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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2593_Библиотеки_им_академика_М_И_Перельмана
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Acetaminophen-induced hepatotoxicity
is universal by 36 hours after ingestion,
but patients who receive NAC within 8
to 10 hours of ingestion rarely exhibit
hepatotoxicity. There is no consensus
as to the best route of NAC
administration, the optimal dosage
regimen, or the optimal duration of
therapy.
INTRODUCTION
This chapter reviews common strategies for the evaluation and
management of drug overdoses and poisonings. Information
regarding the management of specific drug overdoses is best
obtained from a poison control center (reached by calling 1-800-2221222 anywhere in the United States).
Epidemiologic Data
AMERICAN ASSOCIATION OF POISON CONTROL CENTERS
AND DRUG ABUSE WARNING NETWORK
Toxicity secondary to drug and chemical exposure commonly occurs
in children. The incidence of exposure to specific agents and the
severity of outcomes vary based on the population studied.
1–3
The
number of reported toxic exposures in the United States in 2018 was
~2.1 million, according to the American Association of Poison
Control Centers (AAPCC).3 Approximately 70% of the reported
cases were treated at home, saving millions of dollars in medical
costs.
According to the Drug Abuse Warning Network, almost 5.1 million
U.S. emergency department (ED) visits involved drug misuse or
abuse in 2011. Illicit drugs include cocaine, heroin, marijuana,
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ecstasy, γ-hydroxybutyric acid, flunitrazepam (Rohypnol®), ketamine,
lysergic acid, phencyclidine, and hallucinogens. Of those cases, illicit
drug use was mentioned >2.7 million times because many of the
visits involved multiple drugs of abuse.
4
AGE-SPECIFIC DATA
Stratifying patients by age can be useful in assessing the likelihood
of severe toxicity from an exposure. Most unintentional ingestions by
children ages 1 to 6 years occur because children are curious,
becoming more mobile, and beginning to explore their surroundings,
and they often put objects or substances into their mouths.5 Severe
toxicity in young children is relatively uncommon because exposures
usually involve the ingestion of relatively small amounts of a single
substance.
5,6
AAPCC epidemiologic data also report medication
errors, which in the pediatric population commonly result from
confusing units of measurement (eg, teaspoons vs milliliters or
tablespoons vs teaspoons), incorrect formulation or concentration
administered, dispensing cup errors, and incorrect formulation or
concentration dispensed from the pharmacy.
3
In children older than age 6 years, the reasons for toxic exposure
to medications are less clear.7 Adolescent children generally have
poor knowledge of the toxicity of medications and can overdose
themselves unintentionally.
5,8
The potential for suicide attempts or
intentional substance abuse should not be ignored in older children.
These intentional overdoses commonly involve mixed exposures to
illicit drugs, prescribed medications, or ethanol and are associated
with more severe toxicity and death than with unintentional toxic
exposures.
In geriatric patients, overdoses tend to have a greater potential for
severe adverse effects compared with overdoses in other age
groups.9 Although the elderly constitute 13% of the population, they
account for 33% of the drug use and 16% of the suicides.10 Patients
ages 65 years and older take an average of 5.7 prescription
medications along with two to four nonprescription drugs daily.
9,10
The elderly are more likely to have underlying illnesses and often
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have access to a variety of potentially dangerous medications. This
results in higher rates of completed suicides than that in other age
groups.
10,11
Information Resources
COMPUTERIZED DATABASES
A vast number of substances can be involved in a poisoning or
overdose. Reliable data about the contents of products, toxicities of
substances, and treatment approaches need to be readily
accessible. POISINDEX, a computerized database,11 provides
information on thousands of drugs by brand name, generic name,
and street name, as well as foreign drugs, chemicals, pesticides,
household products, personal care items, cleaning products,
poisonous insects, poisonous snakes, and poisonous plants. Annual
subscriptions to POISINDEX are expensive and are generally
available only in large medical centers.
12
PRINTED AND ELECTRONIC PUBLICATIONS
Textbooks and manuals also provide useful clinical information about
the presentation, assessment, and treatment of toxicities.
Goldfrank’s Toxicologic Emergencies13 and Poisoning and Drug
Overdose14 are valuable, less-expensive alternatives to
computerized database programs, and are available in print and
electronically. Books, however, are less useful than are
computerized databases because information must be condensed
and cannot be updated as frequently. Some drug package inserts
also refer to treatment of acute toxicities; however, the information
can be inadequate or inappropriate.
15,16
POISON CONTROL CENTERS
Poison control centers provide the most cost-effective and accurate
information to health care providers and to the general public.
17,18
Poison centers are staffed by trained poison information specialists
who have a pharmacy, nursing, or medical background. Physician
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backup is provided 24 hours a day by board-certified medical
toxicologists. The nonphysician clinical toxicologists, pharmacists,
and nurses who staff poison control centers are certified as
specialists in poison information by the AAPCC or as clinical
toxicologists by the American Board of Applied Toxicology.
19
The poison information specialist must accurately and efficiently
assess event-specific toxicity by telephone, without the benefit of
direct observation of the patient. The specialist must communicate
this assessment along with treatment information quickly, accurately,
and professionally in a reassuring manner. Subsequent to telephone
consultations, poison control center staff should initiate follow-up
calls to determine the effectiveness of the recommended treatment
and the need for additional evaluation or treatment.
20,21
EFFECTIVE COMMUNICATION
Effective communication is essential to the assessment of potential
poisonings. In most situations, the person seeking guidance on the
management of a potentially toxic exposure is the parent of a small
child who may have ingested a substance. The caller is usually
anxious about the child and may feel guilty about the exposure. To
calm the caller, the health care provider should quickly reassure the
individual that telephoning for help was appropriate and that the best
assistance possible will be provided.21 If English is not the first
language of the caller, or if there are other communication barriers
(eg, panic), solutions must be found to enhance outcomes. Most
poison centers subscribe to translation services or have bilingual
staff to communicate with non–English-speaking callers. Poison
centers also have special equipment to serve the hearing- and
speech-impaired populations.
Once calm, effective communication is established, the health
care provider should first determine whether the patient is conscious
and breathing and has a pulse. If life-threatening symptoms have
occurred, the caller should call 911 for emergency services. If the
health care provider does not have the knowledge or resources to
provide poison information, he or she should refer the caller to the
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closest poison control center. Information on the location and phone
number of the nearest poison control center can be found at
http://www.aapcc.org or by calling 1-800-222-1222 in the United
States.
GENERAL MANAGEMENT
Supportive Care and “ABCs”
Management of poisoned or overdosed patients is primarily based
on symptomatic and supportive care. Specific antidotes exist only for
a small percentage of the thousands of potential drugs and
chemicals that can cause a poisoning.
The first aspect of patient management should always be basic
support of airway, breathing, and circulation (the “ABCs”). The
assessment and treatment of the potentially poisoned patient can be
separated into seven primary functions: (a) gathering history of
exposure, (b) evaluating clinical presentation (ie, “toxidromes”), (c)
evaluating clinical laboratory patient data, (d) removing the toxic
source (eg, irrigating eyes, decontaminating exposed skin), (e)
considering antidotes and specific treatment, (f) enhancing systemic
clearance, and (g) monitoring outcome.
22–24
GATHERING EXPOSURE HISTORY
Comprehensive information about the history of the toxic exposure
should be gathered from as many different sources as possible (eg,
patient, family, friends, prehospital health care providers). This
information should be compared for consistency and evaluated
relative to clinical findings and laboratory results. The patient’s
history of the exposure is often inaccurate and should be confirmed
with objective findings.
22,23,25
For example, a patient who presents to
an ED with a supposed hydrocodone and carisoprodol overdose is
expected to be lethargic or comatose. If the patient arrives wide
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awake with tachycardia and agitation, the clinician should suspect
exposure to other substances.
Specific information should be sought concerning the patient’s
state of consciousness, symptoms, probable intoxicant(s), and
maximal amount and dosage form(s) of substance ingested, as well
as when the exposure occurred. Medications, allergies, and prior
medical problems also should be ascertained to facilitate
development of treatment plans (eg, a history of renal failure may
indicate the need for hemodialysis to compensate for decreased
renal drug clearance).
22,23
EVALUATING CLINICAL PRESENTATION AND TOXIDROMES
A thorough physical examination is needed to characterize the signs
and symptoms of overdose, and it should be conducted serially to
determine the evolution or resolution of the patient’s intoxication. An
evaluation of the presenting signs and symptoms can provide clues
to the drug class causing the toxicity, confirm the data on the history
surrounding the toxic exposure, and suggest initial treatment.
22,26–28
The patient may be asymptomatic on presentation, even though a
potentially severe exposure has occurred, if absorption of the drug or
toxic substance is incomplete or if the substance has not yet been
metabolized to a toxic substance.
29–31
Characteristic toxidromes (ie, a constellation of signs and
symptoms consistent with a syndrome) can be associated with some
specific classes of drugs.
23,27,28
The most common toxidromes are
those associated with anticholinergic activity, increased sympathetic
activity, and central nervous system (CNS) stimulation or depression.
Anticholinergic drugs can increase heart rate and body temperature,
decrease gastrointestinal (GI) motility, dilate pupils, and produce
drowsiness or delirium. Sympathomimetic drugs can increase CNS
activity, heart rate, body temperature, and blood pressure (BP).
Opioids, sedatives, hypnotics, and antidepressants can depress the
CNS, but the specific class of CNS depressant often cannot be
easily identified.
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Classic findings may not be present for all drugs within a
therapeutic class. For example, opioids generally induce miosis, but
meperidine can produce mydriasis. Furthermore, the association of
symptoms with a particular class of toxic substances is difficult when
more than one substance has been ingested. Practitioners should
not focus only on the specific clinical findings associated with a
toxidrome. Rather, they should consider all subjective and objective
data gathered from the history of the exposure, the patient’s medical
history, physical examination, and laboratory findings.
27
INTERPRETATION OF LABORATORY DATA
Drug screens
A urine drug screen can be useful in identifying the presence of
drugs and their metabolites in selected patients but is not indicated
in all cases of drug overdose. Urine drug screens can be useful in a
patient with coma of unknown etiology, when the presented history is
inconsistent with clinical findings, or when more than one drug might
have been ingested.
32,33
Pharmacokinetic considerations
The absorption, distribution, metabolism, and elimination of drugs in
the overdosed patient can be quite different from when the drug is
taken in usual therapeutic doses.
29–31
The expected
pharmacodynamic and pharmacokinetic features of drugs can be
substantially altered by large drug overdoses, especially with drugs
that exhibit dose-dependent pharmacokinetics. The rate of drug
absorption is generally slowed by large overdoses, and the time to
reach peak serum drug concentrations can be delayed.
32,34
For
example, peak serum concentrations of phenytoin can be delayed
for 2 to 7 days after an orally ingested overdose.
35,36
The volume of
distribution of an overdosed drug can be increased, and when usual
metabolic pathways become saturated, secondary clearance
pathways can be important. For example, large overdoses of
acetaminophen saturate glutathione mechanisms of metabolism,
resulting in hepatotoxicity.
37
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When the pharmacokinetic parameters of an overdosed drug are
altered, serial plasma concentration measurements can better define
the absorption, distribution, and clearance phases of the ingested
substance. Pharmacokinetic parameters that have been derived
from therapeutic doses should not be used to predict whether
absorption is complete or to predict the expected duration of
intoxication caused by large overdoses.
31,38,39
DECONTAMINATION
After the airway and the cardiopulmonary system are supported,
efforts should be directed toward removing the toxic substance from
the patient (ie, decontamination).
22,40
Decontamination presumes that
both the dose and the duration of toxin exposure are important in
determining the extent of toxicity and that prevention of continued
exposure will decrease toxicity.
29–31,40
This intuitive concept is clearly
relevant to ocular, dermal, and respiratory exposures when local
tissue damage is the primary problem. Respiratory decontamination
involves removing the patient from the toxic environment and
providing fresh air or oxygen to the patient. Decontamination of skin
and eyes involves flushing the affected area with large volumes of
water or saline to physically remove the toxic substance from the
surface.
22,23
Gastrointestinal decontamination
Because most poisonings and overdoses result from oral ingestions,
measures to decrease or prevent continued GI absorption have
commonly been used to limit the extent of exposure.
22,23,37
GI
decontamination should be considered if the ingestion is large
enough to produce potentially significant toxicity, or if the potential
severity of the ingestion is unknown and the time since ingestion is
<1 hour. The following methods have historically been used: (a)
evacuation of gastric contents by emesis or gastric lavage, (b)
administration of activated charcoal as an adsorbent to bind the toxic
substance remaining in the GI tract, (c) use of cathartics or whole-
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bowel irrigation (WBI) to increase the rectal elimination of
unabsorbed drug, or (d) a combination of any of these methods.
41–46
The efficacy of GI decontamination varies, depending on when the
process is initiated relative to the time of ingestion, dose ingested,
and other factors. Furthermore, ipecac-induced emesis, gastric
lavage, cathartics, and activated charcoal are not directly associated
with improved patient outcomes.
41–46
The most appropriate method for GI tract decontamination
remains unclear because sound comparative data for different
methods of GI decontamination are not available. Clinical research in
healthy subjects, by necessity, must use nontoxic doses of drugs.
Studies using nontoxic doses are not applicable to the overdose
situation because alterations in GI absorption can occur with large
doses. In addition, low-dose studies generally rely on
pharmacokinetic end points such as peak plasma concentrations,
area under the plasma concentration–time curve, or quantity of drug
recovered from the urine.
41,42,44–46
In contrast, clinical studies of GI
decontamination methods in patients who have ingested toxic doses
of a substance use clinical outcomes or a directional change in
serum drug concentrations.
41,42,45,46
These latter trials are not
standardized with respect to the dose ingested or to the time interval
between drug ingestion and GI decontamination.
41–46
Ipecac-Induced Emesis and Gastric Lavage
Ipecac-induced emesis and gastric lavage primarily remove
substances from the stomach. Their efficacy is affected significantly
by the time the ingested substance remains in the stomach. Gastric
lavage and ipecac-induced emesis are most effective when
implemented before the substance moves past the stomach into the
intestine (usually within 1 hour).
41,42
The commonly used adult gastric lavage tube (36F) has an
internal diameter too small to allow the recovery of large tablet or
capsule fragments. An even smaller diameter lavage tube is used for
children.42 Gastric lavage may be useful only if large amounts of a
liquid substance were ingested and the patient arrived within 1 hour
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of the ingestion.45 However, patients usually arrive in the ED more
than an hour after ingestion, when absorption of the toxin has most
likely already occurred. As a result, the efficacy of these procedures
in overdose situations is minimal, and no studies have confirmed that
use of gastric lavage or ipecac-induced emesis improves the
outcome of the patient.
41,42,47
For these reasons, ipecac is no longer
used, and gastric lavage is used only in rare, specific situations.
Activated Charcoal
In 1963, a review article concluded that activated charcoal was the
most valuable agent available for the treatment of poisoning.48 This
conclusion was based only on studies in fasting patients who had
nontoxic exposures. Nevertheless, data from those studies were
extrapolated to poisoned patients. Since then, activated charcoal has
become the preferred method of GI decontamination for the
treatment of toxic ingestions.
22,40,48
The goal of the therapy is to decrease the absorption of the
substance and reduce or prevent systemic toxicity.43 Unfortunately,
there are no satisfactorily designed clinical studies assessing the
benefit from the use of activated charcoal to guide the use of this
therapy. There is also no evidence that the administration of
activated charcoal improves clinical outcomes.
43
The use of activated charcoal at a dose of 1 g/kg should be
considered when the patient has ingested a toxic substance that is
known to be absorbed by activated charcoal within 1 hour of the
ingestion. The potential for benefit is unknown if the activated
charcoal is given >1 hour after ingestion.43 It should be noted that
iron and lithium are not absorbed by activated charcoal. Other forms
of GI decontamination must be used to remove those substances
from the GI tract.
43
Generally, the use of activated charcoal is safe. Although there are
relatively few reports of adverse effects from the use of activated
charcoal, there are numerous reports of complications, usually
involving aspiration. It is essential that the patient has an intact or a
protected airway (intubation) before activated charcoal is
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