Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States

TOXICOLOGY/ORIGINAL CONTRIBUTION

Combined Evidence-Based Literature Analysis and Consensus Guidelines for Stocking of Emergency Antidotes in the United States

See Appendix for author affiliations. Received for publication October 28, 1999. Revision received March 22, 2000. Accepted for publication April 28, 2000. Presented in abstract form at the American College of Emergency Physicians Research Forum, Las Vegas, NV, October 1999. Supported by the United States Health Resource Services Administration and the American Association of Poison Control Centers. Address for reprints: Richard C. Dart, MD, PhD, Rocky Mountain Poison and Drug Center, 1010 Yosemite Circle, Denver, CO 80230; 303-729-1100, fax 303-729-1119. Copyright © 2000 by the American College of Emergency Physicians. 0196-0644/2000/$12.00 + 0 47/1/108182 doi:10.1067/mem.2000.108182

Richard C. Dart, MD, PhD Lewis R. Goldfrank, MD Peter A. Chyka, PharmD Donna Lotzer, RPh, CSPI Alan D. Woolf, MD, MPH Jude McNally, RPh, ABAT Wayne R. Snodgrass, MD, PhD Kent R. Olson, MD Elizabeth Scharman, PharmD, ABAT Robert J. Geller, MD Daniel Spyker, MD, PhD Monica Kraft, MD Robert Lipsy, PharmD

Study objective: To develop guidelines for the stocking of antidotes at hospitals that accept emergency admissions using combined evidence-based and consensus methods. Methods: Study participants were 12 medical care providers from disciplines that are affected by insufficient stocking of emergency antidotes (clinical pharmacology, critical care, clinical pharmacy, emergency medicine, hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology, pediatrics, poison control centers, pulmonary medicine, regulatory medicine). Selection of individuals for the study panel was based on evidence of previous antidote research or perspective regarding the purchase and use of antidotes. The literature regarding each antidote was systematically amassed using pre-1966 literature files, current MEDLINE searches, the reference lists of major medical textbooks, and citations solicited from the consensus panel. Articles relevant to 4 defined core questions were included. These articles formed the basis of an evidence-based analysis performed by the principal investigator. After literature analysis, a literature summary and proposed guidelines for antidote stocking were submitted to the panel. Consensus was formed by electronic iterative presentation of alternatives to each panel member using a modified Delphi method. All panel members participated in 5 rounds of guideline analysis of 20 antidotes. Results: Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N-acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol, ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime, physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be reached for 2 antidotes (flumazenil, physostigmine).

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Conclusion: These guidelines provide a tool to be used in revising or creating policies and procedures with regard to the stocking of antidotes in hospitals that accept emergency patients. [Dart RC, Goldfrank LR, Chyka PA, Lotzer D, Woolf AD, McNally J, Snodgrass WR, Olson KR, Scharman E, Geller RJ, Spyker D, Kraft M, Lipsy R. Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States. Ann Emerg Med. August 2000;36:126-132.] INTRODUCTION

Although antidotes are an important treatment for certain poisonings, the unavailability of antidotes is common in the United States. Antidotes such as digoxin immune Fab can be lifesaving when used at the appropriate time. For many poisons, an antidote must be available during the early stages of poisoning to prevent irreversible injury. For example, delay in administration of the cyanide kit to a patient may allow hypoxic brain injury to occur. Over the past 15 years, several studies have documented that antidotes are often not available in hospitals that accept emergency patients.1-7 The precise cause of this serious problem is unknown, but appears to be related to limited hospital resources. Larger hospitals are more likely than smaller or rural hospitals to stock antidotes adequately.1,2 Other possible causes are the costs of antidotes, as well as pharmacist and physician unfamiliarity with antidotes. The Joint Commission on Accreditation of Healthcare Organizations requires that hospitals stock antidotes, but does not provide specific requirements.8 Several regional poison control centers and some textbooks have created recommendations for antidote stocking, but accepted national guidelines are not currently available.9,10 In one study, hospital pharmacy directors overwhelmingly supported the creation of uniform guidelines for antidote stocking.2 In recent years, the concept of evidence-based patient management has gained popularity as a method of guiding medical practice.11 One difficulty with evidencebased medicine is that the evidence needed for an analysis may not be available, particularly for uncommon diseases. Antidotes are a good example of this difficulty. Most of the evidence available in the medical literature for antidotes is limited to simple documentation of patient improvement following administration of an antidote. For many antidotes, the presumption of efficacy is sup-

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ported only by retrospective case series, case reports, and single-author reviews. Another method of guiding clinical practice is the consensus guideline. Consensus guidelines are often desired during a period of change when practitioners desire advice on the value of a new approach or therapy. The consensus approach may be attractive because it continues the medical tradition of didactic instruction by authorities. Further, consensus is a seductively simple process: no special equipment or skills are apparently needed. One need only gather the appropriate experts. This perception is likely incorrect and may lead to numerous problems, the most important being that a consensus process can create erroneous guidelines.12 In the case of antidotes, however, there appears to be little alternative to the use of a consensus process. Rigorous evidence is lacking in most instances. On the other hand, it seems unreasonable to focus on a consensus approach alone and thereby neglect quality information. To emphasize the use of the evidence available and yet still produce useful guidelines, we combined an evidence-based review of the existing literature with a modified Delphi consensus method to create guidelines for hospital stocking of emergency antidotes in the United States. M AT E R I A L S A N D M E T H O D S

The project had 2 phases. First, structured evidencebased analyses and synthesis of proposed guidelines were performed. This information was then used by a consenTable 1.

Profile of antidote panel members. Discipline or Specialty Clinical pharmacology Critical care Clinical pharmacy Emergency medicine Hospital pharmacy Internal medicine Managed care pharmacy Clinical toxicology Pediatrics Poison control center administration Pulmonary Regulatory medicine

No. of Participants 2 1 1 2 1 1 1 9 3 8 1 1

Categories were self-selected by panel participants. Total is greater than 12 because of multiple roles of some individuals.

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sus panel to produce guidelines specifically for use by hospitals that accept emergency patients. A modified Delphi approach was used to form consensus.13 Stocking of antidotes for mass releases of hazardous materials, accidental, or terrorist acts was not included in the panel’s deliberations.

A diverse group of 12 individuals representing various perspectives participated (Table 1). Individuals were selected by the principal investigator based on evidence of previous antidote research or professional experience and perspective regarding the purchase and use of antidotes. The principal investigator was not a panel member.

Table 2.

Guidelines for stocking of antidotes needed in hospitals accepting emergency patients.

Antidote Name

Poisoning Indication(s)

Stocking Recommended? (Yes/No)

Strength of Dose Evidence* No. of (70-kg Q1† Q2‡ Q3§ Q4II Patients Patient)

Acetylcysteine solution Antivenin (Crotalidae) Polyvalent

Acetaminophen Crotalid snakes

Yes Yes

1 3

N N

N N

1 3

2 1

19.6 g 10 vials

Antivenin (Latrodectus mactans) Atropine sulfate

Black widow spider Carbamate or organophosphate insecticide

No Yes

3 2

N N

N 3

3 2

1 2

1 vial 75 mg

Calcium gluconate and calcium chloride

Hydrogen fluoride (HF) or calcium channel blocker

Yes

3

N

N

3

2

100 mEq

Cyanide kit Deferoxamine mesylate Digoxin immune Fab Dimercaprol (BAL) CaNa2 EDTA Ethanol, solution for injection (100%) Flumazenil Fomepizole (4-methylpyrazole)

Cyanide Iron Digoxin, digitoxin, or natural product (plants, toads) Acute arsenic, inorganic mercury, lead (with encephalopathy) Lead (1) Methanol, (2) ethylene glycol

Yes Yes Yes Yes No Yes

3 1 2 2 2 1

N N N N N N

N N N N N 3

3 3 2 2 2 1

2 1 1 1 1 2

1 kit 8.4 g 15 vials 280 mg 1g 90.7 mL

Benzodiazepines (1) Methanol, (2) ethylene glycol

Consensus not achieved Yes

1 1

N N

N 3

1

1 2

4.0 mg 1.05 g

Glucagon Methylene blue Naloxone hydrochloride Physostigmine salicylate Pralidoxime chloride (PAM)

(1) β-adrenergic antagonist, (2) calcium channel blocker Methemoglobinemia Acute opioid poisoning Anticholinergic agents Organophosphate insecticide

Yes Yes Yes Consensus not achieved Yes

3 3 1 1 1

N N N N N

N 3 N 3 3

3 3 2 2 1

1 2 2 2 2

50 mg 140 mg 15 mg 2–4 mg 1g

Pyridoxine Sodium bicarbonate Total

Isoniazid (INH) (1) Tricyclic antidepressant, (2) cocaine, (3) salicylates

Yes Yes

2 2

N N

N N

2 2

1 1

10 g 500 mEq

N, No evidence available; NAC, N-acetylcysteine; BAL, British antilewisite; EDTA, ethylenediamine tetraacetic acid. *Strength of evidence: class 1—properly controlled randomized and blinded clinical trials; class 2—prospective nonrandomized or nonblinded clinical trials, cohort, or well-designed case-control studies, dramatic results in uncontrolled studies and volunteer studies; class 3—retrospective case series, case studies, relevant expert opinions, or animal studies. † Question 1: Is the antidote effective? ‡ Question 2: Is the antidote needed within 1 hour of patient presentation to prevent major morbidity or death? § Question 3: How many patients should a facility prepare for? II Question 4: What amount of the antidote is needed to treat a 70-kg patient? ¶ Total stocking amount=[No. of patients]×[Dose recommended to treat 1 patient for first 4 hours]. # Based on average wholesale price (AWP), using generic products when available.19 Please note that the total includes more than one patient for several antidotes. **The antivenin for coral snakes is a different product. This antivenin should be stocked by all hospitals in indigenous regions (Florida, Georgia, Alabama, Mississippi, Louisiana, and Texas), but may be stocked by selected hospitals on a regional basis. †† Please note that fomepizole is available only in 4-vial traypacks. Some institutions have created methods for sharing traypacks.

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The evidence-based analysis was formulated to provide information to the panel regarding the 4 fundamental questions involved in the selection of each antidote: 1. Is the antidote effective? 2. Is the antidote needed within 1 hour of patient presentation to prevent major morbidity or death?

Total Stocking Amount¶

Total Cost of Stocking# ($)

39.2 g 10 vials

$22.32 $4,504.40

1 vial 150 mg

NA $420.00

200 mEq

$67.56

2 kits 8.4 g 15 vials 280 mg 1g 181.4 mL absolute alcohol

$549.12 $241.35 $8,053.20 $74.76 NA $798.10

4.0 mg 2.1 g

NA $2,400.00

50 mg 280 mg 30 mg 2–4 mg 2g

$1,922.50 $133.28 $411.75 NA $128.26

10 g 500 mEq

$50.00 $32.00 $19,808.60

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3. How many patients should a facility prepare for? 4. What amount of the antidote is needed to treat a 70kg patient? (An initial 4-hour treatment period was selected by the panel.) An antidote was recommended for stocking only if the panel consensus was affirmative for the first 2 questions.

Special Comments Because vomiting following NAC administration is common, the facility should maintain a repeat dose for each patient. Should be stocked in areas with indigenous crotalid snake species (rattlesnakes, water moccasins, and copperheads). Crotalid snakes are indigenous to all states of the United States except Alaska, Hawaii, and Maine. In areas without indigenous crotalid snakes, antivenom should be available because of the practice of collecting nonindigenous snakes. Facilities in areas with snakes that may cause severe envenomation (Eastern diamondback, Western diamondback, Mojave rattlesnake, canebrake rattlesnake) should individually assess their need for antivenom. In many areas, 20 vials and as much as 40 vials can be needed in a severe envenomation.** Although not routinely recommended, antivenin stocking should be considered by hospitals in endemic areas. Agricultural regions often use organophosphate or carbamate insecticides. Hospitals in these areas should ensure that they maintain sufficient stocks of atropine. The amount needed may exceed the standard recommendation. Each institution should ensure that both calcium gluconate and calcium chloride forms are available for emergency use. The chloride form is recommended for intravenous administration. The gluconate form is recommended for dermal application, or intradermal, subcutaneous, intra-arterial, or intravenous injection. 1 kit=1 amyl nitrite ampule, 300 mg of sodium nitrite and 12.5 g of sodium thiosulfate.

Although not routinely recommended, hospitals may choose to stock CaNa2 EDTA because of endemic lead poisoning. A hospital should stock at least one alcohol dehydrogenase–blocking drug. The panel did not reach consensus regarding which agent is preferred. Either fomepizole or ethanol may be stocked. If a hospital decides to stock flumazenil because of its patient population, a total of 4.0 mg is recommended. A hospital should stock at least one alcohol dehydrogenase–blocking drug. The panel did not reach consensus regarding which agent is preferred. Either fomepizole or ethanol may be stocked.††

If a hospital decides to stock physostigmine because of its patient population, a total of 2.0 to 4.0 mg is recommended. Agricultural regions often use organophosphate insecticides. Hospitals in these areas should ensure that they maintain sufficient stocks of pralidoxime. The amount needed may exceed the standard recommendation. Hospitals in areas where isoniazid is used frequently (eg, where tuberculosis is common) should consider stocking of 20 g.

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Twenty commonly used antidotes were selected for critical analysis (Table 2). Articles for consideration were collected from a MEDLINE search for each antidote using Ovid software (Ovid Technologies, New York, NY; 1998), as well as a review of pre-1966 references from a large poison control center collection and review of the references from pertinent chapters in the leading textbooks of toxicology.14-16 More general textbooks were examined, but did not provide additional references. In addition, the reference list of each article included in the analysis was examined for further pertinent references, and panel participants were asked to provide references. Because our goal was to produce stocking guidelines for hospitals in the United States, searches were limited to the English language and human use. The principal investigator initially summarized and analyzed each article individually. Any article that contained original data considered relevant to 1 of the 4 fundamental questions listed previously was included. Each article was classified according to its methodology using a common method (class 1—properly controlled, randomized and blinded clinical trials; class 2—prospective, nonrandomized or nonblinded clinical trials, cohort, or well-designed case-control studies, dramatic results in uncontrolled studies and volunteer studies; class 3—retrospective case series, case studies, relevant expert opinions, or animal studies) and summarized using a structured form by a single experienced investigator.13 This evidence-based literature summary was then presented to the panel as described below. The evidence-based analysis initially screened approximately 2,000 manuscripts; 443 were included in development of the evidence-based summary and recommendations. Class 1 evidence was occasionally available, class 2 evidence was commonly available, but in small amounts, and class 3 evidence was plentiful. Because there were 4 questions per antidote, the panel was required to form consensus on a total of 80 issues. For each issue, the panel was presented with a 3- to 5-page evidence-based summary of the literature as well as a proposed and strictly evidence-based recommendation regarding each antidote. The summary addressed each of the 4 fundamental questions. Panel members were also asked to provide comments and pertinent additional literature citations. Consensus was defined as agreement of at least 11 panel members with no dissenting responses (eg, one member could abstain). Paper and electronic communications were used exclusively (no face-to-face meetings were used). The panel members were asked to complete each questionnaire independently, to avoid the

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use of substitute participants, to refrain from discussing the consensus exercise with other panel members, and to support a dissenting opinion with evidence (eg, literature citations, anecdotal information). After the panel responded to the first round of summaries and proposed guidelines, the results, anonymous verbatim transcripts of all comments received, and proposed revised guidelines were distributed to the panel again. Each member responded again based on the revised information. This process was repeated until consensus was reached. The consensus exercise began with the distribution of the first questionnaire on December 11, 1998, and ended, after 5 rounds, on April 30, 1999. All participants completed the questionnaire for each round. R E S U LT S

The panel recommended that 16 of the 20 antidotes under consideration should be stocked in hospitals that accept emergency patients (Table 2). Each decision included a recommendation on whether the antidote should be stocked, the amount of antidote that should be kept in stock, and special comments regarding stocking issues unique to each antidote. The special comments concept was developed during the consensus process to address the concerns of panelists and allow consensus to be reached. The panel approved these comments by majority vote. DISCUSSION

Insufficient stocking of antidotes needed on an emergency basis has been documented repeatedly in the United States and other countries.1-7 However, it is difficult for hospitals to correct this situation because widely accepted guidelines for antidote stocking have not emerged. Regional guidelines have been promulgated in some cases.9,10 Personal communication with hospitals throughout the United States indicated that several hospitals subsequently adopted the research criteria of one of the published studies as their guideline for antidote stocking. Unfortunately, these studies were designed to emphasize the inadequacy of antidote stocking and therefore used low amounts in their studies. For example, Dart et al2 studied the rate of insufficient stocking of antidotes needed on an emergency basis by using a criterion of just one patient.2 The selection of one patient was an arbitrary decision designed to demonstrate the extreme degree of insufficient

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stocking and was not intended to be used as a standard. Without alternatives, however, it is apparent that some hospitals adopted these research criteria for clinical use.17 We used a combined evidence-based medicine and modified Delphi consensus exercise to develop recommendations. Our approach consists of presenting evidence-based summaries of the medical information to a consensus panel. The panel members combined this information with their perspective and experience to reach individual decisions regarding each antidote. Consensus is then formed by iterative presentation of alternatives to each panel member. This approach helped to constrain the undocumented or unsubstantiated opinion of panel members in 2 ways. First, the complete published medical evidence was presented and created the expectation that conclusion would be evidence-based within the limits of information available. Second, the other panel members (who reviewed the evidence simultaneously) acted as a counterbalance against idiosyncratic individual positions. Several caveats regarding this exercise should be emphasized. Limitations of our approach include that little class 1 and 2 information was available for most antidotes; therefore, the panel’s recommendations are based on consensus. We did not include some less frequently used antidotes. We also did not address unusual circumstances such as terrorist acts and disaster situations. Finally, these guidelines should not be considered absolute rules for several reasons. Antidote use will change as new toxins are discovered, antidotes receive more study, and medical practice evolves. In addition, each hospital is faced with unique social, political, and geographic challenges. If hospital personnel cannot reasonably expect to restock within the 4-hour time frame adopted in these guidelines, they should increase appropriately the amount of antidote maintained in stock. If a hospital is in an agricultural region, the staff would likely want to maintain higher stocks of atropine and pralidoxime for the treatment of organophosphate insecticide poisoning. Similarly, more than one cyanide kit may be appropriate in mining areas. Hospitals in rural areas may need to maintain much larger stocks of several antidotes because of prolonged transit times. The fundamental concern is that each facility formally address the geopolitical challenges of antidote stocking. These are currently overlooked in most hospitals. Emergency physicians, critical care physicians, and regional poison control centers are useful sources of information in forming these policies and procedures.

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Some practitioners may conclude that they can obtain antidotes from neighboring facilities. The antidotes considered in these guidelines are those needed within 1 hour of patient presentation to the emergency department. Poison control center experience indicates that it is very difficult for hospitals, even neighboring hospitals or hospitals in the same financial system, to transfer antidotes quickly. These delays seem to arise from lack of a dedicated person or system to facilitate transfer and the increasing workload of many hospital pharmacies. It is difficult for an already busy hospital pharmacy to rapidly prioritize the delivery of a medication to another facility. Further, evidence suggests that less frequently used antidotes may be difficult to find within a facility in the event of an emergency.17 To address this issue, some facilities have created charts listing antidotes and their location within that hospital (personal communication, Lotzer DL, poison center coordinator; University of Wisconsin Hospital Poison Center, Madison, WI, March 15, 1999; and reference 18), another has created a special area in the pharmacy specifically for the stocking of antidotes, whereas others have created a poisoning cart similar to a code cart.17 It is recommended that each facility ensure that the place of storage, as well as the amount of each antidote stocked, is known and immediately accessible to all hospital personnel providing patient care. REFERENCES 1. Chyka PA, Conner HG. Availability of antidotes in rural and urban hospitals in Tennessee. Am J Hosp Pharm. 1994;51:1346-1348. 2. Dart RC, Stark Y, Fulton B, et al. Insufficient stocking of poisoning antidotes in hospital emergency departments. JAMA. 1996;276:1508-1510. 3. Howland MA, Weisman R, Sauter D, et al. Nonavailability of poison antidotes. N Engl J Med. 1986;314:927-928. 4. Kanatani MS, Kearney TE, Levin RH, et al. Treatment of toxicologic emergencies: an evaluation of Bay Area hospital pharmacies and its impact on emergency planning [abstract]. Vet Human Toxicol. 1992;34:319. 5. Nogue S, Soy D, Munne P, et al. Antidotes: availability, use and cost in hospital and extrahospital emergency services of Catalonia (Spain). Arch Toxicol. 1997;Suppl 19:299-304. 6. Spoerke DG, Spoerke SE, Rumack BH. International opinion concerning indications, safety and availability of poison centre antidotes and treatment. Hum Toxicol. 1987;6:361-364. 7. Woolf AD, Chrisanthus K. On-Site availability of selected antidotes: results of a survey of Massachusetts hospitals. Am J Emerg Med. 1998;15:62-66. 8. Joint Commission on Accreditation of Healthcare Organizations. Comprehensive Accreditation Manual for Hospitals. Oakbrook Terrace, IL: Joint Commission on Accreditation of Healthcare Organizations; 1998:1:111. 9. 911 Receiving Hospitals Advisory Committee, New York City Emergency Medical Service. Emergency Department Standards, 5th ed. New York, NY: New York City Health and Hospitals Corporation Emergency Medical Service; 1992. 10. Olson KR, ed. Poisoning & Drug Overdose. Norwalk, CT: Appleton & Lange; 1994. 11. Evidence-Based Medicine Working Group. Evidence-Based medicine: a new approach to teaching the practice of medicine. JAMA. 1992;268:2420-2425.

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12. Frazier HS, Mosteller F, eds. Medicine Worth Paying For: Assessing Medical Innovations. Cambridge, MA: Harvard University Press; 1995. 13. Vermuelen LC, Ratko TA, Erstad BL, et al. A paradigm for consensus: the University Health Consortium guidelines for the use of albumin, nonprotein colloid and crystalloid solutions. Arch Intern Med. 1995;155:373-379. 14. Ellenhorn MJ. Ellenhorn’s Medical Toxicology, 2nd ed. Baltimore, MD: Williams & Wilkins; 1997. 15. Goldfrank LR, Flomenbaum NE, Lewin NA, et al, eds. Goldfrank’s Toxicologic Emergencies, 6th ed. Norwalk, CT: Appleton & Lange; 1998. 16. Haddad LM, Shannon MW, Winchester JF, eds. Clinical Management of Poisoning and Drug Overdose, 3rd ed. Philadelphia, PA: WB Saunders; 1998. 17. Pettit HE, McKinney PE, Achusim LE, et al. Toxicology cart for stocking sufficient supplies of poisoning antidotes. Am J Health Syst Pharm. 1999;56:2537-2539. 18. Berndt E. Posted list of emergency drugs and antidotes. [letter]. Am J Hosp Pharm. 1994;51:2602. 19. 1999 Drug Topics Red Book. Montvale, NJ: Medical Economics Company; 1999.

APPENDIX.

Richard C. Dart, MD, PhD Rocky Mountain Poison and Drug Center Denver Health & Hospital Authority Department of Surgery University of Colorado Health Sciences Center Denver, CO

Kent R. Olson, MD California Poison Control System, San Francisco Division San Francisco, CA Elizabeth Scharman, PharmD, ABAT West Virginia Poison Center Charleston, WV Robert J. Geller, MD Georgia Poison Center Department of Pediatrics Emory University School of Medicine Atlanta, GA Daniel Spyker, MD, PhD Division of Cardiovascular & Respiratory Devices Center for Devices and Radiological Health Food and Drug Administration Washington, DC Monica Kraft, MD Division of Pulmonary and Critical Care Medicine University of Colorado Health Sciences Center National Jewish Medical and Research Center Denver, CO Robert Lipsy, PharmD Intergroup of Arizona University of Arizona Tucson, AZ

Lewis R. Goldfrank, MD Department of Emergency Medicine Bellevue Hospital Center New York University Medical Center New York University School of Medicine New York, NY Peter A. Chyka, PharmD Southern Poison Center Department of Pharmacy University of Tennessee Memphis, TN Donna Lotzer, RPh, CSPI University of Wisconsin Hospital Poison Center Madison, WI Alan D. Woolf, MD, MPH Massachusetts/Rhode Island Poison Control Center Department of Pediatrics Harvard Medical School Program in Clinical Toxicology, Department of Medicine Children’s Hospital Boston, MA Jude McNally, RPh, ABAT Arizona Poison and Drug Information Center University of Arizona Tucson, AZ Wayne R. Snodgrass, MD, PhD Southeast Texas Poison Center Department of Pediatrics University of Texas Medical Branch Galveston, TX

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