a) Methylene chloride is suspected of causing occupational heart disease, including coronary atherosclerosis, dysrhythmias and myopathy (Clayton & Clayton, 1994). Methylene chloride is also reported to produce engorgement of blood vessels of the brain and dilation of the heart (ILO, 1998).
b) CASE REPORT: A 24-year-old man was found unconscious 6.5 hours after applying one gallon of paint stripper (containing 70% to 85% dichloromethane, methanol, isopropyl alcohol, 2-butoxyethanol, and ethanol) to the floor of a baptismal font in a church. He did not respond to resuscitative efforts and was pronounced dead. During an autopsy, cardiomegaly with 4-chamber dilatation and coronary atherosclerosis with 50% occlusion of the left anterior descending artery were observed. Postmortem laboratory results showed a COHb of 10% and a blood dichloromethane concentration of 37.8 mg/dL. It was determined that dichloromethane poisoning, resulting in hypoxia and dysrhythmias, was the cause of death (Macisaac et al, 2013).

a) Myocardial ischemia and infarction related to methylene chloride use were reported (Harbison, 1998).
b) CASE REPORT - A 66-year-old man developed chest pain on three separate occasions after working with methylene chloride based paint remover in a poorly ventilated room. On the first two occasions he sustained acute myocardial infarctions; the second infarction was complicated by cardiogenic shock, dysrhythmias and congestive heart failure. On the third occasion he sustained a cardiac arrest prior to the arrival of paramedics (Stewart & Hake, 1976). Carboxyhemoglobin levels were not reported.

a) Hypotension followed by hypertension was reported in two patients after ingesting 300 to 350 mL methylene chloride (Chang et al, 1999).

a) Hypertension was reported in 3 of 6 patients who ingested 100 to 350 mL of methylene chloride (Chang et al, 1999).

a) Tachycardia (heart rate: 110 to 126 beats per minute) was reported in two patients following ingestion of 300 mL and 75 mL methylene chloride, respectively. The patient who had ingested 300 mL became comatose and died 9 days after ingestion (Chang et al, 1999).

a) Syncope has been reported (Fagin et al, 1980).

a) CASE REPORT: A 52-year-old man with a history of hyperlipidemia experienced a sudden cardiorespiratory arrest after refinishing a bathtub with an aircraft paint stripper (Tal-Strip II Aircraft coating remover) containing 60% to 100% methylene chloride. Resuscitation attempts were not successful Laboratory results revealed a blood methylene chloride concentration of 50 mg/L. An autopsy showed mild coronary atherosclerosis and mucus plugging of bronchi and bronchioles. It was estimated that 6 fluid ounces (177 mL) of methylene chloride-based stripper was used during a similar job and methylene chloride vapor concentration of 92,949 to 154,916 ppm in the bathtub and 5099 to 8499 ppm in the bathroom were estimated. It was determined that this patient was exposed to 637 to 1062 ppm of methylene chloride in the bathroom and 11,618 to 19,364 ppm of methylene chloride in the tub during 1 hour of exposure (OSHA's short-term exposure limit: 125 ppm; 8-hour permissible exposure limit: 25 ppm; NIOSH immediately dangerous to life and health level: 2300 ppm). An investigation revealed that at least 13 professional bathtub refinishers died while using methylene chloride based products on bathtubs in bathrooms with inadequate ventilation between the years 2000 and 2010 (Centers for Disease Control and Prevention (CDC), 2012).

a) Smokers who have a history of angina or coronary artery disease, and who have moderate or high methylene chloride exposure may be at risk of adverse cardiovascular effects. Smokers exposed to the methylene chloride vapor concentrations equal to or exceeding the current permissible workplace exposure limit have had carboxyhemoglobin levels of 15% or greater (US DHHS, 1990).

a) Cough, chest discomfort and dyspnea may develop after inhalation (Snyder et al, 1992; Buie et al, 1986; Nager & O'Connor, 1998) and after ingestion (Chang et al, 1999).

a) Prolonged exposure can result in shortness of breath, painful cough, and possibly pulmonary edema (ILO, 1998).
b) Acute lung injury (pulmonary edema) has been reported after severe inhalation exposure and has been found at autopsy (Buie et al, 1986; Winek et al, 1981; Snyder et al, 1992; Manno et al, 1992; Leikin et al, 1990; Tay et al, 1995). However, it is not common (US DHHS, 1990).
c) CASE SERIES - After ingestion, 1 of 6 patients developed pulmonary edema (Chang et al, 1999).

a) Respiratory failure may develop secondary to CNS depression in severe exposures (Manno et al, 1990; (Chang et al, 1999).
b) CASE REPORT - Sudden death occurred to a 27-year-old male following inhalation of a paint stripping agent containing 77% methylene chloride, which was being used in a poorly ventilated area. The main autopsy findings showed bilateral pulmonary congestion and edema, petechiae in the lungs, and portal inflammation of the liver. Methylene chloride levels in the blood and pulmonary exudate were 140 and 540 mg/L, respectively. The combination of the autopsy findings and the lab analysis of the biological fluids established the cause of death as asphyxia secondary to inhalation of fumes from a cleaning agent containing methylene chloride (Zarrabeitia et al, 2001).
c) CASE REPORT - A 22-year-old male died while removing lacquer, in a poorly ventilated area, using a solvent containing 84% methylene chloride. An autopsy showed facial erythema, petechial bleeding of the ocular conjunctiva and visceral pleura, acute dilatation of the right heart ventricle, and pulmonary and cerebral edema. Methylene chloride levels in the blood of the left and right heart ventricles and in pulmonary tissue were 5420 mcg/mL, 4590 mcg/mL, and 7280 mcg/mL, respectively. It is believed that death occurred due to asphyxiation following inhalation of excessive amounts of methylene chloride fumes in a poorly ventilated workplace (Fechner et al, 2001).

a) Absorption occurs easily through the lungs (Raffle et al, 1994). Physical exertion increases absorption of methylene chloride, as well as its conversion to carbon monoxide with subsequent elevation of the carboxyhemoglobin levels (Harbison, 1998).

a) Exposure to methylene chloride may cause a number of neurologic symptoms, including headache, giddiness, light-headedness, dizziness, euphoria, irritability, loss of appetite, sleepiness, weakness, fatigue, stupor, convulsions, numbness, anesthesia and limb dysesthesias (ILO, 1998; ACGIH, 1991; Baselt, 1997; Budavari, 1996). The central nervous system depressant effects have reportedly produced fatalities (Baselt, 1997).
b) CASE REPORT: A 45-year-old man developed nausea and vomiting, and lost consciousness after using a commercial solvent containing methylene chloride for stripping wall paint. Following oxygen therapy, he regained consciousness, and presented to the ED with drowsiness, headache, neck pain, and numbness in the right thumb and index finger. An ECG, chest x-ray, and all laboratory results were normal; however, his carboxyhemoglobin (COHb) level was 8.7% (normal, less than 5% in nonsmokers), which increased to 17.3% the following day. Non-contrast computed axial tomographic scan of the head showed subtle bilateral hypodensities in globus pallidus. Following supportive care, including 2 sessions of hyperbaric oxygen therapy (46 minutes each at 2.8 atmospheres) on day 1 and 2, his condition improved gradually (Cabrera et al, 2011).
c) Headaches, dizziness, nausea, and throat irritation were reported in 11 soldiers following inhalational exposure to a paint stripping agent containing methylene chloride (dichloromethane) while working in a small closed room. All 11 soldiers recovered with supportive therapy (Jacubovich et al, 2005).
d) COMBINATION INGESTION - A man developed altered mental status and toxic hepatitis after ingesting approximately half of the content of a 250-mL bottle of chloroform and dichloromethane. Following supportive care, he gradually recovered and was discharged 2 weeks after ingestion (Kim, 2008).
e) COMBINATION EXPOSURE: A 37-year-old chemist with a 5-year history of headaches, dizziness, and fatigue due to a long-term inhalational exposure to dichloromethane and iodomethane, presented with ataxia, increasing inhibition, dizziness, dysarthria, and a confusional and delirious state a day after distilling dichloromethane and iodomethane at work. His symptoms deteriorated in the next several hours and his lethargy progressed to stupor and shallow coma, with episodes of confusion, restlessness, and aggression. All laboratory tests and a CT scan were normal. An MRI scan of the brain revealed the presence of a T2-hyperintense lesion in the splenium of the corpus callosum, suggestive of myelinolysis. His symptoms gradually improved and a repeat MRI of the brain 16 days later revealed complete resolution of all lesions in the corpus callosum as well as in the cerebellar hemispheres (Ehler et al, 2011).

a) Coma has been reported (Ehler et al, 2011).
b) High concentrations of methylene chloride produce an anesthetic effect that ranges from fatigue to light-headedness, drowsiness and unconsciousness; there is a narrow margin of safety between mild and severe effects (ILO, 1998).
c) Methylene chloride is a general anesthetic. All phases of anesthesia may develop after exposure, beginning with excitation up to and including coma and death (Leikin et al, 1990; Hall & Rumack, 1990) Rioux & Myers; 1989; (Budavari, 1996). Generally methylene chloride induced CNS depression is reversible. Victims typically regain consciousness within several hours, except in cases of hypoxic encephalopathy (Chang et al, 1999).
d) CASE SERIES: Chang et al (1999) reported on six patients who ingested methylene chloride. All six developed some degree of CNS depression, ranging from somnolence and weakness to deep coma.

a) Acute inhalation of methylene chloride vapors commonly produces dizziness, headache and drowsiness (Cabrera et al, 2011; Ehler et al, 2011) (Rioux & Myers, 1988) (Leikin et al, 1990; Rudge, 1990; Hall & Rumack, 1990). These and other CNS effects are generally transient, resolving after exposure has ceased (Lash et al, 1991).
b) CASE REPORT - A 26-year-old male reported headaches after repeated workplace exposure to methylene chloride (Mahmud & Kales, 1999).
c) CASE SERIES - Mild light-headedness that resolved within 5 minutes of exposure occurred in three persons exposed for 1 hour to concentrations of 868 to 1,000 ppm (Stewart et al, 1972).
d) CASE SERIES - Forty-six workers exposed to methylene chloride (75 to 100 ppm) reported significantly more neurological complaints (e.g., headache, dizziness, incoordination) than did 12 unexposed workers. Persistent CNS effects were not clinically measurable in a follow-up of 29 of the exposed workers (Cherry et al, 1981).
e) CASE SERIES - No statistically significant increase in complaints of dizziness or recurring severe headaches were reported in a group of 150 workers chronically exposed for 10 or more years to methylene chloride (average 475 ppm 8 hr Time Weighted Average), as compared to unexposed workers (Soden, 1993).

a) Ataxia may occur with exposure (Ehler et al, 2011).

a) ALTERED HEARING/VISION/SMELL - Short-term (e.g. 3 to 4 hours) inhalation of vapors equal to or in excess of 300 ppm may cause temporarily decreased hearing and vision (US DHHS, 1993).

a) ORGANIC BRAIN SYNDROME has been reported following occupational exposure.

a) PSYCHOMOTOR SLOWING has been reported following acute exposures.

a) Paresthesias of the extremities as well as neurasthenic disorders are symptoms of methylene chloride exposure (ACGIH, 1991; ITI, 1995).
b) CASE SERIES - No statistically significant excess reports of paresthesias were reported in 150 workers chronically exposed for 10 or more years to methylene chloride (average 475 ppm 8 hr Time Weighted Average), as compared to unexposed workers (Soden, 1993).
c) CASE REPORT - Left-sided paresthesias were reported in a 52-year-old female following inhalation of a spray paint containing methylene chloride (Nager & O'Connor, 1998).

a) CASE SERIES - No significantly abnormal EEGs, motor nerve conduction velocities and psychological test results were identified in 29 workers chronically exposed to methylene chloride vapors ranging from 75 to 100 ppm (Cherry et al, 1981).
b) CASE SERIES - No statistically significant abnormalities in physiological (e.g., smell, color vision, grip strength, evoked response) and psychological functions (e.g. task performance, memory, attention, spatial ability) were reported in a study of 25 retired airline mechanics previously exposed for an average of 23.8 years to methylene chloride vapors (82 to 826 ppm), as compared to 21 retired unexposed workers (Lash et al, 1991).

a) A 21-year-old soldier reported headache, dizziness, and nausea 2 hours after 3 hours of exposure, in a small closed room, to a paint stripping agent containing methylene chloride (dichloromethane). Ten other soldiers also reported headache, dizziness, and throat irritation following exposure to the paint stripping agent. Following supportive care, the 21-year-old soldier's symptoms resolved. The next morning, the patient presented with peripheral facial nerve palsy with weakness and asymmetry of the left side of his face. Laboratory data revealed normal kidney and liver function, O2 saturation of 98%, and serial blood carboxyhemoglobin levels of 0.3% to 0.4%. His facial palsy resolved following supportive therapy. The ten other soldiers exposed to the paint stripping agent did not report the development of peripheral facial palsy. It is unclear whether methylene chloride was the causative agent, however due to the patient's lack of other medical risk factors and the temporal association with methylene chloride exposure, a causal relationship cannot be ruled out (Jacubovich et al, 2005).

a) Nausea and vomiting are common after inhalation exposure (Cabrera et al, 2011; Jacubovich et al, 2005; ITI, 1995; Rudge, 1990; Rioux & Myers, 1989; Nager & O'Connor, 1998) and ingestion (Chang et al, 1999). Loss of appetite is due to CNS depression(ILO, 1998).

a) Ingestion of methylene chloride has caused death from gastrointestinal hemorrhage (Morgan, 1993).
b) CASE REPORT - Duodenal and jejunal ulcers with associated hemorrhage developed in a 38-year-old man after ingesting one to two pints of a methylene-chloride- based paint remover. Six months later diverticula developed in the areas of ulceration (Hughes et al, 1976).
c) CASE SERIES - Corrosive gastrointestinal injury was reported in two of six patients with methylene chloride ingestion. Two of three patients undergoing panendoscopic examination showed corrosive GI injury patterns. All of the patients reported GI symptoms (Chang et al, 1999).

a) CASE SERIES - Pancreatitis was reported in one of six patients after methylene chloride ingestion (Chang et al, 1999). The exact mechanism is unknown, but may be either a direct effect of the toxin or a result of pancreatic hypoperfusion.

a) One case of hepatitis and several cases of elevated hepatic enzymes have been reported, but significant hepatotoxicity is unlikely with exposures that are within the current occupational exposure limits (US DHHS, 1990).

a) Liver disease has been reported after occupational exposure to methylene chloride (ACGIH, 1991). Ingestion has resulted in severe liver damage (Morgan, 1993).

a) For rats, the liver is a primary target organ; increased hepatocellular vacuolization and increased multinuclear hepatocytes have been reported after exposure to methylene chloride by inhalation or by ingestion via drinking water (ACGIH, 1991).

a) Ingestion of methylene chloride has caused renal injury (Morgan, 1993). Hematuria is unusual but has been reported after ingestion and inhalation (Keogh et al, 1984; Miller et al, 1985) Hughes et al, 1976; (Chang et al, 1999).

a) CASE REPORT: Hematuria and acute tubular necrosis developed in a 19-year-old male after working with methylene chloride based tile remover in a poorly ventilated room (Miller et al, 1985).
b) CASE SERIES: Acute tubular necrosis was reported in two of six patients after methylene chloride ingestion (Chang et al, 1999). The authors speculate that the necrosis may be related to either a direct effect of methylene chloride or to renal hypoperfusion.

a) CASE REPORT: A 16-year-old woman developed Goodpasture's syndrome associated with occupational exposure to hydrocarbon fumes, including methylene chloride and trichloroethane(Keogh et al, 1984).

a) The toxic effects of methylene chloride exposure are related in part to its conversion to carbon monoxide, which yields increased concentrations of carboxyhemoglobin in the blood (Cabrera et al, 2011; Morgan, 1993; Baselt, 1997). In general, the concentrations are usually not high enough to produce symptoms of carbon monoxide poisoning (Morgan, 1993), however there is a report of a carboxyhemoglobin level of 35% in a patient who subsequently developed persistent hypotension and hypoxemia, became comatose, and died approximately 9 days after intentionally ingesting 300 mL of methylene chloride (Chang et al, 1999).
b) The increase in carboxyhemoglobin is directly proportional to the magnitude of the vapor exposure. Significant amounts of carbon monoxide and carboxyhemoglobin were produced in humans exposed to 500 to 1,000 ppm methylene chloride (ACGIH, 1991).
c) CASE REPORT: A 24-year-old man was found unconscious 6.5 hours after applying one gallon of paint stripper (containing 70% to 85% dichloromethane, methanol, isopropyl alcohol, 2-butoxyethanol, and ethanol) to the floor of a baptismal font in a church. He did not respond to resuscitative efforts and was pronounced dead. During an autopsy, cardiomegaly with 4-chamber dilatation and coronary atherosclerosis with 50% occlusion of the left anterior descending artery were observed. Postmortem laboratory results showed a COHb of 10% and a blood dichloromethane concentration of 37.8 mg/dL. It was determined that dichloromethane poisoning, resulting in hypoxia and dysrhythmias, was the cause of death (Macisaac et al, 2013).
d) CASE REPORT: A 65-year-old man was found unconscious 2.5 hours after entering an empty paint-mixing tank and using a chemical paint stripper containing 60% to 100% dichloromethane, 10% to 30% methanol, and 1% to 5% Stoddard solvent. Another worker, a 45-year-old man, entered the tank to rescue him, but he also lost consciousness. Both men were removed from the tank an hour later, but the first man did not respond to resuscitative efforts and was pronounced dead. Postmortem laboratory results showed a COHb concentration below the limit of detection (less than 5%) and a blood dichloromethane concentration of 220 mg/dL. On presentation, the second patient had a pulse rate of 100 beats/min, a blood pressure of 118/68 mmHg, and he was combative with a GCS 1-4-1. Laboratory analysis showed a respiratory acidosis (pH of 7.32, pCO2 51 mmHg), a COHb concentration of 4%, an osmol gap of 17 mOsm/kg (normal less than 10 mOsm/kg), and serum methanol concentration of 15.1 mg/dL (normal less than 1.5). Following supportive care, his mental status improved after 4 hours and he was extubated. His COHb concentrations continued to increase for the first 24 hours to a peak concentration of 10.2%, but returned to normal after about 60 hours and he was discharged on day 4 (Macisaac et al, 2013).
e) CASE REPORT: A 23-year-old man developed altered mental status and toxic hepatitis after ingesting approximately half of the content of a 250-mL bottle of chloroform and dichloromethane. His blood carboxyhemoglobin concentration was 8.9% (Ref range, nonsmokers 0% to 1.9%; smokers, 1.9% to 4.9%). Following supportive care, he gradually recovered and was discharged 2 weeks after ingestion (Kim, 2008).
f) CASE REPORT: Carboxyhemoglobin levels up to 12.1% developed in an adult female after ingestion of an estimated 300 mL of a product (Nitromors) that contained methylene chloride, methanol, cellulose acetate, triethanolamine, paraffin wax and detergents (Hughes & Tracey, 1993).
g) CASE SERIES: In a study of volunteers exposed to 200 ppm for 7.5-hour work days, the maximum carboxyhemoglobin concentration was 6.8% (DiVincenzo & Kaplan, 1981).
h) CASE SERIES: A one- to two-hour exposure of 11 nonsmokers to 500 to 1,000 ppm produced increased carboxyhemoglobin levels of up to 15%. Carboxyhemoglobin was increased for 17 to 24 hours in some individuals (Stewart et al, 1972).
i) CASE REPORT: Occupational exposure to methylene chloride resulted in dose-related increases in carboxyhemoglobin (Ott et al, 1983).
j) CASE REPORT (ADULT) - Carboxyhemoglobin concentrations of 26% and 40% were reported after the use of methylene-chloride-containing paint removers (Langehennig et al, 1976).
k) CASE SERIES: Chang et al (1999) documented carboxyhemoglobin levels of 35% and 8.4%, respectively, in 2 patients after ingestion of methylene chloride.
l) CASE SERIES - Carboxyhemoglobin levels of 12% to 20.4% were reported in 4 patients exposed to a personal defense spray containing 49% methylene chloride and 0.8% CS after the contents were discharged into a closed space. Associated symptoms included headache, dizziness, and nausea. All recovered uneventfully after treatment with 100% normobaric oxygen (Duenas et al, 2000).
m) Carboxyhemoglobin concentrations as high as 50% have been reported (Fagin et al, 1980; Langehennig et al, 1976).
n) Smokers who are exposed to methylene chloride concentrations of 500 ppm or greater have had carboxyhemoglobin levels of 15% or greater (US DHHS, 1990).

a) In rats and mice exposed to methylene chloride at 200, 500, or 1000 ppm for 12-hour periods, the conversion to carboxyhemoglobin was saturable and no greater than after 8 hours of exposure (Kim & Carlson, 1986).

a) Contact with liquid methylene chloride produces pain, skin irritation, and burns if the liquid is not removed (ACGIH, 1991). Immersion can result in pain and numbness (Harbison, 1998).
b) Extreme dryness and fissuring may occur due to the 'degreasing' action of the solvent (Harbison, 1998). Methylene chloride is mildly irritating to skin with repeated contact. This problem is accentuated if the chemical is 'sealed' to skin by shoes or tight clothing, and is most severe with paint remover formulations that form a 'skin' or film (Clayton & Clayton, 1994).

a) Dry scaly dermatitis is an effect of exposure to methylene chloride (Lewis, 1998).

a) Skin irritation and burns are an effect of exposure to methylene chloride (ITI, 1998). Severe chemical burns have been reported with prolonged skin contact or immersion (Raffle et al, 1994; Hall & Rumack, 1990; Tay et al, 1995).

a) Although methylene chloride can be absorbed through the skin sufficiently to cause systemic symptoms, chlorinated hydrocarbons are considered to be poorly absorbed through the skin (Zenz, 1994; Harbison, 1998).

a) Listed as: Dichloromethane (methylene chloride)
b) Carcinogen Rating: 2A

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.

a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).

a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).

a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).

a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.

a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).

a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).

a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).

a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

a) The methylene chloride blood concentration in a 47-year-old male following a fatal inhalational exposure was 150 milligrams/liter (Goulle et al, 1999). In another fatal exposure, the methylene chloride concentration was 510 mg/L (Baselt, 1997).
b) Blood levels should not exceed 1 mg/L methylene chloride in workers exposed to 100 ppm methylene chloride, and blood carboxyhemoglobin should not exceed 5 percent (Baselt, 1997).
c) The post mortem methylene chloride blood concentration was 281 milligrams/liter in a worker who died after inhalation and dermal exposure to a paint stripper containing 75% methylene chloride, 8% methanol, 2% hydrofluoric acid and 3% o-dichlorobenzene while working in a tank. Autopsy revealed cerebral edema, mucosal hemorrhages in the larynx, hemorrhagic shock lung with congestion and pulmonary edema, fatty liver and partial thickness burns of 25% to 30% BSA (Tay et al, 1995).
d) CASE REPORT: A 52-year-old man with a history of hyperlipidemia experienced a sudden cardiorespiratory arrest after refinishing a bathtub with an aircraft paint stripper (Tal-Strip II Aircraft coating remover) containing 60% to 100% methylene chloride. He was found unconscious in the bathroom and died at the hospital. Laboratory results revealed a blood methylene chloride concentration of 50 mg/L. An autopsy showed mild coronary atherosclerosis and mucus plugging of bronchi and bronchioles. It was estimated that 6 fluid ounces (177 mL) of methylene chloride-based stripper was used during a similar job and methylene chloride vapor concentration of 92,949 to 154,916 ppm in the bathtub and 5099 to 8499 ppm in the bathroom were estimated. It was determined that this patient was exposed to 637 to 1062 ppm of methylene chloride in the bathroom and 11,618 to 19,364 ppm of methylene chloride in the tub during 1 hour of exposure (OSHA's short-term exposure limit: 125 ppm; 8-hour permissible exposure limit: 25 ppm; NIOSH immediately dangerous to life and health level: 2300 ppm) (Centers for Disease Control and Prevention (CDC), 2012).
e) CASE SERIES: Dichloromethane blood concentrations of 2 workers who died following inhalational exposure to paint stripping agents containing 60% to 100% of dichloromethane, were 37.8 mg/dL and 220 mg/dL, respectively (Macisaac et al, 2013).
f) In one study, 42 bathtub stripping products from the Internet and several hardware stores contained 60% to 100% methylene chloride. OSHA has reported 13 bathtub refinisher fatalities associated with methylene chloride stripping agents in 9 states from 2000 to 2011. Blood methylene chloride concentrations of 6 patients ranged from 18 to 223 mg/L (Centers for Disease Control and Prevention (CDC), 2012).
g) Methylene chloride concentrations in the lung tissue of two workers, who died following inhalation of paint stripping agents containing 77% and 84% methylene chloride, were 540 mg/L and 7280 mcg/mL, respectively. The methylene chloride concentration in the blood of the worker exposed to 77% methylene chloride was 140 mg/L. The methylene chloride concentrations of the blood from the left and right heart ventricles, of the other worker, were 5420 mcg/mL and 4590 mcg/mL, respectively (Fechner et al, 2001; Zarrabeitia et al, 2001).

1) Dichloromethane

a) TWA:
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): See Appendix A

a) IDLH: 2300 ppm
b) Note(s): Ca

a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

a) B2 : Probable human carcinogen - based on sufficient evidence of carcinogenicity in animals.

a) 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

a) Category 3A : Substances for which the criteria for classification in Category 4 or 5 are fulfilled but for which the database is insufficient for the establishment of a MAK value.

a) 8-hour TWA:

a) 8-hour TWA:
b) Acceptable Ceiling Concentration:
c) Acceptable Maximum Peak above the Ceiling Concentration for an 8-hour Shift:
d) Notation(s): Not Listed

a) 16,000 ppm for 7H plus 1H observation (HSDB, 2002)

a) 437 mg/kg

a) 873 mg/kg

a) 6460 mg/kg

a) 916 mg/kg
b) 2000 ppm (OHM/TADS, 2002)

a) 1600 mg/kg -- ataxia
b) 14D old, 2385 mg/kg (Hayes, 1991)
c) young adult, 2120 mg/kg (Hayes, 1991)
d) older adult, 3047 mg/kg (Hayes, 1991)
e) 1600 mg/kg (HSDB, 2002)
f) 3000 mg/kg (HSDB, 2002)

a) 500 ppm for 1Y - intermittent -- altered sleep time; somnolence; change in heart rate
b) 500 ppm for 8H -- behaviorial changes

a) 2000 ppm for 5H/2Y - continuous -- carcinogenic; tumors
b) Female, 1250 ppm for 7H at 6-15D of pregnancy -- musculoskeletal system abnormalities
c) 150 ppm for 24H/30D - continuous -- changes in liver, spleen weight; biochemical changes
d) 300 ppm for 24H/90D - continuous -- liver and spleen weight changes; biochemical changes
e) 13,000 ppm for 6H/19D - intermittent -- death
f) 5000 ppm for 24H/7D - continuous -- liver weight changes; weight loss or decreased weight gain

a) Female, 4500 ppm for 24H at 1-17D of pregnancy -- behavioral effects on newborn
b) 3500 ppm for 6H/2Y - intermittent -- carcinogenic; tumors
c) 500 ppm for 6H/2Y (Lewis, 2000)
d) 1000 ppm for 2H/3W - intermittent -- behavioral, liver, and blood changes
e) 5000 ppm for 24H/14W - continuous -- liver changes; chages in tubules and bladder weight
f) 8400 ppm for 6H/13W - intermittent -- changes in liver wright; death
g) 500 ppm for 6H/2W - intermittent -- kidney, ureter and bladder changes; blood and biochemical changes
h) 3700 ppm for 5H/4W - intermittent -- biochemical changes; lung, thorax, or respiration changes
i) 1000 ppm for 6H/3D - intermittent -- brain and coverings changes; biochemical effects