Transcript Toxic Alcohols and Opiods

Toxic Alcohols and Opioids
Jamil A. Alarafi, D.O.
02.01.2007
Toxic Alcohols
Ethanol
Methyl Alcohol
Ethylene Glycol
Isopropyl Alcohol
Ethanol
Everybody's favorite!
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Unique among abused drugs
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Most frequently used and abused in most societies
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Estimated to contribute to 100,000 deaths/yr
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40% of MVC’s are related to ETOH use
Ethanol
Pathophysiology
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CNS Depressant
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Absorption: mouth to small bowel
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Elimination:
2 – 10% from lungs, urine, and sweat
Primary metabolized in the liver
Ethanol
Clinical Features
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Slurred speech, nystagmus, disinhibited behavior,
CNS depression ( a spectrum which my lead to
coma), and poor motor coordination and control
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Hypotension
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Tolerance
Ethanol
Treatment
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Mainstay of treatment is supportive
Attention to ABC’s, associated injuries, or comorbid conditions.
Bedside glucose check
Thiamine, Folate, Multivitamins, Magnesium,
Fluids (D5NS)
Ethanol
Treatment
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Careful serial examines are crucial
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Respiratory depression may require intubation
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Most eliminate ethanol at a rate of 0.20-0.25/hr
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Cocaethylene
Metabolite formed by the combination of ETOH and Cocaine
Ethanol
Disposition
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Most rarely require hospitalization and can be
sent home as long as certain conditions are in
place
State legal limits very
Ohio 0.08
Overview
Methanol
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Also called methyl alcohol or “wood alcohol”
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Colorless,volatile liquid, with a distinctive odor
Common Sources
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Sterno, paint removers, varnishes, shellacs,
windshield fluids, and antifreeze
Toxic Metabolites
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Formaldehyde & Formic acid
Methanol
Pharmacology and Metabolism
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Rapidly absorbed
Transdermal and respiratory absorption has resulted
in toxicity
As little as 1.5ml of 100% methanol can produce a toxic level
in small children
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High risk for inhalation exposure: painting, glazing,
varnishing, lithography, and printing
Methanol
Pharmacology and Metabolism
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Serum levels peak 30 to 60 minutes
Half life is 24 to 30 hours
Prolonged by Ethanol
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Smallest lethal dose
15 mL in adults and 1.5 mL in toddlers
Methanol
Pharmacology and Metabolism
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Methanol has little toxicity and produces less
inebriation than ethanol
Methanol  Formaldehyde  Formic Acid CO2
and Water
Formic Acid responsible for much of Anion Gap and
Ocular toxicity
Methanol
Pathophysiology/Clinical Features
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Optic Neuropathy
“Snow blindness”: diplopia, photophobia, and blindness
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Putaminal Injury
Parkinsonian type motor dysfunction, hypokinesis, and rigidity
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Mechanism
Formic Acid has a high affinity for iron and inhibits mitochondrial
cytochrome oxidase, halting cellular respiration
Metabolism in the cytosol and mitochondria account for a second
mechanism of ATP depletion
Methanol
Clinical Features
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Symptoms may not appear until 12 to 18 hours after the
ingestion
“Cardinal” signs of toxicity:
CNS effects similar to ETOH intoxication with N/V, abdominal pain,
visual disturbances, and a wide anion gap metabolic acidosis
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Coma and seizures can develop in severe cases
Hypotension and bradycardia are late findings and suggests a poor
outcome
Methanol
Prognosis
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Correlates with the degree of acidosis, not with the serum
methanol level.
Treatment initiation within 8 hours of exposure
Poor prognosis associated with coma, hypotension, bradycardia,
seizures, or arterial pH less than 7.0
Patients who survive may have permanent blindness or severe
neurologic deficits
Methanol
Laboratory Features
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Anion Gap
may be delayed 12 to 24 hours
Absence with concomitant ethanol, lithium, or
bromide ingestion
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Elevated “Osmolar Gap”
OG = Meas. Serum Osm. - Cal. Osmolality
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Normal gap is (-14 to +10)
Calculated osmolality= 2Na + BUN/2.8 +
glucose/18 + ethanol/4.6
Ethylene Glycol
Overview
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Viscous, colorless, slightly sweet-tasting
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Primarily used in antifreeze and coolants
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Also in airplane deicing solutions, hydraulic brake
fluids, industrial solvents, paints, lacquers, and
cosmetics
Most poisonings involve Antifreeze
Ethylene Glycol
Epidemiology
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In 2001, there were 4938 exposures with 16 fatalities
90% unintentional
Most were children or suicide attempts
12% moderate to severe effects
Rapid treatment is imperative!
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If treated early and aggressively, death is unlikely, but
delay will result in multiorgan failure in 24 to 36 hours
Ethylene Glycol
Pharmacology/Metabolism
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Rapid absorption after ingestion
Distributes evenly in the tissues, with peaked levels at
1-4 hours
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Nonvolatile and inhalation absorption is unlikely
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Half life of 3 to 8.6 hours
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Toxic doses of 0.2 ml/kg - 1.4 ml/kg
Ethylene Glycol
Pathophysiology
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Metabolized in the liver (70%) and kidneys (30%) to toxic
metabolites- aldehydes, glycolate, oxalate, and lactate
2.3% converted to Oxalic acid, of which a small portion
complexes with calcium to form calcium oxalate crystals
These precipitate in kidney, brain, and peripheral tissues
these are harmful but the generation of toxic metabolites appear to
be most responsible for the lethal effects to target tissues
Ethylene Glycol
Clinical Features
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Four Stages of Ethylene Glycol toxicity
Acute Neurologic
Cardiopulmonary
Renal
Delayed Neurologic Injury
Ethylene Glycol
Diagnosis
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Crystalluria is the hallmarks of EG ingestion, however
its absence does not exclude the diagnosis
Useful test include:
Electrolytes, calcium, BUN, Creatinine, glucose, serum
osmolality, ethanol level, ABG, ethylene glycol level, EKG,
UA
Wood’s lamp fluorescence on a freshly voided urine
specimen may be helpful if EG is suspected
Ethylene Glycol
Diagnostic Test
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Leukocytosis is nonspecific and non-sensitive
QT prolongation with hypocalcemia secondary to
crystal formation
CPK may be elevated
Anion gap acidosis seen secondary to metabolites
glycolic acid and glyoxylic acid
Methanol and Ethylene Glycol
Management
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Treatment essentially the same
As in the OD setting, resuscitation and stabilization
are paramount
Gastric emptying is not effective due to rapid
absorption
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Only if ingestion in last 30 to 60 minutes
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Activated charcoal not effective
Methanol and Ethylene Glycol
Management
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Severely obtunded patients should receive attention
to ABC’s and “DON’T” therapy
(dextrose,oxygen,naloxone, and thiamine)
Forced diuresis is of no value and may cause
pulmonary edema or ARDS
Early intubation may be indicated
Methanol and Ethylene Glycol
Management
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Treatment goals
Correction of Metabolic Acidosis
ADH Blockade thereby inhibiting the generation of
toxic metabolites
Hemodialysis to remove alcohol
Methanol and Ethylene Glycol
Management
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Metabolic Acidosis
Large doses of bicarbonate may be required to correct the
acidosis
Early correction is imperative to reduce the chance of
methanol induced visual loss
Target pH is 7.45 to 7.50
Bicarbonate may worsen hypocalcemia with Ethylene Glycol
Methanol and Ethylene Glycol
Management
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Blocking ADH
Either Ethanol or Fomepizole may be used
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ETOH
Target level of ethanol is 100 to 150 mg/dL
ETOH increases the half-life to 30 hours Methanol and 17
hours Ethylene Glycol
Fomepizole
blocks ADH and has more predictable pharmacokinetics
and improved safety profile
more expensive
Methanol and Ethylene Glycol
Management
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Hemodialysis
Indications: triad of hx, clinical, and lab results confirm
toxic ingestion, EG > 20, ARF, metabolic acidosis
Removes preformed metabolites
Peritoneal dialysis is less effective
Endpoint is undetectable serum ethylene glycol or
methanol concentration
Isopropyl Alcohol
Overview
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Clear, colorless, slightly bitter
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Second most commonly ingested alcohol
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Found in nail polish removers, household disinfectants,
and window cleaners, and common rubbing alcohol
Less toxic than methanol or ethylene glycol
Isopropyl Alcohol
Epidemiology
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In 2002
31,187 exposures
91% unintentional
3% moderate to major effects
4 fatalities
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Fatalities are usually associated with chronic
alcoholics with mixed ingestions
Isopropyl Alcohol
Phamacology/Metabolism
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Absorption is rapid and complete, with peak serum
levels in 30 min, with a half-life of 3-7 hours
Potentially lethal dose is 150 to 240 mL (2 to 4
mL/Kg) but adults have survived up to 1 Liter
80% undergoes hepatic metabolism to acetone
Remaining 20% undergoes renal elimination
unchanged
Isopropyl Alcohol
Clinical Features
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CNS
Inebriation with acetone odor
Headache, dizziness
Neuromuscular dysfunction, confusion, nystagmus
Coma in severe ingestions
Respiratory depression or failure may occur
Isopropyl Alcohol
Clinical Features
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GI
Gastritis may occur
Hematemesis associated with gastritis but not
common
Abdominal pain, nausea, vomiting common
Isopropyl Alcohol
Clinical Features
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Hypotension
Rare but associated with severe ingestions, mortality rate is 45%
Caused by peripheral vasodilatation and direct myocardial
depression
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Sinus tachycardia
common but other dysrythmias if found are usually associated with
hypoxia, acidosis, or shock
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Myoglobinuria, ATN, or hemolytic anemias may be present
Isopropyl Alcohol
Diagnostic Test:
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Isopropanol level
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electrolytes, osmolality, serum and urine ketones
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Ketosis
most common lab abnormality (from acetone)
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Increased osmolar gap
Isopropyl Alcohol
Diagnostic Strategies
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“Pseudo-renal failure”
Early diagnostic clue with elevated creatinine and normal
BUN
100mg/dL of Isopropanol falsely elevates the creatinine
1mg/dL
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CPK should be obtained
Isopropyl Alcohol
Management
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ABC’s, glucose check, thiamine, narcan
Gastric emptying or charcoal is not useful unless
ingestion was large and recent
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ADH blockade not indicated
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Manage hypotension with fluids/vasopressors
Isopropyl Alcohol
Management
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Dialysis is indicated for refractory hypotension or
patients vital signs deteriorate
Coma not an indication for dialysis
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Hemodynamic stability without coma in first 6 hours
rarely develops significant sequelae
Care can generally be supportive in this case
Toxic Alcohols
Key Concepts
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Small doses can kill
Latent periods can fool you (EG & Methanol)
Double gap acidosis, think: ethylene glycol or
methanol ingestions
Early treatment improves outcomes, you must act
quickly
Toxicity can not be excluded based on “normal”
osmolar gap
Opioids
II
Opioids
Historical perspective
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In use for over 5000 years
Term for opium is derived from the Greek word for
poppy juice
Receptors and endogenous opioids have been
recognized and characterized only in the last 25 years
Opioids
Terms/Definitions:
Opioids
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natural, synthetic, and semi synthetic agent with morphine like
properties
In the US, heroin and opioid derivatives are abused most often and
the cause of most deaths
Opiate
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only natural agent
Narcotics
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any agent that induces sleep and is nonspecific
Endorphins
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Any peptide in the three opioid family: enkephalins, B-endorphins,
and dynorphins
Opioids
Mechanism of Action:
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Modulate nociception in the terminals of afferent
nerves in the CNS and PNS
Three endogenous receptors
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OP1 (delta)
OP2 (kappa)
OP3 (mu)
Concentrated in pain pathways, periaqueductal grey matter,
locus ceruleus, limbic system, nucleus raphe
Opioids
Clinical Features
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Wide variety of signs and symptoms
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Miosis is not universal
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Respiratory effects are variable
Look for shallow respirations, cyanosis,
bradypnea, or hypercarbia
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Diagnostic triad:
CNS depression, miosis, and respiratory
depression
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strongly suggest opioid intoxication
Opioids
Differential Diagnosis
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Clonidine
Periods of apnea that respond to tactile stim
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Organophosphates and Carbamates
Muscle fasciculations, profuse N/V
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Phenothiazines
CNS depression and miosis
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Carbon Monoxide exposure
Profound CNS depression
Opioids
Management:
ABC’s…Airway management
Interventions may include supplemental oxygen,BiPaP, or
BVM leading to intubation
GI Decontamination
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Usually not routine
Consider whole bowel irrigation for “body packers”
Activated Charcoal
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1 g/Kg
may be beneficial to promote motility with large
ingestions
Hypotension
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Treat with IV fluids, pressor agents as needed
Opioids
Reversal Agents
Narcan (Naloxone)
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a pure opioid antagonist with rapid onset of action
IV, SC, down ETT, and IM…not effective PO!
Acts by competitive binding at the receptor site
Revex (Nalmefene)
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Opioid antagonist alternative with long half-life and
rapid onset
PO, IV, SC, IM routes
Initial IV dose is 0.5 to 1.5mg
Opioids
Withdrawal
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Not life threatening
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Heroin Half-life : 0.5 hours
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Signs and symptoms may include CNS excitation, tachypnea,
tachycardia, hypertension, and mydriasis
Care is supportive and focused at minimizing symtoms in
tolerant individuals
Withdrawal can be managed in the outpatient setting
Patients who have refractory N/V, electrolyte abnormalities, or those
with an uncertain diagnosis should be admitted
Opioids
Withdrawal Agents
Methadone or l-a-acetylmethadol (LAAM)
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Long and longer acting opioids
Used to treat chronic herion addiction
20mg PO or 10mg IM
Controls cravings with limited euphoric effect
LAAM dose is 30mg PO
Clonidine
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Central a2-agonist
Controls symptoms by suppressing sympathetic hyperactivity
Dose is 0.1mg PO, patches are an option
Hypotension may limit treatment but usually not common in withdraw
treatment
Opioids
Key Concepts
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Diagnosis is based on history& physical exam
Key triad: CNS depression, respiratory depression, and miosis
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Supportive care is the mainstay, with attention to airway
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Duration of opioids is longer than narcan
So…don’t discharge your patient until your certain the opioid
properties are fully metabolize
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This depends on the agents involved!
Opioid withdrawal is supportive and focused at minimizng the
symptoms of withdrawal
THE END!!!
Questions?