60,112 The response of these patients to naloxone might have been secondary to
opioids that were not detected by the urine toxicology screens (e.g., 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
Administering naloxone to an opioid-addicted patient can precipitate withdrawal
symptoms (e.g., agitation, combativeness, vomiting, diarrhea, lacrimation,
rhinorrhea) that can further complicate the intoxication picture.
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.
CASE 5-4, QUESTION 3: The paramedics arrive at the ED with A.G. 30 minutes after his mother called.
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
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.
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 that suggest ingestion of a specific
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
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.
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
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 findings. Changes in pupil size, reflexes, and vital signs can provide
insights into the pharmacologic class of drug involved in the intoxication.
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
27 which are often difficult to differentiate from seizure
activity caused by TCA overdoses, although the spasms are often asymmetric and
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, while overdoses of cardiac
glycosides or β-blockers can slow the heart rate. Although drugs can increase or
decrease heart rate directly, indirect cardiac effects (e.g., 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
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 a drug-induced metabolic
27 Aspiration of gastric contents after vomiting is common in drug ingestions.
Aspiration pneumonitis is the most common pulmonary abnormality associated with
43 Noncardiogenic acute pulmonary edema has been
associated with salicylate overdoses
(especially with chronic intoxications) and
drugs of abuse (e.g., cocaine and heroin).
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 (e.g., cocaine, amphetamines, ecstasy), salicylates,
hallucinogens (e.g., phencyclidine), or anticholinergic drugs or plants (e.g.,
jimsonweed) can have serious consequences.
27,29,40 Body temperature should be
measured rectally to obtain an accurate representation of core body temperature.
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
(e.g., BUN, serum creatinine) and a serum creatine kinase measurement to determine
whether rhabdomyolysis has occurred secondary to breakdown of muscle
The GI tract should be assessed for decreased motility because drug absorption can
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
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 provide evidence of drug intoxication, especially with IV or
subcutaneous drug injection needle marks.
27 Drugs can be hidden in the rectum or
27 Drug patches (e.g., 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.
Muscle tone should also be assessed.
Increased tone or myoclonic spasms can be
caused by some drug overdoses (e.g., TCAs) and can produce rhabdomyolysis or
27,125 Dry, hot, red skin may also be an indication of anticholinergic
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.
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
22,129 The status of oxygenation, acid–base balance, and blood glucose
concentration must be determined, especially in patients with altered mental status
40 Oxygenation can be assessed initially by pulse oximetry and acid–
base status by ABGs and serum electrolyte concentrations.
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 (e.g., diabetes,
hypertension) that can damage organs of elimination (e.g., kidney, liver) will also
guide the need for laboratory tests. A serum creatinine concentration and liver
function tests (e.g., aspartate aminotransferase [AST], alanine aminotransferase
[ALT]) should be ordered. Other more specific tests reflective of his past medical
history can be ordered subsequent to 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
A baseline electrocardiogram (ECG) should be obtained when exposure to a
cardiotoxic drug is suspected or whenever the cardiovascular or hemodynamic status
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
A chest radiograph is useful when the potential exists for either direct pulmonary
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.
substance? Explain 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 biological fluids.
24,129,130 The identification and quantification of
compounds should be considered as two distinct types of toxicologic testing.
Qualitative screening is used to identify which substance or class of substances is
involved in the toxic exposure. Quantitative testing determines how much of a known
Screening of various biological fluids can identify unknown substances. Urine is
screened much more commonly than 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 other body fluids.
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 (e.g., marijuana).
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 more than 90% of all drug overdoses.
32 Some urine toxicology screens
only detect common drugs of abuse (e.g., amphetamines, barbiturates,
benzodiazepines, cocaine, marijuana, opioids).
130 Some drugs of abuse are not
detected on routine drug screening (e.g., gamma hydroxybutyrate, ketamine,
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
the synthetic opioids such as fentanyl and methadone.
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.
screen results rarely change clinical management of the patient. Monitoring mental,
cardiovascular, and respiratory status and other laboratory parameters provide better
clues than the results of a urine toxicology screen.
Toxicology screening can be appropriate when the history of a suspected toxic
exposure is unavailable, inaccurate, or inconsistent with the clinical findings.
However, it is important to know which drugs are detected on a given toxicology
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.
CASE 5-4, QUESTION 8: Should a quantitative toxicology laboratory test be ordered for A.G. as well?
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 (e.g., 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 (e.g., ethylene glycol,
methanol). The concentration of a drug in serum is sometimes much more predictive
of end-organ damage than clinical findings (e.g., 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.
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.
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.
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 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.
screen, blood acetaminophen, blood alcohol, and ABGs have been ordered. The 12-lead ECG shows a
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 depressive illness (history
from mother) are all consistent with a TCA drug overdose. The antidepressant could
have been ingested alone or with other agents.
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 (e.g., amitriptyline) ingestion.
135,141 Antidepressants with different structures and
actions (e.g., trazodone [Desyrel], fluoxetine [Prozac], sertraline [Zoloft]) generally
do not produce toxicity as severe as that of the TCAs.
Gastrointestinal Decontamination
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. Additionally, 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 decontamination. In consideration of these concerns,
many would not support GI decontamination for A.G.
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.
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.
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 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 AG.
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-laden stool, the activated charcoal can be considered to have successfully
Sodium Bicarbonate and Hyperventilation
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 3,000 mg based on
his suicide note that said he took 30 tablets. If he weighs about 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.
believed that the anticholinergic effect causes the tachycardia and the quinidine-like
effect causes the ECG changes.
In addition, TCAs are sodium-channel blockers.
slows the maximum uptake stroke of phase 0 of the action potential and decreases
automaticity. Blockade decreases conduction velocity in the Purkinje fibers, which
144 Myocardial depression, ventricular tachycardia,
and ventricular fibrillation are the most common causes of death from TCAs.
Therefore, admission to the ICU with continuous cardiac monitoring is essential for
The primary therapy for reversing ventricular arrhythmias and conduction delays is
alkalinization of the serum and sodium loading with IV hypertonic sodium
Indications for sodium bicarbonate include
hypotension, widened QRS interval (more than 100 milliseconds), right bundle
branch block, and wide complex tachycardia.
135,145 Alkalinization increases serum
protein binding of the TCAs and reduces the amount of free active drug (likely a
116,133,136,145 Correction of the serum pH is beneficial because
underlying acidosis worsens TCA-induced cardiotoxicity.
bicarbonate has been found useful even in patients with a normal pH because sodium
bicarbonate purportedly overcomes the sodium-channel blockade and reduces
On the basis of A.G.’s tachycardia and a widened QRS segment on ECG, he
should be treated with IV sodium bicarbonate with the goal of achieving an arterial
136,145 Sodium bicarbonate could have been administered earlier
because the suspicion of an antidepressant overdose was strong initially, his ECG
demonstrated QRS widening and worsening myocardial conduction, and his BP
continued to decline from the time he was first seen by the paramedics. If not
monitored closely, the use of IV sodium bicarbonate could introduce the risk of
sodium overload and subsequent pulmonary edema.
An alternative is to hyperventilate the patient to a pH of 7.5 by adjusting his
ventilator setting, thereby reducing the cardiotoxicity of the TCA.
combination of IV bicarbonate and mechanical ventilation is more likely to produce
severe alkalemia. Careful and frequent monitoring of the serum pH of patients on
CASE 5-4, QUESTION 14: How should the sodium bicarbonate therapy in A.G. be monitored?
Patients intoxicated with TCAs often present with severe acidosis. Large doses of
sodium bicarbonate may be required to normalize the arterial pH. The efficacy of
sodium bicarbonate administration can be evaluated by monitoring acid–base status
using ABGs, especially if the patient is also being ventilated mechanically.
Sodium bicarbonate should be administered IV as a bolus of 1 to 2 mEq/kg for a 1-
to 2-minute period. Continuous ECG monitoring is needed to monitor results of the
bolus on cardiac abnormalities. Repeat bolus doses are administered as needed until
the QRS interval narrows and tachycardia slows. Blood pH should be tested after
several boluses to determine whether a target pH of 7.5 to 7.55 has been obtained.
At a minimum, ABGs should be determined within an hour of starting sodium
bicarbonate therapy to determine pH response.
148 Bicarbonate boluses can be
followed by a constant sodium bicarbonate infusion of 150 mEq/L to maintain an
145 ABGs must be monitored frequently to ensure a response.
Serial ECGs to measure the QRS interval are useful for evaluating the efficacy of
sodium bicarbonate therapy. A widened QRS interval will generally normalize after
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