Managing the Acutely Agitated Patient

   Management of acutely agitated patients can present a challenge both in the field and in the emergency department. There are a variety of techniques that can be used to manage agitated behavior in the prehospital setting, including verbal management techniques and physical restraints. This discussion will focus on chemical restraint of the acutely agitated patient.

   In September 2009, the American College of Emergency Physicians' Task Force on Excited Delirium published a white paper that concluded that some episodes of excited delirium "may be amenable to early therapeutic intervention in some cases in the pre-mortem state," and that "physical restraints should be rapidly supplemented with chemical restraints" in agitated patients who require restraint.¹ Options for chemical sedation in the prehospital setting include benzodiazepines, antipsychotics (also called neuroleptics), antihistamines and, rarely, dissociative agents such as ketamine. A survey of 34 larger metropolitan city EMS agencies at the annual Gathering of Eagles conference revealed that 33 of these agencies use some method of chemical restraint. Of those, 26 use midazolam (Versed), nine use diazepam (Valium), four use lorazepam (Ativan), eight use haloperidol (Haldol), two use droperidol (Inapsine), and one uses ketamine. (Some agencies have more than one agent available for chemical sedation.)

   While benzodiazepines are excellent agents in many settings, particularly to treat patients with acute agitation related to cocaine or methamphetamine ingestion, they may not be ideal in all situations. Antipsychotics are also effective in managing agitated behavior and may result in fewer episodes of oversedation.² In particular, antipsychotics may be a better choice when dealing with agitated behavior related to alcohol use or psychiatric conditions. There are both typical antipsychotics such as haloperidol and droperidol and newer, atypical antipsychotics such as ziprasidone (Geodon) and olanzapine (Zyprexa).

   First introduced in the United States in 1970, droperidol is a butyrophenone and a potent antagonist of dopamine subtype 2 receptors in the limbic system. It is a potent antipsychotic used both for chemical restraint and as an antiemetic. Droperidol has been shown to be an effective sedative agent with few treatment failures and no respiratory depression.^3,4 It has also been shown to be safe in a variety of clinical settings, including emergency management of acute agitation.^5-7 In a randomized controlled trial, droperidol was found to result in more rapid control of agitated patients than haloperidol, with no increase in undesirable effects.⁸ In another trial comparing droperidol to midazolam, no difference was found in the onset of adequate sedation, but patients receiving midazolam showed an increased need for active airway management.⁹

   So why is droperidol not more widely used in EMS? In December 2001, the FDA issued a "black box" warning for the drug based on reports of QT prolongation and/or torsade de pointes in patients receiving it. This warning came after more than 30 years of clinical use, making it the longest latency period from initial FDA approval to black box warning to date. The warning was also issued despite the fact that no clinical trial or systematic review had reported any adverse cardiac events. It resulted in a dramatic decrease in the use of droperidol across the country despite a number of published articles questioning the warning's validity.^10-13 Among the conclusions of these articles was that "the evidence is not convincing for a causal relationship between therapeutic droperidol administration and life-threatening cardiac events," and that "the black box warning appears to have originated from post-marketing surveillance data rather than data reported in peer-reviewed medical literature." Hennepin County, MN, published a review in 2005 concluding that since the removal of droperidol from its system as a treatment option for out-of-hospital agitated patients, it had seen an increased frequency of continuous pulse oximetry monitoring, intubation, ED critical care management and ICU admission.¹⁴

   In September 2007, the FDA issued a similar warning for haloperidol, stating that torsade de pointes and QT prolongation had been observed in patients receiving it. In response to this warning, in January 2009 Denver went back to using droperidol rather than haloperidol. Since then, we have had the same experience as the authors of those many published reports: We've found droperidol both safe and effective. Authors from Camden, NJ, published similar experiences with safety and effectiveness earlier this year.⁷

   The care of agitated patients in the field is challenging on many levels, and chemical restraint is sometimes necessary to safely manage them. While benzodiazepines are great in many cases, they are not the ideal agent for all situations. Antipsychotics such as droperidol should be an option in some cases, such as for patients experiencing agitation related to alcohol use or an acute psychiatric condition. There is growing experience with newer, atypical antipsychotics, and these may be an option to consider in the future.

References

1. ACEP Excited Delirium Task Force. White paper report on excited delirium syndrome, 2009.

2. 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 12(12): 1,167-1,172, 2005.

3. Hick JL, Mahoney BD, Lappe M. Prehospital sedation with intramuscular droperidol: A one-year pilot. Preh Emerg Care 5: 391-4, 2001.

4. Rosen CL, Ratcliff AF, Wolfe RE, et al. The efficacy of intravenous droperidol in the prehospital setting. J Emerg Med 15: 13-7, 1997.

5. 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 9: 1,402-10, 2002.

6. Szuba MP, Bergman KS, Baxter LR, et al. Safety and efficacy of high-dose droperidol in agitated patients. J Clin Psychopharmacol 12: 144-5, 1992.

7. Szwak K, Sacchetti A. Droperidol use in pediatric emergency department patients. Pediatr Emer Care 26: 248-250, 2010.

8. Thomas H, Schwartz E, Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med 21: 407-13, 1992.

9. 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 47(1): 61-7, Jan 2006.

10. Dershwitz M. Droperidol: Should the black box be light gray? J Clin Anesth 14: 598-603, 2002.

11. Horowitz BZ, Bizovi K, Moreno R. Droperidol--behind the black box warning. Acad Emerg Med 9: 615-8, 2002.

12. Mullins M, Zwieten K, Blunt J. Unexpected cardiovascular death associated with droperidol: A smoking gun or just smoke and mirrors? J Toxicol Clin Toxicol 40: 600-1, 2002.

13. Kao LW, Kirk MA, Evers SJ, et al. Droperidol, QT prolongation, and sudden death: What is the evidence? Ann Emerg Med 41: 546-48, 2003.

14. Martel M, Miner J, Fringer R, et al. Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients. Preh Emerg Care 9(1): 44-8, 2005.

   Christopher B. Colwell, MD, FACEP, is medical director for the Denver Fire Department and Denver Paramedic Division, and an associate professor at the University of Colorado Health Sciences Center.