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32
Acute Poisoning
Emergencies
Christopher P. Holstege
David Lawrence
INTRODUCTION
Toxicologic emergencies are commonly encountered
by emergency personnel. Patients can be exposed
to potential toxins either by accident (e.g., workplace incidents or drug interactions) or by intention
(e.g., drug abuse or suicide attempt). In 2006, over
2.4 million human exposures to toxins were reported
to the American Association of Poison Control Centers.1 More than 75% of exposures were reported
from the home, with routes of exposure by ingestion,
through the skin, inhalation, and through the eye in
77%, 8%, 6%, and 5% of the cases, respectively. Two
thirds of the reported exposures involved pediatric patients under the age of 20 years.
The outcome following a poisoning depends on
numerous factors, such as the dose taken, the time to
presentation before care by healthcare providers, and
the preexisting health status of the patient. If a poisoning is recognized early and appropriate supportive
care is initiated quickly, the majority of patient outcomes will be good. In the modern healthcare setting,
the case fatality rate for self-poisonings is approximately 0.5%. However, this can be as high as 10%
to 20% in the developing world.2 It is imperative that
EMS personnel understand the basic management of
the poisoned patient.
EVALUATION
When evaluating a patient who has presented with a
potential toxicologic emergency it is important not to
limit the differential diagnosis.3 A comatose patient
who smells of alcohol may be harboring an intracranial
hemorrhage; an agitated patient who appears anticholinergic may actually be encephalopathic from an infectious etiology. Patients must be thoroughly assessed
and appropriately stabilized. There is often no specific
antidote or treatment for a poisoned patient, and careful supportive care is typically the most important
intervention.
History
EMS personnel should attempt to gather as much
information as possible about the type of toxin(s) to
which the patient was exposed. Obtaining bottles of
substance can be a tremendous aid to hospital personnel and poison centers. Other information to attempt
to obtain includes the time of exposure (acute versus
chronic), amount taken, route of exposure (i.e., ingestion, IV, inhalation, or dermal), reason for the exposure
(i.e., accidental, suicide attempt, or abuse), and what
other medicines are taken routinely by the patient (including prescription, over-the-counter, vitamins, and
alternative medical preparations). Poisoned patients
commonly are unreliable historians, particularly if
suicidal or presenting with altered mental status.4 If
information cannot be obtained from the patient, it is
often beneficial to attempt to obtain the information
from others at the scene, such as family and friends.
Physical Examination
In the emergency setting, performing an overly detailed
physical examination is a low priority compared with
patient stabilization. However, even a rapid directed examination can yield important diagnostic clues. Once
the patient is stable, a more comprehensive physical
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examination can reveal additional signs suggesting
a specific poison. Additionally, a dynamic change in
clinical appearance over time may be a more important
clue than findings on a single examination. There are
classic presentations (toxidromes) that occur with specific drug classes, and EMS personnel need to be able
to recognize the more common of these.
In many cases, the clinician may be able to deduce
the class of drug or toxin taken simply by addressing the patient’s vital signs. Mnemonics and phrases
may help EMS personnel recall pertinent associations
and narrow the differential diagnosis when the patient
has signs such as tachycardia, bradycardia, or hypotension.5 Some poisons produce odors characteristic
enough to suggest the diagnosis upon first encounter
(Table 32.1).
A systematic neurologic evaluation is important, particularly with patients exhibiting altered
mental status. The Glasgow Coma Scale (GCS), although useful in head trauma victims, has little role
in predicting the prognosis of the poisoned patient.6
Seizures are a common presentation of an unknown
overdose, and the list of toxins that can induce a
convulsion is lengthy (Table 32.2). Eye findings that
can help to narrow the differential diagnosis include
miosis and mydriasis (Table 32.3). Other general
neurologic signs to evaluate include fasciculations
(from organophosphate poisoning), rigidity (tetanus
and strychnine), tremors (lithium and theophylline),
and dystonic posturing (neuroleptic agents).
A careful examination of the skin should be performed. The patient’s clothing should be removed
and the skin assessed for color, temperature, and the
presence of dryness or diaphoresis. The absence of
TABLE 32.2
Examples of Diverse Classes of Agents That
Can Potentially Cause Seizures
Category
Examples of Specific Agents
Analgesics
Meperidine, propoxyphene,
tramadol
Diphenhydramine
Isoniazid, penicillin
False morel mushrooms,
tobacco, water hemlock
Amphetamines, cocaine,
phencyclidine
Carbon monoxide, chlorinated
hydrocarbons
Caffeine, theophylline
Vupropion, cyclic antidepressants, venlafaxine
Lindane, organophosphates
Antiepileptic medications,
ethanol, sedative hypnotics
Antihistamines
Antimicrobials
Botanicals
Drugs of abuse
Inhalants
Methylxanthines
Psychiatric
medications
Pesticides
Withdrawal
diaphoresis is an important clinical distinction between anticholinergic and sympathomimetic poisoning. The presence of bites or similar marks may suggest spider or snake envenomations. The presence
of erythema or bullae over pressure points may suggest rhabdomyolysis in the comatose patient. Track
marks suggest IV or subcutaneous drug abuse.
TABLE 32.3
Examples of Potential Toxins Associated with
Miosis or Mydriasis
TABLE 32.1
Odors That Suggest a Toxicologic Diagnosis
Odor
Possible Source
Bitter almonds
Fruity
Garlic
Gasoline
Mothballs
Pears
Minty
Rotten eggs
Freshly mowed hay
Cyanide
Isopropanol, acetone
Organophosphates
Petroleum distillates
Naphthalene, camphor
Chloral hydrate
Methylsalicylate
Hydrogen sulfide
Phosgene
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Miosis
Antipsychotic agents
Carbamates
Clonidine
Opiates
Organophosphates
Sedative-hypnotics
Mydriasis
Anticholinergics
Sympathomimetics
Selective serotonin reuptake inhibitors
Withdrawal
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Toxidromes
alert with stimulation and then drift rapidly back to
sedation with no stimulation.
A toxidrome is a toxic syndrome or constellation of
signs and symptoms associated with a certain class of
poisons. Rapid recognition of a toxidrome, if present,
can help determine whether a poison is involved in a
patient’s condition and can help determine the class
of toxin involved. Table 32.4 lists selected toxidromes
and their characteristics. It is important to note that
patients may not present with every component of
a toxidrome and that toxidromes can be clouded in
mixed ingestions.
Certain aspects of a toxidrome can have great
significance. For example, noting dry axilla may be
the only way to differentiate an anticholinergic patient from a sympathomimetic patient, and miosis
may distinguish opioid toxicity from a benzodiazepine overdose. There are several notable exceptions
to the recognized toxidromes. For example, several
opioid agents (meperidine, propoxyphene, and tramadol) are not always associated with miosis. In most
cases, a toxidrome will not indicate a specific poison
but rather a class of poisons. Several poisons have
unique presentations that make their presence virtually diagnostic. For example, clonidine is associated
with sedation, miosis, bradycardia, shallow respirations, and hypotension, yet the patient will become
Cardiac Monitor
and Electrocardiogram
The interpretation of findings on a cardiac monitor or
an ECG in the poisoned patient can challenge even
the most experienced clinician. There are numerous
drugs that can cause ECG changes. The incidence of
ECG changes in the poisoned patient is unclear, and
the significance of various changes may be difficult to
define.7 Despite the fact that drugs have widely varying
indications for therapeutic use, many unrelated drugs
share common electrocardiographic effects if taken
in overdose. Potential toxins can be placed into broad
classes based on their cardiac effects. Two such classes,
agents that block the cardiac fast sodium channels and
agents that block cardiac potassium efflux channels,
can lead to characteristic changes in cardiac indices
consisting of QRS prolongation and QT prolongation
respectively. The recognition of specific ECG changes
associated with other clinical data (toxidromes) can be
potentially life saving.8
The ability of drugs to induce cardiac sodium
channel blockade and thereby prolong the QRS
TABLE 32.4
Toxidromes
Toxidrome
Signs and Symptoms
Potential Agent Examples
Opioid
Sedation, miosis, decreased bowel sounds,
decreased respirations
Anticholinergic
Mydriasis, dry skin, dry mucous membranes,
decreased bowel sounds, sedation,
altered mental status, hallucinations,
and urinary retention
Sedation, decreased respirations, normal
pupils, normal vital signs
Agitation, mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis
Miosis, lacrimation, diaphoresis, bronchospasm, bronchorrhea, vomiting, diarrhea,
bradycardia
Altered mental status, tachycardia,
hypertension, hyperreflexia, clonus,
hyperthermia
Codeine, fentanyl, heroin, hydrocodone, methadone, morphine,
oxycodone
Atropine, antihistamines, cyclic antidepressants, cyclobenzaprine, phenothiazines, scopolamine,
Sedative hypnotic
Sympathomimetic
Cholinergic
Serotonin syndrome
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Benzodiazepines, barbiturates,
zolpidem
Amphetamines, cocaine, ephedrine,
phencyclidine, pseudoephedrine
Organophosphates, carbamates, nerve
agents
Overdose of serotonergic agents alone
or in combination (i.e., selective
serotonin reuptake inhibitors,
dextromethorphan, meperidine)
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complex has been well described in numerous literature reports.9 This sodium channel blockade activity has been described as a membrane stabilizing
effect, a local anesthetic effect, or a quinidine-like
effect. Cardiac voltage-gated sodium channels reside in the cell membrane and open in conjunction
with cell depolarization. Sodium channel blockers
bind to the transmembrane sodium channels and
decrease the number available for depolarization.
This creates a delay of sodium entry into the cardiac myocyte during phase 0 of depolarization. As
a result, the upslope of depolarization is slowed and
the QRS complex widens.10 In some cases, the QRS
complex may take the pattern of recognized bundle
branch blocks.11,12 In the most severe cases, the QRS
prolongation becomes so profound that it is difficult
to distinguish between ventricular and supraventricular rhythms.13,14 Continued prolongation of the
QRS may result in a sine wave pattern and eventual
asystole. It has been theorized that the sodium channel blockers can cause slowed intraventricular conduction, unidirectional block, the development of a
re-entrant circuit, and a resulting ventricular tachycardia.15 This can then degenerate into ventricular
fibrillation (VF). Differentiating a prolongation of
the QRS complex due to sodium channel blockade
in the poisoned patient versus other non-toxic etiologies can be difficult. Rightward axis deviation of the
terminal 40 msec of the QRS axis has been associated with tricyclic antidepressant poisoning.16,17 The
occurrence of this finding in other sodium channel
blocking agents is, however, unknown.
Myocardial sodium channel blocking drugs comprise a diverse group of pharmaceutical agents (Table
32.5). Patients poisoned with these agents will have
a variety of clinical presentations. For example, sodium channel blocking medications such as diphenhydramine, propoxyphene, and cocaine may also develop anticholinergic, opioid, and sympathomimetic
syndromes, respectively.18–20 In addition, specific
drugs may effect not only the myocardial sodium
channels but also calcium influx and potassium efflux
channels.21,22 This may result in ECG changes and
rhythm disturbances not related entirely to the drug’s
sodium channel blocking activity. All the agents
listed in Table 32.5, however, are similar in that they
may induce myocardial sodium channel blockade
and may respond to therapy with hypertonic saline or
sodium bicarbonate.14,19,20 It is therefore reasonable
to treat poisoned patients with a prolonged QRS
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interval, particularly those ith hemodynamic instability, empirically with 1 to 2 mEq/kg of sodium
bicarbonate, although no studies of such treatment
delivered in the field exist. A shortening of the QRS
can confirm the presence of a sodium channel blocking agent. Also, it can improve inotropy and help
prevent arrhythmias.9
Studies suggest that approximately 3% of all
noncardiac prescriptions are associated with the potential for QT prolongation.23 Myocardial repolarization is driven predominantly by outward movement of
potassium ions.24 Blockade of the outward potassium currents by drugs prolongs the action potential.25 This subsequently results in QT interval
prolongation and the potential emergence of T or
U wave abnormalities on the ECG.26 The prolongation of repolarization causes the myocardial
cell to have less charge difference across its membrane, which may result in the activation of the
inward depolarization current (early after-depolarization) and promote triggered activity. These
changes may lead to reentry and subsequent polymorphic ventricular tachycardia (VT), most often
as the torsades de pointes variant of polymorphic
VT.27 The QT interval is simply measured from the
beginning of the QRS complex to the end of the
T wave. Within any ECG tracing, there is leadto-lead variation of the QT interval. In general,
the longest measurable QT interval on an ECG or
TABLE 32.5
Sodium Channel Blocking Drugs
Amantadine
Carbamazepine
Chloroquine
Class IA antiarrhythmics
Disopyramide
Quinidine
Procainamide
Class IC antiarrhythmics
Encainide
Flecainide
Propafenone
Citalopram
Cocaine
Cyclic antidepressants
Diltiazem
Diphenhydramine
Hydroxychloroquine
Loxapine
Loxapine
Orphenadrine
Phenothiazines
Medoridazine
Thioridazine
Propranolol
Propoxyphene
Quinine
Verapamil
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monitor strip is regarded as determining the overall
QT interval for a given tracing.28 The QT interval is
influenced by the patient’s heart rate. Several formulas have been developed to correct the QT interval for the effect of heart rate (QTc) using the RR
interval, with Bazett’s formula (QTc ⫽ QT/RR1/2)
being the most commonly used. QT prolongation
is considered to occur when the QTc interval is
greater than 440 ms in men and 460 ms in women,
with arrhythmias most commonly associated with
values greater than 500 ms. However, the potential
for an arrhythmia for a given QT interval will vary
from drug to drug and patient to patient.24 Drugs
associated with QT prolongation are listed in Table
32.6.29 Management of QT prolongation includes
infusion of magnesium to prevent the development
of polymorphic VT.
There are multiple agents that can result in human cardiotoxicity and resultant ECG changes from
the indices changes noted to bradycardia (e.g., calcium channel blocker and beta-blocker toxicity) or
tachycardia (e.g., sympathomimetics and anticholinergics). EMS personnel managing patients who
have taken overdoses on medications should be aware
of the various electrocardiographic changes that can
potentially occur in the overdose setting.
TABLE 32.6
Potassium Efflux Channel Blocking Drugs
Antihistamines
Astemizole
Clarithromycin
Diphenhydramine
Loratadine
Terfenadine
Antipsychotics
Chlorpromazine
Droperidol
Haloperidol
Mesoridazine
Pimozide
Quetiapine
Risperidone
Thioridazine
Ziprasidone
Arsenic trioxide
Bepridil
Chloroquine
Cisapride
Citalopram
Clarithromycin
Class IA antiarrhythmics
Disopyramide
Quinidine
Procainamide
TREATMENT
All patients presenting with toxicity or potential
toxicity should be aggressively managed as the majority of outcomes are good. The patient’s airway
should be patent and adequate ventilation ensured.
If necessary, endotracheal intubation (ETI) should
be performed. Too often EMS personnel are lulled
into a false sense of security when a patient’s oxygen saturation is adequate on high-flow oxygen. If
the patient has either inadequate ventilation or a
poor gag reflex, he or she may be at risk for subsequent carbon dioxide narcosis with worsening acidosis or aspiration. The initial treatment of hypotension for all poisonings consists of IV fluids. Close
monitoring of the patient’s pulmonary status should
be performed to ensure that pulmonary edema does
not develop as fluids are infused. The EMS providers should place the patient on continuous cardiac
monitoring with pulse oximetry and make frequent
neurologic checks, documenting any changes in
these variables over time. In all patients with altered
mental status, the patient’s glucose level should be
checked. Also, EMS personnel must have a low
threshold for suspecting carbon monoxide exposure in the patient with altered mental status. Carbon monoxide is a relatively common, potentially
deadly, and due to its varied clinical presentation,
easily missed poisoning. Testing for this should be
done as early as feasible because carbon monoxide
levels can diminish greatly during transport, especially if supplemental oxygen is being administered.
IV access is generally recommended for poisoned
patients.
Many toxins can cause seizures. In general,
toxin-induced seizures are treated in a similar fashion to other seizures. EMS personnel should ensure
the patient maintains a patent airway, and the blood
glucose should be measured. Most toxin-induced
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Class III antiarrhythmics
Amiodarone
Dofetilide
Ibutilide
Sotalol
Cyclic antidepressants
Amitriptyline
Amoxapine
Desipramine
Doxepin
Imipramine
Nortriptyline
Maprotiline
Erythromycine
Fluoroquinolones
Ciprofloxacin
Gatifloxacin
Levofloxacin
Moxifloxacin
Sparfloxacin
Halofantrine
Hydroxychloroquine
Levomethadyl
Methadone
Pentamidine
Quinine
Tacrolimus
Venlafaxine
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seizures will be self-limiting. However, for seizures
requiring treatment, the first-line agent should be
parenteral benzodiazepines for all poisonings. If a
poisoned patient requires intubation, it is important to avoid the use of long-acting paralytic agents
because these agents may mask seizures if they
develop.
After initial evaluation and stabilization of the
poisoned patient, it is time to initiate specific therapies if appropriate. Decontamination should be considered. Also several poisons have specific antidotes
which, if used in a timely and appropriate manner, can
be of great benefit.
Decontaminating the Poisoned
Patient
Nearly 80% of all poisonings occur by ingestion,
which has prompted studies examining the use of
gastrointestinal decontamination performed in the
prehospital setting. Poisonings may also occur by
dermal and ocular routes, which necessitate external
decontamination.
Dermal Decontamination
Although most chemical exposures do not pose a risk
of secondary exposure, patients who present with
dermal contamination pose a potential risk to healthcare personnel. Contaminated patients should not be
transported by EMS before decontamination. Personnel
involved in the dermal decontamination may need to
don personal protective equipment (PPE), depending on the contaminating agent. In general, patients
exposed to gas or vapor do not require decontamination; removal from the site should be sufficient.
However, contaminated clothing should be removed
at the site and sealed in plastic bags to avoid potential off-gassing.30 Patients exposed to toxic liquids or
solids will require dermal decontamination.30 Starting
from head to toe, irrigate the exposed skin and hair
for 10 to 15 minutes and scrub with a soft surgical
sponge, with careful attention not to abrade the skin.
Patient privacy should be respected if possible, and
warm water should be used to avoid hypothermia.30
Irrigate wounds for an additional 5 to 10 minutes with
water or saline. Stiff brushes and abrasives should be
avoided because they may enhance dermal absorption
of the toxin and can produce skin lesions that may
be mistaken for chemical injuries. Sponges and
disposable towels are effective alternatives.
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Ocular Decontamination
Ocular irrigation should be performed immediately
by instillation of a gentle stream of irrigation fluid
into the affected eye(s).31 The skin contiguous to
the eye should also be irrigated. The patient should
undergo ocular irrigation with sterile normal saline
or lactated Ringer’s solution for a period of at least
15 to 30 minutes.32 Tap water is acceptable if that
is the only solution available. However, due to its
hypotonicity relative to the stroma, it may facilitate
penetration of corrosive substances into the cornea and potentially worsen outcome.31,33 Lactated
Ringer’s solution may be a preferable irrigant due
its buffering capacity and neutral pH.31,33 Irrigation of the eyes should be directed away from the
medial canthus to avoid forcing contaminants into
the lacrimal duct. Longer irrigation times may be
needed with specific substances and the endpoint
of irrigation should be normalization of the eye’s
pH. Because this requires measurement with pH
paper, which is not typically carried by EMS units
(although they may be available on hazardous materials units), continuing irrigation during transport to
the emergency department is frequently required.
Gastrointestinal Decontamination
Significant controversy exists concerning the need
for routine gastric emptying in the poisoned patient. Gastric decontamination may be considered
in select cases and specific scenarios, but in general,
the prehospital care provider should focus on rapid
transportation of the poisoned patient to the hospital and not waste precious time on attempts at gastrointestinal decontamination. Before performing
any gastrointestinal decontamination techniques,
including the oral administration of activated
charcoal, the EMS personnel responsible for the
care of the poisoned patient must clearly understand that these procedures are not without hazards,
and any decision on their use must consider whether the benefit of decontamination outweighs any
potential harm. Contacting the local poison center
(i.e., U.S. poison centers at 1-800-222-1222) can
help make such decisions.
Syrup of ipecac, previously a mainstay of poisoning management, is no longer recommended in
the management of poisoning.34–36 Emesis, either by
mechanical stimulation (i.e., placing a finger down
the throat) or by use of syrup of ipecac, should be
avoided. The prehospital use of activated charcoal
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Antidotes
is currently controversial, and it is premature to recommend the administration of activated charcoal
by EMS personnel.35 The clinical efficacy of prehospital administration of activated charcoal (AC)
has not been demonstrated. The majority of patients
are resistant to ingestion of AC. In a recent study,
it was shown that 60% of children less than 3 years
old drank less than one quarter of the recommended dose of AC.37 The administration of charcoal is
contraindicated in any person who demonstrates
compromised airway protective reflexes unless he or
she is intubated.38 Intubation will reduce the risk of
aspiration pneumonia but will not totally eliminate
its occurrence.39 Charcoal is also contraindicated
in persons who have ingested corrosive substances
(acids or alkalis). Charcoal not only provides no
benefit in a corrosive ingestion, but its administration could precipitate vomiting, obscure endoscopic
visualization, or lead to complications if a perforation develops and charcoal enters the mediastinum,
peritoneum, or pleural space. Charcoal should be
avoided in cases of pure aliphatic petroleum distillate ingestion. Hydrocarbons are not well adsorbed
by activated charcoal, and its administration could
lead to further aspiration risk.
The number of pharmacologic antagonists or antidotes
that EMS personnel may have access to in prehospital
management is quite limited. There are few agents that
will rapidly reverse toxic effects and restore a patient
to a previously healthy baseline state. Administering
some pharmacologic antagonists actually may worsen
patient outcome compared with simply optimizing basic supportive care. As a result, antidotes should be used
cautiously and with clearly understood indications and
contraindications. Table 32.7 gives a list of potential antidotes available to EMS providers.
Atropine
Atropine is the initial drug of choice in symptomatic patients poisoned with organophosphates or carbamates.
Atropine acts as a muscarinic receptor antagonist and
blocks neuroeffector sites on smooth muscle, cardiac
muscle, secretory gland cells, peripheral ganglia,
and in the central nervous system (CNS). Atropine
is therefore useful in alleviating bronchoconstriction
and bronchorrhea; relieving tenesmus, abdominal
cramps, nausea, and vomiting; resolving bradydysrhythmias; and halting seizure activity. Atropine can
TABLE 32.7
Antidotes
Agent or Clinical Finding
Antidote
Acetaminophen
Benzodiazepines
Beta-blockers
Cardiac glycosides
Crotalid envenomation
Cyanide
Ethylene glycol
Iron
Isoniazid
Methanol
Methemoglobinemia
Opioids
Organophosphates
N-acetylcysteine
Flumazenil*
Glucagon*
Digoxin immune Fab
Crotalidae polyvalent immune Fab
Hydroxocobalamin*
Fomepizole
Deferoxamine
Pyridoxine
Fomepizole
Methylene blue
Naloxone*
1. Atropine*
2. Pralidoxime*
1. Glucose*
2. Octreotide
Sulfonylureas
*Antidotes that may be available to EMS personnel
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be administered by IV, intramuscular, or endotracheal
routes. The dose varies with the type of exposure.
For the mildly and moderately symptomatic patient,
2 mg for adults and 0.02 mg/kg for children (minimum of 0.1 mg) is administered every 5 minutes. In
the severely poisoned patient, dosages will need to be
increased and given more rapidly.40 Tachycardia is not
a contraindication to atropine administration in these
patients. Drying of the respiratory secretions and resolution of bronchoconstriction are the therapeutic end
points used to determine the appropriate dose of atropine. This will be clinically apparent as the patient
will have ease of respiration.41 Atropine has no effect
on the nicotinic receptors and therefore has no effect
on autonomic ganglia and neuromuscular junctions.40
Therefore muscle weakness, fasciculations, tremors,
and paralysis are not indications for further atropine
dosing. Atropine does have a partial effect on the
CNS and is important for treatment and prevention
of seizures.42 Patients who require administration of
atropine following organophosphate exposure should
also emergently receive pralidoxime.
Flumazenil
Benzodiazepines are involved in many intentional
overdoses. Although these overdoses are rarely fatal
when a benzodiazepine is the sole ingestant, they often complicate overdoses with other CNS depressants
(e.g., ethanol, opioids, and other sedatives) due to their
synergistic activity. Flumazenil should not be administered as a nonspecific coma-reversal drug and should
be used with extreme caution after intentional benzodiazepine overdose because it has the potential to
precipitate withdrawal in benzodiazepine-dependent
individuals and/or induce seizures in those at risk.43,44
The initial flumazenil dose is 0.2 mg administered intravenously over 30 seconds. If no response occurs after an additional 30 seconds, a second dose is recommended. Additional incremental doses of 0.5 mg may
be administered at 1 minute intervals until the desired
response is noted or until a total of 3 mg has been administered. At present, flumazenil is very rarely used
in the out-of-hospital setting.
Hydroxocobalamin
Hydroxocobalamin is a safe alternative that is currently being used in Europe for the treatment of
cyanide toxicity and has recently been approved for
use in the United States. It acts as a chelating agent
for cyanide. The reaction of hydroxocobalamin with
cyanide results in the displacement of a hydroxyl
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group by a cyano group to form cyanocobalamin
(vitamin B12), which is then excreted in the urine.45 The
usual adult dose of hydroxocobalamin is 5 g, which may
be repeated in cases of massive cyanide poisoning.46,47
The pediatric dose is 70 mg/kg up to 5 grams.48 Virtually every patient receiving this antidote will develop
orange-red discoloration of the skin, mucous membranes, and urine that will resolve within 24 to
48 hours.49 At present, definitive outcome studies of
prehospital use of hydroxocobalamin are lacking.
Naloxone
Opioid poisoning from the abuse of morphine derivatives or synthetic narcotic agents may be reversed
with the opioid antagonist naloxone.50 Naloxone is
commonly used in comatose patients as a therapeutic
and diagnostic agent. The standard dosage regimen
is to administer from 0.4 to 2 mg slowly, preferably
intravenously. Intramuscular administration is an alternative parenteral route, but if the patient is hypotensive, naloxone may not be absorbed rapidly from
the intramuscular injection site. The IV dose should
be readministered at 5-minute intervals until the desired endpoint is achieved—restoration of respiratory
function, ability to protect airway, and an improved
level of consciousness.51 If the IV route of administration is not viable, alternative routes in addition to
intramuscular injection are intraosseous, intranasal,
or via nebulization.51 A patient may not respond to
naloxone administration for a variety of reasons: insufficient dose of naloxone, the absence of an opioid
exposure, a mixed overdose with other central nervous and respiratory system depressants, or medical
or traumatic reasons.
Naloxone can precipitate profound withdrawal
symptoms in opioid dependant patients. Symptoms
include agitation, vomiting, diarrhea, piloerection,
diaphoresis, and yawning.51 Use care in administering
this agent. Only give the amount that is necessary to
restore adequate respiration and airway protection.
Pralidoxime Chloride
Acetylcholine (ACh) is a neurotransmitter found
throughout the nervous system, including the CNS, the
autonomic nervous system, and at the skeletal muscle
motor end-plate. ACh acts in both the CNS and peripheral nervous system by binding to and activating
muscarinic and nicotinic cholinergic receptors. The
enzyme acetylcholinesterase (AChE), terminates the
activity of ACh within the synaptic cleft. ACh binds to
AChE’s active site where the enzyme hydrolyzes ACh
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to choline and acetic acid. These hydrolyzed products
rapidly dissociate from AChE so that the enzyme is
free to act on another molecule. Organophosphate
and carbamates act by binding the AChE active site,
rendering the enzyme incapable of inactivating ACh.
As a result, ACh accumulates in the synapse and excessive stimulation occurs. Carbamates will, with
time, spontaneously dissociate from AChE, thereby
allowing the enzyme to again function. Organophosphates, however, do not spontaneously dissociate.
Rather, over time, a portion of the bound organophosphate is cleaved, producing a stable, covalent bond
between the organophosphate and AChE. This process is called aging. The time it takes for aging to occur depends on the organophosphate. Before aging
occurs, pralidoxime chloride (2-PAM, Protopam chloride) can remove the organophosphate and restore enzyme function. However, once this aged covalent bond
forms, AChE cannot be reactivated and activity is not
restored until new enzyme is synthesized.
Pralidoxime chloride reactivates AChE by exerting a nucleophilic attack on the phosphorus resulting in an oxime-phosphate bond that splits from the
AChE leaving the regenerated enzyme. This reactivation is clinically most apparent at skeletal neuromuscular junctions, with less activity at muscarinic sites.52
Pralidoxime must therefore be administered concurrently with adequate atropine doses. The process of
aging will prevent pralidoxime from regenerating the
AChE active site and, as a result, is ineffective after
aging has occurred. Therefore, the sooner pralidoxime is administered, the greater the clinical effect.
The recommended dose of pralidoxime is 1 to 2 g for
adults or 20 to 50 mg/kg for children by IV route.
Slow administration over 15 to 30 minutes has been
advocated to minimize side effects.41,53 These side effects include hypertension, headache, blurred vision,
epigastric discomfort, nausea, and vomiting. Rapid
administration can result in laryngospasm, muscle
rigidity, and transient impairment of respiration.52
PROTOCOLS
The development of protocols for treating each individual type of poisoning is impossible due to the
vast number of potential toxins. It is also impractical
to have one protocol that could easily pertain to all
cases of poisoning. It may be necessary to construct
protocols for the different problems that require different treatments in the field (e.g., suspected opioid
intoxication, carbon monoxide toxicity, and chemical
dermal contamination). Integral to these protocols is
an outline of the relevant history and physical findings that guide the provider to appropriate generalized
management of the intoxicated patient. In addition,
each protocol should contain the toll free national
poison center number (1-800-222-1222) where the
EMS provider can obtain guidance 24/7 by experts in
the field of medical toxicology.
SUMMARY
EMS providers will often be required to care for poisoned patients. Many of these patients will do well
with standard medical management and never develop
significant toxicity. However, for patients who present
with serious toxic effects or after potentially fatal ingestions, prompt action must be taken. Because many
poisons have no true antidote and the poison involved
may initially be unknown, the first step is good supportive care. Attention to supportive care, vital signs,
and prevention of complications are the most important steps. Taking care of these issues will often be all
that is necessary to ensure recovery.
C L I NI C A L VI G N E T T E S
Case 1
EMS is called to the scene of a confused and agitated 41-year-old previously healthy, suicidal female.
Family members state she ingested seventy-five
25-mg diphenhydramine tablets. Her initial vitals
are: pulse 165/minute, blood pressure 85/35 mm Hg,
respiratory rate 20/minute, and pulse oximetry 97%
on room air. Her physical examination is significant
for pupils that are 7 mm in diameter and minimally
reactive to light, and skin that is warm and dry. She
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is actively hallucinating and intermittently agitated,
with slurring of her speech. A wide-complex tachycardia is noted on the monitor with QRS of 140 ms
in duration. Differentiation between a VT and an
aberrantly-conducted supraventricular tachycardia
cannot be conclusively achieved. IV access is established, and a 1-L normal saline bolus is initiated. Two
ampules of sodium bicarbonate are infused with
noted narrowing of her QRS complex to 100 ms duration, and her systolic blood pressure increases to
110 mm Hg. Two milligrams of lorazepam are infused
with calming of her agitation. The remaining transport progresses without complication.
Comment
The placement of an IV with subsequent normal
saline fluid bolus is an appropriate first step in the
care of this patient’s hypotension. Noting a wide
complex tachydysrhythmia in a poisoned patient
should prompt the EMS personnel to administer
sodium bicarbonate. Diphenhydramine is a known
cardiac fast sodium channel blocker and will respond to sodium bicarbonate infusions. The patient
is also manifesting the signs and symptoms of an
anticholinergic toxidrome (i.e., confusion, tachycardia, mydriasis, dry skin, and mumbling speech).
Administration of a benzodiazepine to calm the agitated poisoned patient is the appropriate first step
in sedation in such circumstances.
Case 2
EMS arrives to the scene of a sedate 24-year-old male
with a history of schizophrenia. Family members
state he was in his normal state of health 3 hours
ago. On arrival home from shopping, they found
him unresponsive on the floor. His airway is intact
with a strong gag reflex. He arouses to stimulation,
moans, and localizes to pain, but rapidly drifts back
to sleep without stimulation. His initial vital signs
are: pulse 90/minute, blood pressure 85/35 mm Hg,
respiratory rate 16/minute, and pulse oximetry 99%
on room air. Further examination is significant for
pupils that are 2 mm in diameter and minimally reactive to light. A narrow complex rhythm is noted
on monitor with a QT of 520 ms in duration. IV
access is established and a 1-L normal saline bolus
is begun. Because his gag is intact with good respirations, naloxone is not administered. Due to the
prolongation of the QT interval, 2 g magnesium sulfate is infused. On search of the premises by police,
an empty bottle of olanzapine is found in the bathroom trash. The patient’s blood pressure responds
nicely to the IV fluids and he is transported without
complication.
Comment
This patient manifests a typical presentation for
an antipsychotic overdose consisting of sedation,
hypotension, miosis, and QT prolongation. These
overdoses can mimic opioid toxicity. Naloxone is
not necessary due to the patient’s intact airway and
adequate respirations, and the fact this is not an
opioid overdose. He is hypotensive and sedate due
to olanzapine’s alpha1-blocking activity, which typically responds well to simply IV fluids. Administering magnesium sulfate to a poisoned patient with
QT prolongation is appropriate to prevent the development of polymorphic VT.
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