EM physicians often must treat these patients for reasons other than agitation.
There is very little evidence-based guidance for how and when to sedate the intoxicated agitated patient. Three studies conducted in the emergency department are worthy of note. First, Martel, et al. compared IM droperidol 5 mg vs. IM ziprasidone 20 mg vs. IM midazolam 5 mg.44 This prospective, double-blind emergency department study compared 144 patients with undifferentiated agitation. Greater than 90% in each group had alcohol use. Agitated patients required additional medications less in the droperidol and ziprasidone groups. Respiratory depression requiring supplemental oxygen occurred in 4 of 50 patients receiving droperidol, 7 of 46 patients receiving ziprasidone, and 10 of 48 patients receiving midazolam, but was statistically similar regardless of medication choice. No patients required endotracheal intubation.
Nobay and colleagues compared IM midazolam 5 mg vs IM lorazepam 2 mg vs IM haloperidol 5 mg.80 This randomized prospective study examined a convenience sample of 111 physically restrained patients in a county teaching hospital emergency department. There was approximately 30% alcohol use across groups. In this study, there was a shorter time to sedation and subsequent arousal with midazolam. Although the raw data were not reported, the authors state that no differences were found either in respiratory rate or oxygen saturation across groups.
Finally, Knott, et al. compared IV midazolam 5 mg vs IV droperidol 5 mg.81 This randomized double-blind trial examined 153 patients with undifferentiated agitation. Approximately one-third of these patients had alcohol use. In this study, 4 of 74 patients in the midazolam group had documented hypoxia below 90%, with airway management required in 3 patients. Three patients of 79 in the droperidol group had documented hypoxia, with none requiring airway management.
There is limited evidence of superiority for certain agents to be used in treating patients with acute agitation in the ED. In general, all patients who can be approached safely should have a verbal intervention first and be placed into a dark, quiet room if the fear of acute decompensation is very low. If either intervention is successful, medication becomes unnecessary. If medication is required, either second-generation antipsychotics or benzodiazepines may be used and should be offered orally if deemed an option by the physician. Cardiac monitoring and arousal checks should be performed in patients who require significant doses of medication to control the agitation or who were significantly sedated by the medications. The latest expert consensus guidelines also make no first-line medication recommendations in this situation, although benzodiazepines are preferred second-line agents because of the possibility that a component of alcohol withdrawal is contributing to the patient's agitation.3
Conclusions
Agitated patients are a common problem faced by emergency physicians. Although many EM physicians traditionally have believed this to be a simple problem that just requires treatment with haloperidol plus lorazepam, this medication combination can cause side effects and create more sedation in the patients, making evaluation challenging for consultants and ultimately delaying disposition.
Based on current consensus evidence and experimental trials, a simplified algorithm may be developed for agitation in the emergency department. (See Figure 1.) First, any agitated patient should be approached with safety in mind. A trial of verbal de-escalation and then a "show of concern" in patients who require it should be attempted if this can be done safely. Patients who require medication should have a focused history and physical examination to determine the cause of the agitation. Underlying medical problems should be treated first, as a potential pitfall is administering antipsychotics to a patient who really has an underlying disorder such as hypoxemia or hypoglycemia. If the cause of the agitation cannot be determined, benzodiazepines are first-line agents. If the cause of the agitation is a medical condition that persists after treatment or that is not better treated with other medications, low-dose haloperidol alone may be useful.82
If, on the other hand, the agitation most likely is psychiatric in origin, atypical antipsychotics such as risperidone, olanzapine, or ziprasidone are preferred to haloperidol alone. If haloperidol is administered, it should not be given alone in order to prevent the occurrence of motor-related side effects. If haloperidol is given, it should be given with an anticholinergic such as promethazine. Although haloperidol plus benzodiazepines also may be given in combination, the scant evidence in the literature would suggest that the risk of motor-related side effects still is higher than with second-generation antipsychotics (approximately 6% in Battaglia et al for haloperidol plus lorazepam31). At the time of this review, there is insufficient evidence to recommend atypical antipsychotics over haloperidol plus promethazine in the emergency department, although haloperidol plus promethazine may be more sedating. In general, however, newer antipsychotic agents have an established track record of safety in the emergency department and have fewer side effects such as dystonic reactions than haloperidol alone and may require less repeat dosing.28
Although restraints sometimes are necessary, they should be used sparingly and only to protect the staff or patient from harm while medications are administered. Although agitated patients often elicit hostile or angry feelings from staff, restraints never should be used as punishment. Uncooperative patients who are capable of making their own decisions should be discharged from the emergency department instead.
In summary, agitation usually requires a team-oriented approach. It makes little sense for a physician to attempt to calm a patient, for instance, if the staff does not appreciate the necessity of verbal de-escalation. In addition, physicians continually should be aware that nursing staff often bear the brunt of patient violence, and so should remain sensitive to nursing requests for additional sedation or the need for restraints. Physician presence at the bedside may be helpful until a potentially violent patient is chemically or physically restrained. Calming sedation, however, does not mean sleep. Antipsychotics should be chosen judiciously to allow patients to participate in their own care if possible and eventually to obtain a disposition from the emergency department.
Acknowledgements: The authors would like to acknowledge Kai S. MacDonald, MD, for helpful discussions on earlier portions of this work, particularly the suggested agitation protocol, and Kathy Harper, RN, for helpful research on the bibliography of this work.
References
1. Freud S, Brill AA, ed. The Basic Writings of Sigmund Freud. New York: New York Modern Library: 1995;973.
2. Shahabuddin S, Allen MH, Currier GW, et al. Clinical policy: Critical issues in the diagnosis and management of the adult psychiatric patient in the emergency department. Ann Emerg Med 2006;47:79-99.
3. Allen MH, Currier GW, Hughes DH, et al. Expert consensus guideline series: Treatment of behavioral emergencies. Postgrad Med 2001:1-88.
4. Kansagra SM, Rao SR, Sullivan AF, et al. A survey of workplace violence across 65 US emergency departments. Acad Emerg Med 2008;15:1268-1274.
5. Pane GA, Winiarski AM, Salness KA. Aggression directed toward emergency department staff at a university teaching hospital. Ann Emerg Med 1991;20: 283-286.
6. 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;6:301-304.
7. Anglin D, Kyriacou DN, Hutson HR. Residents' perspectives on violence and personal safety in the emergency department. Ann Emerg Med 1994;23:1082-1084.
8. Hobbs FD, Keane UM. Aggression against doctors: A review. J R Soc Med 1996;89: 69-72.
9. Atawneh FA, Zahid MA, Al-Sahlawi KS, et al. Violence against nurses in hospitals: Prevalence and effects. Br J Nurs 2003;12:102-107.
10. Catlette M. A descriptive study of the perceptions of workplace violence and safety strategies of nurses working in level I trauma centers. J Emerg Nurs 2005;31:519-525.
11. Richards CF, Gurr DE. Psychosis. Emerg Med Clin North Am 2000;28:253-262.
12. Pitts SR, Niska RW, Xu J, et al. National hospital ambulatory medical care survey: 2006 emergency department summary. Natl Health Stat Report 2008;7:1-38.
13. Binder RL, McNiel DE. Contemporary practices in managing acutely violent patients in 20 psychiatric emergency rooms. Psychiatr Serv 1999;50:1553-1554.
14. Murphy BA. Delirium. Emerg Med Clin North Am 2000;18:243-252.
15. Talbot-Stern JK, Green T, Royle TJ. Psychiatric manifestations of systemic illness. Emerg Med Clin North Am 2000;18:199-209.
16. Zimbroff DL. Pharmacologic control of acute agitation. CNS Drugs 2008;22: 199-212.
17. Marco CA, Vaughan J. Emergency management of agitation in schizophrenia. Amer J Emerg Med 2005;23:767-776.
18. Villari V, Rocca P, Bogetto F. Emergency psychiatry. Minerva Med 2007;98:525-541.
19. Elbogen EB, Johnson SC. The intricate link between violence and mental disorder. Arch Gen Psychiatry 2009;66:152-161.
20. Fazel S, Langstrom N, Hjern A, et al. Schizophrenia, substance abuse, and violent crime. JAMA 2009;301:2016-2023.
21. Marder SR. A review of agitation in mental illness: Treatment guidelines and current therapies. J Clin Psychiatry 2006;67(suppl 10):13-21.
22. Hill S, Petit J. The violent patient. Emerg Med Clin North Am 2000;18:301-315.
23. Rund DA, Ewing JD, Mitzel K, et al. The use of intramuscular benzodiazepines and antipsychotic agents in the treatment of acute agitation or violence in the emergency department. J Emerg Med 2006;31: 317-324.
24. Blanchard J C, Curtis KM. Violence in the emergency department. Emerg Med Clin North Am 1999;17:717-31, viii.
25. Miller SS, Marin DB. Assessing capacity. Emerg Med Clin North Am 2000;18: 233-242.
26. Battaglia J. Pharmacologic management of acute agitation. Drugs 2005;65:1207-1222.
27. Killeen J, Castillo E, Chan TC, et al. Impact of psychiatric patient holds in the emergency department on overcrowding. 2008; Abstract presented at the conference of the American College of Emergency Physicians, Chicago, Illinois.
28. MacDonald KS, Wilson M, Minassian A, et al. A naturalistic study of haloperidol versus intramuscular olanzapine for the management of acute agitation. Manuscript in submission.
29. Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: Version III – the final common pathway. Schizophr Bull 2009;35:549-562.
30. Clinton JE, Sterner S, Stelmachers Z, et al. Haloperidol for sedation of disruptive emergency patients. Ann Emerg Med 1987;16:319-322.
31. Battaglia J, Moss S, Rush J, et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Amer J Emerg Med 1997;15:335-340.
32. Gillies D, Beck A, McCloud A, et al. Benzodiazepines alone or in combination with antipsychotic drugs for acute psychosis. Cochrane Database Syst Rev 2005;4:CD003079.
33. Strange PG. Antipsychotic drug action: Antagonism, inverse agonism or partial agonism. Trends Pharmacol Sci 2008;29: 314-321.
34. Warrington L, Lombardo I, Loebel A, et al. Ziprasidone for the treatment of acute manic or mixed episodes associated with bipolar disorder. CNS Drugs 2007;21: 835-849.
35. Zacher JL, Roche-Desilets J. Hypotension secondary to the combination of intramuscular olanzapine and intramuscular lorazepam. J Clin Psychiatry 2005;66: 1614-1615.
36. Harrigan EP, Micelli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol 2004;24:62-69.
37. Ray W, Chung CP, Murray KT, et al. Atypical antipsychotics and the risk of sudden cardiac death. N Engl J Med 2009; 260:225-235.
38. 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 Clin Exp 2007;22:455-462.
39. Currier GW, Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001;62:153-157.
40. Currier GW, Chou JC, Feifel D, et al. Acute treatment of psychotic agitation: A randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004;65: 386-394.
41. Damsa C, Adam E, Lazignac C, et al. Intramuscular olanzapine in patients with schizophrenia: An observational study in an emergency room. Bull Soc Sci Med 2008; 209:209-216.
42. Jangro WC, Preval H, Southard R, et al. Conventional intramuscular sedatives versus ziprasidone for severe agitation in adolescents: Case-control study. Child Adolesc Psychiatry Ment Health 2009;3:9.
43. Kohen I, Preval H, Southard R, et al. Naturalistic study of intramuscular ziprasidone versus conventional agents in agitated elderly patients: Retrospective findings from a psychiatric emergency service. Amer J Geriatr Pharmacother 2005;3:240-245.
44. Martel M, Sterzinger A, Miner J, et al. Management of acute undifferentiated agitation in the emergency department: A randomized double-blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005;12:1167-1172.
45. Preval H, Klotz SG, Southard R, et al. Rapid-acting IM ziprasidone in a psychiatric emergency service: A naturalistic study. Gen Hosp Psychiatry 2005;27:140-144.
46. Raveendran NS. Rapid tranquilisation in psychiatric emergency settings in India: Pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine. BMJ 2007;335:865.
47. San L, Arranz B, Querejeta I, et al. A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients. Eur Psychiatry 2006;21;539-543.
48. Veser FH, Veser BD, McMullan JT, et al. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006;12:103-108.
49. Yildiz A, Turgay A, Alpay M, et al. Observational data on the antiagitation effect of risperidone tablets in emergency settings. Int J Psych Clin Pract 2003;7: 217-221.
50. Andrezina R, Josiassen RC, Marcus RN, et al. Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: A double-blind, placebo-controlled comparison with intramuscular haloperidol. Psychopharmacology 2006;188:281-292.
51. 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 schizophrenia. Arch Gen Psychiatry 2002;59:441-448.
52. Brook S, Lucey JV, Gunn KP, and the Ziprasidone IM study group. Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. J Clin Psychiatry 2000;61:933-941.
53. Daniel DG, Potkin SG, Reeves KR, et al. Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis. Psychopharmacology (Berl) 2001;155:128-134.
54. Jones B, Taylor CC, Meehan K. The efficacy of a rapid-acting intramuscular formulation of olanzapine for positive symptoms. J Clin Psychiatry 2001;62(suppl 2):22-24.
55. Lesem MD, Zajecka JM, Swift RH, et al. Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients. J Clin Psychiatry 2001;62:12-18.
56. Meehan K, Zhang F, David S, et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001;21:389-397.
57. Meehan K, Wang H, David SR, et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, or placebo in treating acutely agitated patients with dementia. Neuropsychopharmacology 2002;26: 494-504.
58. Tran-Johnson TK, Sack DA, Marcus RN, et al. Efficacy and safety of intramuscular aripiprazole: A randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2007;68:111-119.
59. Wright P, Birkett M, David SR, et al. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry 2001;7:1149-1151.
60. Wright P, Lindborg SR, Birkett M, et al. Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia: Antipsychotic efficacy and extrapyramidal safety during the first 24 hours of treatment. Can J Psychiatry 2003;48:716-721.
61. Zimbroff DL, Marcus RN, Manos G, et al. Management of acute agitation in patients with bipolar disorder: Efficacy and safety of intramuscular aripiprazole. J Clin Psychopharmacol 2007;27:171-176.
62. Battaglia J, Lindborg SR, Alaka K, et al. Calming versus sedative effects of intramuscular olanzapine in agitated patients. Am J Emerg Med 2003;21:192-198.
63. Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: A systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 2007;64: 442-455.
64. Smith LA, Cornelius V, Warnock A, et al. Pharmacologic interventions for acute bipolar mania: A systematic review of randomized placebo-controlled trials. Bipolar Disord 2007;9:551-560.
65. Citrome L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: A quantitative review of efficacy and safety. J Clin Psychiatry 2007;68: 1876-1885.
66. Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry 2008;21:151-156.
67. Currier GW, Trenton A. Pharmacologic treatment of psychotic agitation. CNS Drugs 2002;16:219-228.
68. Dolder CR, Jeste DV. Incidence of tardive dyskinesia with typical versus atypical antipsychotics in very high-risk patients. Biol Psychiatry 2003;53:1142-1145.
69. Kane JM. Tardive dyskinesia rates with atypical antipsychotics in adults: Prevalence and incidence. J Clin Psychiatry 2004; 65suppl 9:16-20.
70. San L, Arranz B, Escobar R. Pharmacological management of acutely agitated schizophrenic patients. Curr Pharm Des 2005;11:2471-2477.
71. Huf G, Alexander J, Allen MH, et al. Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database Syst Rev 2009;3:CD005146.
72. Satterthwaite TD, Wolf DH, Rosenheck RA, et al. A meta-analysis of the risk of extrapyramidal symptoms with intramuscular antipsychotics for the treatment of agitation. J Clin Psychiatry 2008;69:1869-1879.
73. Currier GW, Allen MH. Physical and chemical restraint in the psychiatric emergency service. Psychiatr Serv 2000;52:717-719.
74. Lavoie FW. Consent, involuntary treatment, and the use of force in an urban emergency department. Ann Emerg Med 1992;21:25-32.
75. Tueth MJ. Management of behavioral emergencies. Amer J Emerg Med 1995; 13:344-350.
76. Park KS, Korn CS, Henderson SO. Agitated delirium and sudden death: Two case reports. Prehosp Emerg Care 2001; 5:214-216.
77. Vilke GM, Chan TC. Agitated delirium and sudden death. Prehosp Emerg Care 2002; 6:259.
78. Rintoul Y, Wynaden D, McGowan M. Managing aggression in the emergency department: Promoting an interdisciplinary approach. Int Emerg Nursing 2009; in press.
79. D'Onofrio G, Becker B, Woolard RH. The impact of alcohol, tobacco, and other drug use and abuse in the emergency department. Emerg Med Clin North Am 2006; 24:925-967.
80. Nobay F, Simon BC, Levitt MA, et al. 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;11:744-749.
81. Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med 2006;47:61-67.
82. Lonergan E, Britton AM, Luxenberg J, et al. Antipsychotics for delirium. Cochrane Database Syst Rev 2007;2:CD005594.
83. Zyprexa (olanzapine) package insert. 2005; Indianapolis: Lilly Research laboratories. 81. Zyprexa (olanzapine) package insert. 2005; Indianapolis: Lilly Research Laboratories.
84. Wilson MP, MacDonald KS, Feifel D. Is respiratory depression a safety risk when combining olanzapine and benzodiazepines? Manuscript in preparation.
Does this happen in your ED? About half-way through your shift, the triage nurse brings you a restraint order form and asks you to sign it. You ask what is going on and are told that EMS is bringing in a combative patient, so Security is going to meet them at the ambulance entrance to restrain the patient and they need an order to so do.Subscribe Now for Access
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