1a. List the abnormal signs and symptoms displayed in these patients after exposure to the unknown chemical. Which of these findings are consistent with inhalation of cyanide? Abnormal signs and symptoms displayed by these patients include hypotension, bradycardia, tachypnea, cherry red-colored skin, myridasis, GI pain, nausea, emesis, headaches, dizziness, seizures, coma and "nutty" smelling breath, seemingly drunk, confusion, unconsciousness, weakness, and anxiety.
Hypotension, bradycardia, tachypnea, cherry red-colored skin, myridasis, GI pain, nausea, emesis, headaches, dizziness, seizures, coma and "nutty" smelling breath are all common symptoms of cyanide toxicity.
1b. List the laboratory tests that may be abnormal in patients exposed to cyanide. Explain the pathophysiology underlying these abnormalities.
Blood pH will exhibit metabolic acidosis, elevated lactate levels and increased anion gap, and cyanide can be detected in the blood.
Cyanide block mitochondrial enzymes; one enzyme blocked is cytochrome oxidase, which is responsible for aerobic metabolism. Glycolysis continues to run uninterrupted, causing a buildup of pyruvate and lactic acid, resulting in lactic acidosis and an ATP deficiency.
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1c. What are the potential short and long-term sequelae from this exposure?
Short-term sequelae of cyanide poisoning include bradycardia, hypotension, reflex tachycardia, pulmonary edema, headache, anxiety, agitation, confusion, lethargy, seizures, coma, hemorrhagic gastritis, abdominal pain, N/V, cherry red-colored skin, pain/irritation of eyes and optic neuropathy.
Long-term delayed neurological symptoms tend to mimic Parkinson's disease, causing dystonia, dysarthria, rigidity, bradykinesia.
2. What are the goals of pharmacotherapy for these patients?
Goals of therapy for cyanide poisoning include decreasing the amount of cyanide available for cellular binding and maintaining cellular oxygen utilization.
3a. What nonpharmacologic measures are available to treat cyanide poisoning?
Nonpharmacologic measures that are available to treat cyanide poisoning include airway support, administration of 100% oxygen, and decontamination of exposed patient.
3b. What feasible pharmacotherapeutic alternatives are available for treating cyanide poisoning?
Cyanide antidote kits of nitrites (amyl nitrite), sodium nitrite, thiosulfate or hydroxocobalamin are currently available, as well as activated charcoal (1g per 35 mg cyanide) in case of ingestion.
4a. Outline your pharmacotherapeutic plan for treating cyanide poisoning in these patients. Include dose(s), route(s), and repeat dosing information (if any) for both adult and pediatric patients. Also describe use of administration devices or ancillary supplies required.
Treatment should not wait for lab test confirmation.
The patient should be decontaminated of offending substance immediately.
Cyanokit, containing hydroxocobalamin, is a 5 g IV infusion that is administered over 15 minutes to binding cyanide for excretion. If clinical condition severe, a second dose of 5 g may be infused over 15 minutes to 2 hours. No dosages have been determined for pediatric patients.
Cyanide Antidote Kit includessodium nitrite,sodium thiosulfate Injection, and amyl nitrite Inhalants. For each kit, a specific method of administration is required. Amyl Nitrite in a handkerchief/gauze sponge should be held in front of the patient's mouth for 15 seconds - followed by a rest for 15 seconds, reapplying until Sodium Nitrite can be administered. Then 300 mg of Sodium Nitrite should be infused at 2.5 to 5 mL/minute (0.2 mL/kg dose for pediatric patients, not to exceed 10 mL infused). Then inject 12.5 g of Sodium Thiosulfate (7 g/m2for pediatric, not to exceed 12.5 g). If ingested, gastric lavage should be performed immediately. Monitor patient for 24 to 48 hours. If signs reappear, repeat Sodium Nitrite and Sodium Thiosulfate, but at half the original dose.
If patient has pulse but is not breathing, begin artificial respiration and lay handkerchief/gauze spongeamyl nitrite over patient's nose to hasten resumption of breathing.
4b. What supportive care measures may be necessary for optimal management
Airway support and 100% oxygen should be administered to the patient.
5a. Describe the clinical and laboratory parameters required to determine whether the treatment for these patients has been successful.
Stabilization and normalization of blood pH, lactate level, anion gap, and blood oxygen levels.
5b. How often should the nursing and medical staff attempt to assess and re-assess the patients?
After administration of antidote, if no adequate clinical response is seen within 30 minutes, repeat with one-half the initial dose.
Patients should be kept for observation for at least 24-48 hours
6a. For patients who are alert and oriented, what information would you share with them about the possible immediate side effects of each of the antidotes?
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Most common side effects:
Hypotension, flushing, tachycardia, headache, dizziness, skin rash, nausea, vomiting, anemia, intraocular pressure
Tachycardia, cyanosis, hypotension, flushing, dizziness, headache, nausea, vomiting, methemoglobin formation.
Hypotension, Coma, CNS depression, psychosis, confusion, muscle weakness, tinnitus
Serious side effects include allergic reactions (chest tightness, trouble breathing, swelling, hives, itching, rash) and hypertension
Other side effects include red colored urine/skin/mucous membranes, N/V, diarrhea, blood stool, stomach pain, trouble swallowing, throat tightness, headache, dizziness, memory problems, restlessness, eye irritation, feet/ankle swelling, tachycardia, pulmonary edema.
6b. How long might it take for patients to recover from potential long-term effects of acute cyanide exposure?
Some injuries of acute cyanide exposures will never fully recover, including brain damage, memory deficits, and impaired motor skills. These typically are a result of the hypoxia suffered during the exposure.
Nerve Agent: Case Study 8
1a. Create a list of potential chemical agents that the patients may have been exposed to based on presenting signs and symptoms.
Chemical agents the patients may have been exposed to include organophosphates (Parathion, Malathion, Fenthion, Dimethoate, Monocrotophos, Metamidophos), carbamates (Aldicarb, Carbaryl, Carbofuran, Propanocarb, Thiodicarb), or cholinergic nerve agent (sarin, tabun, soman, cyclohexyl sarin, VX, novichok agents).
1b. How serious is this exposure, and what could be some potential sequelae?
The exposure could be rated moderate to severe due to some patients presenting with serious effects.
Symptoms of cholinergic toxicities can be life threatening.Common sequelae of cholinergic toxicity include diarrhea, urination, miosis, bradycardia, bronchorrhea, bronchospasm, emesis, lacrimation, and salivation.
2a. What are the goals of pharmacotherapy in this case?
Decontaminate, stabilize and support patient, antagonize muscarinic symptoms, stop aging of enzyme blockade, and prevent and terminate seizures
2b. How do your goals change if there were 15 patients presenting with these symptoms and differing degrees of severity and exposure?
The goals do not change, but emphasis of treatment would be placed toward the more severe exposures.
3a. What nonpharmacologic measures are available to treat these patients?
Decontamination and respiratory support
3b. What feasible pharmacotherapeutic alternatives are available for treating these patients?
Atropineto antagonize cholinergic effects, 2-PAM for enzyme blockage aging, and diazepam for seizures
3c. Suppose there are 100 patients in your hospital's emergency department needing an antidote, and you only have enough antidote to treat 25 patients. How do you decide who gets life-saving treatment?
Determine which patients are capable of being saved. Then determined which of the savable patients are most life-threatened. If the number of life-threatened patients is greater than 25, treat the worse cases with the antidotes, while investigating other ways of treating the other patients.
4a. What antidotes are required for this chemical exposure? Provide the adult doses, routes, and repeat dosing information for each antidote.
IV 2-4 mg adults
IV 0.015-0.05 mg/kg
Repeat every 10-15 minutes as needed
2-PAM (pralidoxime chloride)
Adults: 2 g IV over 10 to 15 min
Kids: 25 - 50 mg/kg IV
Give dose every 6 hours until patient is asymptomatic for 24 hrs
4b. There are special dosing kits and administration devices available for these antidotes. Describe how these kits should be administered.
Antidotes are available in Mark-I autoinjector kits as atropine (2 mg/0.7 mL) and 2-PAM (600 mg/2 mL). Injections should be made into patient's outer thigh. Hold injector in place for 10 seconds following injection to ensure complete delivery. If symptoms persist after 15 minutes, repeat injection.
4c. If a patient's condition worsens and seizure activity occurs, what class of medications should be used for this chemical-induced seizure?
Benzodiazepines are used to treatchemical-induced seizures associated with cholinergic agents.
5. Outline a monitoring plan to assess if the pharmacotherapy treatment for these patients is successful.
Regularly monitor and maintain respiration
With atropine, repeat dosages as needed until cholinergic effects diminish and anti-cholinergic effects appear.
Monitor skeletal muscle response to 2-PAM (response usually within minutes). If muscular weakness not reversed, may repeat dose in 1-2 hours.
6a. What information would you share with the patient about immediate side effects of each of the antidotes?
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Side effects that can be expected from atropine include fever, tachycardia, lack of diaphoresis, flushed skin, delirium, urinary retention, and mydriasis.
Side effects that may occur from 2-PAM include tachycardia, hypertension, drowsiness, seizures, nausea, and muscle weakness.
Side effects that can be expected from diazepam include sedation, hypnosis, muscle relaxation, nystagmus, and hypotension.
6b. How long might it take for patients to recover from the ocular effects of the chemical exposure? Incorporate this information into your educational efforts.
Recovery of ocular effects usually takes 18-24 hours following administration of antidotes.
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CYANOKIT (hydroxocobalamin) injection, powder, lyophilized, for solution [Dey, L.P.]. U.S. National Library of Medicine. April 2009. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=11009#section-8Â
CYANIDE ANTIDOTE PACKAGE. http://www.abopharmaceuticals.com/ProductSheets/CyanideAntidoteKit.pdf
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Murfin PA-C, PharmD, Melissa. Toxidromes. LECOM School of Pharmacy. 16 November 2010.
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