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Alcohols
and Opioids
Tintinalli 6th edition
Chapters 166 & 167
February 9, 2006
ALCOHOLS
ETHANOL
Unique drug of abuse b/c legal and
socially accepted
most medical morbidity assoc. with acute
intoxication is not direct drug effect but
from secondary injuries
most frequently used and abused in the
U.S.
Nearly 3/4 of adult Americans consume at
least 1 alcoholic drink yearly
Beer ranks as fourth most popular
beverage in terms of volume consumed
Etoh use in the U.S. costs $185 billion (in
1998) and contributes to approx. 100,000
deaths yearly
40% of motor vehicle fatalities are related
to etoh (15,000/yr)
Etoh abuse as reported by injured women
is the strongest predictor for acute injury
related to domestic violence
Prevalence and lifelong risk of etoh abuse
or dependence are 7% and 13%,
respectively
From a 1995 Nat’l Hospital Ambulatory
Medical Care survey, 2.7% of all ED visits
are related to alcohol use
Etoh is detected in the blood of 15-40%
of ED patients, depending on location
ER doctors and inpatient specialists fail to
recognize 50% of pts with ethanol
dependence
One drink...
Considered to be 0.5 oz or 15 gm of Etoh
equivalent to:
12 oz. (335 cc) of beer
5 oz. (148 cc) of wine
1.5 oz. (44cc) of 80 proof spirits
Remember etoh is also in mouthwashes
(up to 75% volume), colognes (40-60%),
and medicinal preparations (0.4-65%)
Pathophysiology of Ethanol
CNS depressant which inhibits neuronal
activity
Alcohol intoxication is assoc. with:
depression of the glutamate (excitatory
neurotransmitter)
 increases GABA and glycine (inhibitory
neurotransmitters)
Absorption
Absorption of ethanol:
mouth and esophagus= small amt
stomach and large bowel= moderate amt
proximal portion of small bowel= lg. Amt
Elimination
Approx. 2-10% of Etoh is excreted by
lungs, in urine, or in sweat (proportion
excreted dependent on BAL)
Remainder in metabolized by the Liver
into acetaldehyde
Gender related differences in metabolism
of Etoh explains higher BAL in women vs.
men after same amount ingested
Elimination
Unhabituated pts eliminate etoh from the
blood at 15-20 mg/dL per hour
Alcoholics average 25-35 mg/dL per hour
Note: Most states adopt 80 or 100 mg/dL
as the legal definition of intoxication
Clinical Features
Slurred speech
nystagmus
disinhibited behavior
CNS depression
Decr motor
coordination and
control
Hypotension d/t decr
in total peripheral
resistance or volume
loss
syncope
Tolerance
Because of tolerance, BAL correlate poorly
with degree of intoxication
Death from respiratory depression can
occur at levels of 400-500 mg/dL
yet some individuals with a high tolerance
can appear minimally intoxicated at levels of
400.
Impairment may be seen with levels as
low as 5mg/dL unhabituated individuals
Labs
Mild lactic acidosis may be seen in Etoh
intoxication
However, significant acidosis should never
be attributed to ethanol intoxication
Ethanol does causes an osmolar gap
If an anion gap metabolic acidosis is present,
search for a co-ingestion
Mild contraction alkalosis and/or pre-renal
azotemia may be noted if volume
depletion is present
Treatment
Etoh levels are not required for mild or
moderate intoxication when no other
abnormality is suspected
check levels in altered mental status
D5NS is the most appropriate fluid to use,
give thiamine, folate, and MVI with IVF
Fluids do not hasten alcohol elimination, so
in uncomplicated cases may not be needed
Ethanol doesn’t bind to charcoal
Serial observation is crucial
the majority improve over a few hours
Mental status that fails to improve and any
deterioration should prompt a search for
another cause of altered MS
Note: Resp depression is due to carbon
dioxide retention; patient may need
airway secured
Question concomitant drug use
Cocaine and Alcohol
become the most common combination
forms a metabolite, Cocaethylene, which is
less potent than cocaine but has longer half
life (3-5X longer)
risk of sudden death increases to as high as
20 times than with cocaine use alone
Disposition
Acute ethanol intoxication alone rarely
requires hospitalization
Medical judgment of mental competence
should not be confused with any particular
BAL
Discharge the patient when…
intoxication has resolved to the extent they
are no longer a danger to themselves or
others
Another individual (not impaired) is going to
take the responsibility for the care of the
patient
Pts BAL is near zero (if driving self home) not
just below the legal limit.
ISOPROPANOL
Commonly found in rubbing alcohol,
solvent, disinfectant, skin/hair products,
jewelry cleaners, detergents, paint
thinners, anti freeze
Poisoning can occur from ingestion,
inhalation, or dermal exposure
Principal metabolite= acetone
does not cause eye, kidney, cardiac, or metabolic
toxicity like methanol or ethylene glycol
metabolites
Twice as potent as ethanol in causing CNS
depression
Duration is 2-4 times longer than ethanol
After ethanol, it is the second most
ingested alcohol
Pathophysiology
of Isopropanol
Clear, volatile liquid with bitter taste and
aromatic odor
80% of oral dose absorbed after 30 min
and complete absorption with 2 hrs
kidneys excrete 20-50% of absorbed dose
unchanged
Majority of the metabolism occurs in the
liver by alcohol dehydrogenase to acetone
Acetone is then primarily excreted by the
kidneys and to a lesser extent by the
lungs
Hallmark of isopropanol toxicity
ketonemia and ketonuria without elevation of
blood glucose or glucosuria
Presence of ketones differentiates isoprop
ingestion from methanol or ethylene
glycol
Follows concentration dependent (first
order ) kinetics
Half life of isoprop is the absence of Etoh is
6-7 hrs
half life of acetone is 22-28 hrs.
Dose of 0.5mL/kg can cause symptoms
in children, 3 swallows can be toxic
Toxic dose of 70% isoprop is 1mL/kg
Lethal dose is 2-4mL/kg
Clinical Features
Similar to ethanol intoxication
Duration of s/s is longer & CNS
depression may be more profound b/c of
acetone
Nystagmus usually present
Severe poisoning= early onset of coma,
resp depression, and hypotension
Serious dysrhythmias are rare
Massive ingestion may cause hypotension
due to peripheral vasodilation &/or from
hemorrhagic gastritis
Hemorrhagic gastritis is feature of
isopropanol ingestions
results in N/V, abd pain, UGI bleeding
Hypoglycemia occurs due to depression of
gluconeogenesis
Less common complications: hepatic
dysfunction, ATN, myoglobinuria,
hemolytic anemia, rhabdo, myopathy
Fruity odor of acetone or smell of rubbing
alcohol is usually present on the breath
Treatment of
Isopropanol intoxication
Check blood glucose at bedside
Give thiamine and naloxone
No use in gastric lavage b/c of its rapid
absorption
Activated charcoal binds isoprop poorly
thus is not necessary
LABS: CMP, CBC, glucose, acetone, type
and screen (if necessary)
If significant acidosis is present, look for
another cause of intoxication
Hemodialysis (HD) is indicated
1. hypotension is refractory to conventional tx
2. hemodynamic instability
3. when predicted peak isoprop level is > 400
HD eliminates both isoprop and acetone
Disposition
Prolonged CNS depression or lethargy
should be hospitalized
Patients asymptomatic for 6-8 hours in
the ED may be discharged, referred to
substance abuse counseling, or referred
psych eval
METHANOL
Referred to as methyl alcohol, wood
spirits, and wood alcohol
Used in commerical, industrial, and
marine solvents
Also present in measurable but smalll amts in
wine and distilled spirits, thus may be
detectable in blood after binge drinking
Methanol’s toxic metabolites:
formaldehyde and formic acid
Pathophysiology
of Methanol
Well absorbed from GI tract
peak levels attained 30-90 min after
ingestion
Toxicity can occur after oral ingestion,
along w/ exposure via the lungs and skin
Amount of methanol required to cause
toxicity varies
Half life after mild toxicity is 14-20 hrs
increases to 24-30 hrs after severe toxicity
Following ingestion, highest conc found in
the kidney, liver, and GI tract
high levels also found in the vitreous humor
and optic nerve
90-95% of methanol is eliminated by the
liver
In overdose situations, elimation follows
saturation (zero-order) kinetics
Formaldehyde
and formic acid
Formaldehyde in the retina causes optic
papillitis and retinal edema
severe cases can lead to blindness
Folate is a co-factor in the breakdown of
formic acid
therefore alcoholics already deficient in folate
are highly susceptible to methanol toxicity via
formic acid accumulation
Clinical Features
of Methanol
Symptoms may not appear for up to 1218 hrs after ingestion
delay in symptoms may be longer if ethanol
is co-ingested and competing with methanol
for the alcohol dehydrogenase
Cardinal manifestations: CNS depression,
visual disturbances, abd pain, n/v, wide
anion gap metabolic acidosis (with wide or
nml osmolar gap)
Visual disturbances seen in approx. 50%
of patients
diplopia, blurred vision, decreased visual
acuity, photophobia, descriptions of “looking
into a snow field”, constricted visual fields,
blindness
Clinician may find nystagmus, retinal
edema, fixed/dilated pupils, optic atrophy
or hyperemia of optic disk
Hypotension and bradycardia are late
findings and suggests a poor prognosis
Prognosis is best correlated to severity of
acidosis than serum methanol level
Serum Methanol Levels
Normal methanol levels from endogenous
sources is 0.05mg/dL
In asymptomatic individuals, levels usually
peak at 20 mg/dL
Serous poisoning indicated by levels >50
Symptoms
CNS-- levels >20
Eye-- levels >50
Risk of fatality rises with levels > 150-200 mg/dL
Wide Anion Gap
Metabolic Acidosis
Differential Diagnosis
methanol
ethylene glycol
DKA
paraldehyde
INH
Salicylates
iron
lactic acidosis
uremia
phenformin
carbon monoxide
cyanide
alcoholic ketoacidosis
toluene
Treatment of
Methanol Intoxication
Initially, establish IV access, bedside
blood glucose, thiamine, and narcan
General measures in treatment are:
1. Supportive care
2. Correction of acidosis
3. Admin. Fomepizole or ethanol to decr
conversion to toxic metabolites
4. Dialysis to eliminate methanol
Gastric aspiration or lavage of no benefit
unless pt presents immediately after
ingestion
activated charcoal ineffective unless other
absorbable substances ingested
LABS (minimum): CMP, CBC, glucose,
Etoh, methanol
Secure airway when necessary
Administer Sodium Bicarbonate
goal is to maintain near normal pH
correction of acidosis inhibits some of the
toxic effects, especially with visual
impairment
Prevention of Methanol’s
Toxic Metabolites
Ethanol and fomepizole competitively
inhibit alcohol dehydrogenase
Fomepizole is superior drug to ethanol
has an affinity for alcohol dehydrogenase
that is 8000 times that of ethanol
doesn’t produce CNS depression or metabolic
toxicity
doesn’t require monitoring of levels and
dosage adjustments
Fomepizole
Loading dose of 15 mg/kg
Then 10 mg/kg every 12 hrs for 4 doses
given as infusion over 30min
Dosing is increased to every 4 hours when
patient is also getting hemodialysis
fomepizole is dialyzable
Fomepizole
Considered Drug of Choice
Ethanol is considered DOC if a known allergy
to fomepizole exist
Case reports suggest fomepizole is safe in
children
Costs: loading dose alone is $1000
compared to a few dollars for ethanol
Use of fomepizole (or ethanol) doe not
alter the indications for dialysis
Ethanol
Has affinity for alcohol dehydrogenase 1020 times of methanol
Blood ethanol levels should be maintained
b/w 100-150 mg/dL to completely inhibit
formation of metabolites
Administered po, IV, or via NG
oral admin uses 20-30% conc (higher conc
can lead to gastritis and/or alterations of MS)
Ethanol
IV admin of ethanol is preferred
can result in superficial thrombophlebitis
solution contains 10% ethanol in D5W
Loading dose is 10cc/kg
Maintenance is 1.5cc/kg/hr
If dialysis is initiated, maintenance infusion
starts at 0.24gm/kg/hr
Must check ethanol levels frequently and
adjust gtt to maintain BAL of 100-150
Further Treatment
Folic Acid-- 50mg IV every 4 hrs for
several days is recommended
especially in folate deficient individuals
Dialysis Indications
1.
2.
3.
4.
Signs of visual or CNS dysfunction
Peak methanol levels > 20 mg/dL
pH< 7.15
History of ingesting >30 mg/dL
Hemodialysis is more effective than
peritoneal but if HD is not available start
peritoneal dialysis when indicated
Disposition
Asymptomatic patients with any ingestion
of methanol should be admitted and
treatment initiated, even if no acidosis is
evident
**Remember there is a delayed onset of
symptoms
ETHYLENE GLYCOL (EG)
Used in antifreeze, preservatives, polishes
lacquers, glycerine substitutes, cosmetics,
detergents
In 2001, EG Accounted for 4938 poison
exposures and 16 deaths in the U.S. as
reported by poison control centers
EG’s toxicity is from the formation of 2
toxic metabolites: glycoaldehyde and
glycoxalic acid
Pathophysiology
of Ethylene glycol
Colorless, odorless, sweet tasting
substance
highly water soluble and rapidly absorbed
when ingested orally
no absorption via lungs or skin
Peak blood levels occur within 1-4 hrs of
ingestion
Half life is 3-5 hours
Metabolized by the liver and kidneys to
toxic metabolites: aldehydes, glycolate,
oxalate, and lactate
These metabolites are:
toxic to the lungs, heart, and kidneys
the cause of metabolic acidosis associated
with EG poisoning
Deficiency of either pyridoxal phosphate
or thiamine may shift the metabolism of
EG to metabolites
Oxalate crystalluria is found in the urine
of about 50% of cases
Levels greater than 20 mg/dL are likely to
result in toxicity
Potentially lethal dose: 2 mL/kg
Clinical Features
of EG intoxication
Exhibits three phases (dependent on the
amount ingested)
1. CNS phase
2. Cardiopulmonary phase
3. Nephrotoxicity phase
EG Phases
1. CNS Phase
CNS depression within 1-12 after ingestion
appear inebriated but w/o the odor of ethanol
hallucinations, coma, seizures, and death may
occur during this initial phase
CNS symptoms correlate with peak glycoaldehyde
production
Optic fundus is nml (differ from methanol),
may have nystagmus & opthalmoplegia
LP: incr CSF pressure and protein, few polys
EG Phases
2. Cardiopulmonary Phase
develops 12-24 hrs after ingestion
tachycardia, mild HTN, tachypnea are
common
may see CHF, ARDS, cardiomegaly, circulatory
collapse
EG Phases
3. Nephrotoxicity Phase
occurs 24-72 hours after ingestion
Early symptoms: flank pain and CVA
tenderness
Oliguria renal failure and ATN develop
Complete anuria may occur, but most recover w/o
renal damage if appropriate tx started
Nephrotoxicity caused by aldehyde
metabolites and oxalic acide
More Clinical
Features of EG
Hypocalcemia may develop secondary to
precipitation of calcium as calcium oxalate
may be severe enough to cause tetany and
prolonged QT interval
Elevated CPK may accompany and explain
generalized myalgias
Leukocytosis is common
Look for wide anion gap metabolic
acidosis with osmolar gap
Treatment of Ethylene
Glycol Intoxication
Similar to tx of methanol poisoning
Indications for gastric emptying and bicarb
are the same as for methanol
If the pt is hypocalcemic, 10cc of calcium
glucanate 10% should be given IV
pyridoxine(B12) 100mg and thiamine
100mg IV or IM should be administered
daily
facilitates metabolism of EG to nontoxic pathways
Magnesium supplementation
shown to be a cofactor in metabolism of
toxic metabolites
may be deficient in alcoholics
LABS:
CBC, CMP, acetone, Mg, CPK, Ca
alcohol toxicology panel with ethanol,
isoprop, and methanol determinations
serum ethylene glycol levels
salicylate level
UA (& HCG)
ABG
Ethanol or Fomepizole
should initiate in the ER if overdose is
suspected or confirmed
Ethanol affinity for alcohol dehydrogenase is
100x that of EG, thus prolonging EG half life
to 17 hours
treatment and dosing for EG is same as for
methanol intoxication
Indications for Dialysis in EG Poisoning
1. The triad of history, clinical presentation,
and lab results consistent with EG poisoning
are present
2. Ethylene glycol >20 mg/dL
3. Signs of nephrotoxicity
4. Metabolic acidosis present
Disposition
Admit to the ICU
Admit to a facility that has hemodialysis
capabilites
Patient will be in the hospital until lab
testing are normal if they are initially
asymptomatic
OPIOIDS
Opioids
Refers to all agonist, antagonist,
endogenous, and exogenous substances
that possess morphine-like activity
In the U.S., most commonly abused
opioids are heroin and methadone
Pharmacology of Opioids
Modulate nociception in the terminals of
afferent nerves in the CNS, PNS, and GI
tract
Agonists at the mu, kappa, and theta
receptors in the tissues
receptors now called OP3, OP2, and OP1,
respectively--reflecting the order of discovery
OP3 Receptor
Subdivided into a and b: analgesia,
respiratory depression, cough
suppression, euphoria
Most of the analgesic effect of morphine
is mediated via OP3a stimulation
All currently available opioids have some
activity at the OP3b receptor, resulting in
some degree of respiratory compromise
Other receptors
Stimulation of OP2 receptors results in
spinal analgesia, miosis, and diuresis
Role of OP1 is clinically unknown
Pharmacokinetics
Most opioids more effective parenterally
than orally
due to significant first pass elimination
Opioids with good oral potency= codeine,
oxycodone, levorphanol, methadone
In most opioids, metabolism is through
the liver and creates pharmacologically
active metabolites
Clinical Features
of Opioids
Resp depression
mental status change
analgesia
miosis*
orthostatic hypotn
n/v
urticaria
bronchospasm
Decr GI motility
urinary retention
*not universally
present; may see
mydriasis with coingestants or may
signal cerebral
hypoxia
Diagnosis
Diagnosis of opioid overdose or withdrawl
remains clinical
Triad of coma, miosis, and respiratory
depression strongly suggests opioid
intoxication
Differential Diagnosis
of Opioid Overdose
Effects of other
agents:
clonidine
organophosphates
and carbamates
 phenothiazines
 sedative-hypnotic
agents
 carbon monoxide
Hypoglycemia
 hypoxia
CNS infections
post-ictal states
pontine hemorrhages
Treatment
ABC’s
Naloxone
Gastric decontamination
Acetaminophen Level with Tox Screen
Observation
Disposition
Naloxone (Narcan)
pure antagonist at all OP receptors
particular affinity for OP3
Binds to OP receptors without producing
any effects (positive or negative)
Onset of action is rapid (1-2 min)
Duration of action is 20-60 min
 shorter than duration of action of most
opioids
Naloxone
In patients with CNS depression without
respiratory depression:
in opioid dependent- 0.05 mg IV is
recommended
in non-opioid dependent- 0.4mg IV is
recommended
Incremental dosing will avoid the acute
precipitation of opioid withdrawl
Give 2.0mg IV to the patient presenting
with significant resp distress, regardless of
drug history
Exposure to sustained release opioids may
require larger doses of narcan to reverse
the effects
Recent literature recommends the same
dose ranges in the pediatric patient
Exception, the neonate in the immediate
postpartum period,
suggested dosage is 0.01 mg/kg IV
Gastric Decontamination
Syrup of ipecac and gastric lavage are not
recommended
activated charcoal should be administered
ideally within 1 hour after ingestion
Dosage: 50 gm of activated charcoal po
followed by sorbitol 0.5-1.0gm po
Delayed and multiple doses useful in:
1. hydrochloride-atropine sulfate (Lomotil)
overdoses
2. Overdose of sustained release opioids
Special
Considerations
Meperidine
Active metabolite= Normeperidine
largely renally excreted
accumulates in pt with diminished renal
function
Proconvulsive (esp. Normeperidine)
pts with drug induced seizure must be
observed for 24-48 hours
treatment: benzos and avoid meperidine
Serotonin Sydrome
Example: Meperidine or
Dextromethorphan plus MAOI
Characterized by disorientation, severe
hyperthermia, hypo/hypertn, muscle
rigidity
Treatment: benzos, cooling, avoid narcan
Propoxyphene
Active metabolite= norpropoxyphene
Cardiotoxic and neurotoxic
Overdoses cause blockade of fast sodium
channels
results in intraventricular conduction
disturbances, heart block, prolonged QT,
ventricular bigemny
Treatment: Sodium Bicarb 1mEq/kg IV
(can reverse cardiotoxic effects)
Tramadol (Ultram, Ultracet)
Overdoses associated with agitation, HTN,
resp depression, seizure, and death (at
levels > 500 mg)
Treatment: supportive
Narcan is ineffective in reversing seizures
Acute Lung Injury
Rare complication assoc. with toxicity
from certain drugs, including opioids
can occur immediately or be delayed up
to 24 hours following use
Suspect in any pt with tachycardia,
tachypnea, rales, or decr oxygen sat with
nml CXR
pathophysiology poorly understoon
Opioid Withdrawal
Not life-threatening
Onset within 12h of last heroin use and
within 30h of last methadone exposure
Clinical features:
anxiety, insomnia, yawning, lacrimation,
diaphoresis, rhinorrhea, diffuse myalgias
followed by piloerection, mydriasis, nausea,
profuse vomiting, diarrhea and abd cramping
Opioid Withdrawal
Symptoms more tolerable by giving:
 alpha 2 agonist (i.e. Clonidine)
antiemetics (i.e. Reglan)
antidiarrheal agents (i.e. Bentyl)
Questions??
1. A 36 yo M presents to the ER. Pt appears
inebriated but does not smell of alcohol.
Patients UA shows calcium oxalate crystals.
Which of the following would be false?
a. Ingestion of ethylene glycol has occurred
b. Pt most likely will have no anion gap
c. Pt most likely will have an osmolar gap
d. Pt will be admitted to the hospital
e. Pt EKG may show prolonged QT intervals in
24 hours
2. True or False: Hemodialysis only
removes the toxic metabolites formed in
methanol poisoning.
3. True or False: Significant metabolic
acidosis is found in all forms of alcohol
intoxication
4. In propoxyphene overdoses, which
therapy is most appropriate in reversing
the cardiotoxic effects?
a.
b.
c.
d.
e.
Narcan
Fluid restriction
Sodium bicarbonate
Normal saline infusion
None of the above
True or False: Opioids are not as effective
when given orally (vs. parenterally)
Answers: b, false, false, c, true