Medical Aspects of Chemical Warfare (2008) - The Black Vault

Toxins: Established and Emergent Threatsenzyme creatine kinase MB can be elevated. Serumelectrolytes can be monitored for abnormalities dueto dehydration, vomiting, and diarrhea. In addition,serum sodium, serum osmolality, and urine osmolalityare useful for diagnosing suspected secondarydiabetes insipidus in TTX intoxication. 86 CPK levels,which maybe elevated in STX intoxication, should bemonitored. Urinary levels of TTX have been detectedfrom suspected intoxication. 122STX has a direct action on the conducting systemof the frog heart, producing decreases in heart rateand contractile force with severe bradycardia, bundlebranch block, or complete cardiac failure. In cats, STXproduces a reversible depression in contractility ofpapillary muscle. 77 In rats, TTX given intraarteriallyproduces a rapid hypotension, beginning within 1to 2 minutes and lethal by 6 minutes. 108 In severalanimal models, large doses of TTX cause conductionslowing, AV dissociation, and failure of myocardialcontractility. 83 Seizures have been reported in severalanimals intoxicated with TTX. 35,83Dermatologic abnormalities, including pruritis,excessive diaphoresis, 104 and rash, 85 are reported forSTX, while pallor, 93 bullous eruptions, petechiae,desquamation, 92,123 and diaphoresis 92,99 occur in pufferfish poisoning. Other abnormalities shared by bothtoxins include low back pain, muscle weakness, andelevated CPK levels. 102 Progression of any symptomis dependent on dose, route of exposure (ingestion ordermal), and rate of elimination, and not all individualswill react the same way to intoxication. Outbreaksof contamination may involve multiple toxins, sosymptoms may appear to be characteristic of one toxinbut clinical evidence may suggest the involvement ofother toxins, further contributing to morbidity andmortality. 124Treatment. While there are no antidotes for TTXand STX intoxication, treatment is predominantlysupportive and symptomatic. Good cardiovascularand respiratory support is critical, 83 and prognosisis excellent if supportive care is instituted early. 83,97Activated charcoal can be administered after ingestionof either toxin, especially within 1 hour of ingestionof either toxin. 104,125 Cathartics and syrup of ipecac arenot recommended for treatment of toxin ingestion.Most patients will recover with supportive care alone,but they should be monitored for signs of respiratorydepression and neurotoxicity, requiring endotrachealintubation and mechanical ventilation. Electrolytesshould be replaced, and fluids should be regulatedaccording to arterial blood pressure and urinaryoutput. 93,126 Fluid therapy can improve renal eliminationof STX 105 because it is excreted into the urine. 106Hypoxia, acidemia, and conduction abnormalitiesshould be corrected with careful EKG and blood gasmonitoring. Bolus sodium bicarbonate may reverseventricular conduction, slowing and dysrhythmias.Lidocaine IV can be given for ventricular tachycardiaand ventricular fibrillation. 127 Bradycardia can bemanaged with supplemental oxygen and atropine;however, atropine alone may increase the lethalityof TTX. 88,97 Adrenergic antagonists may prolongneuromuscular blockade of TTX and are not recommended.128 Atropine can be given for asystolic cardiacarrest. Treatment with cholinesterase inhibitors hasbeen attempted for TTX-induced muscle weakness,but data concerning their efficacy is scant. One studyshows improvement of muscle weakness after TTXingestion using IV edrophonium (10 mg) or intramuscularneostigmine (0.5 mg). 97,116Hemodialysis might aid recovery, but there is littledata concerning the effectiveness of this treatmentfor TTX and STX intoxication. Hemodialysis wasattempted because both toxins are low molecularweight, water-soluble molecules that are significantlybound to protein. 119 For example, an uremic womanwho received regularly scheduled hemodialysis developedsevere symptoms of TTX intoxication aftereating fish soup. An hour after hemodialysis (and 21hours after symptom onset), the patient recovered. 119Hemodialysis was tried with mixed results for STXintoxication; one patient recovered and the other didnot. 79 Desmopressin IV has been shown to be effectivefor TTX-induced central diabetes insipidus. 86 Allother symptoms (hypotension, seizures, etc) can bemanaged as discussed previously.StabilityTTX is water soluble at neutral pH and soluble in adilute citrate or acetate buffer at acidic pH. In citrate oracetate buffers, it can be stored at −20°C for extendedperiods without loss of efficacy. It is unstable bothin strong acid and alkaline solutions, and is rapidlydestroyed by boiling at pH 2. TTX is likewise unstablein dilute hydrochloric or sulfuric acid, slowlyprotonating into the less toxic anhydrotetrodotoxin atequilibrium. It is relatively heat stable in neutral andorganic acid solutions. Lyophilized TTX, availablefrom commercial sources, should be refrigerated tomaintain stability for long periods.STX is remarkably stable 129,130 and readily soluble.Lyophilized STX is stable under the same storageconditions as TTX. Solutions of STX in acidic, aqueoussolvent, or aqueous methanol, stored at a rangeof −80° to 4°C, are stable for several years. STX solutionsstored at higher temperatures (37°C) are muchless stable.627