Emergency Management of the Agitated Patient

By: Kelvy Levit, PGY3
​Reviewed by: David Slattery, MD

Violence is rising at a concerning rate in emergency departments. According to a national survey by American College of Emergency Physicians’ (ACEP), almost 50% of emergency physicians and nearly 70% of emergency nurses report being physically assaulted at work. A troubling 97% of assailants were patients (1).
 
With these staggering statistics in mind, it’s important to not only have preventative measures in place, but also a management plan when dealing with agitated, combative, and altered patients.
 
Dealing with the agitated patient can be distressing to not only the emergency physician but also to the staff involved directly or indirectly. As providers, we are prone to cognitive errors during times of high stress. This blog will discuss the approach to the agitated patient to include verbal de-escalation techniques, options for chemical sedation, and an overview of the current literature supporting practice recommendations.

There is no one size that fits all. As EM providers, we’re used to having a stepwise approach to patient care. Managing these patients can be messy, intimidating, and often dangerous. The etiology of the patient’s agitation may be due to primary psychiatric illness, drugs, hypoxia, endocrine emergencies, central causes, or any combination of the above.  Because of the patient’s altered mental status, it is vital to obtain critical historical information from pre-hospital personnel, family or friends.  As we know, diagnostic and therapeutic considerations often occur simultaneously.
 
Your immediate goals when taking care of these patients are to:
 

1. Protect yourself, the staff, and the patient from harm.
2. Take control of the situation, the patient, and your own stress levels. Identify and treat reversible causes.

                                     
Current experts recommend classifying patients into one of 3 levels of agitation when trying to determine the most appropriate approach (6).
          Levels of Agitation

1. Mild
2. Moderate
3. Severe

  
Mildly Agitated
Examples of common patient presentations in this category include: elderly patients with dementia, schizophrenia, or other psychosis, decompensation with minimal symptoms, and those who present with intoxication. You have little to no concern of an organic etiology of their symptoms. These patients are generally cooperative and will behave if they have someone sit with them.

1. The experienced clinician will be able to quickly determine which patients will be amenable to verbal de-escalation. If the patient is confused, violent, or without insight, this step will likely be skipped. 
2. As a reminder, here are some tips when attempting verbal de-escalation (2).
   1. Maintain eye level
      • If the patient is seated, join them.
   2. Check yourself before you wreck yourself
      • Manage your own emotions. It’s easy to get flustered by the agitated patient but do your best to avoid being confrontational. You can do this by presenting at an angle. Demonstrate good body language and keep your hands and avoid clenching your fists. Maintain safety and be near an exit. One person should be engaging the patient in a low tone, calm manner. Don’t convey weakness.
      • Remember the sage advice of Dr. Peter Rosen, paraphrased here: “Just put your mind in neutral and do the right thing”. 
   3. Be concise. Set boundaries.
      • Be honest with the patient and don’t lie. Set boundaries with the patient and advising them that making statements of violence or aggression will not be tolerated.
   4. Listen, Identify, and Offer
      • Listen closely and identify what they want. Is this a patient that’s upset due to long wait times or poorly managed expectations? Even if you had been working a cardiac arrest, a simple apology can go a long way.  Remember to be your patient’s advocate. Offer them basic needs like water, a blanket or when all else fails… the infamous turkey sandwich.

 
At this point you can also offer them medications which may decrease the chance of needing something intramuscular. Keep in mind, for the elderly patient, you may have to decrease dosages.   Benzodiazepines and other sedative hypnotics should be used with caution in the elderly as they may worsen dementia and delirium related agitation. For antipsychotics, consider olanzapine 5 – 10 mg PO or Risperidone 2mg PO. For benzodiazepines, consider Lorazepam 1-2 mg PO. (3).
  
Moderately Agitated
These are the loud, disruptive intoxicated patient. They typically make a scene but aren’t a danger to themselves and others. They usually can’t be verbally re-directed due to the inherit nature of their intoxicants. These are also patients that you can do a reasonable history and physical exam, and in the absence of any red-flag findings, the clinician may feel pretty confident that the patient just needs to be serially observed while they metabolize the alcohol or drug. These patients can typically be observed in an unmonitored bed. The classic “B52” (Benadryl 50mg + Haldol 5mg + Ativan 2mg) has historically been used for this category of agitation. Although this “agitation cocktail” works in many patients, we believe that there are better options. Ideally, the best pharmacologic sedative will be fast acting, have a short half-life, hemodynamically stable, and allow our patient to sleep and metabolize to freedom.

Droperidol is back on the market and this once commonly used medication is now gaining popularity again. It was initially approved by the USFDA for nausea, vomiting, anxiety and sedation. It is an effective and safe agent for undifferentiated agitation (9).

In 2001, the FDA issued a suspicious black box warning about droperidol, stating there was a significant risk of cardiac arrhythmias related to QT prolongation. This was incredibly surprising, as at the time, droperidol was a very popular antiemetic used for post-operative nausea and vomiting for thirty years. 277 cases were reported to the FDA. No one had noticed a problem until 71 adverse events were reported on the same day. Even more suspiciously, around this time, Ondansetron came on the market, also treating post-operative nausea and vomiting, except at a much more expensive price. Eventually, it stopped being produced in the US, except at Mayo Clinic, where they made their own. There have been many studies supporting the safety and efficacy of droperidol. An article by Jackson et al. reviews the 277 cases of adverse events associated with droperidol that were reported to the FDA (5). They did this by a written request to the FDA to provide any and all reports of cardiovascular events related to droperidol use that were part of the decision to place the black-box warning. They found that many of the reports were duplicates, leaving a total of only 65 individual cases. Of these cases, only 2 described adverse cardiovascular events possibly caused by droperidol in dosages used in the US. They also found that in addition to these reports, 2 European studies prompted the FDA to place its black box warning on droperidol. Both studies used droperidol in 50 to 100 times higher than those used in the US.
 
There have been numerous studies that have addressed the safety of droperidol.
 

• Gaw CM, Cabrera D, Bellolio F, Mattson AE, Lohse CM, Jeffery MM. Effectiveness and safety of droperidol in a United States emergency department. Am J Emerg Med. 2020;38(7):1310-1314. doi:10.1016/j.ajem.2019.09.007

 

• Gaw et al. performed an observational, retrospective, cohort study of 6,353 visits in which patients received droperidol (8). The primary endpoint was mortality within 24 hours of droperidol administration. Secondary endpoint included rescue analgesics as droperidol was used as an analgesic for pain (21.8%) and headache (57.0%), as an antiemetic (12.5%), and as a sedative (8.7%). 5.4% of administrations were children and 8.2% in older adults greater than 65. No deaths secondary to droperidol administration were recorded within 24 hr. No patients had fatal arrhythmias. Akathisia occurred in 2.9%. As their secondary endpoint, they found that over 90% of patients required no rescue medications when used for headache or other pain. They concluded that droperidol is safe when given in usual lower doses of 0.625 to 2.5mg.

 

• Calver L, Page CB, Downes MA, et al. The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2015;66(3):230-238.e1. doi:10.1016/j.annemergmed.2015.03.016

 

• Another study by Calver et al. investigated the safety and effectiveness of droperidol for sedation of acute behavioral disturbance in the emergency department (9). The primary outcome was the proportion of patients with an abnormal QT interval. Secondary outcomes were effectiveness determined by the time to sedation. This was a prospective observational study in 6 EDs in Australia. They administered 10 mg of IV or IM droperidol and this dose was repeated in 15 minutes if the patient was still agitated. Patients received an ECG as soon as possible and there was no control group in this study. 1009 patients received an ECG within 2 hours of droperidol administration. 13 patients had QT prolongation. However, when analyzed further, 7 of these patients had other obvious reasons for QT prolongation including previous documentation of a prolonged QT from other medications. In total, 0.6% of the patients had a prolonged QT that could be attributed to droperidol. There were no events of dysrhythmia, torsade’s de pointes, or cardiac arrest. For their secondary outcome, the median time to sedation was 20 minutes and 70% of patients were effectively sedated after the second dose. This study’s main limitation is that it’s not a randomized control trial. That being said, the risk of prolonged QT in this large group of patients was minimal and when present very mild.

 
Other studies have compared droperidol to midazolam or the combination of the two.
 

• Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010;56(4):392-401.e1. doi:10.1016/j.annemergmed.2010.05.037

 

• Isbister et al. performed a blinded, randomized control trial conducted in Australia for intramuscular sedation for violent and acute behavioral disturbance comparing droperidol (10mg), midazolam (10mg), or droperidol (5mg) and midazolam (5mg) combination (10). The primary outcome was the duration of the violent and acute behavioral disturbance. Secondary outcomes included time until additional sedation was administered, staff and patient injuries, further episodes of violent and acute behavioral disturbance, and drug related adverse effects. 91 patients were included. 33 received droperidol, 29 received midazolam, and 29 received the combination. They found no difference in the median duration of the violent and acute behavioral disturbance: 20 min for droperidol vs 24 min for midazolam, and 25 min for the combination. However, patients that were treated with midazolam alone were more likely to require additional sedation (62% vs 33% with droperidol alone and 41% with the combination treatment) and to experience drug-related adverse effect (28% vs 6% with droperidol alone and 7% with combination treatment) which mainly included inadvertent deeper sedation. Droperidol was found to produce consistent moderate sedation while midazolam was highly variable and unpredictable. There was no evidence of QT prolongation associated with droperidol.

 
There have also been some studies that compare droperidol to ziprasidone or midazolam.
 

• 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 [published correction appears in Acad Emerg Med. 2006 Feb;13(2):233]. Acad Emerg Med. 2005;12(12):1167-1172. doi:10.1197/j.aem.2005.07.017

 

• Martel et al. conducted a prospective, randomized, double-blind trial of agitated patients ED patients of unknown etiology requiring emergent sedation (11). Patients were randomized to receive droperidol 5mg, ziprasidone 20mg, or midazolam 5mg intramuscularly. Interval measurements were made at 0, 15, 30, 45, 60, and 120 minutes and included Altered Mental Status Scale (AMS) scores, oxygen saturations, and end-tidal carbon dioxide levels. A total of 144 patients were enrolled. 50 patients received droperidol, 46 received ziprasidone, and 48 received midazolam. Adequate sedation was achieved at 15 min in patients receiving midazolam and 30 min for patients receiving droperidol and ziprasidone. Rescue medication for sedation was necessary in 10% of droperidol treatment group, 20% of ziprasidone, and 50% of the midazolam group. There were no cardiac dysrhythmias identified in any treatment group. Respiratory depression that clinically required treatment with supplemental oxygen occurred in 8% of droperidol, 15% in ziprasidone, and 21% in midazolam treatment groups. No patients required endotracheal intubation. They concluded that droperidol, ziprasidone, and midazolam are effective in the management of acute undifferentiated agitation in the ED. However, more patients remained agitated at 15 minutes with ziprasidone and patients receiving midazolam required additional sedation more frequently.

 

• Thomas H Jr, Schwartz E, Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med. 1992;21(4):407-413. doi:10.1016/s0196-0644(05)82660-5

 

• A study by Thomas et al. demonstrates superiority of droperidol when compared to haloperidol for acute agitation (12). This was a randomized, prospective, double blinded study that was performed on patients requiring physical and subsequently chemical restraint in a university hospital (Winston Salem, NC) emergency department. The primary outcome was time to appropriate sedation which was rated on a five-point combativeness scale at 5,10,15,30, and 60 minutes after the treatment drug was administered. There was a total of 68 violent or agitated patients that were given either IM/IV droperidol or haloperidol. 21 were given IM haloperidol 5mg, 26 were given IM droperidol 5mg, 12 were given IV haloperidol 5mg, and 9 were given IV droperidol 5mg. They found that IM droperidol decreased combativeness significantly more than IM haloperidol at ten (P = .006), 15 (P = .01), and 30 (P = .04) minutes. There was no significant difference between the two drugs when given by the IV route. Vital signs in the four treatment groups did not differ significantly. Blood pressure was noted to be 90/60 mmHg or lower in 15% of the patients receiving IM droperidol, 9% of the patients treated with IM haloperidol, and 17% of the patients receiving IV haloperidol, but no significant adverse effects of reduced blood pressure were reported. There was an acute dystonic reaction noted after 18 hours in one patient treated with IM haloperidol but none of the remaining 41 patients discharged from the ED returned with any reported adverse effects. There were no adverse reactions noted in the 26 patients admitted. They concluded that in equal IM doses of 5mg, droperidol results in more rapid control of agitated patients than haloperidol, without any increase in undesirable side effects.

Other studies combining midazolam with droperidol and comparing them to single agent droperidol or olanzapine have been conducted as well. Taylor et al. performed a randomized, controlled, double-blinded, triple-dummy, clinical trial in 2 metropolitan EDs in patients requiring IV medication sedation for acute agitation (13). They were randomized to receive an IV dose of either midazolam-droperidol (5mg each), droperidol 10mg, or olanzapine 10mg. If required, two additional doses were administered: midazolam 5mg, droperidol 5mg, or olanzapine 5mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes. 349 patients were randomized into 3 groups. 75% of patients were sedated in 10 minutes in the combination groups versus 50% in the other two groups. At 15 minutes, 90% of the combination group were adequately sedated vs 60% in the other two groups. In the droperidol and olanzapine groups, 80% of the patients weren’t sedated until 30 minutes after the medications were administered. In the combination group, 28% required more medication for adequate sedation vs 60% of the solo agents. Patients in the combination group required more airway interventions, but no intubations were performed. There were no QTc prolongation or cardiac events. Ultimately, they found that the combination of medications worked faster but require higher level of monitoring. The take home message here is that if a single agent isn’t working, it’s good to keep in mind that a second agent may be a good option, however these patient’s will likely require higher level of monitoring.
 
Severely Agitated
The severely agitated patient is one that is classified as a danger to themselves and to others around them. They are unable to be re-directed verbally and present with hyperactivity, violence, and extreme levels of strength. These patients usually fall into the category of “excited delirium”. Excited delirium is not a pathophysiologic disease entity. It is a description of the way these patients behave. The concept of excited delirium is useful to remind us that the dangerously agitated patient is at high risk for sudden death if they aren’t treated quickly and appropriately. The priority in these patients is to obtain immediate control of the situation in order to identify reversible life-threatening conditions. The agent that has been gaining popularity due to its efficacy and reliability is dissociative dose ketamine. However, patients with excited delirium tranquilized with dissociated dose ketamine are high risk for decompensation. Consider this a procedural sedation and all that entails. These are medical resuscitation cases and ultimately may require intubation. Ketamine dissociated patients have the potential to develop hypoventilation and apnea from a variety of mechanisms: Laryngospasm, airway malpositioning, obstruction, hypersalivation, and central apnea. Unfortunately, strictly from an evidence-based medicine perspective, there isn’t a substantial amount of evidence. Although most of the case series, cohorts, and observational data seem promising, most of it is low level evidence.

Riddell et al performed a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation (14). Pregnant women, prisoners, and persons in police custody were excluded along with those triaged to a low acuity zone of the ED. These were severely agitated patients requiring care in a high acuity treatment area with available cardiorespiratory monitoring. This study’s primary objective was to compare the time to a defined reduction in agitation scores for ketamine vs benzodiazepines (midazolam or lorazepam) and haloperidol, alone or in combination. Due to the observational nature of the study, medication dosages were not uniform. They did, however, use current published dosage recommendations of ketamine 4-6mg intramuscular (IM) or 1-2 mg/kg intravenous (IV), haloperidol 5-10mg IM, midazolam 5-10mg IM or 5mg IV, and lorazepam 1-2mg IM or IV. Secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. Providers measured agitation levels on a previously validated 6-point sedation scale at 0, 10, and 15 minutes after receiving sedation. They assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. 98 patients met eligibility criteria with the study cohort being mostly male. 33 received lorazepam, 24 received ketamine, 19 received midazolam, 14 received Haldol, and 10 received a combination of medications There were no significant differences based on race, stated use of substances, or previous psychiatric history. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5,10, and 15 minutes after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. Of note, there were 2 intubations in the ketamine group (8.7%) and 1 in each other groups. This goes to show how severely agitated these patients were across the board. The main limitations of this study are: It’s underpowered to look at anything but time to sedation, physicians were unblinded, they are assessing subjective outcomes, the dosing was not uniform, and there was an element of selection bias. Ultimately, the study shows us that ketamine can be used to quickly sedate highly agitated patients but can’t really comment of the safety or which patients might benefit most.

Another study by Lin et al compares ketamine to haloperidol plus lorazepam for behavioral disturbance in the emergency department (15). This was the first randomized, prospective clinical trial that sought out to determine the efficacy and safety of ketamine compared to parenteral haloperidol plus lorazepam for initial control of acute agitation. Patients were randomized to ketamine (4mg/kg IM or 1mg/kg IV) or haloperidol/lorazepam (haloperidol 5-10mg IM or IV + lorazepam 1-2 mg IM or IV). The primary outcome was adequate sedation within 5 minutes, as defined by a documented Richmond Agitation and Sedation Scale score <0 or nursing narrative documentation. Secondary outcomes included sedation within 15 minutes, time to sedation, and safety. A total of 93 patients were enrolled. Patients were excluded from the study if they were younger than 18 years old, pregnant, previous diagnosis of schizophrenia, angina, uncontrolled hypertension, heart failure, glaucoma/ocular injury or thyroid disorder. These exclusion criteria were based off the published guidelines on the use of ketamine for dissociative sedation. Prior to arrival, paramedics have standing orders for midazolam 5mg IM once as needed for agitation. If they received midazolam prior to randomization, were hypoxic, at risk for respiratory depression, or were overtly intoxicated, physicians had the option to either omit or lower the dose of lorazepam to 1mg. Physicians also had the option to lower the dose of haloperidol to 5mg for patients weighing less than 60kg, age greater than 80 years, or in the presence of significant medical comorbidities. A total of 44 patients were randomized to receive ketamine and 49 patients were randomized to receive haloperidol plus lorazepam. The majority of the patients (93%) enrolled in the study were administered medications intramuscularly, most commonly for a diagnosis of acute agitated delirium or acute agitation. Of the patients who received haloperidol/lorazepam arm, 61% received the goal dose of 10mg and 2mg respectively. Across both groups, the most common intoxicants were found to be methamphetamines, alcohol, or cannabinoids. Significantly more patients who received ketamine compared to haloperidol/lorazepam were sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p < 0.001). The median time to sedation in patients who received ketamine compared to haloperidol/lorazepam was 15 vs 36 min respectively (p < 0.001). In terms of safety, hypertension and tachycardia were significantly more common with ketamine (33% and 34% vs 11% and 11%), and there was a non-statistically significant difference in hypoxia (21% vs 10%) but no difference across arms in QTc prolongation, hypotension, nausea, and hypersalivation. No emergence reactions were documented in this trial. Some study limitations included that 7 patients were excluded after randomization and no information is given on the other medications patients might have received. Enrolling physicians might have excluded certain high-risk cohorts which may lead to selection bias. The study personnel were not blinded to a highly subjective primary outcome. Doses were frequently lowered in the haloperidol/lorazepam arm. They concluded that patients receiving ketamine for combative agitation was significantly more effective than haloperidol/lorazepam for initial control of acute agitation and is not associated with any significant adverse effects. However, the study’s small sample size, use of a convenience sample of patients, and nonblinded design limits the applicability of the results.

The use of ketamine in the prehospital setting has also been studied. Cole et al. conducted an observational open-label, prospective study, coordinated at the Minnesota Poison Control System (16). The primary objective of this study was to determine if haloperidol or ketamine was superior for the treatment of severe prehospital acute undifferentiated agitation. Specifically, they hypothesized that in patients with severe agitation presenting to their EMS system, 5mg/kg of IM ketamine would be superior to 10mg of IM haloperidol, with time to adequate sedation.  Secondary outcomes included need for redosing in the prehospital environment, the rate of adverse side effects, and rates of intubation between ketamine and haloperidol. They defined severe agitation as an Altered Mental Status Scale (AMSS) score of +2 or +3. Prehospital and ED providers were unblinded to which medication the patients received. All patients in the EMS system with severe acute undifferentiated agitation subsequently transported to the study hospital were included in the study. Exclusion criteria included obviously gravid women, patients less than 18 years of age, patients with “profound agitation”, defined as an AMSS score of +4. Their reasoning behind the last criteria was that they deemed it “unethical and unwise” to withhold ketamine from the most profoundly agitated patients at any time for both patient and caregiver safety. In terms of interventions, for the first 3 months of the study, the standard EMS operating procedure (SOP) for severely agitated patients was to treat acute undifferentiated agitation with 10mg of IM haloperidol. For the next 6 months, the SOP was changed to 5mg/kg of IM ketamine. For the final 3 months, the SOP was returned to haloperidol. A total of 146 patients were enrolled. 64 received ketamine and 82 received haloperidol. In terms of results, they found that time to adequate sedation was significantly faster in the ketamine group. Median time to adequate sedation was 5 min for ketamine and 17 min for haloperidol (p<0.0001, difference 12 min, 95% CI: 9-15). 95% of patients in the ketamine group achieved adequate sedation pre-hospital compared to 65% of patients in the haloperidol group. (p<0.0001, difference 0.3, 95% CI O.18-0.42). 5% of patients in the ketamine arm required additional sedation prehospital whereas 20% of patients in the haloperidol group required a second injection prehospital. Intubation rate was significantly higher in the ketamine group; 39% of patients receiving ketamine were intubated vs 4% of patients receiving haloperidol (p<0.0001, difference 35%, 95% CI 23-48%). No intubations occurred prehospital. These authors report a strikingly high rate of intubations for patients receiving ketamine. They report that “not protecting the airway” was the most common indication for intubation. They speculate that the receiving emergency physicians were either uncomfortable with a dissociated patient or may have misapplied the often-quoted axiom of “GCS less than 8 intubate”. A patient dissociated from ketamine cannot be evaluated properly by GCS. Their complication rates from ketamine administration appear to also be higher than previously reported studies. The procedural sedation literature suggests apnea occurs with a recommended dose of IM ketamine at 4-5 mg/kg, at a rate closer to 0.8% and often transient (9). Their observed rate was much higher at 12%. The comment that the etiology is unclear and may be a reflection of co-intoxication, most commonly with ethanol. The primary limitations of the study are its lack of randomization and blinding. They excluded patients with an AMSS score of +4, which is the exact population of interest, especially when considering excited delirium. The small sample size cannot be applied to the general population. In conclusion, they found that ketamine was superior to haloperidol in terms of time to adequate sedation, however, given the high intubation rate that was observed, risks vs benefits need to be considered. I believe this is an important reminder that these patients can be very sick, quickly decompensate, and should be viewed as a procedural sedation and medical resuscitation, along with all that entails.
​
In conclusion, agitated patients can present on a spectrum from slightly disruptive to dangerous and violent. An organized approach is important for your own safety, the safety of the staff and the patient. Selecting medications for chemical sedation can be difficult. Each patient’s presentation, co-morbidities, co-intoxicants, and psychiatric background needs to be considered prior to picking an agent. Hopefully this blog allows you to review some of the most pertinent studies for chemical sedation of the agitated patient in the emergency department.   
 
References

1. Schertzer K, Staats KS. The Violent Patient. EMRAP CorePendium. https://www.emrap.org/corependium/chapter/recyBMqazT7o2lGZ7/The-Violent-Patient. Published September 1, 2020. Accessed December 15, 2020.
2. Richmond JS, Berlin JS, Fishkind AB, 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. doi:10.5811/westjem.2011.9.6864
3. Walls RM, Hockberger RS, Gausche-Hill M, Bakes KM. Rosen's Emergency Medicine: Concepts and Clinical Practice. Philadelphia, PA: Elsevier; 2018.
4. Strayer R. Podcast 185 - Disruption, Danger and Droperidol by Reub Strayer. EMCrit Project. https://emcrit.org/emcrit/disruption-danger-droperidol/. Published December 13, 2016. Accessed February 5, 2021.
5. Jackson CW, Sheehan AH, Reddan JG. Evidence-based review of the black-box warning for droperidol. Am J Health Syst Pharm. 2007;64(11):1174-1186. doi:10.2146/ajhp060505
6. Strayer R. Podcast 185 - Disruption, Danger and Droperidol by Reub Strayer. EMCrit Project. https://emcrit.org/emcrit/disruption-danger-droperidol/. Published December 13, 2016. Accessed February 5, 2021.
7. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57(5):449-461. doi:10.1016/j.annemergmed.2010.11.030
8. Gaw CM, Cabrera D, Bellolio F, Mattson AE, Lohse CM, Jeffery MM. Effectiveness and safety of droperidol in a United States emergency department. Am J Emerg Med. 2020;38(7):1310-1314. doi:10.1016/j.ajem.2019.09.007
9. Calver L, Page CB, Downes MA, et al. The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2015;66(3):230-238.e1. doi:10.1016/j.annemergmed.2015.03.016
10. Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010;56(4):392-401.e1. doi:10.1016/j.annemergmed.2010.05.037
11. 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 [published correction appears in Acad Emerg Med. 2006 Feb;13(2):233]. Acad Emerg Med. 2005;12(12):1167-1172. doi:10.1197/j.aem.2005.07.017
12. Thomas H Jr, Schwartz E, Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med. 1992;21(4):407-413. doi:10.1016/s0196-0644(05)82660-5
13. Taylor DM, Yap CYL, Knott JC, et al. Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A Randomized Clinical Trial. Ann Emerg Med. 2017;69(3):318-326.e1. doi:10.1016/j.annemergmed.2016.07.033
14. Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Ketamine as a first-line treatment for severely agitated emergency department patients. Am J Emerg Med. 2017;35(7):1000-1004. doi:10.1016/j.ajem.2017.02.026
15. Lin J, Figuerado Y, Montgomery A, et al. Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study [published online ahead of print, 2020 Apr 11]. Am J Emerg Med. 2020;S0735-6757(20)30241-2. doi:10.1016/j.ajem.2020.04.013
16. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol (Phila). 2016;54(7):556-562. doi:10.1080/15563650.2016.1177652