Educational Articles

Much has been published lately about Excited Delirium and the prevalence of it as a law enforcement excuse for unexplained deaths during the person's arrest and custody that follows. Families and plaintiff attorneys would like public opinion to believe some nefarious cover up by law enforcement for brutality, chemical spray or tasers as the root cause of a loved ones death in custody. This misconception has been fueled in the past due to no clear understanding of the syndrome or acceptance of an accrediting medical body to recognize the existence of what is now known as Excited Delirium Syndrome or as will be known in this paper as EXDS.

EXDS is a relative new name for a syndrome that has been around for some time. It was just not named yet, or the criteria put in place to recognize it as EXDS. EXDS "was first described in the mid 1800's" and has been called many different things. Some of the names it has been called are "Bell's mania", acute exhaustive mania and agitated delirium. In the 1980's, there were multiple similar cases reported of acute uncontrolled psychiatric episodes with sudden death that could have been EXDS. Regardless of what we call it, there are certain symptoms or a series of events that occur or are associated with the syndrome: delirium with agitation (often severe), sudden cessation of struggling, respiratory / cardiac arrest and death. A majority of cases also exhibited hyperthermia and unexpected physical strength.

This paper will discuss the signs and symptoms, possible pathophysiology as well as treatment and management options in hope to educate and guide the emergency physician (EP). Most cases are described or identified post-mortem and are described by medical examiners. The diagnosis has caused concern due to the reluctance or slow adoption by medical organizations. However in 2009, ACEP published a White Paper Report on Excited Delirium Syndrome thereby accepting the existence of the syndrome. In this paper, it was worded: "It is the consensus of the task force that EXDS is a unique syndrome, which may be identified by the presence of a distinctive group of clinical and behavioral characteristics that can be recognized in the pre-mortem state. EXDS, while potentially fatal, may be amendable to early therapeutic intervention in some cases".

While the actual pathophysiology remains a mystery, there are several theories that attempt to explain what may occur that produces the combinations of delirium, extreme agitation, and hyperthermia that results in the death of the patient. Most of these cases of EXDS were following the usage of a stimulant drug (cocaine being the main drug noted). Fewer cases were attributed to a pre-existent psychiatric illness or disease. Most of these deaths occurred either prior to arrest, unwitnessed at home, or in the ED. Studies have shown however, that the levels of cocaine in patients diagnosed to have died of EXDS are similar with levels of cocaine in recreational users and actually lower than in fatal cocaine overdoses. But, the reports/research shows other data that supports the pattern of chronic usage with "repeated binges are associated with the development of fatal EXDS".

Dopamine is responsible for neurotransmission in several neural pathways, and it has been suspected that cocaine usage might cause an aberrant processing in the mesolimbic pathway resulting in hyperthermia and hyperactivity. In cases of EXDS, it has been shown the processing of dopamine has been significantly altered compared to non-psychotic cocaine users. There have been certain studies that show/suggest perhaps EXDS patients might have a defective or a different pattern of alpha-synuclein (that regulates the compensatory mechanism that keeps the rapid elevation of dopamine from occurring). If dopamine rises too fast or there is an inability to degrade dopamine, the mesolimbic system takes a big surge and overloads it causing hyperactivity and hyperthermia. There also appears to be a defect in the serotonin up regulation in EXDS patients. While there is an increase in dopamine and serotonin in EXDS victims, there was also an increase in heat shock protein confirming the presence of severe hyperthermia as a symptom of EXDS.

So, EXDS victims lack the normal neural protective mechanisms. This produces the EXDS victim that has an alteration in neuroanatomy and neurophysiology "characterized by high dopamine levels and a hyperactive autonomic nervous system." Victims die from either respiratory arrest or cardiac dysrrhymias. This is supported by autopsy findings of pulmonary and cerebral edema. The few that live long enough die often from DIC, renal failure and rhabdomyolysis.

Epidemiology stats are nearly impossible to determine because there are no current standardized definitions for EXDS, but as a general finding, the incidence of death is 8.3% in patients that exhibit signs and symptoms of EXDS. The average EXDS victim is male with a mean age of 36. Stimulate drug use such as cocaine, PCP and methamphetamine have a clear association with EXDS fatalities. There exists literature that also cites the abrupt cessation of psychotherapeutic medications as a cause of EXDS. Victims also tend to show delirium (the fundamental manifestation), extreme hyper-aggressiveness, increased combativeness with strange behavior, have a very high pain threshold, tachycardia and hyperthermia. While not universally fatal, there is a clear progression in a majority of EXDS victims to cardiac arrest and death.

Many of the deaths from EXDS are not preventable. There may be as of yet a subset of the population that has not been identified and may benefit from early therapeutic intervention. Remember that a majority of EXDS victims die from cardiac arrest that can be first noted as bradycardia and asystole present on the monitor. A majority of lethal EXDS cases die after a violent struggle that may result in severe acidosis, which may play a role in lethal cardiovascular collapse.

Emergency physicians need to be educated about the clinical features of EXDS and be included in any differential diagnosis in a patient with altered mental status and agitation. EPs should recognize that this is a multifactorial syndrome that has an interaction between delirium, and agitation leading to hyperthermia and acidosis often in the setting of stimulant drug use. EPs should suspect EXDS in younger patients that present in cardiac arrest with metabolic acidosis higher than expected and a history of profound agitation and hyperthermia. A history of stimulant drug abuse is not needed for the diagnosis of EXDS. When death occurs, it does so suddenly following physical control measures. Because there is no gold standard test, the EPs must rely on history and clinical findings and presentation.

Treatment should be geared to sedating quickly and correcting the acidosis and hyperthermia. For this paper, we will discuss the treatment for each symptom and sign separately but know that all maybe going on at same time. We will discuss the agitation first. The recommended first line treatment is benzodiazepines, antipsychotics or a dissociate agent such as Ketamine. The preferred route of all these medication is IV. If you are unable to give the medications IV, then IM is acceptable. Just remember and know, the onset of action will be slower. A few examples are Lorazopam, which has an onset of 3-5 minutes IV but 15-30 minutes IM, and the duration is the same at 60-120 minutes. Haloperidol has an onset of 10 minutes IV (FDA has issued a black warning on IV of potential severe cardiac side effects) and 15 minutes IM with duration of 180-360 minutes. Ketamine has an onset of 1 minute IV and 3-5 minutes IM; however, duration for IV is 20-30 minutes and 60-90 minutes IM. So, as shown, IV administration can reduce the time the patient is in an agitated state. These medications are just examples for onset of action, and by no means, the only benzodiazepines or antipsychotics available for use. In some circumstances, there is a need for sedation and paralysis. In these cases, standard RSI medications and techniques may be utilized.

Hyperthermia can be treated by removal of clothing and placing the patient in a cool environment. Similar to cases of heat stroke, you can utilize radiant heat loss by using misting and fans, external cooling with ice packs to the axilla and groin and cool IV fluids to cool the patient. In severe cases, the patient can be immersed in cool water. Care must be taken to not put the patient into a hypothermic state. There are a variety of commercial devices that can be used to cool patients.

Acidosis may be treated by fluid resuscitation, or in extreme conditions, you can give sodium bicarbonate. Empirically and routinely using sodium bicarbonate is controversial and has questionable efficacy. The current literature does not support its use unless the pH is < 7.1 and unless the acidosis is severe. If using sodium bicarbonate, one must weigh the benefits of its use versus the risks associated. If used, it can be given in a bolus or as a continuous infusion. Other complications such as rhabdomyolysis are treated in standard fashion.

In summary, EXDS is a clinical diagnosis based on the constellation of signs and symptoms or features that include; male, mean age of around 36, destructive or bizarre behavior, known alcohol intoxication, psycho stimulant drug use or suspected use, suspected or known psychiatric illness, delirium, erratic behavior unusual physical strength, hyperthermia, ongoing struggling despite futility and cardiopulmonary collapse post struggle. Treat according to the features exhibited. There is insufficient data to have a definitive treatment at current and no gold standard test so it must be a clinical diagnosis but we as EPs must keep it in our DDX lest we miss an opportunity to potentially save the EXDS victim.

*References available upon request.