TREATMENT
OF COMMON SPECIFIC POISONINGS
ACETAMINOPHEN
Acetaminophen
is a common analgesic found in many nonprescription
and prescription products. After absorption, it is metrabolized
mainly by glucuronidation and sulfation, with a small
fraction metabolized via the P450 mixed-function oxidase
system to a highly toxic reactive intermediate. This
toxic intermediate is normally detoxified by cellular
glutahione. With acute acetaminophen overdose, hepatocellular
glutathione is rapidly depleted and the reactive intermediate
attacks other cell proteins, causing necrosis. Patients
with enhanced P450 activity, such as chronic alcoholics
and patients taking anticonvulsants, are at increased
risk of developing hepatotoxicity. Hepatic toxicity
may also occur after chronic accidental overuse of acetaminophen
- eg, as little as 1 g of acetaminophen every 4 - 6
hours for 1 - 2 days in a patient with chronic accidental
overuse of acetaminophen - eg, as little as 1g of acetaminophen
every 4 - 6 hours for 1 - 2 days in a patient with chronic
excessive alcohol use.
Clinical
Findings
Shortly
after ingestion, patients may have nausea or vomiting,
but there are usually no other signs of toxicity until
24 - 48 hours after ingestion, when hepatic aminotransferase
levels begin to increase. With severe poisoning, massive
hepatic necrosis may occur, resulting in jaundice, hepatic
encephalopathy, renal failure, and death.
The diagnosis of severe poisoning after acute over-dose
is based on measurement of the serum acetaminophen level.
Plot the serum level versus the time since ingestion
on the acetaminophen nomogram. Ingestion of sustained-release
produces or coingestion of an anticholinergic agent,
salicylate, or opioid drug may cause delayed elevation
of serum levels.
Treatment
A.
Emergency and Supportive Measures :
Empty
the stomach by emesis or gastric lavage. Administer
activated Charcoal. Although charcoal may bind the oral
antidote aceylecysteine, this is not considered clinically
significant.
B.
Specific Treatment
If
the serum acetaminophen level is higher than the upper
toxic line on the nomogram, begin treatment with a loading
dose of acetylcysteine, 140 mg/kg orally, followed by
70 mg/kg every 4 hours. Dilute the solution to 5% with
water, juice, or soda. If vomiting interferes with oral
acetylcysteine administration, give the dose by gastric
tube and use metoclopramide, 1 - 2 mg/kg intravenously.
The most widely used protocol in the USA continues treatment
for 72 hours. However, other regimens have demonstrated
equivalent success with 20 - 48 hours of treatment.
Treatment with acetylcysteine is most effective if started
within 8 --10 hours after ingestion. If the precise
time of ingestion is unknown or if the patient is at
higher risk of hepatotoxicity, then use a lower threshold
for initiation of acetylcysteine.
Acetylcysteine may also be given intravenously; this
is the preferred method in Europe and Canada, but there
is no approved parenteral formulation or dosing schedule
in the United States. If the patient cannot tolerate
acetylcysteine despite antiemetics and administration
via a gastric tube, the United States formulation may
be give intravenously. Call a regional poison control
centre or medical toxicologist for assistance.
ACIDS,
CORROSIVE
The
strong mineral acids exert primarily a local corrosive
effect on the skin and mucous membranes. Symptoms include
severe pain in the throat and upper gastrointestinal
tract; bloody vomitus; difficulty in swallowing, breathing,
and speaking; discoloration and destruction of skin
and mucous membranes in and around the mouth; and shock.
Severe systemic metabolic acidosis may occur both as
a result of cellular injury and from systemic absorption
of the acid.
Severe deep destructive tissue damage may occur after
exposure to hydrofluoric acid because of the penetrating
and highly toxic fluoride ion. Systemic hypocalcemia
and hyperkalemia also may occur after fluoride absorption,
even following skin exposure.
Inhalation of volatile acids, fumes, or gases such as
chlorine, fluorine, bromine, or iodine causes severe
irritation of the throat and larynx and may cause upper
airway obstruction and noncardiogenic pulmonary edema.
Treatment
A.
Ingestion
Do
not induce emesis. Dilute immediately by giving a glass
of milk or water to drink. Do not give bicarbonate or
other neutralizing agents. Some experts recommend immediate
gastric lavage.
Perform flexible endoscopic esophagoscopy promptly to
determine the presence and extent of injury. X-rays
of the chest and abdomen may reveal the presence of
free air in patients with esophageal or gastric perforation.
Perforation, peritonitis, and major bleeding are indications
for surgery.
B.
Skin Contact :
Flood
with water for 15 minutes. Use no chemical antidotes;
the heat of the reduction may cause additional injury.
For hydrofluoric acid burns, soak the affected area
in magnesium sulfate solution or apply 2.5% calcium
gluconate gel; then arrange immediate consultation with
a plastic surgeon or other specialist. Binding of the
fluoride ion may be achieved by injecting 0.5 mL of
5% calcium gluconate per square centimeter under the
burned area. (Caution : Do not use calcium chloride).
C.
Eye Contact
Anesthetize
the onjunctiva and corneal surfaces with topical local
anesthetic drops. Flood with water for 15 minutes, holding
the eyelids open. Check pH with pH 6.0 - 8.0 test paper,
and repeat irrigation, using 0.9% saline, pH is near
7.0. Check for corneal damage with fluorescein and slitlamp
examination; consult an ophthalmologist about further
treatment.
D.
Inhalation
Remove
from further exposure to fumes or gas. Check skin and
clothing. Treat pulmonary edema.
ALKALIES
The
strong alkalies are common ingredients of some household
cleaning compounds and may be suspected by their "soapy"
texture. Those with alkalinity above pH 12.0 are particularly
corrosive. Clinitest tables and disk batteries are also
a source. Alkalies cause liquefactive necrosis, which
is deeply penetrating. Symptoms include burning pain
in the upper gastrointestinal tract, nausea, vomiting,
and difficulty in swallowing and breathing. Examination
reveals destruction and edema of the affected skin and
mucous membranes and bloody vomitus and stools. X-ray
may reveal the presence of disk batteries in the esophagus
or lower gastrointestinal tract.
Treatment
A.
Ingestion
Do
not induce emesis. Dilute immediately with a glass of
water. Some gastroenterologists recommend immediate
gastric lavage after ingestion of liquid caustic substances
to remove residual material.
Immediate endoscopy is recommended to evaluate the extent
of damage. If X-ray reveals the location of ingested
disk batteries in the esophagus, immediate endoscopic
removal is mandatroy.
The use of corticosteroids to prevent stricture formation
is of no proved benefit and is definitely contraindicated
if there is evidence of esophageal perforation.
B.
Skin Contact :
Wash
with running water until the skin no longer feels soapy.
Relieve pain and treat shock.
C.
Eye Contact :
Anesthetize
the conjunctival and corneal surfaces with topical anesthetic.
Irrigate with water or saline continuously for 20 -
30 minutes, holding the lids open. Check pH with pH
test paper, and repeat irrigation, using 0.9% saline,
for additional 30 minute periods until the pH is near
7.0. Check for corneal damage with fluorescein and slitlamp
examination; consult an ophthalmologist for further
treatment.
AMPHETAMINES
& COCAINE
Amphetamines
and cocaine are widely abused for their euphorigenic
and stimulant properties. Both drugs may be smoked,
snorted, ingested, or injected. Amphetamines and cocaine
produce central nervous system stimulation and a generalized
increase in central and peripheral sympathetic activity.
The toxic does of each drug is highly variable and depends
on the route of administration and individual tolerance.
The onset of effects is most rapid after intravenous
injection or smoking. Amphetazine derivatives and related
drugs include methamphetamine, and methcarthinone. Nonprescription
medications and nutritional supplements may contain
stimulant or sympathomimetic drugs such as ephedrine
or caffeine. Phenylpropanolamine was recently withdrawn
from the market because of an increased incidence of
hypertensive intracerebral hemorrhage in young women.
Clinical
Findings
Patients
may present with anxiety, tremulousness, tachycardia,
hypertension, diaphoresis, dilated pupils, agitation,
muscular hyperactivity , and psychosis. Metabolic acidosis
may occur. In severe intoxication, seizures and hyperthermia
may occur. Sustained or severe hypertension may result
in intracranial hemorrhage, aortic dissection, or myocardial
infarction. Hyponatremia has been reported after MDMA
use; the mechanism is not known but may involve excessive
water intake, SIADH, or both.
The diagnosis is supported by finding amphetamines,
cocaine, or the cocainemetabolite benzoylecgonine in
the urine. Blood screening is not sensitive enough to
detect these drugs.
Treatment
A.
Emergency and Supportive Measures
Maintain
a patent airway and assist ventilation, if necessary.
Treat coma or seizures. Rapidly lower the body temperature
in patients who are hyperthermic. Treat agitation or
psychosis with a benzodiazeine such as diazepam, 5 -
10 mg intravenously, o rmidazolam, 0.1 - 0.2 mg/kg intramuscularly.
For poisoning by ingestion, perform gastric lavage and
administer activated charcoal, or administer activated
charcoal alone without prior gut emptying. Do not induce
emesis, because of the risk of seizures.
B.
Specific Treatment
Treat
agitation with a sedative as lorazepam, 2 - 3 mg intravenously.
Treat hypertension with a vasodilator drug such as phentolamine
or nifedipine or a combined - and - adrenergic blocker
such as labetalol. Do not administer a pure beta - blocker
such as propranolol alone, as this may result in paradoxic
worsening of the hypertension as a result of unopposed
- adrenergic effects. Treat tachycardia or tachyarrhythmias
with a short-acting beta-blocker such as esmolol.
ANTICOAGULANTS
Warfarin
and related compounds inhibit the clotting mechanism
by blocking hepatic synthesis of vitamin K-dependent
clotting factors.
Anticoagulants may cause hemoptysis, gross hematuria,
bloody stools, hemorrhages into organs. Wide spread
bruising, and bleeding into joint spaces. The prothrombin
time is increased within 12 - 24 hours after a single
overdose. After ingestion of brodifacoum and indanedione
rodenticides, inhibition of clotting factor synthesis
may persist for several weeks or even months after a
single dose.
Treatment
A.
Emergency and Supportive Measures:
Discontinue
the drug at the first sign of gross bleeding, and determine
the prothrombin time. If the patient has ingested an
acute overdose, empty the stomach by emesis or lavage
and administer activated charcoal.
B.
Specific Treatment
Do
not treat prophylactically - wait for the evidence of
anticoagulation. If the prothrombin time is elevated,
give phytonadione, 5 - 10 mg subcutaneously or 10 -
25 mg orally, and additional doses as needed to restore
the prothrombin time to normal. Give fresh-frozen plasma
as needed to rapidly correct the coagulation factor
deficit if there is serious bleeding. If the patient
is chronically anticoagulated and has strong medical
indications for being maintained in that status, give
much smaller doses if vitamin k and flesh - frozen plasma
as titrate to the desired prothrombin time.
If the patient has ingested brodifacoum or a related
superwarfarin, prolonged observation and repeated administration
of large doses of vitamin k may be required.
ANTICONVULSANTS
(Carbamazepine, Phenytoin, Valporic Acid)
There
drugs are widely used in the management of seizure disorders.
In addition, carbamazepine and valproxic acid are increasingly
used for treatment of mood disorders.
Phenytoin
can be given orally or intravenously. Rapid intravenous
injections of phenytoin can cause acute myocardial depression
and cardiac arrest owing to the solvent propylene glycol;
a never form of phenytoin is available that does not
contain this diluent. Phenytoin intoxication can occur
with only slightly increased doses because of the small
toxic- therapeutic window. Phenytoin intoxication can
also occur following acute intentional of accidental
overdose. The overdose syndrome is usually mild even
with high serum levels. The most common manifestations
are ataxia, nystagmus, and drowsiness. Choreoathetoid
movements have been described.
Carbamazepine
was first used for the treatment of trigeminal neuralgia.
It has since become a first-line agent for temporal
lobe epilepsy and other seizure disorders. Intoxication
causes drowsiness, stupor, and, with high levels, coma
and seizures. Dilated pupils and tachycardia are common.
Toxicity may be seen with serum levels greater than
20 mg/L, though severe poisoning is usually associated
with concentrations greater than 30 - 40 mg/L. Because
of erratic and slow absorption, intoxication may progress
over several hours to days.
Valporic
acid intoxication produces a unique syndrome consisting
of hypernatremia, metabolic acidosis, hypocalcemia,
elevated serum ammonia, and mild liver aminotransferase
elevation. Hypoglycemia may occur as a result of hepatic
metabolic dysfunction, Coma with small pupils may be
seen and can mimic opioid poisoning. Encephalopathy
and cerebral edema can occur.
Treatment
A.
Emergency and Supportive Measures :
For
recent ingestion, give activated charcoal orally or
by gastric tube. For large ingestions of carbamazepine
or valporic acid - especially of sustained-release for
mulations - consider whole bowel irrigation. Multiple-dose
activated charcoal may be beneficial in ensuring gut
decontamination for large ingestions and may enhance
elimination of absorbed drugs.
B.
Specific Treatment
There
are no antidotes. Naloxone was reported to have reversed
valptoic acid overdose in one anecdotal case. Consider
hemodialysis or hemoperfusion for massive intoxication.
ARSENIC
Arsenic
is found in pesticides and industrial chemicals. Symptoms
of poisoning usually appear within 1 hour after ingestion
but may be delayed as long as 12 hours. They include
abdominal pain, vomiting, watery diarrhea, and skeletal
muscle cramps. Profound dehydration and shock may occur.
In chronic poisoning, symptoms can be vague but often
include those of peripheral sensory neuropathy. Urinary
arsenic levels may be misleading and are falsely elevated
after certain meals that contain large quantities of
relatively nontoxic organic arsenic.
Treatment
A.
Emergency Meausres
Induce
vomiting or perform gastric lavage, and administer 60
- 100 g of activated charcoal.
B.
Antibote :
For
symptomatic patients or those with massive overdose,
give dimercaprol injection, 10% solution in oil, 3 -
5 mg/kg dimercaprol intramuscularly every 4 - 6 hours
for 2 days. The side effects include nausea, vomiting,
headache, and hypertension. Follow dimercaprol with
oral penicillamine, 100 mg/kg/d in four divided doses,
10 mg/kg every 8 hours, for 1 week. Consult a medical
toxicologist or regional poison control centre for advice
regarding chelation.
ATROPINE
& ANTICHOLINERGICS
Atropine,
scopolamine, belladonna, diphenoxylate with atropine.
Datura stramonium, Hyoscyamus niger, some mushrooms,
tricyclic antidepressants, and antihistamines are antimuscarinic
agents with variable central nervous system effects.
The patient complains of dryness of the mouth, thirst,
difficulty in swallowing, and blurring of vision. The
physical signs include dilated pupils, flushed skin,
tachycardia, fever, delirium, myocolonus, ileus, and
flushed appearance. Antidepressants and antihistamines
may induce convulsions.
Antihistamines are commonly available with or without
prescription. Diphenhydramine commonly causes delirium,
tachycardia, and seizures. Massive overdose may mimic
tricyclic antidepressant poisoning. The nonsedating
agents terfenadine and astemizole have caused QT interval
prolongation and torsade de pointes. Loratidine has
not caused this problem.
Treatment
A.
Emergency and Supportive Measures
Perform
gastric lavage, and administer activated charcoal. Do
not induce emesis in patients who have ingested antihistamines
or antidepressants, because seizures may occur abruptly.
Tepid sponge baths and sedation are indicated to control
high temperatures.
B.
Specific Treatment
For
pure atropine or related anticholinergic syndrome, if
symptoms are severe, give p hysostigmine salicylate,
o.5 - 1 mg slowly intravenously over 5 minutes, with
electrocardiographic monitoring, until symptoms are
controlled. Bradyarrhythmias and convulsions are a hazard
with physostigmine administration, and it should not
be used in patients with tricyclic antidepressed overdose.
BETA-ADRENERGIC
BLOCKERS
There
are wide variety of beta-adrenergic blocking drugs,
with varying pharmacologic and pharmacokinetic properties.
The most commonly used and most toxic beta-blocker is
propranolol. Propranolol competitively blocks beta1
and beta2 adrenoceptors and also has direct membrane
depressant and central nervous system effects.
Clinical
Findings
The
most common findings with mild or moderate intoxication
are hypotension and bradycardia. Cardiac depression
from more severe poisoning is often unresponsive no
conventional therapy with beta-adrenergic stimulants
such as dopamine and norepinephrine. In addition, with
propranolol and other lipid - soluble drugs, seizures
and coma may occur.
The diagnosis is based on typical clinical findings.
Routine toxicology screening does not usually include
beta-blockers.
Treatment
A.
Emergency and Supportive Measures :
Initially,
treat bradycardia or heart b lock with atropine, isoproterrenol
by intravenous infusion, titrated to the desited, or
an external transcutaneous cardiac pacemaker. Specific
antidotal treatment may be necessary.
For ingested drugs, empty the stomach by gastric lavage
and administer activated charcoal. Do not induce emesis
because of the risk of seizures.
B.
Specific Treatment :
If
the above measures are not successful in reversing bradycardia
and hypotension, give glucagon, 5 - 10 mg intravenously,
followed by an infusion of 1 - 5 mg/h. Glucagon in an
inotropic agent that acts as a different receptor site
and is therefore not affected by beta-blockade.
CALCIUM
CHANNEL BLOCKERS
Calcium
channel blockers used in the United States include verapamil,
diltiazem, nifedipine, nicardipine, amlodipine, felodipine,
isradipine, nisoldipine, and nimodipine. These drugs
share the ability to cause arteriolar vasodilation and
depression of cardiac contractility, especially after
acute overdose. Patients may present with bradycardia.
AV nodal block, hypotension, or a combination of these
effects. With severe poisoning, cardiac arrest may occur.
Treatment
A.
Emergency and Supportive Measures
Maintain
a patient airway and assist ventilation, if necessary.
Treat coma, hypotension, and seizures as described at
the beginning of this chapter. Treat bradycardia with
atropine, isoproterenol, or a transcutaneous or internal
cardiac pacemaker.
For ingested drugs, perform gastric lavage and administer
activated charcoal. In addition, whole bowel irrigation
should be initiated as soon as possible if the patient
has ingested a sustained - release product. Because
of the risk of hypotension and seizures, do not induce
emesis.
B.
Specific Treatment :
If
bradycardia and hypotension are not reversed with these
measures, administer calcium chloride intravenously.
Start with calcium chloride 10%, 10 mL, or calcium gluconate,
20 mL. Repeat the dose every 3 - 5 minutes. The optimum
dose has not been established, but there are reports
of success after as much as 10 - 12 g of calcium chloride.
Calcium is most useful in reversing negative inotropic
effects and is less effective for AV nodal blockade
and bradycardia. Epinephrine infusion and glucagon,
5 - 10 mg intravenously, have also been recommended.
CARBON
MONOXIDE
Carbon
monoxide is a colorless, odorless gas produced by the
combustion of carbon-containing materials. Poisoning
may occur as a result of suicidal or accidental exposure
to automobile exhaust, smoke inhalation in a fire, or
accidental exposure to an improperly vented gas heater
or other appliance. Carbon monoxide avidly binds to
hemoglobin, with an affinity approximately 250 times
that of oxygen. This results in reduced oxygen-carrying
capacity and altered delivery of oxygen to cells.
Clinical
Findings
At low carbon monoxide levels, victims may have headache,
dizziness, abdominal pain, and nausea. With higher levels,
confusion, dyspnea, and syncope may occur. Hypotension,
coma, and seizures are common with levels greater than
50 - 60%. Survivors of acute severe poisoning may develop
permanent neurologic deficits. The fetus and newborn
may be more susceptible because of high carbon monoxide
affinity for fetal hemoglobin.
Carbon monoxide poisoning should be suspected in any
person with severe headache or acutely altered mental
status, especially in cold weather, when improper heating
systems may have been used. Diagnosis depends on specific
measurement of the arterial or venous carboxyhemoglobin
saturation, although the level may have declined if
high-flow oxygen therapy, has already been administered.
Routine arterial blood gas testing and pulse oximetry
are not useful because they may give fulsely normal
oxyhemoglobin saturation determination.
Treatment
A.
Emergency and Supportive Measures :
Maintain
a patent airway and assist ventilation, if necessary.
Remove the victim from exposure. Treat patients with
coma. Hypotension, or seizures, as described at the
beginning of this chapter.
B.
Specific Treatment :
The
half-life of the carboxyhemoglobin complex is about
4 - 5 hours in room air but is reduced dramatically
by high concentration of oxygen. Administer 100% oxygen
by tight-fitting high flow reservoir face mask or endotracheal
tube. Hyperbaric oxygen can provide 100% oxygen under
higher than atmosphere pressures, further shortening
the half-life; it may be useful if immediately available
for patients with coma or seizures and in pregnant women,
though controlled studies have failed to prove that
HBO is superior to high - flow oxygen at normal pressure.
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