Ingestions of environmental toxins
- OVERVIEW: What every practitioner needs to know
Are you sure your patient has ingestion of environmental toxins? What are the typical findings for this disease?
- Toxic Alcohol Ingestion
- Availability and Epidemiology of Ethylene glycol and Methanol
- Pathophysiology and Toxicokinetics of Ethylene glycol and Methanol
- Example of Calculation of Quantity Ingested that can result in a potentially toxic serum concentration
- Hydrocarbon Ingestion
- Ingestion of hydrocarbons
- Inhalational abuse of hydrocarbons
- Pathophysiology and Clinical Findings in Hydrocarbon Ingestion
- Mushroom Ingestion
- Pathophysiology and Clinical Findings
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has ingestions of environmental toxins, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of ingestions of environmental toxins?
What is the evidence?
OVERVIEW: What every practitioner needs to know
Are you sure your patient has ingestion of environmental toxins? What are the typical findings for this disease?
Toxic Alcohol Ingestion
Ethylene glycol and methanol toxicity is well described and is responsible for more than 5000 exposures annually in the United States requiring treatment.
Methanol and ethylene glycol, as parent compounds, are relatively non-toxic. But depending on the dose, even the parent compounds can cause CNS toxicity including inebriation or lethargy. Alcohols with a higher molecular weight are more lipophilic and thereby are more inebriating: Isopropyl alcohol > ethylene glycol > ethanol > methanol. The lack of CNS symptoms, however, does not exclude a toxic alcohol ingestion.
Early on after exposure it is common for the patient to be asymptomatic. However, the ingestion of ethylene glycol or methanol may result in minor GI toxicity with symptoms of nausea and vomiting. It may also cause CNS inebriation. Symptoms including altered mental status and an anion gap metabolic acidosis. Other end-organ manifestations will occur once the toxic alcohols are metabolized to their toxic by-products. The toxic alcohols are metabolized by alcohol dehydrogenase (ADH) to toxic metabolites with subsequent end-organ damage and potential lethality. The metabolic pathway will be discussed in detail below.
Because of the relative lack of symptoms early on and the potential for catastrophic toxicity, it is imperative that children exposed to ethylene glycol or methanol be risk-assessed and treated empirically and aggressively as described below. This chapter will focus on exposure to ethylene glycol and methanol only.
Availability and Epidemiology of Ethylene glycol and Methanol
Methanol and ethylene glycol are commonly available toxic alcohols are often easily accessible in most homes.
Ethylene glycol is primarily used as a coolant and is the most common ingredient in antifreeze. Because of the sweet taste of ethylene glycol, it is not uncommon for children, small pets, or animals to ingest it. Even a small quantity can result in toxicity.
Methanol exposure most commonly results from ingestion of windshield washer fluid. Methanol is also in dry gas (gas line antifreeze) as well as in Sterno products. It continues to be involved in mass poisonings when attempting to make wood alcohol.
Pathophysiology and Toxicokinetics of Ethylene glycol and Methanol
Alcohols are hydrocarbons and all undergo the same metabolic pathways. This chapter will focus only on ethylene glycol and methanol as they are the two most common clinically relevant toxic alcohols.
Ethylene glycol is metabolized by ADH to glycoaldehyde and then to its toxic metabolites, glycolic acid and oxalic acid. It generally takes from 30 minutes up to 6 hours to metabolize ethylene glycol to its toxic metabolites. In patients with normal renal function, ethylene glycol is cleared unchanged with a half-life of about 11-17 hours. Glycolic acid is the metabolite that causes the anion gap metabolic acidosis and oxalic acid results primarily in renal toxicity due to the formation of calcium oxalate crystals. The renal toxicity that occurs is an acute tubular necrosis and is often reversible over 4-6 weeks. Dermal and pulmonary absorption is negligible in ethylene glycol exposure.
Methanol is metabolized by ADH to formaldehyde and then to its toxic metabolite, formic acid. Formic acid causes a resultant anion gap metabolic acidosis and ocular toxicity. The retinal toxicity is often irreversible. Methanol does not have appreciable renal elimination and is cleared much more slowly than ethylene glycol. It is presumably eliminated as a vapor in expired air with a half-life of 30 hours. It generally takes up to 24 hours for methanol to be metabolized through ADH to formic acid. Methanol can be absorbed through the pulmonary route and there have been cases of patients becoming methanol toxic after inhalant abuse of methanol.
The aim of therapy is to inhibit the metabolism of ethylene glycol and methanol to its toxic metabolites. The specific therapeutic interventions are discussed in detail below.
Serum concentrations of greater than 25 mg/dL can result in toxicity.
Isopropanol is a commonly found substance in the home. It has three carbons and therefore is the most inebriating of the toxic alcohols. It causes significant GI toxicity if a significant amount is ingested however, because of its bitter taste, most children do not drink a significant quantity. Isopropyl is metabolized to acetone so causes a ketosis without an acidosis. Care is largely supportive with treatment focused on antiemetics in a patient with GI toxicity. Alcohol dehydrogenase inhibitors are not recommended because the parent compound is the more significantly toxic compound.
Example of Calculation of Quantity Ingested that can result in a potentially toxic serum concentration
Though the majority of exposures with toxicity is due to suicidal or homicidal methods, there are a significant number of pediatric patients that are exposed to these substances. It is important to highlight the potential severity of these exposures. Because of the relatively high concentrations of ethylene glycol and methanol in consumer products, it takes only a small amount ingested to result in a potentially toxic serum concentration. The relative sweet taste of ethylene glycol is also concerning because a small child may actually be able to ingest a toxic quantity. Methanol is relatively bitter tasting so this may help deter a significant exposure.
To appreciate that ingestion of a small quantity may result in a potentially toxic serum concentration (>25 mg/dL), a calculation is described below.
For this calculation, there will be several assumptions made:
1. The calculation will be based on a 20 kilogram child
2. The volume of distribution will be 0.6 L/kg
3. The consumer product is 100% of the parent toxic alcohol
4. Complete absorption and no metabolism
5. The toxic serum concentration is 25 mg/dL
Calculation to be used:
Serum Concentration = Dose/Vd
Vd = 0.6 L/kg (20 kg) = 12 L = 120 dL
25 mg/dL = Dose/120 dL
Dose = 3000 mg = 3 grams
Assuming that the product is 100% ethylene glycol or methanol:
100 g/100 mL = 3 grams/x
Solving for X
X = 3 mL
In a 20 kilogram child that has been exposed to 100% ethylene glycol or methanol, it would only take 3 mL (less than a teaspoon) ingested to result in a toxic serum concentration of 25 mg/dL. In general terms, a mouthful in a small child is a teaspoon. Therefore, less than a mouthful of a toxic alcohol can be toxic.
This calculation highlights that these patients only require a small exposure to be potentially toxic and therefore, observation in an Emergency Department with diagnostic testing for serum concentrations and treatment aimed to inhibit the metabolism is essential.
Hydrocarbons are pervasive in our society and are commonly used as solvents. There are three populations of people that are at risk for hydrocarbon related illness: children with accidental ingestion; workers with occupational exposures (usually dermal and inhalational) and adolescents/adults with intentional abuse of inhaled hydrocarbons in an attempt to get high. There are numerous hydrocarbons available and for the purpose of this review, we will focus on hydrocarbons in general rather than specific qualities of different agents.
Hydrocarbons are organic compounds and contain mainly carbon and hydrogen atoms. There are three types of hydrocarbons based on the structure and chemical substitutions: aliphatics, aromatics and halogenated hydrocarbons.
Aliphatic hydrocarbons are straight chained or branched chained hydrocarbons. Examples of these include: gasoline, kerosene and turpentine.
Aromatic hydrocarbons have a ring structure. Examples include: benzene and toluene.
Halogenated hydrocarbons have a substituted halogen atom instead of a hydrogen atom. Examples of halogenated hydrocarbons include: methylene chloride; difluoroethane and carbon tetrachloride.
This review will focus only on ingestions of hydrocarbons and intentional inhalational abuse of hydrocarbons and specific management recommendations.
Consultation with the regional poison center is indicated for a hydrocarbon exposure as there are differences of toxicity associated with different agents that require special attention.
Ingestion of hydrocarbons
Generally speaking, ingestions of hydrocarbons result in minimal direct toxicity except for minor GI upset. The absorption of hydrocarbons from the GI tract is minimal and inversely related to the molecular weight.
Aspiration is the main complication from the ingestion of a hydrocarbon. Most patients who develop pulmonary toxicity will have an episode of coughing, choking or gagging. This occurs within the first 30 minutes after ingestion. Aspiration and pulmonary toxicity from hydrocarbons may manifest as crackles, rhonchi, rales, tachypnea, hypoxia or respiratory distress. Cyanosis occurs rarely. Clinical findings worsen over the first several days after aspiration but generally improve within a week. In the United States, mortality is rare (<2%) and occurs after severe, progressive respiratory insult with severe hypoxia.
Inhalational abuse of hydrocarbons
Inhalant abuse is not an uncommon drug of abuse and is particularly popular amongst adolescents and even pre-adolescents. Most notably, halogenated hydrocarbons have been implicated as commonly abused though all of the hydrocarbons have been used inappropriately with the intent to get high. They are desirable because they cause CNS effects including euphoria, inebriation and are general CNS depressants.
Inhalation of hydrocarbons cause a wide array of symptoms dependent on the dose, the specific hydrocarbon as well as the patient's tolerance. In addition to the CNS depressant effects, hydrocarbons can cause serious cardiotoxic including the "Sudden Sniffing Death Syndrome". Sudden sniffing death syndrome has occurred even after first time abuse, and although it is incompletely understood it is believed to be due to the hydrocarbons ability to prolong the QTc interval and cause ventricular dysrhythmias.
Pathophysiology and Clinical Findings in Hydrocarbon Ingestion
There are no specific criteria that best predict the risk of aspiration and subsequent toxicity. The patient's symptoms are the most helpful and predictive of injury. The presence of coughing, choking or gagging shortly after ingestion suggest that aspiration has occurred. Pulmonary toxicity after hydrocarbon ingestion is correllated with the specific type of hydrocarbon; the quantity ingested and the occurrence of emesis. Viscosity, surface tension and volatility of the ingested hydrocarbon are all correllated with aspiration potential. The lower the viscosity, the higher aspiration potential. The lower the surface tension, the higher aspiration potential. The higher the volatility, the more likely the aspiration potential because of the ability to cause transient hypoxia.
Radiographic evidence is present in 44-88% of patients with aspiration. Chest radiographic findings can develop as early as 15 minutes after exposure though can be delayed up to 24 hours after exposure.
The most concerning manifestation of cardiac toxicity due to hydrocarbons is the potential of ventricular dysrhthymias after exposure to a hydrocarbon. This is described as "Sudden Sniffing Death Syndrome" and is due to myocardial sensitization to catecholamines in the face of a prolonged QTc. This results in ventricular dysrhythmias, most notably torsades de Pointes. Halogenated hydrocarbons are the most frequently responsible though all hydrocarbons have the potential for cardiotoxicity. Classically, sudden death follows a period of sudden exertion.
There are generally three patients exposed to potentially toxic mushrooms: children with unintentional ingestions while outdoors, foragers who consume the mushrooms they pick, and adolescents/adults with intentional abuse of hallucinogenic mushrooms.
Mushroom species are diverse and vary in different parts of the world. Because of this, mushroom foragers may ingest a potentially toxic species when they are in a new area. This is of particular concern with immigrants to our country. In the majority of cases, the exact species of mushrooms is never identified after exposure.
This review will focus on the most common mushrooms and those at risk for greatest toxicity.
Generally speaking, most patients with intentional abuse of hallucinogenic mushrooms do not present to healthcare unless they are having an undesired effects or they are brought to medical attention by those who have observed the patient having unusual behavior.
As mentioned above, most mushrooms are not identified and therefore one must rely on clinical symptoms to determine if a toxic mushroom was possibly ingested. Vomiting can be a key clinical symptoms. A general rule of thumb is that if vomiting occurs within the first 6 hours after ingestion of a mushroom, that the mushroom is probably nontoxic. By contrast, vomiting that begins or persists after 6 hours of ingestion is worrisome for a possible toxic ingestion.
For children who have an unintentional ingestion of mushrooms, a poison center will generally recommend that the parents save the mushroom in a brown paper bag and place it in a cool, dry place so that a positive identification of the species of mushroom can be determined if that becomes necessary. The child is then observed at home for vomiting. If the child vomits but at 6 hours is asymptomatic with no further GI effects, it is generally assumed that the child ingested a nontoxic mushroom. If vomiting persists beyond 6 hours or if vomiting begins 6 hours after the ingestion, the child is referred to the Emergency Department for observation with monitoring of liver function tests. Ingestion of amanita mushrooms are the most concerning.
Pathophysiology and Clinical Findings
Most mushrooms fatalities are due to cyclopeptide containing mushrooms. These mushrooms include a number of Amanita species including Amanita Phalloides; Amanita Virosa; Galerina species and Lepiota species.
The amatoxins are the most toxic of the cyclopeptides and cause hepatic, renal and CNS toxicity. Alpha-Amanitin is the principal amatoxin responsible for toxicity. These polpeptides are heat stable. Alpha-amanitin absorption appears to be facilitated by the sodium dependent bile acid tranporter. The organic anion-transporter polypeptide (OATP) also appears to facilitate hepatocellular alpha-amanitin uptake. Alpha-amanitin also undergoes enterohepatic recirculation.
The cyclopeptides cause severe gastroenteritis with profuse diarrhea occurring 5 to 24 hours after ingestion. Hepatic and renal toxicity generally occurs from day 2 to day 6 after ingestion. The initial hepatotoxicity begins within the first 12 to 36 hours but clinical hepatotoxicity demonstrates on day 2 or day 3 after ingestion. Elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and other markers of intrinsic hepatic dysfunction occur. Pathologic manifestations include steatosis and centrilobular necrosis.
Gyromitra esculenta (known as the false morel) is commonly mistaken for Morchella Spp known as the true morel particularly in the spring months. This leads to significant toxicity. Certain cooking methods may destroy the toxin however, even inhaling the fumes while cooking may result in toxicity. All members of this mushroom family are toxic and should not be consumed.
Gyromitra mushrooms contain gyromitin which splits into N-methyl-N-formyl hydrazine. Hydrazines all cause similar toxicity. Isoniazid is a hydrozine and causes identical toxicity as gyromitrin containing mushrooms. Hydrazines react with pyridoxine and inhibits pyridoxal phosphate-related enzymatic reactions and thereby decreases the production of GABA from the excitatory neurotransmitter, glutamate. This depletion of GABA and this excess of glutamate causes profound, refractory seizures and status epilepticus. The initial signs of toxicity for these mushrooms include nausea, vomiting, diarrhea and abdominal pain that begin 5-10 hours after ingestion. In the first 12-48 hours, seizures develop.
Muscarine containing mushrooms include numerous members of the Clitocybe genus and Amanita muscaria and amanita pantherina. Muscarine and acetycholine are structurally similar and have similar clinical effects. Clinical manifestations are generally mild and begin within 30 minutes to 2 hours after ingestion. Peripheral manifestations including bradycardia, miosis, salivation, lacrimation, diarrhea, bronchorrhea and bronchospasm occur. The central cholinergic effects do not occur because the muscarine can't cross the blood brain barrier.
Most of the mushrooms in this group are primarily in the Amanita genus and include Amanita muscaria. They have a bright red cap and is commonly depicted in childrens books. Small quantities of ibotenic acid and muscimol are found in these mushrooms. Ibotenic acid is structurally similar to glutamate and muscimol acts as a GABA agonist. Patients that develop symptoms after ingestion of these are generally intentionally ingesting them with an effort to experience hallucinations. Within 30 minutes to 2 hours, patients can experience somnolence, dizziness, hallucinations, dysphoria and delirium. In children, myoclonic movements, seizures and other neurologic findings tend to predominate.
Psilocybin containing mushrooms are by far the most common mushrooms used for its hallucinogenic properties. Psilocybin is hydrolyzed to psilocin after ingestion. Psilocybin and psilocin structurally resemble serotonin and therefore have serotonergic like properties. Ingestion of these mushrooms result in predominatly CNS effects including visual illusions and hallucinations.
Some patients may experience tachycardia, anxiety, agitation and mydriasis though for the most part, most patients exposed to psilocybin mushrooms rarely present to healthcare. The onset of effects occur within the first 1 hour after ingestion. Vomiting is not an uncommon finding depending on the dose ingested though all symptoms dissipate within 4 hours after use.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Testing for Toxic Alcohols
Testing for toxic alcohols is not generally available. It is imperative to know if your hospital has the capability to do this testing and where the testing can be performed. Depending on location, the testing may only be done as a send-out test to a reference lab and results may take several days to return, lessening the clinical usefulness of the test. If this is the case, surrogate testing needs to be done to determine the need for treatment and the end point of therapy.
Early on after ingestion, there will be no end-organ manifestations such as anion gap acidosis or renal dysfunction.
If a test for toxic alcohol concentrations is readily available, the level can guide management decisions. Traditionally, a serum concentration of ethylene glycol or methanol considered to be toxic is 25 mg/dL. Treatment with ADH inhibitors and co-factors should be employed with serum concentrations of greater than 25 mg/dL. Empiric hemodialysis is recommended for methanol levels of greater than 25 mg/dL.
When serum concentrations of toxic alcohols are not readily available, surrogate markers are used to guide therapeutic decisions. Routine initial laboratory evaluation should include a basic metabolic profile to assess acid-base status and renal function. Serum osmolality should be determined. In a patient with suspicion of intentional drug overdose, serum ethanol concentrations should be obtained as well as other toxicologic studies including acetaminophen and salicylates. Most pediatric exposures however are going to be the unintentional exposure to a toxic alcohol, and they are more likely to present early following ingestion.
Anion Gap and Osmol Gap
The metabolites of ethylene glycol and methanol are dissociated organic acids thereby resulting in an anion gap acidosis. The acidosis takes time to develop and therefore, the absence of an anion gap early after reported toxic alcohol ingestion does not exclude the diagnosis.
An early surrogate marker in toxic alcohol poisoning is the osmol gap. The parent compounds are osmotically acting and thereby, can result in an osmolar gap before they undergo ADH metabolism.
The osmolar gap is not sensitive or specific for toxic alcohol exposure. The normal range of a normal osmolar gap is -14 to +10 so a patient with a normal osmolar gap does not exclude poisoning. A large osmolar gap (>40), however, is difficult to explain by anything other than a toxic alcohol.
The osmolar gap and anion gap are inversely related to each other. As the osmolar gap decreases (as parent compound is being metabolized into toxic by-products), the anion gap increases (because of the presence of organic acids).
Fluorscein is often added to ethylene glycol containing antifreeze preparations. It is added so that, under a black light, it is easier for a leak in a vehicle to be identified. In one healthy volunteer study, fluorscein is present in the urine for about 1-2 hours after ingestion and this may help confirm the diagnosis. Because of interfering substances that may also fluoresce, it is important to place the urine on a piece of gauze or a bed-sheet and compare it to a control urine that you do not suspect toxic alcohol exposure. The lack of fluorescence does not exclude an ingestion of an ethylene glycol containing product.
Once metabolism has occurred and oxalic acid is formed (in the case of ethylene glycol), a urinalysis with the presence of calcium oxalate crystals will also aid in the diagnosis.
Isopropyl alcohol is metabolized to acetone so can cause ketosis without acidosis.
Testing for Hydrocarbon Exposure
Laboratory studies should be guided by the nature of the specific hydrocarbon ingested and by the patient's clinical findings. In ingestion of hydrocarbons with suspected aspiration and pulmonary toxicity, pulse oximetry and arterial blood gas monitoring should be performed as clinically indicated.
Methylene chloride is metabolized in vivo to carboxyhemoglobin; a carboxyhemoglobin level should be obtained and repeated in 4-6 hours after exposure for assessment.
Toluene was classically abused as an inhalant and causes a renal tubular acidosis. If toluene is suspected, basic metabolic profile and urinalysis should be done as clinically indicated.
Carbon tetrachloride, though rarely available currently, causes a centrilobular necrosis and liver function tests should be obtained.
Benzene causes bone marrow toxicity and aplastic anemia as well as acute myelogenous leukemia after chronic exposure.
Testing for Mushroom Exposure
In patients with delayed or prolonged GI toxicity, basic metabolic profile, ALT, AST, Bilirubin and coagulation studies should be observed closely for at least 2-3 days after ingestion. If there are no changes in liver function tests on day 3, it is reasonable to assume that the hepatotoxicity will not occur. In those demonstrating toxicity, close monitoring including every 8 to 12 hour laboratory testing to trend the severity of the hepatic and renal dysfunction is necessary.
In a patient with refractory seizures due to these mushrooms, basic metabolic profile should be done to assess acid-base status though there are no particular tests to prove toxicity.
No specific laboratory testing is necessary. In patients with diarrhea and vomiting, basic metabolic profile should be done to assess electrolytes and acid base status.
No specific laboratory testing is necessary or particularly useful.
No specific laboratory testing is necessary or particularly useful.
Would imaging studies be helpful? If so, which ones?
In patients with respiratory symptoms, a chest radiograph should be obtained. Routine chest radiograph is not necessary for asymptomatic patients. Radiographic findings are present in up to 88% of cases of hydrocarbon ingestions where there is suspected aspiration. The findings can be immediate or delayed up to 24 hours. 90% of patients that develop radiographic findings do so within the first 4 hours of exposure. Specific radiographic findings include: perihilar densities; bibasilar infiltrates and pneumonic consolidation. Pneumothorax and pneumomediastinum occur rarely. Radiographic resolution does not correlate with clinical improvement.
In patients with inhalational abuse of hydrocarbons, there is a risk of QTc prolongation and dysrhythmias. In any patient with syncope or altered mental status or presumed cardiac toxicity, an electrocardiogram should be performed.
Confirming the diagnosis
Confirming Ethylene or Methanol Exposure
Emergency Department management of an unintentional pediatric exposure to ethylene glycol or methanol:
Is the history of exposure consistent with a potentially toxic serum concentration?
If yes, determine if toxic alcohol concentrations can be obtained within a reasonable turn around time.
If yes, send off serum concentrations for analysis
Obtain baseline basic metabolic profile and measured osmolality; calculate the anion gap and the osmolar gap.
Treatment with Fomepizole and co-factors should be employed as soon as toxic alcohols are suspected in the differential diagnosis.
Give fomepizole 15 mg/kg as a loading dose; initiate co-factors (see below)
If the treating facility does not have fomepizole, it is imperative to classify the risk of ethanol versus the benefit.
Follow BMPs every hour and if signs of anion gap acidosis develop, then to initiate treatment.
Hemodialysis should be performed for any anion gap acidosis or markedly elevated levels of toxic alcohols.
Consultation with the regional poison center should be considered in all of these patients.
If you are able to confirm that the patient has ingestions of environmental toxins, what treatment should be initiated?
Treatment for Toxic Alcohol
As always, immediate resuscitation with careful attention to airway, breathing and circulation. Toxic alcohols are rapidly absorbed and gastrointestinal decontamination has little role.
ADH inhibition with fomepizole is the mainstay of therapy. ADH inhibition prevents the formation of toxic metabolites. This allows for time for establishment of a definate diagnosis as well as time for other interventions such as hemodialysis.
Fomepizole competitively inhibits ADH and is a safe and effective antidote in the management of ethylene glycol and methanol toxicity. Ethanol also inhibits alcohol dehydrogenase and though there are no head to head studies comparing the efficacy, the ease of its administration and the relative lack of serious adverse effects makes fomepizole to the preferred antidote. This is of particular importance in the pediatric population where ethanol causes CNS depression; inebriation; hypoglycemia; gastritis (if given orally) and phlebitis and hypertonicity with hyponatremia (if given intravenously).
The dose of fomepizole is 15 mg/kg intravenously over 30 minutes (in either 100 mL of D5W or NS) followed by 10 mg/kg every 12 hours.
If used, the dose of ethanol is variable as the goal of therapy is to maintain a serum ethanol concentration of 100 - 150 mg/dL.
In addition to ADH inhibition, IV administration of 50 mg folic acid or folinic acid every 6 hours will enhance methanol elimination and has been shown to prevent the retinal toxicity in animal models.
Urinary alkalinization (urine pH > 8) with IV sodium bicarbonate (for serum pH < 7.3) will enhance the formate elimination and may reduce the distribution of formic acid to the eye.
For ethylene glycol, IV thiamine 100 mg every 6 hours and IV pyridoxine 50 mg every 6 hours theoretically shunts the metabolism away from oxalic acid towards less toxic metabolites. There is no human data to support this however, these agents are well tolerated and the potential benefits outweigh any risks.
Treatment for Hydrocarbons
Aspiration of hydrocarbon
Patients with evidence of aspiration and pulmonary toxicity should be managed supportively. Close attention should be paid to airway and breathing. Endotracheal intubation and ventilation may be required in severely ill patients. Patients with severe hydrocarbon toxicity pose unique problems and are often difficult to ventilate. Ventilatory support may require use of positive end expiratory pressure (PEEP) or even high frequency jet ventilation. In severely poisoned patients despite this, ECMO has been effective.
Antibiotics are often employed in the severely ill patients. Antibiotic therapy should be based on sputum cultures if the patient can provide a reliable sputum sample.
Though corticosteroids have been used prophylactically, there is little data to suggest that it improves the acute course of toxicity. Because of the risks of corticosteroids and the relative lack of benefit, they are not recommended routinely.
Inhalational Abuse of Hydrocarbons
Management of the dysrhythmias associated with hydrocarbons should include consideration of electrolyte abnormalities and acid base disturbances. In the setting of ventricular dysrhythmias, it is presumed that hydrocarbons sensitize the myocardium to catecholamines and directly prolong the QTc interval. In this setting, catecholamines should be avoided. Lidocaine and beta-adrenergic antagonists have been successfully used. Esmolol is a logical choice because it is given intravenously and has a short duration of effect which allows for it to be discontinued if the condition of the patient deteriorates.
Treatment for Mushroom Ingestion
Fluid and electrolyte repletion is essential especially in the face of fluid loss due to vomiting and diarrhea. Activated charcoal adsorbs the amatoxins and should be given as long as the vomiting can be controlled. Activated charcoal can be given even delayed after the ingestion and multiple doses of charcoal can be considered because of the enterohepatic recirculation of the amatoxins. Activated charcoal 1 g/kg without sorbitol should be given every 2-4 hours.
Milk thistle's active complex, silymarin consists of silibinin, silychristin and silydianin. Silibinin may modify or occupy cell membrane receptor sites and inhibit hepatocellular penetration of alpha-amanitin. A dose of silibinin 20-50 mg/kg/day should be used. Legalon SIL is a new commercially available FDA approved product containing a highly purified intravenous preparation of silybinin. It is now available in the United States and will be delivered within 24 hours of request. Any physician with suspicion that a patient ingested a cyclopeptide containing mushroom should call 866-520-4412. Contact with your regional poison center can help facilitate this.
N-acetylcysteine should be given as an antidote for cyclopeptide mushrooms. NAC has well known hepatoprotective benefits and though no data supports a specific benefit in this setting, its good safety profile and its potential benefit, yields it a reasonable antidote. The dosing of NAC is the same as for acetaminophen toxicity. There is limited role for extracorporeal removal of the toxins. In severely ill patients, transplant may be the only alternative.
Activated charcoal 1 g/kg should be given if the ingestion is known and the patient is not demonstrating signs of altered mental status. Benzodiazepines are appropriate for the initial management of seizures however, due to the mechanism of toxicity, the seizures will be refractory to benzodiazepines. Pyridoxine (Vitamin B6) should be given for seizure activity in conjunction with benzodiazepines. Pyridoxine 70 mg/kg IV is the dose in pediatric patients and the adult dose is 5 grams IV.
Symptoms are generally mild and treatment is often largely supportive. In rare cases, atropine 0.02 mg/kg IV (minimum: 0.1 mg) in pediatric patients can be given to reverse the symptoms.
Treatment is largely supportive. Supportive care is the mainstay of therapy. In children experiencing predominantly the neurologic manifestations, treatment with a benzodiazepine is not unreasonable.
Treatment is largely supportive. A calm, quiet environment is the best approach to a person that is experiencing a 'bad trip'. In patients with frightening hallucinations; agitation; anxiety or tachycardia, benzodiazepines are a logical intervention.
What are the adverse effects associated with each treatment option?
Toxic Alcohol Treatment Adverse Effects
Fomepizole is very well tolerated. Adverse events include mild irritation to the IV site, headache, nausea, dizziness and a bad or metallic taste in the mouth.
Ethanol is associated with significant adverse events of particular concern in the pediatric patient including CNS depression; hypoglycemia; nausea and vomiting. It also requires frequent serum ethanol concentrations to maintain a serum concentration of 100 - 150 mg/dL. Frequent venous blood glucose monitoring is required.
There is little to no adverse effects secondary to the adjuvant co-factor therapies.
What are the possible outcomes of ingestions of environmental toxins?
Outcomes of Toxic Alcohol
Toxic alcohols cause severe morbidity and mortality. Even a small, unintentional exposure in a pediatric patient can result in catastrophic effects if left untreated. If untreated, they cause anion gap acidosis and end-organ manifestations including retinal toxicity and renal toxicity. The availability of a commerically available antidote, fomepizole, has improved the management of these patients compared to the difficulties in dosing and the side effect profile of ethanol.
Methanol toxicity can cause retinal toxicity. The visual impairment ranges from blurry or hazy vision to snowfield vision to complete blindness. Central scotoma may be present on visual field testing. Hyperemia and pallor of the optic disc, papilledema and an afferent papillary defect are described as characteristic findings.
Outcomes of Hydrocarbon Exposure
In the majority of cases, exposures to hydrocarbons result in minor toxicity and resolve with supportive care. In patients with aspiration of hydrocarbons have high morbidity due to the acute lung injury. These patients are managed supportively with close attention paid to maintaining oxygenation and ventilation. The majority of patients with aspiration from hydrocarbons improve over time with no long term sequelae.
Inhalation of hydrocarbons in an attempt to get high is a concerning epidemic and can result in hypoxia as well as sudden sniffing death syndrome. Long term abuse of hydrocarbons can also result in irreversible neurologic problems.
Outcomes of Mushroom Exposure
Though there are numerous classes of toxic mushrooms, the majority of pediatric exposures in the United States are due to mushrooms that only cause gastrointestinal irritation. In this scenario, the gastrointestinal illness manifests as nausea, vomiting and potentially diarrhea and is self-limited and rapidly resolves without any specific intervention. The relative time to onset of gastrointestinal symptoms (less than 5 hours) is often predictive that the exposure was a nontoxic mushroom. In patients exposed to toxic mushrooms, by far, the most concerning mushroom are cyclopeptide-containing mushrooms. These cause hepatocellular necrosis and depending on the severity of toxicity, patients may require aggressive care potentially including liver transplant.
It is imperative that if a patient is exposed to a mushroom that they call the regional poison center for specific recommendations and treatment modalities.
What is the evidence?
Bronstein, AC, Spyker, DA, Cantilena, LR. "2009 annual report of the American Association of Poison Control Centers National Poison Data System (NPDS):27th annual report". Clin Tox. vol. 48. 2010. pp. 979-1178.
McMartin, KE, Brent, J. "Pharmacokinetics of fomepizole in patients". J Tox Clin Tox. vol. 36. 1998. pp. 450-1.
Brent, J, McMartin, K, Phillips, S. "Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the Treatment of Methanol Poisoning". NEJM. vol. 344. 2001. pp. 424-429.
Brent, J, McMarin, K, Phillips, S. "Fomepizole for the treatment of ethylene glycol poisoning. Methypyrazole for toxic alcohols study group". NEJM. vol. 340. 1999. pp. 832-838.
Sanaei-Zadeh, H, Zamani, N, Shadnia, S. "Outcomes of visual disturbances after methanol poisoning". Clin Tox. vol. 49. 2011. pp. 102-107.
Barceloux, DG, Bond, GR, Krenzelok, EP. "American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol poisoning. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning". J Tox Clin Tox. vol. 40. 2002. pp. 415-446.
Noker, PE, Ells, JT, Tephly, TR. "Methanol toxciity: Treatment with folic acid and 5-formyl tetrahydrofolic acid". Alcohol Clin Exp Res. vol. 4. 1980. pp. 378-383.
Bond, GR, Pieche, S, Sonicki, Z. "A Clinical Decision Rule for Triage of Children under 5 years of age with hydrocarbon (kerosene) aspiration in developing countries". Clin Tox. vol. 46. 2008. pp. 222-229.
Moritz, F, de La Chapelle, A, Bauer, F. "Esmolol in the treatment of severe arrhythmia after acute trichloroethylene poisoning". Intensive Care Med. vol. 26. 2000. pp. 256.
Tong, TC, Hernandez, M, Richardson, WH. "Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid and silybinin in a murine model". Ann Emerg Med. vol. 50. 2007. pp. 282-288.
Rengstoerff, DS, Osorio, RW, Bonacini, M. "Recovery from severe hepatitis causes by mushroom poisoning without liver transplantation". Clin Gastroenterol Hepatol. vol. 1. 2003. pp. 392-396.
Jacobs, BP, Dennehy, C, Ramirez, G. "Milk thistle for the treatment of liver disease: a systematic review and meta-analysis". Am J Med. vol. 113. 2002. pp. 506-515.
Enjalbert, F, Rapior, S, Nouguier-Soule, J. "Treatment of amatoxin poisoning: 20 year retrospective analysis". J Tox Clin Tox. vol. 40. 2002. pp. 715-757.
Covic, A, Goldsmith, DJA, Gusbeth-Tatomir, P. "Successful use of molecular absorbent regenerating system (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion". Liver Int. vol. 23. 2003. pp. 21-27.
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.
Endocrinology Advisor Articles
- Two Phases of C-Peptide Decline Identified in Type I Diabetes
- Dulaglutide Effective for Patients With T2D, Moderate to Severe CKD
- Incidence of Diabetes Influenced by Endocrine-Disrupting Chemicals in the Environment
- Guidelines for Management of Hypothalamic-Pituitary, Growth Disorders in Childhood Cancer Survivors
- Subclinical Hypothyroidism: Controversies in Testing and Treatment
- Using Latent Class Trajectory Analysis to Determine Glucose Response Curve Patterns
- First CGM System With Implantable Glucose Sensor Approved
- Adjunctive Metformin for Insulin Resistance in T1D: A Clinical Perspective
- Risk for Below Knee Amputations With Canagliflozin vs Other Antihyperglycemic Agents
- Empagliflozin, Linagliptin Combination Therapy vs Linagliptin Monotherapy for Type 2 Diabetes
- Type 2 Diabetes and Alzheimer Disease: What's the Connection?
- Government and Industry Lead the Way in Funding USPSTF Systematic Reviews
- New Romosozumab BLA Includes Data from Additional Osteoporosis Trials
- Impact of Maternal Diabetes on Outcomes in Very Preterm, Very Low-Birth-Weight Infants
- Age-Related Differences in Manifestation of Cushing Disease Identified