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CALL US...TM
The Official Newsletter of the California
Volume 7, Number 2
Spring 2009
Hydrocarbon
Toxicity and Abuse
INTRODUCTION
Hydrocarbons
(HC) are organic compounds containing primarily hydrogen and carbon atoms,
although they may contain other molecules such as halogens or alcohols.
Generally speaking there are two types of HC, aliphatic or straight chained and
cyclic, aromatic, or other ringed structures. Hydrocarbons are derived from
many different sources including: plant materials, animal fat, natural gas, and
coal. Hydrocarbons are widely used in daily life and industrial applications as
fuel, lubricants, solvents, degreasers, etc. Some HC are used medicinally such
as chloral hydrate, chlorobutanol, and alcohols. Three
general “methods” of inhaled HC abuse are employed: 1) “sniffing,” whereby the
HC is directly smelled from a container e.g., glue, correction fluid, 2) “huffing,” where HC is applied to cloth and
held to the face and 3) “bagging,” where HC is placed in a plastic bag and
inhaled.
CASE PRESENTATION
A
16 year old male was being chased by a police officer when he suddenly
collapsed and was found to be pulseless and
unresponsive. The police officer had found the child behind a school with a
spray paint can and a rag in his hand. When the police officer told the child
to drop the paint can and rag, the child ran. The child collapsed within 100
yards of running. The police officer immediately called for paramedics and
began CPR. When the paramedics arrived three minutes later, an automatic
external defibrillator was applied and found the patient to be in ventricular
fibrillation. A single biphasic shock was delivered, followed by return of
spontaneous circulation with a blood pressure of 130/70 mm Hg, heart rate of
120 bpm and respiratory rate of 40/minute. The
patient became responsive and was transported to the emergency department (ED).
In the ED he was awake but somnolent. On physical examination a small amount of
gold colored paint was seen below each nostril with local erythema.
Vital signs were now blood pressure 120/80, pulse rate of 90, and respiratory
rate of 20. He was afebrile.
No signs of trauma were seen on exam. Laboratory analysis was unremarkable
except for a mildly elevated white blood cell count, serum chloride of 120 mEq/L and serum bicarbonate of 16 mEq/L. In addition, there was protein in his urine.
Once awake, the patient admitted to abusing metallic spray paint several times
a day for the past several months. He stated he now notices that he is having
some difficulty walking and some slurring of his words. He was admitted to the
intensive care unit for observation. A computerized tomography scan of his
brain showed some early diffuse white matter changes. He was noted to have a slightly wide based
gait during admission but otherwise a normal neurologic examination. The
patient did not have any subsequent episodes of ventricular dysrhythmias. He
was discharged the following day in the care of his parents with outpatient
referral to a neurologist and also a support group for teenagers that abuse
inhalants.
Questions:
1.
What is the name of the
syndrome that is described in the case above?
2. Based
on the laboratory analysis, which hydrocarbon do you suspect the patient has
been abusing?
3. Can
brain white matter changes be seen following chronic hydrocarbon abuse?
EPIDEMIOLOGY
The majority of HC exposures are unintentional and result in
minimal or no toxicity. However, both intentional and occupational exposures
can result in severe morbidity and mortality. In 2005 the American Association
of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS)
reported almost 54,000 exposures to HC, 2.2% of all calls, with a large number
occurring in children less than 6 years of age. On average there are 13 deaths
per year resulting from HC exposures reported to poison control centers in the
PATHOPHYSIOLOGY
Depending
upon the physicochemical properties of an individual HC, the toxicokinetics can vary greatly. HC that are highly
volatile exert their toxicity primarily through the inhalation route. These
volatile HC are also abused for central nervous system (CNS) depressant effects.
Absorption from the gastrointestinal (GI) tract is also variable with lower
molecular weight (MW) compounds being absorbed more so than higher MW HC. For
example, a 14 carbon containing HC can be as much as 60% absorbed compared to
5% for a 28 carbon containing HC with virtually zero being absorbed with a greater
than 32 carbon containing product.
Hydrocarbon absorption
following dermal exposure is generally low.
However HC have a “defatting” property
resulting in destruction of the stratum corneum.
Prolonged contact, abraded skin, and repeated exposure all may increase dermal
absorption.
As many HC
are quite lipophilic, distribution into fat can be substantial.
Hydrocarbons may be eliminated unchanged as parent compounds or metabolized to
various metabolites, some of which may be toxic. There are two well known HC
that get converted in vivo to toxic
metabolites. The first is carbon
tetrachloride, a compound that was once used extensively in the dry cleaning
industry and in fire extinguishers.
Hepatic metabolism of carbon tetrachloride produces a free radical that
can be hepatotoxic, leading to fulminent
hepatic necrosis. The second is
methylene chloride, a chemical and gas that is converted in the body to carbon
monoxide. The elimination half life
varies greatly amongst different HC and can be on the order of several hours to
several days. The most common organ
affected by HC aspiration is obviously the lungs. Besides directly damaging lung parenchyma, HC
dissolve lung surfactant, leading to alveolar collapse and extensive
pneumonitis.
CLINICAL PRESENTATION
Although
pulmonary toxicity from these agents was once believed to be caused by GI
absorption and subsequent delivery to the lungs, it is now thought to be a
direct toxic effect of the HC from aspiration into the pulmonary system.
Probably the most important physicochemical property determining pulmonary
toxicity is the viscosity of the individual agent, with less viscous or more
“water-like” compounds such as kerosene and gasoline increasing risk of
aspiration and subsequent pneumonitis. Agents with a much higher viscosity like
motor oil are less frequently aspirated and therefore considered less toxic. Vomiting
after HC ingestion greatly increases the risk of aspiration and should be
prevented if at all possible. The larger the volume of HC ingested the
increased risk of vomiting and possible aspiration. For this reason induction
of vomiting and the administration of large volumes of liquids to “dilute” HC
should be avoided.
Clinically,
signs and symptoms following aspiration of HC are generally seen soon after
exposure, often manifesting as coughing or choking and often described as
“sputtering.” Early signs include tachypnea, hypoxia
and occasionally hemoptysis. A ventilation perfusion
mismatch can be seen from local destruction of lung parenchyma and alveolar
collapse. There is often a radiographic “lag time” of HC pneumonitis following
the onset of clinical signs and symptoms that can be delayed up to 24 hours.
However, the majority of chest radiograph abnormalities are seen within 4 to 6
hours.
Many HC are
rapidly and extensively delivered to the brain based on the high degree of lipophilicity, particularly following the inhalational
route. As mentioned above, HC are often abused for their CNS effects. Due to
the high lipid content in myelin in CNS white matter, chronic abuse can result
in a leukoencephalopathy and permanent neurologic sequelae. CNS depression and coma may be seen with large
exposures, although these may be preceded by an initial period of agitation.
Clues on physical examination of inhaled HC abuse include paint or redness
around the nose and mouth and defatting dermatitis of
the hands. Ataxia, dementia, and dysarthria may occur
with prolonged, chronic abuse.
Certain HC
are notorious for causing peripheral nervous system effects, primarily an axonopathy. Probably the most well known of these are n-hexane and methyl-n-butyl ketone, both metabolized to a common
toxic metabolite.
“Sudden
sniffing death syndrome” (SSDS) is a phrase that has been used for the clinical
presentation described in the case above.
It can occur following any HC exposure, but primarily after inhalation exposures.
This syndrome is thought to be caused by “cardiac sensitization,” whereby cardiac
myocytes become more sensitive to endogenous
catecholamines (e.g., epinephrine) and tachydysrhythmias
after exposure to a HC. SSDS was once thought to be only seen in halogenated HC
exposure, but it has now been reported with exposures to many non-halogenated
HC. The sequence of events begins when a person being exposed to a HC is
startled or frightened (e.g., being chased by police) resulting in an
adrenaline surge precipitating a fatal ventricular dysrhythmia.
Hydrocarbons
are irritants to skin and can cause erythema and
dryness, in addition to their defatting properties
resulting in loss of normal dermal adipose. Defatted as well as abraded skin
can increase systemic absorption of the HC. Severe morbidity has been
associated with high pressure “injection” of HC following occupational
exposures (e.g., grease guns), generally involving the upper extremities. This
is a true orthopedic emergency requiring immediate referral and surgical
debridement.
Several HC,
particularly those with halogenated components, have been shown to be hepatoxic. The best described of these is carbon
tetrachloride, which as noted above is converted in vivo to a toxic metabolite resulting in centrilobular
hepatic necrosis. Other agents, such as
trichloroethylene may also cause injury to the liver following excessive
exposures.
Hydrocarbons may
also affect the renal system. The most well described of these is toluene,
found in a number of different products such as paints. Many of these products are abused since
toluene can lead to CNS intoxication when inhaled. Heavy toluene exposure can cause a hyperchloremic renal tubular acidosis. In addition, toluene is metabolized to benzoic
acid that can further contribute to a metabolic acidosis.
DIAGNOSIS
The diagnosis
of HC toxicity is generally known on presentation based on exposure history.
Clues in a comatose or unresponsive patient include a hydrocarbon odor on the breath.
There are a limited number of laboratory tests that can be used to identify
hydrocarbon exposure, and most are used predominantly in an occupational
setting. These would include urine hippuric acid for toluene exposure and urine phenol for
benzene exposure. Other than for methylene chloride that is metabolized to
carbon monoxide, there are no other readily available tests for acute
hydrocarbon poisoning. Any patient that had initial coughing or choking following
HC ingestion should be referred to an emergency department for evaluation.
Clinical signs and symptoms are usually manifested within 6 hours of HC
exposure, particularly after aspiration. Therefore, a patient that remains
asymptomatic or was initially minimally symptomatic but then asymptomatic
during an observation period of at least 6 hours can be safely discharged with
strict return precautions. If a chest
radiograph is obtained around 6 hour after exposure, it should also be normal.
Some halogenated hydrocarbons are radio opaque and may be seen on abdominal
radiograph after ingestion. While this may rarely confirm exposure there is
little utility in routine abdominal radiography for HC exposures. Consider
hydrocarbon exposure in a young patient following ventricular tachycardia or a ventricular
fibrillation arrest, particularly if hydrocarbon containers or paraphernalia are
found near the patient.
TREATMENT
Dermal
decontamination following topical HC exposure should include removal of all
clothing and copious irrigation with soap and water. Defatting of skin
may occur with prolonged contact of contaminated clothing.
Ophthalmic HC
exposures should immediately be irrigated with copious water for at least 15
minutes, ideally at an eye wash station if available and before transport to a
health care facility. Copious irrigation should be continued or repeated if the
patient is still symptomatic in the emergency department. This should be
followed by thorough physical examination including visual acuity and slit lamp
examination and ophthalmologist referral as indicated.
There is
generally no role for gastrointestinal decontamination following HC exposure as
activated charcoal does not bind HC well and may increase aspiration risk.
Gastric lavage and dilution are not recommended following most HC exposures. There is generally no role for extracorporeal
removal methods (e.g., hemodialysis, hemoperfusion) following HC exposures unless severe rhabdomyolysis or other metabolic issues need to be addressed.
For patients
being observed in the emergency department an initial chest radiograph is not
generally indicated unless the patient is symptomatic, but should be considered
at 6 hours even if the patient remains asymptomatic before discharge to ensure subtle
aspiration findings are not present. If
radiographic abnormalities potentially secondary to HC exposure are found at
any time this should prompt extended observation or possible admission to a
monitored setting.
If the
patient is symptomatic at the time of arrival to the emergency department
following HC exposure, immediate attention to the ABCs should be addressed.
Intravenous access, supplemental oxygen, and continuous monitoring including
pulse oximetry should be obtained. The mainstay of
treatment is primarily aggressive supportive care. Early endotracheal
intubation should be considered in patients with respiratory distress or
depressed mental status, and in those at risk of vomiting with inability to
protect the airway. Obtaining a twelve lead electrocardiogram should be
considered in symptomatic inhalational exposures, particularly if abnormal
vital signs are present or irregular cardiac rhythms suspected. An initial
chest radiograph should be obtained in symptomatic individuals with subsequent
daily chest radiographs as needed.
Following HC
aspiration, a severe chemical pneumonitis can be seen and may progress to acute
respiratory distress syndrome. Corticosteroid use in this setting is
controversial, however, if used the administration of empiric antibiotics
should be considered. If corticosteroids are not used, antibiotics are
generally withheld unless evidence of a secondary bacterial pneumonia is
present.
In severe
cases, patients with hydrocarbon aspiration my present or rapidly develop adult
respiratory distress syndrome (ARDS).
These cases are difficult to manage and often require advanced airway
support. Mechanical ventilation with
100% oxygen and liberal use of positive end expiratory pressure (PEEP) can be
beneficial. Symptoms may persist for
extended periods and fatalities can occur. Heroic life support measures to
treat hydrocarbon-induced pneumonitis and hypoxia have been utilized, including
ECMO and the administration of pulmonary perfluorocarbon
solutions, but have had limited success.
Occasionally,
patients inhaling hydrocarbons can present with ventricular dysrhythmias. Most often these will have resolved by the
time of arrival at the ED. If PVCs or
ventricular rhythms are still present after arrival, blockade of hyperstimulated beta-receptors on cardiac myocytes with a beta-receptor blocking agent such as esmolol may effectively eliminate these dysrhythmias.
Hydrocarbons are
ubiquitous in our society and both intentional and unintentional exposures are
common. The key to minimizing or eliminating morbidity and mortality is
prevention. Hydrocarbons and other chemicals should always be kept in original,
well marked child resistant containers out of the reach of children.
- What is the name of the syndrome
that is described in the case above?
The
above case describes “sudden sniffing death syndrome”, which is thought to be
due to cardiac sensitization by hydrocarbons to endogenous catecholamines.
- Based on the laboratory analysis,
which hydrocarbon do you suspect the patient has been abusing?
This
patient has a hyperchloremic metabolic acidosis and
protein in his urine suggestive of a renal tubular acidosis. Toluene is well
known to cause a renal tubular acidosis and is found in paints.
- Can white matter changes be seen
following chronic hydrocarbon abuse?
Chronic
hydrocarbon abuse can result in destruction of myelin in the white matter and
progress to a leukoencephalopathy.
CONSULTATION ASSISTANCE
Consultation
with a specialist in poison information or with a medical toxicologist can be
obtained free of charge by calling the California Poison Control System at
1-800-222-1222.
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