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Excited delirium (also known as agitated delirium) is a diagnosis given to a person who is manifesting a collection of symptoms that includes; aggressiveness, agitation, ranting, hyperactivity, increased/profuse sweating, heightened physical strength, paranoia, panic, hyperthermia, violence, public disturbance, respiratory arrest, and death. Typically this condition is reported to be a result from substance intoxication, trauma, alcohol withdrawal or a mental disorder. This diagnosis has been seen in patients dating back to the 19th century, but it gained significant notoriety in the 1980s as it became more common and linked to a large increase in cocaine use. Victims often end up first going into police custody before being transported to a hospital, and in this period of time they often die when being restrained. This has lead to significant controversy due to speculation of police brutality being the real cause. Despite excited delirium's lack of recognition as an official diagnosis, it is clear that its symptoms are life threatening so research is being conducted to figure out the best way to care for these patients.

History
In 1849, Dr. Luther Bell first described the condition currently known as "excited delirium" that manifested with mania and fever, and he called it "Bell's Mania." Dr. Bell reported that out of around 40 cases he had experienced in his career, about 75% of them were fatal. In the 1960s a very similar condition was described that manifested in delirium and death resulting from withdrawal from psychiatric medication that blocks dopamine re-uptake, and this was termed "neuroleptic malignant syndrome

This phenomenon actually became well known in the 1980's around the same time that recreational cocaine use became common. It was first described in 1985 as a state resulting from cocaine intoxication that involved bizarreness, paranoia, violence, surprising physical strength, hyperthermia and fatal respiratory collapse within minutes to hours after being restrained. In 1985, Dr. Charles Wetli and Davis Fishbain reported this condition in patients who had hidden packets of cocaine rupture inside of their bodies. Recently, it is highly criticized as an excuse for deaths experienced that may be due to "excessive use of force and inappropriate use of control techniques by officers during an arrest". Researchers and clinicians debate over whether the condition exists because no clear, widely-accepted definition or cause exists.

Statistics
About 8 - 14% of people who experience this syndrome are thought to die from it.

More than 95% of all published, fatal cases of excited delirium were found in men with a mean age of 36 years old.

About 10-20% of excited delirium cases involve someone who has been previously diagnosed with a mental illness (e.g. schizophrenia)

Excited delirium is known to kill anywhere from 250 to 600 people nationwide each year.

Mechanism
The exact pathophysiology is not identified, but there are many ideas about how exactly this condition occurs. Postmortem brain examination has shown that the loss of specific dopamine transporters as seen in chronic cocaine abusers may cause excessive dopamine stimulation. Also, hypothalamic dopamine receptors are responsible for thermoregulation, which could explain the hyperthermia in patients. Autopsies have also shown elevated levels of proteins associated with heat shock .The finding of the significant elevation of heat shock proteins in these patients was further supported as being pathological from finding that the mean core body temperature among all 90 of one study's participants being about 105 degrees fahrenheit.

Since the majority of cases are associated with cocaine use, it is hypothesized that cocaine's ability to blockade monamine neurotransmitters is the starting point of the whole syndrome. Cocaine is known to have addictive properties due to its ability to increase dopamine levels and may cause aberrant dopamine processing in the brain's mesolimbic pathway. This may also happen in other areas of the brain and could be what causes the hyperactivity and hyperthermia experienced by patients. Dopamine's regular processing is disrupted and in large quantities, it is thought to be causing massive brain malfunction.

Signs and symptoms
In an effort to identify people whose deaths could be avoided with early intervention. Identification of the condition early is very important, and it is done through identifying the three hallmarks of excited delirium.

The three hallmarks of excited delirium include:
 * Delirium
 * Psychomotor agitation
 * Physiological Excitation

Some specific signs and symptoms characteristic of excited delirium may include:
 * Aggressiveness
 * Hyperactivity
 * Panic
 * Paranoia
 * Violence
 * Profuse sweating
 * Dehydration
 * Hyperthermia
 * Tachycardia
 * Hypertension
 * Rapid breathing
 * Being impervious to pain
 * Respiratory Arrest
 * Death without proper treatment

Diagnosis
Excited delirium is not currently recognized as an actual psychiatric or medical diagnosis according to either the American Psychiatric Association, the International Classification of Diseases of the World Health Organization, or the Diagnostic and Statistical Manual of Mental Disorders. This has lead to controversy about whether it is a legitimate condition or if it is used as a diagnosis by medical examiners and police departments to explain why people die in police custody. However, it is important to remember that a lack of recognition does not minimize the seriousness of the symptoms.

Causes and Prevention
The exact causes of excited delirium are currently unknown. Typically cases are attributed to drug intoxication (usually from cocaine), or history of mental illness treated through medication. Because people who exhibit the characteristics of excited delirium are often aggressive and erratic, police often become involved and need to use physical or chemical force in order to control the patient. Many point to this physical force used by police and say it could be the cause of deaths, while physicians suspect intoxication.

Prevention
Avoiding drug use, especially stimulants, is something that can help prevent this condition because drug use is strongly linked to development of excited delirium symptoms. Currently prevention of deaths due to excited delirium is what is researchers are aiming for through finding ways to detect, recognize, diagnose and treat patients who have excited delirium through a standard, immediate approach.

Treatment and Prognosis
There is no standard of care for patients who have excited delirium. Many treatments are currently being developed based on first recognizing when a patient is exhibiting behaviors associated with excited delirium so that early and immediate treatment can occur before the patient goes into respiratory arrest or even dies.

Currently experts believe that initial assessment should include:
 * Vital signs
 * Cardiac monitoring
 * IV access
 * Glucose measurement
 * Pulse oximetry
 * Oxygen
 * Physical examination
 * Chemical sedation with drugs (e.g. Ketamine)

Recent Research
Since Excited Delirium is not widely researched yet or accepted as an actual clinical diagnosis, research tends to focus on identification and management of the risks associated with its characteristic and severe symptoms. One recent research study called, "Prehospital Use of IM Ketamine for Sedation of Violent and Agitated Patients," explored the idea of rapid sedation in order to decrease the total time on scene and increase safety for both the patient and the first responders. This study was published in 2014 in the Western Journal of Emergency Medicine. It is known that sedation is often required and used for these patients but the best choice of medication is not known. This study focused on 52 patients that were all given 4 mg/kg IM (intramuscular) of ketamine, following normal protocol. About half of these patients were also given parenteral (through IV access) Midazolam, in order to prevent any emergent reactions associated with the Ketamine, after speaking with medical control. The results showed that 50 out of the 52 patients were rapidly sedated, and only 3 patients experienced any side effects from it. The 3 patients that did experience difficulties all experienced respiratory depression resulting from sedation with Ketamine along with the Midazolam. All of the patients were transported to the hospital before the Ketamine wore off. This study demonstrated that Ketamine is a good drug to choose in rapid sedation and transport of patients experiencing excited delirium symptoms. However, further sedation of Midazolam is typically not needed and may be more harmful than helpful especially in situations when the patient is adequately sedated by Ketamine alone.

In another study conducted to investigate biological indications of excited delirium, researchers measured specific biomarkers in autopsies of patients who were suspected to have experienced excited delirium. This study was called "Brain Biomarkers for Identifying Excited Delirium as a cause of Sudden Death," and was published in 2009 in Forensic Science International. This study investigated an apparent link excited delirium has to central nervous system dysfunction of dopamine signaling. A mortality review was conducted on all of these patients to try and find the presence of heat shock protein 70 and heat shock protein A1B. The results showed both to be present, and HSPA1B was elevated by a factor between 1.8-4 times the normal amount in a person for all patients involved in the autopsies. This verified that the hyperthermia experienced by patients was indeed what caused death, and was supported by an average core body temperature upon death measured at about 105 degrees fahrenheit in each patient. Dopamine transporter levels were also below the average, healthy range in a control population of people and this supports the idea that dopamine signaling is interrupted in this condition and is very likely to have a pathological effect on patients. The implications of this study are important since there previously was no way to identify excited delirium in a patient, and from these findings hopefully future studies will be able to investigate ways to identify the condition and legitimize it before a patient dies.