Acetaminophen

Acetaminophen  Kent R. Olson, MD

Acetaminophen (Anacin-3, Liquiprin, Panadol, Paracetamol, Tempra, Tylenol, and many other  brands) is a widely used drug found in many over-the-counter and prescription analgesics and cold remedies. When it is combined with another drug such as diphenhydramine, codeine, or  propoxyphene, the more dramatic acute symptoms caused by the other drug may mask the mild and nonspecific symptoms of early acetaminophen toxicity, resulting in a missed diagnosis or delayed antidotal treatment. Common combination products containing acetaminophen include Darvocet, Excedrin ES, Lorcet, Norco, NyQuil, Percocet, Unisom Dual Relief Formula, Sominex 2, Tylenol with Codeine, Tylox, Vicks Formula 44-D, and Vicodin. I. Mechanism of toxicity A. Hepatic injury.  One of the products of normal no rmal metabolism of acetaminophen by cytochrome P-450 mixed-function oxidase enzymes enz ymes is highly toxic; normally this reactive metabolite (NAPQI) is detoxified rapidly by glutathione in liver cells. However, i n an overdose, production of NAPQI exceeds glutathione capacity and the metabolite reacts directly with hepatic macromolecules, causing liver injury. B. Renal damage may occur by the same mechanism, owing to renal P-450 metabolism. C. Overdose during pregnancy  has been associated with fetal death and spontaneous abortion. D. Pharmacokinetics. Rapidly absorbed, with peak levels usually reached within 30–120 minutes (Note:  Absorption  Absorption may be delayed dela yed after ingestion of sustained-release products or with co-ingestion co-ingestion of opioids or anticholinergics). Volume of distribution (Vd) = 0.8–1 L/kg. Elimination is mainly by liver conjugation (90%) to nontoxic glucuronides or sulfates; cytochrome P-450 mixed-function mixed-function oxidase (CYP 2E1, 1A2) accounts for only about 3–8% 3–8%  but produces a toxic intermediate (see A, above). The elimination half-life half-life is 1–3 hours after a therapeutic dose and may be b e greater than 12 hours after an overdose. (See also Table II–59.) II. Toxic dose A. Acute ingestion  of more than 200 mg/k g in children or 6–7 g in adults is potentially hepatotoxic. 1. Children younger than 10–12 years of age appear to be less susceptible to hepatotoxicity because of the smaller contribution of cytochrome P-450 to acetaminophen metabolism. 2. In contrast, the margin of safety is lower in patients with indu ced cytochrome P-450

microsomal enzymes, because more of the toxic metabolite may be produced. High-risk patients  include alcoholics and patients taking inducers of CYP 2E1 such as isoniazid. Fasting and malnutrition also increase the risk of hepatotoxicity, presumably b y lowering cellular glutathione stores. B. Chronic toxicity  has been reported after daily consumption of supratherapeutic doses by alcoholic patients and persons taking isoniazid. Children have developed toxicity after receiving as little as 60–150 mg/kg/day for 2†“8 days. III. Clinical presentation.  Clinical manifestations depend on the time after ingestion. A. Early after acute acetaminophen overdose, there are usually no symptoms other than anorexia, nausea, or vomiting. Rarely, a massive overdose may cause altered mental status and metabolic acidosis. Transient prolongation of the prothrombin time (PT/INR) in the absence of hepatitis has been noted in the first 24 hours; some, but not all, of these patients go on to develop liver injury. B. After 24–48 hours,  when transaminase levels [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] begin to rise, hepatic necrosis becomes evident. If acute fulminant hepatic failure occurs, death may ensue. Encephalopathy, metabolic acidosis, and a continuing rise in PT/INR indicate a poor pro gnosis. Acute renal failure occasionally occurs, with or without concomitant liver failure.

IV. Diagnosis. Prompt diagnosis is possible only if the ingestion is suspected and a serum acetaminophen level is obtained. However, patients may fail to provide the history of acetaminophen ingestion, because they are unable (eg, comatose from another ingestion), unwilling, or unaware of its importance. Therefore, many clinicians routinely order acetaminophen levels in all overdose patients regardless of the histor y of substances ingested. A. Specific levels 1. After an acute overdose,  obtain a 4-hour postingestion acetaminophen level and use the nomogram (Figure II–1) to predict the likelihood of tox icity. Do not attempt to interpret a level drawn before 4 hours unless it is "nondetectable." Obtain a second level at 8 hours if the 4-hour value is borderline or if delayed absorption is anticipated. 2. The nomogram should not be used to assess chronic or repeated ingestions. 3. Falsely elevated acetaminophen levels may occur in the presence of high levels of salicylate and other interferents by various methods (see Table I–33). This problem is rare with currently used analysis methods. B. Other useful laboratory studies  include electrolytes, glucose, BUN, creatinine, liver transaminases, and PT/INR. V. Treatment

A. Emergency and supportive measures 1. Spontaneous vomiting  may delay the oral administration of antidote or charcoal (see  below) and should be treated with metoclopramide (see Metoclopramide) or a 5-HT3 receptor antagonist such as ondansetron (Ondansetron). 2. Provide general supportive care for hepatic or renal failure if it occurs. Emergency liver transplant  may be necessary for fulminant hepatic failure. Enceph alopathy, metabolic acidosis, hypoglycemia, and progressive rise in the prothrombin time are in dications of severe liver injury. B. Specific drugs and antidotes.  If the serum level falls above the upper ("probable toxicity") line on the nomogram or if stat serum l evels are not immediately available, initiate antidotal therapy with N -acetylcysteine  (NAC, Acetylcysteine). The effectiveness of NAC depends on early treatment,  before the metabolite accumulates; it is of maximal benefit if started within 8–10 hours and of diminishing value after 12–16 hours (however, treatment should not be withheld even if the delay is 24 hours or more). If vomiting interferes with or threatens to delay oral acetylcysteine administration, give the N AC intravenously. 1. If the serum level falls between the two nomo gram lines, consider giving NAC if the  patient is at increased risk for toxicity; eg, the patient is alcoholic, malnourished or fasting or is taking drugs that induce P-450 2E1 activity [(eg, isoniazid (INH)]; after multiple or subacute overdoses; or if the time of ingestion is u ncertain or unreliable. 2. If the serum level falls below the lower nomogram line, treatment is not indicated unless the time of ingestion is uncertain or the patient is considered to be at particularly high risk. 3. Note:  After ingestion of extended-release tablets (eg, Tylenol Ar thritis Painâ„¢), which are designed for prolonged absorption, there may be a delay before the peak acetaminophen level is reached. This can also occur after co-ingestion of drugs that dela y gastric emptying, such as opioids and anticholinergics. In such c ircumstances, repeat the serum acetaminophen level at 8 hours and possibly 12 hours. In such cases, it may be prudent to initiate NAC therapy before 8 hours while waiting for subsequent lev els. 4. Duration of NAC treatment.  The conventional US protocol for treatment of acetaminophen poisoning calls for 17 doses of oral NAC given over approximately 72 hours. However, for decades successful protocols in Canada, the United Kingdom, and Europe have utilized intravenous NAC for only 20 hours. In uncomplicated cases, give  NAC (orally or IV) for 20 hours and follow hepatic transaminase levels and the PT/INR until 36 hours have passed since the time of ingestion. If evidence of liver injury develops,  NAC is continued until liver function tests are improving. 5. Chronic acetaminophen ingestions: Patients may give a history of several doses taken over 24 hours or more, in which case the nomogram cannot accurately estimate the risk of hepatotoxicity. In such cases, we advise NAC treatment if the amount ingested was more than 150–200 mg/kg or 6–7 g within a 24-hour period, if liver enzymes are elevated, or

if the patient falls within a high-risk group (see above). Treatment may be stopped 24–36 hours after the last dose of acetaminophen if liver enzymes and PT/INR are normal. C. Decontamination  (see Decontamination). Administer activated charcoal orally if conditions are appropriate (see Table I–38). Gastric lavage is n ot necessary after small to moderate ingestions if activated charcoal can be given promptly. 1. Although activated charcoal adsorbs some of th e orally administered antidote N acetylcysteine, this effect is not considered clinically important. 2. Do not administer charcoal if more than 3–4 hours has passed since ingestion unless delayed absorption is suspected (eg, as with Tylenol Arthritis Painâ„¢ or co-ingestants containing opioids or anticholinergic agents). D. Enhanced elimination.  Hemodialysis effectively removes acetaminophen from the blood  but is not generally indicated because antidotal therapy is so effective. Dialysis should be considered for massive ingestions with very high levels (eg, >1000 m g/L) complicated by coma and/or hypotension.

Figure II–1.

 Nomogram for prediction of acetaminophen hepatotoxicity after acute overdose. The upper line defines serum acetaminophen concentrations likely to be associated with hepatotoxicity; the lower line defines serum levels 25% below those ex pected to cause hepatotoxicity. (Courtesy of McNeil Consumer Products, Inc.)

Barbiturates Timothy E. Albertson, MD, PhD

Barbiturates are used as hypnotic and sedative a gents, for the induction of anesthesia, and for the treatment of epilepsy and status epilepticus. They often are divided into four major groups by their pharmacologic activity and clinical use: ultrashort-acting, short-acting, intermediateacting,  and long-acting  (Table II – 13). Common combination products containing barbiturates include Fiorinal™ (50 mg butalbital) and Donnatal™ (16 mg phenobarbital). Veterinary euthanasia products often contain barbiturates such as pentobarbital. Table II – 13. Barbiturates

Drug

Normal Terminal Elimination HalfLife (h)

Usual Duration of Effect (h)

Usual Hypnotic Dose (Adult) (mg)

Minimum Toxic Level (mg/L)

Methohexital

3 – 5

< 0.5

50 – 120

>5

Thiopental

8 – 10

< 0.5

50 – 75

>5

Pentobarbital

15 – 50

> 3 – 4

50 – 200

>10

Secobarbital

15 – 40

> 3 – 4

100 – 200

>10

Amobarbital

10 – 40

> 4 – 6

65 – 200

>10

Aprobarbital

14 – 34

> 4 – 6

40 – 160

>10

Butabarbital

35 – 50

> 4 – 6

100 – 200

>10

Butalbital

35

100 – 200

>7

Ultrashortacting

Short-acting

Intermediateacting

Long-acting

Mephobarbital

10 – 70

> 6 – 12

50 – 100

>30

Phenobarbital

80 – 120

> 6 – 12

100 – 320

>30

I. Mechanism of toxicity A. All barbiturates cause generalized depression of neuronal activity  in the brain. Interaction with a barbiturate receptor leads to enhanced gamma-aminobutyric acid (GABA)mediated chloride currents and results in synaptic inhibition. Hypotension t hat occurs with large doses is caused by depression of central sympathetic tone as well as by direct depression of cardiac contractility. B. Pharmacokinetics  vary by agent and group (see Tables II – 13 and II – 59). 1. Ultrashort-acting  barbiturates are highly lipid soluble and rapidly penet rate the brain to induce anesthesia, then are quickly redistributed to other tissues. For this reason, the clinical duration of effect is much shorter than the elimination half-life for these compounds. 2. Long-acting barbiturates  are distributed more evenly and have long elimination halflives, making them useful for once-daily treatment of epilepsy. Primidone (Mysoline) is metabolized to phenobarbital and phenylethylmalonamide (PEMA); although phenobarbital accounts for only about 25% of the metabolites, it has the greatest anticonvulsant activity. II. Toxic dose. The toxic dose of barbiturates varies widely and depends on the drug, the route and rate of administration, and individual patient tolerance. In general, toxicity is likely when

the dose exceeds 5 – 10 times the hypnotic dose. Chronic users or abusers may have striking tolerance to depressant effects. A. The potentially fatal oral dose of the shorter-acting agents is 2 – 3 g, compared with 6 – 10 g for phenobarbital. B. Several deaths were reported in young women undergoing therapeutic abortion after the y received rapid intravenous injections  of as little as 1 – 3 mg/kg of methohexital. III. Clinical presentation.  The onset of symptoms depends on the drug and the route of administration. A. Lethargy, slurred speech, nystagmus, and ataxia are common with mild to moderate intoxication. With higher doses, hypotension, coma, and respiratory arrest commonly occur. With deep coma, the pupils are usually small or midposition; the patient may lose all reflex activity and appear to be dead. B. Hypothermia is common in patients with deep coma, especially if the victim has suffered exposure to a cool environment. Hypotension and bradycardia commonly accompany hypothermia. IV. Diagnosis  is usually based on a history of ingestion and should be suspected in an y epileptic patient with stupor or coma. Although skin bullae sometimes are seen with barbiturate overdose, they are not specific for barbiturates. Other causes of coma should also be considered (see Coma and stupor). A. Specific levels  of phenobarbital are usually readily available from hospital clinical laboratories; concentrations greater than 60 – 80 mg/L are usually associated with coma, and those greater than 150 – 200 mg/L with severe hypotension. For short- and intermediate-acting  barbiturates, coma is likely when the serum concentration exceeds 20 – 30 mg/L. Barbiturates are easily detected in routine urine toxicologic screening. B. Other useful laboratory studies  include electrolytes, glucose, BUN, creatinine, arterial  blood gases or pulse oximetry, and chest x-ray. V. Treatment A. Emergency and supportive measures 1. Protect the airway and assist ventilation (see Airway) if necessary. 2. Treat coma (see Coma and stupor), hypothermia (Hypothermia), and hypotension (Hypotension) if they occur. B. Specific drugs and antidotes.  There is no specific antidote.

C. Decontamination  (see Decontamination). Administer activated charcoal orally if conditions are appropriate (see Table I – 38). Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. D. Enhanced elimination 1. Alkalinization of the urine (see Urinary manipulation) increases the urinary elimination of phenobarbital but not other barbiturates. Its value in acute overdose is unproved, and it may potentially contribute to fluid overload and pulmonary edema. 2. Repeat-dose activated charcoal  has been shown to decrease the half-life of  phenobarbital, but data are conflicting regarding its effects on the duration of coma, time on mechanical ventilation, and time to extubation. 3. Hemodialysis or hemoperfusion may be necessary for severely intoxicated patients who are not responding to supportive care (ie, with intractable hypotension).

Carbon Monoxide  Kent R. Olson, MD

Carbon monoxide (CO) is a colorless, odorless, tasteless, and nonirritating gas produced b y the incomplete combustion of any carbon-containing material. Common sources of human exposure include smoke inhalation in fires; automobile exhaust fumes; faulty or po orly ventilated charcoal, kerosene, or gas stoves; and, to a lesser extent, cigarette smoke and methylene chloride (see Methylene Chloride). Carbon monoxide poisoning accounts for approximately 40,000 emergency department visits every year in the Uni ted States. I. Mechanism of toxicity.  Toxicity is a consequence of cellular hypoxia and ischemia. A. CO binds to hemoglobin with an affinity 250 times that of oxygen, resulting in reduc ed oxyhemoglobin saturation and decreased blood oxygen-carrying capacity. In addition, the oxyhemoglobin dissociation curve is displaced to the left, impairing oxygen delivery at the tissues. B. CO may also directly inhibit cytochrome oxidase, further disrupting cellular function, and it is known to bind to myoglobin, possibly contributing to impaired myocardial contractility. C. In animal models of intoxication, damage is most severe in a reas of the brain that are highly sensitive to ischemia and often correlates with the severity of systemic hypotension. Postanoxic injury appears to be complicated b y lipid peroxidation, excessive release of excitatory neurotransmitters, and inflammatory changes, including adherence of neutrophils to cerebral vessels.

D. Fetal hemoglobin is more sensitive to binding by CO, and fetal or neonatal levels may be higher than maternal levels. E. Pharmacokinetics. The carboxyhemoglobin complex gradually dissociates after removal from exposure. The approximate half-life of elimination of CO-Hgb during treatment with high-flow oxygen by tight-fitting mask or endotracheal tube is 74 minutes (range 24 – 148). In room air the approximate half-life is as much as 2 00 minutes, and during hyperbaric ox ygen therapy it is as short as 12 – 20 minutes. II. Toxic dose. The recommended workplace limit (ACGIH TLV-TWA) for carbon mono xide is 25 ppm as an 8-hour time-weighted average. The level considered immediately dangerous to life or health (IDLH) is 1200 ppm (0.12%). However, the duration of exposure is very important. Whereas exposure to 1000 ppm (0.1%) even tually will result in 50% saturation of carboxyhemoglobin, it may take several hours to reach that level. In 1895 Haldane experimented on himself by breathing 2100 ppm CO for over an hour, and it was only after 34 minutes, when his level would have been approximately 25%, that he described a throbbing headache. Brief exposure to much higher levels may produce a more rapid rise in CO-Hgb. III. Clinical presentation.  Symptoms of intoxication are predominantly in o rgans with high oxygen consumption such as the brain and heart. A. The majority of patients complain of headache, dizziness, and nausea. Patients with coronary disease may experience angina or myocardial infarction. With more severe exposures, impaired thinking, syncope, coma, convulsions, cardiac arrhythmias, hypotension, and death may occur. Although blood carboxyhemoglobin levels may not correlate reliably with the severity of intoxication, levels greater than 25% are considered significant and levels greater than 40 – 50% usually are associated with obvious intoxication. B. Survivors of serious poisoning may suffer numerous overt neurologic sequelae consistent with a hypoxic-ischemic insult, ranging from gross deficits such as parkinsonism and a  persistent vegetative state to subtler personality and memory disorders. Various studies suggest that the incidence of subtle neuropsychiatric sequelae such as impaired memory and concentration and mood disorders may be as high as 47%. C. Exposure during pregnancy may result in fetal demise. IV. Diagnosis  is not difficult if there is a history of exposure (eg, the patient was found in a car in a locked garage) but may be elusive if it is not suspected in less ob vious cases. There are no specific reliable clinical findings; cherry-red skin coloration or bright red venous blood is highly suggestive but not frequently noted. The routine arterial blood gas machine measures the partial pressure of oxygen dissolved in plasma (pO2), but oxygen saturation is calculated from the pO2 and is therefore unreliable in patients with C O poisoning. Pulse oximetry also gives falsely normal readings because it is unable to distinguish between oxyhemoglobin and carboxyhemoglobin. A. Specific levels.  Obtain a specific carboxyhemoglobin concentration. Persistence of fetal

hemoglobin may produce falsely elevated carboxyhemoglobin levels in young infants. B. Other useful laboratory studies  include electrolytes, glucose, BUN, creatinine, ECG, and pregnancy tests. Metabolic acidosis suggests more serious poisoning. With smoke inhalation, obtain the blood cyanide level and methemoglobin concentration. V. Treatment A. Emergency and supportive measures 1. Maintain an open airway and assist ventilation if necessary (see Airway). If smoke inhalation has also occurred, consider early intubation for airway p rotection. 2. Treat coma (Coma and stupor) and seizures (Seizures) if they occur. 3. Continuously monitor the ECG for several hours after exposure. 4. Because smoke often contains other toxic gases, consider the possibility of cyanide  poisoning (see Cyanide), methemoglobinemia (Methemoglobinemia), and irritant gas injury (Gases, Irritant). B. Specific drugs and antidotes.  Administer oxygen in the highest possible concentration (100%). Breathing 100% oxygen speeds the elimination of CO from hemoglobin to approximately 1 hour, compared with 6 hours in room air. Use a tight-fitting mask and highflow oxygen with a reservoir (nonrebreather) or administer the oxygen by endotracheal tube. Treat until the carboxyhemoglobin level is less than 5%. Consider hyperbaric oxygen  in severe cases (see below). C. Decontamination. Remove the patient immediately from exposure and give supplemental oxygen. Rescuers exposed to potentially high concentrations of CO should wear selfcontained breathing apparatus. D. Enhanced elimination.  Hyperbaric oxygen provides 100% oxygen under 2 – 3 atmospheres of pressure and can enhance elimination of CO (half-life reduced to 20 – 30 minutes). In animal models it reduces lipid peroxidation and n eutrophil activation, and in a recent randomized controlled trial in humans it reduced the incidence of subtle cognitive sequelae compared with normobaric 100% oxygen, although an earlier similar study found no benefit. Hyperbaric oxygen may be useful in patients with severe intoxication, especially when there is ready access to a chamber. It remains unclear whether its benefits over normobaric oxygen apply to victims who present many hours after exposure or have milder degrees of intoxication. Consult a regional poison control c enter ([800] 222-1222) for advice and for the location of nearby hyperbaric chambers. See Table II – 19 for a list of proposed indications for hyperbaric oxygen. a

Table II – 19. Hyperbaric Oxygen: Proposed Indications for CO Poisoning

Loss of consciousness CO Hgb > 25% Age > 50 years Metabolic acidosis (base excess less than 2 mEq/L) Cerebellar dysfunction

Cyanide  Paul D. Blanc, MD, MSPH

Cyanide is a highly toxic chemical with a variety of uses, including chemical synthesis, laboratory analysis, and metal plating. Aliphatic nitriles (acrylonitrile and propionitrile) used in  plastics manufacturing are metabolized to cyanide. The vasodilator drug [dx id=""]nitroprusside[/dx] releases cyanide upon exposure to light or through metabolism. Natural sources of cyanide (amygdalin and many other cyanogenic glycosides) are found in apricot pits, cassava, and many other plants and seeds, some of which may be important, depending on ethnobotanical practices. Acetonitrile, a component of some artificial nail glue removers, has caused several pediatric deaths. Hydrogen cyanide  is a gas easily generated by mixing acid with cyanide salts and is a common combustion by-product of burning plastics, wool, and many other natural and synthetic products. Hydrogen cyanide poisoning is an important cause of death from structural fires, and deliberate cyanide exposure (through cyanide salts) remains an important instrument of homicide and suicide. Hydrogen cyanamide, an agricultural chemical used as a plant regulator, is a potent toxin that inhibits aldehyde dehydrogenase but does not act as a cyanide analog. I. Mechanism of toxicity.  Cyanide is a chemical asphyxiant; binding to cellular cytochrome oxidase, it blocks the aerobic utilization of ox ygen. Unbound cyanide is detoxified by metabolism to thiocyanate, a much less toxic compound that is excreted in the urine. II. Toxic dose A. Exposure to hydrogen cyanide gas (HCN) even at low levels (150–200 ppm) can be fatal. The air level considered immediately dangerous to life or health (IDLH) is 50 ppm. The 3 recommended workplace ceiling limit (ACGIH TLV-C) for HCN is 4.7 pp m (5 mg/m  for cyanide salts). The OSHA permissible exposure limit (PEL) is 10 ppm. HCN is well absorbed across the skin. B. Adult ingestion  of as little as 200 mg of the sodium or potassium salt may be fatal. Solutions of cyanide salts can be absorbed through intact skin. C. Acute cyanide poisoning is relatively rare with [dx id=""]nitroprusside[/dx] infusion (at

normal infusion rates) or after ingestion of amygdalin-containing seeds (unless they have  been pulverized). III. Clinical presentation.  Abrupt onset of profound toxic effects shortly after exposure is the hallmark of cyanide poisoning. Symptoms include headache, nausea, dyspnea, and confusion. Syncope, seizures, coma, agonal respirations, and cardiovascular collapse ensue rapidly after heavy exposure. A. A brief delay may occur if the cyanide is ingested as a salt, especially if it is in a capsule or if there is food in the stomach. B. Delayed onset (minutes to hours) also may occur after ingestion of nitriles and plantderived cyanogenic glycosides, because metabolism to cyanide is required. C. Chronic neurologic sequelae may follow severe c yanide poisoning consistent with anoxic injury. IV. Diagnosis  is based on a history of exposure or the presence of rapidly progressive symptoms and signs. Severe lactic acidosis is usually present with significant exposure. The measured venous oxygen saturation  may be elevated owing to blocked cellular oxygen consumption. The classic "bitter almond" odor of hydrogen cyanide may or may not be noted, in part because of genetic variability in the ability to detect the smell. A. Specific levels.  Cyanide determinations are rarely of use in emergency management  because they cannot be performed rapidly enough to influence initial treatment. In addition, they must be interpreted with caution because o f a variety of complicating technical factors. 1. Whole- blood levels higher than 0.5–1 mg/L are considered toxic. 2. Cigarette smokers may have levels up to 0.1 mg/L. 3. Rapid [dx id=""]nitroprusside[/dx] infusion may produce levels as high as 1 mg/L, accompanied by metabolic acidosis. B. Other useful laboratory studies include electrolytes, glucose, serum lactate, arterial  blood gases, mixed venous oxygen saturation, and carboxyhemoglobin (if the patient experienced smoke inhalation exposure). V. Treatment A. Emergency and supportive measures.  Treat all cyanide exposures as potentially lethal. 1. Maintain an open airway and assist ventilation if necessary (see Airway). Administer supplemental oxygen. 2. Treat coma (see Coma and stupor), hypotension (Hypotension), and seizures (Seizures)

if they occur. 3. Start an intravenous line and monitor the patient's vital signs and ECG closely. B. Specific drugs and antidotes 1. The cyanide antidote package (Taylor Pharmaceuticals) consists of amyl and sodium nitrites (see Nitrite, Sodium and Amyl), which produce cyanide-scavenging methemoglobinemia, and sodium thiosulfate (Thiosulfate, Sodium), which accelerates the conversion of cyanide to thiocyanate. a. Break a pearl of amyl nitrite under the nose of the victim and administer [dx id=""]sodium nitrite[/dx],  300 mg IV (6 mg/kg for children, not to exceed 300 mg). Adjust the dose downward if anemia is present (see Nitrite, Sodium and Amyl). Caution :  Nitrite-induced methemoglobinemia can be extremely dangerous and even lethal. Nitrite should not be given if the symptoms are mild or if the diagnosis is uncertain, especially if concomitant carbon monoxide poisoning is suspected. b. Administer sodium thiosulfate,  12.5 g IV. Thiosulfate is relatively benign an d may be given empirically even if the diagnosis is uncertain. It also may be useful in mitigating [dx id=""]nitroprusside[/dx] toxicity (see Thiosulfate, Sodium). 2. The most promising alternative antidote is hydroxocobalamin  (see Hydroxocobalamin). Although available in Europe, it remains an investigational drug in the United States. Dicobalt edentate is also used outside the United States. 3. Hyperbaric oxygen  has no proven role in cyanide poisoning treatment. C. Decontamination  (see Decontamination). Caution : Avoid contact with cyanidecontaining salts or solutions and avoid inhaling vapo rs from vomitus (which may give off hydrogen cyanide gas). 1. Inhalation. Remove victims from hydrogen cyanide exposure and give supplemental oxygen if available. Each rescuer should wear a positive-pressure, self-contained breathing apparatus and, if possible, chemical-protective clothing. 2. Skin. Remove and isolate all contaminated clothing and wash affected areas with copious soap and water. 3. Ingestion (see Gastrointestinal decontamination). Even though charcoal has a relatively low affinity for cyanide, it will effectively bind the doses typically ingested (eg, 100– 500 mg). a. Prehospital. Immediately administer activated charcoal if it is available and the patient is alert. Do not  induce vomiting unless the victim is more than 30 minutes from a medical

facility and charcoal is not available. b. Hospital. Immediately place a gastric tube and administer activated charcoal, then  perform gastric lavage. Give additional activated charcoal and a cathartic after the lavage. D. Enhanced elimination.  There is no role for hemodialysis or hemoperfusion in cyanide  poisoning treatment. Hemodialysis may be indicated in patients with renal insufficiency who develop high thiocyanate levels while on extended [dx id=""]nitroprusside[/dx] therapy.