350 SECTION 13 • TOXICOLOGY PYRETHRINS • Pyrethrins block the sodium channel at the neu- ronal cell membrane, causing repetitive neuronal discharges. Pyrethrins most commonly cause hy- persensitivity responses, which include broncho- spasm and anaphylaxis. They may produce der- mal, pulmonary, gastrointestinal (GI), and neurologic findings. HERBICIDES • Toxicity of herbicides, which are pesticides used to kill weeds, leads to a wide variety of symptoms generally based upon which organ system has been exposed. • Chlorphenoxy compounds may cause tachycardia, dysrhythmias, and hypotension, and muscle toxic- ity manifested by muscle pain, fasciculations, and rhabdomyolysis. • Common bipyridial herbicides are paraquat and diquat. Paraquat is especially toxic with caustic effects resulting in severe dermal, corneal, and mucous membrane burns, including the respira- tory and GI epithelium. Cardiovascular collapse may occur early, especially in the case of large ingestions, and results in pulmonary edema, renal failure, hepatic necrosis, and multisystem organ failure. Metabolic acidosis is due to hypoxemia and multisystem organ failure. • Urea-substituted compounds are much less toxic than other herbicides and generally cause few systemic effects other than methemoglo- binemia. RODENTICIDES • Sodium monofluoroacetate, a commercial exter- minator compound, is converted to a metabolite, fluorocitrate, which interferes with the Krebs cycle. Signs and symptoms of toxicity include nausea, lactic acidosis, respiratory depression, cardiovascular collapse, and altered mental status. • Strychnine toxicity results from its competitive an- tagonism of the inhibitory neurotransmitter gly- cine at the postsynaptic spinal cord motor neuron. Signs and symptoms of strychnine toxicity include facial grimacing, muscle twitching, severe extensor spasms, and opisthotonos; it eventually may lead to medullary paralysis and death. • Thallium sulfate is absorbed through the skin, by inhalation, and through the GI tract. Exposure to thallium sulfate initially causes GI hemorrhage followed by a latent period, in turn succeeded by the development of neurologic symptoms, respira- tory failure, and dysrhythmias. • Zinc phosphide ingestion results in the liberation of phosphine gas, which subsequently causes GI irritation, hepatocellular toxicity, direct pulmo- nary injury (if the gas is inhaled), cardiovascular collapse, altered mental status, seizures, and non- cardiogenic pulmonary edema. • Yellow phosphorous causes severe topical burns to areas of contact and also may cause jaundice, seizures, and cardiovascular collapse. • ANTU exhibits primarily pulmonary effects with dyspnea, pleuritic chest pain, and noncardiogenic pulmonary edema, while cholecalciferol causes the typical symptoms of vitamin D excess. • Red squill poisoning is a low-toxicity rodenticide that presents as severe GI distress and cardiac dysrhythmias. • The most common low-toxicity agent poison- ing occurs with superwarfarins and related compounds. Superwarfarins inhibit vitamin K– dependent clotting factors. Exposures most com- monly come to attention on a delayed basis with symptoms of an unexplained coagulopathy. DIAGNOSIS AND DIFFERENTIAL • The diagnosis of pesticide poisoning is made on the basis of the history and physical examination in the majority of cases. • In the case of organophosphate poisoning, an assay of both serum and red blood cell cholinester- ase activity can be obtained for diagnosis and to guide treatment, though results seldom become available for decision making in the emergency de- partment. • Nausea, vomiting, and cardiac dysrhythmia sug- gest red squill toxicity. • In the case of superwarfarin ingestion, determina- tion of the prothrombin time at 24 and 48 h is recommended. EMERGENCY DEPARTMENT CARE AND DISPOSITION • The mainstay of treatment for pesticide exposure is identification of the specific agent involved and supportive monitoring and treatment. CHAPTER 111 • PESTICIDES 351 TABLE 111-1 Pesticides and Specific Antidotes PESTICIDE ANTIDOTE DOSING Organophosphates Atropine 0.5 mg/kg up to 2–4 mg IV q 5–15 min—consider IV infusion and titrate to effect (drying secretions) 2-PAM 20–40 mg/kg up to1gIV—mayrepeat in 1–2 h, then every 6–8 h for 48 h Carbamates Atropine As for organophosphates 2-PAM Use is controversial and may be contraindicated Urea-substituted herbicides Methylene blue As for treatment of methemoglobinemia Zinc phosphide NaHCO 3 Used for intragastric alkalinization Yellow phosphorous K Permanganate or H 2 O 2 Used for gastric lavage Arsenic Heavy metal chelators As for heavy metal poisoning Red squill Antidysrhythmics, Fab fragments As for digoxin toxicity Superwarfarins Vitamin K Up to 20 mg IV, repeated and titrated to effect A BBREVIATIONS :IVϭ intravenous; 2-PAM ϭ pralidoxime. • Symptomatic patients require attention to airway protection and ventilation with supplemental oxy- gen to maintain saturation to Ն95%. Tracheal in- tubation and mechanical ventilation with high ox- ygen concentrations may be necessary in severe poisoning. Maintenance of intravascular volume and urine output should be assured. • Meticulous attention to patient decontamination (dermal, ocular, or GI) is important as is preven- tion of absorption by the patient and caretakers involved in patient care. • Administration of a specific antidote may be ap- propriate for selected individual agents (Table 111-1). • Pralidoxime (2-PAM) displaces organophos- phates from the cholinesterases. It restores cholin- esterase activity and detoxifies the remaining or- ganophosphate molecules. Clinically, 2-PAM ameliorates the CNS, nicotinic, and muscarinic ef- fects. • Disposition depends upon the pesticide involved in the exposure. Asymptomatic patients with a history of contact with a pesticide may require decontamination and a 6- to 8-h observation pe- riod only. Close follow-up should be arranged for patients with exposure to rodenticides that pro- duce symptoms on a delayed basis. • A low threshold for admission should be main- tained for patients with intentional ingestions. Any patient with a history of paraquat or diquat exposure should be admitted because of the ex- treme lethality of these compounds. Consider- ation for admission to the intensive care unit is an individual one based upon the specific toxin involved and the overall clinical picture of the pa- tient. B IBLIOGRAPHY Bismuth C, Garnier R, Dally S, et al:Prognosisandtreatment of paraquat poisoning: A review of 28 cases. J Toxicol Clin Toxicol 19:46, 1982. Chi CH, Chen KW, Chan SH, et al: Clinical presentation and prognostic factors in sodium monofluoroacetate intox- ication. J Toxicol Clin Toxicol 34:707, 1996. Freedman MD: Oral anticoagulants: Pharmacodynamics, clinical indications, and adverse effects. J Clin Pharmacol 32:196, 1992. Lipton RA, Klass EM: Human ingestion of ‘‘superwarfarin’’ rodenticide resulting in prolonged anticoagulant effect. JAMA 252:3004, 1988. Litovitz TL, Klein-Schwartz W, Dyer KS, et al: Annual Re- port of the American Association of Poison Control Cen- ters toxic exposure surveillance system. Am J Emerg Med 16:443, 1998. Onyon LJ, Volans GN: The epidemiology and prevention of paraquat poisoning. Hum Toxicol 6:19, 1987. Saadeh AM, Al-Ali MK, Farsakh NA: Clinical and sociode- mographic features of acute carbamate and organophos- phate poisoning: A study of 70 adult patients in North Jordan. Clin Toxicol 34:45, 1996. Smolinske SC, Scherger DL, Kearns PC, et al: Superwarfarin poisoning in children: A prospective study. Pediatrics 84:490, 1989. Vale JA, Meredith TJ, Buckley BM: Paraquat poisoning: Clinical features and immediate general management. Hum Toxicol 6:41, 1987. For further reading in Emergency Medicine: A Com- prehensive Study Guide, 5th ed., see Chap. 176, ‘‘Insecticides, Herbicides, Rodenticides,’’ by Walter C. Robey III and William J. Meggs. 352 SECTION 13 • TOXICOLOGY 112 CARBON MONOXIDE AND CYANIDE M. Chris Decker CARBON MONOXIDE EPIDEMIOLOGY • Carbon monoxide (CO) is responsible for more morbidity and mortality than any other toxin. • CO is formed from the incomplete combustion of fossil fuel or tobacco and as a metabolite of methylene chloride (paint remover). • CO toxicity is more common in northern climates and during winter months. PATHOPHYSIOLOGY • CO—which binds to hemoglobin, myoglobin, and cytochromes P450 and AA3—competes with oxy- gen for binding sites and prevents oxygen utili- zation. • CO binds to hemoglobin about 210 to 280 times more tenaciously than oxygen. The binding of CO to hemoglobin shifts the oxyhemoglobin dissocia- tion curve to the left. Therefore, carboxyhemoglo- bin (COHb) holds on to oxygen at lower oxy- gen tensions. • When CO binds to mitochondrial cytochromes, it stops the electron chain reaction and prevents oxidative phosphorylation. • Poisoning of the myocardial myoglobin reduces cardiac contractility, cardiac output, and oxygen delivery. • White blood cells adhere to CO-poisoned tissue. Upon reperfusion of those tissues, the white blood cells accelerate lipid peroxidation. This is termed reperfusion injury. • The half-life of COHb is 320 min when a patient is breathing room air, 60 min when breathing 100% normobaric oxygen, and 23 min when breathing 100% hyperbaric oxygen at 2.8 atmospheres of pressure. CLINICAL FEATURES • High oxygen-extracting organs such as the brain and heart easily become dysfunctional from CO intoxication. • The clinical picture at the site of poisoning often corresponds to the severity of poisoning and to on-scene COHb levels (Table 112-1). • Symptoms and signs are worse in situations where neurologic and myocardial oxygen demand in- creases, such as trauma, burns, drug ingestion, and increased activity. • Fetuses and neonates are particularly susceptible to the toxic effects of the gas due to the presence of fetal hemoglobin and an oxygen dissociation curve that is already shifted to the left. Children are frequently affected and make up almost 40 percent of patients treated with hyperbaric oxy- gen therapy. DIAGNOSIS AND DIFFERENTIAL • The primary key to the diagnosis is maintaining a high degree of clinical suspicion. • The most useful laboratory test is the determina- tion of the COHb level. Pulse oximetry may be normal in CO poisoning. • Psychometric testing can detect subtle deficits in mental status and assess for indications for hyper- baric oxygen therapy. • In cases of symptomatic exposure, an electrocar- diogram (ECG) and cardiac enzyme determina- tions are suggested. Chest radiographs are gener- ally obtained for fire victims, and other pulmonary function testing may be helpful as well. • The differential diagnosis is extremely broad and includes a wide variety of toxins, infectious agents, and cardiac/pulmonary diseases as well as the host of causes for altered mental status. Particularly in colder months, patients with headache, nausea, weakness, fatigue, difficulty in concentrating, diz- ziness, chest pain, and abdominal pain must be evaluated with CO toxicity in mind. • Victims of house fires with appropriate symptoms TABLE 112-1 Symptoms and Signs at Various Carboxyhemoglobin Concentrations COHb LEVEL(%) SYMPTOMS AND SIGNS 0 Usually none 10 Frontal headache 20 Throbbing headache, dyspnea with exertion 30 Impaired judgment, nausea, dizziness, visual disturbances, fatigue 40 Confusion, syncope 50 Coma, seizures 60 Hypotension, respiratory failure Ն70 Death CHAPTER 112 • CARBON MONOXIDE AND CYANIDE 353 and signs must be evaluated specifically for CO poisoning. EMERGENCY DEPARTMENT CARE AND DISPOSITION • Emergent priorities remain airway, breathing, and circulation. Cardiac monitoring and an IV line should be instituted. Oxygen (100%) should be administered through a tight-fitting mask. • Table 112-2 outlines appropriate treatment guide- lines for CO poisoning. • Hyperbaric oxygen (HBO) therapy is indicated for severe poisoning based upon clinical findings and the COHb level. The goal of treatment is not only amelioration of the acute event but also to prevent delayed neuropsychiatric sequelae. HBO should be carefully considered, especially for patients at the extremes of age and in preg- nancy. CYANIDE EPIDEMIOLOGY • Cyanide is found in large amounts in certain nuts, plants, and fruit pits in the form of cyanogenic glycoside. Sodium nitroprusside contains cyanide. • Acute cyanide poisonings occur in the following settings: (1) inadvertent occupational exposure TABLE 112-2 CO Poisoning Treatment Guidelines Mild poisoning Criteria COHb levels Ͻ30% No symptoms or signs of impaired cardiovascular or neurologic function May have complaint of headache, nausea, vomiting Treatment 100% oxygen by tight-fitting nonrebreathing mask until COHb level remains Ͻ5% Admission for COHb level of Ͼ25% Admission for patients with underlying heart disease regardless of COHb level Moderate poisoning Criteria COHb levels 30–40% No symptoms or signs of impaired cardiovascular or neurologic function Treatment 100% oxygen by tight-fitting nonrebreathing mask until COHb level remains Ͻ5% Cardiovascular status followed closely even in asymptomatic patients, consider ECG and cardiac en- zymes Determination of acid-base status (will be corrected by high-flow oxygen) Admission for observation and cardiovascular monitoring Severe poisoning Criteria COHb levels Ͼ40% or Cardiovascular or neurologic impairment at any COHb level Treatment 100% oxygen by tight-fitting nonrebreathing mask Cardiovascular function monitoring Determination of acid-base status Admission or Transfer to a HBO facility immediately if available or if no improvement in cardiovascular or neuro- logic function within 4 h (inhalation of hydrogen cyanide gas used in the production of solvents, enamels, paints, glues, wrinkle-resistant fabrics, herbicides, pesticides, and fertilizers and in electroplating); (2) inhalation of smoke from burning plastics in closed-space fires; (3) inadvertent, suicidal, or homicidal inges- tion; (4) iatrogenic toxicity due to infusion of so- dium nitroprusside; (5) ingestion of plant products containing cyanogenic glycosides. PATHOPHYSIOLOGY • Cyanide disrupts oxidative phosphorylation by binding to cytochrome A3 and blocks the ability of tissues to use oxygen, which leads to anaerobic metabolism. Anaerobic metabolism results in the accumulation of lactic acid and a metabolic aci- dosis. CLINICAL FEATURES • The most common modes of poisoning are inhala- tion, oral ingestion, and dermal contact. Absorp- tion of cyanide gas is immediate. Ingestion of cya- nide salts produces symptoms within minutes. Ingestion of cyanogenic compounds produces symptoms within hours. • The hallmark of cyanide poisoning is apparent hypoxia without cyanosis. 354 SECTION 13 • TOXICOLOGY • Metabolic acidosis is prominent, with high lactate levels due to failed oxygen utilization. • Awake patients complain of breathlessness and anxiety. In more severe cases, loss of conscious- ness (often with seizures) and tachydysrhythmias are apparent, which may proceed on to bradycar- dia and apnea and finally asystolic cardiac arrest. • Other clues to cyanide toxicity are bright red reti- nal blood vessels, oral burns from ingestions, the smell of bitter almonds on the patient’s breath, and high peripheral venous oxygen saturations (acyanosis). DIAGNOSIS AND DIFFERENTIAL • The diagnosis of cyanide toxicity should always be considered in the poisoned patient with profound metabolic acidosis. Further support for the diag- nosis is any finding suggesting decreased oxygen utilization. Arterial blood gas assays can identify acid-base disturbances and the presence of an oxy- gen saturation gap, while serum lactate levels may provide additional supporting evidence. • The differential diagnosis includes other cellular toxins such as carbon monoxide, hydrogen sulfide, and simple asphyxiants. In the setting of an inges- tion, other possibilities are methanol, ethylene gly- col, iron, and salicylates. Severe isoniazid or co- caine poisoning may mimic the effects of cyanide, causing severe metabolic acidosis and seizures. • Iatrogenic thiocyanate toxicity may occur in a pa- tient who is on nitroprusside and becomes enceph- alopathic or complains of tinnitus. Thiocyanate levels Ͼ100 mg/L support the diagnosis. EMERGENCY DEPARTMENT CARE AND DISPOSITION • Emergent priorities remain airway, breathing, and circulation. Cardiac monitoring and an IV line should be instituted. Those with altered mental status must be considered for IV glucose, thia- mine, and naloxone administration. • Gastric lavage and administration of activated charcoal are standard for cyanide ingestion; der- mal contacts require skin decontamination, and inhalational exposures require removal from the source. • Specific treatment with nitrite-thiosulfate antidote therapy in the form of a kit from Taylor Pharma- ceuticals must be considered (Table 112-3). Asymptomatic patients or those with minimal symptoms should be observed and treated only TABLE 112-3 Treatment of Cyanide Poisoning CHILDREN 1. 100% oxygen 2. Administration of IV sodium nitrite and sodium thiosulfate: Hb (g/100 mL) 3% NaNO 2 (mL/kg) 25% Na 2 S 2 O 3 (mL/kg) 7 0.19 1.65 8 0.22 1.65 9 0.25 1.65 10 0.27 1.65 11 0.30 1.65 12 0.33 1.65 13 0.36 1.65 14 0.39 1.65 3. May repeat once at half dose if symptoms persist. 4. Monitor methemoglobin to keep level less than 30% ADULTS 1. 100% oxygen. 2. Amyl nitrite; crack and inhale 30 s/min.* 3. Sodium nitrite: 10 mL IV (10-mL ampule of 3% solution ϭ 300 mg). 4. Sodium thiosulfate: 5 mL IV (50-mL ampule of 25% solution ϭ 12.5 g). 5. May repeat once at half dose if symptoms persist. * Administration of amyl nitrite is necessary only if venous access has not been obtained. if clinical deterioration is noted. Severely toxic patients with a clear history of exposure demand full and immediate treatment. • Due to the potential side effects of hypotension and induction of methemoglobinemia, hypoten- sive acidotic patients without clear cyanide toxic- ity or with smoke inhalation are best served by administration of IV sodium thiosulfate only. B IBLIOGRAPHY Bozeman WP, Myers RAM, Barish RA: Confirmation of the pulse oximetry gap in carbon monoxide poisoning. Ann Emerg Med 30:608, 1997. Caravati EM, Adams CJ, Joyce SM, Schafer NC: Fetal toxic- ity associated with maternal carbon monoxide poisoning. Ann Emerg Med 17:714, 1988. Chen KK, Rose CL: Nitrite and thiosulfate therapy in cya- nide poisoning. JAMA 149:113, 1952. Curry SC, Arnold-Capell P: Toxic effects of drugs used in the ICU: Nitroprusside, nitroglycerine, and angiotensin- converting enzyme inhibitors. Crit Care Clin 7:555, 1991. Gorman DF, Clayton D, Gilligan JE, Webb RK: A longitudi- nal study of 100 consecutive admissions for carbon monox- ide poisoning to the Royal Adelaide Hospital. Anesth In- tens Care 20:311, 1992. Hall AH, Rumack BH: Clinical toxicology of cyanide. Ann Emerg Med 15:1607, 1986. Kirk MA, Gerace R, Kulig KW: Cyanide and methemoglo- CHAPTER 113 • HEAVY METALS 355 bin kinetics in smoke inhalation victims treated with the cyanide antidote kit. Ann Emerg Med 22:1413, 1993. Kulig K: Cyanide antidotes and fire toxicology. N Engl J Med 325:1801, 1991. Merridith T, Vale A: Carbon monoxide poisoning, BMJ 296:77, 1988. Messeir LD, Myers RAM: A neuropsychological screening battery for emergency assessment of carbon monoxide- poisoned patients. J Clin Psychol 47:675, 1991. Scheinkestel CD, Jones K, Cooper DJ, et al: Interim analy- sis—Controlled clinical trial of hyperbaric oxygen in acute carbon monoxide (CO) poisoning. Undersea Hyperbar Med 23(suppl):7, 1996. Thom SR, Keim L: Carbon monoxide poisoning, a review: Edipemiology, pathophysiology, clinical findings and treatment options including hyperbaric oxygen therapy. Clin Toxicol 27:141, 1989. Thom SR, Taber RL, Mendiguren II, et al: Delayed neurop- sychologic sequelae after carbon monoxide poisoning: Pre- vention by treatment with hyperbaric oxygen. Ann Emerg Med 25:474, 1995. Tibbles PM, Perrotta PL: Treatment of carbon monoxide poisoning: A critical review of human outcome studies comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med 24:269, 1994. Way JL, Leung P, Cannon E, et al: The mechanisms of cyanide intoxication and its antagonism. Ciba Found Symp 140:232, 1988. For further reading in Emergency Medicine: A Com- prehensive Study Guide, 5th ed., see Chap. 198, ‘‘Carbon Monoxide Poisoning,’’ by Keith W. Van Meter, and Chap. 182, ‘‘Cyanide,’’ by Kathleen Delaney. 113 HEAVY METALS Lance H. Hoffman LEAD • Lead is the most common cause of chronic metal poisoning, affecting approximately 890,000 chil- dren, ages 1 to 5 years, with a blood lead level of 10 Ȑg/dL or more. 1 • Lead toxicity should be considered in patients with a combination of central nervous system (CNS) symptoms (e.g., delirium, seizures, coma, and memory deficit), abdominal symptoms (e.g., col- icky pain, constipation, and diarrhea), or hemato- logic manifestations (e.g., hypoproliferative or he- molytic anemia). • Serum lead levels Ͼ10 Ȑg/dL are diagnostic of lead toxicity. Radiographic evidence of lead toxic- ity includes horizontal, metaphyseal bands on long bones, especially involving the knee, and radi- opaque material in the alimentary tract. • Chelation therapy is the mainstay of treatment in patients with encephalopathy or children with lead levels greater than 45 Ȑg/dL. Dimercaprol (BAL) 3 to 5 mg/kg intramuscularly (IM) every 4 h and CaNa2-EDTA 1500 Ȑg/m 2 every 24 h by continu- ous intravenous infusion beginning4hafter the ini- tial BALdoseare the standardagents.Radiopaque lead material in the alimentary tract requires whole-bowel irrigation for decontamination. • Admission is indicated for all symptomatic pa- tients, asymptomatic children with lead levels Ͼ45 Ȑg/dL, and patients who would otherwise return to the environment of lead exposure. ARSENIC • Arsenic is the most common cause of acute metal poisoning and the second most common cause of chronic metal poisoning. It is found in agricultural chemicals and contaminated well water, and it is used in mining and smelting. • Arsenic inhibits pyruvate dehydrogenase, inter- feres with the cellular uptake of glucose, and un- couples oxidative phosphorylation. 2 • Acute arsenic toxicity results in nausea, vomiting, severe diarrhea, and hypotension a few hours after the exposure. Chronic arsenic toxicity presents as generalized weakness, malaise, morbilliform rash, and an ascending, stocking-glove sensory or motor peripheral neuropathy. • Evaluation may reveal Mee lines (1 to 2 mm trans- verse, white lines on the nails), prolonged QT interval on electrocardiogram, and radiopaque ar- senic in the alimentary tract. 3 • Volume resuscitation is used to treat hypotension. Cardiac tachydysrhythmias are best treated with lidocaine and bretylium; class Ia, Ic, and III anti- dysrhythmics should be avoided since they may worsen QT prolongation. • Chelation therapy with BAL 3 to 5 mg/kg IM every 4 h should be instituted in suspected arsenic toxicity. Whole-bowel irrigation is needed if arse- nic is present in the alimentary tract on abdomi- nal radiographs. MERCURY • Short-chained alkyl mercury compounds and ele- mental mercury predominantly affect the CNS, 356 SECTION 13 • TOXICOLOGY producing erethism, which includes anxiety, de- pression, irritability, mania, sleep disturbances, shyness, and memory loss. 4 Tremor is also common. 5 • Mercury salts spare the CNS, but cause a corrosive gastroenteritis resulting in abdominal pain and cardiovascular collapse with a high likelihood of acute tubular necrosis within a day of inges- tion. • All forms of mercury, except the short-chained alkyl mercury compounds, produce the immune- mediated condition in children called acrodynia, consisting of a generalized rash, irritability, hypo- tonia, and splenomegaly. • Mercury inhalation produces a pneumonitis, acute respiratory distress syndrome, and progressive pulmonary fibrosis. 6 • Although BAL is contraindicated in short-chained alkyl mercury compound toxicity because it may exacerbate CNS symptoms, it is the chelator of choice for mercury salts. Dimercaprol should be administered 3 to 5 mg/kg IM every 4 h, in addi- tion to initial gastric decontamination. • Dimercaptosuccinic acid is gaining favor as the treatment of choice for short-chained alkyl mer- cury compound toxicity. 7 R EFERENCES 1. Pirkle JL, Brody DJ, Gunter EW, et al: The decline of blood lead levels in the United States: The National Health and Nutrition Examination Surveys. JAMA 272:284, 1994. 2. Leibl B, Muckter H, Doklea E, et al: Reversal of oxyphe- nylarsine-induced inhibition of glucose uptake in MDCK cells. Fund Appl Toxicol 27:1, 1995. 3. Hilfer RJ, Mandel A: Acute arsenic intoxication diag- nosed by roentgenograms. N Engl J Med 266:633, 1962. 4. Eto K: Pathology of Minamata disease. Toxicol Pathol 25:614, 1997. 5. Taueg C, Sanfilippo DJ, Rowens B, et al: Acute and chronic poisoning from residential exposures to elemen- tal mercury—Michigan 1989-1990. J Toxicol Clin Tox- icol 30:63, 1992. 6. Lim HE, Shim JJ, Lee SY, et al: Mercury inhalation poisoning and acute lung injury. Korean J Intern Med 13:127, 1998. 7. Roels HA, Boeckx M, Ceulemans E, et al: Urinary excre- tion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3- dimercaptosuccinic acid (DMSA). Br J Ind Med 48: 247, 1991. For further reading in Emergency Medicine: A Com- prehensive Study Guide, 5th ed., see Chap. 178, ‘‘Metals and Metalloids,’’ by Marsha D. Ford. 114 HAZARDOUS MATERIALS EXPOSURE Joseph J. Randolph EPIDEMIOLOGY • A hazardous material is any substance (chemical, nuclear, or biologic) that poses a risk to health, safety, property, or the environment. • Eighty percent of events occur at fixed facilities, 20 percent are transportation related, and over 10 percent occur within hospitals and schools. 1 • Sixty-five percent of fatalities result from associ- ated trauma, 22 percent from burns, and 10 per- cent from respiratory compromise. 2 • Most injuries and deaths are associated with expo- sure to chlorine, ammonia, nitrogen fertilizer, or hydrochloric acid. Other commonly involved chemicals include petroleum products, pesticides, corrosives, metals, and volatile organic com- pounds. 2 • Data on involved chemicals are essential. Re- sources include regional poison centers, material safety data sheets, transportation-specific mark- ings [Department of Transportation (DOT) placards, shipping papers], private agencies (CHEMTREC), government agencies [National Regulatory Commission, Center for Disease Con- trol, Environmental Protection Agency (EPA), and ATSDR], computer databases (Poisindex, Safetydex, Tomes Plus, ToxNet), and the in- ternet. 3–5 EMERGENCY DEPARTMENT CARE AND DISPOSITION • Triage occurs outside the hospital where both ur- gency of care and adequacy of decontamination are assessed. Under no circumstances is a patient allowed into the hospital unless fully decontami- nated. CHAPTER 114 • HAZARDOUS MATERIALS EXPOSURE 357 • Level A attire (fully encapsulated chemical-resis- tant suit and self-contained breathing apparatus) is recommended by the EPA when the concentra- tion or identity of toxins is unknown (most hazard- ous incidents). • Medical stabilization prior to decontamination should be limited to opening the airway, cervical spine stabilization, oxygen administration, ventila- tory assistance, and application of direct pressure to arterial bleeding. • Decontamination is performed in three ‘‘zones.’’ The ‘‘hot zone’’ is the area at the scene or outside the hospital where patients with no prior decon- tamination are held. The ‘‘warm zone’’ is the area outside (or physically isolated from) the hospital where decontamination occurs. The ‘‘cold zone’’ is where fully decontaminated victims are trans- ferred. There should be no movement of person- nel between zones. • Access to the hot and warm zones is restricted to personnel with suitable protective clothing (in- cluding, but not limited to, a chemical-resistant suit and self-contained breathing apparatus when the highest level of protection is needed). • Removing all clothing and brushing away gross particulate matter begins decontamination. Whole-body irrigation is then initiated with copious amounts of water and mild soap or de- tergent, except in cases where water-reactive substances (lithium, sodium, potassium, calcium, lime, calcium carbide, and others) may be involved. • The hands and face are generally the most contam- inated; decontamination should begin at the head and work downward, taking care to avoid runoff onto other body parts. Decontamination should continue for at least 3 to 5 min. Patients should then be wrapped in clean blankets and transferred to the cold zone. SPECIFIC MEDICAL MANAGEMENT INHALED TOXINS • This group includes gases, fumes, dusts, and aero- sols, resulting in upper airway damage or pulmo- nary toxicity. Specific agents include phosgene, chlorine, ammonia, and riot control agents (mace and pepper spray). • Oxygen and bronchodilators should be adminis- tered, along with examination of the upper airway for respiratory compromise. Patients should be intubated if they develop respiratory distress or airway edema. • Riot control agents [including capsaicin (CS) used by law enforcement and mace (CN) sold for self- protection] result in self-limited irritation of ex- posed mucous membranes and skin. NEUROTOXINS • The most likely neurotoxins are the nerve agents. Five organophosphate compounds are recognized as nerve agents: tabun (GA), sarin (GB), soman (GD), GF, and VX. • These agents inhibit acetylcholinesterase, result- ing in build-up of acetylcholine at brain synapses (causing seizures and coma), motor endplates (causing weakness, paralysis, and respiratory in- sufficiency), and the autonomic nervous system (causing salivation, lacrimation, urination, diar- rhea, bronchorrhea, and miosis). • Treatment consists of complete decontamination, oxygen administration, administration of atropine 2 mg and pralidoxime (2-PAMCL) 600 mg intrave- nously (IV) or intramuscularly (IM), and support- ive care. DERMAL TOXINS • Dermal toxins include alkalis (sodium hydroxide and cement), phenol, hydrofluoric acid, and vesi- cants [mustard (sulfur mustard; H; HD), Lewisite (L), and phosgene oxime (CX)]. These agents cause significant pulmonary toxicity and ocular toxicity. • Skin decontamination with large volumes of water is the mainstay of treatment. • Hydrofluoric acid burns result in dysrhythmias, seizures, local tissue destruction, and electrolyte abnormalities. Treatment consists of intravenous (IV) calcium or magnesium as well as topical cal- cium gluconate gel. • Injection of calcium gluconate into the affected area at a maximum of 0.5 mL/cm 2 of tissue may be considered for intractable pain to neutralize the fluoride ion. Intraarterial calcium through a radial artery line has been recommended for digi- tal burns. OCULAR EXPOSURES • Ocular exposures demand immediate irrigation with large volumes of water. Prehospital irrigation 358 SECTION 13 • TOXICOLOGY for up to 20 min prior to transport (in stable pa- tients) is recommended. Gross particulate matter should be brushed from around the eye, and con- tact lenses should be removed. • Absence of pain may not indicate cessation of ocular damage, and irrigation should continue un- til ocular pH returns to 7.4. • Visual acuity, fluorescein staining, and slit-lamp evaluation are indicated, with ophthalmologic consultation in all but the most trivial of expo- sures. BIOLOGIC WEAPONS • Biologic weapons include microbes (anthrax, plague, tularemia, Q fever, and viruses), mycotox- ins (trichothecene), and bacterial toxins (ricin, staphylococcal enterotoxin B, botulinum, and shi- gella). • Biologic agents used as weapons are almost invari- ably delivered by droplet (aerosol) spread, re- sulting in fulminant infectious complications after a variable incubation period. • Anthrax spores are stable and easy to cultivate and have become an agent of choice among terrorist groups. After an incubation period of 1 to 6 days, infected patients develop fever, myalgia, cough, chest pain, and fatigue. Hemorrhagic meningitis and necrotizing hemorrhagic mediastinitis also are seen. Treatment involves IV ciprofloxacin or doxycycline. • Botulism, the most potent toxin known, exerts its effects through entering presynaptic cholinergic neurons and blocking acetylcholine release. Fol- lowing an incubation period of 24 to 36 h, bulbar palsies, diplopia, ptosis, mydriasis, and dysphagia develop. A classic descending, symmetric skeletal muscle paralysis ensues, followed by respiratory failure and death. The diagnosis is clinical, and treatment is directed primarily at providing respi- ratory support. • Sodium hypochlorite 0.5% solution (household bleach diluted 1 : 9 with water) is effective at neu- tralizing most biohazard materials and should be used for patient decontamination. R EFERENCES 1. Chemical Manufacturer’s Association, FAX Back Docu- ment Number 104. 2. Phelps AM, Morris P, Giguere M: Emergency events in- volving hazardous substances in North Carolina, 1993– 1994. N Carolina Med J 59(2):120, 1998. 3. Burgess JL, Keifer MC, Barnhart S, et al: Hazardous materials exposure information service: Development, analysis, and medical implications. Ann Emerg Med 29(2):248, 1997. 4. Tong TG: Role of the regional poison center in hazardous materials accidents, in Sullivan JB, Kreiger GR (eds): Hazardous Materials Toxicology: Clinical Principles of Environmental Health. Baltimore, Williams & Wilkins, 1992, pp 396–401. 5. Greenberg MI, Cone DC, Roberts JR: Material Safety Data Sheet: A useful resource for the emergency physi- cian. Ann Emerg Med 27(3):347, 1996. For further reading in Emergency Medicine: A Com- prehensive Study Guide, 5th ed., see Chap. 181, ‘‘Hazardous Materials Exposure,’’ by Suzanne R. White and Edward M. Eitzen, Jr. 115 DYSHEMOGLOBINEMIAS Alex G. Garza METHEMOGLOBINEMIA PATHOPHYSIOLOGY • Methemoglobinemia is acquired when the normal mechanisms responsible for the elimination of methemoglobin are overwhelmed by an exoge- nous oxidant stress, such as a drug or chemical agent. • At present, most cases of methemoglobinemia are due to phenazopyridine (Pyridium), benzocaine (topical anesthetic), and dapsone (antibiotic often used in HIV-related therapy). • Methemoglobinemia can affect any age group but, due to an underdeveloped methemoglobin reduc- tion mechanism, the prenatal and infant age groups are more susceptible. Another common cause of acquired infantile methemoglobinemia is gastroenteritis. CLINICAL FEATURES • The clinical suspicion of methemoglobinemia should be raised when the patient’s pulse oximetry CHAPTER 115 • DYSHEMOGLOBINEMIAS 359 approaches 85 percent, there is no response to supplemental oxygen, and brownish-blue skin and ‘‘chocolate-brown’’ blood discoloration are noted. • Patients with normal hemoglobin concentrations do not develop clinically significant effects until the methemoglobin levels rise to about 15 percent of the total hemoglobin. • Patients may seek evaluation for the profound cyanosis that occurs when the methemoglobin concentration reaches about 1.5 g/dL. • At methemoglobin levels between 15 to 30 percent, symptoms such as anxiety, headache, weakness, and light-headedness develop, and patients may exhibit tachypnea and sinus tachy- cardia. • Methemoglobin levels of 50 to 60 percent impair oxygen delivery to vital tissues, resulting in myo- cardial ischemia, dysrhythmias, depressed mental status (including coma), seizures, and lactic acido- sis. Levels above 70 percent are largely incompati- ble with life. • Anemic patients may not exhibit cyanosis until the methemoglobin level rises dramatically above 10 percent, because it is the absolute concentra- tion, not the percentage of methemoglobin, that determines cyanosis. Anemic patients may like- wise suffer significant symptoms at lower methe- moglobin concentrations because the relative per- centage of hemoglobin in the oxidized form is greater. • Patients with preexisting diseases that impair oxy- gen delivery to red blood cells (e.g., chronic ob- structive pulmonary disease and congestive heart failure) will manifest symptoms with less signifi- cant elevations of methemoglobin levels. • Conditions that shift the oxyhemoglobin dissocia- tion curve to the right, such as acidosis or elevated 2,3-DPG, may result in somewhat better tolera- tion of methemoglobinemia. DIAGNOSIS AND DIFFERENTIAL • Pulse oximetry cannot distinguish oxyhemoglobin from methemoglobin. It may read an inappropri- ately normal value in patients with moderate methemoglobinemia, and it may trend toward 85 percent in patients with severe methemoglo- binemia. • Definitive identification of methemoglobinemia relies on co-oximetry. • The oxygen saturation obtained from a conven- tional arterial blood gas analyzer also will be falsely normal because it is calculated from the dissolved oxygen tension, which may be appropri- ately normal. EMERGENCY DEPARTMENT CARE AND DISPOSITION • Patients with methemoglobinemia require opti- mal supportive measures to ensure oxygen de- livery. • The efficacy of gastric decontamination is limited due to the substantial time interval from exposure to development of methemoglobin. If an on-going source of exposure exists, a single dose of oral activated charcoal is indicated. • Therapy with methylene blue is reserved for those patients with documented methemoglobinemia or a high clinical suspicion of the disease. Unstable patients should receive methylene blue, but may require blood transfusion or exchange transfusion for immediate enhancement of oxygen delivery. The initial dose of methylene blue is 1 to 2 mg/ kg intravenously (IV), and its effect should be seen within 20 min. If necessary, repeat dosing of methylene blue is acceptable, but high doses (Ͼ7 mg/kg) may actually induce methemoglobin for- mation. • Treatment failures occur in some groups, which in- clude glucose-6-phosphate dehydrogenase (G6PD) deficiency and other enzyme deficiencies, and may occur with hemolysis. • Patients who have been exposed to agents with long half-lives, such as dapsone, may require serial dosing of methylene blue. • Patients with methemoglobinemia unresponsive to methylene blue therapy should be treated supportively. If clinically unstable, the use of blood transfusion or exchange transfusion is indi- cated. SULFHEMOGLOBINEMIA • Sulfhemoglobinemia is less common than methe- moglobinemia. Although patients with sulfhemo- globinemia have a clinical presentation similar to that of methemoglobin, the disease process is sub- stantially less concerning. • The diagnosis is difficult to confirm, because stan- dard co-oximetry does not differentiate sulfhemo- globin from methemoglobin. • Sulfhemoglobin is not reduced by treatment with methylene blue, and generally patients require [...]... produce effects ranging from mild gastrointestinal (GI) symptoms to organ failure and death • Mushrooms with psilocybin- and psilocin-containing toxins have neuroactive chemicals similar to lysergic acid diethylamide (LSD), causing hallucinogenic effects; they are often intentionally ingested for their mind-altering effects • Gyromitrin is a volatile, heat-labile toxin hydrolyzed in the stomach It is... • • • radical in the liver, causing local hepatic necrosis and inhibiting the activity of the P450 system, glutathione, and other hepatic enzyme systems.2 Amatoxins are absorbed in the intestines and enter the enterohepatic circulation; they bind to hepatocytes and inhibit formation of messenger RNA.3 Ricin, a potent toxalbumin found in castor bean, produces severe cytotoxic effects in multiple organ... scarring is minimal Deep partial-thickness burns extend into the deep dermis The exposed dermis is white to yellow and does not blemish Capillary refill and pain sensation are absent Healing takes 3 weeks to 2 months, and scarring is common Full-thickness burns involve the entire skin thickness The skin is scarred, pale, painless, and leathery Burns may also be associated with smoke inhalation injuries... Table 12 5-1 summarizes clinical syndromes associated with increasing doses DIAGNOSIS AND DIFFERENTIAL CLINICAL FEATURES • Radiation exposure may involve either external or internal contamination, or external irradiation • External contamination can spread to the local environment, leading to internal contamination of the victim or others • Internal contamination occurs through inhalation, ingestion,... • The risk of burns is highest in the 1 8- to 35-yearold age group There is higher incidence of scalds from hot liquids in children 1 to 5 years of age and in the elderly than in any other age group • Burns are defined by their size and depth Burn size is quantified as a percentage of BSA involved • The most common method of approximating the percentage of BSA burned is the ‘‘rule of nines’’ (Fig 12 3-1 )... be helpful in determining the extent of injury FIG 12 3-2 Lund and Browder diagram to estimate percentage of pediatric burn • • • • proach in burn centers: superficial partial-thickness, deep partial-thickness, and full-thickness Superficial partial-thickness burns have blistering exposed dermis that is red and moist with intact capillary refill, and they are very painful to touch They heal in 14 to 21... burns include full-thickness burns greater than 10 percent of the BSA or partial-thickness burns greater than 10 percent of the BSA Burns involving the face, hands, feet, or perineum are also major • Minor burns include partial-thickness burns less than 10 percent of the BSA or full-thickness burns that are less than 2 percent of the BSA • Moderate burns are those not meeting criteria for either major... either major or minor burns • With improvements in the treatment of burn shock and sepsis, inhalation injury has emerged as the main cause of mortality in the burn patient • The diagnosis of smoke inhalation is suggested by the history of a fire in an enclosed space Physical examination signs include soot in the mouth or nose and carbonaceous sputum The chest radiograph may be normal initially Bronchoscopy... years of age 2 Partial- or full-thickness burns of greater than 20% of BSA in other age groups 3 Partial- or full-thickness burns with the threat of functional or cosmetic impairment that involve face, hands, feet, genitalia, perineum, or major joints 4 Full-thickness burns of greater than 5% of BSA in any age group 5 Electrical burns, including lightning injury 6 Chemical burns with the threat of functional... adequate ventilation Incisions need to be made at the anterior axillary line from the level of the second rib to the level of the twelfth rib These two incisions should be joined transversely so that the chest wall can expand • Criteria for transfer to a burn center are outlined in Table 12 3-1 • Outpatient management of minor burns is appropriate Blisters may be left intact or drained; the decision depends . glucose-6-phosphate dehydrogenase de- ficiency. Ann Intern Med 75 :83, 1 971 . For further reading in Emergency Medicine: A Com- prehensive Study Guide, 5th ed., see Chap. 183, ‘‘Dyshemoglobinemias,’’. cholin- esterase activity and detoxifies the remaining or- ganophosphate molecules. Clinically, 2-PAM ameliorates the CNS, nicotinic, and muscarinic ef- fects. • Disposition depends upon the pesticide. oxy- gen therapy. DIAGNOSIS AND DIFFERENTIAL • The primary key to the diagnosis is maintaining a high degree of clinical suspicion. • The most useful laboratory test is the determina- tion of the