Case Title: High School Musical: Unknown Chemical Exposure.
Patient Name: Mr. Wallace Lincoln.
Scenario Name: Recognizing and treating cyanide exposure.
Simulation Developers: Brenda Bray, BPharm, MPH; Colleen Terriff, PharmD, BCPS.
Date of Development: October 2007.
Learner groups: Critical Care, Emergency Medicine residents, medical, nursing and pharmacy students; emergency responders from the community.
Effective emergency preparedness and response planning equips emergency responders to be ready for any type of incident, emergency, or catastrophe, including natural or man-made situations. Intentional acts (terrorism) are commonly categorized by the agent or weapon used, such as chemical, biologic, radiologic, nuclear, or explosive devices. This case was originally designed for doctor of pharmacy students enrolled in an elective Emergency Preparedness and Response course, but it has application for a broader audience, such as emergency responders, medical residents and nursing students, and for interdisciplinary team training.
Learners will be assessed on the following core competencies using the Accreditation Council for Graduate Medical Education Competencies (ACGME Core Competencies):
- Medical knowledge:
- Recognize and describe signs and symptoms consistent with inhalation of a chemical or biologic agent.
- Once the exposure agent is tentatively identified or confirmed, the following needs to be done:
- i. Identify feasible pharmacotherapeutic alternatives to treat the poisoning, including possible antidotes with suggested dosing regimen.
- ii. Identify nonpharmacologic measures available to treat the biologic or chemical poisoning.
- iii. Indicate measures for supportive care.
Interpersonal and communication skills:
- Design and implement the optimal therapeutic plan.
- Administer appropriate antidote and supportive care.
- Anticipate and monitor potential side effects of antidotes.
- Demonstrate the ability to successfully communicate with a critically ill patient.
- Demonstrate the ability to interact with a multidisciplinary group of healthcare providers.
Guided Study Questions
- What is cyanide and how is it absorbed?
- What are the signs, symptoms, and sequelae of cyanide exposure?
- What are the goals of pharmacotherapy?
- What are the therapeutic alternatives (pharmacologic and nonpharmacologic) for cyanide exposure/poisoning?
- What are the potential side effects of the antidotes for treating cyanide poisoning?
References Used During Case Design
- Baud FJ. Cyanide: critical issues in diagnosis and treatment. Hum Exp Toxicol 2007;26:191–201.
- Bond WF, Lammers RL, Spillane LL, et al. The use of simulation in emergency medicine: a research agenda. Acad Emerg Med 2007;14:353–364.
- Colley J, Baker DE. Hydroxocobalamin. In: Cada DJ, Baker DE, Levien TL, eds. Formulary Monograph Service. St. Louis, MO: Wolters Kluwer Health, Inc.; 2007.
- Cyanide Antidote Kit [package insert]. Decatur, IL: Taylor Pharmaceuticals; 2006.
- Cyanokit [package insert]. Napa, CA: Dey/L.P.; 2006.
- Emergency Preparedness and Response [Internet]. Atlanta, GA: Centers for Disease Control and Prevention. Facts about cyanide. Available at: www.bt.cdc.gov/agent/cyanide/basics/facts.asp [updated 2004 Jan 27; cited 2007 Sept].
- Gracia R, Shephard G. Cyanide poisoning and its treatment. Pharmacotherapy 2004;24:1358–1365.
- Mutlu GM, Keikin JB, Oh K, Factor P. An unresponsive biochemistry professor in the bathtub. Chest 2002;122:1073–1076.
- Terriff CM. Cyanide exposure. In: Schwinghammer TL, Koehler JM, eds. Pharmacotherapy Casebook: A Patient-Focused Approach. 7th ed. New York: McGraw-Hill; 2008.
Before participating in this simulation scenario, students were presented with overview lectures on chemical and biological terrorism. Baseline knowledge of recognition and treatment of cyanide toxicity are recommended.
- Refer to debriefing points below, which were used as a clinical checklist.
Supplies and Equipment
- Laerdal SimMan (or other comparable simulator)
- Noninvasive blood pressure cuff
- Pulse oximetry
- Gloves—small, medium, large, and extra-large
- Normal saline large volume IV bag and IV tubing
- Pralidoxime 600 mg, atropine 2 mg (MARK-1 or DuoDote Auto-injectors)
- Diazepam 10-mg autoinjectors
- Hydroxocobalamin (Cyanokit: two 2.5-g vials)
- Levofloxacin 750 mg IV piggyback, doxycycline 100 mg IV vial
- Cotton ball with almond extract placed near patient's head
- IV pole
- IV pump
- Oxygen tubing
- Ambu bag
- Code cart with medication tray
- Hospital gown/scrubs for patient (following decontamination)
- Personal protective equipment
Simulated patient chart: physician order sheets, physician progress notes, nursing notes, emergency department flow sheet, laboratory results for blood gas, lactate level, cyanide levels, CBC < electrolytes, blood culture, sputum culture, chest x-ray, and acetylcholinesterase level.
Duration (Varies Depending on Needs of Learners)
- Set up: 15 to 20 minutes.
- Simulation: 15 to 30 minutes.
- Debriefing: 20 to 30 minutes.
Hundreds of patients have been exposed to an unknown agent during the intermission of the high school musical. Patients are presenting to area emergency departments with a wide spectrum of symptoms, ranging from confusion to seizures. Your hospital emergency department is just starting to admit patients. The team (ie, group of four) is asked to do the following for patients as they are admitted:
- Determine likely exposure.
- Order appropriate laboratory work.
- Initiate therapy.
Patient Data Background and Baseline State
History of Present Illness
Mr. Wallace Lincoln, admitted to bed #2 after a decontamination procedure that included clothing removal and an on-scene water rinse, is a 53-year-old white male, the orchestra conductor at the high school. Mr. Lincoln is complaining of headache, dizziness, weakness, abdominal pain, chest pain, and shortness of breath. Mr. Lincoln is acting confused, intoxicated, and has slurred speech. Laboratory work is pending.
- Medical and surgical history: noncontributory.
- Social history: difficult to obtain; patient denies recent alcohol consumption or illicit drug use.
- Family history: noncontributory.
- Review of systems: patient unable to provide answers to questions.
- SimMan settings:
- Initial state:
- HR = 52
- BP = 155/98
- RR = 28
- O2 saturation = 97% on room air
- Eyes—mydriasis (excessive dilation)
- Bitter almond breath odor (almond extract)
- Progressive state (after 5 minutes):
- HR = 118
- BP = 91/52
- RR = 36
- O2 saturation = 97% on room air
- Eyes—mydriasis (excessive dilation)
- Mr. Lincoln is complaining of headache, dizziness, weakness, abdominal pain, chest pain, and shortness of breath.
- Mr. Lincoln is acting increasingly confused, intoxicated, had slurred speech.
Current Medications and Allergies
- Allergy status: penicillin allergy (unknown reaction).
- Current drug therapy: atorvastatin (Lipitor) for hyperlipidemia.
- General: patient is confused with slurred speech.
- Weight, height: 5′ 11", 210 lbs.
- Vital signs: HR 52, BP 155/98, RR 28, O2 saturation = 97%, temperature = 98°F.
- Lungs: clear to auscultation, rapid, shallow breaths.
- Heart: sinus rhythm, bradycardia initially, progressing to tachycardia.
- Abdomen: normal bowel sounds present; no masses.
- Extremities: no edema noted; pedal pulses present.
- Neurologic examination: deferred.
Laboratory, Radiology, and Other Relevant Studies (Results Provided When Requested by Students)
Basic Metabolic Panel
- Na: 142 (135–146)
- K: 3.7 (3.5–5.1)
- Cl: 105 (98–108)
- CO2: 16 (23–30)
- BUN: 16
- Cr: 0.8
- Glucose: 122
Complete Blood Count
- HgB: 12 (12–16)
- Hct: 38 (36–45)
- RBC: 4 (4–5.1)
- WBC: 6 (4.5–11)
- Lactate: 6 (0.5–1.6)
Blood Gases (Arterial)
- pH: 7.21 (7.35–7.45)
- pO2: 100 (80–100)
- pCO2: 22 (35–45 mm Hg)
- O2 saturation: 95 (85–100)
- HCO3: 14 (22–26)
- Anion gap: 22
- Tox screen: pending
- Cholinesterase: pending
- Cyanide level: pending
- Spinal tap: under consideration
Progressive State After Administration of Appropriate Antidote (After 10–15 minutes):
- HR = 102
- BP = 105/72
- RR = 24
- O2 saturation = 97% on 2 to 4 L oxygen
- Improved cognition
Background Information for Facilitators
Cyanide Exposure Background1–3
Cyanide exposures can occur as a result of smoke inhalation from industrial or residential fires and with poisonings, either accidental or intentional, via a suicide attempt or act of terrorism. Substances of concern are gaseous hydrogen cyanide, water-soluble (ie, potassium cyanide), and poorly water-soluble (ie, silver cyanide) cyanide salts and cyanide-containing compounds, cyanogens, that release cyanide during metabolism, as with sodium nitroprusside. Through a variety of routes (inhalation, injection, ingestion) cyanide can cause cellular metabolism to shift from aerobic to anaerobic conditions, which then increases lactic acid production and leads to a potentially severe metabolic acidosis. Onset of signs and symptoms depends on form of cyanide, with gaseous hydrocyanide causing immediate symptoms and mortality in a matter of minutes, contrasting with cyanogens that may take a few hours. Patients can present with dizziness, confusion, giddiness, loss of consciousness, seizures, and coma. GI symptoms include abdominal pain, nausea, and vomiting. Palpitations, shortness of breath, hyperventilation, and subsequent cardiac arrest may occur. Physical findings may include either bradycardia and hypertension (earlier) or subsequent hypotension with reflex tachycardia. Tachypnea, giving way to apnea, with a normal pulse oximetry, is also concerning. If patients were extracted from a fire, soot around mouth and nose may be present. Eyes might show mydriasis. Finally, patients' breath may smell of bitter almonds (but not everyone in population can detect this odor).
Although the lengthy differential diagnosis list includes concerns such as anxiety attack, acute coronary syndrome, myocardial infarction, and acute drug intoxication, this mass casualty event is most likely a terrorist act. Learners need to differentiate the causative agent, based on information from the scene and signs and symptoms of presenting patients. Potential exposure may include a riot control agent, vesicant or blistering agent, nerve agent or one of a variety of industrial chemicals, including chlorine, ammonia, and cyanide.
Because quick triage and appropriate selection and administration of treatment, including supportive care, are crucial to minimize mortality with cyanide exposure, learners need to react in a timely fashion.
Healthcare workers need to verify that appropriate decontamination has occurred before admission into the facility. Decontamination involves clothing removal and skin washing (water or soap and water), which can be conducted at the scene or outside the facility.
The room is situated like an emergency department patient triage room. Patient is in scrubs (has been decontaminated through clothing removal and skin washing), has pulse oximetry, blood pressure cuff, heart rate monitor, and peripheral IV access. A cotton ball with almond extract is hidden under his head to simulate cyanide metabolite odor on breath.
Students enter the room and perform initial assessment and interview that reveals information as described above in patient background. Students must request the following: blood gas, lactate level, cyanide levels, CBC, electrolytes, blood culture, sputum culture, chest x-ray, and acetylcholinesterase level. Once assessment is complete, students must identify the potential exposure, recommend an appropriate treatment plan, administer antidote, and state monitoring plan for safety and efficacy for exposure and antidote.
- 1 General: teamwork/communication with patient and team members (learning objective 3).
- Self-assess individual and group interactions during stressful simulation scenario.
- Consider appropriate agencies to notify of the incident (ie, CDC, poison control, local emergency management, and public health).
- Consider personal safety and the importance of verifying that appropriate patient decontamination has occurred.
- Patient assessment and treatment1–3: The following points should be reviewed during the debriefing to review patient-specific findings relevant to cyanide toxicity (learning objective 1).
- Assure appropriate decontamination procedure has occurred.
- Immediate care (learning objective 2a): If required, implement immediate life-saving maneuvers including resuscitation measures, such as CPR, intubation, and ventilator support.
- Supportive care should include the following (learning objective 2a):
Information from the patient or observations about the patient should include the following:
- Oxygen delivery 100%.
- Intravenous and intra-arterial lines (for blood gas and hemoximetry).
- Establish IV access for administration of drugs and fluids.
- Treatment of acidosis with sodium bicarbonate titrated according to arterial blood gas and bicarbonate levels.
- Cardiovascular monitoring.
- Determine allergy status
- Current medications and disease states
- General weakness and confusion
- Dizziness, lightheadedness, and headache
- Acting intoxicated
- Abdominal pain, nausea, and vomiting
- Seizures and loss of consciousness
- Tachypnea, hypotension, and bradycardia
- Bitter almond breath odor
- Bitter almond breath odor (discussion point: not everyone can detect this odor)
- Chest pain with shortness of breath
- Vital signs variable: initial bradycardia and hypertension, then hypotension with reflex tachycardia, followed by bradycardia and hypotension
- Pulmonary edema
Design optimal therapeutic plan and administration of appropriate antidote (learning objectives 1b and 2b).
- Basic metabolic panel and CBC help rule out infection, anemia, electrolyte abnormalities, and renal dysfunction
- Blood gas (metabolic acidosis)—consider anion gap
- Lactate level (elevated because of hypoxic intracellular damage and tissue death)
- Cyanide levels (whole blood): expect to be elevated; delay in report; should not delay treatment
- Normal O2 pulse oximetry reading. (This may be falsely reassuring because the oxyhemoglobin cannot be used for cellular oxidative phosphorylation.)
- Carboxyhemoglobin (expected to be elevated): delay in report
Monitoring parameters to evaluate therapeutic plan1: (learning objectives 2b).
- If cyanide toxicity is strongly suspected, administer antidote in the absence of laboratory confirmation.
- Two therapeutic options exist: cyanide antidote kit and hydroxocobalamin. For this case, taking into consideration patient's hypotension and unknown chemical exposure (unsure if carbon monoxide involved), hydroxocobalamin is the preferred antidote.
- Preferred: Cyanokit (hydroxocobalamin)1,4: an active form of vitamin B12 is capable of binding cyanide, forming cyanocobalamin, an inert compound that is subsequently excreted in the urine. Adult dose is 5 g (2 × 2.5-g vials) diluted in normal saline and administered intravenously over 15 minutes. This dose can be repeated as needed (15 minutes or up to 2 hours later.)
- Alternate: Cyanide Antidote Kit1,5: The cyanide antidote kit containing amyl nitrite, sodium nitrite, and sodium thiosulfate is traditionally used to treat cyanide poisoning. Amyl nitrite and sodium nitrite induce methemoglobinemia that preferentially binds cyanide. Sodium thiosulfate acts a sulfur donor, converting cyanide to thiocyanate, which is excreted renally as a nontoxic metabolite. First, amyl nitrite ampule is crushed in gauze and held under patient's nose for inhalation (15 seconds, then 15 seconds of rest, repeat; use new ampule every 3 minutes if necessary as IV access is being established.) Intravenous administration of sodium nitrite (10 mL of 3% solution) should begin as soon as possible at a rate of 2.5 to 5 mL/min in adults. This is followed by sodium thiosulfate (12.5 g in 50 mL) infused intravenously at a rate of 3 to 5 mL/min, which may be repeated at one-half dose if symptoms are persisting after 60 minutes.
- Signs and symptoms of toxicity for patient improvement or deterioration.
- Monitoring for a decrease in lactate levels daily may be useful to gauge improvement in tissue damage.
- Monitor blood gases (to see improvement in acidosis and oxygenation) as needed.
- Other laboratory tests such as co-oximetry (for carboxyhemoglobin or methemoglobin levels) may be useful if results can be made available within hours.
- Cyanide levels may be determined but are not required for patient management.
- Hydroxocobalamin may interfere with certain laboratory parameters (performed by colorimetrics) because of this drug's deep red color. For example, serum creatinine, glucose, and hemoglobin may be artificially increased.
- Monitor heart rate, blood pressure, and pulse oximetry continuously.
- Airway/breathing, cardiovascular system, and CNS changes (ie, mental status deterioration and seizures).
- Potential antidote side effects and monitoring:
- Hydroxocobalamin4: red-colored skin (flushing; may last up to 2 weeks) and urine (may last up to 5 weeks): common; increase in blood pressure, nausea, headache, and infusion site reaction; monitor for allergic reaction (ie, rash, edema, and anaphylaxis). Patient's blood pressure increased after hydroxocobalamin administration.
- Cyanide antidote kit1,5: amyl or sodium nitrite may also cause an allergic reaction, hypotension, and worsen carbon monoxide poisoning (if copresent). In addition, if sodium thiosulfate is infused too rapidly, transient hypotension may result. Methylene blue solution (1%) should be administered (1–2 mg/kg over 5–10 minutes) if vomiting, severe hypotension, and blue skin are observed.