20 mg/kg are usually nontoxic, doses of 20 to 60 mg/kg result in mild-to-moderate
toxicity, and doses greater than 60 mg/kg are potentially fatal.
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%.
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 24.2 pounds (11 kg). Her ingestion of approximately 69 mg/kg (108
mg per tablet × 7 tablets = 756 mg total divided by 11-kg patient weight) of iron
places her at risk of severe toxicity. Although K.M.’s only symptom is vomiting at
this time, absorption could be delayed because she ingested an enteric-coated
Why would an abdominal radiograph be useful to verify the number of iron tablets ingested?
In theory, radio-opaque substances (e.g., 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.
Less than one-third of pediatric abdominal radiographs show positive evidence of
tablets or granules after iron poisoning.
100 Children are more likely than 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.
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.
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.
CASE 5-3, QUESTION 7: What other method of GI decontamination should be considered for K.M.?
Whole bowel irrigation with a polyethylene glycol electrolyte solution can be
considered in this case. WBI fluid can be administered orally or by NG tube at a rate
of 1.5 to 2 L/hour for adults and at a rate of 500 mL/hour for children.
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 NG tube. WBI should be continued until the rectal effluent
is clear, which can take many hours.
MONITORING EFFECTIVENESS OF TREATMENT
CASE 5-3, QUESTION 8: How should the effectiveness of GI decontamination be assessed in the ED?
In order 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
The serum iron concentration provides an indication as to whether more
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
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 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
K.M.’s serum iron concentration of 480 mcg/dL suggests a serious ingestion
because peak serum iron concentrations greater than 500 mcg/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 his iron ingestion.
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.
serum iron concentration was measured approximately 3 hours after ingestion,
Blood Glucose, White Blood Cell Count, and Total Iron
CASE 5-3, QUESTION 10: K.M. was administered WBI through the NG tube for several hours until the
could be helpful in assessing the potential toxicity of iron in K.M.?
Blood glucose concentrations and white blood cell counts usually are increased
when serum iron concentrations are greater than 300 mcg/dL. A white blood cell
count greater than 15,000/μL and a blood glucose concentration greater than 150
mg/dL within 6 hours of ingestion generally suggest a higher likelihood of severe
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
because of the poor sensitivity (about 50%).
94 Treatment should not be based on a
white blood cell and glucose concentration alone.
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
CASE 5-3, QUESTION 11: It is now 6 hours since K.M. ingested the iron tablets. Her second serum iron
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.
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 blood in the vomitus and stool. In more severe intoxications, CNS
and cardiovascular toxicity can be present during stage I.
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.
In most severe cases, stage II does not
occur and the patient’s condition continues to deteriorate.
Stage III generally occurs 12 to 48 hours after iron ingestion and is characterized by
CNS toxicity (e.g., lethargy, coma, seizures) and cardiovascular toxicity (e.g.,
hypotension, shock, pulmonary edema). Metabolic acidosis, hypoglycemia, hepatic
necrosis, renal damage, and coagulopathy can also happen during this stage.
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.
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.
CASE 5-3, QUESTION 12: The second serum iron concentration that was obtained 6 hours after ingestion
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
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 (approximately
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 a pinkish-orange urine, often described as “vin
92,94,95 Deferoxamine therapy should be initiated when serum iron
concentrations exceed 500 mcg/dL and when symptoms of iron toxicity (e.g., GI
symptoms, hemorrhage, coma, shock, seizures) are present.
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.
CASE 5-3, QUESTION 13: What dose of deferoxamine should be prescribed for K.M., and how should it be
Deferoxamine is most effective when administered intravenously as a continuous
infusion because of its short half-life (76 ± 10 minutes).
infusion is preferred over intramuscular administration because the IV dose is better
controlled, less painful, and better absorbed than an IM dose.
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
93–96,104 Administering IV boluses of deferoxamine too rapidly can result in
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 more than 6 g every 24 hours.
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
MONITORING AND DISCONTINUATION
CASE 5-3, QUESTION 14: K.M. is admitted to the pediatric ICU shortly after the initiation of a
The rate of deferoxamine infusion should be increased with symptoms of severe
iron toxicity, and decreased if patients experience adverse effects.
should continue until the serum iron concentration is less than 100 mcg/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.
prolonged chelation therapy should be avoided because deferoxamine infusion for
more than 24 hours has been associated with the development of acute respiratory
The urine color change to vin rose indicates ferrioxamine in the urine.
of a color change is not a reliable indication of adequate deferoxamine therapy
because not all patients experience vin rose urine.
92,96 There is also no correlation
between amount of iron ingested, serum iron concentration, and the urine color
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 treatment has been started.
deferoxamine therapy, the clinical laboratory should be contacted to clarify
whether deferoxamine will interfere with their serum iron analysis.
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
mcg/dL the next morning, and she was discharged home that afternoon.
ASSESSMENT OF CENTRAL NERVOUS SYSTEM
DEPRESSANT VERSUS ANTIDEPRESSANT
suicidal patient be validated?
Assessing the accuracy of historical 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 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 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
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.
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?
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.
cannot measure a blood glucose concentration immediately, A.G. should be given 50
mLof 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
(see Chapter 90, Substance Abuse Disorders). Wernicke 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.
patient should also be evaluated for blood loss, sepsis, hypoxia, and evidence of
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
114 Naloxone reportedly has reversed coma and acute
respiratory depression in intoxicated patients who have no evidence of opioid
Comments
Post a Comment
اكتب تعليق حول الموضوع