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CBRNE - Nerve Agents, Binary: GB2, VX2: Treatment & Medication
Updated: Dec 19, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
Keep in mind that rescue personnel may themselves become affected by nerve agents. The cornerstones of prehospital management are based on rapid termination of exposure (ie, evacuation and decontamination), treatment of life-threatening emergencies, and administration of antidotes, if available. Whenever possible, decontamination should take place prior to transportation of the patient to a clean area. This prevents cross-contamination and additional exposures.
- Decontamination techniques vary according to the extent and route of exposure.
- After exposure to any toxic vapor, evacuation and provision of fresh air is the most important first step. Clothes should be removed, since they can trap enough vapor to cause secondary victims. In the Tokyo subway attack, 10% of the caregivers at the hospital developed miosis after exposure to nondecontaminated victims.
- In dermal exposures, the patient should be undressed. Any visible droplets should be blotted away. Abrasion of the skin by vigorous scrubbing increases absorption of the agent and should be avoided. Nerve agents can be neutralized with alkaline solutions such as soap and water or 0.5% hypochlorite solution (which releases chlorine), followed by a water rinse. However, decontamination should not be delayed to seek hypochlorite or other special solutions; copious water is generally good enough for decontamination.
- The military has autoinjector kits (MARK 1) that contain 2 antidotes, an oxime (AChE reactivator) and atropine. Some ambulance systems and hazardous materials (HAZMAT) teams also have these kits available for use in the prehospital setting.
- During a mass casualty incident, most patients arrive to the emergency department without the benefit of prior emergency medical services (EMS) or HAZMAT intervention. According to the 1998 report by Okumura, in the Tokyo subway sarin attack, 85% of patients arrived to the ED by private car.2 This means that the emergency department must be prepared to treat potentially large numbers of contaminated individuals.
Emergency Department Care
If decontamination has not occurred, the emergency department should be able to provide this service prior to the patient's entrance to the hospital. If weather permits, decontamination stations can be set up outside. All hospital personnel in contact with contaminated individuals must wear full protective gowns (eg, rubber apron, rubber gloves, protective mask). Medical management is discussed in Medication.
Consultations
Contact the regional poison center (1-800-222-1222) whenever nerve agent poisoning is suspected. In case of a multiple casualty incident, activate the hospital emergency plan and notify local authorities for advice and support.
Medication
Table 3 summarizes the different agents used to treat patients with nerve agent poisoning. Table 4 provides some general treatment guidelines.
All but the mildest exposures cause some degree of respiratory compromise. For this reason, oxygen should be readily available. Most of these symptoms are the result of bronchorrhea and bronchoconstriction and improve after appropriate administration of antidotes. Ventilatory support may be needed for severely poisoned patients because of respiratory muscle paralysis. Oxygen is supplied via nasal cannula, face mask, or nonrebreather mask. Remember that inspired oxygen concentrations of 50-100% carry a substantial risk of lung damage when used for more than a few hours.
Table 3. Drugs Used to Treat Patients With Nerve Agent Poisoning*Open table in new window
Table
Drug | Dose (Adult) | Route | Indications | Contraindications |
Atropine | 2 mg q5-10min prn | IV/IM/ETT | Excessive muscarinic symptoms | Relative: IV route in hypoxia has been associated with ventricular fibrillation. |
Pralidoxime chloride (Protopam, 2-PAM) | 15-25 mg/kg over 20 min; can be repeated after 1 h | IV/IM | Symptomatic nerve agent poisoning | Rapid infusion may result in hypertension; may worsen symptoms in carbamate poisoning |
Diazepam (Valium) | 2-5 mg IV | IV/IM | Moderate or severe signs of poisoning, seizures | None |
Drug | Dose (Adult) | Route | Indications | Contraindications |
Atropine | 2 mg q5-10min prn | IV/IM/ETT | Excessive muscarinic symptoms | Relative: IV route in hypoxia has been associated with ventricular fibrillation. |
Pralidoxime chloride (Protopam, 2-PAM) | 15-25 mg/kg over 20 min; can be repeated after 1 h | IV/IM | Symptomatic nerve agent poisoning | Rapid infusion may result in hypertension; may worsen symptoms in carbamate poisoning |
Diazepam (Valium) | 2-5 mg IV | IV/IM | Moderate or severe signs of poisoning, seizures | None |
*Adapted from Sidell, 1992.3
Table 4. Summary of Treatment Modalities According to Severity of Exposure*Open table in new window
Table
Severity/Route of Exposure | Atropine (Adult Dose) | Pralidoxime | Diazepam | Other |
Suspected | No | No | No | Decontamination and 18-h observation for liquid exposures |
Mild | 2 mg for severe | Administer if dyspnea | No | Decontamination and 18-h observation for liquid exposures; oxygen |
Moderate | 6 mg; may need to repeat | Administer with atropine | Administer even in absence of seizures | Decontamination; oxygen |
Severe | Start with 6 mg; may need to repeat | Administer with atropine; should repeat once or twice | Administer even in absence of seizures | Airway, breathing, and circulation; decontamination |
Severity/Route of Exposure | Atropine (Adult Dose) | Pralidoxime | Diazepam | Other |
Suspected | No | No | No | Decontamination and 18-h observation for liquid exposures |
Mild | 2 mg for severe | Administer if dyspnea | No | Decontamination and 18-h observation for liquid exposures; oxygen |
Moderate | 6 mg; may need to repeat | Administer with atropine | Administer even in absence of seizures | Decontamination; oxygen |
Severe | Start with 6 mg; may need to repeat | Administer with atropine; should repeat once or twice | Administer even in absence of seizures | Airway, breathing, and circulation; decontamination |
*Adapted from Sidell, 1992.3
Anticholinergic agents
These agents antagonize ACh at the muscarinic receptor.
Atropine (Isopto, Atropair, Atropisol)
Antagonizes ACh at muscarinic receptor, leaving nicotinic receptors unaffected. In contrast to organophosphate insecticides, nerve agents rarely require >20 mg. Continue administration until excess muscarinic symptoms improve, which can be gauged by increased ease of breathing in the conscious patient or improvement in ease of ventilation in the intubated patient.
Adult
2 mg IV/IM/ETT initial dose; can be repeated after 5-10 min in boluses of 2-4 mg; may repeat dose q5-10min, but infusing larger doses of 4-5 mg is often more practical if initial response is not evident within 5-10 min after administration
Pediatric
0.02 mg IV/ETT (minimal dose 0.1 mg) initial dose; can be repeated q5-10min; titrate to clinical response
Coadministration with other anticholinergics results in additive effects; pharmacologic effects of atenolol and digoxin may increase with atropine; antipsychotic effects of phenothiazines may decrease with this medication; tricyclic antidepressants with anticholinergic activity may increase effects of atropine
Documented hypersensitivity; IV route in hypoxia has been associated with ventricular fibrillation (relative contraindication)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Excessive doses of atropine may result in anticholinergic toxidrome; caution in patients with Down syndrome and in children with brain damage to prevent hyperreactive response; caution in coronary heart disease, congestive heart failure, hypertension, peritonitis, ulcerative colitis, hepatic disease, and hiatal hernia with reflux esophagitis (relative contraindications)
Oximes
These reactivators of AChE enzyme are generally divided into 2 groups, monopyridinium and bispyridinium types. Pralidoxime belongs to the monopyridinium group and is the oxime used in the United States. Oximes should be administered concomitantly with atropine. After aging occurs, the usefulness of pralidoxime is minimal. VX has a slow aging process (estimated at 48 h); thus, delayed treatment with oximes may be beneficial. In contrast, aging half-life for GD is only 2-6 min, which makes pralidoxime impractical in this type of exposure.
A subset of the bispyridinium oximes termed H oximes (H for Hagedorn) contains variations of conventional extant oximes. These include agents such as HI-6, HGG-12, and HGG-42. They have been studied in the military setting but are not available for use in the United States. H oximes have shown promise in reactivating aged enzyme after GD exposure. The bispyridinium oxime termed obidoxime (Toxogonin) has been successfully tested for GB and GA intoxication. Pralidoxime is ineffective in GA.
In most cases, the specific agent involved is unknown. Do not delay or withhold antidote use while awaiting agent identification. The empiric use of pralidoxime is encouraged to prevent aging of the nerve agent with the AChE.
Pralidoxime (Protopam)
Oximes are reactivators of AChE. Can be used IM (as with military autoinjectors) or IV. The IV route is more likely to be practical in ED setting. The half-life of pralidoxime is 1 h, and it is renally excreted.
Adult
15-25 mg/kg IV/IM (IM as with military autoinjectors) recommended dose; dose can be repeated in 1 h, if needed; pralidoxime should be infused over 20 min to prevent hypertension; hypertension is usually transient but can be treated with phentolamine (5 mg IV), if severe
Pediatric
Administer as in adults
The action of the barbiturates is potentiated by AChE inhibitors; pralidoxime is antagonized by neostigmine, pyridostigmine, and edrophonium (medicinal carbamates, which act like the organophosphate insecticides); morphine, theophylline, aminophylline, succinylcholine, reserpine, and the phenothiazines can worsen the condition of patients poisoned by organophosphate (OP) insecticides or nerve agents (should be avoided)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Infuse IV dose over 20 min to prevent hypertension (usually transient but can be treated with phentolamine 5 mg IV) if severe; administration of pralidoxime has been related to worsening of symptoms in carbamate poisoning; rapid injection can cause tachycardia, laryngospasm, muscle rigidity, pain at injection site, blurred vision, diplopia, impaired accommodation, dizziness, drowsiness, nausea, tachycardia, and hyperventilation; can also precipitate a myasthenic crisis in patients with myasthenia gravis; decrease in renal function increases drug levels in blood because pralidoxime is excreted in the urine; pralidoxime can produce transient elevations in creatinine kinase (CK); 1 of 6 patients has an elevation in SGOT, SGPT, or both
Benzodiazepines
Seizures can be observed in severe nerve agent poisoning. For this reason, treatment with benzodiazepines has been advocated as part of the antidotal armamentarium. Experts advocate use of benzodiazepines prophylactically in patients with moderate-to-severe poisoning as well as with patients who are actively seizing. Dose should be 2-5 mg IV or 10 mg IM. With active seizures, diazepam should be titrated to effect.
Diazepam (Valium, Diazemuls, Diastat)
Belongs to benzodiazepine family, members of which act by stimulating GABA (the main inhibitory neurotransmitter in CNS) receptors, resulting in sedation and increased seizure threshold.
Adult
2-5 mg IV or 10 mg IM
Pediatric
0.2-0.4 mg/kg IV
Coadministration of other sedative-hypnotics, such as barbiturates and alcohol, can potentiate the CNS effect of the benzodiazepines
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Exert caution with other CNS depressants and in patients with low albumin levels or hepatic disease (may increase toxicity)
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because midazolam is water soluble, it takes approximately 3 times longer than diazepam to reach peak EEG effects. Wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose.
Adult
Loading dose: 0.2 mg/kg IV
Continuous infusion: 0.1-0.4 mg/kg/h IV; intubation and pressor support will be necessary
Alternatively: 10-15 mg IM; when other access impossible
Pediatric
Loading dose: 0.15 mg/kg IV
Maintenance dose: Infuse 1 mcg/kg/min IV
Titrate dose upward q5min until clinical seizure activity is controlled
Sedative effects of midazolam may be antagonized by theophyllines; narcotics and erythromycin may accentuate sedative effects of midazolam due to decreased clearance
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, and hepatic failure
More on CBRNE - Nerve Agents, Binary: GB2, VX2 |
| Overview: CBRNE - Nerve Agents, Binary: GB2, VX2 |
| Differential Diagnoses & Workup: CBRNE - Nerve Agents, Binary: GB2, VX2 |
 Treatment & Medication: CBRNE - Nerve Agents, Binary: GB2, VX2 |
| Follow-up: CBRNE - Nerve Agents, Binary: GB2, VX2 |
| Multimedia: CBRNE - Nerve Agents, Binary: GB2, VX2 |
| References |
| Further Reading |
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Further Reading
For a discussion about Novichok agents, see Chemical Weapons Disarmament in Russia: Problems and Prospects.
Keywords
nerve agents, binary agents, GB2, VX2, sarin, chemical warfare, acetylcholinesterase inhibitors, AChE inhibitors, GA, tabun, GD, soman, chemical weapons, GB, VX, GD2, acetylcholine, cholinergic overstimulation, organophosphate, carbamate, pralidoxime chloride, Protopam, 2-PAM, anticholinergics, oximes, AChE reactivator, muscarinic receptor
