Supportive Care

Saving lives always depends on ensuring adequate airway, ventilation, and circulation. The larger the exposure, the more likely victims require early intubation and ventilation. Conversely, adequate ventilation may be impossible due to the intense muscarinic effects of nerve gas exposure (copious airway secretions, bronchoconstriction). In this situation, administer atropine before initiating other measures. The use of succinylcholine to assist intubation is not recommended, since nerve agents prolong the drug's paralytic effects.

Treat seizures with adequate oxygenation and liberal doses of benzodiazepines titrated to effect. Termination of seizure activity may reflect onset of flaccid paralysis from the nerve agent rather than adequacy of antiseizure therapy. A bedside electroencephalograph (EEG) may be required to assess ongoing seizure activity.

Animal data suggest that routine administration of diazepam reduces incidence of seizures and decreases severity of pathologic brain injury following nerve agent exposure.

Specific Therapy

Treatment of victims with nerve gas toxicity is broadly similar to the treatment of those poisoned by organophosphate insecticides.

Atropine sulfate

Symptomatic patients require immediate treatment with atropine. Atropine blocks muscarinic effects of nerve agents (eg, bronchorrhea, bronchoconstriction), improving ventilation by drying secretions and decreasing airway resistance. Atropine also blocks other muscarinic effects, such as nausea, vomiting, abdominal cramping, bradycardia, and diaphoresis. Atropine does not have nicotinic effects and thus does not reverse toxicity at autonomic ganglia and neuromuscular junctions. Atropine does not prevent or reverse paralysis.

Atropine therapy is guided by clinical signs and symptoms. Titrate dosing to the desired clinical effect. The goals of atropine therapy are to dry secretions and eliminate bronchoconstriction.

Administer more atropine if assisted ventilation remains difficult or secretions persist. Heart rate and pupil size are poor clinical indicators of adequate atropinization. Presence of tachycardia should not dissuade the clinician from initiating or continuing atropine therapy. Miosis may be absent or delayed in dermal exposures and is not reversed by systemic atropine.

• Adults with mild-to-moderate symptoms: 2 mg of atropine IV/IM/ET q2-5min
• Adults with severe symptoms: 5 mg IV/IM/ET
• Children: 0.02 mg/kg (0.1 mg minimum) IV/IM/ET
• Children with severe symptoms: 0.05 mg/kg IV/IM/ET

Up to 20 mg of atropine may be required the first day, unlike with organophosphate insecticide poisoning, where as much as 3000 mg of atropine may be required over 1 day. In the Tokyo sarin attack, only 19% of poisoned patients required more than 2 mg of atropine. Severely poisoned patients required 1.5-15 mg of atropine.

Oxime therapy

Oximes are nucleophilic substances that bind to the phosphate moiety of the nerve agent more avidly than AChE to reactivate the nerve agent–inhibited enzyme. Reactivation is impossible once dealkylation or "aging" of phosphorylated AChE occurs. Once aging occurs, new AChE must be synthesized. The rate of aging varies among nerve agents. Aging occurs within 2 minutes after soman exposure, 5-8 hours after sarin exposure, and more than 40 hours after tabun and VX exposure.

Pralidoxime chloride (2-PAM) is the only conventional oxime available for clinical use in the US. Administer pralidoxime to symptomatic patients as early as possible, ideally concurrent with adequate doses of atropine. Pralidoxime has its greatest effect at the neuromuscular junction.

• Adult dose: 1-2 g IV
• Pediatric dose: 15-25 mg/kg IV over 30 min

Slowly administer pralidoxime IV to minimize adverse effects such as hypertension, headache, blurred vision, epigastric pain, nausea, and vomiting. When IV access cannot be established, 2-PAM also may be given IM (1 mg with 3 mL sterile saline).

With adequate decontamination and appropriate initial therapy, serious signs and symptoms of nerve agent toxicity rarely last more than a couple of hours. In the unusual event that toxicity persists or worsens clinically, administer repeat doses of 2-PAM at hourly intervals. In the Tokyo sarin attack, severely poisoned patients required 1-36 g. Since 2-PAM is excreted in the urine, lower repeat doses for patients with renal failure and maintain adequate hydration. If hypertension increases during pralidoxime administration, IV phentolamine may help (adults: 5 mg IV; children: 1 mg IV).

Mark I kit

Mark I kit was designed for military self-administration in the field. It consists of two spring-loaded IM Autoinjectors containing 2 mg of atropine and 600 mg of pralidoxime, respectively. These antidote kits are not yet available for civilian use.

Hemodialysis

Japanese physicians reported successful use of hemodialysis and hemoperfusion in one severely intoxicated victim of the Tokyo Subway sarin attack who remained unresponsive to pharmacotherapy.

Date: 2015-01-12; view: 726