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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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decontamination.
93,95,96,103
This prolongation of absorption time is
further complicated when sustained-release or enteric-coated
dosage formulations have been ingested because the onset of
symptoms is unpredictable.
94
K.M.’s serum iron concentration of 480 μg/dL suggests a serious
ingestion because peak serum iron concentrations >500 μg/dL are
usually predictive of significant toxicity.
93–96,100,103
This single serum
iron concentration does not provide information as to whether the
serum concentration is rising or declining or when the serum iron
concentration will peak as a result of her iron ingestion.
104
Iron
tablets may also clump together and form a bezoar, which can result
in prolonged absorption and delay the onset of toxicity.
93,96
Samples
for peak serum iron concentration should be obtained 4 to 6 hours
after ingestion.
94–96,103
Although K.M.’s serum iron concentration was
measured ~3 hours after ingestion, another serum iron level is
needed in 2 to 4 hours because she ingested an enteric-coated
formulation.
Blood Glucose, White Blood Cell Count, and
Total Iron–Binding Capacity
CASE 5-3, QUESTION 10: K.M. was administered WBI through the NG tube for
several hours until the rectal effluent was clear. At this time, K.M. had three
more episodes of vomiting and became drowsy and fussy. A repeat serum iron
concentration was ordered at 6 hours after ingestion. What other laboratory
tests could be helpful in assessing the potential toxicity of iron in K.M.?
Blood glucose concentrations and white blood cell (WBC) counts
usually are increased when serum iron concentrations are >300
μg/dL. A WBC count >15,000/mL and a blood glucose concentration
>150 mg/dL within 6 hours of ingestion generally suggest a higher
likelihood of severe toxicity.93 These tests provide supplemental
confirmation of iron intoxication and may be useful in medical
facilities in which serum iron concentrations cannot be obtained.
These laboratory tests are not routinely monitored in iron poisoning
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because of the poor sensitivity (about 50%).94 Treatment should not
be based on a WBC and glucose concentration alone.
93–95,100
If a
patient with severe iron toxicity presents to a health care facility that
cannot perform timely serum iron levels, either the blood iron sample
must be sent to a laboratory that can do the testing quickly or the
patient must be transferred to a health care facility that can do serum
iron testing for patient monitoring.
It was once believed that if the serum iron concentration exceeded
the total iron–binding capacity concentration, it would indicate
substantial iron toxicity. However, this theory has not held up, and
the total iron–binding capacity test is no longer used to monitor iron
toxicity.
99
Stages of Iron Toxicity
CASE 5-3, QUESTION 11: It is now 6 hours since K.M. ingested the iron tablets.
Her second serum iron concentration is not yet available. She continues to be
drowsy and fussy, and she has missed her usual nap. She is still vomiting. Why
is K.M.’s relatively mild course at this time not particularly reassuring?
The time between the ingestion of an overdose of drugs and the
development of severe toxicity can be delayed. It is unclear why
there may be an asymptomatic period, but it may be secondary to
delayed absorption of the ingested drug, the time required for the
drug distribution, or the time needed to form a toxic metabolite.
Consequently, K.M. may still exhibit further symptoms of severe
toxicity. Four distinct stages of symptoms can be encountered with
iron toxicity.
91–96
STAGE I
Stage I symptoms usually take place within 6 hours of ingestion,
during which nausea, vomiting, diarrhea, and abdominal pain occur,
probably secondary to the erosive effects of iron on the GI mucosa.
The caustic effects of free iron can cause bleeding, as evidenced by
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blood in the vomitus and stool. In more severe intoxications, CNS
and cardiovascular toxicity can be present during stage I.
93–96
STAGE II
The second stage of iron toxicity has been suggested as a period of
reduced symptoms and an apparent clinical improvement. This stage
can last for up to 12 to 24 hours after the ingestion and could be
misinterpreted as resolving toxicity. This stage may represent the
time needed for the absorbed iron to distribute throughout the body
before systemic symptoms develop.91 In most severe cases, stage II
does not occur and the patient’s condition continues to deteriorate.
93–
96
STAGE III
Stage III generally occurs 12 to 48 hours after iron ingestion and is
characterized by CNS toxicity (eg, lethargy, coma, seizures) and
cardiovascular toxicity (eg, hypotension, shock, pulmonary edema).
Metabolic acidosis, hypoglycemia, hepatic necrosis, renal damage,
and coagulopathy can also happen during this stage.
93–96
STAGE IV
The final stage is apparent 4 to 6 weeks after acute iron ingestion
and consists of delayed-onset GI tract sequelae secondary to the
initial local toxicity. In this stage, prior tissue damage can progress to
gastric scarring and strictures at the pylorus, resulting in permanent
abnormalities of GI function.
93–96
Patients can present to the health care facility in any stage of iron
toxicity and can have a fatal outcome in any stage. Determination of
a stage of toxicity should be based on clinical symptoms rather than
time of ingestion.
95
Deferoxamine Chelation
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CASE 5-3, QUESTION 12: The second serum iron concentration that was
obtained 6 hours after ingestion has increased from 480 to 560 μg/dL. The child
has continued to vomit and appears pale. What criteria are most important in
determining whether K.M. is a candidate for the antidote deferoxamine?
Deferoxamine (Desferal®) chelates iron by binding ferric ions in
plasma to form the iron complex ferrioxamine.94 Deferoxamine
prevents iron toxicity at a cellular level by removing iron from
mitochondria.92 Unfortunately, deferoxamine is not a very effective
antidote because a relatively small amount of iron is bound (~9 mg
of iron to 100 mg of deferoxamine).
104,105
The iron–deferoxamine
complex is primarily excreted renally as ferrioxamine.
92,94,95
Renal
elimination of the ferrioxamine usually results in pinkish orange
urine, often described as “vin rosé.”
92,94,95
Deferoxamine therapy
should be initiated when serum iron concentrations exceed 500
μg/dL and when symptoms of iron toxicity (eg, GI symptoms,
hemorrhage, coma, shock, seizures) are present.
92–95
K.M. is
experiencing symptoms, she presumably ingested up to 69 mg/kg of
elemental iron, and iron absorption appears to be ongoing based on
the increase in her serum iron concentration. Therefore, K.M. should
be treated with deferoxamine.
DEFEROXAMINE DOSE
CASE 5-3, QUESTION 13: What dose of deferoxamine should be prescribed for
K.M., and how should it be administered?
Deferoxamine is most effective when administered as a
continuous IV infusion because of its short half-life (76 ± 10
minutes).
95,104
Clinically, a slow IV infusion is preferred over
intramuscular (IM) administration because the IV dose is better
controlled, less painful, and better absorbed than is an IM dose.
95,96
Deferoxamine is usually administered in a continuous IV infusion at a
dose of 15 mg/kg/hour. However, doses up to 45 mg/kg/hour have
been used in patients with severe iron poisoning.
93–96,104
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Administering IV boluses of deferoxamine too rapidly can result in
hypotension.
94,96,104,105
According to the manufacturer, the total
deferoxamine dose should not exceed 6 g every 24 hours in children
or adults, but adverse effects have not been seen in patients who
received >6 g every 24 hours.
105
Deferoxamine therapy should be initiated in K.M. at a lower rate of
about 8 mg/kg/hour, and her clinical status should be monitored
closely. If the dose is tolerated, the rate can be increased every 5
minutes until the desired rate of 15 mg/kg/hour is reached.
90
MONITORING AND DISCONTINUATION
CASE 5-3, QUESTION 14: K.M. is admitted to the pediatric ICU shortly after the
initiation of a deferoxamine infusion at 8 mg/kg/hour. How should deferoxamine
therapy be monitored, and when should it be discontinued?
The rate of deferoxamine infusion should be increased with
symptoms of severe iron toxicity and decreased if patients
experience adverse effects.
93,94,96,105
Treatment should continue until
the serum iron concentration is <100 μg/dL and symptoms of iron
toxicity resolve.
105
Patients usually require chelation therapy for
about 1 to 2 days, depending on the severity of symptoms.
93–95
Unnecessarily prolonged chelation therapy should be avoided
because deferoxamine infusion for >24 hours has been associated
with the development of acute respiratory distress syndrome.
93–98
The urine color change to vin rosé indicates ferrioxamine in the
urine.
92,96
The lack of a color change is not a reliable indication of
adequate deferoxamine therapy because not all patients experience
vin rosé urine.
92,96
There is also no correlation between the amount
of iron ingested, serum iron concentration, and the urine color
change.
92
Deferoxamine can interfere with some laboratory methods used to
measure serum iron concentrations and cause falsely low
values.
92,93,103,106
Atomic absorptive spectroscopy is a recommended
method for monitoring serum iron concentrations once deferoxamine
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treatment has been started.
105
When initiating deferoxamine therapy,
the clinical laboratory should be contacted to clarify whether
deferoxamine will interfere with their serum iron analysis.
Patient Outcome
K.M. was admitted to the pediatric ICU overnight and treated with a
constant infusion of deferoxamine at 15 mg/kg/hour for 13 hours. Her
GI symptoms resolved, she became more alert, and her vital signs
were stable. Her serum iron level was 70 μg/dL the next morning,
and she was discharged home that afternoon.
ASSESSMENT OF CENTRAL NERVOUS
SYSTEM DEPRESSANT VERSUS
ANTIDEPRESSANT INGESTION
Validation of Ingestion
CASE 5-4
QUESTION 1: A.G., a 40-year-old male, was found unconscious in a pool of
vomitus with a suicide note. The note stated that he had ingested 30 of his pills.
A.G.’s 75-year-old mother called paramedics. When the paramedics arrived,
A.G.’s heart rate was 150 beats/minute, BP was 115/70 mm Hg, and
respirations were 14 breaths/minute and shallow. A.G. responded only to painful
stimuli. The paramedics immediately started an IV line after completing their
assessment of his ABCs.
Why should the drug overdose information from this suicidal patient be
validated?
Assessing the accuracy of the ingestion history information in adult
drug exposures is difficult, and many health care professionals
question the validity of information, especially from suicidal
patients.
22–25,27
The ingestion history could be inaccurate because
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the patient’s altered mental status might prevent accurate
recollection of what occurred. He may also try to intentionally
mislead health care providers to avoid appropriate care. Studies
have demonstrated a poor correlation between reported drug
ingestions and urine drug test results.
23–25,27,32,33,107
There are also
numerous false-positive results that can be misleading because of
drug interference.
108,109
Urine drug screens generally detect all recent drug and substance
use, rather than just an overdosed drug. Urine drug screen results,
therefore, are not reliable indicators of acute exposures. Every effort
should be made to validate the history with information from other
sources. In suicidal patients, one should consider all drugs that may
have been available to the patient, as well as the patient’s presenting
symptoms, laboratory tests, and information obtained from family
members, police, paramedics, and other individuals who know the
patient.
22–25,27
Interventions by Protocol
CASE 5-4, QUESTION 2: In addition to managing the ABCs, what pharmacologic
interventions should be authorized for the paramedics to administer to A.G. in
addition to the initiation of an IV solution?
GLUCOSE AND THIAMINE
Emergency medical service personnel often have protocols directing
them to treat patients who are unconscious from an unknown cause.
These protocols generally include administration of glucose,
thiamine, and naloxone.
23,27,60,110
If paramedics cannot measure a
blood glucose concentration immediately, A.G. should be given 50
mL of 50% dextrose to treat possible hypoglycemia. The risks of
hyperglycemia from this dose of glucose are negligible relative to the
significant benefits if the patient is hypoglycemic. Thiamine should
be administered concurrently with glucose because glucose can
precipitate Wernicke–Korsakoff complex in thiamine-deficient
patients
111
(see Chapter 90, Substance Use Disorders). Wernicke
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encephalopathy is a reversible neurologic disturbance consisting of
generalized confusion, ataxia, and ophthalmoplegia. Korsakoff
psychosis is believed to be irreversible and is associated with a more
prolonged deficiency of thiamine.
111,112
The unconscious patient
should also be evaluated for blood loss, sepsis, hypoxia, and
evidence of head trauma.
25
NALOXONE
The pure opioid antagonist, naloxone, is indicated for the treatment
of respiratory depression induced by opioids,
110,113
but many
emergency medical service protocols authorize paramedics to
routinely administer naloxone to all patients with any decreased
mental status.
114
Naloxone reportedly has reversed coma and acute
respiratory depression in intoxicated patients who have no evidence
of opioid use.
60,112
The response of these patients to naloxone might
have been secondary to opioids that were not detected by the urine
toxicology screens (eg, oxycodone, methadone, fentanyl). Reports of
naloxone success in patients without opioid use could also have
been the result of responses to other stimuli rather than a response
to naloxone.
Administering naloxone to a patient with opioid use disorder can
precipitate withdrawal symptoms (eg, agitation, combativeness,
vomiting, diarrhea, lacrimation, rhinorrhea) that can further
complicate the intoxication picture.60 Small doses of naloxone should
be administered initially to determine the patient’s response to this
medication. Violent and aggressive behavior can result when sudden
increased consciousness is induced by naloxone.27 This can
complicate emergency care in an emergency transport vehicle and
put caregivers and patients at risk for trauma.
60
Initial Treatment
CASE 5-4, QUESTION 3: The paramedics arrive at the ED with A.G. 30 minutes
after his mother called. A.G.’s heart rate in the ED is 155 beats/minute, BP is
89/50 mm Hg, and respirations have decreased from 14 to 9 breaths/minute,
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with assisted ventilation. A.G. remains unresponsive. The paramedics were
unable to find any prescriptions or other medications in the house. The mother
thinks her son was taking medication for depression. The medical team will try
to obtain more details from A.G.’s pharmacy. What initial treatment should be
provided for A.G. in the ED?
A.G. should be intubated and mechanically ventilated with 100%
oxygen because of his shallow, slow respirations and the likelihood
that vomitus could have been aspirated into his lungs. A bolus of IV
fluid should be administered to A.G. to determine whether an
increase in intravascular fluid volume will increase his BP and
improve his mental status.
22,40
Antidotes
CASE 5-4, QUESTION 4: A.G. fills his prescriptions at several pharmacies, and it
is taking a while to obtain his medication list. What antidotes can be
administered in the ED for diagnostic purposes? Should flumazenil
(Romazicon®) be administered?
Theoretically, antidotes such as naloxone, flumazenil,
deferoxamine, and digoxin-specific antibody (FAB) fragments could
be administered in a hospitalized setting to identify an unknown
toxin.
22,26,27,113,115,116
However, the cost and time required for
administration, and increased risks from these antidotes, preclude
their use for diagnostic purposes without some plausible suspicion of
a specific drug ingestion.
113,115
Organ System Evaluations
CASE 5-4, QUESTION 5: How can the initial physical assessment, using an
organ systems approach, help in identifying the drugs ingested by A.G.?
The patient’s ABCs and CNS and cardiopulmonary functions
should be assessed, with special attention to clinical manifestations
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that suggest ingestion of a specific class of drugs.
27,40
A.G.’s history
of depression suggests that antidepressants, antipsychotics, lithium,
or benzodiazepines are candidates for ingestion. An organ system
evaluation will help determine whether these (or other) drugs might
have been ingested. Commonly used nonprescription medications
such as aspirin, acetaminophen, decongestants, and antihistamines,
should also be considered because adult drug ingestions usually
involve more than one drug.
CENTRAL NERVOUS SYSTEM FUNCTION
Changes in CNS function are probably the single most common
finding associated with drug intoxication.27 CNS depression or
stimulation, seizures, delirium, hallucinations, coma, or any
combination of these can be seen in intoxicated patients. CNS
changes can be the direct result of an ingested drug or may be
attributed to other underlying CNS processes or medical
conditions.
116
Clinical manifestations of drug overdoses may differ
depending on where the patient is in the time course of the
intoxication, and the amount of drug(s) ingested.
27,64
Drugs with anticholinergic properties can produce disorientation,
confusion, delirium, and visual hallucinations early in the course of
the intoxication; coma can become apparent as toxicity progresses.
Generally, overdoses with anticholinergic drugs do not produce true
hallucinations, but rather pseudohallucinations. When a patient with
an intact baseline mental status presents with psychosis, paranoia,
or visual hallucinations, CNS stimulants such as cocaine or
amphetamines should be considered.
30,65
Drug intoxication–induced alterations in CNS function are initially
difficult to distinguish from those caused by underlying psychiatric
disorders, trauma, hypoxia, or metabolic disorders, such as hepatic
encephalopathy or hypoglycemia. However, as time passes,
decreased CNS function secondary to drug toxicity is more likely to
wax and wane in severity in contrast to the persistent CNS
depression that occurs with significant trauma or metabolic
disorders. Drug toxicity also rarely produces focal neurologic
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