Transcript Document

‫هوالـطيف‬
Dr Behnam Behnoush
Assistant professor, Department
of Forensic Medicine, Tehran
University of Medical Sciences
pesticides

Organophosphates

Carbamates

Organochlorine
Organophosphates
Background

Organophosphate (OP) compounds are a
diverse group of chemicals used in both
domestic and industrial settings. Examples of
organophosphates include: insecticides
(malathion, parathion, diazinon, fenthion,
dichlorvos, chlorpyrifos), nerve gases (soman,
sarin, tabun, VX), ophthalmic agents
(echothiophate, isoflurophate), and
antihelmintics (trichlorfon).
(Modified from reference 11)
Pathophysiology

The primary mechanism of action of organophosphate
pesticides is inhibition of carboxyl ester hydrolases,
particularly acetylcholinesterase (AChE). AChE is an
enzyme that degrades the neurotransmitter acetylcholine
(ACh) into choline and acetic acid. ACh is found in the
central and peripheral nervous system, neuromuscular
junctions, and red blood cells (RBCs). Organophosphates
inactivate AChE by phosphorylating the serine hydroxyl
group located at the active site of AChE. The
phosphorylation occurs by loss of an organophosphate
leaving group and establishment of a covalent bond with
AChE.
Pathophysiology

Once AChE has been inactivated, ACh
accumulates throughout the nervous system,
resulting in overstimulation of muscarinic
and nicotinic receptors. Clinical effects are
manifested via activation of the autonomic
and central nervous systems and at nicotinic
receptors on skeletal muscle.
Pathophysiology
Once an organophosphate binds to AChE, the
enzyme can undergo 1 of the following 3
processes:
 Endogenous hydrolysis of the phosphorylated
enzyme by esterases or paraoxonases
 Reactivation by a strong nucleophile such as
pralidoxime (2-PAM)

Complete binding and inactivation (aging)
Pathophysiology

Organophosphates can be absorbed
cutaneously, ingested, inhaled, or injected.
Although most patients rapidly become
symptomatic, the onset and severity of
symptoms depend on the specific compound,
amount, route of exposure, and rate of
metabolic degradation.
Causes


Agricultural exposure is the most common cause of
OPC and carbamate poisoning. The World Health
Organization (WHO) classifies these poisonings as class
I (extremely toxic) to class III (slightly hazardous). The
WHO advocates banning or strong restrictions on the
use of class I pesticides and a reduction in the use of
pesticides to a minimal number of compounds that are
less hazardous than others.
OPCs may also be encountered in the military setting
or the result of a terrorist attack with nerve agents such
as sarin, VX, or soman.
History

Patients usually have a history of OPCs or
carbamates exposure, either suicidal or
unintentional. Pesticides can rapidly be absorbed
through the skin, lungs, GI tract, and mucous
membranes. The rate of absorption depends on
the route of absorption and the type of OP or
carbamate. Symptoms usually occur within a few
hours after GI ingestion and appear almost
immediately after inhalational exposure.
History
Signs and symptoms of organophosphate
poisoning can be divided into 3 broad categories
 (1) muscarinic effects
 (2) nicotinic effects
 (3) CNS effects.
muscarinic effects

muscarinic effects of organophosphates are
SLUDGE (salivation, lacrimation, urination,
diarrhea, GI upset, emesis) and DUMBELS
(diaphoresis and diarrhea; urination; miosis;
bradycardia, bronchospasm, bronchorrhea;
emesis; excess lacrimation; and salivation).
Muscarinic effects by organ systems include the
following:
muscarinic effects
Cardiovascular - Bradycardia, hypotension
 Respiratory - Rhinorrhea, bronchorrhea,
bronchospasm, cough, severe respiratory distress
 Gastrointestinal - Hypersalivation, nausea and
vomiting, abdominal pain, diarrhea, fecal
incontinence
 Genitourinary - Incontinence
 Ocular - Blurred vision, miosis
 Glands - Increased lacrimation, diaphoresis

Nicotinic signs

Nicotinic signs and symptoms include muscle
fasciculations, cramping, weakness, and
diaphragmatic failure. Autonomic nicotinic
effects include hypertension, tachycardia,
mydriasis, and pallor.
CNS effects
CNS effects include anxiety, emotional lability,
restlessness, confusion, ataxia, tremors, seizures,
and coma.
Physical


Physical: Note that clinical presentation may
vary, depending on the specific agent, exposure
route, and amount. Symptoms are due to both
muscarinic and nicotinic effects.
Vital signs: Depressed respirations, bradycardia,
and hypotension are possible symptoms.
Alternatively, tachypnea, hypertension, and
tachycardia are possible. Hypoxia should be
monitored for with continuous pulse oximetry.
Paralysis


Type I: This condition is described as acute paralysis
secondary to continued depolarization at the neuromuscular
junction.
Type II (intermediate syndrome): Intermediate syndrome was
described in 1974 and is reported to develop 24-96 hours
after resolution of acute organophosphate poisoning
symptoms and manifests commonly as paralysis and
respiratory distress. This syndrome involves weakness of
proximal muscle groups, neck, and trunk, with relative
sparing of distal muscle groups. Cranial nerve palsies can also
be observed. Intermediate syndrome persists for 4-18 days,
may require mechanical ventilation, and may be complicated
by infections or cardiac arrhythmias. Although
neuromuscular transmission defect and toxin-induced
muscular instability were once thought to play a role, this
syndrome may be due to suboptimal treatment.
Paralysis

Type III: Organophosphate-induced delayed
polyneuropathy (OPIDP) occurs 2-3 weeks after
exposure to large doses of certain OPs and is
due to inhibition of neuropathy target esterase.
Distal muscle weakness with relative sparing of
the neck muscles, cranial nerves, and proximal
muscle groups characterizes OPIDP. Recovery
can take up to 12 months.
Physical



Neuropsychiatric effects: Impaired memory, confusion,
irritability, lethargy, psychosis, and chronic
organophosphate-induced neuropsychiatric disorders
have been reported. The mechanism is not proven.
Extrapyramidal effects: These are characterized by
dystonia, cogwheel rigidity, and parkinsonian features
(basal ganglia impairment after recovery from acute
toxicity).
Other neurological and/or psychological effects:
Guillain-Barré–like syndrome and isolated bilateral
recurrent laryngeal nerve palsy are possible.
Physical



Ophthalmic effects: Optic neuropathy, retinal
degeneration, myopia, and miosis (due to direct
ocular exposure to organophosphates) are
possible.
Ears: Ototoxicity is possible.
Respiratory effects: Muscarinic, nicotinic, and
central effects contribute to respiratory distress
in acute and delayed organophosphate toxicity.
Physical



Muscarinic effects: Bronchorrhea,
bronchospasm, and laryngeal spasm, for
instance, can lead to airway compromise.
Nicotinic effects: These effects lead to weakness
and paralysis of respiratory oropharyngeal
muscles.
Central effects: These effects can lead to
respiratory paralysis.
Physical


Rhythm abnormalities: Sinus tachycardia, sinus
bradycardia, extrasystoles, atrial fibrillation,
ventricular tachycardia, and ventricular
fibrillation (often a result of, or complicated by,
severe hypoxia from respiratory distress) are
possible.
Other cardiovascular effects: Hypotension,
hypertension, and noncardiogenic pulmonary
edema are possible
Physical
GI manifestations: Nausea, vomiting, diarrhea, and
abdominal pain may be some of the first
symptoms to occur after organophosphate
exposure.
Genitourinary and/or endocrine effects: Urinary
incontinence, hypoglycemia, or hyperglycemia
are possible.
Lab Studies
Organophosphate (OP) toxicity is a clinical diagnosis.
Confirmation of organophosphate poisoning is based
on the measurement of cholinesterase activity; typically,
these results are not readily available. Although RBC
and plasma (pseudo) cholinesterase levels can both be
used, RBC cholinesterase correlates better with CNS
acetylcholinesterase (AChE) and is, therefore, a more
useful marker of organophosphate poisoning.
Lab Studies


Falsely depressed levels of plasma cholinesterase
are observed in liver dysfunction, low-protein
conditions, neoplasia, hypersensitivity reactions,
use of certain drugs (succinylcholine, codeine,
morphine), pregnancy, and genetic deficiencies.
Other laboratory findings include leukocytosis,
hemoconcentration, metabolic acidosis,
hyperglycemia, hypokalemia, and
hypomagnesemia.
MEDICATION
The mainstays of medical therapy in
organophosphate (OP) poisoning include
atropine, pralidoxime (2-PAM), and
benzodiazepines (eg, diazepam). Initial
management must focus on adequate use of
atropine. Optimizing oxygenation prior to the
use of atropine is recommended to minimize the
potential for dysrhythmias.
Anticholinergic agents

These agents act as competitive antagonists at
the muscarinic cholinergic receptors in both the
central and the peripheral nervous system. These
agents do not affect nicotinic effects.
Anticholinergic agents
Atropine (Isopto, Atropair) -- Initiated in patients with OP
toxicity who present with muscarinic symptoms.
Competitive inhibitor at autonomic postganglionic cholinergic
receptors, including receptors found in GI and pulmonary
smooth muscle, exocrine glands, heart, and eye.
The endpoint for atropinization is dried pulmonary secretions
and adequate oxygenation. Tachycardia and mydriasis must not
be used to limit or to stop subsequent doses of atropine. The
main concern with OP toxicity is respiratory failure from
excessive airway secretions.
Anticholinergic agents


Adult Dose:1-2 mg IV bolus, repeated every 3-5 min
as needed for desire effects (drying of pulmonary
secretions and adequate oxygenation) Consider
doubling each subsequent dose for rapid control of
patients in severe respiratory distress
An atropine drip titrated to the above endpoints can be
initiated until the patient's condition is stabilized
Pediatric Dose:0.05 mg/kg IV, repeat every 3-5 min
as needed for control of airway secretions
Anticholinergic agents
Contraindications:Documented hypersensitivity;
narrow-angle glaucoma
Interactions:Coadministration with other anticholinergics
has additive effects
Pregnancy:C - Safety for use during pregnancy has not
been established.
Precautions:Care should be taken in coronary heart
disease, tachycardia, CHF, cardiac arrhythmias, and
hypertension; bladder catheterization may be required
because of urinary retention
Antidotes, OP poisoning
These agents prevent aging of AChE and reverse
muscle paralysis with OP poisoning.
Pralidoxime

Nucleophilic agent that reactivates the phosphorylated AChE by
binding to the OP molecule. Used as an antidote to reverse
muscle paralysis resulting from OP AChE pesticide poisoning
but is not effective once the OP compound has bound AChE
irreversibly (aged). Current recommendation is administration
within 48 h of OP poisoning. Because it does not significantly
relieve depression of respiratory center or decrease muscarinic
effects of AChE poisoning, administer atropine concomitantly to
block these effects of OP poisoning.
Signs of atropinization might occur earlier with addition of 2PAM to treatment regimen. 2-PAM administration is not
indicated for carbamate exposure since no aging occurs.
Pralidoxime
Adult Dose1-2 g (20-40 mg/kg) IV in 100 mL isotonic
sodium chloride soln/D5W over 15-30 min; repeat in 1
h if muscle weakness is not relieved; then repeat q3-8h
if signs of poisoning recur Other dosing regimens have
been used, including a continuous drip.
Pediatric Dose20-40 mg/kg in 100 mL isotonic
sodium chloride soln/D5W IV over 15-30 min; repeat
in 1-2 h if muscle weakness not relieved; repeat q1012h prn to relieve cholinergic symptoms
IM/SC can be used if IV not feasible; can be used with
atropine




Contraindications:Documented hypersensitivity
Interactions:Antagonism with neostigmine,
pyridostigmine, and edrophonium
Pregnancy:C - Safety for use during pregnancy has
not been established.
Precautions:2-PAM can cause brief adverse effects
such as dizziness and blurred vision; hypertension may
occur (increasing the infusion time to 30-40 min can
help reduce this effect)
Cyanide Toxicity
• Cyanide toxicity is generally considered to be a
rare form of poisoning; however, cyanide
exposure occurs relatively frequently in patients
with smoke inhalation from residential or
industrial fires. Cyanide poisoning also may occur
in industry, particularly in the metal trades,
mining, electroplating, jewelry manufacturing,
and radiographic film recovery. Cyanides are also
used as suicidal agents, particularly among
health-care and laboratory workers, and they can
potentially be used in a terrorist attack.
• Numerous forms of cyanide exist, including gaseous
hydrogen cyanide (HCN), water-soluble potassium and
sodium cyanide salts, and poorly water-soluble
mercury, copper, gold, and silver cyanide salts. In
addition, a number of cyanide-containing compounds,
known as cyanogens, may release cyanide during
metabolism. These include, but are not limited to,
cyanogen chloride and cyanogen bromide (gases with
potent pulmonary irritant effects), nitriles (R-CN), and
sodium nitroprusside, which may produce iatrogenic
cyanide poisoning during prolonged or high-dose
intravenous (IV) therapy (>10 mcg/kg/min).
• Finally, chronic consumption of cyanidecontaining foods, such as cassava root or
apricot seeds, may lead to cyanide poisoning.
• Overall, depending on its form, cyanide may
cause toxicity through parenteral
administration, inhalation, ingestion, or
dermal absorption.
Effects of cyanide consumption
• Chronic consumption of cyanide-containing
foods eventually can result in ataxia and optic
neuropathy. Defective cyanide metabolism
due to rhodanese deficiency may explain
development of Leber optic atrophy, leading
to subacute blindness. Cyanide also may cause
some of the adverse effects associated with
chronic smoking, such as tobacco amblyopia.
Etiology
• Cyanide affects virtually all body tissues, attaching
itself to ubiquitous metalloenzymes and rendering
them inactive. Its principal toxicity results from
inactivation of cytochrome oxidase (at cytochrome a3),
thus uncoupling mitochondrial oxidative
phosphorylation and inhibiting cellular respiration,
even in the presence of adequate oxygen stores.
Cellular metabolism shifts from aerobic to anaerobic,
with the consequent production of lactic acid.
Consequently, the tissues with the highest oxygen
requirements (brain and heart) are the most
profoundly affected by acute cyanide poisoning.
Smoke inhalation
• Smoke inhalation is an important source of
cyanide poisoning. Individuals with smoke
inhalation from enclosed space fires who have
soot in the mouth or nose, altered mental status,
or hypotension may have significant cyanide
poisoning (blood cyanide concentrations >40
mmol/L or approximately 1 mg/L).
• Many compounds containing nitrogen and carbon
may produce hydrogen cyanide (HCN) gas when
burned. Some natural compounds (eg, wool, silk)
produce HCN as a combustion product.
Intentional poisoning
• Cyanide ingestion is an uncommon, but
efficacious, means of suicide, often involving
cyanide salts found in hospital and research
laboratories. Not surprisingly, individuals in
certain occupations, such as health-care and
laboratory workers, are at risk for suicidal
ingestion of cyanides.
Industrial exposure
• Countless industrial sources of cyanides exist. Cyanides
serve an extremely important role in the metal plating
and recovery industries. In addition, industry uses
cyanides in the manufacture of plastics, as reactive
intermediates in chemical synthesis, and as solvents (in
the form of nitriles).
• Exposure to salts and cyanogens occasionally causes
poisonings; however, a significant risk for multiple
casualties occurs when these products come into
contact with mineral acids because HCN gas is
produced. Water contact with the soluble salts (eg,
potassium, sodium cyanide) also may liberate HCN.
Iatrogenic exposure
• Sodium nitroprusside, when used in high doses or
over a period of days, can produce toxic blood
concentrations of cyanide. Patients with low
thiosulfate reserves (eg, malnourished,
postoperative) are at increased risk for
developing symptoms, even with therapeutic
dosing. Resultant confusion and combativeness
initially may be mistaken as intensive care unit
(ICU) syndrome (ie, sundowning). Problems may
be avoided by coadministration of
hydroxocobalamin or sodium thiosulfate.
Ingestion of cyanide-containing
supplements
• Ingestion of cyanide-containing supplements is rare.
Amygdalin (synthetic laetrile, also marketed as vitamin
B-17) contains cyanide and can be found in the pits of
many fruits, such as apricots and papayas; in raw nuts;
and in other plants (lima beans, clover, and sorghum).
• The substance was thought to have anticancer
properties due to the action of cyanide on cancer cells.
However, laetrile showed no anticancer activity in
human clinical trials in the 1980s and is not available in
the United States, although it can be purchased on the
Internet.
Prognosis
• The prognosis in cyanide toxicity is reasonably
good if rapid supportive intervention and
effective antidotal therapy are provided.
Suicidal poisonings tend to have severe
outcomes because large doses are often
involved.
History
• The delay between exposure and the onset of
symptoms depends on the type of cyanide involved,
the route of entry, and the dose. Rapidity of symptom
onset, depending on the type of cyanide exposure,
occurs in the following order (most rapid to least
rapid): gas, soluble salt, insoluble salt, and cyanogens.
• A history of recent depression in the patient with
sudden collapse or altered mental status, acidosis, and
tachyphylaxis in the ICU patient on nitroprusside
should evoke suspicion of the diagnosis.
• Symptoms may include the following:
• General weakness, malaise, and collapse
• Neurologic symptoms (reflecting progressive
hypoxia) - Headache, vertigo, dizziness, giddiness,
inebriation, confusion, generalized seizures, coma
• Gastrointestinal symptoms - Abdominal pain,
nausea, vomiting
• Cardiopulmonary symptoms - Shortness of
breath, possibly associated with chest pain,
apnea
Physical Examination
• Vital signs are variable
• Initial bradycardia and hypertension - May rapidly
give way to hypotension with reflex tachycardia,
with resulting final bradycardia and hypotension
• Tachypnea - May generally precede apnea
• High, falsely reassuring pulse oximetry - Oxygen is
present in the blood as oxyhemoglobin but
cannot be effectively used in oxidative
phosphorylation
• Cherry-red skin color - Reflecting absent tissue
oxygen extraction
• Soot in the mouth and nose after smoke inhalation The possibility of cyanide poisoning is particularly
suggested if altered mental status and/or hypotension
are present; mydriasis and bright red retinal arteries
and veins (due to absent tissue oxygen extraction) may
be observed; the smell of bitter almonds on the breath
suggests exposure (cannot be detected by 60% of the
population)
• Cardiopulmonary symptoms - Include possible
cardiogenic pulmonary edema; aspiration can occur
with coma
• Neurologic symptoms may include the
following:
• Confusion, drunken behavior, ataxia
• Mydriasis
• Generalized convulsions
• Coma
Approach Considerations
• Arterial and venous blood gases
• Metabolic acidosis, often severe, combined with a
reduced arterial-venous oxygen saturation difference
(< 10%) suggests diagnosis. Apnea may result in
combined metabolic and respiratory acidosis.
• Blood lactate level
• A plasma lactate concentration of greater than 10
mmol/L in smoke inhalation or greater than 6mmol/L
after reported or strongly suspected pure cyanide
poisoning suggests significant cyanide exposure.
• Red blood cell and plasma cyanide concentration
• Carboxyhemoglobin level
• Evaluation of metabolic acidosis
• Methemoglobin level
• Methemoglobin concentrations provide a guide for
continued therapy after the use of methemoglobininducing antidotes, such as sodium nitrite.
• The presence of methemoglobin suggests little or no
free cyanide for binding because methemoglobin
vigorously binds cyanide to form cyanomethemoglobin
(not measured as methemoglobin).
• Elevated levels of methemoglobin (>10%) indicate that
further nitrite therapy is not indicated and, in fact, may
be dangerous.
Electrocardiography
• Electrocardiography may show nonspecific
changes, including the following:
• Atrioventricular blocks
• Supraventricular or ventricular arrhythmias
• Ischemic electrocardiographic changes and
eventual asystole
Medication
• Provide oxygen as the initial agent in suspected
or confirmed cyanide poisoning. Administer
sodium bicarbonate in severe poisoning because
of marked lactic acidosis. Decontaminate as
appropriate. Upon consideration of cyanide
toxicity diagnosis, immediately administer
antidotal therapy based on clinical criteria, even if
laboratory confirmation of cyanide poisoning has
not been received. Administer anticonvulsants as
indicated.
Cyanide Antidotes
• Sodium nitrite is the drug of choice in the United
States. It induces methemoglobin formation and
vasodilation.
• Sodium thiosulfate is a second-line therapy
because of its slower mechanism of action. It
regenerates sulfur-dependent rhodanese activity.
Coadminister sodium thiosulfate with or after
sodium nitrite or hydroxocobalamin (Cyanokit). It
is a useful adjunct in prolonged (cyanogen)
poisonings.
• Hydroxocobalamin contains cobalt ion, which is able to
bind to cyanide with greater affinity than cytochrome
oxidase to form cyanocobalamin (nontoxic), which is
excreted in urine. Hydroxocobalamin has few adverse
effects, is tolerated by critically ill patients, and is well
tolerated by patients with concomitant carbon
monoxide poisoning (no effect on the oxygen carrying
capacity of hemoglobin). In France, it commonly is
used in combination with sodium thiosulfate. Low-dose
hydroxocobalamin in combination with sodium
thiosulfate has been used successfully to prevent
cyanide toxicity due to prolonged sodium nitroprusside
infusions.
• Amyl nitrite is an alternative temporizing
therapy; it may be useful in the absence of IV
access (eg, in industrial settings).
• Anticonvulsants
• Alpha/Beta Adrenergic Agonists
These agents augment coronary and cerebral
blood flow during the low-flow states
associated with cyanide poisoning.
Alkalinizing Agents
Carbon Monoxide Poisoning
Background

Carbon monoxide (CO) is a colorless, odorless
gas produced by incomplete combustion of
carbonaceous material. Commonly overlooked
or misdiagnosed
Clinical

History
Misdiagnosis commonly occurs because of the
vagueness and broad spectrum of complaints;
symptoms often are attributed to a viral illness.
Specifically inquiring about possible exposures when
considering the diagnosis is important. Any of the
following should alert suspicion in the winter months,
especially in relation to the previously named sources
and when more than one patient in a group or
household presents with similar complaints. Symptoms
may not correlate well with HbCO levels.
‫منابع تولید‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫احتراق ناقص سوختهای فسیلی باعث تولید منواکسیدکربن‬
‫بجای دی اکسیدکربن میگردد‬
‫گاز زغال تا ‪ co %7‬دارد و موتورهای بنزینی در اگزوز‬
‫خود ‪ 5‬تا ‪ co %7‬تولید می کنند‬
‫در جریان آتش سوزیها و حریق علت فوت در بیشتر موارد‬
‫مسمومیت با منواکسید کربن است‬
‫در بعضی از فعالیتهای صنعتی مثل روش موند برای تولید‬
‫نیکل‪،‬تولید گاز آب در صنعت آهن و استیل ودر معادن‬
‫زغال سنگ احتمال مسمومیت با ‪ co‬وجود دارد‬
Pathophysiology


CO toxicity causes impaired oxygen delivery and
utilization at the cellular level. CO affects several
different sites within the body but has its most
profound impact on the organs (eg, brain, heart) with
the highest oxygen requirement.
Toxicity primarily results from cellular hypoxia caused
by impedance of oxygen delivery. CO reversibly binds
hemoglobin, resulting in relative anemia. Because it
binds hemoglobin 230-270 times more avidly than
oxygen, even small concentrations can result in
significant levels of carboxyhemoglobin (HbCO).
History
Acute poisoning

Malaise, flulike symptoms, fatigue

Dyspnea on exertion

Chest pain, palpitations

Lethargy

Confusion

Depression

Impulsiveness

Hallucination

Agitation

Nausea, vomiting, diarrhea

Abdominal pain

Headache, drowsiness

Dizziness, weakness, confusion

Visual disturbance, syncope, seizure

Fecal and urinary incontinence

Memory and gait disturbances

Bizarre neurologic symptoms, coma
History

Chronic exposures also present with the
above symptoms; however, they may present
gradual-onset neuropsychiatric symptoms,
or, simply, recent impairment of cognitive
ability.
Physical


Physical examination is of limited value. Inhalation injury or burns should
always alert the clinician to the possibility of CO exposure.
Vital signs






Tachycardia
Hypertension or hypotension
Hyperthermia
Marked tachypnea (rare; severe intoxication often associated with mild or
no tachypnea)
Skin: Classic cherry red skin is rare (ie, "When you're cherry red, you're
dead"); pallor is present more often .
Ophthalmologic




Flame-shaped retinal hemorrhages
Bright red retinal veins (a sensitive early sign)
Papilledema
Homonymous hemianopsia
Physical








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Noncardiogenic pulmonary edema
Neurologic and/or neuropsychiatric
Patients display memory disturbance (most common), including retrograde and
anterograde amnesia with amnestic confabulatory states .
Patients may experience emotional lability, impaired judgment, and decreased cognitive
ability .
Other signs include stupor, coma, gait disturbance, movement disorders, and rigidity .
Patients display brisk reflexes, apraxia, agnosia, tic disorders, hearing and vestibular
dysfunction, blindness, and psychosis .
Long-term exposures or severe acute exposures frequently result in long-term
neuropsychiatric sequelae. Additionally, some individuals develop delayed
neuropsychiatric symptoms, often after severe intoxications associated with coma .
After recovery from the initial incident, patients present several days to weeks later with
neuropsychiatric symptoms such as those just described. Two thirds of patients
eventually recover completely .
MRI changes may remain long after clinical recovery. Predicting and preventing longterm complications and delayed encephalopathy have been the object of recent studies,
many of which focus on the role of hyperbaric oxygen therapy
Diagnosis


Diagnosis is usually performed by measuring levels of carbon monoxide
bound in the blood. This can be determined by measuring
carboxyhemoglobin, which is a stable complex of carbon monoxide and
hemoglobin that forms in red blood cells. Carbon monoxide is produced
normally in the body, establishing a low background carboxyhemoglobin
saturation. Carbon monoxide also functions as a neurotransmitter. Normal
carboxyhemoglobin levels in an average person are less than 5%, whereas
cigarette smokers (two packs/day) may have levels up to 9%.
Serious toxicity is often associated with carboxyhemoglobin levels above
25%, and the risk of fatality is high with levels over 70%. Still, no consistent
dose response relationship has been found between carboxyhemoglobin
levels and clinical effects.Therefore, carboxyhemoglobin levels are more
guides to exposure levels than effects as they do not reliably predict clinical
course or short- or long-term outcome.
Pathophysiology



CO binds to cardiac myoglobin with an even greater
affinity than to hemoglobin; the resulting myocardial
depression and hypotension exacerbates the tissue
hypoxia.
CO binds to cytochromes c and P450 but with a much
lower affinity than that of oxygen
Studies have indicated that CO may cause brain lipid
peroxidation and leukocyte-mediated inflammatory
changes in the brain, a process that may be inhibited by
hyperbaric oxygen therapy
Pathophysiology

Recent studies have demonstrated release of
nitric oxide free radical (implicated in the
pathophysiology of atherosclerosis) from
platelet and vascular endothelium
Pregnancy
Carbon monoxide poisoning can have significant fetal effects. CO
causes fetal tissue hypoxia by decreasing the release of maternal
oxygen to the fetus, and by carbon monoxide crossing the
placenta and combining with fetal hemoglobin, which has a 10 to
15% higher affinity for CO than adult hemoglobin. Elimination
of carbon monoxide is also slower in the fetus, leading to an
accumulation of CO. The level of fetal morbidity and mortality
in acute carbon monoxide poisoning is significant, so despite
maternal wellbeing, severe fetal poisoning can still occur. Due to
these effects, pregnant patients are treated with normal or
hyperbaric oxygen for longer periods of time than non-pregnant
patients
‫مقدار مجاز ‪co‬‬
‫‪ ‬حد اکثر میزان مجاز ‪ co‬برای هشت ساعت کار در هوای‬
‫کارگاهها ‪ 25ppm‬می باشد‬
‫‪ ‬تماس ناگهانی با سطح ‪ 400ppm‬حداکثر تا ‪ 15‬دقیقه‬
‫مجاز است‬
‫‪ ‬غلظت بیش از ‪ 4000ppm‬مرگ ناگهانی می دهد‬
‫‪ ‬مسمومیت به دو عامل مقدار ‪ co‬در هوای محیط و مدت‬
‫زمان تماس بستگی دارد‬
‫‪ ‬درجه و شدت مسمومیت بر اساس میزان کربوکسی‬
‫هموگلوبین به نسبت هموگلوبین بدن است‬
Treatment
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Prehospital Care
Promptly remove from continued exposure and immediately institute oxygen therapy
with a nonrebreather mask.
Perform intubation for the comatose patient or, if necessary, for airway protection.
Institute cardiac monitoring. Pulse oximetry, although not useful in detecting HbCO,
is still important because a low saturation causes an even greater apprehension in this
setting.
Give notification for comatose or unstable patients because rapid or direct transfer to
a hyperbaric center may be indicated.
If possible, obtain ambient CO measurements from fire department or utility company
personnel, when present.
Early blood samples may provide much more accurate correlation between HbCO and
clinical status; however, do not delay oxygen administration to acquire them.
Obtain an estimate of exposure time, if possible.
Avoid exertion to limit tissue oxygen demand.
Emergency Department Care
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Cardiac monitor: Sudden death has occurred in patients with
severe arteriosclerotic disease at HbCO levels of only 20%.
Pulse oximetry: HbCO absorbs light almost identically to that of
oxyhemoglobin. Although a linear drop in oxyhemoglobin
occurs as HbCO level rises, pulse oximetry will not reflect it.
Pulse oximetry gap, the difference between the saturation as
measured by pulse oximetry and one measured directly, is equal
to the HbCO level.
Continue 100% oxygen therapy until the patient is asymptomatic
and HbCO levels are below 10%. In patients with cardiovascular
or pulmonary compromise, lower thresholds of 2% have been
suggested.
Emergency Department Care
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Calculate a gross estimate of the necessary duration of therapy
using the initial level and half-life of 30-90 minutes at 100%
oxygen. Complicated issues of treatment of fetomaternal
poisoning are discussed in Special Concerns.
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In uncomplicated intoxications, venous HbCO levels and oxygen therapy
are likely sufficient. Evaluate patients with significant cardiovascular
disease and initial HbCO levels above 15% for myocardial ischemia and
infarction.
Consider immediate transfer of patients with levels above 40% or
cardiovascular or neurologic impairment to a hyperbaric facility, if
feasible. Persistent impairment after 4 hours of normobaric oxygen
therapy necessitates transfer to a hyperbaric center.
Emergency Department Care
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Serial neurologic examinations, including funduscopy,
CT scans, and, possibly, MRI, are important in
detecting the development of cerebral edema. Cerebral
edema requires intracranial pressure (ICP) and invasive
blood pressure monitoring to further guide therapy.
Head elevation, mannitol, and moderate
hyperventilation to 28-30 mm Hg PCO2 are indicated
in the initial absence of ICP monitoring.
Glucocorticoids have not been proven efficacious, yet
the negative aspects of their use in severe cases are
limited.
Emergency Department Care
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Do not aggressively treat acidosis with a pH above 7.15
because it results in a rightward shift in the oxyhemoglobin
dissociation curve, increasing tissue oxygen availability.
Acidosis generally improves with oxygen therapy.
In patients who fail to improve clinically, consider other toxic
inhalants or thermal inhalation injury. Be aware that the
nitrites used in cyanide kits cause methemoglobinemia,
shifting the dissociation curve leftward and further inhibiting
oxygen delivery at the tissue level. Combined intoxications of
cyanide and CO may be treated with sodium thiosulfate 12.5
g intravenously to prevent the leftward shift.
Admit patients to a monitored setting and evaluate acid-base
status if HbCO levels are 30-40% or above 25% with
associated symptoms.
Hyperbaric oxygen therapy
o Certain studies proclaim major reductions in delayed
neurologic sequelae, cerebral edema, pathologic
central nervous system (CNS) changes, and reduced
cytochrome oxidase impairment.
Hyperbaric oxygen therapy
The most common selection criteria (regardless of HbCO
level) include the following
 Coma
 Transient loss of consciousness
 Ischemic ECG changes
 Focal neurologic deficits
 Abnormal neuropsychiatric testing
 HbCO levels above 40%
 Pregnancy with HbCO levels above 20%