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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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in whom such findings are likely to be attributed to other causes (eg,
encephalitis, meningitis, diabetic ketoacidosis, myocardial
infarction).
24,75,79
Delay in diagnosis has been associated with
increased mortality.
24,68,75,79
Unfortunately, plasma salicylate
concentrations do not correlate well with the degree of poisoning in
chronically intoxicated patients. It is more important to treat the
patient according to the clinical status rather than according to his or
her salicylate concentration.71 Death in patients with salicylism,
whether acute or chronic, results from CNS or cardiac dysfunction,
or pulmonary edema.
73,75,79
MANAGEMENT
CASE 5-2, QUESTION 5: What would be a reasonable management plan for
A.S.?
Management of salicylate intoxication depends on the degree of
acid–base and electrolyte disturbances.
68,73,75
Activated charcoal is
not indicated for A.S. because the ingestion occurred ~10 hours ago
and she has a somewhat altered mental status.46 The risk of
aspiration is greater than the value of possibly adsorbing any
remaining aspirin from the GI tract. In addition, A.S. already has
symptoms of salicylate poisoning, indicating that the aspirin has
been absorbed. Others might argue that if she ingested 95 tablets,
some of the drug may still be present in the GI tract and giving
activated charcoal late may bind some of the drug still present. The
benefit versus risk of giving activated charcoal must be assessed.
A.S.’s hypokalemia, acidosis, and hypoglycemia must be corrected,
and it is probably best accomplished through the administration of
intravenous (IV) hypotonic saline–dextrose solutions combined with
potassium supplementation. This solution is administered at a rate
that replaces the patient’s deficits and keeps pace with continued
losses.
68,73,75–77
Care should be taken to avoid overzealous fluid
therapy, which can predispose the patient to cerebral or pulmonary
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edema.
73,77
Administration of an IV dextrose bolus is also indicated
because A.S. is hypoglycemic (60 mg/dL).
73,75–77
Sodium bicarbonate
It is important to correct A.S.’s acidosis because acidosis will
increase CSF salicylate concentrations.
74,75
Correction of acidosis
can be accomplished by adding sodium bicarbonate to her IV
fluids.
68,73–76
A.S.’s serum sodium and potassium concentrations
should be monitored closely because adding potassium to IV fluids
will mostly likely be required.81 Providing adequate ventilation to
prevent respiratory alkalosis is essential. With a respiratory rate of
36 breaths/minute, placing the patient on a ventilator to assist with
breathing might be considered. However, forced mechanical
ventilation can interfere with the patient’s need to compensate to
maintain the serum pH. Patients on ventilators can become severely
acidotic, which can result in death because of an inability to
compensate adequately.
73,82
Seizures
Seizures are not evident in A.S. but can be encountered in cases of
severe salicylate poisoning. Seizures generally carry a poor
prognosis and are indicative of severe salicylate intoxication that
requires hemodialysis.73 Other treatable causes of seizures (eg,
marked alkalosis, hypoglycemia, hyponatremia) can be present in
individuals such as A.S. and should be ruled out. If seizures occur,
benzodiazepines are the drugs of choice for treatment.
73
Coagulopathy and hyperthermia
Coagulopathy generally responds to vitamin K1, which should be
given if the PT or INR is prolonged.73 GI bleeding or other
hemorrhage can occur, but it is not common.
73,75,76
Mild hyperthermia
usually does not require therapy, but cooling fans and mist may be
required for extremely elevated temperatures.
73,77
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Pulmonary edema
Noncardiogenic pulmonary edema commonly occurs in salicylate
intoxications, especially when the overdose is attributable to chronic
ingestions.
73,75,78
Pulmonary edema is associated with a high
incidence of neurologic symptoms in patients and can occur even
without fluid overload.
75,78
Increased alveolar capillary membrane
permeability, prostaglandin effects, and a metabolic interaction with
platelets that release membrane permeability substances are the
primary mechanisms for the cause of pulmonary edema associated
with salicylate overdose. Treatment is aimed at reducing salicylate
levels via alkalinization or hemodialysis.
78
Alkalinization
CASE 5-2, QUESTION 6: What measures will enhance salicylate elimination?
Which of these may be indicated in A.S.?
Alkalinization of the urine and hemodialysis can enhance the
excretion of salicylate in overdose situations.
68,74
Hemodialysis is
preferred because it can also correct fluid and electrolyte
imbalances.
75,78,79
Sodium bicarbonate is recommended for
alkalinization to increase the arterial pH with the goal of minimizing
salicylate transport into the CNS.
74,75,77
Although large doses of sodium bicarbonate can enhance the
renal elimination of the weak acid and shorten its half-life, this
treatment does not favorably influence the morbidity or mortality of
patients with salicylism. Alkalinization with forced fluid diuresis can
also place the patient at risk for sodium and fluid retention, as well as
pulmonary edema if too much fluid is given too quickly.
76,78–83
Whether the urine can be adequately alkalinized (pH > 7) in severely
intoxicated pediatric patients has been questioned because of the
large acid load that is excreted.
68,73,74
Nevertheless, urine
alkalinization with sodium bicarbonate should be attempted in
severely salicylate-intoxicated adult patients such as A.S.
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Potassium replacement in patients receiving alkalinization is
essential.
73,75,77
These patients may require large amounts of
potassium supplementation as a result of renal wasting of
potassium. The risk of pulmonary edema can be minimized if this is
done without forcing fluids.
73,75–77
Hemodialysis should be considered in patients who show
progression of severe salicylate intoxication and seizure activity,
renal failure, or plasma salicylate concentrations in the potentially
fatal range.
68,75,76,78,80
Patients with a chronic exposure, acidosis, or
CNS symptoms and those who are elderly or ill are at high risk and
should be considered for early dialysis.
75,80
Because A.S. has many
of the risk factors, she is a candidate for emergent hemodialysis.
CLINICAL OUTCOME
A repeat salicylate level 6 hours later (18 hours after ingestion) had
increased to 95 mg/dL. Her chemistry panel revealed serum sodium,
143 mEq/L; potassium, 2.2 mEq/L; chloride, 99 mEq/L; bicarbonate,
8 mEq/L; glucose, 77 mg/dL; creatinine, 4.9 mg/dL; and BUN, 43
mg/dL. Her hemoglobin was 8.4 g/dL, with a hematocrit of 23% and
a PT of 16.6 seconds. A.S.’s pH on blood gases remained in the 7.2
to 7.3 range. Urinary alkalinization was attempted with a high-dose
IV sodium bicarbonate infusion in an attempt to reach a urine pH of
7.5. However, her urine pH never increased above pH 5.7. A.S.
became fluid overloaded and exhibited dyspnea. She was placed on
a ventilator with worsening of her symptoms. A chest radiograph
showed pulmonary edema. A.S. became confused and agitated,
pulling at her IV lines and trying to get out of bed. Nephrology was
consulted to provide emergent hemodialysis to correct the acidosis,
electrolyte abnormalities, and fluid overload. As the catheter was
being placed, the patient had a tonic-clonic seizure. Lorazepam 2 mg
IV was administered, and the seizure stopped. At this time, the
patient was unresponsive. She had another tonic-clonic seizure,
went into respiratory arrest, and was coded, but could not be
resuscitated.
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ASSESSMENT OF IRON INGESTION
Gathering History and Communications
CASE 5-3
QUESTION 1: The babysitter of K.M., a 21-month-old female, calls the ED
because the child is vomiting and appears to have been playing with an open,
unlabeled bottle of green tablets. The child was left alone in her room for about
20 minutes to take a nap.
Why might the consultation with this babysitter be expected to be more
difficult than was the consultation in Case 5-1, Question 1?
In cases of unintentional pediatric ingestions, phone calls to a
health care provider, a health care facility, or a poison control center
made by individuals other than the parent are usually more difficult to
manage because the caller is often unable to provide all patientspecific information needed (eg, patient weight, chronic medications)
to accurately assess the drug ingestion. Additional information is
often needed from a parent. Nonparent callers also tend to be more
upset about an unintentional ingestion and may have more difficulty
than a parent in taking decisive action.
Triage of Call
CASE 5-3, QUESTION 2: Despite additional questioning, K.M.’s babysitter
cannot identify the tablets. K.M. is still vomiting; and the vomitus is green,
similar to the color of the tablets. According to the babysitter, K.M. is the child of
a single mother who is not known to have flu or any GI illness at this time. The
child’s mother is currently at work and is not answering her cell phone. What
recommendations could be provided to K.M.’s babysitter at this time?
With this history, the practitioner should consider whether the
information presented by K.M.’s babysitter is consistent with a drug
ingestion and whether this incident is likely to be associated with a
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significant adverse outcome. Most 2-year-old children experience
limited toxicity with unintentional drug ingestions because the
amount of substance actually ingested is usually small.
5,6
Nevertheless, some substances (eg, methanol, ethylene glycol,
nicotine, caustic substances, camphor, chloroquine, clonidine,
diphenoxylate-atropine, theophylline, oral hypoglycemic agents,
calcium channel blockers, TCAs, opioids) can produce significant
toxicity even when small amounts are ingested.
6,84,85
Although the history of drug ingestion in K.M. is somewhat vague,
the description of green tablets and green-colored vomitus suggests
possible ingestion of iron tablets. Because this is a possible
exposure with a realistic potential for severe toxicity, K.M. should be
brought to the ED for evaluation. Depending on the distance to the
hospital and the anxiety level of the babysitter, the practitioner might
want to instruct the babysitter to call for an ambulance. She should
be instructed to bring the green tablets to the ED along with the child
so that the tablets can be identified. Other medications in the house
should also be brought to the ED, and the mother should be
contacted.
Substance Identification
CASE 5-3, QUESTION 3: K.M.’s mother was reached and confirmed that the
only green tablets in the house are her iron supplements. The babysitter was
instructed to bring K.M. to the nearest ED, and the mother will meet them there.
On arrival, K.M. is still vomiting but is fully awake and alert, with a heart rate of
122 beats/minute, a respiratory rate of 26 breaths/minute, a rectal temperature
of 98.9 °F (37.17 °C), and pulse oximetry of 100%. How can the maximal
potential severity of this ingestion be estimated at this time?
K.M.’s vital signs, when corrected for age, are normal. Attention
should now focus on identifying the ingested substance and the
maximal potential severity of the ingestion. Although this case
involves an unknown ingestion, with a possibility of being a severe
case of iron intoxication, the identity of the tablets still has not been
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verified. Therefore, K.M. must be carefully assessed, and the
ingestion history reaffirmed.
All solid dosage prescription drugs are required by the U.S. Food
and Drug Administration (FDA) to have identification markings.
Online Resources (eg, Facts and Comparisons,86 Prescriber’s Digital
Reference87), computerized databases (eg, Micromedex),88 and the
product manufacturers can assist in identifying solid dosage forms.
Websites such as http://www.rxlist.com89 and http://www.drugs.com
90
can also be useful in obtaining drug identification information.
The imprint code markings on the green tablet brought to the ED
with K.M. and the mother’s assistance should be sufficient to
correctly identify the medication. Once the tablet has been identified,
the maximal number of tablets ingested should be estimated.
In K.M.’s case, the bottle containing the green tablets was
unlabeled. In most cases, the label on the medication container can
provide information on the identity and number of tablets dispensed.
The date the prescription was obtained, the number of estimated
doses taken, and the number currently remaining in the medication
container can be used to approximate the maximal number of tablets
ingested.
K.M.’s vital signs and symptoms should be monitored closely to
evaluate whether her clinical status is consistent with expectations
based on the suspected ingestion. Nausea, vomiting, diarrhea, and
abdominal pain are common early signs of iron intoxication.
91–96
The
absence of symptoms, especially within a short time of the presumed
ingestion, should not be interpreted as an indication that a poisoning
has not occurred.
91,93–96
Evaluating Severity of Toxicity
CASE 5-3, QUESTION 4: K.M. weighs 24.25 pounds (11 kg), appears to be in no
distress, and has stopped vomiting. About 25 mL of dark-colored vomitus was
recovered, but no tablets are found. The vomitus tested negative for blood. A
maximum of seven tablets was ingested based on the mother’s recall. What
degree of toxicity should be expected in K.M.?
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The potential severity of toxicity can be estimated for commonly
ingested drugs such as acetaminophen,97 salicylates,71 iron,91 and
TCAs98 because of well-established dose–toxicity relationships.
Acute elemental iron ingestions of <20 mg/kg are usually nontoxic,
doses of 20 to 60 mg/kg result in mild-to-moderate toxicity, and
doses >60 mg/kg are potentially fatal.
92,94,96
The independent verification of the tablet by K.M.’s mother and the
tablet imprint indicate that each tablet contained 325 mg of ferrous
fumarate in an enteric-coated formulation. Because the dose–toxicity
relationship of iron is based on the amount of elemental iron
ingested, knowledge of the specific iron salt is important in
calculating the ingested dose. Ferrous fumarate contains 33%
elemental iron, whereas ferrous gluconate contains 12%, and ferrous
sulfate contains 20%.
91,92,94,95
Therefore, each 325-mg ferrous sulfate
tablet contains 108 mg of elemental iron. K.M. ingested a maximum
of seven enteric-coated ferrous fumarate 325-mg tablets, and she
weighs 24.25 pounds (11 kg). Her ingestion of ~69 mg/kg (108 mg
per tablet × 7 tablets = 756 mg total ÷ 24.25-pound [11-kg] patient
weight) of iron places her at risk for severe toxicity. Although K.M.’s
only symptom is vomiting at this time, absorption could be delayed
because she ingested an enteric-coated formulation.
Abdominal Radiographs
CASE 5-3, QUESTION 5: K.M. is expected to experience potentially severe
toxicity from her iron ingestion. Why would an abdominal radiograph be useful
to verify the number of iron tablets ingested?
In theory, radiopaque substances (eg, iron, enteric-coated tablets,
chloral hydrate, phenothiazines, heavy metals) can be visualized in
the GI tract by an abdominal radiograph.99 The ability of a radiograph
to detect the presence of a radiodense substance depends on the
dosage form, concentration, and molecular weight of the substance.
The intact dosage form can often be detected if the tablet has not
already disintegrated or dissolved.
99
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Less than one-third of pediatric abdominal radiographs show
positive evidence of tablets or granules after iron poisoning.
100
Children are more likely than are adults to chew tablets rather than
swallow them whole, and false-negative results can occur when
whole tablets have not started to disintegrate. If the tablets were
chewed, an abdominal radiograph is not likely to be useful for
verifying the number of iron tablets ingested. However, an abdominal
radiograph after the completion of GI decontamination can help
assess whether additional decontamination is needed.
99
Gastrointestinal Decontamination
CASE 5-3, QUESTION 6: Would gastric lavage or activated charcoal not be
indicated for the management of K.M.’s iron ingestion? Why or why not?
When selecting a method of GI decontamination, consider the
substance ingested, maximal potential toxicity expected from the
drug dosage form, potential time course of toxicity, time elapsed
between ingestion and the initiation of treatment, symptoms, and
physical examination findings. Decontamination with activated
charcoal is not indicated in K.M. because iron tablets are not
adsorbed by activated charcoal.
49,91,99
Gastric lavage would also be
ineffective because the removal of large undissolved iron tablets
from the stomach is limited by the small internal diameter of the
gastric lavage tube, especially in pediatric patients.
99,100
Whole-Bowel Irrigation
CASE 5-3, QUESTION 7: What other method of GI decontamination should be
considered for K.M.?
WBI with a polyethylene glycol electrolyte solution can be
considered in this case. WBI fluid can be administered orally or by
an NG tube at a rate of 1.5 to 2 L/hour for adults and at a rate of 500
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mL/hour for children.
59,101
Although the ingestion of a large volume of
fluid over several hours and the likelihood of nausea and vomiting
often result in poor patient compliance, K.M. is hospitalized and the
fluid can be infused by an NG tube. WBI should be continued until
the rectal effluent is clear, which can take many hours.
59,101,102
MONITORING EFFECTIVENESS OF TREATMENT
CASE 5-3, QUESTION 8: How should the effectiveness of GI decontamination
be assessed in the ED?
To assess the effectiveness of GI decontamination, the return fluid
from the WBI is visually inspected for tablets or tablet fragments.
Increasing serum iron concentrations, deteriorating clinical status, or
evidence of radiodense tablets in the GI tract on abdominal
radiograph are all indications for more aggressive treatment.
92,94,102
Serum Iron Concentrations
CASE 5-3, QUESTION 9: At this time, K.M. does not appear to be experiencing
any CNS or cardiovascular symptoms associated with toxic iron ingestions. She
did have one episode of diarrhea that tested negative for blood. A serum iron
concentration, obtained about 4 hours after the ingestion, was 480 μg/dL
(normal, 60–160 μg/dL). What conclusions as to severity or likely clinical
outcome can be derived from this serum iron concentration?
The serum iron concentration provides an indication as to whether
more aggressive therapy is needed.
96,100,103
The higher than normal
serum iron concentration confirms the suspicion that K.M. has
ingested iron tablets despite both her current lack of serious
symptoms and the absence of tablet evidence in the rectal effluent or
by abdominal radiograph.
The time course of absorption is probably the most difficult
pharmacokinetic parameter to evaluate with toxic ingestions. Drug
concentrations can continue to rise after an overdose despite GI
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