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 distressAn 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 2-PAM 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 q10-12h prn to relieve cholinergic symptomsIM/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 cyanide-containing 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 methemoglobin-inducing 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.

تولید منابع

تولید باعث فسیلی سوختهای ناقص احتراقمیگردد اکسیدکربن دی بجای منواکسیدکربن

تا زغال در co% 7گاز بنزینی موتورهای و داردخود کنند co% 7تا 5اگزوز می تولید

در فوت علت حریق و سوزیها آتش جریان درکربن منواکسید با مسمومیت موارد بیشتر

است موند روش مثل صنعتی فعالیتهای از بعضی در

و آهن صنعت در آب گاز نیکل،تولید تولید برایاحتمال سنگ زغال معادن ودر استیل

با دارد coمسمومیت وجود

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 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 long-term 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

مجاز coمقدار

مجاز میزان اکثر کار coحد ساعت هشت برایکارگاهها هوای باشد ppm25در می

سطح با ناگهانی تا ppm400تماس 15حداکثراست مجاز دقیقه

از بیش می ppm4000غلظت ناگهانی مرگدهد

مقدار عامل دو به هوای coمسمومیت دردارد بستگی تماس زمان مدت و محیط

میزان اساس بر مسمومیت شدت و درجهبدن هموگلوبین نسبت به هموگلوبین کربوکسی

است

Treatment 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

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

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. 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

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

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

oCertain 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%