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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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findings. Changes in pupil size, reflexes, and vital signs can provide
insights into the pharmacologic class of drug involved in the
intoxication.
23,27,28
CNS depression, seizures, disorientation, and other CNS changes
that are commonly associated with psychiatric drugs should be
evaluated carefully in A.G. For example, A.G.’s pupil size would
most likely be dilated if he had ingested a TCA because of the
anticholinergic effects of these drugs. TCA intoxications can also
cause myoclonic spasms,27 which are often difficult to differentiate
from seizure activity caused by TCA overdoses, although the
spasms are often asymmetric and more persistent.
117
CARDIOVASCULAR FUNCTION
Assessment of heart rate, rhythm, conduction, and measurements of
hemodynamic function can also be used to help identify the type of
drug ingested. Overdoses of sympathomimetic drugs usually
increase heart rate, whereas overdoses of cardiac glycosides or βblockers can slow the heart rate. Although drugs can increase or
decrease heart rate directly, indirect cardiac effects (eg, reflex
tachycardia in response to hypotension) also need to be considered.
Abnormal heart rates produced by drug overdoses are usually not
treated unless accompanied by hypotension or severe
dysrhythmias.
27,40
PULMONARY FUNCTION
Evaluating the rate and depth of respiration and the effectiveness of
gas exchange in an intoxicated patient can also help identify drugs
ingested. A decrease in respiratory rate is commonly associated with
the ingestion of CNS depressants. An increased respiratory rate and
depth is generally associated with CNS stimulant toxicity and can
also be secondary to respiratory compensation for drug-induced
metabolic acidosis.27 Aspiration of gastric contents after vomiting is
common in drug ingestions. Aspiration pneumonitis is the most
common pulmonary abnormality associated with significant
intoxications.43 Noncardiogenic acute pulmonary edema has been
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associated with salicylate overdoses80 (especially with chronic
intoxications) and drugs of abuse (eg, cocaine and heroin).
114,118–124
TEMPERATURE REGULATION
Body temperature is an important and sometimes overlooked
parameter when assessing potential intoxications.
27,40
Decreased
mental status is often associated with a loss of thermoregulation,
resulting in a body temperature that falls or increases toward the
ambient temperature. Increased body temperature (hyperthermia)
caused by overdoses of CNS stimulants (eg, cocaine,
amphetamines, ecstasy), salicylates, hallucinogens (eg,
phencyclidine), serotonergic agents, or anticholinergic drugs or
plants (eg, jimsonweed) can have serious consequences.
27,29,40
Body
temperature should be measured rectally to obtain an accurate
representation of core body temperature.
125
Hyperthermia caused by drug overdoses is commonly seen in hot,
humid environments or when the intoxication is associated with
physical exertion, increased muscle tone, or seizures. In these
patients, it is important to obtain renal function tests (eg, BUN, serum
creatinine) and a serum creatine kinase measurement to determine
whether rhabdomyolysis has occurred secondary to breakdown of
muscle tissue.
27,40,125
GASTROINTESTINAL FUNCTION
The GI tract should be assessed for decreased motility because drug
absorption can be delayed or prolonged.
27,126,127
When this is the
case, decontamination may be beneficial after an oral ingestion even
if a long time has elapsed since the ingestion. The presence of blood
in either emesis or stool may suggest ingestion of a GI irritant or
caustic substance.
128
SKIN AND EXTREMITIES
The physical examination should include a thorough examination of
the body surface for causes of trauma that may also explain the
patient’s condition. Examination of the skin and extremities can
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provide evidence of drug intoxication, especially with IV or
subcutaneous drug injection needle marks.27 Drugs can be hidden in
the rectum or vagina.27 Drug patches (eg, fentanyl) may be found in
hidden areas of the body such as the back of the neck or scrotum.
Fluid-filled bullae at gravity-dependent sites that have been in
contact with hard surfaces for a long time suggest prolonged coma.
27
Muscle tone should also be assessed.30 Increased tone or myoclonic
spasms can be caused by some drug overdoses (eg, TCAs) and can
produce rhabdomyolysis or hyperthermia.
27,125
Dry, hot, red skin may
also be an indication of anticholinergic toxicity.
27,40
In summary, an organ system assessment of A.G. can provide
useful insights into the identity of drugs that might have been
ingested, the viability of organ function that might have been
adversely affected, and the treatment needed.
Laboratory Tests
CASE 5-4, QUESTION 6: What laboratory tests should be ordered for A.G.?
The laboratory assessment of an intoxicated patient should be
guided by the history of the events surrounding the ingestion, clinical
presentation, and past medical history.
22,129
The status of
oxygenation, acid–base balance, and blood glucose concentration
must be determined, especially in patients with altered mental status
such as A.G.40 Oxygenation can be assessed initially by pulse
oximetry, and acid–base status by ABGs and serum electrolyte
concentrations.
129,130
A.G. was given oxygen and a bolus of IV fluid
on arrival at the ED, and paramedics administered glucose during
transportation.
A medical history of organ dysfunction or medical disorders (eg,
diabetes, hypertension) that can damage organs of elimination (eg,
kidney, liver) will also guide the need for laboratory tests. A serum
creatinine concentration and liver function tests (eg, aspartate
aminotransferase [AST], alanine aminotransferase [ALT]) should be
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ordered. Other more specific tests reflective of his past medical
history can be ordered subsequent to a dialogue with his
psychiatrist. A complete blood cell count, complete chemistry panel,
serum osmolality, and other baseline laboratory tests should be
obtained.27 Pregnancy tests should be considered in female patients
of childbearing age because unwanted pregnancies are common
causes of overdose.
131,132
A baseline electrocardiogram (ECG) should be obtained when
exposure to a cardiotoxic drug is suspected or whenever the
cardiovascular or hemodynamic status is altered.
23,26,40,130
A 12-lead
ECG should be ordered because A.G. is likely to have ingested a
psychotropic agent. Continuous cardiac monitoring should be
instituted because of the significant cardiotoxicity associated with
overdoses of these agents. Patients with severe TCA overdoses
frequently present with symptoms of coma, tachycardia with a
widened QRS interval, seizures, hypotension, and respiratory
depression.
133–136
A chest radiograph is useful when the potential exists for either
direct pulmonary toxicity or aspiration.
23,26
A chest radiograph is
indicated because A.G. had vomitus in his mouth, and TCAs are
associated with the development of acute respiratory distress
syndrome and pulmonary edema.
133,137,138
Qualitative Screening
CASE 5-4, QUESTION 7: Should A.G.’s urine and blood be screened to assist in
identifying the ingested substance? What is your rationale?
Toxicology laboratory testing can be used to identify the
substances involved in a toxic exposure, to exclude substances, or
to measure the concentration of substances in serum or other
biologic fluids.
24,129,130
The identification and quantification of
compounds should be considered as two distinct types of toxicologic
testing.
24,139
Qualitative screening is used to identify which substance
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or class of substances is involved in the toxic exposure. Quantitative
testing determines how much of a known substance is present.
24
Screening of various biologic fluids can identify unknown
substances. Urine is screened much more commonly than is blood,
whereas gastric fluid is rarely evaluated. A urine drug screen is
preferred to a blood drug screen because urine generally contains a
higher concentration of a drug and its metabolites than do other body
fluids.
140
When reviewing the results of urine screening panels for drugs
and other substances, one must remember that the presence of a
substance in urine is not necessarily related to a concurrent toxicity.
A positive result on a urine screening panel merely indicates that the
patient has ingested or has been exposed to the substance, but it
does not differentiate between toxic and nontoxic doses. If a drug
and its metabolites are eliminated slowly into the urine for a
prolonged time, and if the testing methodology detects small
concentrations of the substance, urine drug screening could identify
the presence of a substance days, weeks, or even months after the
exposure (eg, marijuana).
24,130
It is important to know which drugs or substances are tested at a
given laboratory. Many laboratories restrict the number of drugs for
which they test because 15 drugs account for >90% of all drug
overdoses.32 Some urine toxicology screens only detect common
drugs of abuse (eg, amphetamines, barbiturates, benzodiazepines,
cocaine, marijuana, opioids).
130
Some drugs of abuse are not
detected on routine drug screening (eg, γ-hydroxybutyrate,
ketamine, flunitrazepam).24 Some analyses detect only antibodies to
drug metabolites. For example, a benzodiazepine screen detects
oxazepam, a common benzodiazepine metabolite. However,
alprazolam and lorazepam are not metabolized to oxazepam and will
not be detected in a urine screen. Likewise, an opioid screen may
not detect synthetic opioids such as fentanyl and methadone.
130
Results of qualitative toxicology screening tests are difficult to
interpret. False negatives, false positives, cross-reactivity with
related drugs, chronicity of exposure, and length of time since last
exposure all complicate results.
108,109,130
Urine toxicology screen
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results rarely change clinical management of the patient. Monitoring
mental, cardiovascular, and respiratory status and other laboratory
parameters provide better clues than do the results of a urine
toxicology screen.
23,24,129,130,139
Toxicology screening can be appropriate when the history of a
suspected toxic exposure is unavailable, inaccurate, or inconsistent
with the clinical findings.24 However, it is important to know which
drugs are detected on a given toxicology screen.
130
A
comprehensive qualitative urine drug screen can be considered for
A.G. because information about the substance(s) he ingested is not
yet known.
Quantitative Testing
CASE 5-4, QUESTION 8: Should a quantitative toxicology laboratory test be
ordered for A.G. as well? What is your rationale?
After a qualitative urine analysis for drugs, a quantitative analysis
of drug concentration in blood can help determine the severity of
toxicity and the need for aggressive interventions (eg,
hemodialysis).
24,33,130,139
Quantitative tests are especially useful when
assessing the potential toxicity of drugs with delayed clinical toxicity
or when the toxicity primarily is caused by metabolites (eg, ethylene
glycol, methanol). The concentration of a drug in serum is
sometimes much more predictive of end-organ damage than are
clinical findings (eg, acetaminophen effect on the liver).
Quantifying the amount of drug in serum is useful when (a) the
concentration of the substance correlates with toxic effects, (b) the
turnaround time for results is rapid, and (c) treatment can be guided
by the serum concentration.
32,132,142
To aid in the care of poisoned
patients, stat quantitative serum concentrations of acetaminophen,
carbamazepine, carboxyhemoglobin, digoxin, ethanol, ethylene
glycol, iron, lithium, methanol, methemoglobin, phenobarbital,
salicylates, and theophylline should be available at laboratories of
large health care facilities.
23,24,33,129,139
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When blood samples are collected to quantitate potentially
intoxicating substances, as much information as possible should be
obtained about the time course of events to determine whether
absorption and distribution of the substance is complete. Serial
samples may be needed to determine whether significant absorption
is still occurring.
29,30
In contrast to the interpretation of therapeutic
serum concentrations of chronically administered drugs, the serum
concentration of a substance ingested in an overdose is not likely to
be at a steady state.
Quantitative toxicologic testing will likely not benefit A.G. at this
point in time because the identity of the ingested substance is
unknown. Nevertheless, a serum ethanol concentration could be
obtained because alcohol is often ingested concurrently in overdose
situations.
132
Most poison centers also recommend obtaining a
quantitative acetaminophen level on all intentional ingestions
because serious hepatotoxicity can occur if acetaminophen ingestion
is missed.
24,129,130
Assessment
CASE 5-4, QUESTION 9: A.G.’s clinical status has not changed in the past 10
minutes. A urine toxicology screen, blood acetaminophen, blood alcohol, and
ABGs have been ordered. The 12-lead ECG shows a prolonged QRS interval of
0.13 seconds (normal, <0.1 seconds). No antidotes have been administered.
A.G.’s physical examination did not detect any evidence of trauma to his head.
His pupils were dilated and slowly responsive to light, and his bowel sounds
were hypoactive. What conclusions can be made at this time with regard to the
likely substance ingested by A.G.?
Although the ingested substance still has not been specifically
identified, the available data provide some clues as to the likely
pharmacologic class of drug that was ingested. The presence of
CNS depression (A.G. is unresponsive), slowed ventricular
conduction (widened QRS on ECG), tachycardia (heart rate, 155
beats/minute), hypotension (BP, 89/50 mm Hg), and decreased GI
motility (hypoactive bowel sounds), and the history of a possible
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depressive illness (history from mother) are all consistent with a TCA
drug overdose. The antidepressant could have been ingested alone
or with other agents.
Antidepressant Toxicities
CASE 5-4, QUESTION 10: How would the different toxicities of the many
available antidepressants affect the treatment of A.G.?
The major pharmacologic effects and toxicities of the
antidepressants are similar for all drugs within the same class. When
a specific drug within a therapeutic class has not yet been identified,
the overdose should be managed as if the ingested drug can
produce the most severe toxicity of any drug in the class. Therefore,
A.G.’s presumed antidepressant drug overdose should be evaluated
and managed initially as TCA (eg, amitriptyline) ingestion.
135,141
Antidepressants with different structures and actions (eg, trazodone
[Desyrel®], fluoxetine [Prozac®], sertraline [Zoloft®]) generally do not
produce toxicity as severe as that of the TCAs.
135,141,142
Gastrointestinal Decontamination
CASE 5-4, QUESTION 11: If a TCA ingestion is presumed, why might GI
decontamination be appropriate at this time?
The longer GI decontamination is delayed relative to the time of
ingestion, the less effective it is likely to be because drug absorption
will already have occurred. Because the time of ingestion is unknown
and A.G. is unresponsive, he probably already has absorbed
significant amounts of the drug, making him more vulnerable to
aspiration. In addition, A.G. might already have aspirated because
he was found in a pool of vomitus. TCA overdoses can also cause
seizures, which would be a relative contraindication to GI
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decontamination. In consideration of these concerns, many would
not support GI decontamination for A.G.
41–44,51–54
Others might support GI decontamination because TCAs have
strong central and peripheral anticholinergic properties that slow GI
emptying, which could result in erratic absorption and delayed
toxicity, but A.G. would first need to be intubated to protect his
airway. Furthermore, TCAs have a large volume of distribution (10–
50 L/kg), and both the parent drug and its metabolite undergo
enterohepatic recirculation. The half-life of TCAs in overdose
situations is 37 to 60 hours. For those reasons, activated charcoal
could be reasonably administered in an effort to adsorb any drug that
may not yet be absorbed from the GI tract.
49
Repeated doses of activated charcoal have been used to increase
the elimination of TCAs because of the long half-life of TCAs and the
enterohepatic recirculation. In clinical studies, multiple-dose
activated charcoal has increased the elimination of amitriptyline, but
the data are insufficient to support or exclude its use.
47
MONITORING EFFICACY
CASE 5-4, QUESTION 12: How should the effectiveness of GI decontamination
be monitored in A.G.?
If activated charcoal is administered, A.G. must first be intubated
to protect his airway, and the charcoal must be administered via an
NG tube because he is unconscious. The insertion of the NG tube
could stimulate the gag reflex, causing vomiting and possible
aspiration. A.G.’s lung sounds should be monitored closely to
determine whether aspiration pneumonitis is developing, particularly
because A.G. was found unconscious and had already vomited.
Activated charcoal, especially in multiple doses, can produce ileus,
GI obstruction, or intestinal perforation, particularly when
administered to patients who have ingested drugs that slow GI
motility.
47,49,101
Bowel sounds must be monitored frequently to ensure
that an ileus is not developing. Once the patient passes a charcoal-
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laden stool, the activated charcoal can be considered to have
successfully passed through the GI tract.
Sodium Bicarbonate and Hyperventilation
CASE 5-4, QUESTION 13: According to A.G.’s psychiatrist, he prescribed
amitriptyline 100 mg at bedtime for his severe depression. How does this new
information alter A.G.’s treatment plan?
This information confirms the assumptions that a TCA was
ingested. It also specifically identifies the drug ingested. In TCA
ingestions, severe toxicity has been associated with doses of 15 to
25 mg/kg.98 A.G. ingested a total of 3000 mg based on his suicide
note that said he took 30 tablets. If he weighs about 154.32 pounds
(70 kg) and was truthful about the amount taken, he ingested a
significantly toxic dose (about 43 mg/kg).
On the ECG, TCA toxicity will manifest as tachycardia with
prolongation of the PR, QTc, and QRS intervals, ST- and T-wave
changes, and abnormalities of the terminal 40-millisecond
vector.
98,117,133,136,142–146
TCAs have anticholinergic, adrenergic, and
quinidine-like membrane effects on the heart.
117,133,135,141,144
It is
believed that the anticholinergic effect causes the tachycardia and
the quinidine-like effect causes the ECG changes.
In addition, TCAs are sodium channel blockers.
147
Sodium channel
blockade slows the maximum uptake stroke of phase 0 of the action
potential and decreases automaticity. Blockade decreases
conduction velocity in the Purkinje fibers, which increases the QRS
interval.
144
Myocardial depression, ventricular tachycardia, and
ventricular fibrillation are the most common causes of death from
TCAs.
136
Therefore, admission to the ICU with continuous cardiac
monitoring is essential for A.G.
143
The primary therapy for reversing ventricular arrhythmias and
conduction delays is alkalinization of the serum and sodium loading
with IV hypertonic sodium bicarbonate.
117,133,135,136,144,145,148
Indications
for sodium bicarbonate include hypotension, widened QRS interval
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