++
Carbon monoxide (CO) is an odorless gas produced by incomplete
combustion of carbon-containing material. Common sources of exposure include
house fires, automobile exhaust, and improperly ventilated water
heaters, stoves, furnaces, fireplaces, and space heaters. Inhalation
of CO is the leading cause of poisoning death in the United States.
++
Carbon monoxide causes cellular hypoxia via several mechanisms.
First, CO binds to hemoglobin with an affinity 250 times greater than
that of oxygen, forming carboxyhemoglobin (COHb). This results in
decreased oxyhemoglobin saturation and oxygen delivery to the tissues.
Second, the formation of COHb shifts the oxyhemoglobin dissociation
curve to the left, further diminishing release of oxygen to the
tissues. Third, CO binds to cytochrome oxidase, impairing cellular
respiration and oxidative metabolism. In addition, CO binds to myoglobin,
resulting in myocardial depression, hypotension, dysrhythmias, and
cardiac arrest.
++
The diagnosis of carbon monoxide poisoning is readily suspected
in the patient found unconscious in a house fire or running automobile.
However, the diagnosis is difficult when the patient presents with
nonspecific symptoms after an unrecognized exposure. Mild to moderate
exposures present with malaise, nausea, vomiting, dyspnea, headache, dizziness,
and confusion. Such patients are often misdiagnosed with influenza
or gastroenteritis. Severe poisoning is characterized by syncope,
seizures, coma, cardiorespiratory depression, and death.
++
A high level of suspicion and detailed history of possible carbon
monoxide (CO) exposure is essential when the diagnosis is not obvious.
Once suspected, the exposure can be confirmed by determining the
carboxyhemoglobin (COHb) level from a blood gas sample using co-oximetry.
There is a correlation between COHb levels and clinical presentation (Table 120-7). However, if significant time
has elapsed since exposure, the COHb level will underestimate the
initial severity of the poisoning. Metabolic acidosis is an indicator
of the severity of cellular hypoxia and ischemia. The arterial blood
gas oxygen saturation should be measured with a co-oximeter, which
specifically detects COHb. With CO poisoning, the arterial PO2 is normal
because dissolved oxygen is unaffected by COHb. Routine blood gas
measures the PO2 and calculates the oxygen saturation from that value, reporting
false normal oxygen saturation in the setting of CO poisoning. Likewise,
transcutaneous pulse oximeters give false normal readings because
they do not distinguish between oxyhemoglobin and COHb.
++
++
In addition to general supportive measures, the treatment of
carbon monoxide (CO) poisoning is aimed at reducing the amount of
CO bound to hemoglobin, cytochrome oxidase, and myoglobin by administering
the highest possible oxygen concentration to the patient. The half-life
of carboxyhemoglobin (COHb) decreases from approximately 4 hours
when the patient is breathing room air (21% oxygen) to
1 hour when the patient is on 100% oxygen. Hyperbaric oxygen
treatment at 2 to 3 atm pressure can further decrease the COHb half-life
to 20 to 30 minutes. Although the utility of hyperbaric oxygen therapy
remains controversial because of conflicting research design and
results, it should be considered for patients with significant CO
poisoning if practical (eTable 120.3) .10 The
decision to initiate HBO must be individualized depending on severity
of poisoning, the patient’s stability and suitability for transport,
and distance to the nearest hyperbaric chamber. The regional poison
control center and hyperbaric chamber should be contacted for advice.
++
++
Caustic agents are found in household products such as drain
cleaners, oven cleaners, rust removers, toilet bowl cleaners, tile
cleaners, and hair straighteners. They are capable of causing serious
injury on contact with the skin, eyes, and gastrointestinal tract.
++
The most commonly encountered caustic agents are acids and alkalies.
Acids denature proteins (coagulation necrosis), producing a firm
coagulum that may limit tissue penetration. Acids often have a strong
odor and cause immediate pain, which can limit the amount ingested.
Alkalies dissolve proteins and saponify fats (liquefaction necrosis),
resulting in deeper tissue penetration. Alkalies are often odorless
and do not cause immediate pain on contact, which may allow ingestion
of larger volumes. Strong acids (very low pH) and strong alkalies
(very high pH) cause the greatest damage, but the severity of tissue
injury is also determined by other factors such as duration of contact,
volume of exposure, and physical state of the caustic substance.
++
Ingestion is the most common route of exposure. The complete
absence of signs and symptoms after several hours usually indicates
that significant injury has not occurred. However, the absence of
oropharyngeal burns on physical examination does not completely
rule out the possibility of esophageal or gastric injury. Patients
with caustic burns usually report pain of the mouth, throat, chest,
or abdomen. Young children manifest pain by crying, drooling, and refusing
to swallow. Esophageal perforation usually causes severe mediastinitis.
Gastric injury may result in hematemesis and epigastric or upper-left
quadrant abdominal pain. Peritonitis and metabolic acidosis are
ominous signs, correlating with severity of tissue necrosis, esophageal
or gastrointestinal perforation, and sepsis.
++
Respiratory tract injury may occur via direct extension of esophageal
burns or secondary to aspiration of the caustic while swallowing
or vomiting. Upper airway edema may result in hoarseness, stridor,
and catastrophic upper airway obstruction. Pulmonary involvement
includes bronchospasm and pneumonitis.
++
Ocular exposure to caustic agents, especially strong alkalies,
often results in severe damage. Initial findings include eye pain,
blepharospasm, lacrimation, conjunctival injection, and edema. Necrosis
and opacification of the cornea, lens, and anterior chamber lead
to blindness. Dermal contact results in localized pain, erythema,
blistering, and deeper necrosis when the exposure is severe.
++
The caustic substance should be identified with respect to pH,
concentration, amount, and time of exposure. Immediate decontamination
is of the utmost importance. Patients should be undressed, inspected
for dermal exposures, and washed thoroughly with tepid water. In
the case of ocular exposures, the eyes should be immediately irrigated.
Tap water is usually readily available, and the eyes should be flushed
under running water for a minimum of 15 minutes. In the emergency
department, local anesthetic drops may be applied and each eye irrigated
with a liter of saline. After thorough ocular decontamination, the
pH of the tears is checked with litmus paper or a urine dipstick.
Further irrigation is indicated if the pH has not returned to approximately
7.4. Following irrigation, a Wood’s lamp and fluorescein
dye are used to evaluate for corneal and conjunctival injuries.
Ophthalmologic consultation should be obtained for all ocular caustic
injuries. Following ingestion of a caustic substance, gastrointestinal
decontamination is of limited utility. The mouth should be rinsed
thoroughly in patients with oral burns. Some experts recommend diluting
the gastric contents by having the patient drink small volumes of
water or milk. The placement of a small nasogastric tube to suction
the stomach may be considered in recent and large intentional ingestions.
Activated charcoal does not bind caustics and obscures endoscopy.
++
Imaging for serious caustic ingestions may include lateral neck,
chest, and abdominal radiographs. Patients with respiratory distress
require laryngoscopy to assess for airway burns. Immediate surgical
consultation is required if esophageal or gastrointestinal perforation
is suspected based on hypotension, mediastinitis, abdominal rigidity,
sepsis, metabolic acidosis, and radiographic or endoscopic evidence.
++
Gastroenterology consultation is required for all caustic ingestions
with signs and symptoms of injury. If the patient is stable, endoscopy
is performed 8 to 12 hours after ingestion to evaluate full progression
of the burn. Endoscopic grading of the severity of esophageal injuries
helps to guide subsequent management (Table 120-8).11 Antibiotics
should not be administered prophylactically for mild injuries, but
are indicated for patients with gastrointestinal perforation or
signs of infection.
++
++
Hydrocarbons are found in many common household and automotive
products. They are derived from petroleum distillation and other sources
including coal tar, plant oils, and animal fats. Hydrocarbon exposures
are a frequent cause of pediatric morbidity and mortality. Common
clinical scenarios include toddlers who aspirate a liquid hydrocarbon
and recreational inhalation of volatile hydrocarbons by adolescents.
++
Most hydrocarbons are poorly absorbed from the gastrointestinal
tract after ingestion and lack systemic toxicity. The chief concern is
pulmonary aspiration resulting in chemical pneumonitis. The risk
for aspiration is determined by the hydrocarbon’s physical
properties of viscosity and surface tension. Viscosity is the tendency
to resist flow and is the best predictor of aspiration. Hydrocarbons
with low viscosity have the highest risk for aspiration, while those
with high viscosity are less likely to be aspirated. Surface tension
is the cohesive force between molecules and defines the ability
of the liquid to move along a surface. Hydrocarbons with low surface
tension have a higher risk for aspiration. Volatility is the ability
of a liquid to vaporize into a gas. Volatile hydrocarbons can displace
alveolar oxygen, resulting in hypoxia. These compounds are easily
absorbed across the alveolar-capillary membrane, resulting in systemic
effects such as central nervous system depression.
++
The respiratory injuries caused by hydrocarbon aspiration are
multifactorial. Irritation of the larynx and trachea results in
coughing, choking, and laryngospasm. Spread of the hydrocarbon to
the lower airways results in bronchospasm, bronchial inflammation,
and necrosis. When the hydrocarbon reaches the alveoli, changes
in pulmonary dynamics occur due to lipid solubilization and disruption
of the surfactant layer, resulting in alveolar collapse and decreased
compliance. Direct injury to lung parenchyma results in alveolar
edema, exudates, and hemorrhage, with interstitial inflammation
and necrosis leading to a further ventilation-perfusion mismatch
and decreased compliance.
++
Cardiovascular toxicity is unusual after hydrocarbon ingestion
or aspiration, but is well described with inhalational abuse of
halogenated or aromatic hydrocarbons. Sensitization of the myocardium
to endogenous catecholamines results in ectopy, tachydysrhythmias, ventricular
fibrillation, and sudden death. The term sudden sniffing
death syndrome has been used to describe this phenomenon
associated with inhalational solvent abuse.
++
Central nervous system depression following hydrocarbon aspiration
is most commonly caused by hypoxia secondary to pulmonary injury.
Systemic absorption of volatile hydrocarbons following inhalation
or ingestion can result in central nervous system depression because
of disruption of neuronal membranes. It is this alteration of mental
status that is sought by the inhalant abuser. Chronic inhalational
abuse of volatile hydrocarbons can result in irreversible white
matter degeneration and dementia. Certain hydrocarbons, including
camphor, halogenated hydrocarbons, aromatic hydrocarbons and hydrocarbons
containing metals or pesticides, have systemic toxicities that may
require consultation with a poison control center (eTable 120.4).
++
++
Most patients with hydrocarbon aspiration will have immediate
symptoms of coughing, gagging, and choking. In mild cases, these symptoms
may be transient, but patients with significant aspiration will
have persistent coughing and tachypnea. Patients with severe aspiration
present with severe respiratory distress including coughing, grunting, bronchospasm, tachypnea, intercostal retractions,
use of accessory muscles, cyanosis, agitation, and somnolence. Other
patients may have more gradual development of respiratory distress.
++
Patients who remain asymptomatic for 6 hours after ingestion
are unlikely to have pulmonary aspiration and may be safely discharged
home with careful follow-up instructions. Symptomatic patients are
admitted to the hospital for further observation and management.
Persistent cough or tachypnea should be evaluated with a chest radiograph,
which usually demonstrates pneumonitis. Pneumatoceles are a late
finding, appearing on radiographs a week or two after the initial
necrotizing pneumonitis. In patients with more significant respiratory
distress, blood gas analysis may demonstrate hypoxemia and hypercarbia
with a combined respiratory and metabolic acidosis. The complete
blood count often shows a leukocytosis with a left shift, and many
patients will also manifest a fever in the first day or two due to
inflammatory mediators from the chemical pneumonitis. Empiric antibiotics
are usually not recommended unless the fever and leukocytosis develop
later, suggesting bacterial superinfection. Corticosteroids are
not helpful in limiting the pulmonary injury.
++
Patients with severe respiratory distress require immediate endotracheal
intubation with mechanical ventilation and oxygenation. Decreased
lung compliance necessitates increased positive end-expiratory pressures.
Patients who fail these interventions may be candidates for extracorporeal
membrane oxygenation to allow time for the lungs to heal.
++
The use of gastrointestinal decontamination following hydrocarbon
ingestion is controversial because the primary risk is pulmonary aspiration.
For these agents, gastric decontamination is not indicated because
of the increased risk of aspiration. Some experts recommend gastric
emptying for hydrocarbons with serious systemic toxicity, especially
large intentional ingestions. However, the benefit of gastric emptying
must be weighed against the risk of aspiration pneumonitis. Most
ingestions occur in young children and are unintentional, resulting
in smaller volumes ingested, reducing the need for gastric decontamination.
Activated charcoal has poor adsorptive capacity for most hydrocarbons.
+++
Methanol and Ethylene
Glycol
++
Methanol and ethylene glycol are found in many consumer products.
Ingestion of these toxic alcohols results in significant morbidity and
mortality, but outcomes can be improved with early diagnosis and
treatment.
++
Both alcohols derive their toxicity from the fact that they are
metabolized by alcohol and aldehyde dehydrogenases into more toxic
metabolites (eFig. 120.3). The parent alcohol initially
causes an elevated osmolar gap, followed by the gradual development
of an elevated anion gap metabolic acidosis as toxic metabolites
are formed. Later, the osmolar gap normalizes and severe anion gap
metabolic acidosis predominates.
++
++
The toxic metabolite of methanol is formic acid, which causes
metabolic acidosis as well as optic nerve and brain injury. The
principal toxic metabolites of ethylene glycol are glycolic and oxalic
acid. Glycolic acid is primarily responsible for the metabolic acidosis.
Oxalic acid causes calcium oxalate precipitation in the kidney leading to
renal failure, and in the brain resulting in altered mental status,
coma, seizures, and cerebral edema. Widespread calcium oxalate precipitation may
lead to severe hypocalcemia with seizures, prolonged QT interval
on electrocardiogram, and ventricular dysrhythmias.
++
Suspected methanol and ethylene glycol ingestions must be taken
with extreme caution because the lethal dose is very low. Initial
symptoms include ataxia, altered mental status, and vomiting. Patients
will subsequently exhibit Kussmaul respirations as metabolic acidosis
develops. Both poisonings can result in coma, seizures, myocardial
depression, and hypotension. Visual disturbances and blindness are
specific for methanol, whereas renal failure, calcium oxalate formation,
and hypocalcemia are specific for ethylene glycol poisoning.
++
The diagnosis of methanol or ethylene glycol poisoning is based
on a careful history and interpretation of physical examination
and laboratory data. Measurement of blood methanol and ethylene
glycol levels confirms the diagnosis and guides therapy, but results
may not be immediately available. Other helpful laboratory studies include
serum osmolality, blood gas analysis, blood urea nitrogen, creatinine,
electrolytes, calcium, glucose, and lactate. Elevated anion gap metabolic
acidosis not due to lactate suggests toxic alcohol poisoning. Urinalysis
may reveal calcium oxalate crystals due to ethylene glycol poisoning.
++
The treatment of methanol and ethylene glycol poisoning is aimed
at preventing formation of toxic metabolites by blocking the activity
of alcohol dehydrogenase. Two therapeutic options are available
for the blockade of alcohol dehydrogenase: ethanol and fomepizole.
The newer antidote fomepizole has many advantages over ethanol,
which make it the antidote of choice for toxic alcohol poisoning
(eTable 120.5). The indications for fomepizole
in the setting of suspected methanol or ethylene glycol poisoning
are outlined in Table 120-9. Because the
turnaround time for methanol and ethylene glycol levels may be long,
the decision to start treatment with fomepizole must often be made
based on clinical presentation, an elevated osmolar gap, or an elevated
anion gap metabolic acidosis. The loading dose of fomepizole is
15 mg/kg intravenously (up to 1 g), followed by maintenance doses
of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg
every 12 hours thereafter.12
++
++
++
Hemodialysis eliminates the toxic alcohol and its metabolites
and corrects fluid, electrolyte, and acid–base disturbances.
The indications for hemodialysis are outlined in Table 120-9.
Early nephrology consultation for hemodialysis is critical for seriously
poisoned patients. Treatment with fomepizole and dialysis should
be continued until serum methanol or ethylene glycol levels are
negligible, the increased osmolar gap and anion gap metabolic acidosis
are resolved, and the patient is clinically improved.
++
Methemoglobinemia occurs when hemoglobin is oxidized to form
methemoglobin (MetHb) as a result of exposure to oxidizing drugs,
nitrate-contaminated well water, or other oxidative stress. Normally,
99% of the iron in hemoglobin is in the reduced ferrous
state (Fe2+) and 1% is present as MetHb,
the oxidized ferric state (Fe3+). Methemoglobin
is unable to bind and transport oxygen. The oxyhemoglobin dissociation curve
is shifted to the left, further reducing oxygen delivery to the
tissues. These effects are exacerbated when anemia is present. Many
oxidizing agents also cause hemolysis secondary to oxidative effects on
the cell membrane, especially in patients with glucose-6-phosphate
dehydrogenase (G6PD) deficiency.
++
Two enzyme systems are responsible for reducing MetHb back to
normal hemoglobin (Fig. 120-4). The primary
enzyme is nicotinamide adenine dinucleotide (NADH)-dependent MetHb reductase
that utilizes NADH generated from glycolysis and performs 95% of
this activity. The secondary enzyme is nicotinamide adenine dinucleotide
phosphate (NADPH)-dependent MetHb reductase that relies on the G6PD-dependent
hexose monophosphate shunt. This second enzyme system accounts for
only 5% of normal activity, but can be induced to rapidly
reduce MetHb to hemoglobin. The antidote methylene blue increases
the activity of this second NADPH-dependent pathway.
++
++
Infants are at greater risk of methemoglobinemia because of functional
immaturity of the NADH-dependent methemoglobin reductase enzyme
and may develop methemoglobinemia following gastroenteritis or ingestion of
nitrate-containing well water.13 Nitrates do not directly
result in methemoglobinemia, but they are converted to nitrites
by intestinal bacteria. Nitrites are strong oxidizing agents that readily
cause methemoglobinemia.
++
The signs and symptoms of methemoglobinemia result from cellular
hypoxia. Clinical severity correlates with increasing MetHb levels as
shown in Table 120-10. For a given MetHb level,
the clinical effects will be more severe if the patient has concomitant
anemia. Diagnosis depends on a high index of suspicion and history
of exposure to oxidizing agents. Methemoglobinemia should be suspected
in the cyanotic patient with no obvious cardiac or respiratory disease,
whose cyanosis does not improve with oxygen and is out of proportion
to the degree of respiratory distress. Infants presenting with gastroenteritis
and methemoglobinemia may have severe metabolic acidosis and shock
that is out of proportion to degree of dehydration.
++
++
The patient’s blood has a characteristic chocolate brown
color. The diagnosis is confirmed by sending a blood sample to the
laboratory for measurement of the MetHb level and blood gas analysis
on a co-oximeter. Routine blood gas analysis does not detect MetHb,
and also incorrectly calculates normal oxygen saturation based on
the measured PO2 (which is normal with methemoglobinemia).
With significant cellular hypoxia, blood gas analysis demonstrates metabolic
acidosis and serum lactate is elevated secondary to anaerobic metabolism.
The absorption spectrum of MetHb causes transcutaneous pulse oximeters
to measure oxygen saturation incorrectly.
++
Patients with MetHb levels less than 20% usually improve
simply with supportive care and removal of the oxidizing agent.
More severely affected patients require treatment with methylene
blue. A lower threshold for treatment is indicated in patients with
anemia or cardiopulmonary disease. Methylene blue is a thiazine
dye that increases the reduction of MetHb to hemoglobin. Methylene
blue is first reduced to leukomethylene blue by NADPH-dependent
methemoglobin reductase. Leukomethylene blue in turn reduces methemoglobin
to hemoglobin (Fig. 120-4). This pathway
requires Glucose 6-Phosphate Dehydrogenase (G6PD), and therefore
methylene blue is not effective and may cause hemolysis in patients
with G6PD deficiency. The dose of methylene blue is 1 to 2 mg/kg
intravenously over 5 minutes, repeated in 30 minutes if the response
is inadequate. Methylene blue will transiently cause a false decrease in
oxygen saturation measured by transcutaneous pulse oximetry. Excessive
doses of methylene blue (> 7 mg/kg) may actually cause methemoglobinemia.
If the patient has not responded to a second dose of methylene blue, consider
other problems such as G6PD deficiency or NADPH-dependent methemoglobin
reductase deficiency. Exchange transfusion may be considered in
patients with severe methemoglobinemia if methylene blue has failed
or is contraindicated.
+++
Organophosphorus and
Carbamate Insecticides
++
Organophosphorus and carbamate insecticides prevent the breakdown
of acetylcholine in the synaptic cleft by inhibiting the acetylcholinesterase
(AChE) enzyme, resulting in continued stimulation of muscarinic,
nicotinic, and central nervous system receptors. Carbamates form
reversible bonds with AChE that undergo spontaneous hydrolysis with
full return of AChE activity by 24 hours in most cases. Carbamate toxicity
is shorter and less severe compared to organophosphorus compounds,
which can permanently inhibit AChE, resulting in prolonged toxicity.
The “aging” process during which the reversible
bond becomes a stable covalent bond may take 24 to 72 hours. Infants
are at increased risk of toxicity because they have decreased AChE
activity compared to adults.
++
Inhibition of acetylcholinesterase (AChE) by organophosphorus
and carbamate insecticides results in signs and symptoms of cholinergic
excess, which are summarized in the cholinergic muscarinic and nicotinic
toxidromes. A mixture of muscarinic and nicotinic toxidromes is
usually present. The primary cause of death is respiratory failure.
The pulmonary muscarinic effects include bronchorrhea and bronchospasm,
whereas the nicotinic effects on skeletal muscle result in weakness,
muscular incoordination, and fasciculations. The respiratory compromise
is compounded by central nervous system cholinergic effects of coma
and seizures.
++
Diagnosis is based on history of exposure and clinical presentation
consistent with cholinergic excess (muscarinic and nicotinic toxidromes). Plasma
cholinesterase and red blood cell (RBC) cholinesterase activity
are both decreased after organophosphorus poisoning. Plasma cholinesterase
activity is a more readily available and sensitive measure of organophosphorus
poisoning. A plasma cholinesterase level 20 to 50% of normal
correlates with mild poisoning, 10 to 20% indicates moderate
poisoning, and less than 10% is severe. Red blood cell
cholinesterase activity is a better indicator of neurosynaptic acetylcholinesterase
activity, and is therefore a more specific test for organophosphorus
poisoning, but is not readily available in most hospitals. Plasma cholinesterase
and RBC cholinesterase levels are not helpful with initial management
and diagnosis of organophosphorus compound toxicity but aid management
of prolonged toxicity. Cholinesterase measurements are not helpful
after carbamate poisoning because the inhibition of cholinesterase
activity is usually mild and transient.
++
The first priority of treatment is decontamination of the victim
and protection of health-care providers from secondary exposure.
Resuscitation is focused on correcting respiratory dysfunction.
Atropine is the initial antidote for organophosphorus and carbamate
poisoning because it is a competitive antagonist of muscarinic acetylcholine
receptors. The goal of atropinization is the reduction of pulmonary secretions,
reversal of bronchospasm, and improvement in respiratory distress.
The initial dose of atropine is 0.02 mg/kg intravenously up
to 0.5 to 2 mg in adults, doubling the dose every 5 minutes until
adequate oxygenation is achieved. Extremely high doses are required
to overcome the cholinergic excess, and severely poisoned patients
require frequent dosing or continuous intravenous infusion. Atropine
has no effect at nicotinic receptors, and will not reverse nicotinic
toxicity.
++
The second antidote for organophosphorus poisoning is pralidoxime
chloride (2-PAM), which reactivates acetylcholinesterase (AChE), reverses
both muscarinic and nicotinic effects, and reduces atropine requirements.
Pralidoxime must be administered early for organophosphorus poisoning
because the inhibition of AChE becomes irreversible over time. Pralidoxime
is not necessary for carbamate poisoning because of rapid hydrolysis
of the carbamate–AChE complex. The dose of 2-PAM is 25
to 50 mg/kg intravenously in children up to 1 to 2 g in
adults over 15 to 30 minutes, repeated if there is no improvement
in muscle weakness or fasciculations. Severely poisoned patients
require repeat dosing or continuous infusion, which may be necessary for
several days.14