Sgt. Edward Conover, BA, SJPD
Mary Boudreau Conover BSNed
- Too much of a good thing
- Other causes of excited delirium
- The dope on dopamine
- Brain biomarkers for excited delirium and sudden death
- Police action
- Time-line for drug-related deaths during arrest or in-custody
- Complexity of history taking
- Autopsy in excited delirium
- The path to psychosis and self-destruction
When police officers are called out to subdue an aggressively violent individual who is destroying property and is a serious physical threat to those in the vicinity, they respond to the call knowing from the report that they may encounter a case of excited delirium, a condition in which death is imminent with or without police intervention, but all the same leaving police officers vulnerable to lawsuit. This article has been sparked and has taken life from the mortality review by Mash et al1 published by Forensic Science International in June 2009. The authors of the landmark study, a group of scientists from Miami, Fl; Berkeley, CA; Stockholm, Sweden; and Suffolk County, NY, showed that a 2-protein biomarker signature, when combined with a description of the decedent’s behavior prior to death, serves as a reliable forensic tool for an autopsy identification of excited delirium, a syndrome known to be a terminal event. The depth and breadth of the work involved is revealed in the acknowledgment by the authors of the cooperation of the many physician medical examiners and death investigators from throughout the United States and Europe who are involved in medicolegal investigations of excited delirium deaths. There were 90 cases studied, with 10 more added since publication. The findings and on-going studies give hope to police officers everywhere who are innocent targets when violently aggressive cases of excited delirium die in custody.
TOO MUCH OF A GOOD THING
Fatal excited delirium is a syndrome caused by the excessive chaotic signaling of dopamine, resulting in death. Dopamine’s normal functions are to encourage and support important roles in behavior including regulation of mood, memory, learning, appetite, sleep, and muscle contractions. Dopamine occurs naturally in the body and is released from the cerebral cortex to the frontal lobes of the brain to help us concentrate, learn, form habits, and to reward pleasurable experiences such as good food and sex so that we will continue to pursue them in the interests of self-preservation, social adaptation, learning, and meaningful progress along life’s path.
Remember mom’s warning about
“too much of a good thing”? Mom knows. In the case of
dopamine, too much of this good thing will overtake you with craving,
drive you into a violent psychotic state, destroy you in every way possible,
and then eventually leave you to die in a fit of critically overheated
excited delirium after having lashed out with super-human strength to
destroy everyone and everything in the vicinity.
So, how does a person go about
getting too much of this good thing? It’s easy and it starts
with one “hit” with one of the stimulants of the central nervous
system (CNS) such as cocaine or methamphetamine.
OTHER CAUSES OF EXCITED DELIRIUM
Delirium is a brain dysfunction and clouding of consciousness that may be manifested with widely different symptoms from somnolence to excited agitation, depending on the cause, which includes the somnolent delirium of liver disease or the excited delirium of mental stress, depression, suicidal tendencies, acute exhaustive mania, underlying psychosis, alcohol withdrawal, or head trauma.2 3
Thus, illicit drugs are not the only cause of excited delirium. The excited delirium manifested in other conditions is sometimes referred to as “impulsive aggression”. In such cases, laboratory tests show no trace of illicit drugs. Genetics and hypofunction of the neurotransmitter, serotonin, have been implicated.4-7
Serotonin. Serotonin is a neurotransmitter, as is dopamine. In the central nervous system its functions include the regulation of mood, appetite, sleep, muscle contraction, memory and learning. Disturbances of the serotonin nerve pathway have been implicated in many psychiatric disorders, including alcoholism, aggression, schizophrenia and depression.6 8 It has also been suggested that in such cases hypofunction of serotonin may represent a biochemical trait that predisposes individuals to impulsive aggression, with dopamine hyperfunction compounding the serotonin deficit.4
Genetics. Genetics and environment hold key roles in determining aggressive behavior. In particular, reaction to stress appears to be an important factor in precipitating such episodes and adverse rearing conditions may interact with variants in stress and neurotransmitter pathway genes leading to antisocial or violent behavior.9 Several different genetic markers are thought to be associated with regulation of mood, pain perception, aggression, and psychiatric disturbances such as schizophrenia, depression, and suicide.5
Symptoms. Excited delirium is recognized because of acute loss of behavioral inhibition manifested in a cluster of behaviors that may include aggression, agitation, ranting, hyperactivity, paranoia, panic, violence, public disturbance, surprising physical strength, profuse sweating, hyperthermia, respiratory arrest, and death. Knowing of the many and diverse causes of excited delirium, it is not surprising that when a person exhibiting this hyperexcited cluster of symptoms is subdued by the police, there may be no trace of illicit drugs found in the blood sample taken in-hospital or at postmortem.
THE DOPE ON DOPAMINE
Dopamine is a neurotransmitter,
a chemical that carries messages from one nerve cell (neuron) to another.
Notice the two approximated neurons and the space between them in the
illustration below. This space is called a synapse. It
is here, in the synaptic gap that dopamine is released from the neuron
In all cases of excited delirium and “impulsive aggression”, excessive levels of dopamine in the extracellular fluid of the brain, although they cannot be measured directly, are reflected in “dopamine transporter levels that are below the range of values measured in age-matched controls.”1 Once dopamine has delivered its stimulus, it needs a transporter in order to return into the neuron. The dopamine transporter is blocked by cocaine and methamphetamine and eventually, with continued abuse of the drug, the dopamine transporters fail, leaving unregulated dopamine to produce the sudden unexpected onset of excited delirium.10 14
Cocaine in the Brain
The diagram below shows the sequence from 1-4 of normal activation of the nerve.1 11 12 13 When cocaine is aboard the normal physiology of dopamine is disrupted, as diagrammatically illustrated at #5.
Illustration adapted from the Nat Institute on Drug Abuse Research Advances 13(2), 1998.
- Vesicles are shown in their resting state, ready for the nerve to be activated. Dopamine rests within, protected from destruction by the enzyme, monoamine oxidase.
- The nerve has been activated and the vesicles quickly fuse with the cell membrane and unload the dopamine into the synaptic space.
- The free dopamine diffuses to a receptor on the target neuron, binds, and releases its charge.
- Dopamine then returns
to its dopamine-releasing reurons by binding to a site on its transporter, from wich it is transported across the cell membrane and delivered back to the vesicle.
- When cocaine is present, it binds to sites on the dopamine transporter, inhibiting uptake of dopamine. Note dopamine cannot be reaccumulated and is literally stranded. This represents an increase of dopamine levels in the brain which produce the rewarding and reinforcing feelings of intense euphoria that, if pursued, may lead to addiction, uncontrolled bingeing, and a path to death and destruction.
Amphetamine and substituted amphetamines, including methamphetamine (meth), methylphenidate (Ritalin), methylenedioxymethamphetamine (ecstasy), and the herbs khat and ephedra, are the only widely administered class of drugs that predominantly release dopamine and norepinephrine from the nerve cell by a mechanism other than their normal release from the vesicles. These drugs are used medicinally and socially in many cultures, exert profound effects on mental function and behavior, and can produce the degeneration of nerves and addiction. Meth not only prevents the return transport of dopamine and norepinephrine into the cell, it also works in two ways to increase the amount of dopamine and norepinephrine for reverse transport out of the cell.
- Meth easily crosses the blood/brain barrier and passes directly through the nerve cell membranes into the nerve terminal to disrupt the normal functioning of the CNS stimulants, dopamine and norepinephrine.
- Once inside the cell, meth causes dopamine and norepinephrine to be released from the vesicles where they are stored, and then transports them out of the cell, using their uptake carriers in. a reverse direction.
- It binds to the dopamine and norepinephrine transporters, preventing return of these neurotransmitters back into the nerve cell and thus increasing their concentration in the synapse.
- Meth also blunts the effects of an enzyme in the intracellular fluid (monoamine oxidase) whose job it is to reduce concentrations of dopamine and norepinephrine.
An attempt to adapt. As more and more dopamine transporters are being used up by cocaine or meth, the body adapts by increasing the numbers and function of the dopamine transporter. When this adaptation fails, dopamine transporter levels fall and dopamine itself is no longer regulated, triggering a sudden and potentially fatal bout of excited delirium.1 15 16
BRAIN BIOMARKERS FOR EXCITED DELIRIUM AND SUDDEN DEATH
Findings. For police officers everywhere, support and validation
can be found in the eloquent studies of Mash et al1 at the
Department of Neurology at the University of Miami (www.exciteddelerium.org).1a This group has
conducted a mortality review of ninety excited delirium deaths.
Their findings implicate central nervous system dysfunction involving
the neurotransmitter dopamine as the cause of the excited delirium.
The fatal event for most is hyperthermia; for all it is collapse of
the autonomic nervous system. Important findings at autopsy were:
Core temperature. Measured at autopsy, possibly after a cool-down, mean core body temperature was has been 105.2 degrees F (40.7 degrees C) in cocaine abusers and cases of exhaustive mania.
2-protein biomarker (dopamine transporter and heat shock protein) analysis.
- Heat shock protein elevation. Heat shock protein (Hsp70) was elevated up to 4-fold in the postmortem brain, confirming that hyperthermia is an associated symptom and often a harbinger of death. Heat shock proteins increase their expression in cells with elevated temperatures. They are thought to be defense mechanisms or neuroprotective whenever core body temperature is elevated. This marker is a surrogate for hyperthermia in cases of excited delirium.
- Dopamine transporter blood levels. Low levels are a positive finding for excited delirium. Toxicology and history of drug or alcohol abuse or a psychological autopsy will help to show cause.
Mash and her associates1 have concluded after review of chemical pathology and toxicology results from a case series of 90 excited delirium deaths, that the identification of postmortem biomarkers for excited delirium serve as an objective-testing method for assisting medical examiners at autopsy. The use of postmortem biomarkers when combined with descriptions of the decedent’s behavior prior to death, are reliably associated with the syndrome.
Arriving on scene, police often find the individual involved in dangerous behavior---assaulting friends, family and total strangers, destroying property, running wildly in and out of traffic, throwing off their clothes, kicking in doors, invading homes, and breaking windows.1
This frightening scenario is indeed a challenge to the police who, though strong, do not have the “unexpected superhuman physical strength” of excited delirium. Added to the quagmire is the fact that the combative person is impervious to pain and is unable to respond to verbal commands. The usual police techniques of pain control are useless and it often takes many police officers to control the suspect. Should there be a high intensity physical struggle, vital signs are often lost within minutes of being restrained.1
In the midst of this maelstrom and under extreme psychological and time pressures, the officers need to choose the most appropriate force option available to them at the time that balances the safety of the public, the officers and the suspect. However, even careful use of the options available followed by immediate medical attention does not guarantee survival. In this chemically altered physical condition, it is possible, even with extreme care, that the suspect will die suddenly while being restrained in police custody, especially if a protracted physical struggle is necessary. Ideally, the police officers need to incapacitate the individual as quickly as possible, for the good of the suspect and those endangered by his violence. The longer the fight continues, the worse the outcome for the suspect, especially if the combative person is under the influence of phencyclidine (PCP) or central nervous system (CNS) stimulants such as methamphetamine (meth), amphetamine, or cocaine ("crack"). These stimulants have profound chemical effects on the heart and brain, causing abnormal brain activity which can lead to excited delirium and sudden death.1 Should the suspect be successfully resuscitated, they often die in-hospital from rhabdomyolysis and renal failure.17 18
The cause of death in excited delirium is a gross disruption of the central nervous system causing symptoms that produce very high body temperatures, multisystem organ failure, and death. In such a rapidly declining physical and mental state, case reviews have demonstrated the high risk of mortality for these individuals---all on their own without police intervention.17 19
Avoiding a Potentially Fatal Struggle
Electrical devices. In the past the fastest way to quickly incapacitate the suspect was the carotid restraint. More recently, there is widespread availability of electrical devices that conduct just enough energy to subdue a violent, out-of-control suspect who is impervious to pain and unable to understand police commands. TASER is the most well known manufacturer of such a device and has become the more common force response.
There is a significant difference between the Taser and the ‘stun gun’. The Taser causes Electro Muscular Disruption (EMD) which actually disrupts the muscles and causes involuntary immobilization. The Stun Gun is a Conductive Energy Device that delivers a shock, which is a pain compliance type issue. When hit with a ‘stun gun’ a person with excited delirium can fight through the pain. Whereas, when the Taser works properly, they have no choice in the matter, the pain is secondary and voluntary control of skeletal muscles is disrupted, during which time police can restrain the suspect.
The Taser has come under scrutiny by national and international media and human rights organizations because there have been deaths of persons in custody following its application. Current theories include production of immediate fatal arrhythmias or “some type” of subacute, delayed cardiac or other organ system damage that manifests itself as sudden death at a later time.20
Such opinions have elicited scientific investigations demonstrating that prolonged EMD application in exhausted humans did not cause arrhythmias nor was there a detectable change in their 12-lead ECGs.21 In another study of a resting adult population, for a 24-hour period after a 5-second application of the Taser, the ECG was unaffected, nor were arrhythmias or significant direct cardiac cellular damage that may be related to sudden and unexpected death detected. No evidence of dangerous hyperkalemia , induced acidosis, or an increase in core body temperature was found.22 23 Regarding the human stress response, Dawes, et al have shown that the EMD or other electrical devices do not elicit this response any more than other uses of force and are safer than a prolonged physical struggle for the person in excited delirium.24 These investigators were affiliated with:
- Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN
- Department of Cardiology, Cleveland Clinic and Hospital, Cleveland, OH.22
- Emergency Department, Lompoc District Hospital, Lompoc, CA
- Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN
- Division of Medical and Technical Research, Taser International, Inc., Scottsdale, AZ
- Emergency Department, Meridian Park Hospital, Tualatin, OR23
- Lompoc Valley Medical Center, Lompoc, CA24
- Hennepin County Medical Center, Minneapolis, MN24
Carotid restraint. The carotid restraint used in law enforcement to subdue people with excited delirium has its origin in Jiu-Jitsu---the technique is the same. Although this restraint is sometimes referred to as “the choke hold”, it does not place pressure over the trachea with the intention of cutting off air; it is not a choking hold. The misnomer is unfortunate and misleading for the public and in a court of law. Correctly applied, the trachea lies protected in the bend in the officer’s arm while pressure is applied over the two carotid arteries on the sides of the neck, causing the suspect to lose consciousness. This short period of unconsciousness can be used by officers to take the suspect into custody.
Transport of the prisoner. Violently agitated prisoners should always be taken to a hospital, never to a jail, and they should not be transported in a police car. Whatever the means of transport, victims need close supervision.
Summary. For all police officers, the use or Taser or carotid restraint on an agitated, violently combative person is an attempt to quickly gain control and avoid a prolonged and potentially dangerous life-threatening struggle for a person who is psychotic, unable to process verbal police instructions, and physically unfit for a struggle, something that he is unable to comprehend.
TIME-LINE FOR DRUG-RELATED DEATHS DURING ARREST OR IN CUSTODY
Stephen. B. Karach, M.D. and
Boyd. J. Stephens, M.D.25 report that remedies to treat cases
of excited delirium are currently ineffective and survival is unlikely.
This is as opposed to prevention of death in drug withdrawal, suicide,
and natural causes. As Drs. Karach and Stephens have pointed,
out this critical difference places drug related deaths in a different
category, requiring that they be considered separately.
Time of Drug-Related Deaths in Prisoners Related to Cause
The cause of drug-related deaths in prisoners usually fall into four time periods: during arrest, 2 hours later, within 12 hours, and after 12 hours.26
- During arrest and transport, excited delirium is the principal cause of death and drug dealers swallowing the evidence at the time of arrest being another.
- Approximately 2 hours after arrest rhabdomyolysis and multisystem failure are the causes of death..
- Within 12 hours of arrest, death is usually from massive overdose in smugglers and dealers.
- After 12 hours but while still on remand—most often deaths are related to withdrawal or natural causes.
In some cases, death occurs
at home, unattended. In one study, investigators at the scenes
found the person dead with elevated rectal temperatures, abrasions on
the extremities, and damaged and tossed dwellings. Positive toxicology
confirmed drug-induced excited delirium.1 More often,
police are summoned during the psychotic agitation phase. Taser deployment
is used to quickly subdue and restrain the victim, avoiding a prolonged
struggle involving the efforts of five or six officers or use of chemical
agents which usually have no effect.25
Most, but not all, victims of excited delirium are chronic, long-term, high-dose CNS stimulant abusers. Initially hyperthermic, they soon become psychotic, experiencing several hours of violent agitation followed by cardiac arrest a few hours later, with or without police intervention. Even when medical intervention is immediately available and without the stress of restraint, there is still a high risk of death.17 If attempts at resuscitation are successful, almost all victims die of rhabdomyolysis and multisystem failure a few days later.1 25- 27
Rhabdomyolysis is a well-documented complication of cocaine and other illicit drugs because of the extremely intense and violent muscle activity involved. It has been reported in 24% of cocaine users.37 In fact, Ruttenber, et al17 have concluded that “because cocaine-associated rhabdomyolysis and excited delirium have similar clinical features and risk factors, occur in similar populations of drug users, and can be explained by the same pathophysiologic processes”, they are different stages of the same syndrome and are caused by changes in dopamine processing induced by chronic and intense use of cocaine rather than by the acute toxic effects of the drug.17
COMPLEXITY OF HISTORY TAKING
Tanquay, et al28 relate an unusual case in which a man died suddenly while running naked on the street. The initial death investigation listed excited delirium from drug intoxication, which would have compounded the sorrow for his family. Autopsy revealed obstruction of breathing by an inflammatory laryngeal polyp. Toxicology studies were negative and investigation revealed a visit at a hospital the day before his death when he was complaining of stridor (difficult breathing). He sought help and found none. It is believed he developed airway obstruction while dressing at home, couldn’t breathe, and ran out on the street desperate to find help.
Dr. Tanquay’s case is admittedly unusual. It does, however, impresses one with the importance of a thorough death investigation, especially when that death was a sudden psychiatric death while in police custody. Police officers must realize that although sudden death in the context of excited delirium is not unexpected, the interest and influence of an uninformed media and possible witnesses requires a complex police investigation, including the personal, social, and business milieu in the decedent’s life that would not ordinarily be part of a postmortem police investigation. The complexity of aggression sends the investigation deep into the personal life of the decedent. You are looking for signs of stress, medical problems, aberrant behavior, history of abuse, etc. There is much at stake. The investigation should include:
- Description of the scene and circumstances surrounding the death
- Review of records from emergency departments
- Complete autopsy
- Toxicologic analysis of cocaine and other licit or illicit drugs in the blood
- Personal history
- Reports from social contacts (attitudes, stress, angry outbursts, etc.)
- Medical history
- Recent increases of stress (financial, domestic, personal)
- Prior incidents of aggression
- Activities and situations immediately prior to the violent incident
- Complaints of poor health or unusual symptoms prior to the sudden onset of excited delirium
- Compliancy in taking prescribed medications
- Evidence of adverse rearing conditions
Police officers are referred for more information on history taking to:
AUTOPSY FINDINGS IN EXCITED DELIRIUM
The importance of the findings
at autopsy cannot be over estimated. If death occurs while officers
are trying to restrain a victim, the police may be assumed to be responsible
simply on the basis of proximity. If the case comes to legal review,
the issues raised are predictable, thus, everything should be done to
ensure well documented events and findings.25
Core body temperature: A
body temperature greater than or equal to 103º F (39.44º C) is considered
to be evidence of hyperthermia. A rectal temperature should be taken as soon as qualified medical staff can do so on a suspect admitted
to hospital after such an incident or by the coroner in the case no
temperature was obtained prior to death. Ear canal infrared measurement,
skin strips, and skin palpations should be avoided, as they are unreliable.1
Drug levels in the blood.
Illicit drugs in the blood obviously confirms that the decedent used
drugs, although a negative report does not prove absence of excited
delirium. Brain toxicology is a preferred matrix, since many abused
substances can be detected over longer periods.1
2-protein biomarker (dopamine transporter and heat shock protein) analysis
- Dopamine transporter blood levels. Low levels are a positive finding for excited delirium, Toxicology and history of drug or alcohol abuse or a psychological autopsy will help to show cause.
- Heat shock protein (Hsp70). Elevated whenever core body temperature is increased. This marker is a surrogate for hyperthermia in cases of excited delirium.
Markers for intravenous
drug abuse. These may also be present, but their presence
only provides confirmatory evidence of chronic drug abuse.30 31
Cocaine concentrations in blood and brain. Levels will be modest, but concentrations of the cocaine metabolite benzoylecgonine may be quite high because of its longer half-life32 and it accumulates in the tissues of chronic users.28
Test for chemical agents, particularly capsicum spray. Karch and Stephens25 state that in their experience these agents have no effect on patients with excited delirium, but that if the victim dies, death will be blamed on their use. Failure to recover the sprayed capsicum from the facial area, or from the airway in cases of accidental death, is reasonable evidence that capsicum did not enter the lungs and did not directly cause toxicity or death. Methanolic swabs (saline swabs in the living) can be used to recover capsicum from the skin and clothing. Of course, if capsicum is not a factor, death cannot be attributed to its use.
Pulse oximetry monitoring. Accusations of positional asphyxia can be precluded in this way. If vital signs and oxygen saturation are continuously recorded during transport, then it matters little what position the decedent was in or how he was restrained, provided it can be proven that his respiratory status was not impaired.
The victim’s temperature is recorded as soon as possible. Although
this is rarely done with an agitated person, without documentation of
hyperthermia, it becomes more problematic to prove excited delirium.
If the victim cannot be resuscitated, rectal temperature should be recorded
as soon after death as possible, and again at autopsy.
The victim is photographed to document both the absence of and the presence
of petechiae or bruises. Petechiae can form after death.
If their absence is not documented, and they are found during a second
autopsy charges of incompetence or cover-up may result.
Brain dopamine and kappa receptors. To document these changes, the brain is removed and frozen within 12 hours. Frozen samples can then be sent to a reference neurochemistry laboratory.28
Traumatic injury to the neck. The thoracic organs and the brain should be removed before the neck dissection to decompress venous return and prevent artifactual bleeding into the soft tissues of the neck, the presence of which may falsely suggest traumatic injury. Obviously, a scrupulous well-photographed neck dissection will be required to determine whether a choke hold or neck compression has been applied.33
Heart examination. Careful weighing, measurement of wall thickness, and the taking of multiple sections for histological examination are important.34 Since heart size is an independent risk factor for sudden death,35 the measurement may prove to be a very significant factor in determining the cause of death.
Autopsy report on a case of non-drug related excited delirium. Bunai et al36 the arrest and death in Japan of a 39-year-old man suspected of being a rapist. He “vigorously resisted” arrest, but was eventually restrained after a 20-minute struggle with police officers and several men. He collapsed shortly thereafter, was transported to a hospital, and pronounced dead on arrival. His rectal temperature was 40 degrees C. (104 degrees F) 2.5 hours after death. Autopsy revealed abrasions and subcutaneous hemorrhages of the head, face, arms, and legs. The heart was dilated and there were subendocardial hemorrhages in the left ventricle. The brain and both lungs were congested. Microscopic examination of the lungs revealed intra-alveolar edema and hemorrhages. The skeletal muscles showed contraction band necrosis and hyaline degeneration. The liver showed diffuse coarse-droplet fatty infiltration of hepatocytes. Neither addictive drugs nor alcohol were detected from the blood or urine. It was concluded that cause of death was fatal hyperthermia in a state of excited delirium.
A PATH TO PSYCHOSIS AND SELF-DESTRUCTION13
At low oral doses of CNS stimulants, alertness is improved; mood is
elevated, sexual arousal intensifies and appetite is suppressed.
Pupils dilate; heart rate and blood pressure increase.
Triggers. After this the budding drug addict is at the mercy of internal and external triggers such as a person, place, or thing associated with using. Internal triggers are often emotional such as anger, desire, hurt, or fear. The triggers can lead to the thought about using. If the person does not block the thought or leave the triggering situation, an escalating intense craving takes control and the victim will stop at nothing to have the drug.
doses. Acute intoxication of the CNS occurs, especially after
intravenous use. The effects are intense, distracting, and overwhelming.
The person is exhilarated and euphoric with feelings of great physical
strength and mental capacity, excitation, panic, and sexual arousal.
In some cases even when it is the initial CNS intoxication, the person
may have hallucinations, delusions and combative behavior.
phase. Then enters the phase known as “tweaking”. During
this phase, euphoria is gradually replaced with mounting anxiety, irritability,
delusions, paranoia, and pseudo-hallucinations. Binging continues
in pursuit of the initial “upside”, but the highs collapse into
deeper lows leading to exhaustion---the onset of the “crash phase.”
Crash phase. At this point the user stops administration of the drug and sleeps restlessly for a day or more.
Psychotic phase. Continued binge-type drug use brings true schizophrenic-like hallucinations, delusions, and over-heated, violent behavior. Most are chronic freebase “crack” cocaine users who have recently been on a binge. This excited delirium phase is often a terminal event, with death occurring within hours of the onset of symptoms, alone or in police custody.
We are grateful to Deborah C. Mash Ph.D. for her review of the section on “Brain biomarkers for excited delirium and sudden death. Dr. Mash is Professor of Neurology and Molecular and Cellular Pharmacology, Jeanne C Levey Chair for Parkinson's Disease Research, Dept. of Neurology, Miller School of Medicine, University of Miami, Florida. Co-authors with Deborah C Mash Ph.D on this study were:
- Linda Duque, CAP; John Pablo, PhD; Yujing Qin, PhD; Nikhil Adi, PhD, Dept. of Neurology, Miller School of Medicine, University of Miami, FL.
- W. Lee Hearn, M.D. and Bruce A. Hyma, M.D. Miami-Dade Medical Examiner Dept., Miami, FL.
- Steven B. Karch, MD, FFFLM, Consultant Cardiac Pathologist & Toxicologist, Berkeley, CA.
- Henrik Druid, M.D., PhD, Dept.of Forensic Medicine, Karolinska Institute, Stockholm, Sweden.
- Charles V. Wetli, M.D., Dept. of Health Services, Division of Medical Legal Investigations and Forensic Sciences, Suffolk County, NY.
- We would also like to thank David Sulzer, Ph.D, for his careful review of the section on neurophysiology and the effect of methamphetamine and cocaine. Dr. Sulzer is Associate Professor of Clinical Psychiatry and Neuroscience at Columbia University, NYC, NY with an area of research that includes synapes and circuits, neurodegeneration and repair. He specializes in neurotransmission and mechanisms of neurodegeneration in basal ganglia and dopamine neurons. Thank you, David; your review and changes were greatly appreciated.
1. Mash DC, Duque L, Pablo
J, Oin Y, Adi N, Hearn WL, Hymab BA, Karch SB, Druid H, Wetli CV:
Brain biomarkers for identifying excited delirium as a cause of sudden
death. Forensic Science International 190 (2009) e13–e19.
1a. Excited delerium, education,
research information. www.exciteddelerium.org
2. Ross CA, Peyser CE, Shapiro
I, Folstein MF: Delirium: phenomenologic and etiologic subtypes.
Int Psychogeriatr. 1991 Winter;3(2):135-47.
3. Samuel E, Williams RB, Ferrell
RB.: Excited delirium: Consideration of selected medical and psychiatric
issues. Neuropsychiatr Dis Treat. 2009;5:61-6
4. Seo D, Patrick CJ, Kennealy
PJ: Role of Serotonin and Dopamine System Interactions in the Neurobiology
of Impulsive Aggression and its Comorbidity with other Clinical Disorders.
Aggress Violent Behav. 2008 Oct;13(5):383-395.
5. Haavik J, Blau N, Thöny
B.: Mutations in human monoamine-related neurotransmitter pathway
genes. Hum Mutat. 2008 Jul;29(7):891-902.
6. Popova NK.: On the role
of brain serotonin system in the pathway from gene to behaviour.
Ross Fiziol Zh Im I M Sechenova. 2007 Jun;93(6):569-75.
7. Popova NK: From genes to aggressive behavior: the role of serotonergic system. Bioessays. 2006 May;28(5):495-503.
8. Parsian A, Cloninger CR.: Serotonergic pathway genes and subtypes of alcoholism: association studies. Psychiatr Genet. 2001 Jun;11(2):89-94.
9. Craig IW: The importance of stress and genetic variation in human aggression. Bioessays. 2007 Mar;29(3):227-36.
10. Volkow ND, Chang L, Wang GJ, Fowler JS: Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers. Am J Psychiatry 2001; 158:377–382.
11. Volkow, N.D., et al. Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 386:827-830, 1997
12. Volkow, N.D.; Wang G.-J.; Fowler, J.S.; Legan, J.; Gatley, S.J.; Hitzeman, R.; Chen, A.D.; Dewey, S.L.; Pappas, N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 386:830-833, 1997.
13. Logan BK: Methamphetamine--Effects on human performance and behavior. Forensic Laboratory Services Bureau, Washington State Patrol, Seattle, WA. www.ndaa.org/pdf/ntlc_meth.pdf
14. Sulzer D, Sonders MS, Poulsen
NW, Galli A: Mechanisms of neurotransmitter release by amphetamines:
A review. Progress in Neurobiology 75 (2005) 406–433
15. Grant JR, Southall PE, Mealey J, Scott SR, Fowler DR: Excited delirium in custody, Am. J. Forensic Med. Pathol. 30 (2009) 1–5.
16. Matsunari Y, Kita T, Saraya T, et al: Methamphetamine-induced neurotoxicity and self-injurious behavior in BALB-c mice. Japanese J Pharm, 79 (suppl. 1). 1999. 247P.
17. Ruttenber AJ, McAnally H, Wetli CV: Cocaine-associated rhabdomyolysis and excited delirium: different stages of the same syndrome, Am. J. Forensic Med. Pathol. 20 (2) (1999) 120–127.
18. Toshirou Makisumi, Ken-ichi Yoshida, et al: Sympatho-adrenal involvement in methamphetamine-induced hyperthermia through skeletal muscle hypermetabolism. European J Pharm, 3363;107-112, 1998.
19. Kapur S: Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia, Am. J. Psychiatry 160 (2003) 13–2319.
20. J. D. Ho , MD, James R.
Miner, MD, R. Dhanunjaya. Lakireddy, MD, Laura L. Bultman, MD,
William G. Heegaard, MD, MPH: Cardiovascular and Physiologic Effects
of Conducted Electrical Weapon Discharge in Resting Adults.
Society for Academic Emergency Medicine ISSN 1069-6563 doi: 10.1197/j.aem.2006.01.017
21. Ho JD, Dawes DM, Heegaard
WG, Calkins HG, Moscati RM, Miner JR.: Absence of electrocardiographic
change after prolonged application of a conducted electrical weapon
in physically exhausted adults. J Emerg Med. 2009 May 12
22. Ho JD, Miner JR, Lakireddy DR, Bultman LL, Heegaard WG Cardiovascular and physiologic effects of conducted electrical weapon discharge in resting adults. Acad Emerg Med. 2006 Jun;13(6):589-95
23. Dawes DM, Ho JD, Johnson
MA, Lundin E, Janchar TA, Miner JR.: 15-Second conducted electrical
weapon exposure does not cause core temperature elevation in non-environmentally
stressed resting adults. Forensic Sci Int. 2008 Apr 7;176(2-3):253-7.
24. Dawes D, Ho J, Miner J.:
The neuroendocrine effects of the TASER X26: a brief report.
Forensic Sci Int. 2009 Jan 10;183(1-3):14-9.
25. Steven B Karch MD Boyd G Stephens MD: Drug abusers who die during arrest or in custody. Journal of the Royal Society of Med, 92: March 1999 and Section of Clinical Forensic & Legal Medicine, 20 June 1998.
26.Wetli CV, Fishbain DA. Cocaine-induced psychosis and sudden death in recreational cocaine users. J Forens Sci 1985;30:873-80.
27. Wetli CV, Mash D, Karch SB. Cocaine-associated agitated delirium and the neuroleptic malignant syndrome. Am J Emerg Med 1996;14:425-8
28. Tanguay J, Pollanen M.: Sudden death by laryngeal polyp: a case report and review of the literature. Forensic Sci Med Pathol. 2009;5(1):17-21.
29. Paterson S, Cordero R,
Stearns E.: Chronic drug use confirmed by hair analysis: its role
in understanding both the medical cause of death and the circumstances
surrounding the death. J Forensic Leg Med. 2009 Apr;16(3):143-7.
30. Helpern M, Rho Y. Deaths
from narcotics in New York City. NY State MedJ 1966;66:2391-408
31. Paties C, Peveri V, Falzi G. Liver histopathology in autopsied drugaddicts. Forens Sci Int 1987;35:11-26
32. Cone EJ. Pharmacokinetics
and pharmacodynamics of cocaine. J Anal Toxicol 1995;19:249-78
33. Reay DT. Death in custody. Clin Lab Med 1998;18:1-22
34. Virmani R. Techniques for examination of the heart. In: Karch S, ed. Drug Abuse Handbook. Boca Raton: CRC Press, 1998:86-101
35. Kannel WB, Levy D, Cupples LA. Left ventricular hypertrophy and risk of cardiac failure: insights from the Framingham Study. J Cardiovasc Pharmacol 1987;10(suppl 6):S135-40
36. Bunai Y, Akaza K, Jiang
WX, Nagai A.: Fatal hyperthermia associated with excited delirium
during an arrest. Leg Med (Tokyo). 2008 Nov;10(6):306-9.
37. Derlet RW, Rice P, Horowitz BZ, LordRV: Amphetamine toxicity: experience with 127 cases. J Emerg Med 7:157; 1989.