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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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administered, especially in drowsy patients or in patients who may
rapidly become obtunded.
43
Vomiting with aspiration of activated charcoal occurs in about 5%
of patients who receive activated charcoal.
43,49–51
The resulting
pulmonary problems can be caused by aspiration of acidic stomach
contents or the charcoal. Decreased oxygenation can occur
immediately, or pulmonary effects can occur later.
51–55
Acute
respiratory distress syndrome has resulted after the unintentional
instillation of charcoal into the lung.51 Aspiration of charcoal can
result in chronic lung disease or fatalities, whereas the toxic
exposure, for which the charcoal was administered, is often not
lethal or even serious.
52,56
Cathartics
Historically, sorbitol (a cathartic) was often administered with
activated charcoal to enhance passage of the charcoal–substance
complex through the GI tract. However, decreased transit time
through the bowel has not been proved to decrease absorption
because drug absorption does not take place in the large bowel.
44
Sorbitol is also associated with vomiting and aspiration.
44
Hypernatremia can also develop subsequent to the administration of
repeat doses of activated charcoal with sorbitol.
57,58
Currently, most
EDs use aqueous activated charcoal mixtures rather than charcoal–
sorbitol combinations. Because cathartics are not effective in
reducing drug absorption or increasing patient outcome, their use is
no longer advised.
44
Whole-Bowel Irrigation
WBI with a polyethylene glycol–balanced electrolyte solution (eg,
Colyte®, GoLYTELY®) can successfully remove substances from the
entire GI tract in a period of several hours. WBI is effective with
ingestions of sustained-release dosage forms, as well as with
substances that form bezoars (concretions of tablets or capsules),
such as ferrous sulfate or phenytoin.
23,45,59
WBI is also indicated
when the toxic agent is not adsorbed by activated charcoal (eg, body
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packer packets, lithium, iron, potassium).
22,23,45,59
This method of GI
decontamination takes much longer to complete and is associated
with poor patient compliance because large volumes of fluid (2
L/hour for adults until the effluent is clear) need to be ingested to be
effective.59 A nasogastric (NG) tube can be inserted, and the WBI
fluid can be administered via the NG tube so that lack of patient
compliance is no longer a factor.
45
ANTIDOTES AND SPECIFIC TREATMENTS
An antidote is a drug that reverses the toxicity of another substance.
Some antidotes can displace a drug from receptor sites (eg,
naloxone for opioids, flumazenil for benzodiazepines), and some can
inhibit the formation of toxic metabolites (eg, N-acetylcysteine [NAC]
for acetaminophen, fomepizole for methanol).
23,60,61
Some treatments
are highly effective for the management of individual drug overdoses
but do not meet the definition of an antidote. For example, sodium
bicarbonate is used to treat the cardiotoxicity arising from tricyclic
antidepressant (TCA) overdoses, and benzodiazepines are used to
treat CNS toxicity associated with cocaine and amphetamine
overdoses.
62–64
However, for antidotes to be effective, they must be
readily available at the health care facility in adequate doses to treat
the patient in a timely manner.
65
ENHANCING SYSTEMIC CLEARANCE
Hemodialysis and manipulation of urine pH can enhance the
clearance of substances. Hemodialysis can successfully treat some
specific intoxications (eg, methanol, ethylene glycol, aspirin,
theophylline, lithium). Hemodialysis can also be used in patients with
severe acid–base disturbances or renal dysfunction.47 Alkalinization
of the urine can enhance the elimination of drugs such as aspirin and
phenobarbital.
66–68
MONITORING OUTCOME
Selecting the appropriate parameters and length of time to monitor a
patient who has been exposed to a toxic agent requires knowledge
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of toxic effects and the time course of the intoxication.
33,34
Most
patients who are at risk for moderate or severe toxicity should be
monitored in an intensive care unit (ICU) with assessments of
cardiac, pulmonary, and CNS function.
69,70
ASSESSMENT OF SALICYLATE INGESTION
Gathering a History
CASE 5-1
QUESTION 1: A.J., the mother of a 3-year-old child, states that her son, R.J., has
ingested some aspirin tablets.
What additional information should be obtained from or given to A.J. at this
time?
Obtaining an initial assessment of the patient’s status is essential.
The caller’s telephone number should be obtained in the event that
the call is disconnected, initial recommendations need to be
modified, or subsequent follow-up is needed. The health care
provider should ask for patient-specific information with questions
that are nonthreatening and nonjudgmental. The caller should be
reassured that calling for help was the right thing to do.
Evaluating Clinical Presentation
CASE 5-1, QUESTION 2: On further questioning, A.J. states that R.J. is crying
and has a stomachache. Otherwise, the child is acting normally. R.J. was found
sitting on the bedroom floor with an aspirin bottle in his hand and some partially
chewed tablets on the floor next to him. A.J. states that the child had the same
look on his face that he has when he eats things that he does not like. A.J.
reports that she can see white tablet material on the child’s teeth. The mother
was gone no more than 5 minutes and had asked her 6-year-old son to watch
his brother. What additional information is needed to correctly assess the
potential for toxicity in R.J.?
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To determine the potential toxicity of an unintentional ingestion, it
is important to assess the presence of symptoms and to identify the
substance ingested. Inquiries should begin with open-ended
questions to determine the facts that the caller is certain of versus
what may have been assumed. The answers usually point to more
specific information that is needed to accurately assess the
exposure.
20
R.J.’s symptoms presently are not life-threatening. His behavior is
consistent with being scared in response to the mother’s anxiety.
Once it has been established that the child does not need immediate
life-saving treatment, the caller is generally able to answer additional
questions.
A.J. has already provided information about the child’s symptoms.
More information is needed to determine the identity of the ingested
substance, the time of ingestion, the brand of aspirin (to ensure that
the product is not an aspirin-combination or even an aspirin-free
formulation), the dosage form, the number of dosage units in a full
container, and the number of remaining dosage units in the
container. The parent should be advised to look for tablets under
beds, rugs, or other locations out of sight (eg, wastepaper baskets,
toilets, pet food dishes, pockets). The dosage forms in the container
should be identical in appearance, and the contents should be what
are stated on the label. Information concerning the child’s weight and
health status, as well as whether the child is taking other
medications, is also important. The child’s weight is useful in
determining the maximum milligram per kilogram dose of aspirin that
was ingested.
When more than one child is present during an ingestion, the
caller should be questioned as to whether other children also could
have participated in the ingestion. In this situation, the children could
have shared equally in the missing medication, all of the drug could
have been fed to one child, or all of the drug could have been
ingested by the oldest or most aggressive child. When it is unclear
how much is missing among a group of children, each child should
be evaluated and managed as if he or she may have ingested the
total missing quantity.
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Triage of Call
CASE 5-1, QUESTION 3: A.J. has now determined that a total of seven tablets,
each containing 81 mg per tablet of aspirin, are missing from the bottle.
Because A.J. recalls having taken two aspirin tablets from this bottle, it is not
likely that her son took more than seven tablets. A.J. states that R.J. weighs
41.88 pounds (19 kg). What treatment is needed for this child?
The maximal dose of aspirin ingested by this child is likely to be
much less than the minimal dose required to cause significant
symptoms based on his weight for his age (ie, ~41.88 pounds [19
kg]). A dose of 150 mg/kg of aspirin is the smallest dose at which
treatment or assessment at a health care facility is necessary.
68,71
A.J. is likely to have ingested a maximum of 567 mg of aspirin (ie,
seven 81-mg tablets), which is about 29.8 mg/kg (567 mg divided by
41.88 pounds [19 kg]). If this child is healthy, takes no medications,
and is not allergic to aspirin, the child does not require any
treatment. With this history of ingestion, the only adverse effect that
might occur is some mild nausea. Providing information to the
mother that her child had not ingested a toxic or dangerous amount
will be reassuring.
For many years, aspirin was the most common cause of
unintentional poisoning and poisoning deaths among children.
71–73
However, safety closure packaging and reduction of the total aspirin
content in a full bottle of children’s aspirin to ~3 g has steadily
reduced the frequency of pediatric aspirin poisoning and deaths.
72–74
Although acute aspirin poisoning remains a problem, the largest
percentage of life-threatening intoxications now results from
therapeutic overdose.68 Therapeutic overdoses occur when a dose is
given too frequently, when both parents unknowingly dose the child
with the drug, or when too large a dose is given. Therapeutic
overdoses are especially problematic when excessive doses are
given for a prolonged period and the drug is able to accumulate.
68
Patient Outcome
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Follow-up telephone consultation on toxic ingestions is important to
identify children who unexpectedly develop symptoms that might
need to be treated. A telephone call to A.J. 6 to 24 hours after her
initial call would be appropriate to follow up on the child. On a call
back to A.J., she stated that she gave R.J. lunch at the appropriate
usual time. R.J. then watched cartoons, took his usual nap, and
remained asymptomatic.
Acute and Chronic Salicylism
SIGNS AND SYMPTOMS
CASE 5-2
QUESTION 1: A.S., a 71-year-old, 130.07-pound (59-kg) female with a history of
chronic headaches, has taken 10 to 12 aspirin tablets daily for several months.
On the evening of admission, she became lethargic, disoriented, and
combative. Additional history revealed that she ingested up to 95 aspirin tablets
on the morning of admission (about 11 hours earlier) in a suicide attempt. She
reported ringing in her ears, nausea, and two episodes of vomiting. She is
disoriented and lethargic. Vital signs were BP 148/95 mm Hg, pulse 114
beats/minute, respirations 38 breaths/minute, and temperature 101.2 °F (38.44
°C). A.S.’s laboratory data obtained on admission were as follows:
Serum sodium (Na), 144 mEq/L
Potassium (K+), 2.5 mEq/L
Chloride (Cl–), 103 mEq/L
Bicarbonate, 9 mEq/L
Glucose, 58 mg/dL
Blood urea nitrogen (BUN), 38 mg/dL
Creatinine, 2.5 mg/dL
Arterial blood gas (ABG) values (room air) were as follows: pH, 7.14; PCO2,
18 mm Hg; and PO2, 96 mm Hg. A serum salicylate concentration measured
~12 hours after the acute ingestion was 90 mg/dL. Her hemoglobin was 9.6
g/dL, with a hematocrit of 28.9% and a prothrombin time (PT) of 16.4 seconds.
Is A.S. at high risk because of her ingestion?
The symptoms and severity of salicylate intoxication depend on
the dose consumed; the patient’s age; and whether the ingestion
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was acute, chronic, or a combination of the two.
73,75,76
This case
illustrates an acute ingestion in someone who has also chronically
ingested aspirin. Acute ingestion of 150 to 300 mg/kg of aspirin is
likely to produce mild-to-moderate intoxication, >300 mg/kg indicates
severe poisoning, and >500 mg/kg is potentially lethal.
68,71
A.S., who
ingested ~523 mg/kg, has taken a potentially lethal dose. Chronic
salicylate intoxication is usually associated with ingestion of >100
mg/kg/day for >2 days.
68,71
A.S. has been taking 66 mg/kg/day for
her headaches in addition to her acute ingestion. A.S. demonstrates
many of the findings typical of severe acute salicylism (see sections
on Pathophysiology of Salicylate Intoxication and Assessment of
Toxicity). A.S.’s prognosis is potentially poor because she is elderly
and has taken a potentially lethal overdose of aspirin.
Pathophysiology of Salicylate Intoxication
CASE 5-2, QUESTION 2: What are the pathophysiological and clinical features
of acute and chronic salicylism?
Toxicity from salicylate exposure results in direct irritation of the GI
tract, direct stimulation of the CNS respiratory center, stimulation of
the metabolic rate, lipid and carbohydrate metabolism disturbances,
and interference with hemostasis.
68,71,73,75,76
Toxic doses of salicylate
directly stimulate the medullary respiratory center, leading to nausea,
vomiting, tinnitus, delirium, tachypnea, seizures, and coma and
influence several key metabolic pathways.
68,73–77
Direct stimulation of
the respiratory drive increases the rate and depth of ventilation,
which can result in primary respiratory alkalosis. The respiratory
alkalosis causes increased renal excretion of bicarbonate, resulting
in decreased buffering capacity. The patient usually presents with a
partially compensated respiratory alkalosis.
68,74,75,77
Hypokalemia can
result from increased GI and renal losses of potassium, as well as
from systemic alkalosis.
68,75,76
Although marked metabolic and
neurologic abnormalities are most commonly observed in young
children with advanced salicylate intoxication, adolescents or adults
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acutely poisoned with a large dose of salicylates can exhibit these
symptoms as well.
68,74,75
Acute salicylism in a young child often takes
a more severe course than that typically seen in adults. After acute
ingestion, children quickly pass through the phase of pure respiratory
alkalosis. Renal bicarbonate loss secondary to respiratory alkalosis
reduces the buffering capacity more profoundly in a child and
facilitates the development of metabolic acidosis.
68,73,75,77
Salicylates have toxic effects on several biochemical pathways
that contribute to metabolic acidosis and other symptoms.
68,75,77
Mitochondrial oxidative phosphorylation is uncoupled and results in
an impaired ability to generate high-energy phosphates, increased
oxygen use and carbon dioxide production, increased heat
production and hyperpyrexia, increased tissue glycolysis, and
increased peripheral demand for glucose. Salicylates also inhibit key
dehydrogenase enzymes within the Krebs cycle, resulting in
increased levels of pyruvate and lactate. The increased demand for
peripheral glucose causes increased glycogenolysis,
gluconeogenesis, lipolysis, and free fatty acid metabolism. The latter
results in enhanced formation of keto acids and ketoacidosis.
73,77
The patient may become severely volume depleted through
several mechanisms.
68,75,77
Hyperthermia and hyperventilation
produce increased insensible water loss, vomiting may promote GI
fluid losses, and the solute load caused by altered glucose
metabolism results in osmotic diuresis. Depending on the patient’s
acid–base balance and net fluid and electrolyte intake and output,
serum sodium and potassium concentrations may be normal,
elevated, or decreased. Hypernatremia and hypokalemia are most
common.
73,75
Blood glucose concentration is usually normal or slightly elevated,
although hypoglycemia may accompany chronic salicylism (eg, as
illustrated by A.S.) or occur late in acute intoxication. CNS glucose
levels can be markedly reduced in the presence of normal blood
glucose concentrations because increased CNS glucose utilization
to generate high-energy phosphate exceeds the rate at which
glucose can be supplied.
68,73,75,77
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ASSESSMENT OF TOXICITY
CASE 5-2, QUESTION 3: What signs, symptoms, and laboratory values in A.S.
are consistent with salicylate intoxication?
A.S. demonstrates many of the findings typical of severe acute
salicylism. Hyperventilation has resulted from the direct respiratory
stimulant effects of salicylate and as compensation for her metabolic
acidosis (PCO2, 18 mm Hg; pH, 7.14; serum bicarbonate, 9 mEq/L;
respiratory rate, 38 breaths/minute). Hypokalemia (2.8 mEq/L) in the
presence of metabolic acidosis represents severe potassium
depletion because of increased renal and, possibly, GI losses.
Hyperpyrexia caused by salicylate is present in A.S., although an
infectious cause must also be considered. Her neurologic symptoms
of lethargy, disorientation, and combativeness, as well as tinnitus,
nausea, and vomiting, are commonly seen in severe salicylate
intoxication. In addition, being elderly and taking a lethal amount of
aspirin bodes ill for this patient’s outcome.
LABORATORY EVALUATION
CASE 5-2, QUESTION 4: What objective evaluations should be assessed in a
patient with presumed salicylate intoxication?
A.S.’s workup illustrates a thorough initial patient evaluation.
Laboratory evaluation should include ABG values, serum
electrolytes, BUN, serum creatinine, blood glucose, and a complete
blood cell count.
73,74
Urine should be tested for specific gravity and
pH.73 In symptomatic patients, a PT or an international normalized
ratio (INR) and partial thromboplastin time are useful to assess the
presence of salicylate-induced coagulopathy. Vitals signs should be
monitored for an increased respiratory rate and hyperpyrexia.
74,75
Physical examination should include an evaluation of chest
radiograph, cardiopulmonary and neurologic function, and
measurement of urine output.
75
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A salicylate blood concentration should be obtained immediately
and every 2 hours in patients.
24,64,73,75
Serum salicylate
concentrations should be reassessed every 2 hours to verify that the
original concentration represented a peak level and that the
salicylate level is decreasing rather than increasing.
24,68,73,76,78
Obtaining the units of measurement on salicylate serum
concentrations is essential because different laboratories report
concentrations in different units (eg, mg/dL, μg/mL, mmol/L). An
incorrect interpretation of the salicylate unit of measurement can
result in overestimates or underestimates of the severity.
24
Manifestations of severe acute salicylism include a variety of
neurologic signs and symptoms: disorientation, irritability,
hallucinations, lethargy, stupor, coma, and seizures.
69,73
Hyperthermia may be marked and can result in the inappropriate
administration of aspirin as an antipyretic. Coagulopathy can occur
because of impaired platelet function, hypoprothrombinemia,
reduced factor VII production, and increased capillary fragility,
especially when aspirin is taken chronically.
75–77
Pulmonary edema
and acute renal failure also can occur, but the former occurs more
commonly after chronic intoxication.
75,77,78
Chronic salicylism symptoms are similar to that of acute
intoxications. However, patients with chronic exposures may have
fewer GI symptoms, but they generally appear more ill and have
more CNS symptoms.
71,79
In both adults and children, the principal
signs of chronic salicylism are a partially compensated metabolic
acidosis, increased anion gap, ketosis, dehydration, electrolyte loss,
hyperventilation, tremors, agitation, confusion, stupor, memory
deficits, renal failure, and seizures.
73,75,76,80
The severity of CNS
manifestations is related to the cerebrospinal fluid (CSF) salicylate
concentration.
74,75
CSF concentrations may increase in the presence
of systemic acidosis because a greater fraction of salicylate is not
ionized and can cross the blood–brain barrier. Therefore, metabolic
acidosis is especially dangerous in a salicylate-intoxicated
patient.
73,75
Unless the history of salicylate intake is specifically sought, the
problem may not be immediately apparent, especially in the elderly
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