Download Case # 5

Case # 5
The Case of the Comatose Prisoner
James Roberts, MD, FACEP
A 22-year-old male is brought from the jail after being found unresponsive in his cell.
The patient had been arrested 18 hours earlier for suspected drug dealing. He had been
taken to another hospital where he was “cleared” prior to being incarcerated. There was
no known medical history.
The Cocaine Washout Syndrome
Roberts, MD, MPH
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Overview
Multiple mental status changes have been attributed to the pharmacological effects of
cocaine. Most are neuroexcitatory in nature, consisting of agitation, confusion,
hyperactivity, combativeness, and seizures. Autonomic dysfunction, including
tachycardia, diaphoresis, tremor, mydriasis, and hypertension are well known, common,
and can be quite impressive. Acute cocaine toxicity can also produce ventricular
arrhythmias, stroke, intense vasoconstriction, acute myocardial infarction, and aortic
dissection; these conditions are largely responsible for lethal cocaine reactions. Under
certain circumstances, however, cocaine can produce a state of mild to extreme
neuroinhibition.
Pathophysiology of Cocaine
Many of the CNS effects of cocaine have been related to the drug’s ability to manipulate
neurotransmitter activity in the brain. Many neurotransmitters are likely involved but
most is known about norepinephrine, dopamine, and serotonin.
Norepinephrine is the predominant neurotransmitter in the sympathetic portion of the
autonomic nervous system. It is found in the brainstem (locus ceruleus) and the cerebral
cortex, and excess norepinephrine likely accounts for many of the toxic effects of
cocaine. When cocaine is present norepinephrine is released into the synapse from
presynaptic storage sites. Norepinephrine stimulates receptors on the postsynaptic
neuron, and then undergoes reuptake back into the presynaptic neuron. Cocaine blocks
this reuptake, resulting in excess neurotransmitter in the synaptic cleft. Cocaine may also
directly release neurotransmitters. The result is continued overstimulation of the
postsynaptic receptors. Cocaine probably has a similar effect on dopamine and serotonin,
with the final common pathophysiology being reflected as an excess of numerous
neurotransmitters.
After prolonged cocaine use, the brain’s ability to continually release neurotransmitters
for even normal physiologic purposes is hindered. Essentially they are “used up” and
even additional cocaine use will not have the same physiologic effect. This results in an
overall depletion of synaptic neurotransmitters and a depressed, rather than excitatory,
state.
Although there is much individual sensitivity, all individuals who chronically use
sympathomimetic substances eventually experience a depressed mental state, either from
shear exhaustion, lack of additional drug, or from an intervening medical problem that
separates them from the drug. This well-known phenomenon is called the “crash” and it
can be manifested in numerous ways. Similar to amphetamine users, cocaine users often
experience a significant hypoexcitatory state that leads not only to sleep and exhaustion,
but to frank coma.
This term has been used to describe the end result of prolonged cocaine use that is
manifested as a severe state of hypoactivity. Although known to cocaine users and
The Cocaine Washout Syndrome
Roberts, MD, MPH
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emergency physicians and toxicologists, it is not well described in the medical literature.
There are absolutely no data on the incidence, severity, or exact physiology of this
syndrome. Only 2 anecdotal reports appear in the literature. Although known for years,
the exact physiology is unknown; however, it seems most logical to ascribe etiology to
the neurotransmitter depletion theory.
(Diagnosis): The cocaine washout syndrome is, at present, a diagnosis of exclusion. The
symptoms can mimic a plethora of other serious medical problems that must be
addressed, including head trauma, stroke, hypoglycemia, infection, and numerous
metabolic conditions. While the syndrome may be suspected on clinical grounds, a
thorough search for additional pathology must be undertaken.
(Clinical characteristics): Individuals can present primarily with this syndrome, being
found unresponsive, listless, or lethargic, in the street, crack houses, or in jail. Frequently
it develops after relatively small doses of sedatives, usually benzodiazepines, are
administered in the ED to treat suspected cocaine toxicity. Patients will develop various
stages of hypoactivity, including lethargy, exhaustion, or frank coma. They can be
impressively unresponsive to significant stimuli, including pain, tracheal intubation,
blood drawing, and bladder catheterization. Vital signs are often relatively normal, and
the expected bradycardia and hypotension intuitively expected may be absent.
Specifically patients do not have the tachycardia or hypertension seen with acute cocaine
intoxication. Patients appear to be in a deep sleep, but usually maintain vital signs and
respiration in the normal range.
(Physical examination): There are no characteristic physical findings. Importantly,
findings of acute cocaine toxicity should be absent. Many will exhibit the stigmata of
chronic cocaine abuse. Concomitant trauma or medical illness will complicate the
diagnosis, but in the pure syndrome patients have dry and warm skin, a normal to slightly
lowered core temperature, and demonstrate no signs of autonomic instability. The mental
status will vary from drowsiness to deep coma. Speech may be slurred to nonexistent.
The neurologic examination should be nonfocal, without clonus, Babinski sign, or
fasciculations/tremor. Hyporeflexia to flaccidity may be seen. The response to painful
stimuli and medical interventions will vary. Dysconjugate gaze is common in the
author’s experience, probably reflecting the deep state of sleep. Pupils are normal in size
and normal to sluggishly reactive. The physical examination is primarily directed toward
ruling out concomitant states, such as hypoglycemia, sepsis, trauma, CNS infection, a
focal neurologic finding, or other toxidromes.
(Laboratory testing): There are no characteristic findings on routine laboratory testing.
Abnormalities in vital signs and routine tests (CBC, lytes, urinalysis, EKG, etc) should
prompt additional evaluations. Hypoglycemia should be determined immediately with
bedside testing. A drug screen should be positive for cocaine metabolites and is useful to
evaluate other drug use. Serum ethanol testing is often helpful. When the diagnosis is
obvious and the symptoms mild, patients can be observed clinically. In serious cases the
clinician is forced to include such things as CT scanning, lumbar puncture, and blood gas
The Cocaine Washout Syndrome
Roberts, MD, MPH
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analysis. Currently there is no known role for catecholamine level determination; in fact,
catecholamine levels have not been studied in reference to this syndrome.
(Treatment): Treatment is supportive. Vital signs and pulse oximetry should be
monitored continually. Thiamine administration makes empiric sense, as does
maintenance fluid administration and supplemental oxygen. Standard measures should be
employed to monitor and treat airway compromise. If narcotic use is suspected, naloxone
may be administered in small amounts. Flumazenil is best withheld, even if the syndrome
has developed post benzodiazepine administration. Patients with significant altered
mental status should be admitted to the appropriate level of monitoring. Observation
status for patients minimally affected is reasonable. Often social/psychiatric problems
preclude early discharge. There is no known way to hasten the resolution of this
syndrome, and stimulants are to be avoided. There is no known rationale to administer
empiric dopamine or other pharmacological methods to restore neurotransmitters.
(Clinical course): Patients will slowly awaken over 8-24 hours. Generally there is little
recollection of the events for the past few days and a withdrawal state is not expected
(unless the patient experiences narcotic/ethanol withdrawal). There are no known long
term sequelae of the cocaine washout syndrome, but complications of cocaine abuse are
protean.
The Cocaine Washout Syndrome
Roberts, MD, MPH
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The Cocaine Washout Syndrome
References
1. Trabulsky ME: Cocaine Washed Out Syndrome in a Patient With Acute
Myocardial Infarction. Am J Emerg Med 1995;13:538. (single anecdotal
case)
2. Sporer KA, Lesser SH: Cocaine Washed Out Syndrome Ann Emerg Med
1990;19(12):1422. (letter to editor, describing anecdotal experience)
3. Spivey WH, Euerle B: Neurologic Complications of Cocaine Abuse. Ann Emerg
Med 1990;19:1422. (good discussion of cocaine pharmacolgy but does not
mention syndrome by name)
4. Mendelson JH, Mello NK: Management of Cocaine Abuse and Dependence.
NEJM 1996;334(15):965. (good discussion but does not address the
syndrome specifically)
The Cocaine Washout Syndrome
Roberts, MD, MPH
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The Cocaine Washout Syndrome
Questions
1.) The proposed etiology of the cocaine washout syndrome is:
a.
b.
c.
d.
e.
catecholamine depletion
cerebral edema
occult hypoglycemia
occult sedative/hypnotic overdose
thiamine depletion
2.) The mechanism of action of cocaine toxicity is:
blocked reuptake of neurotransmitters
serotonin depletion
inhibition of sodium influx
dopamine receptor blockade
acute increased intracranial pressure
3.) Which of the following best describes the cocaine washout syndrome?
a.
b.
c.
d.
e.
hypertension and diaphoresis
hyperthermia and tachycardia
normal vital signs and coma
hypotension and bradycardia
hyperreflexia and tremor
4.) Which of the following may precipitate the syndrome?
a.
b.
c.
d.
e.
benzodiazepine administration
ethanol withdrawal
narcotic withdrawal
minor head trauma
rhabdomyolysis
5.) What is the preferred treatment of the cocaine washout syndrome?
a.
b.
c.
d.
e.
low dose dopamine infusion
caffeine and glucose administration
supportive care only
trial of flumazenil and naloxone
alkaline diuresis
The Cocaine Washout Syndrome
Roberts, MD, MPH
The Cocaine Washout Syndrome
Answers
1.) Answer: a.
2.) Answer: a.
3.) Answer: c.
4.) Answer: a.
5.) Answer: c.
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