Excited Delirium: The ED Minefield
- Jun 21st, 2021
- Gabrielle Bunney
Authors: Gabrielle Bunney, MD (Northwestern Emergency Medicine Resident) and Dana Loke, MD (Clinical Instructor and Medical Education Fellow, Department of Emergency Medicine, Northwestern University) // Reviewed by: Cynthia Santos, MD (@Cynthia Santos, MD); Tim Montrief, MD (@EMinMiami); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)
A 25-year-old male presents via EMS with a police escort for agitation and bizarre behavior. He was found running up and down the street and then threatening a bystander. In the resuscitation bay he is pacing and appears diaphoretic. You are unable to obtain a history or vital signs from the patient and attempt verbal de-escalation but the patient remains agitated and uncooperative. You realize the patient is presenting with excited delirium and think carefully about what to do next.
Excited delirium is easily identified in the Emergency Department (ED), but its cause is often illusive. Patients presenting with excited delirium are frequently those heard screaming down the hallway making the entire ED turn their attention to them as they get carted into a resuscitation bay for further management. Despite this incredible and attention-grabbing display, the approach to excited delirium is much more nuanced, complicated, and controversial. Delirium is defined as a waxing and waning of a patient’s mental status, orientation, memory, thought, and perception in an acute setting.1 In excited delirium the patient presents agitated, aggressive, paranoid, and in acute distress.1, 2 This can lead to metabolic acidosis, hyperthermia, and rhabdomyolysis—all possible differentiators from general agitation.2, 3 The “diagnosis, then treatment” paradigm is flipped when caring for a patient with excited delirium as they can be a danger to themselves and staff.
Most recently, excited delirium has gained national attention as a diagnosis that has been associated with those who have died in police custody.2, 4 Interestingly, excited delirium was first described in 1849 and was found to have a mortality rate of 75% at that time.2 Dr. Luther Bell is credited with first describing “Bell’s Mania,” a condition defined by delusions, hallucinations, hyperactivity, sleeplessness and fevers, thought to be similar to the modern excited delirium.2He initially treated patients with sodium amytal, a barbiturate derivative, which reportedly calmed the patient’s excited state, but did not cause them to regain any sleep.5 There is evidence to suggest that elevated dopamine and dysregulated dopamine transporters play a role and a hyperadrenergic surge ultimately leads to hyperthermia, which is an ominous sign of impending death.2 Excited delirium secondary to toxicological causes usually results from a sympathomimetic agent (amphetamines, bath salts, cocaine, etc.) causing a hyperadrenergic state from excess catecholamines.
Ultimately, there is no clearly accepted definition of excited delirium. The American Psychiatric Association and the World Health Organization do not recognize excited delirium as its own entity, while the American College of Emergency Physicians has recognized excited delirium as an entity since 2009.3, 4, 6 At this time, diagnosing excited delirium rests in identifying a constellation of 6 out of 10 symptoms: pain tolerance, tachypnea, sweating, agitation, tactile hyperthermia, police non-compliance, lack of tiring, unusual strength, inappropriate clothing, and mirror/glass attraction.4 There are no pathognomonic features and it often overlaps with other diagnoses which are listed below. Today, excited delirium carries a reported mortality ranging from 8.3-16.7%, and notable independent risk factors include male gender, African-American race, young age (median age of 30), and overweight body habitus.2, 6
Once excited delirium is identified, the cause must be determined and appropriately treated. The differential diagnosis for excited delirium is broad and includes both medical and psychiatric causes. Medical and psychiatric causes as listed in table 1 below. The evaluation of excited delirium requires the investigation of the below wide range of diagnoses. This evaluation often occurs after treatment with chemically sedating medications, and therefore a thoughtful and comprehensive approach is needed and often includes finger-stick glucose, basic metabolic panel, complete blood count, hepatic function panel, thyroid studies, urine drug screen, urinalysis, creatinine kinase, and a CT brain.
Although it is crucial to maintain a broad differential diagnosis, drug ingestions are thought to be the most common cause of excited delirium.4 The surge of cocaine use in the 1980s brought about a renewal of defining excited delirium, which has been attributed to Dr. Wetli and Dr. Fishbain.2 Methamphetamines, LSD, and PCP were all notable contributors, however the most common drug associated with excited delirium at that time was cocaine. Cocaine is known to increase dopamine and so it would follow from the general knowledge of the pathophysiology of excited delirium that cocaine would be a culprit. Excited delirium was initially identified in body stuffers, or those individuals who swallow large quantities of drugs in individual packets in an effort to conceal them when approached by law enforcement.2 Rupture of even one of the bags causes an immediate release of high concentrations of the drugs. As one might expect, ingestion and then rupture of bags containing cocaine can lead to excited delirium. However it does not appear that drug toxicity alone explains a patient developing excited delirium. The amount of cocaine found in the system of those with excited delirium is often much lower than those who have been determined to have died from a drug overdose.3, 7
The goal of treating excited delirium is to stop the hyperadrenergic surge via chemical sedation followed by supportive care geared towards the differential diagnosis above. Benzodiazepines are a frequently proposed treatment.1, 6 Benzodiazepines work by increasing the inhibitory transmitter, GABA, resulting in sedation and anxiolysis.8 The most commonly used benzodiazepines are midazolam, lorazepam, and diazepam. Midazolam has a shorter onset, while lorazepam and diazepam have a longer duration.8, 9 Diazepam also has active metabolites which make its duration of action even longer than lorazepam and so is not used regularly for this indication. Both lorazepam and midazolam can be given IV or IM, although lorazepam’s absorption via the IM route is more erratic and unpredictable.
A treatment option with rapid ability to control agitation is ketamine. Ketamine is an NMDA (N-methyl-D-aspartate) antagonist, causing sedation, amnesia, and analgesia, while allowing the patient to maintain airway reflexes, spontaneous respirations, and cardiopulmonary stability.10 This is what has made ketamine a popular drug for conscious sedation and is therefore being studied for additional applications such as in excited delirium. Dosing options include 1-2mg/kg IV or 4-6mg/kg IM.6, 11 The studies show adverse events are small in number, with most being pulmonary, including the need for intubation.10, 11 However, it is notable that these studies looked at ED administration of ketamine, whereas there have been higher reported adverse effects of ketamine when administered in the prehospital setting.10, 12 Close monitoring is recommended once any medication is administered for agitation. It is important to recognize that ketamine does not last as long as the benzodiazepines and therefore could require redosing.13
Safety is paramount in these cases and so physical restraints are often needed to safely administer these medications. IM medications are preferred over IV medications as an IM stick is safer for staff than attempting to obtain an IV in a writhing, agitated, and uncooperative patient. IM medications can be given in the thigh through clothes when necessary. Physical restraints should be removed as soon as it is safe and clinically appropriate to do so.
Ultimately, the patient requires physical restraint to receive 5mg of IM midazolam. His restraints were removed shortly after the medications took effect. The nurse was then able to safely take vital signs, which were notable for tachycardia to the 120s, blood pressure in the 160s/90s, respiratory rate of 18, temp of 100.2F, and O2 saturation of 99% on room air. Labs were obtained and he was noted to have a CK of 2500U/L and a creatinine of 1.9. He was monitored in the ED and after a few hours his mental status normalized, at which point he divulged that he used PCP earlier that day. He was ultimately admitted for further monitoring and fluid resuscitation for rhabdomyolysis.
- Safety of patients and staff takes precedent in the setting of excited delirium and may warrant the use of restraints and chemical sedation.
- Supportive care is paramount, as these patients can be incredibly sick. Assess for electrolyte abnormalities, rhabdomyolysis, and hyperthermia, and treat accordingly.
- First line agents are benzodiazepines.
- Ketamine is an appropriate second line medication in the ED, although its use in the prehospital setting is still controversial.
- Sekhon S, Fischer MA, Marwaha R. Excited (agitated) delirium. StatPearls. 2020
- Mash DC. Excited delirium and sudden death: A syndromal disorder at the extreme end of the neuropsychiatric continuum. Front Physiol. 2016;7:435
- Takeuchi A, Ahern TL, Henderson SO. Excited delirium. West J Emerg Med. 2011;12:77-83
- States ACoEPU. White paper report on excited delirium. 2009
- Kraines SH. Bell’s mania. American Journal of Psychiatry. 1934;91:29-40
- Gonin P, Beysard N, Yersin B, Carron PN. Excited delirium: A systematic review. Acad Emerg Med. 2018;25:552-565
- Byard RW. Ongoing issues with the diagnosis of excited delirium. Forensic Sci Med Pathol. 2018;14:149-151
- Hui D. Benzodiazepines for agitation in patients with delirium: Selecting the right patient, right time, and right indication. Curr Opin Support Palliat Care. 2018;12:489-494
- Gottlieb M, Long B, Koyfman A. Approach to the agitated emergency department patient. J Emerg Med. 2018;54:447-457
- Li M, Martinelli AN, Oliver WD, Wilkerson RG. Evaluation of ketamine for excited delirium syndrome in the adult emergency department. J Emerg Med. 2019
- Mo H, Campbell MJ, Fertel BS, Lam SW, Wells EJ, Casserly E, et al. Ketamine safety and use in the emergency department for pain and agitation/delirium: A health system experience. West J Emerg Med. 2020;21:272-281
- Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for rapid sedation of agitated patients in the prehospital and emergency department settings: A systematic review and proportional meta-analysis. J Emerg Med. 2018;55:670-681
- Long B, Gottlieb M, Koyfman A. Emdocs cases: Ed approach to agitation. EmDOCs.net – Emergency Medicine Education. 2018
- Midazolam: Drug information.
- Lorazepam: Drug information.
- Koyfman A, Strayer R. Ketamine for agitated/violent patient. EmDOCs.net – Emergency Medicine Education. 2015
- Leedekerken J, Kopec K, Santos C, Koyfman A, Long B. Toxcard: Dexmedetomidine & ketamine in toxicologic causes of agitation. EmDOCs.net – Emergency Medicine Education. 2019