This document discusses hyperdynamic drugs and their associated toxidrome. It defines a toxidrome as a group of signs and symptoms that constitute the basis for a diagnosis of poisoning. The document describes similarities and differences between various hyperdynamic drugs, including amphetamines, methamphetamines, MDMA, synthetic cathinones, and cocaine derivatives. It discusses pathophysiology, complications, treatment including benzodiazepines, antipsychotics, fluids and cooling, and restraint. Key risks are also summarized such as the lethal H's (hypoxia, hypercarbia, acidosis, hyperthermia).
6. What is a Toxidrome?
• syn·drome (ˈsinˌdrōm/)
• noun
• 1. a group of symptoms that
consistently occur together or
a condition characterized by a
set of associated symptoms.
• tox·i·drome (ˈtäksiˌdrōm/)
• noun
• 1. a group of signs and
symptoms constituting the
basis for a diagnosis of
poisoning.
In other words: A toxidrome is a “syndrome” that specifically relates to a
specific toxin
Be cautious, many syndromes/toxidromes are subtle and overlap their
symptoms. Thorough assessment is essential
7. What are the:
Similarities? Most cause….
• Pupils (dilated)
• Decreased Sleep/Insomia
• Increased Heart Rate
• Increased B/P
• Increased Body Temp
• Increased CO2 production ( ↑
ETCO2)
– Decreased pH over Time
• Increased O2 consumption(may
or may not affect SPO2)
Differences?
• Route
• Onset
• Mental Status
– Hallucinations
– Mania
– Agitation
– Paranoia
– Somnolence?
• Cardio Toxic vs. Simply Cardio
stressful?
• Neuro-toxic?
– Seizures?
• Primary and secondary causes of
Mortality
8. Remember…
• Other problems can cause stimulant like
behavior…
• Drug withdrawal
• Psychosis/Behavioral Conditions
• Delirium
• Other Toxins
– Dissascoiatives (i.e. PCP)
– Drug side effects
• Other Medical Conditions
9. Sympathomimetic Toxidrome
• Drug Specific
• Mydriasis
– Dilation of Pupil
• Tachycardia
• Cardiac Stress
– Chest Pain, SOB, etc
– CHF
• HTN
– Increased risk of stroke
– Aneurysms
– Head Ache
– Cerebral Bleeds
• Abd Pain
– Mesenteric Ischemia
• Diaphoresis
– May not occur in severe
hyperthermia and dehydration
• Acute psychosis
– Paranoia
– Combative
– SOB
– Anxiety
• Delirium
• Bruxism
12. Additional
Complications
• Multiple Day Use
– Increased risk of
hyperthermia and
delirium
– Increased paranoia and
agitation
– Increased mortality
• Lack of sleep = Psychosis and
Paranoia
18. Remember…
• If they are altered in their mental status…
– Stroke Assessment
– Check for head trauma and spontanous head
bleeds
– Check BG
– Check Temp
– A.E.I.O.U. T.I.P.S.
21. “…If removal of noxious stimulus
fails to resolve episode,
pharmacologic therapy is
indicated.”
- ACP/ACCESS SWO’s M-14
22. Benzodiazepines
“ Management of agitated or combative patients: Use
of sedatives (Benzodiazepines) is highly recommended
for even moderate agitation from hyperdynamic use,
and may decrease heat production, decrease cardiac
toxicity, and improve outcomes, as well as improve
provider safety”
-ACP/ACCESS SWO R-3 “Hyperdynamic Crisis/Overdose” dates May 1, 2016
23. Benzo Doses
• All Benzo’s require SPO2 and EKG
– (and should also strongly consider Nasal ETCO2)
• High potentiation with opioids and ETOH
– use with caution
• Diazepam
– 2.5-5 mg
• Lorazepam
– 0.5-2 mg
• Midazolam
– 0.5-1 mg
26. Adjunctive Medications
• Adjunctive medications: These medications
are given for their potentiation of other drugs
effects or for the prevention/treatment of
certain side effects (nausea, EPS, etc) of drugs
used in sedation.
• Zofran (ondansetron) IV /IM/IO
– Adult: 4 mg
– Pediatric: 0.1 mg/kg to a maximum of 4 mg
27. The NEW Saturday Night Special ?
• Diazepam
– 2.5-5 mg
• SPO2, EKG, and
ETCO2 monitoring
• Temperature
29. What do our docs say?
• “Benzodiazepines are still first line for the
agitation and hyper dynamic crisis. “
• Dr. Ben Cornett 5/2016
• “There is some discussion at a national level
of what exactly is best. I don't think we
need to rush off and do something because
it is trendy without evaluating what is
right.”
• Dr. Ian Butler-Hall 06/2016
30. Ketamine
(NOT CURRENTLY IN OUR SWOs)
• NOT CURRENTLY IN OUR SWO”S
• Dose is different from RSI!!!
– 0.5-1 mg / kg
• Advantages
– Very rapid onset,
– Airway Reflexes tend to remain intact
– Multiple Routes (IM, IV)
– Typically effective in one dose
• Disadvantages
– No SZ suppression
– Increased monitoring
– Must monitor SPO2 and ETCO2 closely
• Misc
– DEA Schedule III
– Often successful when other drugs fail
– Yes it increases HR and B/P, but this was rarely clinically significant
– SPO2 decreases have been reported, but this may be due to restraint position rather than the
drug.
31. Fluids and Cooling
“Obtain patient’s temperature and cool/warm
as necessary”
-ACP/ACCESS SWO R-3 “Hyperdynamic Crisis/Overdose” dated
May 1, 2016
“Initiate passive cooling for temperature < 103 F or
39.5 C “ and “Promote cooling; initiate active cooling
for significant hyperthermia for temperature > 103 F
or 39.5 C “
-ACP/ACCESS SWO R-3 “Adult Heat Emergencies” dated OCT 15,
2014
32. Restraint
Restraints may be used for patient and/or rescuer
safety:
• Do not restrain prone.
• 4 point restraints are recommended
• Observe and prevent positional asphyxia.
• Monitor airway and respirations closely.
• If restrained, do not release restraints until at the hospital
unless required for essential patient care
• Do not leave patient unattended
• Allow for adequate heat dissipation
34. Chest Pain and Stimulants
• Chest pain and anginal equilivents (such as SOB,
chest pressure, left arm pain) are a common
result of stimulant use.
• Some drugs are directly toxic to the heart. Some
are merely stressful on the heart, aggravating
pre-existing coronary artery disease.
• Nitrates remain indicated for chest pain and
Angina equivalents.
• Benzodiazepines are acceptable adjunctive
therapies as well in addition to nitrates.
35. Drug Induced Symptomatic
Tachycardia
• Cooling
• Fluid Boluses (If no sign of CHF)
• Benzodiazepines
• Symptomatic tachycardias refractory to
Benzodiazepines:
– Lidocaine is the anti-arrhythmic of choice for
refractory monomorphic ventricular tachycardia (VT).
– Magnesium Sulfate remains the antiarrhythmic of
choice for polymorphic VT (Torsades), although should
be used with caution when hypotension is present.
36. Drug Induced Symptomatic
Tachycardia
• Cooling
• Fluid Boluses (If no sign of CHF)
• Benzodiazipines
• Symptomatic tachycardias refractory to
Benzodiazepines: Lidocaine is the anti-arrhythmic
of choice for refractory monomorphic ventricular
tachycardia (VT). Magnesium Sulfate remains the
antiarrhythmic of choice for polymorphic VT
(Torsades), although should be used with caution
when hypotension is present.
37. REMEMBER: overdoses are AMS calls
first, overdoses last
• A - alcohol, alcohol withdrawal, and anoxia
• E - epilepsy and other neurological disorders
• I - insulin (Hyper or Hypo-glycemia)
• O- overdose (Poly-pharmacy?)
• U - uremia, underdose of current medications.
• T- trauma
• I - infection
• P - psychiatric
• S - stroke, shock states
40. How Long has Meth and other Amphetamines been around?
• Jan 18, 1887-Amphetamine was
first synthesized by a German
chemist
• 1919- Methamphetamine is first
synthesized (in Japan)
• WWII -Both Amphetamine and
Methamphetamine (by the
Japanese mostly)are widely
distributed to soldiers to help
improve performance. This led to
addiction problems in Japan after
the war.
cc: Don Hankins - https://www.flickr.com/photos/23905174@N00
41. Background- Meth and other Amphetamines
• “Meth" is methamphetamine,
which is a type of amphetamine.
• The chemical Methamphetamine
is composed of an amphetamine
molecule with an additional
methyl group attached to its
nitrogen (amine group).
• For Methamphetamine, the
methyl allows it a little better fat
solubility and thus better
penetration into the brain.
cc: AZRainman - https://www.flickr.com/photos/10646468@N02
42. MDMA
• Developed in Germany in early 1900’s
• Patent in 1913 as potential
• Dormant recreationally until 1970s
• Banned by DEA in 1985 – Schedule I
• Demographic- HS through mid 30’s
cc: tanjila - https://www.flickr.com/photos/11339074@N00
44. MDMA…What is does…
• MDMA is best described as an _____________ with
_____________ properties.
• Many of the effects are dose dependent.
– Auditory and/or visual hallucinations are not commonly
observed.
– Tactile hallucinations and Tactile euphoria more common.
– Much of the abuse potential lies in its pleasurable
subjective effects (eg, empathy, euphoria, disinhibition,
increased sensuality).
• AKA: “The Hug Drug”
Amphetamine
Hallucinogenic
45. What Kills…
• LETHAL H’s
• HYPERTHERMIA
• HYPOXIA
• Hypercarbia
• H+ (Acidosis)
• Restraint related deaths
• Do not restrain prone
• No not promote the lethal H’s
• Other Causes
• Dehydration
• Kidney Failure
• Misadventure
cc: Anna & Michal - https://www.flickr.com/photos/97006177@N00
46. Long term effects
• Methamphetamine is an anorexant, This is considered a benefit
for many light users, but in regular or heavy users can lead to
malnutrition.
• Methamphetamine is also believed to be neurotoxic.It’s use
causes damage to the neurons in the dopamine portions of the
brain.
• Some possible effect on the serotonin producing parts of the
brain is also suspected.
• Lead Poisoning
• Psuedo-Parkinson's D/O
49. What are Cathinones?
• Cathinone, a central nervous system stimulant found in the leaves
of the “khat” bush (Catha edulis) is also known as African salad,
bushman's tea, gat, kat, miraa, qat, chat, tohai, and tschat
• Khat (Catha edulis) is Ethiopia’s fourth biggest export (after coffee,
leather & oil seeds) and is growing every year.
• It is a traditional narcotic and is exported mainly to
Somalia and Djibouti and then to the U.S. and Europe.
– Degrades rapidly in its natural form
• Causes stimulation, then euphoria and then
depression.
50. What are Synthetic Cathinones?
• Synthetic cathinone's are related to the parent compound
cathinone. They are created synthetically (in a lab) resulting in
much more potent stimulant effect.
• These products are usually encountered as highly pure white
or brown powders.
• Cathinone derivatives are claimed to have effects similar to
those of cocaine, amphetamine or MDMA (ecstasy). Some of
the Synthetic Cathinones have properties tied to some
dissassociatives like PCP and Ketamine.
– Like many stimulants increases secretion of dopamine on the brain,
and blocks it reuptake as well, dramatically increasing levels.
51. Synthetic Cathinones
• Route: Intranasal most
common
• Also: oral, smoking, rectal,
and IV
• White to light brown
crumbly powder
• Degrades if exposed to air
for significant periods of
time
http://www.stompin-gardeners.com/index.
MDMA
57. What makes Synthetic Cathinones different from
other sympathomimetics?
• Duration – Shorter, requiring more frequent
“bumps”
• Recreational Effects- More intense, less enjoyable
• Clinical Effects – More intense, more clinically
significant
– Sympathomimetic toxidrome AND:
• Disassociation
• Impulse/Anger control compromises
• Hallucinations
61. Not Zombies … Yet Bath Salts are deadly
More recent rash of bizarre and deadly bath salts incidents
• - A man was found in the middle of a busy street shouting incoherently at oncoming
traffic that swerved to miss him. Police finally got him out of the traffic when he
“displayed signs of excited delirium” before he stopped breathing. He was
pronounced dead at the hospital and had bath salts on him.
• June 15, 2012. Robinson, Illlinois - A naked man grabs onto random car hood while
naked and surfs car hood for 4 miles. The driver calls 911 and drives 4 miles to meet
police who then arrested the man, who had vials purportedly containing bath salts on
him. He was “hallucinating wildly” … as opposed to hallucinating modestly.
• June 14, 2012. Miami, Florida - A naked woman punched and choked her 3 year old
son before the son was rescued by onlookers. She then grabbed her dog and did the
same before the police came and tasered. She died from cardiac arrest shortly
thereafter
62. KEY POINT
• Many of these behaviors fit in with classic
“Excited Delirium” and are not specific to
Synthetic Cathinones
• Use caution when restraining
• Use lots of benzodiazipines, cooling, etc.
64. Everybody loves cocaine
• “…Woe to you my
Princess, when I come, I
will kiss you quite red
and feed you till you are
plump. And if you are
forward, you shall see
who is the stronger, a
gentle little girl who
doesn't eat enough or a
big wild man who has
cocaine in his body."
-- Sigmund Freud, On
Coca
66. Background
• Sold commercially since 1860’s.
• Cocaine Hydrochloride is available on the
street generally at 30% to 40% purity and
retails at prices ranging from $10.00 to $50.00
per quarter gram.
• Cocaine metabolites are excreted in the urine
and can be detected for between 2 to 4 days
after the drug has been consumed.
67. Physiological effects
• Sodium Blockade Stimulant effects due to
increased Dopamine excretion in the brain (like
most hyperdynamics)
• Stimulant effects to due to reuptake inhibition of
Dopamine, Serotonin, and Norepinephrine.
– Causes central and peripheral effects, including the
release of epinepherine, and hypertension from
vasoconstriction
– Increases nor-epi and epi levels 5x!
• Unlike other hyperdynamics, Cocaine also causes
sodium blockade similar to TCA’s.
71. Comments about IV Use
• Rapid Onset with high bioavailability and short
duration (60 minutes) due to rapid metabolism
– Peak in 3-5 minutes
• Highest incidence of side effects
• “Bell Ringer”
– Tinnitus
– Auditory Distortion
• Risk of stroke from circulatory emboli of
undissolved particulates
72. Comment about Crack and Smoking
• Faster onset than IV (surprisingly)
– 1.5 min vs. 3 min
• Acute Pulmonary Effects
– Atrophy of mucosal membrains
– Wheezing
– Impairs Pulmonary Blood flow due to vasoconstriction
– Pneumothorax
– Pulmonary HTN and Edema
• Chronic Pulmonary Effects: “Crack Lung”
74. Cocaine and Alcohol
• Co-imbibing cocaine and alcohol form toxic
metabolite cocaethylene
– Decreases excretion by 50% = 2-2.5 x longer
duration of effects
• Cocaethylene is also directly cardiotoxic.
– Lower LD50 compared to cocaine alone
– Increased stimulation effects
– Decrease in cardiac output by 45-50%
– Increase in ventricular dysrythmias
75. Cocaine and Alcohol
• “Cocaine and ethanol in combination were
more toxic than either substance alone. Co-
administration resulted in prolonged cardiac
toxicity and was dysrhythmogenic. Peak serum
cocaethylene concentrations were associated
with prolonged myocardial depression.”
– Wilson, L. D.; Jeromin, J; Garvey, L; Dorbandt, A (2001). "Cocaine,
ethanol, and cocaethylene cardiotoxity in an animal model of cocaine
and ethanol abuse". Academic Emergency Medicine 8 (3): 211–22.
76. Cocaine induced chest pain
• MI rates in cocaine induced chest pain between
15-40%.
– High rate of N-STEMI
– MI may occur up to 2 weeks after cocaine use due to
recurrent coronary vasospasm.
– All cocaine induced chest pain should be transported
to PCI capable facilities
• Like other hyperdynamics, benzodiazepines and
NTG are first-line agents in drug-induced acute
coronary syndromes.
77. KEY POINT
• The Sympathetic Toxidrome common to most
hyperdynamic drugs may not be present with
cocaine induced chest pain due to delayed
ischemia and myocardial infarction up to 2
weeks later.
78. Aspirin?
• Aspirin use in cocaine induced chest pain is
poorly studied.
• Aspirin should generally be given to patients
with cocaine-associated chest pain.
• It should only be withheld if there is a
suspicion of intracranial hemorrhage or aortic
dissection.
– Both are real concerns
79. Pleuratic Pain is misleading
• The character of the pain is not helpful
because between 1% and 29% of patients with
cocaine-associated myocardial infarction
complain of pleuritic pain.
• Relatively young age of patient also
misleading.
80. Cocaine induced dysthymias
• Three (likely causes)
– Adrenergic Stimulation causing ischemia and irritability
– Sodium channel blockade causing conduction problems (similar to TCA’s)
– Chronic cocaine use causes structural abnormalities in conduction pathways
leading to re-entry issues.
81. Cocaine induced dysthymias
• Like all hyperdynamics, Benzodiazepines are first line
agents
• Consider Sodium Bicarb for wide complex
dysrhythmias (QRS > 100 ms).
• Cocaine induced dysrhythmias will typically not
respond to Adenocard
• Ca+ channel blockers not well studied in this setting.
• Amiodarone and procainamide should be avoided.
• Lidocaine may be considered for refractory wide
complex dysrhythmias
82. Cocaine induced stroke
• Embolic/TIA
– Vasoconstriction
– IV cocaine = Risk of stroke from circulatory
emboli of undissolved particulates
• Hemorrhagic
– powdered cocaine is four times more likely to
cause hemorrhagic strokes than crack
– Cocaine-induced hemorrhagic strokes are
generally either subarachnoid (SAH) or
intracerebral.