Phase I study of a topical skin protectant against chemical warfare agents.

Vesicants and some nerve agents penetrate exposed skin, mainly through the sensitive integration areas of the personal protective equipment. Therefore, improving dermal barrier with a topical agent should reduce the threat of exposure. A topical skin protectant lotion (IB1) was developed to improve protection against chemical warfare agents. Preclinical studies in several animal models have proven the protective efficacy of IB1. Here we present the results of a randomized placebo-controlled, double-blind phase I clinical study, performed with 34 healthy volunteers. The study tested the safety of repeated applications, including ruling out transdermal permeation of magnesium, which may lead to a dangerous blood magnesium level, since the lotion contains magnesium sulfate. Other objectives included detection of dermatological adverse effects, assessment of application convenience, and effect on daily activities. Importantly, no serious adverse effects were recorded and the lotion did not interfere with daily tasks. There were no significant differences in magnesium levels between the placebo and the study groups in any of the applications. No toxic levels of magnesium were found in either group. We conclude that IB1 is probably safe, easily self-applied, and does not cause any significant inconvenience. Therefore, IB1 can be considered as an adjunctive chemical, biological, and radio-nuclear (CBRN) protective aid to field soldiers.

The possible use of oximes as antidotal therapy in organophosphate-induced brain damage.

Organophosphate (OP) poisoning poses great danger to both military and civilian populations. OP-induced brain injury is characterized by rapid loss of consciousness, seizures, central respiratory inhibition as well as long-term behavioral changes in sub-lethal injuries. The pharmacological treatment of OP poisoning is based on anticholinergic and anticonvulsant drugs as well as oximes, which reactivate the non-aged inhibited enzyme. The commonly used oximes are quaternary compounds with questionable capacity to penetrate through the blood-brain barrier. This implies that the main beneficial effect of oximes may result from reactivation of AChE activity in respiratory muscles rather than in the brain. Importantly, data accumulated over the last few decades suggests a potential beneficial role for oximes in the brain, despite their polarity. Albeit the concentration of oximes in the central nervous system is significantly lower than in the plasma, they do gain access into the brain and are able to reactivate inhibited local AChE. Oximes may also attenuate OP-induced brain insult via different mechanisms other than AChE reactivation. In this review, we focus on the ability of oximes to act in the brain and protect the central nervous system from OP-induced injury, either by direct reactivation of AChE or by other pharmacological mechanisms. While this is a poorly investigated field we believe that the data supports the potential role of oximes in mitigating OP-induced neuronal injury, thus making them valuable in the treatment of severe casualties.

Medical management of toxicological mass casualty events.

The relative accessibility to various chemical agents, including chemical warfare agents and toxic industrial compounds, places a toxicological mass casualty event, including chemical terrorism, among the major threats to homeland security. TMCE represents a medical and logistic challenge with potential hazardous exposure of first-response teams. In addition, TMCE poses substantial psychological and economic impact. We have created a simple response algorithm that provides practical guidelines for participating forces in TMCE. Emphasis is placed on the role of first responders, highlighting the importance of early recognition of the event as a TMCE, informing the command and control centers, and application of appropriate self-protection. The medical identification of the toxidrome is of utmost importance as it may dictate radically different approaches and life-saving modalities. Our proposed emergency management of TMCE values the "Scoop & Run" approach orchestrated by an organized evacuation plan rather than on-site decontamination. Finally, continuous preparedness of health systems - exemplified by periodic CBRN (Chemical, Biological, Radio-Nuclear) medical training of both first responders and hospital staff, mandatory placement of antidotal auto-injectors in all ambulances and CBRN emergency kits in the emergency departments - would considerably improve the emergency medical response to TMCE.

Ammonia--when something smells wrong.

Ammonia is a common household and industrial chemical. In the medical literature and the electronic press there are many descriptions of accidental spills of anhydrous ammonia, but apart from the Chechen war, there is no evidence of its intentional use by a terrorist to date. When considering its characteristics, ammonia tankers may pose an imminent threat for a civilian population nearby. This short review attempts to highlight the main health issues and basic principles of medical management after exposure to ammonia. Ammonia can directly cause damage due to its irritating as well as alkaline properties. The management of toxic exposure to ammonia is largely supportive and there is no specific antidote. Emergency medical response on site includes rapid evacuation, life-saving procedures and decontamination if necessary and if possible. Major clinical manifestations include respiratory symptoms, such as hypoxia, bronchospasm and pulmonary edema, as well as hypovolemia and burns to the skin and eyes. The immediate medical management consists of life-saving procedures and supportive care, while broad-range antibiotics and systemic corticosteroids may have a role in preventing late onset complications.

Hydrogen fluoride--the protoplasmic poison.

HF is a corrosive mineral acid. It has extremely harmful systemic effects through any route of exposure. In dilute solutions the onset of symptoms is latent. It is important for caregivers to remember that HF has distinct clinical signs and a specific antidote, namely calcium gluconate. The industrial use of HF heightens the importance of being prepared for possible exposures. The emergency medical teams should be familiar with its symptoms, should possess the proper protective means and should be ready to respond properly in case of emergency.

Hydrazine--the space era agent.

Hydrazine is considered a dangerous toxic compound. It is flammable, easily ignitable and may explode upon contact with different materials, including clothing. As a volatile liquid, it affects mainly the upper respiratory tract, mucous membranes and skin. The characteristics and availability of this agent warrant our attention. Medical personnel should be familiar with its properties, major health effects and the treatment needed. The key principles in treating hydrazine victims include protection from further exposure and aggressive antidotal treatment with pyridoxine (vitamin B6), as well as supportive treatment as required. Finally, medical teams should also be equipped with the proper protection measures (appropriate suits, gloves and breathing apparatuses) in order to avoid secondary exposure of themselves and others.

Osmium tetroxide: a new kind of weapon.

OsO4 is a powerful oxidizer. It affects mainly the skin and mucous membranes. Although unsuitable for a large-scale terrorist attack, mainly due to its scarcity, it could be used in small-scale attacks. The small quantity contained in a vial would cause irritation to the eyes, nose, throat and skin. Combining the agent with an explosive material will probably destroy most of it, chemically. Thus, releasing the chemical without using explosives may be considerably more dangerous. Medical management is mainly symptomatic. As soon as the chemical enters the body, it rapidly reacts with the tissues in contact. Medical personnel should be aware of its poisonous effects and be equally familiar with the necessary self-protection measures and the treatment protocols.

Bromine--the red cloud approaching.

Bromine is a strong and prevalent irritating agent that can spread both as liquid and as fumes. It has a characteristic reddish-brown color. The mainstay of the medical management is supportive and symptomatic therapy that should be given as soon as possible to prevent further damage. Medical personnel, especially the emergency department staff, should be familiar with its health effects, including the safety precautions needed when caring for casualties following such an exposure.

Mobile chemical detector (AP2C+SP4E) as an aid for medical decision making in the battlefield.

The combination of the AP2C unit with the SP4E kit composes a lightweight mobile detector of chemical warfare agents (CWA), such as nerve and mustard agents, with both vapor- and liquid-sampling capabilities. This apparatus was recently introduced into our military medical units as an aid for detection of CWA on casualties. Importantly, critical information regarding the applicability in the battlefield was absent. In view of the serious consequences that might follow a proclamation of CWA recognition in battlefield, a high false-positive rate positions the utilization of this apparatus as a medical decision tool in question. We have therefore conducted a field experiment to test the false-positive rate as well as analyze possible factors leading to false-positive readings with this device. The experiment was carried out before and after a 4-day army field exercise, using a standard AP2C device, a SP4E surface sampling kit, and a specially designed medical sampling kit for casualties, intended for medical teams. Soldiers were examined at rest, after mild exercise, and after 4 days in the field. The readings with AP2C alone were compared to the combination of AP2C and SP4E and to the medical sampling kit. Various body fluids served as negative controls. Remarkably, we found a false-positive rate of 57% at rest and after mild exercise, and an even higher rate of 64% after the 4-day field exercise with the AP2C detector alone, as compared to almost no false-positive readings with the combination of AP2C and SP4E. Strikingly, the medical sampling kit has yielded numerous false-positive readings, even in normal body fluids such as blood, urine, and saliva. We therefore see no place for using the medical sampling kit due to an unaccepted high rate of false-positive readings. Finally, we have designed an algorithm that uses the entire apparatus of AP2C and SP4E as a reliable validation tool for medical triage in the setting of exposure to nerve agents in the battlefield.

A decade after the Tokyo sarin attack: a review of neurological follow-up of the victims.

OBJECTIVE: On March 20, 1995, sarin gas was used in Tokyo by members of the Japanese "Uhm-Shinrikiu" cult, killing 12 and injuring >5,500 innocent people. Most of the casualties were mildly injured. This article reviews the neurological follow-up data for some of the victims over the past decade. METHODS: We reviewed the published literature regarding neurological follow-up of the victims, dividing the data according to the time elapsed after the attack. RESULTS: The digit span test, finger-tapping test, and computerized posturography were the only performance tests that showed statistically significant differences between the victims and the control groups in some of the surveys. The main sequela 7 years after the attack was post-traumatic stress disorder. CONCLUSIONS: The results emphasize the need for a national preparedness program for such mass casualty events, led by national health systems. This should include long-term, neurological, follow-up monitoring with performance tests and a post-traumatic stress disorder screening test.

[Cyanides--treatment beneath the shade of terror].

Although the use of cyanides as warfare agents has not been documented since the Iran-Iraq war in the 1980s, there are rising fears of cyanide being used by terrorists. An Al-Qaeda terror plot to use cyanide gas in the London Underground was foiled in 2002. The threat of similar events becomes more imminent in light of the terror attacks in our country and worldwide, accompanied by statements and threats by fundamentalist leaders to employ chemical weapons. Therefore, mass-intoxication with cyanides is not merely a hypothetical scenario. The treatment of cyanide poisoning is under constant evaluation and there is no international consensus on the subject. The medical treatment of victims at the scene and in hospitals should be rapid and efficient. Current treatment dictates establishing an intravenous line and a slow rate of administration of antidotes. Both demands are not feasible in this specific mass casualty event. The clinical signs of cyanide poisoning are complex, variable and not necessarily obvious for the medical team. There is great interest in reconsidering the existing treatment protocols for cyanide intoxication in light of current research. This review describes the mechanisms of cyanide toxicity, clinical signs of exposure, and current treatment protocols in use worldwide. On the basis of this evidence we suggest a medical treatment protocol for a mass casualty event caused by cyanide.

Radiation terrorism--the medical challenge.

Ionizing radiation can cause acute as well as chronic and late illnesses, and is a well-known health hazard. Its use by terrorists and nations in the form of a non-conventional weapon is no longer impossible. The release of radioactive materials with the accompanying contamination and radiation has the potential of causing serious medical problems. In analyzing the different radiologic terrorism scenarios, a scheme is proposed for the triage and evacuation of injured, contaminated and non-contaminated casualties from the scene itself as well as from the periphery. Knowledge, plans and drills will lessen the impact of those potential attacks and prepare us to respond to such events.