Authors: Aditya ‘Al’ Lulla (MS-III at UCLA David Geffen School of Medicine) and Manpreet Singh, MD (EM Chief Resident at Harbor-UCLA Medical Center – @MPrizzleER) // Editors: Justin Bright, MD (@JBright2021) and Alex Koyfman, MD (@EMHighAK)

Introduction:

On a daily basis, emergency physicians encounter challenging patients that are acutely agitated, violent, or psychotic. Patients can behave this way for a variety of reasons, which include: intoxication, underlying mental illness, head injury, metabolic disturbances, infection, or a host of other organic and social reasons. Regardless of the cause, it’s imperative that the emergency physician rapidly identify these patients in order to ensure the well being of all healthcare providers, family members, and the patient. This is where the ED take down comes into play. The following article will outline the basics of the ED take down, which can be divided into physical restraint and chemical sedation.

Physical Restraints:

The use of physical restraints has long been a controversial aspect of healthcare with many ethical and legal considerations which vary by state. These legalities are beyond the scope of this topic. Prior to using restraints, verbal techniques should be tried to help de-escalate a potentially volatile patient. While attempting verbal de-escalation, the provider already needs to be planning for physical restraint and/or chemical sedation. Rational patients recognize that they are in a safe place with people who can help them. Irrational, psychotic, angry, intoxicated, and altered patients do not. As a result, verbal de-escalation does not always work, and sometimes it even has the opposite desired effect. If the patient continues to be an imminent harm to self or others, physical restraints should be utilized.

The following stepwise approach can be used to applying physical restraints:

Organize a 6 member team : one for each extremity, one for the head, and one to apply the restraints

: one for each extremity, one for the head, and one to apply the restraints Remove all objects which are potentially dangerous (pens, stethoscopes, reflex hammers etc)

Calmly explain to the patient that restraints are being applied to ensure the safety of the patient and others. It is important to emphasize the restraints are not being used as punishment, but rather have therapeutic value

With the patient supine, restraints should be applied securely to each extremity and tied to the solid frame of the bed (not side rails)

Lower extremities should be tied to the opposite side of the bed to prevent flailing or generation of lateral force

After restraints have been applied, the patient should be closely monitored. Restraints should not be applied indefinitely, and multiple reevaluations should be done to determine when it is safe to remove restraints.

Despite the clinical, ethical and legal controversies surrounding physical restraints, studies have supported that they are generally safe without many significant long term complications. One prospective study of 298 patients who were involuntarily restrained in the ED found that only 20 patients had complications, most related to getting out of the restraints, vomiting, injuring others or themselves, and increased agitation. There were no deaths reported in this study1.

Chemical Sedation:

Often times, chemical sedation is used either in isolation or in addition to physical restraints. As with physical restraints, chemical sedation should be considered in patients who do not respond to verbal de-escalation. Benzodiazepines, typical antipsychotics, and atypical antipsychotics are the classes of drugs that are most commonly used in the ED setting to stabilize a volatile patient. However, not all patients will benefit from a specific medication, and careful history/physical and analysis of potential side effects should be a part of a tailored plan for each individual patient. Ideally, medications used for the purpose of sedation should be rapidly acting with a minimal or tolerable side effect profile.

Adults:

Benzodiazepines : Often used in patients with agitation from an unknown cause, alcohol or drug intoxication, or withdrawal symptoms. They are preferable due to rapid onset of action and short half-life . Patients should be monitored for respiratory depression and somnolence. Most agitated patients will require IV or IM administration. However equivalent PO dosing is favorable in agitated patients who are still somewhat cooperative. Lorazepam : 0.5-2 mg IV / IM every 30 minutes, although can be dosed as frequently as every 10 minutes for very agitated patients. Midazolam : 2.5 to 5 mg IV / IM. Has a more rapid onset but shorter duration of action than lorazepam.

: Often used in patients with agitation from an unknown cause, alcohol or drug intoxication, or withdrawal symptoms. They are preferable due to . Patients should be monitored for respiratory depression and somnolence. Most agitated patients will require IV or IM administration. However equivalent PO dosing is favorable in agitated patients who are still somewhat cooperative.

First generation (typical) antipsychotics : Common first-line agents used to manage acute agitation. However, have an associated risk of QT prolongation and subsequent torsades de pointes. The incidence of extrapyramidal symptoms and neuroleptic malignant syndrome (NMS) with typical antipsychotics has also been well documented. Haloperidol (Haldol): 2.5-10 mg, can be given IM, PO or IV, although IV use does not have current FDA approval for use in acute agitation. Usually dosed every 30 minutes, however can be dosed as frequently as every 15 to 20 minutes if necessary. Droperidol : 2.5-5 mg given IV / IM, has a shorter half life than haloperidol and a faster onset of action (15-30 mins vs 30-60 mins for haloperidol). Unfortunately, droperidol received a black box warning from the FDA in 2001 due to the potential of QT prolongation . However, in the acute setting, treatment should not be delayed to obtain an EKG; cardiac monitoring recommended. It is worth noting that AAEM released a clinical practice statement in which they say the FDA warning is not supported by the literature in doses less than 2.5mg 2 . Further discussion on the safety profile of droperidol is included later in this post. However, the black box warning has still prevented wide spread use in emergency departments.

: Common first-line agents used to manage acute agitation. However, have an associated risk of QT prolongation and subsequent torsades de pointes. The incidence of extrapyramidal symptoms and neuroleptic malignant syndrome (NMS) with typical antipsychotics has also been well documented.

Second generation (atypical) antipsychotics : Have the advantage of decreased incidence of extrapyramidal symptoms (serotonergic activity), while providing more tranquilization and less incidence of somnolence . There are not many good studies that have evaluated the use of second generation antipsychotics in the ED setting, and therefore are they are considered third line agents after benzodiazepines and first generation antipsychotics. Olanzapine (Zyprexa): 10 mg IM / PO, onset of action of 15-45 minutes, and particularly effective for controlling agitation in patients with bipolar mania and schizophrenia. It does have a FDA black box warning for use in the elderly with dementia related psychosis, as there has been an associated increase in mortality in this population due to cardiovascular / infectious causes. Risperidone (Risperdal): 1-2 mg PO / IM. Preferred in patients who require oral medication. Although stated to be a good choice for elderly patients, where it continues to be used for its calming effects, it also has the same FDA black box warning as olanzapine. Ziprasidone (Geodon): 10 to 20 mg IM. Most likely to cause QT prolongation, and has same black box warning as risperidone & olanzapine in dementia related psychosis.

: Have the advantage of . There are not many good studies that have evaluated the use of second generation antipsychotics in the ED setting, and therefore are they are considered third line agents after benzodiazepines and first generation antipsychotics.

Combination therapy : Often thought to have more rapid onset of sedation than when either agent is used individually. However, care should be taken, risks of polypharmacy (ie increased incidence of over sedation, prolonged QT, etc. is common) should be weighed against the benefits. Currently, common practice involves one benzodiazepine and one typical antipsychotic in the following combinations: Midazolam 5 mg IV / IM + Droperidol 5 mg IV / IM Lorazepam 2 mg IV / IM + Haloperidol 5 mg IV / IM “B52”: Benadryl 50mg, Haloperidol 5 mg, Lorazepam 2 mg IM “HAC”: Haloperidol 5 mg, Lorazepam 2 mg, Cogentin 1 mg IM “5150”: Haloperidol 5mg, Lorazepam 1 mg, Benadryl 50mg IM

: Often thought to have more rapid onset of sedation than when either agent is used individually. However, care should be taken, risks of polypharmacy (ie increased incidence of over sedation, prolonged QT, etc. is common) should be weighed against the benefits. Currently, common practice involves one benzodiazepine and one typical antipsychotic in the following combinations:

As listed above, Benadryl and Cogentin are both excellent agents to add to the cocktail of antipsychotics and benzodiazepine given their anticholinergic properties and ability to offset some of the side effects associated with typical antipsychotics, such as haloperidol.

Ketamine : 1-2 mg/kg IV or 4-5 mg/kg IM. Ketamine is relatively fast acting, with an onset of action within 1-2 minutes, and a duration of 10-20 minutes. Ketamine has a relatively good side effect profile. However, physicians should be on the lookout for hypertension and tachycardia, which may not make it an ideal medication in older patients with coronary histories. The big selling point for Ketamine is that it does not cause respiratory depression. However, providers need to know that on rare occasion, laryngospasm or respiratory complications requiring emergent airway management can occur. Ketamine should also be avoided in schizophrenics as it has been known to exacerbate psychotic symptoms.

: 1-2 mg/kg IV or 4-5 mg/kg IM. Ketamine is relatively fast acting, with an onset of action within 1-2 minutes, and a duration of 10-20 minutes. Ketamine has a relatively good side effect profile.

While first generation antipsychotics have long thought to have adverse side effects, a large 2002 retrospective study looking at 2,468 patients who received Droperidol in the ED found only 6 adverse events out of which 1 patient had a cardiac arrest3. Another double-blinded randomized control trial with 153 patients in the ED examined midazolam vs. droperidol for acute agitation. The study found that both medications were equally effective in sedating patients that were agitated, while the midazolam group had 3 patients who had respiratory complications4. Both these trials suggest that Droperidol is both safe and effective in the ED setting in patients with normal QT interval and no underlying electrolyte disturbances.

Studies comparing second generation antipsychotics to benzodiazepines and first generation antipsychotics are lacking. One double blind randomized trial compared the use of droperidol, ziprasidone and midazolam use in 144 patients with acute undifferentiated agitation in the ED. The study concluded that all agents were equally effective at inducing sedation. However there was longer onset to adequate sedation in patients taking ziprasidone. The study also concluded that patients taking droperidol or ziprasidone did not require additional sedation as often as midazolam5. Another double blind randomized trial of 111 agitated patients confirmed that midazolam had shorter time to onset of sedation compared to haloperidol and lorazepam, however all three drugs were found to be equally efficacious6.

With regards to combination therapy, one double blind trial of 336 acutely agitated patients in the ED were randomized to midazolam and droperidol/olanzapine versus midazolam alone. The study found that droperidol or olanzapine used as an adjunct to midazolam was effective and associated with more rapid time to adequate sedation7. Another randomized control trial examined 98 patients with psychotic agitation and found that haloperidol and lorazepam combination therapy was associated with decreased incidence of EPS symptoms (6%) versus haloperidol alone (20%)8.

Children:

Strong clinical trials looking at pediatric patients are currently lacking. Most studies evaluating the efficacy and side effect profile of chemical restraints in the ED are comprised of a primarily adult patient population and subsequently extrapolated to the pediatric population. As of date, there are no established evidence based guidelines for managing acute agitation in children. Regardless, most experts believe that many of the medications used in the adult ED can also be used in pediatric populations, with careful monitoring for side effects and proper dose adjustment. As in adults, most side effects in children are cardiovascular and respiratory depression, CNS side effects, and extrapyramidal symptoms. Fortunately, many of these side effects can be mitigated by supportive measures or anticholinergics.

Hilt and Woodward published the following guidelines for managing agitation in the pediatric emergency patients in the Journal of American Academy of Child and Adolescent Psychiatry9:

If the patient is already taking psychiatric medications, usual PO medications should be continued on schedule

The choice of agent should depend on the specific symptoms ( PO always preferred over other routes of administration) Anxiety: Lorazepam 0.05 mg/kg/dose PO/IM/IV (max 2 mg/dose) Diazepam 0.04-0.2 mg/kg/dose PO/IM/IV (max 10 mg/dose) Diphenhydramine 1 mg/kg/dose PO/IM/IV (max 50 mg/dose) Psychotic thoughts or mania Risperidone 0.25 mg PO (2 mg for teens) Olanzapine 2.5 mg PO (10 mg for teens) Ziprasidone 10-20 mg IM (>16 years old) or 10mg IM (12-16 years old) Haloperidol IM 0.025-0.075 mg/kg/dose IM (max 5 mg/dose) Impulsive, maladaptive aggression Risperidone 0.25 mg PO (2 mg for teens) Olanzapine 2.5 mg PO (10 mg for teens) Delirium Always seek to treat underlying medical cause, although risperidone or haloperidol can also be used In the event that chemical restraint is not obtained by a single agent, it is reasonable to add on a benzodiazepine or an antipsychotic after 30 minutes as needed In the event that muscle stiffness or EPS symptoms manifest after administration of an antipsychotic, it is recommended to give diphenhydramine 1mg/kg/dose to max 50 mg PO, IM or IV.

over other routes of administration)

Ketamine has long been used for procedural sedation in children and has a convincingly strong safety record. Given ketamine has the ability to provide rapid onset and short duration sedation, analgesia and amnesia with minimal side effects, it is a reasonable choice for quick and painful procedures in a child who is resisting intervention in the ED. The current recommended dosage is 1 to 1.5 mg/kg IV or 4-5 mg/kg IM. Most trials have identified that IM administration of ketamine is associated with more adverse effects and longer recovery times. Side effects include vomiting, hallucinations, and in very few cases, laryngospasm or apnea. Vomiting is typically well controlled by premedicating patients with ondansetron, although published evidence is lacking. With regards to laryngospasm which is arguably the most concerning adverse effect, one observational study evaluated 4,252 patients who received IV or IM ketamine and found only 29 patients exhibited laryngospasm (20 of the patients received ketamine via IM route)10. As with adults, patients who have evidence of airway compromise after ketamine administration should be rapidly stabilized and intubated if necessary.

One study evaluated the most commonly used drugs for control in the ED by surveying pediatric emergency medicine fellowship training directors. The study identified that the most commonly used medications included benzodiazepines (71%), haloperidol (46%), and antihistamines (25%)11.

While combination therapy has been studied to an extent in adults, most experts do not recommend combination therapy in the pediatric ED setting due to the lack of published information on safety of these regimens.

Elderly:

The elderly patient population requires special consideration when it comes to chemical sedation in the ED. Complications commonly arise due to the high incidence of co-morbidities, risk of dehydration, falls, respiratory depression, aspiration pneumonia, and polypharmacy in this patient population. As such, doses should usually be lowered as compared to your normal healthy adult. In addition, elderly patients require careful evaluation for delirium vs. dementia as these are two of the more common etiologies for acute agitation in the ED and require different treatment approaches.

First line agents: Second generation antipsychotics are preferred over first generation antipsychotics due to the decreased incidence of EPS, which can be problematic in patients that may have Parkinsonism at baseline. However, as discussed above, there is a FDA black box warning showing increased mortality in elderly patients with dementia-related psychosis . Olanzapine 2.5 mg IM Haloperidol 0.25-0.5 mg IM Risperidone 1 mg PO Quetiapine 50 mg PO

. Second line agents: Benzodiazepines should be deferred to second line treatment due to the high risk of over sedation. In the event that they are indicated, they should be administered at lower doses and should be very slowly titrated to monitor for any adverse effects. Lorazepam 0.5 mg PO



Conclusion:

The ED patient is often times acutely agitated, violent or psychotic and a danger to themselves and those around them. The ED takedown is a useful skillset comprised of physical restraint and chemical sedation, which can be implemented in the management of these challenging patients. Prior to using physical restraints or chemical sedation, identifying the cause of agitation and using verbal de-escalation techniques should always be prioritized. Physical restraints are generally safe to use if done properly as a team effort. The decision to use chemical sedation should take into the consideration the type of patient (adult, child, elderly), the cause of agitation (anxiety, psychosis, organic reason) and potentially detrimental side effects.

Benzodiazepines are good choices in many adult patients due to their rapid onset of action and short duration of action, however, they should be avoided in elderly patients due to risk of respiratory depression and somnolence.

Typical antipsychotics , such as Droperidol, are safe to use in low doses, however providers should be on the lookout for very rare cases of QT prolongation.

Atypical antipsychotics are also a favorable choice given the lower incidence of EPS and somnolence, however there is an associated risk of dementia-related psychosis in the elderly population.

Ketamine is a common favorite in the ED and has a broad spectrum of use in both adult and pediatric patient populations, however there is a very low risk of laryngospasm and worsening of symptoms in psychotic patients.

Different combination therapies can be considered depending on the specific patient and physician preference.

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References:

Zun LS. A prospective study of the complication rate of use of patient restraint in the emergency department. J Emerg Med. 2003;24(2):119-24. Perkins J. and Ho J. Clinical Practice Statement: Safety of Droperidol Use in the Emergency Department. Available at: http://www.aaem.org/UserFiles/file/Safety-of-Droperidol-Use-in-the-ED.pdf Chase PB, Biros MH. A retrospective review of the use and safety of droperidol in a large, high-risk, inner-city emergency department patient population. Acad Emerg Med. 2002;9(12):1402-10. 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(1):61-7. 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 midazolam. Acad Emerg Med. 2005;12(12):1167-72. 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(7):744-9. 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(1):72-81. 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(4):335-40. Hilt RJ, Woodward TA. Agitation treatment for pediatric emergency patients. J Am Acad Child Adolesc Psychiatry. 2008;47(2):132-8. Melendez E, Bachur R. Serious adverse events during procedural sedation with ketamine. Pediatr Emerg Care. 2009;25(5):325-8. Dorfman DH, Kastner B. The use of restraint for pediatric psychiatric patients in emergency departments. Pediatr Emerg Care. 2004;20(3):151-6.