Poison Prevention and Management Pharmacist Learning Objectives: Pharmacy Technician Learning Objectives: Introduction

Transcription

1 Poison Prevention and Management By Aaron LePoire, Pharm.D., PGY1 resident, Meijer/Ferris State University/Pfizer Community-Based Pharmacy Residency Program, Hudsonville Pharmacist Learning Objectives: 1. Identify available resources for poison control education and information. 2. Recognize common poisons and primary prevention practices. 3. Review appropriate management of selected toxicities. Pharmacy Technician Learning Objectives: 1. Identify common potential household toxins. 2. Recognize strategies for primary prevention of poisoning. 3. Describe available resources for poison management. Introduction Since 2011, unintentional poisoning has surpassed motor vehicle accidents as the leading cause of injury-related deaths, with unintentional poisoning accounting for 21% of all injury deaths in Each year, for the last five years, more than one million poison exposures have been reported to the American Association of Poison Control Centers (AAPCC) among children less than six years of age. 2 One of the Healthy People 2020 goals is to prevent an increase in nonfatal poisonings; however, the rate of nonfatal poisonings has been steadily increasing from per 100,000 population in 2008 to per 100,000 population in The AAPCC annual report from 2015 documented that the 55 poison control centers in the United States received nearly three million calls and averaged a call regarding a human exposure every 14.5 seconds. 4 The Children s Hospital of Michigan Regional Poison Control Center in Detroit provides services for the entire state of Michigan, and each poison control center handles calls from a different region in the country. 5 Most human exposures to toxic products are unintended, with 78.4 percent of exposures classified as unintentional in In injury prevention literature, unintentional is the preferred term over accidental, since an accident implies a random happening by chance, while poisonings are a preventable, predictable event, unlike other types of injuries. 2 Unintentional exposures can be attributed to general causes, therapeutic errors and misuse, among others. 4 Exposure to dangerous or potentially dangerous substances primarily occurs in children, with 47 percent of poison control calls for human exposures occurring in children less than six years of age, and 70 percent of calls taking place from a residential location. 4 With the increasing number of deaths due to unintentional poisoning, pharmacists are in a unique and accessible position to identify the toxicological resources available, recognize potential adverse events due to poisoning and provide counseling on actions to take in case of an emergency. Table 1. List of common potential household toxins. 2,4 Household cleaning supplies Cosmetics Vitamins/Dietary supplements Art supplies Essential oils

2 Death Rate Per 100,000 Population Antifreeze Batteries Laundry detergent Figure 1. Injury death rates in the United States 6 Motor vehicle traffic, poisoning, and drug poisoning death rates United States: Year Poisonings Drug Poisonings Motor Vehicle Primary Prevention Primary prevention should be the main focus for reducing the number of unintentional poisoning deaths and includes education, legislation and product engineering. 2 Some examples of product engineering measures to prevent poisoning include bittering agents, poison warning labels and flow restrictors for liquid medications. 2 Flow restrictors such as those found on infant acetaminophen bottles can increase the time it takes to empty a bottle as well as reduce the amount of liquid removed, allowing more time for a child to be discovered with the substance before ingestion. 2 In 2015, the American Academy of Pediatrics issued a statement regarding the dosing of liquid medications, recommending the exclusive use of metric dosing for liquid medications rather than teaspoons or tablespoons, along with providing a milliliter based dosing device for the patient. 7 Legislation and regulation can have a significant impact on reducing unintentional poisoning, and after the 1966 regulation on package sizes of baby aspirin, aspirin poisoning deaths decreased from 144 deaths in 1960 to 12 deaths in Table 2. Significant Legislation and Regulation for Poison Prevention 2 Year Legislation/Regulation Impact 1906 Pure Food and Drug Act Created Food, Drug, and Insecticide Administration which became the Food and Drug Administration (FDA) in 1930.

3 1927 Caustic Poison Act Required warning labels for lye and other caustic substances Durham-Humphrey Amendment Created OTC and prescription medication categories Public Law Designated National Poison Prevention Week as the third week in March Baby aspirin packaging regulation 1970 Poison Prevention Packaging Act 1997 FDA regulation on iron packaging Restricted baby aspirin to 36 tablets per container. Required child-resistant packaging for certain drugs and household products. Required unit-dose packaging for iron products with 30 mg or more per dose. Regulation withdrawn in Public Law Established the nationwide toll-free poison control telephone number FDA OTC cough and cold recommendation 2011 FDA guidance on dosage delivery devices 2016 Child Nicotine Poisoning Prevention Act FDA recommends to not use in children less than two, and the Consumer Healthcare Products Association issued warnings for children less than four. Improved consistency between dosing instructions and devices for liquid OTC medications. Required child-resistant packaging for liquid nicotine used with electronic cigarettes. Resources While most pharmacists may not be in a position to enact legislation or engineer safer products, pharmacists can participate in education, which plays a massive role in preventing unintentional poisonings. There are many resources available for pharmacists and the general public to access and use to educate people of any age or background on poison prevention. The American Association of Poison Control Centers (AAPCC) has educational resources including videos, brochures, and presentations available on their website at 8 The Health Resources & Services Administration (HSRA) provides educational materials on their website, including poison prevention tips and articles, brochures and videos pertaining to poison control. 9 HSRA also sponsors a program called Taking Your Medicines Safely which provides training to individuals interested in delivering an educational program to older adults in settings such as senior centers, libraries or churches. 9 This educational program

4 covers a variety of areas including ways to keep track of medications, the potential problems with over-the-counter medications and questions to ask about medications they are taking. 9 The Central Ohio Poison Center sponsors the Be Poison Safe and Be Poison Wise programs which offer poison prevention educational materials intended for providers, children, parents, and the general public at little or no charge. 10 National Poison Prevention Week, which was established in 1961, occurs every year during the third full week in March. 8 Poison centers and other organizations throughout the country organize events and activities during this week to promote awareness of poison prevention measures. These resources, along with many other programs and organizations, are helpful places to start when promoting awareness and safer practices in the community. There are multiple resources available to inform both healthcare providers and the general population about the dangers of a variety of poisonous substances. The most readily available resources are provided by AAPCC, who through the use of the National Poison Center phone number, also known as the Poison Help line ( ), can connect an individual to a trained medical expert at the closest poison control center. The staff at the poison centers are comprised of registered nurses, pharmacists, physicians, physician assistants and medical and clinical toxicologists who have received specialized toxicology training. 4 Not only do poison control centers assist with acute exposure, they also answer questions regarding drug identification, compounding, drug-food and drug-drug interactions, safe handling and disposal of chemicals, withdrawal, foreign medications, drug use during pregnancy and breastfeeding, environmental exposure, and toxicological information for specific substances. 4,11 During 2015, poison control centers also made almost 2.7 million follow-up calls in 46.8 percent of human exposure cases in order to monitor management and outcomes of cases. 4 Monitoring these cases helps to inform guidelines and prevention education. Poison control centers can also help reduce healthcare costs by decreasing the amount of emergency department visits. A study conducted at the Utah Poison Control Center found that among patients who called the center from , the poison center potentially saved an annual cost of $16.6-$24.4 million dollars in unneeded medical charges, with the annual expenses for a poison control center averaging only $2.5 million dollars. 12 Poison control centers are an invaluable resource for the public and healthcare professionals, and should be considered a first line option when encountering questions on toxicology. Table 3. Strategies to prevent exposure to potential toxins in children. 2 Do not refer to medications as candy, refer to it by the correct name. Safely dispose of unneeded medications and store other medications appropriately. Keep products in their original containers. Do not transfer substances to alternate containers. Post poison control center number near a telephone or program it into your cell phone. Keep potential poisons out of sight and reach of children. Use safety latches on drawers and cabinets where potential household toxins are kept. Do not eat or drink while using art products and wash skin after using. Do not take medication in view of children who may copy the behavior. Replace safety caps immediately after medication use. Another resource available through AAPCC is their website ( which launched in March of 2017 and allows an individual to input a substance, answer questions about the exposure and receive advice on how to proceed. 13 For more in-depth information on specific

5 medications and chemicals, the National Library of Medicine Toxicology and Environmental Health Information Program (TEHIP) provides resources for healthcare professionals and the general public on poison control through the TOXNET database. 14 Some of the resources available through the TEHIP website include the Hazardous Substances Data Bank, Toxicology Literature Online (TOXLINE) and the Household Products Database. 14 The TEHIP website also has information available to consumers, with interactive learning for both children and adults. Pharmacists may utilize these resources to answer questions patients may have about specific products or to review literature regarding a product or chemical. While prevention is an important aspect of poison control, acute exposure to dangerous or potentially dangerous substances may warrant a more emergent response. As a pharmacist, it is vital to know how to respond to an emergency situation involving an intentional or unintentional poisoning. If an individual has collapsed, had a seizure, has trouble breathing or cannot be awakened, call 911 immediately. 13 If a patient or caregiver needs urgent assistance, but the exposure does not necessarily warrant a 911 call, the Poison Help line can be called for further instructions. For the poisoned patient, the cornerstone to treatment is supportive care, and many patients can be treated with supportive care and decontamination alone. In the following sections, more specific management principles will be discussed for a few of the more common exposures. Gastrointestinal Decontamination The American Academy of Pediatrics no longer recommends the use of ipecac syrup in the event of acute ingestion of a potential toxin. 15 Inducing vomiting can increase the difficulty of administering needed poison treatment in a healthcare setting, and could lead to other adverse events, including lethargy and diarrhea. 15 Activated charcoal has also been historically used for gastric decontamination and works by adsorbing chemicals and preventing gastrointestinal absorption of the toxic substance. The use of activated charcoal has also been declining, with use in 3.7 percent of pediatric poisoning cases in 1993 compared to percent in While there is evidence to use activated charcoal in select situations, the use of activated charcoal at home is not recommended without the specific guidance of a healthcare professional. 15 The efficacy of activated charcoal is greatest if used within one hour of acute ingestion, although benefits can still be seen if given later than one hour. 16 Activated charcoal can be administered orally as a single dose or as multiple doses, although evidence is limited with the use of multiple doses. 17 A serious risk of activated charcoal administration is pulmonary aspiration due to improper administration, which can lead to aspiration pneumonitis or death. 15 Because of this, activated charcoal is commonly administered via nasogastric tubes in emergency departments. 15 Other adverse events include bowel obstruction and emesis. 16 The tolerability of activated charcoal can also pose a problem, with one randomized trial reporting adults consumed on average only 83 percent of their first dose of oral activated charcoal suspension and 27 percent of patients vomited after administration. 16 Whole bowel irrigation (WBI) is another form of gastrointestinal decontamination where an osmotically balanced polyethylene glycol electrolyte solution is administered in order to induce liquid stool and flush the ingested substance from the bowel. 17 WBI may be useful when sustained-release formulations of medications or toxins not adsorbed by activated charcoal are ingested. 17 Gastric lavage may also be used for gastric decontamination, and has been commonly referred to as stomach pumping. 17 A large bore orogastric tube is used and small amounts of fluid are instilled and then aspirated repeatedly in order to extract toxins from the stomach. 17 Gastric lavage has

6 largely fallen out of favor due to risk of complications and unclear benefit, with the American Academy of Clinical Toxicology issuing a statement in 2004 recommending that gastric lavage not be routinely used in the management of poisoned patients. 18 Other gastrointestinal decontamination methods include endoscopy or surgery which may be indicated if less invasive methods are inadequate to remove a life-threatening toxin. 17 Table 4. Top 5 substance classes involved in human exposures in Analgesics Household products Cosmetic/Personal care products Sedatives/Hypnotics/Antipsychotics Antidepressants Iron Iron toxicity is common among children, although incidence has been decreasing since the implementation of various public health initiatives, including the 1997 FDA regulation requiring products with 30 mg or more of elemental iron to be in unit-dose packaging. 2 However, this regulation was withdrawn in 2003 due to a court decision that ruled the FDA did not have the authority to regulate the packaging of dietary supplements for poison prevention. 2 Iron is available in many different forms, with some of the more toxic forms being ferrous fumarate, sulfate and gluconate. 19 Iron is also commonly found in prenatal vitamins. Iron can become toxic following ingestion of 20 mg/kg elemental iron, with symptoms including nausea, vomiting, diarrhea, abdominal pain and hematemesis. 19 Iron tablets may have some radiopacity depending on the formulation and the amount of elemental iron, and a plain radiograph of the abdomen may show the presence of iron, although radiographs showing little or no iron do not necessarily rule out a significant ingestion. 20 Management of iron toxicity can include whole bowel irrigation, but should not include activated charcoal due to reduced binding to iron. 19 Deferoxamine is another therapeutic option which binds to ferric iron and the complex is then excreted through the kidneys, causing the urine to become orange or reddish brown. 20 Patients should be treated with a continuous IV infusion of deferoxamine when exhibiting signs of systemic toxicity, anion gap metabolic acidosis, significant number of tablets on abdominal radiograph or with an iron level >500 mcg/dl. 19,20 Initial administration can cause hypotension, and fluid replacement is preferred for reversal of hypotension over slowing the rate of administration. 20 Duration of deferoxamine treatment can vary based on resolution of toxicity or the patient s clinical status, but a typical duration of treatment is 24 hours. 20 Duration longer than 24 hours should be avoided due to the toxicities associated with prolonged deferoxamine use including acute respiratory distress syndrome. 19,20

7 Active Learning RM, a 32-year-old female, comes into the pharmacy to pick up her prenatal vitamins from the pharmacy with her two-year-old daughter. What counseling points could you give RM to decrease the chances of an unintentional poisoning? Feedback RM could be counseled about the importance of keeping the vitamins out of reach of her daughter, not taking them in front of her daughter and keeping the poison control number programmed in her cell phone. She should also be educated that prenatal vitamins contain iron, which can be harmful if too much is ingested, especially in children. Acetaminophen Acetaminophen toxicity can occur in a variety of settings, in part due to acetaminophen being an ingredient in a variety of combination products and having numerous brand names. A survey on patient knowledge of acetaminophen found only 11 percent of patients could correctly identify acetaminophen and APAP as alternative names for the brand name. 21 Some of the symptoms that may occur in acetaminophen toxicity include nausea, vomiting, malaise, pallor and diaphoresis; although, many patients are asymptomatic. 22 Treatment is determined by use of the Rumack-Matthew nomogram evaluating the acetaminophen concentration and time since ingestion. 23 Other indications besides using the nomogram could include evidence of liver injury, an unknown amount of time since ingestion with an acetaminophen concentration >10 mcg/ml or ingestion of >150 mg/kg or 7.5 grams of acetaminophen where concentration will not be known until more than eight hours after ingestion. 23 Treatment for early presentation can include activated charcoal or gastric emptying, although gastric lavage is not routinely recommended. 22,23 N- Acetylcysteine (NAC) should be administered either IV or orally and the FDA-approved treatment protocols include a 20-hour IV and 72-hour oral protocols. 23 Oral NAC is not tolerated well, with approximately 33 percent of patients experiencing nausea and vomiting. 23 If vomiting occurs within 60 minutes of an orally administered dose, the dose should be repeated. 23 The most likely mechanism of action of NAC in acetaminophen toxicity is the restoration of hepatic glutathione stores, which helps prevent the conversion of acetaminophen to the toxic metabolite N-acetyl-pbenzoquinoneimine (NAPQI) and helps to detoxify the already formed NAPQI. 23 Additional options for acetaminophen removal include hemodialysis, plasma exchange or liver dialysis. 22 Beta-Blockers Beta-adrenergic antagonist toxicity may result in bradycardia, hypotension, bronchospasm, hypoglycemia, delirium, coma and seizures. 24,25 Symptoms usually present within six hours of ingestion; however, sotalol and sustained-release products may have delayed toxicity in overdose. 25 Agents with more lipophilic properties such as propranolol may have an increased risk of delirium, coma and seizures even without the presence of hypotension. 24,25 Propranolol poisoning may also have an increase in bradycardia, hypotension, impaired atrioventricular conduction and widened

8 QRS interval due to propranolol having the most membrane-stabilizing activity among the betaadrenergic antagonists. 24,25 Sotalol in particular can cause electrocardiogram changes with a prolonged QT interval. 25 For patients presenting with beta-adrenergic antagonist poisoning, initial treatment should consist of atropine and intravenous fluids to resolve bradycardia and hypotension. 24,25 For patients who do not respond to initial treatment, glucagon may be trialed as a positive inotrope. 25 Glucagon can be initiated with an initial slow bolus, which may be repeated if no response is seen. 24 When a response is seen through increased pulse or blood pressure, a continuous infusion may be started. 24 A common adverse event with glucagon administration is emesis, which may require the administration of an antiemetic. 25 IV calcium salts may also be useful to reverse hypotension, with both calcium gluconate and calcium chloride being used. 25 Calcium must be monitored if using one of the IV calcium salts. Vasopressors may also be used if a combination of the above treatments are ineffective. An epinephrine infusion may be useful by exerting a positive inotropic and chronotropic effect. 25 Insulin and glucose present another possible option for those who are refractory to other treatment options. A high-dose insulin infusion is combined with a continuous IV infusion of dextrose in order to maintain euglycemia. 24 Response to high-dose insulin therapy may be delayed for up to 60 minutes, and it is important to maintain other treatments during this window. 24,25 Other possible therapies in patients who are refractory to the previous treatments include lipid emulsion therapy, sodium bicarbonate or magnesium with arrhythmias and hemodialysis. 25 Salicylates Salicylate toxicity can cause a variety of symptoms, including increased respiratory rate, tinnitus, hyperpyrexia, vertigo, altered mental status, anion gap metabolic acidosis and acute respiratory distress syndrome. 26,27 Aspirin can be fatal with as few as ten 325 milligram tablets in children. 27 Another common salicylate toxicity occurring in children is ingestion of oil of wintergreen. The active ingredient in oil of wintergreen is methyl salicylate, and pure oil of wintergreen contains at least 98 percent methyl salicylate, with five milliliters equivalent to seven grams of aspirin. 28 As essential oils become more popular, patients must be aware that children younger than six years can experience systemic toxicity with as little as a taste of oil of wintergreen. 26 During management of salicylate toxicity, activated charcoal binds to aspirin and can be used for decontamination, with earlier administration preferred. 26,27 Supportive care is an essential aspect of salicylate overdose; however, patients should not be intubated unless absolutely necessary. Intubation and sedation increase the possibility of respiratory acidosis which may allow more salicylate diffusion across the blood-brain barrier and increase toxicity. 27 The mainstay treatment in salicylate toxicity is supportive care along with serum and urine alkalinization. 26,27 Alkalinization helps shift salicylate out of the central nervous system into the serum, where it can be eliminated by the kidneys. 26,27 Salicylate is also more easily excreted by the kidneys when the urine is alkalinized. 26,27 A sodium bicarbonate bolus followed by infusion is used for alkalinization, maintaining a urine ph between 7.5 and Hypokalemia and hypovolemia must also be corrected, since hypokalemia may prevent alkalinization of the urine due to potassium and hydrogen exchange in the renal tubules. 26,27 Salicylate poisoning may also interfere with glucose metabolism, and dextrose administration may be required to correct hypoglycemia, especially in patients with altered mental status. 27 Hemodialysis may also be indicated in select patient populations. 26,27

9 Active Learning One of your patients has questions about using eucalyptus oil for sinus problems in her fouryear-old child. What resources could you use to find information on the toxicity profile of eucalyptus oil? Feedback: Some of the resources available to find toxicology information on substances include contacting the Poison Help Line at , the Poison Help website ( and the TOXNET databases online through the U.S. National Library of Medicine. Conclusion Pharmacists are in a unique position to be involved with poison prevention and control. Pharmacists are one of the most easily accessible healthcare providers, and patients may be unaware of the resources available to them or the significance of preventing unintentional poisoning in both children and adults. There are many ways pharmacists can make a difference to help decrease the rate of unintentional poisonings, including working in poison control centers and promoting primary prevention at their practice sites. With the rate of nonfatal and fatal poisonings increasing in the United States, pharmacists play a vital role in helping to reverse the trend. Primary prevention should be the main focus for reducing the amount of poisonings, and education is one of the easiest ways pharmacists can get involved. Pharmacists can educate patients they encounter in the pharmacy or take their efforts into the community and present materials to a variety of different audiences. People of all ages are at risk for unintentional poisoning, and educating the public on how to prevent poisoning is crucial to decreasing preventable injuries and death. Pharmacists should also be prepared to respond to an acute poisoning situation, and know what resources are available to be more confident when encountering situations where someone may have come into contact with a dangerous or potentially dangerous substance. References 1. Kochanek KD, Murphy SL, Xu J, Tejada-vera B. Deaths: final data for Natl Vital Stat Rep. 2016;65(4): Kelly, NR. Prevention of poisoning in children. In: Post TW, ed, UpToDate, Waltham, MA;2013. Up To Date website. Updated June 15, Accessed on July 12, U.S. Department of Health and Human Services. Injury and violence prevention. Healthy People 2020 website. Updated July 13, Accessed July 14, Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 33rd annual report. Clin Toxicol (Phila). 2016;54(10):

10 5. Michigan Regional Poison Control Center. Meet the team. Children s Hospital of Michigan DMC website. Accessed July 14, Center for Disease Control and Prevention. Fatal injury reports, national, regional, and state, WISQARS website. Updated February 19, Accessed July 12, Metric units and the preferred dosing of orally administered liquid medications. Committee on Drugs. Pediatrics. 2015;135(4): ; DOI: /peds American Association of Poison Control Centers (AAPCC). Prevention. AAPCC website. Accessed July 14, Health Resources & Services Administration. Resources. Poison Help website. Accessed July 14, Central Ohio Poison Center. Poison prevention resources. Nationwide Children s Hospital website. Accessed July 14, Armahizer MJ, Johnson D, Deusenberry CM, Foley JJ, Krenzelok EP, Pummer TL. Evaluation of pharmacist utilization of a poison center as a resource for patient care. J Pharm Pract. 2013;26(3): Tak CR, Malheiro MC, Bennett HK, Crouch BI. The value of a poison control center in preventing unnecessary emergency department visits and hospital charges: A multi-year analysis. Am J Emerg Med American Association of Poison Control Centers (AAPCC). I need help. Poison Help website. Published March Accessed July 14, National Library of Medicine. NLM resources on poison control. Toxicology and Environmental Health Information Program website. Published April 22, Updated June 1, Accessed July 14, Poison treatment in the home. American Academy of Pediatrics Committee on Injury, Violence, and Poison Prevention. Pediatrics. 2003;112(5): Juurlink D. Activated charcoal for acute overdose: a reappraisal. British Journal of Clinical Pharmacology [serial online]. March 2016;81(3): Hendrickson RG, Kusin S. Gastrointestinal decontamination of the poisoned patient. In: Post TW, ed, UpToDate, Waltham, MA;2013. Up To Date website. Updated January 24, Accessed on July 13, Vale JA, Kulig K. Position paper: gastric lavage. J Toxicol Clin Toxicol. 2004;42(7): Perrone J. Iron. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; Accessed July 10, Liebelt EL. Acute iron poisoning. In: Post TW, ed, UpToDate, Waltham, MA;2013. Up To Date website. Updated May 30, Accessed on July 11, Hornsby LB, Whitley HP, Hester EK, Thompson M, Donaldson A. Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity. J Am Pharm Assoc. 2010;50(4):485-9.

11 22. Hendrickson RG. Acetaminophen. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; Accessed July 10, Heard K, Dart R. Acetaminophen (paracetamol) poisoning in adults: treatment. In: Post TW, ed, UpToDate, Waltham, MA;2013. Up To Date website. Updated May 18, Accessed on July 11, Brubacher JR. β-adrenergic Antagonists. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; Barrueto F. Beta blocker poisoning. In: Post TW, ed, UpToDate, Waltham, MA;2013. Up To Date website. Updated April 11, Accessed on July 11, Lugassy DM. Salicylates. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; Accessed July 11, Boyer EW, Weibrecht, KW. Salicylate (aspirin) poisoning in adults. In: Post TW, ed, UpToDate, Waltham, MA;2013. Up To Date website. Updated January 9, Accessed on July 12, Shawn L. Essential Oils. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; Accessed July 12, 2017.