The Agitated Patient in the ED: Moderate & Severe Agitation

In Medical Concepts by Brent Thoma10 Comments

In my first post of a trilogy on the agitated patient in the ED I outlined BARS sedation score for defining levels of agitation, discussed how to risk stratify a potentially agitated patient and offered some tips on how to deal with the mildly agitated patient. This post will discuss what to do with moderately and severely agitated patients while the final chapter will delve into the work-up of these challenging patients. If you’ve been enjoying these posts, be sure to check out Kane Guthrie‘s gem of an overview of behavioral emergencies on LITFL and the more recent post on EMDocs.

While dangerously agitated patients require a more aggressive approach than the patients discussed in my first post, I think the strategies suggested for treating those patients still apply to these ones. At every level of the agitation spectrum it is important to consider a patient’s potential for violence and attempt to calm them using effective communication strategies. However, moderately and severely agitated patients will likely require more medication and possibly physical restraint. What should you use? How should it be done?

The Moderately Agitated Patient: Medications

In my first post I defined a moderately agitated patient as meeting the 6th level of the BARS criteria.1 They are “extremely or continuously active, not requiring restraint.” While I criticized the BARS criteria for defining a level of agitation with a treatment (restraint), I do see some merit in this definition. Patients can get extremely worked up while still not being such a danger to themselves or others that they require physical restraint. I think determining which patients require a rapid take-down is part of the art of emergency medicine and may partially be influenced by a patient’s response to the suggestion of a medication to help them calm down.

In conjunction with medications, seclusion may also be used to isolate an agitated patient. The American Association of Emergency Psychiatry recommends its use for agitated patients who are at low risk of harming themselves or others.2

The options for chemical restraint are extensive but generally include benzodiazepines and antipsychotics. At this level of agitation, I would attempt to convince the patient to take a medication cooperatively. Based on the approaches that I have read to prepare this post, many would advocate for the use of an IM or combination of IM medications. However, I think there is a role for the use of SL or PO medications in a patient that is agitated but has not demonstrated harmful or threatening behavior.

Discussing Medications

The American Association of Emergency Psychiatry (AAEP) provides several recommendations for broaching the topic of medications.3 When you have determined that the patient will need medication to calm down, they advice using five strategies, three of which I felt were appropriate for a moderately agitated patient:

  • Invitation: “What helps you at times like this?” – Invite the patient to come up with the idea of medication on their own. This strategy is likely more appropriate for a mildly agitated patient.
  • Fact: “I think you would benefit from medication.” – State a fact plainly for the consideration of the patient.
  • Persuasion: “I really think you need a little medication.” – Try to demonstrate to the patient why it would be helpful.
  • Inducing: “You’re in a crisis and I’m going to get you some medication.” – This takes the decision out of the hands of the patient. If they disagree or become more agitated it may be necessary to escalate your assessment of their level of agitation.
  • Coercion: “I’m going to have to insist.” – This is advertised as dangerous, but I think that is putting it lightly. To me it seems like asking for a fight. If it has come to this I think the patient would be more appropriately lumped with the severely agitated patients as the treatment options are much the same.

The AAEP advises offering the patient a choice in the route of administration and/or medication to give them some semblance of control.3 They may be more agreeable to going with something that they are familiar with. If this is the case, I’d go with it. All of the medications that are commonly used in this setting work and if they take it willingly I think you’ll be further ahead with building a therapeutic relationship than you would be if you insisted on something else.

Medication Route

In a patient with this level of agitation, I would prefer sublingual or intravenous dosing as opposed to oral or intramuscular.

  • Sublingual medications have a slightly faster onset than oral and because they can not be cheeked. As an aside, check out this slightly gross but very interesting post on creative methods of cheeking from an intriguing FOAM site called “Jail Medicine.”
  • While intramuscular medications are often used in this context (presumably because they have a faster onset than oral/sublingual), intravenous medications have a faster onset and more consistent absorption while also making second doses easier to give and securing vascular access to a potentially ill patient.

Medication Choice

Generally, agitated patients are treated with a benzodiazepaine, an antipsychotic, or a combination of the two. The selection of sublingual medications for use in this context is not large. The centers that I have worked in have a sublingual benzodiazepine (Lorazepam) and atypical antipsychotic (Olanzipine or Risperidone) available. What to choose?

Medication

This 2010 Cochrane Review examined the efficacy of benzopiazepines vs antipsychotics vs both in acutely psychotic patients. It concluded that there no significant difference between the efficacy of the three interventions, but that the antipsychotic group had a higher incidence of extrapyrimidal side effects than the other two groups. With no evidence from which to draw, my practice would be to primarily use antipsychotic medications in patients whose agitation seems to have psychotic components and benzodiazepines primarily in patients whose agitation is likely due to stimulant medications or withdrawal from sedative medications. How to tell? Stay tuned for part 3 (which may be written some day, but may not – it’s been years and it isn’t up yet! -BT).

Route

There is not much good evidence on time to onset of action of sublingual medications. The studies on sublingual olanzapine and lorazepam that I found did not examine a clinically significant marker to quantify time to decreased agitation.

  • The time to peak plasma level following 5mg doses of olanzapine was similar when given orally and by oral disintegrating tablet (ODT) at 3-4 hours.4 However, the ODT groups had detectable plasma concentrations significantly before the oral group – (30 minutes versus <10 minutes).4
  • The time to peak plasma level of 2mg of ativan is similar when given orally (2.37h) and sublingually (2.25h).5 This study did not specify when plasma levels were detectable.

In both studies the peak plasma levels were similar regardless of the route given, suggesting that oral and sublingual routes both have good bioavailability.

There are a ton of intravenous benzodiazepines (lorazepam, midazolam, diazepam, etc) and some typical antipsychotics (haloperidol & droperidol – watch the QTc) that are available for this indication. Because they will all work quite quickly when given intravenously and can be titrated to effect with small doses I’m not going to delve into them further than this. In the future, we may see more treatment of this category of patients with intranasal medications such as midazolam and loxapine.

Bottom line: I recommend giving moderately agitated patients sublingual medications (unless they already have an IV). Benzo’s and antipsychotics have relatively similar efficacy and should be selected based upon the presumed cause of the agitation.

The Severely Agitated Patient: Rapid Take-down

There is a lot of adrenaline associated with the severely agitated patient. Likely because of that, the emergency medicine and critical care FOAM world has been exceptionally good at writing about it! Rather than attempt to reinvent the wheel by getting into the subtleties of this topic, I have decided to summarize the conclusions of some of the FOAMites that have already done so.

Medications

Michelle Lin has a post and a great PV card on drug choices and Scott Weingart of EMCrit dedicated to the art of the chemical takedown. Some pearls from his podcast:

  • He uses Droperidol 5mg IM and Midazolam 5mg IM mixed in a single syringe with a repeat dose if needed as his take-down drugs of choice because Haloperidol/Lorazepam/Atypicals are too slow.
  • These patients generally need an ECG anyways so you can document/treat a QTc post takedown if Haloperidol or Droperidol are used.
  • Substance abusers are more likely to be resistant.
  • If these patients become hypoxic after sedation it’s probably because they aren’t breathing. Don’t put oxygen on them or you might miss this!

But Droperidol is the long-QT devil, isn’t it? He has some thoughts on that. So do Lauren Westafer at the Short Coat and this great review, among others.

In terms of antipsychotics, this study and this study several studies support their assertion that Droperidol beats Haloperidol by demonstrating significantly lower scores on an agitation scale at 15 and 30 minutes.6,7 However, with the more recent availability of intramuscular olanzapine, this should be considered given the decreased incidence of side effects8 and the faster onset9 than haloperidol even when it is combined with lorazepam. One recent publication goes so far as to suggest that haloperidol is obsolete.10 Notably, there is an FDA warning against using IM olanzapine along with benzodiazepines, however, some evidence suggests that the risks of coadministration are overblown.11 Putting this all together, my go-to agent for patients with agitation that is felt to be secondary to psychosis is Olanzapine 10mg IM.

On the benzodiazepaine side, 5mg of IM midazolam has a faster time to sedation (18 minutes) than 2mg of IM lorazepam (28 minutes).12 The patients given Midazolam also roused 130 minutes earlier which may be beneficial in facilitating further assessment (but also may require repeat dosing).12 Given the importance of the time to onset in these patients, my go-to agent for patients with agitation that is felt to be secondary to stimulants or withdrawal is midazolam 5-10mg IM.

A new area of research in the treatment of agitation has focused on the use of intramuscular ketamine for rapid take-down – especially in the prehospital setting. This research was started with several case reports13,14  describing how it can be used effectively to take-down agitated patients with exceptional speed. Minh Le Cong put together podcasts reviewing the literature on the use of Ketamine for agitation, listed recent updates in the literature in another post, collaborated with Kane Guthrie on a podcast focused on excited delirium that discussed the use of ketamine in the rapid take-down, and published some of the literature on ketamine in aeromedical retrieval. More literature on the use of ketamine in the prehospital environment for agitation continues to be published.15,16 Minh uses ketamine as a second line drug to sedate patients with infusions during flight. In situations where safety is a concern and/or the patient is extraordinarily agitated, I do think this is a reasonable option although some studies have found higher rates of adverse events such as intubation in these patients.17 An IM dose of 5mg/kg is generally used.

All of these medications have the potential to affect cardiorespiratory parameters and their use requires pre-sedation assessment and planning for post-sedation airway management and monitoring. After sedation is achieved an IV should be obtained and additional sedation can be guided by a sedation scoring system (ie – BARS or RASS). Depending on their response to sedation and disposition (ie need for transport?) RSI may be indicated for some of these patients but that discussion is beyond the scope of this post.

Bottom line: Olanzapine 10mg IM (psychosis-related agitation) or Midazolam 5-10mg IM (withdrawal / stimulant-related agitation) are the best-supported medications for use in a rapid take-down. Ketamine 5mg/kg IM has the fastest onset but a higher side-effect profile so it should be reserved for use in specific contexts. Prior to initiating a rapid takedown be sure to anticipate and plan for airway management and cardiorespiratory monitoring.

Physical Restraints

The AAEP Consensus Statement advises avoiding the use of physical restraints as much as possible as it can be both psychologically and physiologically damaging to the patient.2 However, a survey of psychiatry medical directors primarily working in academic centers estimated that restraints were used in approximately 8.5% of emergency psychiatric presentations for an average of 3.3 hours per episode.18 While acknowledging that this study tells us almost nothing as a result of its methodology, I mention it to illustrate that, at least anecdotally, we are still doing this with some frequency.

I will not address the ethical or legal aspects of the use of physical restraints in this post. However, I think there is wide agreement that, while undesirable, physical restraints are occasionally a necessary evil. Patients that are out of control are at risk of harming themselves or others and need to be restrained so that they can be safely sedated and assessed.

A prospective study of 298 patients physically restrained in the ED found them to be extremely safe.19 The complications listed (9 got out, 3 vomited, 2 injured others, 2 spit, and 1 injured themselves) were quite minor. However, restraints have been found to be harmful when used incorrectly in other settings when larger populations were reviewed. This 2012 study examined 27,353 deaths in patients that were physically restrained to find 22 that were felt to be caused by the physical restraint.20 In 21 of these 22 cases the restraints were fastened incorrectly (19) or weird things were used (2). In most cases, the error was not using side straps or raising the bedrails. While this population is less analogous to agitated patients in the ED, it demonstrates the importance of ensuring that physical restraints are applied correctly.

Appropriate technique (references: eMedicine and EMCrit 60) requires the following:

  • 6 trained staff: 1 for each extremity, 1 for the head and 1 to give medications and help apply restraints
  • Personal protective equipment: Gloves, gowns and face-masks when possible
  • Medical-grade restraints: These should be easy for staff to remove but difficult for the patient. Knots are too difficult for staff and velcro is too easy for the patient. Straps are better.
  • Secured to the bedframe (not the siderail)
  • Supine (not prone)
  • Arms beside body, legs extended
  • Head of bed at 30 degrees (decrease aspiration risk)
  • No pillows (decrease suffocation risk)
  • Pre-restraint briefing with staff
  • Pre-mixed medications for sedation as discussed above
  • Plan for cardiorespiratory monitoring +/- airway management
  • Plan for ongoing sedation needs

I have been searching the internet for a solid physical restraint video, but I have yet to find one. If you have one please send me a link! If I don’t find one I’ll be looking at SOCMOB to make one.

(EDIT April 2, 2013: Dr. Weingart has reposted the video by Gary Marks, DO showing how to effectively restrain patients on his show notes for EMCrit Podcast 60. I strongly urge you to check it out! Differences from the technique described above include tying each leg to the opposite side of the bed [GREAT tip!] and having 1 arm up which decreases movement but may increase aspiration risk).

Conclusion

Moderately and severely agitated patients are at high risk of hurting themselves and others and require the same level of attention as critically ill patients. Preemptive planning and training is necessary to sedate and restrain uncooperative patients and the treatment of a severely agitated patient only begins with physical restraints. Be sure to plan for ongoing sedation, monitoring and airway management prior to sedation. Having addressed the agitation of these challenging patients, my next post (which will hopefully be much shorter!) will address their needs for sedation

Thanks for reading! If you found this post helpful please support BoringEM by following on twitter, facebook, google+, RSS or email (all links at the top of the sidebar). Tweets, retweets and e-mails are also appreciated.

Peer Review: Dr. Minh Le Cong of PHARM. This post was updated in February of 2019.

References

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Finkel S, Lyons J, Anderson R. A brief agitation rating scale (BARS) for nursing home elderly. J Am Geriatr Soc. 1993;41(1):50-52. [PubMed]
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Knox D, Holloman G. Use and avoidance of seclusion and restraint: consensus statement of the american association for emergency psychiatry project Beta seclusion and restraint workgroup. West J Emerg Med. 2012;13(1):35-40. [PubMed]
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Richmond J, Berlin J, Fishkind A, et al. Verbal De-escalation of the Agitated Patient: Consensus Statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup. West J Emerg Med. 2012;13(1):17-25. [PubMed]
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Markowitz J, DeVane C, Malcolm R, et al. Pharmacokinetics of olanzapine after single-dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers. J Clin Pharmacol. 2006;46(2):164-171. [PubMed]
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Greenblatt D, Divoll M, Harmatz J, Shader R. Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepam. J Pharm Sci. 1982;71(2):248-252. [PubMed]
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Thomas H, Schwartz E, Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med. 1992;21(4):407-413. [PubMed]
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Resnick M, Burton B. Droperidol vs. haloperidol in the initial management of acutely agitated patients. J Clin Psychiatry. 1984;45(7):298-299. [PubMed]
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Zun L. Evidence-Based Review Of Pharmacotherapy For Acute Agitation. Part 2: Safety. J Emerg Med. 2018;54(4):522-532. [PubMed]
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Zeller S, Citrome L. Managing Agitation Associated with Schizophrenia and Bipolar Disorder in the Emergency Setting. West J Emerg Med. 2016;17(2):165-172. [PubMed]
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Williams A. Coadministration of intramuscular olanzapine and benzodiazepines in agitated patients with mental illness. Ment Health Clin. 2018;8(5):208-213. [PubMed]
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Nobay F, Simon B, Levitt M, Dresden G. 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):744-749. [PubMed]
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Ho J, Smith S, Nystrom P, et al. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013;17(2):274-279. [PubMed]
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Hick J, Ho J. Ketamine chemical restraint to facilitate rescue of a combative “jumper”. Prehosp Emerg Care. 2005;9(1):85-89. [PubMed]
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Cole J, Klein L, Nystrom P, et al. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med. 2018;36(5):789-796. [PubMed]
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Linder L, Ross C, Weant K. Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting. Pharmacotherapy. 2018;38(1):139-151. [PubMed]
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Dunn S. Internationalisation as a vehicle for professional development. Aust Crit Care. 1996;9(4):118-119. [PubMed]
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Allen M, Currier G. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26(1):42-49. [PubMed]
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Zun L. A prospective study of the complication rate of use of patient restraint in the emergency department. J Emerg Med. 2003;24(2):119-124. [PubMed]
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Brent Thoma
+ Brent Thoma is a medical educator, blogging geek, and emergency physician who works at the University of Saskatchewan College of Medicine. He founded BoringEM and is a senior editor / tech support / jack-of-all trades at CanadiEM.
Brent Thoma
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Brent Thoma